FN Thomson Reuters Web of Science™ VR 1.0 PT J AU LAI, JC WAWROUSEK, EF SIPE, JD WHITCUP, SM CHAN, CC GERY, J AF LAI, JC WAWROUSEK, EF SIPE, JD WHITCUP, SM CHAN, CC GERY, J TI OCULAR AND SYSTEMIC IMMUNOLOGICAL PROFILE OF INTERLEUKIN-1-BETA (IL-1-BETA) TRANSGENIC MICE SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 NEI,BETHESDA,MD 20892. BOSTON UNIV,SCH MED,BOSTON,MA 02118. HOWARD HUGHES MED INST,COCONUT GROVE,FL 33133. NR 1 TC 1 Z9 1 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 15 PY 1994 VL 35 IS 4 BP 1988 EP 1988 PG 1 WC Ophthalmology SC Ophthalmology GA MZ585 UT WOS:A1994MZ58503390 ER PT J AU WAWROUSEK, EF CHAN, CC LAI, JC GERY, J AF WAWROUSEK, EF CHAN, CC LAI, JC GERY, J TI PROGRESSIVE INFLAMMATORY DISEASE AND NEOVASCULARIZATION IN THE EYES OF INTERLEUKIN-1-BETA TRANSGENIC MICE SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 HOWARD HUGHES MED INST,COCONUT GROVE,FL 33133. NEI,MOLEC & DEV BIOL LAB,BETHESDA,MD 20892. NEI,IMMUNOL LAB,BETHESDA,MD 20892. NR 0 TC 1 Z9 1 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 15 PY 1994 VL 35 IS 4 BP 1988 EP 1988 PG 1 WC Ophthalmology SC Ophthalmology GA MZ585 UT WOS:A1994MZ58503391 ER PT J AU GRAZIOSI, P MARAINI, G AF GRAZIOSI, P MARAINI, G TI LOCATION AND SEVERITY OF CORTICAL OPACITIES IN THE DIFFERENT SECTORS OF THE LENS IN AGE-RELATED CATARACT SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 UNIV PARMA,INST OPHTHALMOL,I-43100 PARMA,ITALY. IST SUPER SANITA,I-00161 ROME,ITALY. NEI,BETHESDA,MD 20892. 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 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAR 15 PY 1994 VL 35 IS 4 BP 1990 EP 1990 PG 1 WC Ophthalmology SC Ophthalmology GA MZ585 UT WOS:A1994MZ58503397 ER PT J AU LYSZ, TW ARORA, JK ZELENKA, PS AF LYSZ, TW ARORA, JK ZELENKA, PS TI EXPRESSION OF 12-LIPOXYGENASE IN HUMAN LENS EPITHELIAL-CELLS SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 UMD,NEW JERSEY MED SCH,DEPT ANAT CELL BIOL & INJURY SCI,NEWARK,NJ. NEI,BETHESDA,MD 20892. 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 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAR 15 PY 1994 VL 35 IS 4 BP 1997 EP 1997 PG 1 WC Ophthalmology SC Ophthalmology GA MZ585 UT WOS:A1994MZ58503425 ER PT J AU TOMAREV, SI CHUNG, S ZINOVIEVA, RD PIATIGORSKY, J AF TOMAREV, SI CHUNG, S ZINOVIEVA, RD PIATIGORSKY, J TI STRUCTURE AND IN-VITRO EXPRESSION OF S-CRYSTALLINS AND GLUTATHIONE-S-TRANSFERASE OF THE SQUID SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 NEI,LMDB,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 1 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 15 PY 1994 VL 35 IS 4 BP 1997 EP 1997 PG 1 WC Ophthalmology SC Ophthalmology GA MZ585 UT WOS:A1994MZ58503428 ER PT J AU WANG, X OHTAKAMARUYAMA, C CHEPELINSKY, AB AF WANG, X OHTAKAMARUYAMA, C CHEPELINSKY, AB TI CIS-REGULATORY ELEMENTS OF THE HUMAN MIP GENE PROMOTER SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 NEI,BETHESDA,MD 20892. 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 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAR 15 PY 1994 VL 35 IS 4 BP 1997 EP 1997 PG 1 WC Ophthalmology SC Ophthalmology GA MZ585 UT WOS:A1994MZ58503426 ER PT J AU CHEPELINSKY, AB ROBINSON, ML OVERBEEK, PA PARKER, DM CHAN, CC JAMIESON, S DICKSON, C AF CHEPELINSKY, AB ROBINSON, ML OVERBEEK, PA PARKER, DM CHAN, CC JAMIESON, S DICKSON, C TI FGF-3 ECTOPIC EXPRESSION INDUCES DIFFERENTIATION OF CENTRAL LENS EPITHELIA AND APPEARANCE OF SECRETORY EPITHELIA IN THE EYES OF TRANSGENIC MICE SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 NEI,BETHESDA,MD 20892. BAYLOR COLL MED,HOUSTON,TX 77030. IMPERIAL CANC RES FUND,LONDON WC2A 3PX,ENGLAND. 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 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAR 15 PY 1994 VL 35 IS 4 BP 1998 EP 1998 PG 1 WC Ophthalmology SC Ophthalmology GA MZ585 UT WOS:A1994MZ58503430 ER PT J AU SEDDON, J AJANI, U SPERDUTO, R YANNUZZI, L BURTON, T HALLER, J BLAIR, N FARBER, M MILLER, D GRAGOUDAS, E WILLETT, W AF SEDDON, J AJANI, U SPERDUTO, R YANNUZZI, L BURTON, T HALLER, J BLAIR, N FARBER, M MILLER, D GRAGOUDAS, E WILLETT, W TI DIETARY-FAT INTAKE AND AGE-RELATED MACULAR DEGENERATION SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 HARVARD UNIV,SCH MED,MEEI,BOSTON,MA 02115. NEI,BETHESDA,MD 20892. MED COLL WISCONSIN,MILWAUKEE,WI 53226. WILMER EI,BALTIMORE,MD. UNIV ILLINOIS,URBANA,IL 61801. HARVARD UNIV,SCH PUBL HLTH,CAMBRIDGE,MA 02138. NR 0 TC 12 Z9 13 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 15 PY 1994 VL 35 IS 4 BP 2003 EP 2003 PG 1 WC Ophthalmology SC Ophthalmology GA MZ585 UT WOS:A1994MZ58503449 ER PT J AU NAGINENI, CN DETRICK, B RHAME, J HOOKS, JJ AF NAGINENI, CN DETRICK, B RHAME, J HOOKS, JJ TI INFLAMMATORY CYTOKINES IFN-GAMMA, TNF-ALPHA AND IL-1 INDUCE ICAM-1 SECRETION SHEDDING BY HUMAN RETINAL-PIGMENT EPITHELIAL-CELLS SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 NEI,BETHESDA,MD 20892. GEORGE WASHINGTON UNIV,MED CTR,WASHINGTON,DC 20037. 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 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAR 15 PY 1994 VL 35 IS 4 BP 2040 EP 2040 PG 1 WC Ophthalmology SC Ophthalmology GA MZ585 UT WOS:A1994MZ58503635 ER PT J AU REUTER, LM CARUSO, RC CHRISTOFORIDIS, JB KAISERKUPFER, MI AF REUTER, LM CARUSO, RC CHRISTOFORIDIS, JB KAISERKUPFER, MI TI DIM RED-LIGHT AND THE GANZFELD ELECTRORETINOGRAM SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 NEI,OPHTHALM GENET & CLIN SERV BRANCH,BETHESDA,MD 20892. 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 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAR 15 PY 1994 VL 35 IS 4 BP 2047 EP 2047 PG 1 WC Ophthalmology SC Ophthalmology GA MZ585 UT WOS:A1994MZ58503672 ER PT J AU SILVER, PB RIZZO, LV CHAN, CC DONOSO, LA WIGGERT, B CASPI, RR AF SILVER, PB RIZZO, LV CHAN, CC DONOSO, LA WIGGERT, B CASPI, RR TI IDENTIFICATION OF A MAJOR PATHOGENIC EPITOPE IN THE IRBP MOLECULE RECOGNIZED BY MICE OF THE H-2R HAPLOTYPE SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 NEI,BETHESDA,MD 20892. WILLS EYE HOSP & RES INST,PHILADELPHIA,PA 19107. RI Rizzo, Luiz Vicente/B-4458-2009 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 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAR 15 PY 1994 VL 35 IS 4 BP 2061 EP 2061 PG 1 WC Ophthalmology SC Ophthalmology GA MZ585 UT WOS:A1994MZ58503738 ER PT J AU SMITH, SB DUNCAN, T WIGGERT, B AF SMITH, SB DUNCAN, T WIGGERT, B TI ELEVATION OF RETINOIDS IN THE RPE AND LIVER OF THE C57BL/6-MIVIT/MIVIT MOUSE MODEL OF RETINAL DEGENERATION SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 MED COLL GEORGIA,AUGUSTA,GA 30912. NEI,BETHESDA,MD 20892. NR 1 TC 0 Z9 0 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 15 PY 1994 VL 35 IS 4 BP 2061 EP 2061 PG 1 WC Ophthalmology SC Ophthalmology GA MZ585 UT WOS:A1994MZ58503739 ER PT J AU FREDERIKSE, P PIATIGORSKY, J AF FREDERIKSE, P PIATIGORSKY, J TI NOVEL AND HEAT INDUCIBLE BINDING OF HSF PROTEINS TO ALPHA-CRYSTALLIN REGULATORY SEQUENCES SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 NEI,LMDB,BETHESDA,MD 20892. NR 0 TC 4 Z9 4 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 15 PY 1994 VL 35 IS 4 BP 2073 EP 2073 PG 1 WC Ophthalmology SC Ophthalmology GA MZ585 UT WOS:A1994MZ58503787 ER PT J AU WISTOW, GJ SEGOVIA, L AF WISTOW, GJ SEGOVIA, L TI MU-CRYSTALLIN - AN UNEXPECTED MARKER FOR PHOTORECEPTORS SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 NEI,LMDB,MOLEC STRUCT & FUNCT SECT,BETHESDA,MD 20892. RI Segovia, Lorenzo/A-5206-2008 OI Segovia, Lorenzo/0000-0002-4291-4711 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 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAR 15 PY 1994 VL 35 IS 4 BP 2073 EP 2073 PG 1 WC Ophthalmology SC Ophthalmology GA MZ585 UT WOS:A1994MZ58503786 ER PT J AU CALLANAN, DG CHEUNG, MK MARTIN, DF DESMET, MD WHITCUP, SM NUSSENBLATT, RB AF CALLANAN, DG CHEUNG, MK MARTIN, DF DESMET, MD WHITCUP, SM NUSSENBLATT, RB TI OUTCOME OF UVEITIS PATIENTS TREATED WITH LONG-TERM CYCLOSPORINE SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 TEXAS RETINA ASSOCIATES,DALLAS,TX. NEI,BETHESDA,MD 20892. EMORY UNIV,ATLANTA,GA 30322. WILMER EYE INST,BALTIMORE,MD. 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 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAR 15 PY 1994 VL 35 IS 4 BP 2094 EP 2094 PG 1 WC Ophthalmology SC Ophthalmology GA MZ585 UT WOS:A1994MZ58503869 ER PT J AU WANG, Y PERCOPO, C DETRICK, B HOOKS, JJ AF WANG, Y PERCOPO, C DETRICK, B HOOKS, JJ TI LYMPHOID TRAFFICKING IN THE RETINA DURING MURINE CORONAVIRUS-INDUCED RETINOPATHY SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 NEI,BETHESDA,MD 20892. GEORGE WASHINGTON UNIV,MED CTR,WASHINGTON,DC 20037. 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 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAR 15 PY 1994 VL 35 IS 4 BP 2097 EP 2097 PG 1 WC Ophthalmology SC Ophthalmology GA MZ585 UT WOS:A1994MZ58503888 ER PT J AU MAINIGI, S RENGARAJAN, K WIGGERT, B CHADER, GJ NUSSENBLATT, RB DESMET, MD AF MAINIGI, S RENGARAJAN, K WIGGERT, B CHADER, GJ NUSSENBLATT, RB DESMET, MD TI ELEVATION OF SERUM ANTIBODY-LEVELS TO HEAT-SHOCK PROTEIN-70 DURING OCULAR INFLAMMATORY EPISODES IN BEHCETS PATIENTS SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 NEI,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 1 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 15 PY 1994 VL 35 IS 4 BP 2098 EP 2098 PG 1 WC Ophthalmology SC Ophthalmology GA MZ585 UT WOS:A1994MZ58503896 ER PT J AU GIESER, SC ADLER, WH VITALE, S THOMAS, R SEN, S RAJEEV, B SCHEIN, OD AF GIESER, SC ADLER, WH VITALE, S THOMAS, R SEN, S RAJEEV, B SCHEIN, OD TI SERUM CYTOKINE CONCENTRATIONS IN PATIENTS WITH EALES-DISEASE IN SOUTH-INDIA - A CONTROLLED-STUDY SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 JOHNS HOPKINS UNIV HOSP,WILMER OPHTHALMOL INST,DANA CTR PREVENT OPHTHALMOL,BALTIMORE,MD 21205. NIA,CLIN IMMUNOL SECT,BALTIMORE,MD 21224. CHRISTIAN MED COLL & HOSP,VELLORE,INDIA. LV PRASAD EYE INST,HYDERABAD,INDIA. 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 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAR 15 PY 1994 VL 35 IS 4 BP 2100 EP 2100 PG 1 WC Ophthalmology SC Ophthalmology GA MZ585 UT WOS:A1994MZ58503903 ER PT J AU HOOKS, JJ PERCOPO, C WANG, Y DETRICK, B AF HOOKS, JJ PERCOPO, C WANG, Y DETRICK, B TI CHARACTERIZATION OF VIRUS-INDUCED ANTI-RETINAL AUTOANTIBODIES SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 NEI,BETHESDA,MD 20892. GEORGE WASHINGTON UNIV,MED CTR,WASHINGTON,DC 20037. 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 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAR 15 PY 1994 VL 35 IS 4 BP 2103 EP 2103 PG 1 WC Ophthalmology SC Ophthalmology GA MZ585 UT WOS:A1994MZ58503921 ER PT J AU KOMURASAKI, Y NAGINENI, C WANG, Y HOOKS, JJ AF KOMURASAKI, Y NAGINENI, C WANG, Y HOOKS, JJ TI VIRAL-RNA PERSISTS WITHIN THE RETINA IN CORONAVIRUS RETINOPATHY SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 NEI,BETHESDA,MD 20892. 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 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAR 15 PY 1994 VL 35 IS 4 BP 2103 EP 2103 PG 1 WC Ophthalmology SC Ophthalmology GA MZ585 UT WOS:A1994MZ58503919 ER PT J AU PADMA, T AYYAGARI, R MURTY, JS BASTI, S RAO, GN SCOTT, M WOZENCRAFT, L KAISERKUPFER, M HEJTMANCIK, JF AF PADMA, T AYYAGARI, R MURTY, JS BASTI, S RAO, GN SCOTT, M WOZENCRAFT, L KAISERKUPFER, M HEJTMANCIK, JF TI LINKAGE ANALYSIS OF CANDIDATE GENE REGIONS FOR AUTOSOMAL-DOMINANT AND RECESSIVE HEREDITARY CATARACTS SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 NATL EYE INST,HYDERABAD,INDIA. OSMANIA UNIV,HYDERABAD 500007,ANDHRA PRADESH,INDIA. PRASAD EYE INST,HYDERABAD,INDIA. 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 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAR 15 PY 1994 VL 35 IS 4 BP 2114 EP 2114 PG 1 WC Ophthalmology SC Ophthalmology GA MZ585 UT WOS:A1994MZ58503977 ER PT J AU HEINZMANN, C KOJIS, TL FLODMAN, P MULLEN, ML GONZALEZ, P ZIGLER, JS SPENCE, MA BATEMAN, JB AF HEINZMANN, C KOJIS, TL FLODMAN, P MULLEN, ML GONZALEZ, P ZIGLER, JS SPENCE, MA BATEMAN, JB TI LINKAGE STUDIES OF ZETA-CRYSTALLIN WITH HUMAN AUTOSOMAL-DOMINANT CONGENITAL CATARACTS SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 UNIV CALIF LOS ANGELES,JULES STEIN EYE INST,DEPT OPHTHALMOL,LOS ANGELES,CA 90024. UNIV CALIF IRVINE,DEPT PEDIAT,IRVINE,CA 92717. NEI,BETHESDA,MD 20892. 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 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAR 15 PY 1994 VL 35 IS 4 BP 2115 EP 2115 PG 1 WC Ophthalmology SC Ophthalmology GA MZ585 UT WOS:A1994MZ58503980 ER PT J AU ULYANOVA, T SZEL, A KUTTY, RK WIGGERT, B CHADER, GJ VANVEEN, T AF ULYANOVA, T SZEL, A KUTTY, RK WIGGERT, B CHADER, GJ VANVEEN, T TI INDUCTION OF HEME OXYGENASE-IMMUNOREACTIVITY IN MULLER CELLS OF ISOLATED MOUSE RETINA SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 GOTHENBURG UNIV,S-41124 GOTHENBURG,SWEDEN. NEI,BETHESDA,MD 20892. NR 0 TC 1 Z9 1 U1 0 U2 1 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 15 PY 1994 VL 35 IS 4 BP 2135 EP 2135 PG 1 WC Ophthalmology SC Ophthalmology GA MZ585 UT WOS:A1994MZ58504077 ER PT J AU DILLON, J ELLOZY, A RESZKA, K CHIGNELL, C AF DILLON, J ELLOZY, A RESZKA, K CHIGNELL, C TI THE PHOTOCHEMISTRY OF 3-HYDROXYKYNURENINE AND KYNURENINE AS STUDIED BY ESR SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 COLUMBIA UNIV,DEPT OPHTHALMOL,NEW YORK,NY 10027. FORDHAM UNIV,BRONX,NY 10458. NIEHS,RES TRIANGLE PK,NC 27709. NR 0 TC 2 Z9 2 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 15 PY 1994 VL 35 IS 4 BP 2137 EP 2137 PG 1 WC Ophthalmology SC Ophthalmology GA MZ585 UT WOS:A1994MZ58504087 ER PT J AU HESS, HH AF HESS, HH TI INCIDENCE OF BILATERAL NATURE CATARACTS IN ROYAL-COLLEGE OF SURGEONS (RCS) RATS AND ENVIRONMENTAL LIGHT STRESS SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 NEI,BETHESDA,MD 20892. 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 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAR 15 PY 1994 VL 35 IS 4 BP 2137 EP 2137 PG 1 WC Ophthalmology SC Ophthalmology GA MZ585 UT WOS:A1994MZ58504089 ER PT J AU AYYAGARI, R SMITH, RJH POLYMEROPOULOS, M CHINAULT, AC DAIGER, S PELIAS, MZ WOZENCRAFT, L KAISERKUPFER, M HEJTMANCIK, JF AF AYYAGARI, R SMITH, RJH POLYMEROPOULOS, M CHINAULT, AC DAIGER, S PELIAS, MZ WOZENCRAFT, L KAISERKUPFER, M HEJTMANCIK, JF TI LINKAGE AND HAPLOTYPE ANALYSIS AND PHYSICAL MAPPING OF THE USH1C GENE SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 NEI,BETHESDA,MD 20892. NIH,CHGR,BETHESDA,MD 20892. UNIV IOWA,IOWA CITY,IA 52242. UNIV TEXAS,HLTH SCI CTR,HOUSTON,TX 77225. LSU,MED CTR,NEW ORLEANS,LA. BAYLOR COLL MED,HOUSTON,TX 77030. NR 0 TC 3 Z9 3 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 15 PY 1994 VL 35 IS 4 BP 2143 EP 2143 PG 1 WC Ophthalmology SC Ophthalmology GA MZ585 UT WOS:A1994MZ58504114 ER PT J AU KADOR, PF LEE, YS RODRIGUEZ, L CARPER, D BARTOZKOMALIK, A PANNELL, L AF KADOR, PF LEE, YS RODRIGUEZ, L CARPER, D BARTOZKOMALIK, A PANNELL, L TI CHARACTERIZATION OF THE ALDOSE REDUCTASE INHIBITOR SITE SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 NEI,OCULAR THERAPEUT LAB,BETHESDA,MD 20892. NEI,MECHANISMS OCULAR DIS LAB,BETHESDA,MD 20892. NIDDKD,ANALYT CHEM LAB,BETHESDA,MD. 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 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAR 15 PY 1994 VL 35 IS 4 BP 2152 EP 2152 PG 1 WC Ophthalmology SC Ophthalmology GA MZ585 UT WOS:A1994MZ58504151 ER PT J AU MURA, U CECCONI, I VOLTARELLI, M MARINI, I DALMONTE, M CAPPIELLO, M GIANNESSI, M GARLAND, D DELCORSO, A AF MURA, U CECCONI, I VOLTARELLI, M MARINI, I DALMONTE, M CAPPIELLO, M GIANNESSI, M GARLAND, D DELCORSO, A TI SITE-SPECIFIC OXIDATION OF BOVINE LENS ALDOSE REDUCTASE INDUCED BY COPPER-ION SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 UNIV MODENA,INST CHIM BIOL,I-41100 MODENA,ITALY. UNIV PISA,DIPARTIMENTO FISIOL & BIOCHIM,I-56100 PISA,ITALY. NEI,BETHESDA,MD 20892. NR 0 TC 1 Z9 1 U1 0 U2 1 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 15 PY 1994 VL 35 IS 4 BP 2152 EP 2152 PG 1 WC Ophthalmology SC Ophthalmology GA MZ585 UT WOS:A1994MZ58504150 ER PT J AU OLD, SE CARPER, DA AF OLD, SE CARPER, DA TI SITE-DIRECTED MUTAGENESIS OF HUMAN ALDOSE REDUCTASE SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 NEI,BETHESDA,MD 20892. 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 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAR 15 PY 1994 VL 35 IS 4 BP 2152 EP 2152 PG 1 WC Ophthalmology SC Ophthalmology GA MZ585 UT WOS:A1994MZ58504149 ER PT J AU RUSSELL, P TUMMINIA, SJ PICHEL, JMC AF RUSSELL, P TUMMINIA, SJ PICHEL, JMC TI COMPARISON OF LENS EPITHELIAL-CELL LINES FROM TRANSGENIC ANIMALS SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 NICHHD,BETHESDA,MD 20892. NEI,BETHESDA,MD 20892. 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 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAR 15 PY 1994 VL 35 IS 4 BP 2204 EP 2204 PG 1 WC Ophthalmology SC Ophthalmology GA MZ585 UT WOS:A1994MZ58504392 ER PT J AU RAMPALLI, AM ZELENKA, PS AF RAMPALLI, AM ZELENKA, PS TI EXPRESSION OF CELL-CYCLE MARKERS DURING LENS FIBER CELL-DIFFERENTIATION IN-VITRO SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 NEI,BETHESDA,MD 20892. 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 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAR 15 PY 1994 VL 35 IS 4 BP 2206 EP 2206 PG 1 WC Ophthalmology SC Ophthalmology GA MZ585 UT WOS:A1994MZ58504404 ER PT J AU MATSUNO, K GARLAND, DL AF MATSUNO, K GARLAND, DL TI M2+ INDUCED PRECIPITATION OF BOVINE LENS CRYSTALLINS SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 NEI,BETHESDA,MD 20892. 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 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAR 15 PY 1994 VL 35 IS 4 BP 2211 EP 2211 PG 1 WC Ophthalmology SC Ophthalmology GA MZ585 UT WOS:A1994MZ58504423 ER PT J AU TUMMINIA, SJ RUSSELL, P AF TUMMINIA, SJ RUSSELL, P TI ALPHA-B-CRYSTALLIN EXPRESSION AND CHAPERONE FUNCTION IN HUMAN ASTROGLIOMA CELL-LINE U373 SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 NEI,MECHANISMS OCULAR DIS LAB,BETHESDA,MD 20892. 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 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAR 15 PY 1994 VL 35 IS 4 BP 2212 EP 2212 PG 1 WC Ophthalmology SC Ophthalmology GA MZ585 UT WOS:A1994MZ58504433 ER PT J AU CHAMBERS, CA GALLINGER, S ANDERSON, SK GIARDINA, S ORTALDO, JR HOZUMI, N RODER, J AF CHAMBERS, CA GALLINGER, S ANDERSON, SK GIARDINA, S ORTALDO, JR HOZUMI, N RODER, J TI EXPRESSION OF THE NK-TR GENE IS REQUIRED FOR NK-LIKE ACTIVITY IN HUMAN T-CELLS SO JOURNAL OF IMMUNOLOGY LA English DT Article ID NATURAL-KILLER-CELLS; TOXIC LYMPHOCYTES-T; CIS-TRANS ISOMERASE; FUNCTIONAL-HETEROGENEITY; LESCH-NYHAN; CLONES; RNA; RECOGNITION; CYCLOPHILIN; PROTEINS AB NK cells lyse target cells without previous immune sensitization. A small subset of T cells also exhibits NK-like activity, which is distinct from TCR-mediated, MHC-restricted, and MHC-unrestricted cytotoxicity. We recently cloned a gene, NK-TR, which is postulated to be part of the NK target-recognition/triggering complex. To determine whether the NK-TR gene product is requisite for NK-like killing, stable antisense transfectants were generated by using a human T cell clone with NK-like activity. Two distinct antisense regions of the sequence were used to generate the transfectants alpha NK-TR and alpha Cyclo. Transfectants lost the ability to lyse NK sensitive targets but did not lose lectin-mediated cytotoxic activity. This effect was not seen with the control vector transfectant cell line. The loss of NK-like activity by the antisense transfectant alpha NK-TR correlated with the specific decrease in endogenous NK-TR mRNA and protein. These results demonstrate the requirement for the NK-TR protein for NK-like killing. Moreover, the results have important implications for examining developmental relationship between T and NK cells and the possible roles for T cells with NK-like activity in vivo. C1 MT SINAI HOSP,SAMUEL LUNENFELD RES INST,DIV MOLEC IMMUNOL & NEUROBIOL,TORONTO M5G 1X5,ON,CANADA. MT SINAI HOSP,DEPT SURG,TORONTO M5G 1X5,ON,CANADA. UNIV TORONTO,DEPT IMMUNOL,TORONTO,ON,CANADA. NCI,FREDERICK CANC RES & DEV CTR,EXPTL IMMUNOL LAB,FREDERICK,MD 21702. NCI,FREDERICK CANC RES & DEV CTR,DYNCORP,PROGRAM RESOURCES INC,FREDERICK,MD 21702. RI Anderson, Stephen/B-1727-2012; Gallinger, Steven/E-4575-2013; Roder, John/G-6468-2013 OI Anderson, Stephen/0000-0002-7856-4266; NR 34 TC 17 Z9 17 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 15 PY 1994 VL 152 IS 6 BP 2669 EP 2674 PG 6 WC Immunology SC Immunology GA NC773 UT WOS:A1994NC77300004 PM 8144875 ER PT J AU EICHER, DM TAN, TH RICE, NR OSHEA, JJ KENNEDY, ICS AF EICHER, DM TAN, TH RICE, NR OSHEA, JJ KENNEDY, ICS TI EXPRESSION OF V-SRC IN T-CELLS CORRELATES WITH NUCLEAR EXPRESSION OF NF-KAPPA-B SO JOURNAL OF IMMUNOLOGY LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; PROTEIN-TYROSINE KINASE; LONG TERMINAL REPEAT; DNA-BINDING SUBUNIT; ANTIGEN RECEPTOR; TRANSCRIPTION FACTOR; SIGNAL TRANSDUCTION; INTERLEUKIN-2 GENE; LYMPHOCYTES-T; REL ONCOGENE AB NF-kappa B is a rapidly inducible transcriptional activator that responds to a variety of signals and influences the expression of many genes involved in the immune response. Protein tyrosine kinases transmit signals from cytokine and immune receptors. Very little information exists linking these two important classes of signaling molecules. We now demonstrate that v-scr expression correlates with nuclear expression of a kappa B binding complex similar to that induced by phorbol ester and ionomycin, as detected by electrophoretic mobility shift assay using a variety of kappa B sites. This complex was blocked by the tyrosine kinase inhibitor, herbimycin A. The v-src-induced complex comprised the p50 and p65 components of NF-kappa B, as determined by supershift and immunoblot analysis. As a functional correlate of this finding, transient co-transfection of HIV-1 LTR reporter constructs in a different T cell line demonstrated that v-src activated this promoter in a kappa B-dependent manner. We found that transactivation of the HIV-1 LTR by v-src was more sensitive to mutations of the proximal, rather that the distal, kappa B element. The implications for T cell receptor signaling and HIV-1 gene expression are considered. C1 NCI,FCRDC,BIOL RESPONSE MODIFIERS PROGRAM,EXPTL IMMUNOL LAB,LEUKOCYTE CELL BIOL SECT,FREDERICK,MD 21702. BAYLOR COLL MED,DEPT MICROBIOL & IMMUNOL,HOUSTON,TX 77030. NCI,FCRDC,ADV BIOSCI LABS INC,MOLEC VIROL & CARCINOGENESIS LAB,FREDERICK,MD 21702. RI Tan, Tse-Hua/E-3983-2010 OI Tan, Tse-Hua/0000-0003-4969-3170 FU NCI NIH HHS [N01-CO-74101] NR 70 TC 39 Z9 39 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 15 PY 1994 VL 152 IS 6 BP 2710 EP 2719 PG 10 WC Immunology SC Immunology GA NC773 UT WOS:A1994NC77300009 PM 8144878 ER PT J AU CEMAN, S PETERSEN, JW PINET, V DEMARS, R AF CEMAN, S PETERSEN, JW PINET, V DEMARS, R TI GENE REQUIRED FOR NORMAL MHC CLASS-II EXPRESSION AND FUNCTION IS LOCALIZED TO APPROXIMATELY 45 KB OF DNA IN THE CLASS-II REGION OF THE MHC SO JOURNAL OF IMMUNOLOGY LA English DT Article ID MAJOR HISTOCOMPATIBILITY COMPLEX; PUTATIVE PEPTIDE TRANSPORTER; ANTIGEN PRESENTATION; HLA-DR; LYMPHOBLASTOID-CELLS; MOLECULES; DQ; MUTATIONS; SEQUENCES; DELETION AB In certain mutant human B cell lines, MHC-encoded class II molecules displayed at the cell surface have an abnormal conformation and are unstable in the presence of SDS. The mutants cannot present exogenous protein Ags to T cells but elicit responses with exogenous antigenic peptides; thus, formation of intracellular complexes between antigenic peptides and class II molecules is impaired. Previous analysis of LCL deletion mutants, .82, .174, and 5.2.4, showed that genes needed for this function must be present in approximate to 230 kb of DNA in the class II region of the MHC. We now describe a new deletion mutant, .61, which has normal class II-mediated Ag processing/presentation. The TAP1, TAP2, LMP2, and LMP7 genes are deleted from .61, demonstrating that those genes are not needed for normal formation of intracellular class II/peptide complexes. The genes in question must be located in DNA that is present in .61 and .82 (both normal) and absent from .174 and 5.2.4. (both defective). Mapping of the deletion breakpoints indicates that genes needed for normal class II-associated Ag processing/presentation are either: 1) in an approximate to 40 kb L DNA segment located between the DMB and LMP2 loci or 2) in an R region between the DQA2 and DQB1 loci and are completely included on a 5.1-kb fragment formed by joining of DNA that flanks the deletion in .61. The evidence favors location of the genes in the L DNA segment. C1 UNIV WISCONSIN,GENET LAB,MADISON,WI 53706. NIAID,IMMUNOGENET LAB,ROCKVILLE,MD 20852. RI PINET, Valerie/G-6085-2012 FU NIAID NIH HHS [AI15486]; NIGMS NIH HHS [GM0713317] NR 30 TC 14 Z9 14 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 15 PY 1994 VL 152 IS 6 BP 2865 EP 2873 PG 9 WC Immunology SC Immunology GA NC773 UT WOS:A1994NC77300026 PM 8144887 ER PT J AU CHEN, Y SIDNEY, J SOUTHWOOD, S COX, AL SAKAGUCHI, K HENDERSON, RA APPELLA, E HUNT, DF SETTE, A ENGELHARD, VH AF CHEN, Y SIDNEY, J SOUTHWOOD, S COX, AL SAKAGUCHI, K HENDERSON, RA APPELLA, E HUNT, DF SETTE, A ENGELHARD, VH TI NATURALLY PROCESSED PEPTIDES LONGER THAN 9 AMINO-ACID-RESIDUES BIND TO THE CLASS-I MHC MOLECULE HLA-A2.1 WITH HIGH-AFFINITY AND IN DIFFERENT CONFORMATIONS SO JOURNAL OF IMMUNOLOGY LA English DT Article ID LYMPHOCYTE-T; SEQUENCE; COMPLEX; IDENTIFICATION; RECOGNITION; HLA-AW68; ANTIGENS; HLA-B27 AB An equilibrium binding assay was used to directly measure the relative affinities of naturally processed 9-mer, 10-mer, and 12-mer peptides for the human class I MHC molecule HLA-A2.1. The peptides exhibited a range of affinities with IC50 values of 11 to 214 nM. The mode of interaction between these peptides and HLA-A2.1 was examined using peptides in which Asp had been substituted for suspected anchor residues. Regardless of length, the previously identified Leu at position 2 relative to the amino terminus was critical for peptide binding. While the carboxyl terminal residue was also critical for the binding of a 9-mer peptide, it was much less important in the binding of longer peptides. Additional residues close to the carboxyl terminus that contained aliphatic hydrocarbon side chains were of similar or greater importance in peptide binding. In addition, residue at position 3 also appeared to be important for the binding of longer peptides. The data suggest that different naturally occurring longer peptides can bind in different conformations to class I MHC molecules. While one of these is similar to the kinked conformation described by others, another conformation would involve an extension of the carboxyl terminus out of the class I binding site. The ability of MHC molecules to accommodate the same peptide indifferent conformations would appear to have distinct advantages to the immune system. C1 UNIV VIRGINIA,SCH MED,HLTH SCI CTR MR4,BEIRNE CARTER CTR IMMUNOL RES,CHARLOTTESVILLE,VA 22908. UNIV VIRGINIA,SCH MED,DEPT MICROBIOL,CHARLOTTESVILLE,VA 22908. UNIV VIRGINIA,DEPT CHEM,CHARLOTTESVILLE,VA 22901. CYTEL CORP,SAN DIEGO,CA 92121. NCI,CELL BIOL LAB,BETHESDA,MD 20892. RI Hunt, Donald/I-6936-2012; Ain, Kenneth/A-5179-2012 OI Hunt, Donald/0000-0003-2815-6368; Ain, Kenneth/0000-0002-2668-934X FU NIAID NIH HHS [AI18634, AI20693]; NIGMS NIH HHS [GM37537] NR 31 TC 93 Z9 98 U1 0 U2 2 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD MAR 15 PY 1994 VL 152 IS 6 BP 2874 EP 2881 PG 8 WC Immunology SC Immunology GA NC773 UT WOS:A1994NC77300027 PM 8144888 ER PT J AU KASAIAN, MT IKEMATSU, H BALOW, JE CASALI, P AF KASAIAN, MT IKEMATSU, H BALOW, JE CASALI, P TI STRUCTURE OF THE V-H AND V-L SEGMENTS OF MONOREACTIVE AND POLYREACTIVE IGA AUTOANTIBODIES TO DNA IN PATIENTS WITH SYSTEMIC LUPUS-ERYTHEMATOSUS SO JOURNAL OF IMMUNOLOGY LA English DT Article ID IMMUNOGLOBULIN HEAVY-CHAIN; VARIABLE REGION GENES; CIRCULATING IMMUNE-COMPLEXES; HUMAN-ANTIBODY RESPONSE; NO SOMATIC MUTATION; EPSTEIN-BARR VIRUS; GERM-LINE GENES; B-CELLS; RHEUMATOID-ARTHRITIS; PREFERENTIAL UTILIZATION AB Anti-DNA IgA autoantibodies play an important immunopathologic role in SLE patients. To analyze the cellular origin and the V-H and V-L structure of anti-DNA IgA autoantibodies, we generated five IgA1 mAbs to DNA using B lymphocytes from three SLE patients. Two mAbs bound to ssDNA only and one to both ssDNA and dsDNA (monoreactive antibodies). The remaining two mAbs bound to DNA (one to ssDNA and the other to both ssDNA and dsDNA) and to other self and foreign Ag (polyreactive antibodies). The IgA mAb relative avidity for DNA ranged from 7.5 x 10(-8) to 8.0 X 10(-10) g/mu l. The anti-DNA IgA mAb used V-H segments of the VHI (VI-3b), VHII (V(H)2-MC2), VHIII (WHG16G and V(H)26c), and VHIV (V71-2) families in conjunction with V kappa I, V kappa IIIb, or V lambda I segments. All IgA mAb V-H segments were juxtaposed with J(H)4b segments. The heavy chain CDR3 sequences were divergent in composition and length. When compared with those of the closest reported germ line genes, the IgA mAb V-H and V-L gene sequences displayed a number of differences. That these differences represented somatic point mutations was formally proved in both the monoreactive IgA mAb 412.67.F1.3 and the polyreactive IgA mAb 412.66.F1 V-H segments by differential PCR amplification and cloning and sequencing of genomic DNA from the mAb-producing cell lines and autologous polymer-phonuclear cells. The sequences of the germ line genes that putatively gave rise to the mAb 412.67.F1.3 and mAb 412.66.F1 V-H segments were identical with those of the WHG16G and V(H)26c genes, respectively. In not only the monoreactive mAb 412.67.F1.3 but also the polyreactive mAb 412.66.F1 and mAb 448.9G.F1 V-H segments, the higher concentration of replacement (R) mutations and the higher R:S (silent) mutation ratios in the complementarity-determining region (infinity; 19:0) than in the framework region (1.0) (p = 0.00001, chi(2) test) were highly consistent with selection by Ag. In the five IgA mAb V-H and V-L segments, the putative and verified somatic point mutations yielded 68 amino acid replacements, of which 38 were nonconserved. Twenty of these yielded positively charged or polar residues that play a major role in DNA binding, including seven Arg, five Lys, three Tyr, two Gln, two His, and a Thr. The conserved amino acid changes included seven Asn. These findings suggest that anti-DNA IgA autoantibodies use a broad selection of V-H and V-L genes and enhance their fit for Ag by undergoing somatic hypermutation and Ag selection. Such a hypermutation and Ag selection process would apply to originally polyreactive, in addition to monoreactive natural DNA binding IgA autoantibodies. C1 NYU,SCH MED,DEPT PATHOL,NEW YORK,NY 10016. NYU,SCH MED,KAPLAN COMPREHENS CANC CTR,NEW YORK,NY 10016. NIDDKD,BETHESDA,MD 20892. RI Casali, Paolo/F-6579-2010 FU NCRR NIH HHS [BRSC S07 RR05399-30]; NIAMS NIH HHS [AR-40908, R01 AR040908] NR 86 TC 57 Z9 57 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 15 PY 1994 VL 152 IS 6 BP 3137 EP 3151 PG 15 WC Immunology SC Immunology GA NC773 UT WOS:A1994NC77300055 PM 8144908 ER PT J AU CASINO, PR KILCOYNE, CM QUYYUMI, AA HOEG, JM PANZA, JA AF CASINO, PR KILCOYNE, CM QUYYUMI, AA HOEG, JM PANZA, JA TI INVESTIGATION OF DECREASED AVAILABILITY OF NITRIC-OXIDE PRECURSOR AS THE MECHANISM RESPONSIBLE FOR IMPAIRED ENDOTHELIUM-DEPENDENT VASODILATION IN HYPERCHOLESTEROLEMIC PATIENTS SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Article ID FOREARM RESISTANCE VESSELS; CHOLESTEROL-FED RABBITS; L-ARGININE; SMOOTH-MUSCLE; CORONARY MICROCIRCULATION; VASCULAR RELAXATION; NITROGEN-OXIDES; ATHEROSCLEROSIS; ARTERIES; CELLS AB Objectives. The purpose of this study was to determine whether the impaired endothelium dependent vasodilation of hypercholesterolemic patients is due to decreased availability of L arginine, the substrate for nitric oxide. Background. Patients with hypercholesterolemia have impaired endothelium dependent vasodilation that is related to a defect in the endothelium derived nitric oxide system. However, the precise location of this abnormality has not been determined. Methods. The study included 12 hypercholesterolemic patients (6 men, 6 women; 52 +/- 9 years old; serum cholesterol >240 mg/dl) and 15 normal volunteers (8 men, 7 women; 50 +/- 6 years old; serum cholesterol <210 mg/dl). The forearm vascular responses to intraarterial infusion of acetylcholine, an endothelium-dependent vasodilator (7.5, 15, 30 mu g/min), and sodium nitroprusside, a direct smooth muscle dilator (0.8, 1.6, 3.2 mu g/min) were studied before and during infusion of L- or D-arginine (a stereoisomer of arginine that is not a nitric oxide precursor). Results. The response to acetylcholine was lower in hypercholesterolemic patients than in control subjects. However, no significant difference was observed with sodium nitroprusside infusion. L-Arginine augmented the response to acetylcholine in normal subjects (maximal blood flow increased from 14.4 +/- 7 to 18.9 +/- 10 ml/min per 100 ml, p < 0.002). In contrast, in the hypercholesterolemic lesterolemic patients, only a mild but not significant improvement in the response to acetylcholine was observed with the infusion of L-arginine (maximal blood flow increased from 6.8 +/- 4 to 8.4 +/- 5 ml/min per 100 mi; p = 0.16); however, a similar mad but not significant change was also observed with D-arginine (maximal blood flow increased from 6.8 +/- 4 to 8.3 +/- 4 ml/min per 100 ml,, p = 0.07). L-Arginine did not modify the response to sodium nitroprusside in either group. Conclusions. The augmentation of endothelium-dependent vasodilation by L arginine, the nitric oxide precursor, is defective in hypercholesterolemic patients. This supports the concept of an abnormal endothelium derived nitric oxide system in hypercholesterolemia and indicates that decreased availability of nitric oxide substrate is not responsible for the impaired endothelial function in this condition. C1 NHLBI,CARDIOL BRANCH,BETHESDA,MD 20892. NR 42 TC 72 Z9 73 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 15 PY 1994 VL 23 IS 4 BP 844 EP 850 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA PH370 UT WOS:A1994PH37000002 PM 8106688 ER PT J AU MANOLIO, TA FURBERG, CD RAUTAHARJU, PM SISCOVICK, D NEWMAN, AB BORHANI, NO GARDIN, JM TABATZNIK, B AF MANOLIO, TA FURBERG, CD RAUTAHARJU, PM SISCOVICK, D NEWMAN, AB BORHANI, NO GARDIN, JM TABATZNIK, B TI CARDIAC-ARRHYTHMIAS ON 24-H AMBULATORY ELECTROCARDIOGRAPHY IN OLDER WOMEN AND MEN - THE CARDIOVASCULAR HEALTH STUDY SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Article ID VENTRICULAR ECTOPIC ACTIVITY; ACUTE MYOCARDIAL-INFARCTION; ISCHEMIC-HEART-DISEASE; PROGNOSTIC-SIGNIFICANCE; PREMATURE BEATS; ELDERLY POPULATION; PREVALENCE; FREQUENT; MORTALITY; SURVIVORS AB Objectives. This study describes the prevalence and correlates of cardiac arrhythmias in older persons. Background. Cardiac arrhythmias are frequent in selected samples of elderly persons, but their prevalence and association with cardiovascular disease and its risk factors have not been examined in a large population based sample. Methods. In 1,372 participants in the Cardiovascular Health Study, a population-based study of cardiovascular disease risk factors, 24-h ambulatory electrocardiography was performed. Results. Serious arrhythmias, such as sustained ventricular tachycardia and complete atrioventricular block, were uncommon, but brief episodes of ventricular tachycardia (greater than or equal to 3 consecutive ventricular depolarizations) were detected in 4.3% of women and 10.3 % of men. Ventricular arrhythmias as a group (excluding ectopic beats <15/h) were more common in men than in women but were not significantly associated with age. The same patterns were true for bradycardia/conduction blocks. Supraventricular arrhythmias as a group (excluding ectopic beats <15/h), in contrast, did not differ by gender but were strongly associated with increased age. Multivariate analyses showed associations with arrhythmias to differ by gender, with only one association (increased age and supraventricular arrhythmias) present in both women and men. Ventricular arrhythmias, particularly in men, were associated with a higher prevalence of cardiovascular disease and its risk factors and with subclinical disease, as measured by increased left ventricular mass and impaired left ventricular function. Conclusions. Arrhythmias are common in the elderly, and their association with cardiovascular disease differs by gender. Although risk related to arrhythmias can only be determined by prospective study, such studies should have adequate power to examine potential gender differences in associations. C1 BOWMAN GRAY SCH MED,DEPT PUBL HLTH SCI,WINSTON SALEM,NC. UNIV ALBERTA,EPICORE CTR,EDMONTON,AB,CANADA. UNIV WASHINGTON,DEPT BIOSTAT,SEATTLE,WA 98195. UNIV PITTSBURGH,GRAD SCH PUBL HLTH,DEPT EPIDEMIOL,PITTSBURGH,PA. UNIV CALIF IRVINE,DEPT MED,ORANGE,CA. JOHNS HOPKINS UNIV,SCH MED,DEPT MED,BALTIMORE,MD 21205. RP MANOLIO, TA (reprint author), NHLBI,DIV EPIDEMIOL & CLIN APPLICAT,FED BLDG,ROOM 301,7550 WISCONSIN AVE,BETHESDA,MD 20892, USA. RI Newman, Anne/C-6408-2013 OI Newman, Anne/0000-0002-0106-1150 FU NHLBI NIH HHS [N01-HC-85079, N01-HC-85080, N01-HC-85081] NR 40 TC 89 Z9 93 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 15 PY 1994 VL 23 IS 4 BP 916 EP 925 PG 10 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA PH370 UT WOS:A1994PH37000012 PM 8106697 ER PT J AU PANYUTIN, IG HSIEH, P AF PANYUTIN, IG HSIEH, P TI THE KINETICS OF SPONTANEOUS DNA BRANCH MIGRATION SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID ESCHERICHIA-COLI; CRUCIFORM TRANSITIONS; HOLLIDAY JUNCTIONS; PROTEIN; RECOMBINATION; RUVA AB An important step in genetic recombination is DNA branch migration, the movement of the Holliday junction or exchange point between two homologous duplex DNAs. We have determined kinetic parameters of spontaneous branch migration as a function of temperature and ionic conditions. The branch migration substrates consist of two homologous duplex DNAs each having two single-strand tails at one end that are complementary to the corresponding single strand tails of the other duplex. Upon rapid annealing of the two duplex DNAs, a four-stranded intermediate is formed that has a Holliday junction at one end of the duplexes. Branch migration to the opposite end of the duplexes results in complete strand exchange and formation of two duplex products. The rate of branch migration is exceedingly sensitive to the type of metal ions present. In magnesium, branch migration is quite slow with a step time, tau, equal to 300 msec at 37 degrees C. Surprisingly, branch migration in the absence of magnesium was 1000 times faster. Despite this difference in rates, apparent activation energies for the branch migration step in the presence and absence of magnesium are similar. Since metal ions have a profound effect on the structure of the Holliday junction, it appears that the structure of the branch point plays a key role in determining the rate of spontaneous DNA branch migration. We discuss the role of proteins in promoting the branch migration step during homologous recombination. RP PANYUTIN, IG (reprint author), NIDKDD,GENET & BIOCHEM BRANCH,BETHESDA,MD 20892, USA. NR 21 TC 199 Z9 200 U1 2 U2 14 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 15 PY 1994 VL 91 IS 6 BP 2021 EP 2025 DI 10.1073/pnas.91.6.2021 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA NC043 UT WOS:A1994NC04300012 PM 8134343 ER PT J AU FATATIS, A HOLTZCLAW, LA AVIDOR, R BRENNEMAN, DE RUSSELL, JT AF FATATIS, A HOLTZCLAW, LA AVIDOR, R BRENNEMAN, DE RUSSELL, JT TI VASOACTIVE-INTESTINAL-PEPTIDE INCREASES INTRACELLULAR CALCIUM IN ASTROGLIA - SYNERGISM WITH ALPHA-ADRENERGIC RECEPTORS SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE ASTROCYTES; VASOACTIVE INTESTINAL PEPTIDE RECEPTORS ID CENTRAL-NERVOUS-SYSTEM; RAT CEREBRAL-CORTEX; RADIORECEPTOR ASSAY; INOSITOL PHOSPHATES; BRAIN MEMBRANES; GUINEA-PIG; CYCLIC-AMP; BINDING; ASTROCYTES; CELLS AB In type I astrocytes from rat cerebral cortex, vasoactive intestinal peptide (VIP) at concentrations below 1 nM evoked an increase in intracellular calcium ion concentration. This response, however, was observed in only 18% of the astrocytes examined. alpha-Adrenergic stimulation with phenylephrine or norepinephrine also resulted in an intracellular calcium response in these cells and the threshold sensitivity of astrocytes to phenylephrine was vastly different from cell to cell. Treatment of these astrocytes with VIP (0.1 nM) together with phenylephrine at subthreshold concentrations produced large increases in intracellular Ca2+ concentration ([Ca2+](i)) and oscillations. The continued occupation of the alpha-adrenergic receptor was required for sustained synergism. Both alpha-receptor stimulation and stimulation with the mixture of agonists induced the cellular calcium response by triggering release of calcium from cellular stores, since the response persisted in the absence of extracellular calcium. Furthermore, thapsigargin pretreatment, which depletes intracellular stores, abolished the agonist-induced [Ca2+](i) response. VIP (0.1 nM) and phenylephrine were found to increase cellular levels of inositol phosphates; however, there was no apparent additivity in this response when the agonists were added together. These observations suggest a calcium-mediated second messenger system for the high-affinity VIP receptor in astrocytes and that alpha-adrenergic receptors act synergistically with the VIP receptor to augment an intracellular calcium signal. The synergism between diverse receptor types may constitute an important mode of cellular signaling in astroglia. C1 NICHHD,DEV NEUROBIOL LAB,BETHESDA,MD 20892. RP FATATIS, A (reprint author), UNIV NAPLES,SCH MED 2,DEPT PHARMACOL,NAPLES,ITALY. NR 36 TC 73 Z9 74 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 15 PY 1994 VL 91 IS 6 BP 2036 EP 2040 DI 10.1073/pnas.91.6.2036 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA NC043 UT WOS:A1994NC04300015 PM 8134346 ER PT J AU BOBO, RH LASKE, DW AKBASAK, A MORRISON, PF DEDRICK, RL OLDFIELD, EH AF BOBO, RH LASKE, DW AKBASAK, A MORRISON, PF DEDRICK, RL OLDFIELD, EH TI CONVECTION-ENHANCED DELIVERY OF MACROMOLECULES IN THE BRAIN SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE INTERSTITIAL INFUSION; BULK FLOW; AUTORADIOGRAPHY ID BULK FLOW; VENTRICULOCISTERNAL PERFUSION; INTERSTITIAL FLUID; RAT-BRAIN; CHEMOTHERAPY; TUMOR; EDEMA; METHOTREXATE; TRANSFERRIN; CISPLATIN AB For many compounds (neurotrophic factors, antibodies, growth factors, genetic vectors, enzymes) slow diffusion in the brain severely limits drug distribution and effect after direct drug administration into brain parenchyma. We investigated convection as a means to enhance the distribution of the large and small molecules In-111-labeled transferrin (In-111-Tf; M(r), 80,000) and [C-14]sucrose (M(r), 359) over centimeter distances by maintaining a pressure gradient during interstitial infusion into white matter to generate bulk flow through the brain interstitium. The volume of distribution (V-d) containing greater than or equal to 1% concentration of infusion solution increased linearly with the infusion volume (V-i) for In-111-Tf(V-d/V-i, 6:1) and [C-14]sucrose (V-d/V-i, 13:1). Twenty-four hours after infusion, the distribution of In-111-Tf was increased and more homogeneous, and penetration into gray matter had occurred. By using convection to supplement simple diffusion, enhanced distribution of large and small molecules can be obtained in the brain while achieving drug concentrations orders of magnitude greater than systemic levels. C1 NINCDS,SURG NEUROL BRANCH,BETHESDA,MD 20892. NIH,NATL CTR RES RESOURCES,DIV INTRAMURAL RES RESOURCES,BETHESDA,MD 20892. RI Kipke, Daryl/A-2167-2009 NR 44 TC 767 Z9 785 U1 0 U2 37 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 15 PY 1994 VL 91 IS 6 BP 2076 EP 2080 DI 10.1073/pnas.91.6.2076 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA NC043 UT WOS:A1994NC04300023 PM 8134351 ER PT J AU CAMPBELL, DB NASH, HA AF CAMPBELL, DB NASH, HA TI USE OF DROSOPHILA MUTANTS TO DISTINGUISH AMONG VOLATILE GENERAL-ANESTHETICS SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE HALOTHANE; ENFLURANE; ISOFLURANE; UNITARY HYPOTHESIS ID CAENORHABDITIS-ELEGANS; SENSITIVITY; HALOTHANE AB The way general anesthetics cause their clinically useful effects on the nervous system is not known. Since the principal determinant of the potency of these agents is their solubility in oil, the role of chemical structure in affecting anesthetic targets has been obscured. In this work, we use an intense beam of light (Tinklenberg, J. A., Segal, I. S., Tianzhi, G. and Maze, M. (1991) Ann. N.Y. Acad. Sci. 625, 532-539) to assess the effect of general anesthetics on the capacity of fruit flies to sense a noxious stimulus and respond to it. By examining the effect of halothane resistant (har) mutations on the potency of various volatile anesthetics in this assay, we establish similarities and differences between these agents that highlight the way chemical structure influences anesthetic action. In general, the potencies of anesthetics with different chemical structure are affected to different extents by one or more har mutations. However, three anesthetics of related structure (enflurane, isoflurane, and desflurane) show quantitatively indistinguishable alterations in potency in each of four genetic tests. These results not only identify important structural features of an esthetics but also place limits on the classical view that all anesthetics act at a common target. RP CAMPBELL, DB (reprint author), NIMH,MOLEC BIOL LAB,BETHESDA,MD 20892, USA. NR 18 TC 57 Z9 58 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 15 PY 1994 VL 91 IS 6 BP 2135 EP 2139 DI 10.1073/pnas.91.6.2135 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA NC043 UT WOS:A1994NC04300035 PM 8134360 ER PT J AU WANG, XW FORRESTER, K YEH, H FEITELSON, MA GU, JR HARRIS, CC AF WANG, XW FORRESTER, K YEH, H FEITELSON, MA GU, JR HARRIS, CC TI HEPATITIS-B-VIRUS-X PROTEIN INHIBITS P53 SEQUENCE-SPECIFIC DNA-BINDING, TRANSCRIPTIONAL ACTIVITY, AND ASSOCIATION WITH TRANSCRIPTION FACTOR ERCC3 SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID HEPATOCELLULAR-CARCINOMA; SV40-TRANSFORMED CELLS; CELLULAR PROTEIN; TUMOR-ANTIGEN; T-ANTIGEN; GENE; EXPRESSION; TRANSFORMATION; TRANSFECTION; PRODUCT AB Chronic active hepatitis caused by infection with hepatitis B virus, a DNA virus, is a major risk factor for human hepatocellular carcinoma. Since the oncogenicity of several DNA viruses is dependent on the interaction of their viral oncoproteins with cellular tumor-suppressor gene products, we investigated the interaction between hepatitis B virus X protein (HBX) and human wild-type p53 protein. HBX complexes with the wild-type p53 protein and inhibits its sequence-specific DNA binding in vitro. HBX expression also inhibits p53-mediated transcriptional activation in vivo and the in vitro association of p53 and ERCC3, a general transcription factor involved in nucleotide excision repair. Therefore, HBX may affect a wide range of p53 functions and contribute to the molecular pathogenesis of human hepatocellular carcinoma. C1 NCI,DIV CANC ETIOL,HUMAN CARCINOGENESIS LAB,BETHESDA,MD 20892. THOMAS JEFFERSON UNIV,JEFFERSON MED COLL,DEPT PATHOL & CELL BIOL,PHILADELPHIA,PA 19107. SHANGHAI CANC INST,DEPT MOLEC BIOL & BIOCHEM,SHANGHAI,PEOPLES R CHINA. RI Wang, Xin/B-6162-2009 NR 48 TC 589 Z9 617 U1 0 U2 5 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD MAR 15 PY 1994 VL 91 IS 6 BP 2230 EP 2234 DI 10.1073/pnas.91.6.2230 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA NC043 UT WOS:A1994NC04300055 PM 8134379 ER PT J AU HANSEN, JC WOLFFE, AP AF HANSEN, JC WOLFFE, AP TI A ROLE FOR HISTONES H2A/H2B IN CHROMATIN FOLDING AND TRANSCRIPTIONAL REPRESSION SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE NUCLEOSOME; H3/H4 TETRAMER; RNA POLYMERASE III; 5S RIBOSOMAL-RNA GENES; ANALYTICAL ULTRACENTRIFUGATION ID RNA POLYMERASE-II; MINICHROMOSOMES ASSEMBLED INVITRO; ONE H2A.H2B DIMER; NUCLEOSOMAL CORES; XENOPUS-LAEVIS; DNA; GENE; INITIATION; INVIVO; COMPLEX AB Histone octamers or histone H3/H4 tetramers were reconstituted onto either closed circular plasmids containing a single Xenopus 5S rRNA gene or a reiterated array of Lytechinus. 5S rRNA genes. All ''reconstitutes'' were found to undergo both Na+-dependent and Mg2+-dependent compaction, However, in each case, the compaction of nucleosomal templates containing H2A/H2B was much more extensive than compaction of templates containing only H3/H4 tetramers. inclusion of 5 mM MgCl2 in the transcription buffer increased the level of compaction of nucleosomal templates and led to a marked inhibition of both transcription initiation and elongation by RNA polymerase III. The inhibitory effect of Mg2+ was reduced significantly when DNA templates contained only H3/H4 tetramers, consistent with their lesser extent of Mg2+-dependent compaction. Thus, the removal of histones H2A/H2B from nucleosomal arrays enhances gene activity, in part because of decreased levels of chromatin folding. C1 NICHHD,MOLEC EMBRYOL LAB,BETHESDA,MD 20892. RP HANSEN, JC (reprint author), UNIV TEXAS,HLTH SCI CTR,DEPT BIOCHEM,7703 FLOYD CURL DR,SAN ANTONIO,TX 78284, USA. FU NIGMS NIH HHS [GM 45916] NR 52 TC 79 Z9 79 U1 1 U2 2 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 15 PY 1994 VL 91 IS 6 BP 2339 EP 2343 DI 10.1073/pnas.91.6.2339 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA NC043 UT WOS:A1994NC04300077 PM 8134397 ER PT J AU ELLENBERG, SS FOULKES, MA AF ELLENBERG, SS FOULKES, MA TI THE UTILITY OF LARGE, SIMPLE TRIALS IN THE EVALUATION OF AIDS TREATMENT STRATEGIES SO STATISTICS IN MEDICINE LA English DT Article; Proceedings Paper CT NIH Conference on Current Topics in Biostatistics CY JAN 25-26, 1992 CL BETHESDA, MD SP NIH ID IMMUNODEFICIENCY-VIRUS INFECTION; PLACEBO-CONTROLLED TRIAL; CLINICAL-TRIALS; HIV-INFECTION; DOUBLE-BLIND; ZIDOVUDINE; EFFICACY; MARKERS; ISSUES; DESIGN C1 NIAID,DIV AIDS,BETHESDA,MD 20892. NR 38 TC 3 Z9 3 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 15 PY 1994 VL 13 IS 5-7 BP 405 EP 415 DI 10.1002/sim.4780130505 PG 11 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 NE525 UT WOS:A1994NE52500004 PM 7912842 ER PT J AU SIMON, R THALL, PF ELLENBERG, SS AF SIMON, R THALL, PF ELLENBERG, SS TI NEW DESIGNS FOR THE SELECTION OF TREATMENTS TO BE TESTED IN RANDOMIZED CLINICAL-TRIALS SO STATISTICS IN MEDICINE LA English DT Article; Proceedings Paper CT NIH Conference on Current Topics in Biostatistics CY JAN 25-26, 1992 CL BETHESDA, MD SP NIH ID BINARY OUTCOMES; 2-STAGE DESIGN AB The most important aspect of phase III randomized clinical trials is the selection of the experimental treatments to be tested. Often this decision is based on uncontrolled phase II trials. Substantial statistical attention has been focused on the design of phase III trials and for simple phase II trials, which determine whether a new drug has any anti-disease activity. Much less statistical effort has been devoted to the design and analysis of phase II trials for screening active experimental treatments to determine whether they are sufficiently active, relative to standard treatments, to warrant the conduct of a large randomized phase III trial. This problem is particularly acute in the development of drug combinations where many regimens are possible. We review several designs for such screening trials which we have developed. C1 UNIV TEXAS,MD ANDERSON CANC CTR,DEPT BIOMATH,HOUSTON,TX 77030. US FDA,CTR BIOL EVALUAT & RES,DIV BIOSTAT & EPIDEMIOL,OFF ESTAB LICENSING & PROD SURVEILLANCE,ROCKVILLE,MD 20852. RP SIMON, R (reprint author), NCI,DIV CANC TREATMENT,BIOMETR RES BRANCH,6130 EXECUT BLVD,ROCKVILLE,MD 20852, USA. NR 16 TC 34 Z9 34 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 15 PY 1994 VL 13 IS 5-7 BP 417 EP 429 DI 10.1002/sim.4780130506 PG 13 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 NE525 UT WOS:A1994NE52500005 PM 8023026 ER PT J AU CHEN, TT SIMON, R AF CHEN, TT SIMON, R TI MULTIPLE DECISION PROCEDURE IN CLINICAL-TRIALS SO STATISTICS IN MEDICINE LA English DT Article; Proceedings Paper CT NIH Conference on Current Topics in Biostatistics CY JAN 25-26, 1992 CL BETHESDA, MD SP NIH AB In some multiple treatment arm clinical trials there is an order of preference for the treatments based on secondary considerations like toxicity or cost. In this paper, we consider the case where two or more treatments could have equal prior preference. This formulation includes the problem of comparing several equally preferred experimental treatments to one control, or the comparison of a combination with its components. Our decision procedures will guarantee a high selection probability for the correct treatment(s) when that selection is appropriate. We establish sample size requirements for our decision procedures which can be applied to clinical trials with normal, binomial, or right censored exponential endpoints. RP CHEN, TT (reprint author), NCI,BIOMETR RES BRANCH,EPN-739,BETHESDA,MD 20892, USA. NR 15 TC 0 Z9 0 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 15 PY 1994 VL 13 IS 5-7 BP 431 EP 446 DI 10.1002/sim.4780130507 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 NE525 UT WOS:A1994NE52500006 PM 8023027 ER PT J AU ALBERT, PS MCFARLAND, HF SMITH, ME FRANK, JA AF ALBERT, PS MCFARLAND, HF SMITH, ME FRANK, JA TI TIME-SERIES FOR MODELING COUNTS FROM A RELAPSING-REMITTING DISEASE - APPLICATION TO MODELING DISEASE-ACTIVITY IN MULTIPLE-SCLEROSIS SO STATISTICS IN MEDICINE LA English DT Article; Proceedings Paper CT NIH Conference on Current Topics in Biostatistics CY JAN 25-26, 1992 CL BETHESDA, MD SP NIH ID STATISTICAL-ANALYSIS; LIKELIHOOD; LESIONS AB Many chronic diseases are relapsing-remitting diseases, in which subjects alternate between periods with increasing and decreasing disease activity; relapsing-remitting multiple sclerosis is an example. This paper proposes two classes of models for sequences of counts observed from a relapsing-remitting disease. In the first, the relapsing-remitting nature of the data is modelled by a Poisson time series with a periodic trend in the mean. In this approach, the mean is expressed as a function of a sinusoial trend and past observations of the time series. An algorithm that uses GLIM is developed, and it results in maximum-likelihood estimation for the amplitude, frequency and autoregressive effects. In the second class of models, the relapsing-remitting behaviour is described by a Poisson time series in which changes in the man follow a lat Markov chain. An EM algorithm is developed for maximum-likelihood estimation for this model. The two models are illustrated and compared with data from a study evaluating the use of serial magnetic resonance imaging as a measure of disease activity in relapsing-remitting multiple sclerosis. C1 NINCDS,NEUROIMMUNOL BRANCH,BETHESDA,MD 20892. NIH,CTR CLIN,DEPT DIAGNOST RADIOL,BETHESDA,MD 20892. RP ALBERT, PS (reprint author), NINCDS,BIOMETRY & FIELD STUDIES BRANCH DIR,FED BLDG,ROOM 7C06,BETHESDA,MD 20892, USA. NR 20 TC 25 Z9 25 U1 1 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 15 PY 1994 VL 13 IS 5-7 BP 453 EP 466 DI 10.1002/sim.4780130509 PG 14 WC Mathematical & Computational Biology; Public, Environmental & Occupational Health; Medical Informatics; Medicine, Research & Experimental; Statistics & Probability SC Mathematical & Computational Biology; Public, Environmental & Occupational Health; Medical Informatics; Research & Experimental Medicine; Mathematics GA NE525 UT WOS:A1994NE52500008 PM 8023028 ER PT J AU FOLLMANN, D AF FOLLMANN, D TI MODELING TRANSITIONAL AND JOINT MARGINAL DISTRIBUTIONS IN REPEATED CATEGORICAL-DATA SO STATISTICS IN MEDICINE LA English DT Article; Proceedings Paper CT NIH Conference on Current Topics in Biostatistics CY JAN 25-26, 1992 CL BETHESDA, MD SP NIH ID OUTCOMES AB When a repeated measures endpoint classifies people into several categories, marginal and transitional models provide two distinct approaches for data analysis. Marginal models estimate the probabilities of being in different categories over time. Transitional models estimate the probability of changing between any two given states during follow-up visits. This paper develops transitional and marginal models and applies them to a clinical trial of treatments of opiate addiction. The primary outcome was the presence or absence of opiates in a thrice weekly urine test, administered for 17 weeks. Subjects frequently miss visits, however, and in effect respond in one of three ways to a visit: missing, opiates present or opiates absent. Thus we have three possible states. Our transitional model conditions on the current state and models the transition from state k to one of the other (0,...,K-1) states using a mutinomial legit model. This model generalizes previous work of Muenz and Rubinstein. Significant covariates in this model are predictive of state changes. Our marginal model views the state at each time point, rather than the transitions, as the primary response. Here we model the probability of being in state k with a multinomial legit model. Correlation within individuals over visits can be handled by applying the approach of Zeger and Liang or the bootstrap. Significant covariates in this model can include more 'global' summaries of a person such as extent of previous opiate use. Both marginal and transitional models are needed to provide a complete description of an individual's behaviour over time since global summaries might not affect transitions. Of particular substantive interest is how the opiate treatments affect both the marginal and transition probabilities. RP FOLLMANN, D (reprint author), NHLBI,BIOSTAT RES BRANCH,FED BLD,ROOM 2A11,BETHESDA,MD 20892, USA. NR 16 TC 3 Z9 3 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 15 PY 1994 VL 13 IS 5-7 BP 467 EP 477 DI 10.1002/sim.4780130510 PG 11 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 NE525 UT WOS:A1994NE52500009 PM 8023029 ER PT J AU MARK, SD GAIL, MH AF MARK, SD GAIL, MH TI A COMPARISON OF LIKELIHOOD-BASED AND MARGINAL ESTIMATING EQUATION METHODS FOR ANALYZING REPEATED ORDERED CATEGORICAL RESPONSES WITH MISSING DATA - APPLICATION TO AN INTERVENTION TRIAL OF VITAMIN PROPHYLAXIS FOR ESOPHAGEAL DYSPLASIA SO STATISTICS IN MEDICINE LA English DT Article; Proceedings Paper CT NIH Conference on Current Topics in Biostatistics CY JAN 25-26, 1992 CL BETHESDA, MD SP NIH ID LONGITUDINAL DATA; OUTCOMES; MODELS AB The purpose of this research was to develop appropriate methods for analysing repeated ordinal categorical data that arose in an intervention trial to prevent oesophageal cancer. The measured response was the degree of oesophageal dysplasia at 2.5 and 6 years after randomization. An important feature was that some response measurements were missing, and the missingness was not 'completely at random' (MCAR). We show that standard likelihood-based methods and standard methods based on marginal estimating equations yield biased results, and we propose adaptations to both these approaches that yield valid inference under the weaker 'missing at random' (MAR) assumption. On the basis of efficiency calculations, simulation studies of finite sample properties, ease of computation, and flexibility for testing and exploring a range of treatment models, we recommend the adapted likelihood-based approach for problems of this type, in which there are abundant data for estimating parameters. RP MARK, SD (reprint author), NCI,6130 EXECUT BLVD,EPN-403,ROCKVILLE,MD 20892, USA. NR 19 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 15 PY 1994 VL 13 IS 5-7 BP 479 EP 493 DI 10.1002/sim.4780130511 PG 15 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 NE525 UT WOS:A1994NE52500010 PM 8023030 ER PT J AU GRAUBARD, BI KORN, EL AF GRAUBARD, BI KORN, EL TI REGRESSION-ANALYSIS WITH CLUSTERED DATA SO STATISTICS IN MEDICINE LA English DT Article; Proceedings Paper CT NIH Conference on Current Topics in Biostatistics CY JAN 25-26, 1992 CL BETHESDA, MD SP NIH ID LONGITUDINAL DATA; BLOOD-LEAD; MODELS; COVARIANCE; ESTIMATORS; OUTCOMES AB Clustered data are found in many different types of studies, for example, studies involving repeated measures, inter-rater agreement studies, household surveys, crossover designs and community randomized trials. Analyses based on population average and cluster specific models are commonly used for estimating treatment (exposure) effects with clustered data. This paper discusses conditions when one or both types of models are appropriate for estimating causal effects and when there is agreement between population average and cluster specific analyses. Applications of survey sampling methods to the robust estimation of standard errors of estimated treatment parameters are discussed. RP GRAUBARD, BI (reprint author), NCI,BETHESDA,MD 20892, USA. NR 37 TC 39 Z9 40 U1 2 U2 5 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 15 PY 1994 VL 13 IS 5-7 BP 509 EP 522 DI 10.1002/sim.4780130514 PG 14 WC Mathematical & Computational Biology; Public, Environmental & Occupational Health; Medical Informatics; Medicine, Research & Experimental; Statistics & Probability SC Mathematical & Computational Biology; Public, Environmental & Occupational Health; Medical Informatics; Research & Experimental Medicine; Mathematics GA NE525 UT WOS:A1994NE52500013 PM 8023032 ER PT J AU WACLAWIW, MA LIANG, KY AF WACLAWIW, MA LIANG, KY TI EMPIRICAL BAYES ESTIMATION AND INFERENCE FOR THE RANDOM EFFECTS MODEL WITH BINARY RESPONSE SO STATISTICS IN MEDICINE LA English DT Article; Proceedings Paper CT NIH Conference on Current Topics in Biostatistics CY JAN 25-26, 1992 CL BETHESDA, MD SP NIH ID GENERALIZED LINEAR-MODELS; LONGITUDINAL DATA; CONFIDENCE-INTERVALS; LIMITING RISK; PARAMETERS AB Waclawiw and Liang introduced an estimating function-based approach for estimating the parameters of the classical two-stage random effects model for longitudinal data. In the present paper, the authors conduct a case study of the general approach for the binary response setting, where the fully specified parametric two-stage model with fixed and univariate random effects has an analytically intractable likelihood. With successful convergence of the algorithm, the authors propose a fully parametric bootstrapping method for deriving empirical Bayes confidence intervals for all model parameters. The bootstrapping approach is a blend of the estimating function technique with the developments of Laird and Louis. The estimating function approach to estimation and inference provides a general framework for the analytis of a wide variety of medical data, including the setting of small and varying numbers of discrete repeated observations. An application of the methdology to the analysis of binary responses in a crossover clinical trial is presented. C1 JOHNS HOPKINS UNIV,DEPT BIOSTAT,BALTIMORE,MD 21205. RP WACLAWIW, MA (reprint author), NHLBI,BIOSTAT RES BRANCH,FED BLDG,ROOM 2A11,BETHESDA,MD 20892, USA. RI Liang, Kung-Yee/F-8299-2011 FU NIGMS NIH HHS [GM39261] NR 35 TC 5 Z9 5 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 15 PY 1994 VL 13 IS 5-7 BP 541 EP 551 DI 10.1002/sim.4780130516 PG 11 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 NE525 UT WOS:A1994NE52500015 PM 8023034 ER PT J AU KAFADAR, K PROROK, PC AF KAFADAR, K PROROK, PC TI A DATA-ANALYTIC APPROACH FOR ESTIMATING LEAD TIME AND SCREENING BENEFIT BASED ON SURVIVAL CURVES IN RANDOMIZED CANCER SCREENING TRIALS SO STATISTICS IN MEDICINE LA English DT Article; Proceedings Paper CT NIH Conference on Current Topics in Biostatistics CY JAN 25-26, 1992 CL BETHESDA, MD SP NIH ID BREAST-CANCER; DISEASE AB Screening tests are used frequently for control of diseases such as cancer. The increased survival time of screen-detected cases over those that are detected clinically may be due in part to 'lead time', or the length of time by which the disease is diagnosed earlier by screening in the presence or absence of any real extension in survival time. A realistic evaluation of screening needs to assess the true benefit of screening; that is, the length of time by which survival has been extended, beyond merely the time of the advanced diagnosis. The comparison of survival measured from time of entry between cases in a screening arm and in a control arm in randomized studies avoids the lead time bias. If the effects of average lead time and average benefit on survival are additive, these effects can be estimated by recognizing that (a) the difference in survival curves since time of diagnosis confounds benefit and lead time, but (b) the difference in survival curves since time of start of study involves benefit only. The method is evaluated on simulated data for its accuracy and may be used on data from randomized studies. RP KAFADAR, K (reprint author), NCI,BIOMETRY BRANCH,BETHESDA,MD 20892, USA. NR 16 TC 19 Z9 19 U1 0 U2 3 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 15 PY 1994 VL 13 IS 5-7 BP 569 EP 586 DI 10.1002/sim.4780130519 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 NE525 UT WOS:A1994NE52500018 PM 8023036 ER PT J AU PEARSON, JD MORRELL, CH LANDIS, PK CARTER, HB BRANT, LJ AF PEARSON, JD MORRELL, CH LANDIS, PK CARTER, HB BRANT, LJ TI MIXED-EFFECTS REGRESSION-MODELS FOR STUDYING THE NATURAL-HISTORY OF PROSTATE DISEASE SO STATISTICS IN MEDICINE LA English DT Article; Proceedings Paper CT NIH Conference on Current Topics in Biostatistics CY JAN 25-26, 1992 CL BETHESDA, MD SP NIH ID RADICAL PROSTATECTOMY; LONGITUDINAL DATA; ANTIGEN; CANCER; ADENOCARCINOMA; HYPERPLASIA; DIAGNOSIS; SERUM; MEN AB Although prostate cancer and benign prostatic hyperplasia are major health problems in U.S. men, little is known about the early stages of the natural history of prostate disease. A molecular biomarker called prostate specific antigen (PSA), together with a unique longitudinal bank of frozen serum, now allows a historic prospective study of changes in PSA levels for decades prior to the diagnosis of prostate disease. Linear mixed-effects regression models were used to test whether rates of change in PSA were different in men with and without prostate disease. In addition, since the prostate cancer cases developed their tumours at different (and unknown) times during their periods of follow-up, a piece-wise non-linear mixed-effects regression model was used to estimate the time when rapid increases in PSA were first observable beyond the background level of PSA change. These methods have a wide range of applications in biomedical research utilizing repeated measures data such as pharmacokinetic studies, crossover trials, growth and development studies, aging studies, and disease detection. C1 LOYOLA COLL,DEPT MAT SCI,BALTIMORE,MD 21210. JOHNS HOPKINS UNIV,JOHNS HOPKINS HOSP,SCH MED,JAMES BUCHANAN BRADY UROL INST,DEPT UROL,BALTIMORE,MD 21205. RP PEARSON, JD (reprint author), NIA,GERONTOL RES CTR,LONGITUDINAL STUDIES BRANCH,4940 EASTERN AVE,BALTIMORE,MD 21224, USA. NR 20 TC 49 Z9 49 U1 1 U2 4 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 15 PY 1994 VL 13 IS 5-7 BP 587 EP 601 DI 10.1002/sim.4780130520 PG 15 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 NE525 UT WOS:A1994NE52500019 PM 7517570 ER PT J AU BAKER, SG AF BAKER, SG TI COMPOSITE LINEAR-MODELS FOR INCOMPLETE MULTINOMIAL DATA SO STATISTICS IN MEDICINE LA English DT Article; Proceedings Paper CT NIH Conference on Current Topics in Biostatistics CY JAN 25-26, 1992 CL BETHESDA, MD SP NIH ID MAXIMUM-LIKELIHOOD; EM ALGORITHM; CATEGORICAL VARIABLES; MARGINAL HOMOGENEITY; REGRESSION; NONRESPONSE; TABLES AB A composite linear model (CLM) is a matrix model for incomplete multinomial data. A CLM provides a unified approach for maximum likelihood inference which is applicable to a wide variety of problems involving incomplete multinomial data. By formulating a model as a CLM, one can simplify computation of maximum likelihood estimates and asymptotic standard errors. As an example, we use CLM to test marginal homogeneity for ordered categories, subject to both ignorable and non-ignorable missing-data mechanisms. RP BAKER, SG (reprint author), NCI,DIV CANC PREVENT & CONTROL,BIOMETRY BRANCH,EPN 344,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 26 TC 25 Z9 25 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 15 PY 1994 VL 13 IS 5-7 BP 609 EP 622 DI 10.1002/sim.4780130522 PG 14 WC Mathematical & Computational Biology; Public, Environmental & Occupational Health; Medical Informatics; Medicine, Research & Experimental; Statistics & Probability SC Mathematical & Computational Biology; Public, Environmental & Occupational Health; Medical Informatics; Research & Experimental Medicine; Mathematics GA NE525 UT WOS:A1994NE52500021 PM 8023037 ER PT J AU WACHOLDER, S CARROLL, RJ PEE, D GAIL, MH AF WACHOLDER, S CARROLL, RJ PEE, D GAIL, MH TI THE PARTIAL QUESTIONNAIRE DESIGN FOR CASE-CONTROL STUDIES SO STATISTICS IN MEDICINE LA English DT Article; Proceedings Paper CT NIH Conference on Current Topics in Biostatistics CY JAN 25-26, 1992 CL BETHESDA, MD SP NIH ID 2-STAGE CASE-CONTROL; LOGISTIC-REGRESSION; DISEASE; SMOKING; EXPOSURE; CANCER AB We propose an alternative to a long questionnaire that may increase quality while reducing the cost and effort of participants and researchers. In the 'partial questionnaire design', information about the exposure of interest is obtained from all subjects, while zero, one, or more disjoint subsets of questions about possible confounders are asked to randomly selected subgroups. The proposed analyses exploit the fact that the uncollected data can be considered to be missing at random. We show that it is possible to obtain high efficiency for estimating the effect of exposure of interest, adjusted for confounding, while substantially shortening average questionnaire length. C1 TEXAS A&M UNIV,DEPT STAT,COLLEGE STN,TX 77842. INFORMAT MANAGEMENT SYST,ROCKVILLE,MD 20852. RP WACHOLDER, S (reprint author), NCI,BIOSTAT BRANCH,EPIDEMIOL METHODS SECT,6130 EXECUT BLVD,EPN 403,ROCKVILLE,MD 20852, USA. NR 25 TC 23 Z9 23 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 15 PY 1994 VL 13 IS 5-7 BP 623 EP 634 DI 10.1002/sim.4780130523 PG 12 WC Mathematical & Computational Biology; Public, Environmental & Occupational Health; Medical Informatics; Medicine, Research & Experimental; Statistics & Probability SC Mathematical & Computational Biology; Public, Environmental & Occupational Health; Medical Informatics; Research & Experimental Medicine; Mathematics GA NE525 UT WOS:A1994NE52500022 PM 8023038 ER PT J AU WU, MC HUNSBERGER, S ZUCKER, D AF WU, MC HUNSBERGER, S ZUCKER, D TI TESTING FOR DIFFERENCES IN CHANGES IN THE PRESENCE OF CENSORING - PARAMETRIC AND NONPARAMETRIC METHODS SO STATISTICS IN MEDICINE LA English DT Article; Proceedings Paper CT NIH Conference on Current Topics in Biostatistics CY JAN 25-26, 1992 CL BETHESDA, MD SP NIH ID MODELS AB Some commonly used parametric and non-parametric methods for analysing repeated measures with incomplete observations are briefly reviewed. The performances of these methods in the presence of completely random, as well as informative censoring are compared in simulated experiments generated under the linear random effects model with parameter values derived from realistic examples. The effects of some moderate model deviations are also compared. The results indicate that in the presence of informative censoring, the usual parametric and nonparametric methods derived under the assumption of random censoring could either suffer severe loss of power or provide false positive results. The conditional linear model for informative censoring when used in conjunction with the bootstrap variance estimation procedure performed well under both random and informative censoring mechanisms. The non-parametric procedure obtained by ranking the individual summary statistics, although not as efficient as the conditional linear model with robust variance, also performed relatively well in most situations. Therefore, in situations in which informative censoring is likely to occur it is important to select the proper method of analysis to test for the informativeness of censoring and to account for its effects. RP WU, MC (reprint author), NHLBI,7550 WISCONSIN AVE,ROOM 2A11,BETHESDA,MD 20892, USA. NR 12 TC 13 Z9 13 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 15 PY 1994 VL 13 IS 5-7 BP 635 EP 646 DI 10.1002/sim.4780130524 PG 12 WC Mathematical & Computational Biology; Public, Environmental & Occupational Health; Medical Informatics; Medicine, Research & Experimental; Statistics & Probability SC Mathematical & Computational Biology; Public, Environmental & Occupational Health; Medical Informatics; Research & Experimental Medicine; Mathematics GA NE525 UT WOS:A1994NE52500023 PM 8023039 ER PT J AU BENICHOU, J WACHOLDER, S AF BENICHOU, J WACHOLDER, S TI A COMPARISON OF 3 APPROACHES TO ESTIMATE EXPOSURE-SPECIFIC INCIDENCE RATES FROM POPULATION-BASED CASE-CONTROL DATA SO STATISTICS IN MEDICINE LA English DT Article; Proceedings Paper CT NIH Conference on Current Topics in Biostatistics CY JAN 25-26, 1992 CL BETHESDA, MD SP NIH ID REGRESSION-MODELS; BREAST-CANCER; LINEAR-MODELS AB In population-based case-control studies, an attempt is made to identify all incident cases diagnosed in a specified population during a fixed time interval. Assuming that this goal is met allows one to obtain measures of risk other than relative risks. In this paper, we describe three approaches to estimate exposure-specific incidence rates. Approach 1 relies on estimating crude incidence rates of the disease in strata defined, for instance, by age and geographic area, and combining them with relative risk estimates from the case-control data. In approaches 2 and 3, baseline incidence rates and relative risks are estimated jointly. Approach 2 is based on a pseudo-likelihood, while, in approach 3, the problem is regarded as a missing data problem and a full likelihood is maximized. We applied these three approaches to a study of bladder cancer. Our three sets of estimates of exposure-specific incidence rates were in close agreement, while there appeared to be greater precision with approaches 2 and 3. RP BENICHOU, J (reprint author), NCI,BIOSTAT BRANCH,6130 EXECUT BLVD,EPN-403,ROCKVILLE,MD 20892, USA. NR 26 TC 14 Z9 14 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 15 PY 1994 VL 13 IS 5-7 BP 651 EP 661 DI 10.1002/sim.4780130526 PG 11 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 NE525 UT WOS:A1994NE52500025 PM 8023040 ER PT J AU HUNSBERGER, S SORLIE, P GELLER, NL AF HUNSBERGER, S SORLIE, P GELLER, NL TI STOCHASTIC CURTAILING AND CONDITIONAL POWER IN MATCHED CASE-CONTROL STUDIES SO STATISTICS IN MEDICINE LA English DT Article; Proceedings Paper CT NIH Conference on Current Topics in Biostatistics CY JAN 25-26, 1992 CL BETHESDA, MD SP NIH AB New methodology for early stopping of observational epidemiologic studies is developed. To indicate the likelihood of a positive result at the end of a study, the conditional power (CP) is calculated using an approach similar to that of Halperin et al. Given the current result, the conditional probability of a positive result for the entire study is determined. An expression relating the new approach to an approach given by Lan and Wittes is derived. As an example, the CP is calculated based on information from the first third of a matched case-control study embedded in an epidemiological study. C1 NHLBI,DIV EPIDEMIOL & CLIN APPLICAT,BIOMETRY & FIELD STUDIES BRANCH DIR,BETHESDA,MD 20892. RP HUNSBERGER, S (reprint author), NHLBI,DIV EPIDEMIOL & CLIN APPLICAT,BIOSTAT RES BRANCH,BETHESDA,MD 20892, USA. NR 6 TC 8 Z9 8 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 15 PY 1994 VL 13 IS 5-7 BP 663 EP 670 DI 10.1002/sim.4780130527 PG 8 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 NE525 UT WOS:A1994NE52500026 PM 8023041 ER PT J AU WEINBERG, CR BAIRD, DD WILCOX, AJ AF WEINBERG, CR BAIRD, DD WILCOX, AJ TI SOURCES OF BIAS IN STUDIES OF TIME TO PREGNANCY SO STATISTICS IN MEDICINE LA English DT Article; Proceedings Paper CT NIH Conference on Current Topics in Biostatistics CY JAN 25-26, 1992 CL BETHESDA, MD SP NIH ID FECUNDABILITY; REGRESSION; WOMEN AB Among sexually active:couples who are not using contraception, there is considerable heterogeneity in fertility, even among those who eventually achieve pregnancy. The number of menstrual cycles required, measured in integer time, is greatly overdispersed compared to the geometric, suggesting that the per cycle probability of conception varies considerably among couples. Some of this variability may reflect the effect of reproductive toxicants on fertility, and studies of time to pregnancy can be useful in identifying such toxic effects. We describe models for analysing time-to-pregnancy data, and discuss seven sources of bias that can lead the reproductive epidemiologist to spurious conclusions. Certain analytic and design strategies can help protect against some of the pitfalls, RP WEINBERG, CR (reprint author), NIEHS,MD A3-03,PO 12233,RES TRIANGLE PK,NC 27709, USA. OI Wilcox, Allen/0000-0002-3376-1311; Baird, Donna/0000-0002-5544-2653 NR 25 TC 146 Z9 148 U1 2 U2 6 PU JOHN WILEY & SONS LTD PI W SUSSEX PA BAFFINS LANE CHICHESTER, W SUSSEX, ENGLAND PO19 1UD SN 0277-6715 J9 STAT MED JI Stat. Med. PD MAR 15 PY 1994 VL 13 IS 5-7 BP 671 EP 681 DI 10.1002/sim.4780130528 PG 11 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 NE525 UT WOS:A1994NE52500027 PM 8023042 ER PT J AU DINSE, GE AF DINSE, GE TI A COMPARISON OF TUMOR-INCIDENCE ANALYSES APPLICABLE IN SINGLE-SACRIFICE ANIMAL-EXPERIMENTS SO STATISTICS IN MEDICINE LA English DT Article; Proceedings Paper CT NIH Conference on Current Topics in Biostatistics CY JAN 25-26, 1992 CL BETHESDA, MD SP NIH ID CARCINOGENICITY EXPERIMENTS; NONPARAMETRIC-ESTIMATION; SURVIVAL EXPERIMENTS; TUMORIGENICITY DATA; TESTS; DEATH; ONSET; RATES; MORTALITY; TREND AB Monte Carlo methods are used to evaluate the operating characteristics of several trend tests for comparing incidence rates of occult tumours. The candidate tests are applicable in long-term animal experiments that have just one sacrifice time and no information on cause of death. When survival decreases with dose and the tumour is lethal, the tests that do not adjust for survival or that assume tumours are non-lethal behave conservatively, whereas the test that assumes tumours are rapidly lethal rejects the hypothesis of equal incidence rates too frequently. The only test which consistently operates at the correct level is one that specifies a constant difference between the death rates for animals with and without the tumour. Surprisingly, the test that specifies a constant ratio of these death rates often is conservative. Finally, a test based on a simple modification of the unadjusted test, which accounts for differential mortality by scaling down the size of the risk set, performs reasonably well in many cases. Among the tests that operate at the proper level, the constant risk difference test consistently exhibits high power across a wide range of situations. RP DINSE, GE (reprint author), NIEHS,STAT & BIOMATH BRANCH,POB 1233,A3-03,RES TRIANGLE PK,NC 27709, USA. NR 36 TC 20 Z9 23 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 15 PY 1994 VL 13 IS 5-7 BP 689 EP 708 DI 10.1002/sim.4780130530 PG 20 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 NE525 UT WOS:A1994NE52500029 PM 8023043 ER PT J AU FREEDMAN, LS AF FREEDMAN, LS TI METAANALYSIS OF ANIMAL-EXPERIMENTS ON DIETARY-FAT INTAKE AND MAMMARY-TUMORS SO STATISTICS IN MEDICINE LA English DT Article; Proceedings Paper CT NIH Conference on Current Topics in Biostatistics CY JAN 25-26, 1992 CL BETHESDA, MD SP NIH ID CLINICAL-TRIALS; RANDOMIZED TRIALS; OVERVIEWS AB I describe a meta-analysis of animal experiments designed to investigate the effects of dietary fat intake upon mammary tumour development. These experiments involve one or more of three types of dietary manipulation: (i) varying the proportion of fat in the diet; (ii) varying the source of fat; and (iii) varying the amount of energy consumed. I use linear logistic regression models to investigate questions about the relative effects of fat and total energy intake upon mammary tumour development and about the effects of different sources of fat. The results of these analyses are presented and discussed. The regression models employed are characterized by the inclusion of an experiment 'effect' to ensure that estimated nutrient effects are based only upon within-experiment comparisons. Homogeneity of nutrient effects across experiments is assumed. The method differs from the usual meta-analysis of clinical trials in that the nutrient effects may not be estimable from each individual experiment, but only from combinations of experiments. This poses problems for the development of a model that allows heterogeneity of nutrient effects. RP FREEDMAN, LS (reprint author), NCI,DIV CANC PREVENT & CONTROL,BIOMETRY BRANCH,EXECUT PLAZA N,ROOM 344,BETHESDA,MD 20892, USA. NR 17 TC 8 Z9 8 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 15 PY 1994 VL 13 IS 5-7 BP 709 EP 718 DI 10.1002/sim.4780130531 PG 10 WC Mathematical & Computational Biology; Public, Environmental & Occupational Health; Medical Informatics; Medicine, Research & Experimental; Statistics & Probability SC Mathematical & Computational Biology; Public, Environmental & Occupational Health; Medical Informatics; Research & Experimental Medicine; Mathematics GA NE525 UT WOS:A1994NE52500030 PM 8023044 ER PT J AU KOUTSOUKOS, AD RUBINSTEIN, LV FARAGGI, D SIMON, RM KALYANDRUG, S WEINSTEIN, JN KOHN, KW PAULL, KD AF KOUTSOUKOS, AD RUBINSTEIN, LV FARAGGI, D SIMON, RM KALYANDRUG, S WEINSTEIN, JN KOHN, KW PAULL, KD TI DISCRIMINATION TECHNIQUES APPLIED TO THE NCI IN-VITRO ANTITUMOR DRUG SCREEN - PREDICTING BIOCHEMICAL-MECHANISM OF ACTION SO STATISTICS IN MEDICINE LA English DT Article; Proceedings Paper CT NIH Conference on Current Topics in Biostatistics CY JAN 25-26, 1992 CL BETHESDA, MD SP NIH AB The National Cancer Institute currently tests approximately 400 compounds per week against a panel of human tumour cell lines in order to identify potential anti-cancer drugs. We describe several approaches, based on these in vitro data, to the problem of identifying the primary biochemical mechanism of action of a compound. Using linear and non-parametric discriminant procedures and cross-validation, we find that accurate identification of the mechanism of action is achieved for approximately 90 per cent of a diverse collection of 141 known compounds, representing six different mechanistic categories. We demonstrate that two-dimensional graphical displays of the compounds in terms of the initial three principal components (of the original data) result in suggestive visual clustering according to mechanism of action. Finally, we compare the classification accuracy of the statistical discrimination procedures with the accuracy obtained from a neural network approach and, for our example, we find that the results obtained from the various approaches are similar. C1 CAPITAL TECHNOL INFORMAT SERV,ROCKVILLE,MD 20850. NCI,INFORMAT TECHNOL BRANCH,BETHESDA,MD 20892. NCI,MOLEC PHARMACOL LAB,BETHESDA,MD 20892. RP KOUTSOUKOS, AD (reprint author), NCI,BIOMETR RES BRANCH,BETHESDA,MD 20892, USA. NR 13 TC 39 Z9 39 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 15 PY 1994 VL 13 IS 5-7 BP 719 EP 730 DI 10.1002/sim.4780130532 PG 12 WC Mathematical & Computational Biology; Public, Environmental & Occupational Health; Medical Informatics; Medicine, Research & Experimental; Statistics & Probability SC Mathematical & Computational Biology; Public, Environmental & Occupational Health; Medical Informatics; Research & Experimental Medicine; Mathematics GA NE525 UT WOS:A1994NE52500031 PM 8023045 ER PT J AU BARTKO, JJ AF BARTKO, JJ TI MEASURES OF AGREEMENT - A SINGLE PROCEDURE SO STATISTICS IN MEDICINE LA English DT Article; Proceedings Paper CT NIH Conference on Current Topics in Biostatistics CY JAN 25-26, 1992 CL BETHESDA, MD SP NIH ID CORRELATION-COEFFICIENT; RELIABILITY AB An assessment of measurement agreement made by devices, laboratories, or raters is important in medical practice and research. The setting in which each randomly selected subject is rated by the same two raters raises assorted questions regarding rater agreement. The intraclass correlation coefficient (ICC) is one measure of reliability. The paired t-test can be used to evaluate the overall ratings or bias of the two raters, while their variances can be assessed with Pitman's test. The Bradley-Blackwood test can be used for a simultaneous test of their means and variances. A single method that provides results for these approaches is proposed and the bivariate confidence ellipse is suggested to provide boundaries for dispersion. RP BARTKO, JJ (reprint author), NIMH,DIV EPIDEMIOL & SERV RES,NIH CAMPUS,BLDG 10,ROOM 3N-204,BETHESDA,MD 20892, USA. NR 13 TC 79 Z9 84 U1 0 U2 3 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 15 PY 1994 VL 13 IS 5-7 BP 737 EP 745 DI 10.1002/sim.4780130534 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 NE525 UT WOS:A1994NE52500033 PM 8023046 ER PT J AU PODGOR, MJ GASTWIRTH, JL AF PODGOR, MJ GASTWIRTH, JL TI ON NONPARAMETRIC AND GENERALIZED TESTS FOR THE 2-SAMPLE PROBLEM WITH LOCATION AND SCALE CHANGE ALTERNATIVES SO STATISTICS IN MEDICINE LA English DT Article; Proceedings Paper CT NIH Conference on Current Topics in Biostatistics CY JAN 25-26, 1992 CL BETHESDA, MD SP NIH ID RANK-SUM STATISTICS; MEDICAL-RESEARCH AB Various tests have been proposed for the two-sample problem when the alternative is more general than a simple shift in location: non-parametric tests; O'Brien's generalized t and rank sum tests; and other tests related to the t. We show that the generalized tests are directly related to non-parametric tests proposed by Lepage. As a result, we obtain a wider, more flexible class of O'Brien-type procedures which inherit the level robustness property of non-parametric tests. We have also computed the tests' empirical sizes and powers under several models. The non-parametric procedures and the related O'Brien-type tests are valid and yield good power in the settings investigated. They are preferable to the t-test and related procedures whose type I errors differ noticeably from nominal size for skewed and long-tailed distributions. C1 GEORGE WASHINGTON UNIV,DEPT STAT,WASHINGTON,DC 20052. RP PODGOR, MJ (reprint author), NEI,DIV BIOMETRY & EPIDEMIOL,BLDG 31,ROOM 6A52,BETHESDA,MD 20892, USA. NR 33 TC 21 Z9 22 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 15 PY 1994 VL 13 IS 5-7 BP 747 EP 758 DI 10.1002/sim.4780130535 PG 12 WC Mathematical & Computational Biology; Public, Environmental & Occupational Health; Medical Informatics; Medicine, Research & Experimental; Statistics & Probability SC Mathematical & Computational Biology; Public, Environmental & Occupational Health; Medical Informatics; Research & Experimental Medicine; Mathematics GA NE525 UT WOS:A1994NE52500034 PM 8023047 ER PT J AU ZERBE, GO WU, MC ZUCKER, DM AF ZERBE, GO WU, MC ZUCKER, DM TI STUDYING THE RELATIONSHIP BETWEEN CHANGE AND INITIAL-VALUE IN LONGITUDINAL-STUDIES SO STATISTICS IN MEDICINE LA English DT Article; Proceedings Paper CT NIH Conference on Current Topics in Biostatistics CY JAN 25-26, 1992 CL BETHESDA, MD SP NIH ID MODELS AB Blomqvist's problem of studying the relationship between change and initial value in a linear growth curve setting is reformulated from a random effects model perspective. First, a maximum likelihood estimate of the between-individual covariance matrix for a simple linear regression model with stochastic parameters is obtained via an EM algorithm as discussed by Laird and Ware, Second, the regression coefficient of the individual-specific slopes on the individual-specific intercepts is estimated as a ratio of elements of the between-individual covariance matrix as discussed by Zucker et al. Then a Fieller's type confidence interval for this ratio is proposed. Discussion is facilitated by recognizing the Laird-Ware model as a special case of a more general model discussed by Hocking. C1 NHLBI,BIOSTAT RES BRANCH,BETHESDA,MD 20892. RP ZERBE, GO (reprint author), UNIV COLORADO,HLTH SCI CTR,DIV BIOMETR,DENVER,CO 80262, USA. NR 12 TC 6 Z9 6 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 15 PY 1994 VL 13 IS 5-7 BP 759 EP 768 DI 10.1002/sim.4780130536 PG 10 WC Mathematical & Computational Biology; Public, Environmental & Occupational Health; Medical Informatics; Medicine, Research & Experimental; Statistics & Probability SC Mathematical & Computational Biology; Public, Environmental & Occupational Health; Medical Informatics; Research & Experimental Medicine; Mathematics GA NE525 UT WOS:A1994NE52500035 PM 8023048 ER PT J AU KINGMAN, A ZION, G AF KINGMAN, A ZION, G TI SOME POWER CONSIDERATIONS WHEN DECIDING TO USE TRANSFORMATIONS SO STATISTICS IN MEDICINE LA English DT Article; Proceedings Paper CT NIH Conference on Current Topics in Biostatistics CY JAN 25-26, 1992 CL BETHESDA, MD SP NIH ID T-TEST; ROBUSTNESS; VARIANCE; SYMMETRY AB Conventional wisdom suggests that for small data sets having substantial skew, one should attempt to determine the correct distributional form, if possible, and apply statistical methods appropriate for that distribution. Transformations such as the log or square root are often used. If an appropriate distributional form cannot be determined, a distribution-free procedure such as a rank transformation or a randomization test procedure can be used. To better appreciate the effect of such alternatives on both the type I error and power of detecting differences between treatment groups, simulation studies were conducted for responses having specific gamma G(r, theta) and log-normal In(M, V) distributions. The gamma and log-normal distributions were selected so that they had the same first two moments. A simple two group design was assumed. The reference group always had an average disease level mu = 3.0 (mu = r theta for gamma, mu = M for log-normal), and the treatment group always had means whose reductions ranged from 0 per cent to 50 per cent. The effect of distributional type and the degree of skewness was investigated by varying the population parameter values. Six statistical test procedures were compared for the gamma distributions. All test procedures were robust relative to the type I error. The UMP test based on a ratio of sample means produced the greatest power for all combinations of n, r and R(T) The power losses associated with the randomization test, the t-test on original scale, and the t-test on the square root scale were very small, (3 per cent to 6 per cent in absolute value) for n = 10 and 15, and less than 2 per cent for group sizes of 25 or more. The power loss associated with the t-test on the log scale was much larger, ranging from 5 per cent to 10 per cent smaller power than the t-test on original scale. The Wilcoxon rank test produced similar results to that of the LOG t-test for small samples. The power for the shifted LOG (X + c) test increased monotonically to the asymptotic value of the ORIG t-test. The same five test procedures based on differences in sample means were then compared for the corresponding log-normal distributions. The UMP test, that is, LOG(X), produced the highest power. There was very little power lost for the SORT t-test. The loss in power varied between 2 per cent and 5 per cent for the RANK test. The RANK test performed considerably better than the t-test on the original scale. In contrast to the results for the gamma the power for the shifted LOG (X + c) test had its maximum for c = 0, and decreased monotonically to the asymptotic value of the ORIG t-test. The results suggest that statistical inferences can be highly dependent on the distributional form and the scale of measurement of the response used in the statistical analysis. RP KINGMAN, A (reprint author), NIDR,EPIDEMIOL & ORAL DIS PREVENT PROGRAM,BETHESDA,MD 20892, USA. NR 25 TC 12 Z9 12 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 15 PY 1994 VL 13 IS 5-7 BP 769 EP 783 DI 10.1002/sim.4780130537 PG 15 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 NE525 UT WOS:A1994NE52500036 PM 8023049 ER PT J AU YU, KF AF YU, KF TI TRUNCATING SAMPLE WEIGHTS REDUCES VARIANCE SO STATISTICS & PROBABILITY LETTERS LA English DT Article DE TRUNCATION; SAMPLE WEIGHTS; VARIANCE AB A simple proof is given to confirm the intuitive notion that truncation of extreme sample weights in a complex design sample survey for the estimation of the mean reduces the variance. C1 NIH,BETHESDA,MD 20892. NR 4 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0167-7152 J9 STAT PROBABIL LETT JI Stat. Probab. Lett. PD MAR 15 PY 1994 VL 19 IS 4 BP 267 EP 269 DI 10.1016/0167-7152(94)90175-9 PG 3 WC Statistics & Probability SC Mathematics GA NB002 UT WOS:A1994NB00200002 ER PT J AU ROZWARSKI, DA GRONENBORN, AM CLORE, GM BAZAN, JF BOHM, A WLODAWER, A HATADA, M KARPLUS, PA AF ROZWARSKI, DA GRONENBORN, AM CLORE, GM BAZAN, JF BOHM, A WLODAWER, A HATADA, M KARPLUS, PA TI STRUCTURAL COMPARISONS AMONG THE SHORT-CHAIN HELICAL CYTOKINES SO STRUCTURE LA English DT Article DE CYTOKINE; HELICAL BUNDLE; HOMOLOGY MODELING; PROTEIN EVOLUTION; PROTEIN FOLDS ID COLONY-STIMULATING FACTOR; HUMAN GROWTH-HORMONE; CRYSTAL-STRUCTURE; 3-DIMENSIONAL STRUCTURE; CHROMOSOMAL GENE; HUMAN INTERLEUKIN-4; SECONDARY STRUCTURE; GLOBULAR-PROTEINS; MOLECULAR-CLONING; INTERFERON-GAMMA AB Background: Cytokines and growth factors are soluble proteins that regulate the development and activities of many cell types. One group of these proteins have structures based on a four-helix bundle, though this similarity is not apparent from amino acid sequence comparisons. An understanding of how diverse sequences can adopt the same fold would be useful for recognizing and aligning distant homologs and for applying structural information gained from one protein to other sequences. Results: We have approached this problem by comparing the five known structures which adopt a granulocyte-macrophage colony-stimulating factor (GM-CSF)-like, or short-chain fold: interleukin (IL)-4, GM-CSF, IL-2, IL-5, and macrophage colony-stimulating factor. The comparison reveals a common structural framework of five segments including 31 inner-core and 30 largely exposed residues. Buried polar interactions found in each protein illustrate how complementary substitutions maintain protein stability and may help specify unique core packing. A profile based on the known structures is not sufficient to guarantee accurate amino acid sequence alignments with other family members. Comparisons of the conserved short-chain framework with growth hormone define the optimal structural alignment. Conclusions: Our results are useful for extrapolating functional results among the short-chain cytokines and growth hormone, and provide a foundation for similar characterization of other subfamilies. These results also show that the placement of polar residues at different buried positions in each protein complicates sequence comparisons, and they document a challenging test case for methods aimed at recognizing and aligning distant homologs. C1 CORNELL UNIV,BIOCHEM MOLEC & CELL BIOL SECT,ITHACA,NY 14853. UNIV CALIF SAN FRANCISCO,DEPT BIOCHEM & BIOPHYS,SAN FRANCISCO,CA 94143. UNIV CALIF BERKELEY,CALVIN LAB,BERKELEY,CA 94720. NIDDKD,CHEM PHYS LAB,BETHESDA,MD 20892. NCI,FREDERICK CANC RES & DEV CTR,ABL BASIC RES PROGRAM,MACROMOLEC STRUCT LAB,FREDERICK,MD 21702. ARIAD PHARMACEUT,CAMBRIDGE,MA 02139. RI Clore, G. Marius/A-3511-2008; Bazan, J. Fernando/B-4562-2010 OI Clore, G. Marius/0000-0003-3809-1027; FU NCI NIH HHS [N01-CO-74101]; NIGMS NIH HHS [NIGMS GM43566-03] NR 58 TC 142 Z9 145 U1 0 U2 4 PU CURRENT BIOLOGY LTD PI LONDON PA 34-42 CLEVELAND STREET, LONDON, ENGLAND W1P 6LB SN 0969-2126 J9 STRUCTURE JI Structure PD MAR 15 PY 1994 VL 2 IS 3 BP 159 EP 173 DI 10.1016/S0969-2126(00)00018-6 PG 15 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA ND069 UT WOS:A1994ND06900003 PM 8069631 ER PT J AU FULOP, V PHIZACKERLEY, RP SOLTIS, SM CLIFTON, IJ WAKATSUKI, S ERMAN, J HAJDU, J EDWARDS, SL AF FULOP, V PHIZACKERLEY, RP SOLTIS, SM CLIFTON, IJ WAKATSUKI, S ERMAN, J HAJDU, J EDWARDS, SL TI LAUE DIFFRACTION STUDY ON THE STRUCTURE OF CYTOCHROME-C PEROXIDASE COMPOUND-I SO STRUCTURE LA English DT Article DE ELECTRON TRANSFER; FREE RADICALS; MICROSPECTROPHOTOMETRY; OXYFERRYL HEME; TIME-RESOLVED CRYSTALLOGRAPHY ID CRYSTAL-STRUCTURE; MACROMOLECULAR CRYSTALLOGRAPHY; WEISSENBERG CAMERA; ES; OXIDATION; CATALYSIS; SITES AB Background: Cytochrome c peroxidase from yeast is a soluble haem-containing protein found in the mitochondrial electron transport chain where it probably protects against toxic peroxides. The aim of this study was to obtain a reliable structure for the doubly oxidized transient intermediate (termed compound I) in the reaction of cytochrome c peroxidase with hydrogen peroxide. This intermediate contains a semistable free radical on Trp191, and an oxyferryl haem group. Results: Compound I was produced in crystals of yeast cytochrome c peroxidase by reacting the crystalline enzyme with hydrogen peroxide in a flow cell. The reaction was monitored by microspectrophotometry and Laue crystallography in separate experiments. A nearly complete conversion to compound I was achieved within two minutes of the addition of hydrogen peroxide, and the concentration of the intermediate remained at similar levels for an additional half an hour. The structure of the intermediate was determined by Laue diffraction. The refined Laue structure for compound I shows clear structural changes at the peroxide-binding site but no significant changes at the radical site. The photographs were processed with a new software package (LEAP), overcoming many of the former problems encountered in extracting structural information from Laue exposures. Conclusions: The geometry of the haem environment in this protein allows structural changes to be extremely small, similar in magnitude to those observed for the Fe2+/Fe3+ transition in cytochrome c. The results suggest that these molecules have evolved to transfer electrons with a minimal need for structural adjustment. C1 UNIV OXFORD,MOLEC BIOPHYS LAB,OXFORD OX1 3QU,ENGLAND. STANFORD UNIV,STANFORD SYNCHROTRON RADIAT LAB,SLAC,STANFORD,CA 94305. NO ILLINOIS UNIV,DEPT CHEM,DE KALB,IL 60115. NIH,BETHESDA,MD 20892. RP FULOP, V (reprint author), UNIV OXFORD,OXFORD CTR MOLEC SCI,S PARKS RD,OXFORD OX1 3QU,ENGLAND. RI Erman, James/D-2890-2011 NR 28 TC 110 Z9 111 U1 1 U2 5 PU CURRENT BIOLOGY LTD PI LONDON PA 34-42 CLEVELAND STREET, LONDON, ENGLAND W1P 6LB SN 0969-2126 J9 STRUCTURE JI Structure PD MAR 15 PY 1994 VL 2 IS 3 BP 201 EP 208 DI 10.1016/S0969-2126(00)00021-6 PG 8 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA ND069 UT WOS:A1994ND06900006 PM 8069633 ER PT J AU LAROSA, JC APPLEGATE, W CROUSE, JR HUNNINGHAKE, DB GRIMM, R KNOPP, R ECKFELDT, JH DAVIS, CE GORDON, DJ AF LAROSA, JC APPLEGATE, W CROUSE, JR HUNNINGHAKE, DB GRIMM, R KNOPP, R ECKFELDT, JH DAVIS, CE GORDON, DJ TI CHOLESTEROL-LOWERING IN THE ELDERLY - RESULTS OF THE CHOLESTEROL REDUCTION IN SENIORS PROGRAM (CRISP) PILOT-STUDY SO ARCHIVES OF INTERNAL MEDICINE LA English DT Article ID DENSITY-LIPOPROTEIN CHOLESTEROL; EXPANDED CLINICAL-EVALUATION; SERUM TRIGLYCERIDES; LOVASTATIN EXCEL; HEART-DISEASE; EFFICACY; LIPIDS AB Background: Total and lipoprotein cholesterol levels continue to be predictors of coronary heart disease risk in men and women over 65 years old. Cholesterol-lowering trials, however, while sometimes including such subjects, have not concentrated on this age group. The Cholesterol Reduction in Seniors Program was a five-center pilot study to assess feasibility of recruitment and efficacy of cholesterol lowering in this age group. Methods: The study was a randomized, double-masked clinical trial with placebo, 20-mg lovastatin, and 40-mg lovastatin arms. Major efforts were made to recruit women and minorities. Participants were followed up for 1 year on a cholesterol-lowering diet plus placebo or study drug. End points were changes in blood lipid levels. Data on other blood chemistry values, as well as quality-of-life measures and coronary heart disease morbidity and mortality, were also collected. Results: Four hundred thirty-one subjects with low-density lipoprotein cholesterol levels greater than 4.1 and less than 5.7 mmol/L (159 and 221 mg/dL) were randomized, of whom 71% were women and 21% were African Americans; the mean age was 71 years. In the 20- and 40-mg lovastatin groups, total cholesterol levels fell 17% and 20%; low-density lipoprotein cholesterol levels fell 24% and 28%; triglyceride levels fell 4.4% and 9.9%, respectively. High-density lipoprotein cholesterol levels rose 7.0% and 9.0%, respectively. No changes were observed in the placebo group. Gender, race, and age did not significantly affect responses. Coronary heart disease morbidity and mortality data were collected but not analyzed for this study. Conclusion: Older subjects of both genders and a variety of racial and ethnic groups can be successfully recruited into a cholesterol-lowering trial. Lovastatin has effects similar to those reported in younger subjects in previous controlled trials. There is little advantage to the higher lovastatin daily dose. Side effects were remarkably low in all groups. C1 UNIV N CAROLINA,CTR COLLABORAT STUDIES COORDINATING,DEPT BIOSTAT,CHAPEL HILL,NC 27514. GEORGE WASHINGTON UNIV,MED CTR,DEPT MED,WASHINGTON,DC 20037. UNIV TENNESSEE,DEPT PREVENT MED,MEMPHIS,TN. BOWMAN GRAY SCH MED,DEPT INTERNAL MED & ENDOCRINOL,WINSTON SALEM,NC. UNIV MINNESOTA,DEPT MED & PHARMACOL,MINNEAPOLIS,MN. UNIV MINNESOTA,DEPT INTERNAL MED,MINNEAPOLIS,MN. UNIV MINNESOTA,DEPT LAB MED & PATHOL,MINNEAPOLIS,MN. UNIV WASHINGTON,DEPT MED,SEATTLE,WA. NHLBI,BETHESDA,MD. FU NHLBI NIH HHS [UO1-HL44298, UO1-HL44311, UO1-HL44299] NR 22 TC 69 Z9 72 U1 1 U2 3 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0003-9926 J9 ARCH INTERN MED JI Arch. Intern. Med. PD MAR 14 PY 1994 VL 154 IS 5 BP 529 EP 539 DI 10.1001/archinte.154.5.529 PG 11 WC Medicine, General & Internal SC General & Internal Medicine GA NA075 UT WOS:A1994NA07500005 PM 8122946 ER PT J AU GALLANT, JE MOORE, RD RICHMAN, DD KERULY, J CHAISSON, RE BARTLETT, J MCAVINUE, S BRYSON, Y COHEN, H FISCHL, M BOLIN, T BURROUGH, Y MILDVAN, D FOX, A RICHMAN, D FREEMAN, B SIMON, G GRABOWY, KW CHERNOFF, D DUFF, P THOMPSON, S BARRETT, K AWE, R LEONARD, S TURNER, P HAWKINS, M MURRAY, H BOWERS, J TILSON, H SMILEY, L AF GALLANT, JE MOORE, RD RICHMAN, DD KERULY, J CHAISSON, RE BARTLETT, J MCAVINUE, S BRYSON, Y COHEN, H FISCHL, M BOLIN, T BURROUGH, Y MILDVAN, D FOX, A RICHMAN, D FREEMAN, B SIMON, G GRABOWY, KW CHERNOFF, D DUFF, P THOMPSON, S BARRETT, K AWE, R LEONARD, S TURNER, P HAWKINS, M MURRAY, H BOWERS, J TILSON, H SMILEY, L TI RISK-FACTORS FOR KAPOSIS-SARCOMA IN PATIENTS WITH ADVANCED HUMAN-IMMUNODEFICIENCY-VIRUS DISEASE TREATED WITH ZIDOVUDINE SO ARCHIVES OF INTERNAL MEDICINE LA English DT Article ID YOUNG HOMOSEXUAL MEN; NON-HODGKINS-LYMPHOMA; LONG-TERM CULTURE; CYTOMEGALO-VIRUS; INSITU HYBRIDIZATION; NATURAL-HISTORY; AIDS PATIENTS; SEROLOGICAL ASSOCIATION; ANTIBODY PATTERNS; HIV-INFECTION AB Background: Although the cause of Kaposi's sarcoma (KS) is unknown, its unique epidemiology suggests that an infectious, sexually transmitted agent or agents may contribute to its pathogenesis. Methods: To assess the natural history of KS associated with the acquired immunodeficiency syndrome and to identify factors associated with its development, data were analyzed from a multicenter, observational cohort study of 1044 persons with the acquired immunodeficiency syndrome or the acquired immunodeficiency syndrome-related complex and a total CD4 cell count of less than 0.25 x 10(9)/L who were treated with zidovudine between April 1987 and April 1988. Records were reviewed bimonthly. Follow-up continued for 2 years or until death. Results: One hundred thirty-one patients (13%) had KS at study enrollment, and 143 developed KS (14%) during follow-up, with a 2-year actuarial risk of 21%. The probability of KS at 2 years for patients with initial CD4 cell counts of less than 0.1X10(9)/L was 25%, compared with 15% for those with counts of 0.1X10(9)/L or more. By logistic regression, a baseline CD4 cell count of less than 0.1x10(9)/L (relative odds, 1.43; 95% confidence interval, 1.04 to 1.95), homosexuality (relative odds, 3.71; 95% confidence interval, 1.82 to 7.56), cytomegalovirus disease (relative odds, 1.56; 95% confidence interval, 1.01 to 2.41), and white race (relative odds, 1.64; 95% confidence interval, 1.11 to 2.43) were independently associated with KS. Median survival after KS was 408 days, and KS was an independent predictor of death (relative hazard, 1.78; 95% confidence interval, 1.26 to 2.52). Conclusions: Kaposi's sarcoma contributes to human immunodeficiency virus-related morbidity and mortality, especially among male homosexuals. This large cohort study provides further evidence for an association between risk for cytomegalovirus infection and KS. C1 VET AFFAIRS MED CTR,DEPT PATHOL,SAN DIEGO,CA 92161. VET AFFAIRS MED CTR,DEPT MED,SAN DIEGO,CA 92161. UNIV CALIF SAN DIEGO,SAN DIEGO,CA 92103. JOHNS HOPKINS UNIV,SCH MED,DEPT MED,BALTIMORE,MD. UNIV CALIF LOS ANGELES,SCH MED,LOS ANGELES,CA 90024. UNIV MIAMI,MIAMI,FL 33152. RUSH PRESBYTERIAN ST LUKES MED CTR,CHICAGO,IL 60612. BETH ISRAEL MED CTR,NEW YORK,NY 10003. GEORGE WASHINGTON UNIV,MED CTR,WASHINGTON,DC 20037. UNIV CALIF SAN FRANCISCO,SAN FRANCISCO,CA 94143. EMORY UNIV,ATLANTA,GA 30322. LYNDON B JOHNSON GEN HOSP,HOUSTON,TX. KAISER PERMANENTE MED GRP,LOS ANGELES,CA. CORNELL UNIV,MED CTR,NEW YORK,NY 10021. NIAID,BETHESDA,MD 20892. BURROUGHS WELLCOME CO,RES TRIANGLE PK,NC 27709. JOHNS HOPKINS UNIV,SCH MED,DEPT MED,BALTIMORE,MD 21205. NR 83 TC 33 Z9 33 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0003-9926 J9 ARCH INTERN MED JI Arch. Intern. Med. PD MAR 14 PY 1994 VL 154 IS 5 BP 566 EP 572 DI 10.1001/archinte.154.5.566 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA NA075 UT WOS:A1994NA07500009 PM 8122950 ER PT J AU ARMSTRONG, DM IKONOMOVIC, MD SHEFFIELD, R WENTHOLD, RJ AF ARMSTRONG, DM IKONOMOVIC, MD SHEFFIELD, R WENTHOLD, RJ TI AMPA-SELECTIVE GLUTAMATE-RECEPTOR SUBTYPE IMMUNOREACTIVITY IN THE ENTORHINAL CORTEX OF NONDEMENTED ELDERLY AND PATIENTS WITH ALZHEIMERS-DISEASE SO BRAIN RESEARCH LA English DT Article DE ALZHEIMERS DISEASE; GLUTAMATE; EXCITOTOXICITY; RECEPTOR; AMPA ID METHYL-D-ASPARTATE; AMINO-ACID RECEPTORS; BINDING-SITES; RAT-BRAIN; NERVOUS-SYSTEM; NMDA RECEPTORS; NEURONAL LOSS; SUBUNIT; HIPPOCAMPUS; EXPRESSION AB The present work employed immunocytochemical techniques and examined the distribution and cytological features of the AMPA receptor subunits, GluR2/3 and GluR1 within the entorhinal cortex of non-demented elderly (NC), patients with neuropathological and clinical verification of Alzheimer's disease (AD) and patients without a clinical history of dementia yet exhibiting sufficient quantities of senile plaques to meet neuropathological criteria of Alzheimer's disease (HPND). In NC cases, GluR2/3-immunolabeled neurons were abundantly distributed throughout layers II, III, V and VI of the entorhinal cortex. In contrast, GluR1-positive cells were comparatively sparse in number and largely restricted to layers V and VI. In AD, GluR2/3- and GluR1-labeled neurons were markedly reduced. Similarly, adjacent Niss1-stained tissue sections revealed substantial cell loss in the entorhinal cortex thus providing a reasonable explanation for the loss of these receptor subunits. Importantly, a dramatic loss of GluR2/3- and GluR1-immunolabeled neurons is also observed in the HPND cases, although examination of Niss1-stained tissue sections reveals little if any evidence of cell loss. The latter data suggest that a 'down-regulation' of these receptor subunits occurs prior to the actual loss of these cells. Furthermore, we hypothesize that the decrease of specific AMPA receptor subunits may influence neuronal vulnerability via a mechanism involving increased intracellular calcium and the destabilization of intracellular calcium homeostasis. C1 GEORGETOWN UNIV,FIDIA GEORGETOWN INST NEUROSCI,WASHINGTON,DC 20007. NIDCD,NEUROCHEM LAB,BETHESDA,MD 20892. FU NIA NIH HHS [AG08206] NR 52 TC 72 Z9 72 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0006-8993 J9 BRAIN RES JI Brain Res. PD MAR 14 PY 1994 VL 639 IS 2 BP 207 EP 216 DI 10.1016/0006-8993(94)91732-9 PG 10 WC Neurosciences SC Neurosciences & Neurology GA NB657 UT WOS:A1994NB65700004 PM 8205474 ER PT J AU AKIYAMA, SK LAFLAMME, SE AF AKIYAMA, SK LAFLAMME, SE TI BIOADHESION AND CELL BEHAVIOR SO COLLOIDS AND SURFACES B-BIOINTERFACES LA English DT Proceedings Paper CT International Conference on the Fundamental Aspects of Bioadhesion and Flocculation and their Implications in Technological, Ecological and Medical Fields CY MAY 23-27, 1993 CL LOUVAIN, BELGIUM SP COMMISS EUROPEAN COMMUNITIES, USN, OFF NAVAL RES, EUROPEAN OFF, INT ASSOC COLLOID & INTERFACE SCIENTISTS, MINIST DEV TECHNOL & EMPLOI REG WALLONNE, MINIST ENVIRONM RESOURCES NAT & AGR REG WALLONNE, FONDS NATL RECH SCI, MINIST EDUC RECH & FORMAT COMMUNAUTE FRANCAISE BELGIQUE DE CELL ADHESION; FIBRONECTIN; INTEGRINS; LAMININ; TYROSINE PHOSPHORYLATION ID AMINO-ACID-SEQUENCE; CHICKEN-EMBRYO FIBROBLASTS; MEMBRANE GLYCOPROTEIN-IIB; ROUS-SARCOMA VIRUS; FIBRONECTIN RECEPTOR DISTRIBUTION; SITE-DIRECTED MUTAGENESIS; VINCULIN-BINDING-PROTEINS; HUMAN-PLASMA FIBRONECTIN; EXTRACELLULAR-MATRIX; CYTOPLASMIC DOMAIN C1 NIDR,DEV BIOL LAB,BETHESDA,MD 20892. NR 131 TC 8 Z9 8 U1 1 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0927-7765 J9 COLLOID SURFACE B JI Colloid Surf. B-Biointerfaces PD MAR 14 PY 1994 VL 2 IS 1-3 BP 241 EP 250 DI 10.1016/0927-7765(94)80038-3 PG 10 WC Biophysics; Chemistry, Physical; Materials Science, Biomaterials SC Biophysics; Chemistry; Materials Science GA NB842 UT WOS:A1994NB84200028 ER PT J AU PTITSYN, OB UVERSKY, VN AF PTITSYN, OB UVERSKY, VN TI THE MOLTEN GLOBULE IS A 3RD THERMODYNAMICAL STATE OF PROTEIN MOLECULES SO FEBS LETTERS LA English DT Article DE PROTEIN DENATURATION; PROTEIN FOLDING; MOLTEN GLOBULE STATE ID ALPHA-LACTALBUMIN; INTERMEDIATE; NMR AB Analysis of published data on conformational transitions in relatively small proteins shows that the slopes of these transitions are proportional to the protein molecular weight. It is true both for transitions from the native (N) to the unfolded (U) states (when protein denaturation is coupled to its unfolding) and for transitions from the native to the molten globule (MG) states and from the molten globule to the unfolded state (when protein denaturation is decoupled from protein unfolding). This is precisely the behaviour predicted by thermodynamics for first order phase transitions ('all-or-none' transitions) in small systems. It follows that N --> U, N --> MG and MG --> U transitions in proteins are all of the 'all-or-none' type. Thus the molten globule state of protein molecules is separated by an 'all-or-none' transition both from the native and the unfolded state, i.e. the molten globule state is a third thermodynamic state of protein molecules in addition to the two previously established states - the native and the unfolded. C1 NCI,MATH BIOL LAB,WSC,BETHESDA,MD 20892. RP PTITSYN, OB (reprint author), RUSSIAN ACAD SCI,INST PROT RES,PUSHCHINO 142292,RUSSIA. RI Uversky, Vladimir/F-4515-2011 OI Uversky, Vladimir/0000-0002-4037-5857 NR 32 TC 132 Z9 135 U1 0 U2 4 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 14 PY 1994 VL 341 IS 1 BP 15 EP 18 DI 10.1016/0014-5793(94)80231-9 PG 4 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA NB189 UT WOS:A1994NB18900004 PM 8137915 ER PT J AU YOO, SH LEWIS, MS AF YOO, SH LEWIS, MS TI PH-DEPENDENT INTERACTION OF AN INTRALUMINAL LOOP OF INOSITOL 1,4,5-TRISPHOSPHATE RECEPTOR WITH CHROMOGRANIN-A SO FEBS LETTERS LA English DT Article DE PH; INTRALUMINAL LOOP; IF3 RECEPTOR; CHROMOGRANIN A; 5-HYDROXY-TRYPTOPHAN ID CONFORMATIONAL CHANGE; INSP3 RECEPTOR; CA-2+; 5-HYDROXYTRYPTOPHAN; EXPRESSION; VESICLES; PROTEINS; BINDING; CA2+ AB The inositol 1,4,5-trisphosphate (IP3)-sensitive Ca2+ store role of the secretory vesicles of adrenal medullary chromaffin cells is attributed to the presence of high capacity, low affinity Ca2+ binding protein chromogranin A. Chromogranin A has recently been shown to interact with the protein component(s) on the intraluminal side of the secretory vesicle membrane at the intravesicular pH of 5.5 but to dissociate from them at the near physiological pH of 7.5. Further, one of the chromogranin A-interacting membrane proteins was tentatively identified as the IP3 receptor. Therefore, the pH-dependent potential interaction of the intraluminal loop domains of the IP3 receptor with chromogranin A was studied by analytical ultracentrifugation utilizing synthetic intraluminal loop peptides of the IP3 receptor labeled with 5-hydroxy-tryptophan at the N-terminus as a chromophore. One of the intraluminal loop domains was found to interact with chromogranin A at pH 5.5 but not at pH 7.5, suggesting the importance of the intraluminal loop domain in transmitting Ca2+ mobilization signals to chromogranin A. C1 NIH,NATL CTR RES RESOURCES,BIOMED ENGN & INSTRUMENTAT PROGRAM,BETHESDA,MD 20892. RP YOO, SH (reprint author), NATL INST DEAFNESS & OTHER COMMUNICAT DISORDERS,CELLULAR BIOL LAB,BLDG 36,ROOM 5D-13,BETHESDA,MD 20892, USA. NR 22 TC 18 Z9 18 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 14 PY 1994 VL 341 IS 1 BP 28 EP 32 DI 10.1016/0014-5793(94)80234-3 PG 5 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA NB189 UT WOS:A1994NB18900007 PM 8137917 ER PT J AU ACCILI, D MOSTHAF, L LEVYTOLEDANO, R ULLRICH, A TAYLOR, SI AF ACCILI, D MOSTHAF, L LEVYTOLEDANO, R ULLRICH, A TAYLOR, SI TI MUTAGENESIS OF PHE(381) AND PHE(382) IN THE EXTRACELLULAR DOMAIN OF THE INSULIN-RECEPTOR - EFFECTS ON RECEPTOR BIOSYNTHESIS, PROCESSING, AND LIGAND-DEPENDENT INTERNALIZATION SO FEBS LETTERS LA English DT Article DE INSULIN RECEPTOR; MUTAGENESIS; INTRACELLULAR TRANSPORT; GENETIC DISEASE; INSULIN RESISTANCE ID GROWTH-FACTOR RECEPTOR; CELL-SURFACE; IMPAIRS TRANSPORT; ALPHA-SUBUNIT; MUTATION; BINDING; GENE; SUBSTITUTION; SEQUENCE; AUTOPHOSPHORYLATION AB Mutations of the extracellular domain of the insulin receptor impair processing and transport of receptors to the plasma membrane. We have previously reported that a mutation substituting Val for Phe(382) in the alpha-subunit of the insulin receptor impairs intracellular processing and insulin-induced autophosphorylation of the mutant receptor. In this investigation, we have generated two independent mutations of amino acids Phe(381) and phe(382) of the insulin receptor: Val for Phe(381) and Leu for Phe(382). These substitutions cause a slight impairment of intracellular processing and transport of the mutant receptors. Furthermore, insulin-dependent internalization of the mutant receptors is unaffected by these mutations. Thus, of the three substitutions studied to date, Val for Phe(382) is the only mutation of the Phe(382)-Phe(382) sequence that causes a major defect in posttranslational processing of the receptor. C1 MAX PLANCK INST BIOCHEM,DEPT MOLEC BIOL,W-8033 MARTINSRIED,GERMANY. RP ACCILI, D (reprint author), NIDDK,DIABET BRANCH,BLDG 10,ROOM 8S-239,BETHESDA,MD 20892, USA. NR 30 TC 1 Z9 2 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 14 PY 1994 VL 341 IS 1 BP 104 EP 108 DI 10.1016/0014-5793(94)80249-1 PG 5 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA NB189 UT WOS:A1994NB18900022 PM 8137907 ER PT J AU BURKE, TR SMYTH, MS OTAKA, A NOMIZU, M ROLLER, PP CASE, RD SHOELSON, SE AF BURKE, TR SMYTH, MS OTAKA, A NOMIZU, M ROLLER, PP CASE, RD SHOELSON, SE TI FLUORINATED PHOSPHONOMETHYL PHENYLALANINE ANALOGS AS PHOSPHOTYROSYL MIMETICS IN SH2-BINDING PEPTIDES SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 NCI,DCT,DTP,MED CHEM LAB,BETHESDA,MD 20892. HARVARD UNIV,JOSLIN DIABET CTR,BOSTON,MA 02215. HARVARD UNIV,SCH MED,BOSTON,MA 02115. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD MAR 13 PY 1994 VL 207 BP 6 EP MEDI PN 1 PG 0 WC Chemistry, Multidisciplinary SC Chemistry GA MY954 UT WOS:A1994MY95403314 ER PT J AU JANSSEN, CL COLVIN, ME SEIDL, ET AF JANSSEN, CL COLVIN, ME SEIDL, ET TI OBJECT-ORIENTED IMPLEMENTATION OF PARALLEL AB-INITIO PROGRAMS SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 SANDIA NATL LABS,DEPT 8117,LIVERMORE,CA 94550. NIH,DCRT,BETHESDA,MD 20892. NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD MAR 13 PY 1994 VL 207 BP 13 EP COMP PN 1 PG 0 WC Chemistry, Multidisciplinary SC Chemistry GA MY954 UT WOS:A1994MY95401732 ER PT J AU LIN, SL FISCHER, D TSAI, CJ WOLFSON, H NUSSINOV, R AF LIN, SL FISCHER, D TSAI, CJ WOLFSON, H NUSSINOV, R TI SURFACE DESCRIPTION, BIOMOLECULAR RECOGNITION (DOCKING) AND SEQUENCE-ORDER INDEPENDENT, SUBSTRUCTURAL MOTIFS IN PROTEINS SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 NCI,MATH BIOL LAB,FREDERICK,MD 21702. NCI,FCRDC,PRI DYNCORP,FREDERICK,MD 21702. TEL AVIV UNIV,DEPT COMP SCI,IL-69978 TEL AVIV,ISRAEL. RI Wolfson, Haim/A-1837-2011 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD MAR 13 PY 1994 VL 207 BP 29 EP COMP PN 1 PG 0 WC Chemistry, Multidisciplinary SC Chemistry GA MY954 UT WOS:A1994MY95401747 ER PT J AU LUNNEY, EA HUMBLET, C HAGEN, SE TAIT, B WILSON, M DOMAGALA, JM HUPE, L FERGUSON, D TUMMINO, PJ HUPE, D BHAT, TN ERICKSON, JW AF LUNNEY, EA HUMBLET, C HAGEN, SE TAIT, B WILSON, M DOMAGALA, JM HUPE, L FERGUSON, D TUMMINO, PJ HUPE, D BHAT, TN ERICKSON, JW TI THE APPLICATION OF COMPUTER-ASSISTED DRUG DESIGN IN THE DISCOVERY OF NONPEPTIDE HIV-1 PROTEASE INHIBITORS SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 PARKE DAVIS PHARMACEUT RES,ANN ARBOR,MI 48105. NCI,FREDERICK CANC RES & DEV CTR,PRI DYNCORP,STRUCT BIOCHEM PROGRAM,FREDERICK,MD 21702. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD MAR 13 PY 1994 VL 207 BP 45 EP COMP PN 1 PG 0 WC Chemistry, Multidisciplinary SC Chemistry GA MY954 UT WOS:A1994MY95401763 ER PT J AU MARK, GE PADLAN, EA AF MARK, GE PADLAN, EA TI CDR-GRAFTING AND VENEERING APPROACHES TO MAB HUMANIZATION SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 MERCK RES LABS,RAHWAY,NJ 07065. NIDDK,MOLEC BIOL LAB,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD MAR 13 PY 1994 VL 207 BP 53 EP BIOT PN 1 PG 0 WC Chemistry, Multidisciplinary SC Chemistry GA MY954 UT WOS:A1994MY95400454 ER PT J AU MULARD, LA NASHED, EM KOVAC, P GLAUDEMANS, CPJ AF MULARD, LA NASHED, EM KOVAC, P GLAUDEMANS, CPJ TI MAPPING OF THE BINDING-SITE OF A MONOCLONAL IGM ANTIBODY TO SHIGELLA-DYSENTERIA TYPE-1 SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 NIDDK,LMC,CARBOHYDRATES SECT,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 1 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD MAR 13 PY 1994 VL 207 BP 53 EP MEDI PN 1 PG 0 WC Chemistry, Multidisciplinary SC Chemistry GA MY954 UT WOS:A1994MY95403362 ER PT J AU WEISZ, A SCHER, AL ANDRZEJEWSKI, D ITO, Y AF WEISZ, A SCHER, AL ANDRZEJEWSKI, D ITO, Y TI PREPARATIVE SEPARATION OF BROMINATED TETRACHLOROFLUORESCEINS BY PH-ZONE-REFINING COUNTERCURRENT CHROMATOGRAPHY WITH COMPUTERIZED SCANNING UV/VIS DETECTION AND CONTINUOUS PH MONITORING SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 NHLBI,BIOPHYS CHEM LAB,BETHESDA,MD 20892. US FDA,OFF COSMET & COLORS,WASHINGTON,DC 20204. US FDA,OFF SCI ANAL & SUPPORT,WASHINGTON,DC 20204. NR 0 TC 1 Z9 1 U1 1 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD MAR 13 PY 1994 VL 207 BP 58 EP ANYL PN 1 PG 0 WC Chemistry, Multidisciplinary SC Chemistry GA MY954 UT WOS:A1994MY95400334 ER PT J AU ANTONUCCI, JM SKRTIC, D EANES, ED AF ANTONUCCI, JM SKRTIC, D EANES, ED TI POLYMERIC CALCIUM-PHOSPHATE COMPOSITES WITH REMINERALIZATION POTENTIAL SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 NIST,DIV POLYMERS,GAITHERSBURG,MD 20899. NIDR,BONE RES BRANCH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD MAR 13 PY 1994 VL 207 BP 60 EP BTEC PN 2 PG 0 WC Chemistry, Multidisciplinary SC Chemistry GA MY955 UT WOS:A1994MY95501803 ER PT J AU KOEPKE, MBK SCHMIDT, BF TANEYHILL, LA KLINE, AM SNYDER, EA MICHEJDA, CJ SMITH, RH AF KOEPKE, MBK SCHMIDT, BF TANEYHILL, LA KLINE, AM SNYDER, EA MICHEJDA, CJ SMITH, RH TI DNA ALKYLATION BY 1,3-DIALKYL-3-ACYLTRIAZENES - ADDUCT SPECIFICITY DEPENDENCE ON ACYL GROUP-STRUCTURE SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 NCI,FCRDC,ABL BASIC RES PROGRAM,MOLEC ASPECTS DRUG DESIGN SECT,FREDERICK,MD 21702. WESTERN MARYLAND COLL,DEPT CHEM,WESTMINSTER,MD 21157. RI Taneyhill, Lisa/K-1815-2013 NR 0 TC 0 Z9 0 U1 0 U2 2 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD MAR 13 PY 1994 VL 207 BP 65 EP MEDI PN 1 PG 0 WC Chemistry, Multidisciplinary SC Chemistry GA MY954 UT WOS:A1994MY95403374 ER PT J AU JEONG, LS MARQUEZ, VE AF JEONG, LS MARQUEZ, VE TI SYNTHESIS OF 1-(2,3-DIDEOXY-2,3-DIFLUORO-BETA-D-LYXOFURANOSYL)CYTOSINE SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 NCI,DCT,DTP,MED CHEM LAB,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD MAR 13 PY 1994 VL 207 BP 66 EP MEDI PN 1 PG 0 WC Chemistry, Multidisciplinary SC Chemistry GA MY954 UT WOS:A1994MY95403375 ER PT J AU SHARMA, R MARQUEZ, VE BLUMBERG, PM LEWIN, NE AF SHARMA, R MARQUEZ, VE BLUMBERG, PM LEWIN, NE TI 4-BIS(HYDROXYMETHYL)-4-BUTANOLIDE - A PROMISING TEMPLATE FOR THE CONSTRUCTION OF CONFORMATIONALLY CONSTRAINED DIACYLGLYCEROLS SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 NCI,DCT,DTP,MED CHEM LAB,BETHESDA,MD 20892. NCI,CELLULAR CARCINOGENESIS & TUMOR PROMOT LAB,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD MAR 13 PY 1994 VL 207 BP 67 EP MEDI PN 1 PG 0 WC Chemistry, Multidisciplinary SC Chemistry GA MY954 UT WOS:A1994MY95403376 ER PT J AU SMITH, RH SCHMIDT, BF ENSEL, SM MICHEJDA, CJ AF SMITH, RH SCHMIDT, BF ENSEL, SM MICHEJDA, CJ TI PREPARATION AND HYDROLYTIC DECOMPOSITION OF ALKYLTRIAZININES SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 WESTERN MARYLAND COLL,DEPT CHEM,WESTMINSTER,MD 21157. NCI,FCRDC,ABL BRP,MSL,MOLEC ASPECTS DRUG DESIGN SECT,FREDERICK,MD 21702. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD MAR 13 PY 1994 VL 207 BP 79 EP CHED PN 1 PG 0 WC Chemistry, Multidisciplinary SC Chemistry GA MY954 UT WOS:A1994MY95400909 ER PT J AU LEVY, HB AF LEVY, HB TI CLINICAL-STUDIES WITH POLYICLC SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD MAR 13 PY 1994 VL 207 BP 103 EP BTEC PN 2 PG 0 WC Chemistry, Multidisciplinary SC Chemistry GA MY955 UT WOS:A1994MY95501846 ER PT J AU PINTO, JC RICE, KC HOWLETT, A CANTRELL, C AF PINTO, JC RICE, KC HOWLETT, A CANTRELL, C TI ARACHIDONIC-ACID DERIVATIVES AS PROBES FOR THE CANNABINOID RECEPTOR SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 NIDDK,MED CHEM LAB,BETHESDA,MD 20852. ST LOUIS UNIV,SCH MED,DEPT PHARMACOL & PHYSIOL SCI,ST LOUIS,MO 63104. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD MAR 13 PY 1994 VL 207 BP 107 EP MEDI PN 1 PG 0 WC Chemistry, Multidisciplinary SC Chemistry GA MY954 UT WOS:A1994MY95403415 ER PT J AU DOUGLAS, T BULTE, JWM PANKHURST, QA DICKSON, DP FRANKEL, RB MANN, S AF DOUGLAS, T BULTE, JWM PANKHURST, QA DICKSON, DP FRANKEL, RB MANN, S TI INORGANIC-PROTEIN INTERACTIONS IN THE SYNTHESIS OF A FERRIMAGNETIC NANOCOMPOSITE SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 UNIV BATH,SCH CHEM,BATH BA2 7AY,AVON,ENGLAND. NIH,BETHESDA,MD 20892. UNIV LIVERPOOL,DEPT PHYS,LIVERPOOL L69 3BX,ENGLAND. CALIF POLYTECH STATE UNIV SAN LUIS OBISPO,DEPT PHYS,SAN LUIS OBISPO,CA 93407. RI Bulte, Jeff/A-3240-2008; Mann, Stephen/D-1332-2012 OI Bulte, Jeff/0000-0003-1202-1610; Mann, Stephen/0000-0003-3012-8964 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD MAR 13 PY 1994 VL 207 BP 119 EP PMSE PN 2 PG 0 WC Chemistry, Multidisciplinary SC Chemistry GA MY955 UT WOS:A1994MY95501578 ER PT J AU HUTCHINSON, KD DALY, JW AF HUTCHINSON, KD DALY, JW TI AN APPROACH TO THE SYNTHESIS OF DEHYDROHOMOPUMILIOTOXIN-235C SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD MAR 13 PY 1994 VL 207 BP 123 EP ORGN PN 2 PG 0 WC Chemistry, Multidisciplinary SC Chemistry GA MY955 UT WOS:A1994MY95500200 ER PT J AU LEVY, LA RHEE, CK AF LEVY, LA RHEE, CK TI ALKYLATION OF TRIFLUOROETHYL SUBSTITUTED DERIVATIVES SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 NIEHS,MOLEC BIOPHYS LAB,RES TRIANGLE PK,NC 27709. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD MAR 13 PY 1994 VL 207 BP 124 EP ORGN PN 2 PG 0 WC Chemistry, Multidisciplinary SC Chemistry GA MY955 UT WOS:A1994MY95500201 ER PT J AU ZWANZIG, R AF ZWANZIG, R TI ENTROPY BARRIERS SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 NIH,CHEM PHYS LAB,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 3 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD MAR 13 PY 1994 VL 207 BP 124 EP PHYS PN 2 PG 0 WC Chemistry, Multidisciplinary SC Chemistry GA MY955 UT WOS:A1994MY95500763 ER PT J AU SUFFNESS, M AF SUFFNESS, M TI CURRENT STATUS OF TAXOL (PACLITAXEL) RESEARCH SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 NCI,DIV CANC TREATMENT,DEV THERAPEUT PROGRAM,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD MAR 13 PY 1994 VL 207 BP 141 EP MEDI PN 1 PG 0 WC Chemistry, Multidisciplinary SC Chemistry GA MY954 UT WOS:A1994MY95403448 ER PT J AU VISWANADHAN, VN REDDY, MR WLODAWER, A WEINSTEIN, JN AF VISWANADHAN, VN REDDY, MR WLODAWER, A WEINSTEIN, JN TI AN ANALYSIS OF FREE-ENERGY COMPONENTS OF PEPTIDIMIMETIC INHIBITORS OF THE HIV-1 PROTEASE SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 NCI,MOLEC PHARM LAB,BETHESDA,MD 20892. AGOURON PHARM,SAN DIEGO,CA. FCRDC,FREDERICK,MD. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD MAR 13 PY 1994 VL 207 BP 145 EP COMP PN 1 PG 0 WC Chemistry, Multidisciplinary SC Chemistry GA MY954 UT WOS:A1994MY95401862 ER PT J AU TSAI, AM BETENBAUGH, MJ SHILOACH, J AF TSAI, AM BETENBAUGH, MJ SHILOACH, J TI THE KINETICS OF RCC1 INCLUSION-BODY FORMATION IN ESCHERICHIA-COLI SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 JOHNS HOPKINS UNIV,DEPT CHEM ENGN,BALTIMORE,MD 21218. NIDDK,BIOTECHNOL UNIT,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD MAR 13 PY 1994 VL 207 BP 178 EP BIOT PN 1 PG 0 WC Chemistry, Multidisciplinary SC Chemistry GA MY954 UT WOS:A1994MY95400576 ER PT J AU OLIVER, C STARKEREED, P AF OLIVER, C STARKEREED, P TI OXIDATIVE MODIFICATION OF PROTEINS IN-VIVO AND IN-VITRO BY METAL-CATALYZED OXIDATION REACTIONS SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 MERCK SHARP & DOHME LTD,W POINT,PA 19486. NIA,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 3 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD MAR 13 PY 1994 VL 207 BP 210 EP BIOT PN 1 PG 0 WC Chemistry, Multidisciplinary SC Chemistry GA MY954 UT WOS:A1994MY95400608 ER PT J AU JACOBSON, KA GALLORODRIGUEZ, C JI, X MELMAN, N KIM, HO SANDERS, LH SIEGMAN, BD ORLINA, J FISCHER, B PU, QL VANGALEN, PJM OLAH, ME STILES, GL AF JACOBSON, KA GALLORODRIGUEZ, C JI, X MELMAN, N KIM, HO SANDERS, LH SIEGMAN, BD ORLINA, J FISCHER, B PU, QL VANGALEN, PJM OLAH, ME STILES, GL TI N(6)-BENZYLADENOSINE 5'-URONAMIDES - SELECTIVE AGONISTS FOR A(3) RECEPTORS SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 NIDDK,BIOORGANIC CHEM LAB,BETHESDA,MD 20892. DUKE UNIV,MED CTR,DURHAM,NC 27710. RI Gallo-Rodriguez, Carola/E-1732-2012; Jacobson, Kenneth/A-1530-2009 OI Jacobson, Kenneth/0000-0001-8104-1493 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD MAR 13 PY 1994 VL 207 BP 244 EP MEDI PN 1 PG 0 WC Chemistry, Multidisciplinary SC Chemistry GA MY954 UT WOS:A1994MY95403549 ER PT J AU BOUMENDJEL, A MILLER, SPF AF BOUMENDJEL, A MILLER, SPF TI SPHINGOSINE-1-PHOSPHATE LYASE INHIBITORS SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD MAR 13 PY 1994 VL 207 BP 259 EP ORGN PN 2 PG 0 WC Chemistry, Multidisciplinary SC Chemistry GA MY955 UT WOS:A1994MY95500336 ER PT J AU PIPPIN, CG GANSOW, OA AF PIPPIN, CG GANSOW, OA TI THE BISMUTH(III) ION IN MEDICINE SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 NCI,RADIAT ONCOL BRANCH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD MAR 13 PY 1994 VL 207 BP 366 EP INOR PN 1 PG 0 WC Chemistry, Multidisciplinary SC Chemistry GA MY954 UT WOS:A1994MY95403127 ER PT J AU RAO, PN CESSAC, JW KIM, HK AF RAO, PN CESSAC, JW KIM, HK TI PREPARATIVE CHEMICAL METHODS FOR AROMATIZATION OF 19-NOR-DELTA(4)-3-OXOSTEROIDS SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 SW FDN BIOMED RES,DEPT ORGAN CHEM,SAN ANTONIO,TX 78284. NICHHD,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD MAR 13 PY 1994 VL 207 BP 418 EP ORGN PN 2 PG 0 WC Chemistry, Multidisciplinary SC Chemistry GA MY955 UT WOS:A1994MY95500494 ER PT J AU NICKLAUS, MC WANG, SM MILNE, GWA DRISCOLL, JS AF NICKLAUS, MC WANG, SM MILNE, GWA DRISCOLL, JS TI CONFORMATIONAL-CHANGES OF LIGANDS DURING BINDING SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 NCI,DCT,DTP,MRD CHEM LAB,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD MAR 13 PY 1994 VL 207 BP A133 EP COMP PN 1 PG 0 WC Chemistry, Multidisciplinary SC Chemistry GA MY954 UT WOS:A1994MY95401850 ER PT J AU MELBYE, M COTE, TR KESSLER, L GAIL, M BIGGAR, RJ LEMP, G WEST, D SINGLETON, J YOUNG, J KERNDT, P DEAPEN, D GINZBERG, M ANTONCULVER, H LIEB, S HOPKINS, R WILLIAMS, B LIFF, J MORGAN, D PARKIN, W AF MELBYE, M COTE, TR KESSLER, L GAIL, M BIGGAR, RJ LEMP, G WEST, D SINGLETON, J YOUNG, J KERNDT, P DEAPEN, D GINZBERG, M ANTONCULVER, H LIEB, S HOPKINS, R WILLIAMS, B LIFF, J MORGAN, D PARKIN, W TI HIGH-INCIDENCE OF ANAL CANCER AMONG AIDS PATIENTS SO LANCET LA English DT Article ID IV HIV DISEASE; INTRAEPITHELIAL NEOPLASIA; PAPILLOMAVIRUS INFECTION; HUMAN IMMUNODEFICIENCY; HOMOSEXUAL MEN; MARITAL-STATUS; CARCINOMA; ASSOCIATION; PARALLEL AB Until now, the only cancers that have been strongly associated with AIDS are Kaposi's sarcoma and non-Hodgkin lymphoma. We used a linkage between AIDS (50 050 reports) and cancer (859 398 reports) registries in seven health departments in the USA to investigate the association between HIV infection and epidermoid anal cancer. We compared the numbers of observed cases and expected cases, calculated from general population rates with adjustment for age, sex, and race. The relative risk of anal cancer at and after AIDS diagnosis was 84.1 (95% CI 46.4-152) among homosexual patients (11 cases) and 37.7 (9.4-151) among non-homosexual patients (2 cases). The relative risk of anal cancer up to 5 years before the AIDS diagnosis (23 cases) was also increased; it was 13.9 (6.6-29.2) in the period 2-5 years before AIDS and 27.4 (15.9-47.2) during the 2 years before AIDS diagnosis (p for trend = 0.004). Among homosexual men, the relative risk of anal cancer was inversely related to age at AIDS onset (p for trend < 0.001). Excess risks were found in all geographical areas. This study establishes a strikingly increased risk of anal cancer among people with AIDS, These data are consistent with a previously hypothesised association between HIV-induced immunodeficiency and anal cancer development, but because homosexual men were at increased risk of anal cancer even before the AIDS epidemic, we cannot say how much of the increased risk is attributable to HIV infection. Nevertheless, clinicians should be aware that AIDS patients have an increased risk of anal cancer. C1 NCI,DIV CANC ETIOL,VIRAL EPIDEMIOL BRANCH,ROCKVILLE,MD 20852. STATE SERUM INST,DANISH EPIDEMIOL SCI CTR,COPENHAGEN,DENMARK. NCI,DIV CANC PREVENT & CONTROL,APPL RES BRANCH,ROCKVILLE,MD 20852. NCI,DIV CANC ETIOL,BIOSTAT BRANCH,ROCKVILLE,MD 20852. NR 29 TC 196 Z9 198 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 MAR 12 PY 1994 VL 343 IS 8898 BP 636 EP 639 DI 10.1016/S0140-6736(94)92636-0 PG 4 WC Medicine, General & Internal SC General & Internal Medicine GA NA093 UT WOS:A1994NA09300009 PM 7906812 ER PT J AU SOH, J DONNELLY, RJ KOTENKO, S MARIANO, TM COOK, JR WANG, N EMANUEL, S SCHWARTZ, B MIKI, T PESTKA, S AF SOH, J DONNELLY, RJ KOTENKO, S MARIANO, TM COOK, JR WANG, N EMANUEL, S SCHWARTZ, B MIKI, T PESTKA, S TI IDENTIFICATION AND SEQUENCE OF AN ACCESSORY FACTOR REQUIRED FOR ACTIVATION OF THE HUMAN INTERFERON-GAMMA RECEPTOR SO CELL LA English DT Article ID HUMAN IMMUNE INTERFERON; EXTRACELLULAR DOMAIN; IFN-GAMMA; TYROSINE PHOSPHORYLATION; MOLECULAR-CLONING; SIGNAL TRANSDUCER; ALPHA RECEPTOR; HAMSTER-CELLS; EXPRESSION; CDNA AB Human chromosomes 6 and 21 are both necessary to confer sensitivity to human interferon gamma (Hu-IFN-gamma), as measured by induction of class I human leukocyte antigen (HLA) and protection against encephalomyocarditis virus (EMCV) infection. Whereas human chromosome 6 encodes the Hu-IFN-gamma receptor, human chromosome 21 encodes accessary factors for generating biological activity through the Hu-IFN-gamma receptor. Probes from a genomic clone were used to identity cDNA clones expressing a species-specific accessory factor. These cDNA clones are able to substitute for human chromosome 21 to reconstitute the Hu-IFN-gamma receptor-mediated induction of class I HLA antigens. However, the factor encoded by the cDNA does not confer full antiviral protection against EMCV, confirming that an additional factor encoded on human chromosome 21 is required for reconstitution of antiviral activity against EMCV. We conclude that this accessory factor belongs to a family of such accessory factors responsible for different actions of IFN-gamma. C1 UNIV MED & DENT NEW JERSEY,ROBERT WOOD JOHNSON MED SCH,DEPT MOLEC GENET & MICROBIOL,PISCATAWAY,NJ 08854. NCI,DIV CANC ETIOL,CELL & MOLEC BIOL LAB,BETHESDA,MD 20892. FU NCI NIH HHS [R01 CA46465] NR 76 TC 232 Z9 235 U1 1 U2 6 PU CELL PRESS PI CAMBRIDGE PA 1050 MASSACHUSETTES AVE, CIRCULATION DEPT, CAMBRIDGE, MA 02138 SN 0092-8674 J9 CELL JI Cell PD MAR 11 PY 1994 VL 76 IS 5 BP 793 EP 802 DI 10.1016/0092-8674(94)90354-9 PG 10 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA NA890 UT WOS:A1994NA89000005 PM 8124716 ER PT J AU KEEGAN, AD NELMS, K WHITE, M WANG, LM PIERCE, JH PAUL, WE AF KEEGAN, AD NELMS, K WHITE, M WANG, LM PIERCE, JH PAUL, WE TI AN IL-4 RECEPTOR REGION CONTAINING AN INSULIN-RECEPTOR MOTIF IS IMPORTANT FOR IL4-MEDIATED IRS-1 PHOSPHORYLATION AND CELL-GROWTH SO CELL LA English DT Article ID STIMULATORY FACTOR-I; HUMAN INTERLEUKIN-4 RECEPTOR; SIGNAL TRANSDUCTION; FC-EPSILON; EXPRESSION CLONING; MOLECULAR-CLONING; B-CELLS; IDENTIFICATION; TRANSMISSION; SUPERFAMILY AB Interleukin-4 (IL-4) treatment of 32D cells overexpressing insulin receptor substrate 1 (IRS-1) causes prompt tyrosine phosphorylation of IRS-l. Transfection of truncation mutants of the human IL-4 (huIL-4) receptor into 32D-IRS-1 cells demonstrated that the region from amino acid 437-557 is important for IL-4 signaling. This region of the IL-4 receptor (IL-4R) contains the motif (488)PL-X4-NPXYXSXSD(502) (insulin/IL-4R [I4R]) found in the insulin and insulin-like growth factor 1 receptors. Mutation of Y497 to F yielded receptors that caused little or no IRS-1 phosphorylation in response to huIL-4 when expressed in 32D-IRS-1 cells. Most cell lines expressing Y497F also failed to proliferate in response to huIL-4. Furthermore, a glutathione-S-transferase fusion protein containing the I4R motif-bound IRS-1,tyrosine kinase(s), and other unidentified phosphoproteins with molecular sizes of 140, 80, and 55 kd. Thus, the central tyrosine of the I4R motif has a major role in IL-4-mediated signal transduction in 32D cells. C1 HARVARD UNIV,DEPT MED,JOSLIN DIABET CTR,BOSTON,MA 02215. NCI,CELLULAR & MOLEC BIOL LAB,BETHESDA,MD 20892. RP KEEGAN, AD (reprint author), NIAID,IMMUNOL LAB,BETHESDA,MD 20892, USA. NR 43 TC 287 Z9 290 U1 0 U2 2 PU CELL PRESS PI CAMBRIDGE PA 1050 MASSACHUSETTES AVE, CIRCULATION DEPT, CAMBRIDGE, MA 02138 SN 0092-8674 J9 CELL JI Cell PD MAR 11 PY 1994 VL 76 IS 5 BP 811 EP 820 DI 10.1016/0092-8674(94)90356-5 PG 10 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA NA890 UT WOS:A1994NA89000007 PM 8124718 ER PT J AU KAROUM, F EGAN, MF WYATT, RJ AF KAROUM, F EGAN, MF WYATT, RJ TI SELECTIVE REDUCTION IN DOPAMINE TURNOVER IN THE RAT FRONTAL-CORTEX AND HYPOTHALAMUS DURING WITHDRAWAL FROM REPEATED COCAINE EXPOSURE SO EUROPEAN JOURNAL OF PHARMACOLOGY LA English DT Article DE DOPAMINE TURNOVER; 3-METHOXYTYRAMINE; DOPAC (3,4-DIHYDROXYPHENYLACETIC ACID) ID MEDIAL PREFRONTAL CORTEX; NUCLEUS-ACCUMBENS; 6-HYDROXYDOPAMINE LESIONS; BRAIN; METABOLISM; 3-METHOXYTYRAMINE; RELEASE; AMPHETAMINE; NEURONS; INVIVO AB The effects of 7 days repeated cocaine administration on the dynamics of dopamine release and metabolism in four rat brain regions (frontal cortex, hypothalamus, nucleus accumbens and striatum) were evaluated 1 week (long-term effects) after the final cocaine injection. 3-Methoxytyramine and 3,4-dihydroxyphenylacetic acid (DOPAC) rates of formation were respectively used to assess the dynamics of dopamine release and metabolism. Consistent with a previous report, cocaine withdrawal was associated with marked reductions in DOPAC rate of formation in the frontal cortex and hypothalamus but not in the nucleus accumbens or the striatum. Dopamine release as indicated by 3-methoxytyramine steady-state concentration and its rate of formation was normal in air four brain regions 1 week after repeated cocaine exposure. The ratios of 3-methoxytyramine rate of formation to that of DOPAC were calculated and found to be increased in the frontal cortex and hypothalamus suggesting dopamine reuptake inhibition, at least 1 week after cocaine withdrawal, continued to be depressed in these regions. It is concluded that repeated cocaine has no long-term effect on dopamine release but produces selective long-term reductions in dopamine turnover in frontal cortex and hypothalamus. Cocaine withdrawal is therefore better associated with changes in dopamine turnover than with its release. RP KAROUM, F (reprint author), NIMH,NEUROSCI RES CTR,INTRAMURAL RES PROGRAM,NEUROPSYCHIAT BRANCH,WASHINGTON,DC 20032, USA. NR 40 TC 11 Z9 11 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0014-2999 J9 EUR J PHARMACOL JI Eur. J. Pharmacol. PD MAR 11 PY 1994 VL 254 IS 1-2 BP 127 EP 132 DI 10.1016/0014-2999(94)90379-4 PG 6 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA NB717 UT WOS:A1994NB71700018 PM 8206108 ER PT J AU CONOVER, CA DELEON, DD AF CONOVER, CA DELEON, DD TI ACID-ACTIVATED INSULIN-LIKE GROWTH FACTOR-BINDING PROTEIN-3 PROTEOLYSIS IN NORMAL AND TRANSFORMED-CELLS - ROLE OF CATHEPSIN-D SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID BREAST-CANCER-CELLS; PROTEASE; PREGNANCY; SECRETION; INDUCTION; COMPLEX; SURGERY AB Insulin like growth factor-binding protein-3 (IGFBP-3) is an important member of a family of proteins which binds IGF peptides and modulates their biological actions. In this study, we describe an acid-activated IGFBP-3 protease in media derived from a variety of human cell lines. Radiolabeled IGFBP-3 remained intact during incubation (pH 5.5-8) in media conditioned by normal and transformed human fibroblasts, MG-63 osteoblastic cells, and breast cancer cell lines MCF-7 and Hs578T. However, acidification of the conditioned medium samples (pH < 5.5) resulted in I-125-IGFBP-3 hydrolysis and the appearance of specific radiolabeled fragments. No proteolysis of I-125-IGFBP-3 occurred during incubation in unconditioned medium at neutral or acid pH. Estrogen treatment of estrogen receptor-positive MCF-7 cells enhanced acid-activatable IGFBP-3 proteolysis in the cell conditioned medium but had no effect on proteolytic activity in estrogen receptor negative Hs578T cells. The cell-derived IGFBP-3 protease was identified as the aspartic proteinase cathepsin D, based on acidic pH optimum, inhibition by pepstatin, distinctive proteolytic fragment pattern, and immunoreactivity with cathepsin D antisera. Furthermore, immunodepletion of cathepsin D effectively attenuated acid-activated IGFBP-3 proteolysis. These data suggest a role for cathepsin D in the regulation of cellular IGF action by virtue of its potential to alter the structure/function of IGFBP-3. C1 MAYO CLIN & MAYO FDN,ENDOCRINE RES UNIT,ROCHESTER,MN 55905. NCI,BETHESDA,MD 20892. OI De Leon, Daisy D./0000-0002-2693-0957 FU NIDDK NIH HHS [DK-43258] NR 31 TC 90 Z9 90 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 11 PY 1994 VL 269 IS 10 BP 7076 EP 7080 PG 5 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA NA032 UT WOS:A1994NA03200008 PM 7510281 ER PT J AU YANG, LJ RHEE, SG WILLIAMSON, JR AF YANG, LJ RHEE, SG WILLIAMSON, JR TI EPIDERMAL GROWTH FACTOR-INDUCED ACTIVATION AND TRANSLOCATION OF PHOSPHOLIPASE C-GAMMA-1 TO THE CYTOSKELETON IN RAT HEPATOCYTES SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID ACTIN-BINDING PROTEIN; FACTOR RECEPTOR; TYROSINE PHOSPHORYLATION; PERTUSSIS TOXIN; C-GAMMA; SIGNAL TRANSDUCTION; CALCIUM RELEASE; DNA-SYNTHESIS; EGF RECEPTOR; SH3 DOMAINS AB In this study, we have examined the relationship between epidermal growth factor (EGF)-induced tyrosine phosphorylation of phospholipase C-gamma 1 (PLC-gamma 1) and its translocation from the cytosol to the Triton X-100-insoluble cytoskeleton fraction in rat hepatocytes. The translocation of PLC-gamma 1 was specific for EGF stimulation, because a similar effect was not observed with insulin or vasopressin. EGF caused a transient increase of PLC activity in the cytoskeleton fraction which could be abolished by immunoprecipitating PLC-gamma 1. Tyrosine phosphorylated PLC-gamma 1 was seen only in the cytoskeleton fraction, suggesting that tyrosine phosphorylation is required for PLC-gamma 1 translocation to the cytoskeleton. This process may involve binding of PLC-gamma 1 to actin filaments, since actin was immunoprecipitated together with PLC-gamma 1 in the cytoskeleton after EGF treatment. EGF-induced translocation of PLC-gamma 1 to the cytoskeleton was not inhibited by pertussis toxin, but Gi alpha was translocated in an EGF dependent manner, suggesting that the interaction of PLC-gamma 1 with its activated Gi-protein is downstream from both PLC-gamma 1 tyrosine phosphorylation and its translocation to the cytoskeleton. Taken together, the present studies indicate that EGF-induced tyrosine phosphorylation of PLC-gamma 1, its association with the cytoskeleton, and its interaction with activated Gi alpha protein are all obligatory for PLC-gamma 1 activation in hepatocytes. C1 NHLBI,BIOCHEM LAB,BETHESDA,MD 20892. RP YANG, LJ (reprint author), UNIV PENN,DEPT BIOCHEM & BIOPHYS,37TH & HAMILTON WALK,PHILADELPHIA,PA 19104, USA. FU NIDDK NIH HHS [DK-15120, DK-07314, DK-19525] NR 59 TC 106 Z9 106 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 11 PY 1994 VL 269 IS 10 BP 7156 EP 7162 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA NA032 UT WOS:A1994NA03200021 PM 8125925 ER PT J AU SCHWABE, M ZHAO, J KUNG, HF AF SCHWABE, M ZHAO, J KUNG, HF TI DIFFERENTIAL EXPRESSION AND LIGAND-INDUCED MODULATION OF THE HUMAN INTERLEUKIN-6 RECEPTOR ON INTERLEUKIN-6-RESPONSIVE CELLS SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID IL-6 SIGNAL TRANSDUCER; TUMOR-NECROSIS-FACTOR; GROWTH-FACTOR; INTERFERON RECEPTOR; BREAST-CARCINOMA; MULTIPLE-MYELOMA; RAT HEPATOCYTES; DOWN-REGULATION; GAMMA-RECEPTOR; IFN-GAMMA AB The human interleukin-6 receptor (IL-6) was differentially expressed on IL-6-dependent (U266 and SKO-007) and -independent (RPMI8226) myeloma cells as well as melanoma cells (A375-C6) that are growth-inhibited by IL-6. U266 and SKO-007 cells expressed four distinct IL-6R complexes (molecular masses of 100, 120, 145, and 165 kDa) as revealed by affinity cross-linking of iodinated IL-6. RPMI8226 and A375-C6 cells primarily expressed the 165-kDa complex relative to the others. Immunoprecipitation and antibody competition studies showed that the 100- and 120-kDa complexes contained the gp80 subunit, whereas the 145- and 165-kDa complexes contained the gp130 subunit of the IL-6R. Assay solubilized U266 plasma membrane proteins by affinity cross-linking or ligand blotting revealed that only gp80 bound IL-6 specifically. Induction of an IL-6 response was associated with ligand-induced down-regulation of gp130 and was inhibited by neutralizing antin-IL-6 antibodies. Furthermore, the relative ratios of gp80 to gp130 determined the binding kinetics of the IL-6R, yielding high- and low affinity binding sites by Scatchard plots. Our data imply that distinct IL-6 bioactivities are based upon the differential expression and regulation by IL-6 of its ligand binding (gp80) and signal-transducing (gp130) receptor subunits. RP SCHWABE, M (reprint author), NCI,FREDERICK CANC RES & DEV CTR,BIOCHEM PHYSIOL LAB,BIOL RESPONSE MODIFIERS PROGRAM,BLDG 560,FREDERICK,MD 21701, USA. NR 54 TC 17 Z9 17 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 11 PY 1994 VL 269 IS 10 BP 7201 EP 7209 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA NA032 UT WOS:A1994NA03200028 PM 8125932 ER PT J AU CHAO, TSO FOSTER, DA RAPP, UR ROSNER, MR AF CHAO, TSO FOSTER, DA RAPP, UR ROSNER, MR TI DIFFERENTIAL RAF REQUIREMENT FOR ACTIVATION OF MITOGEN-ACTIVATED PROTEIN-KINASE BY GROWTH-FACTORS, PHORBOL ESTERS, AND CALCIUM SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID MAP KINASE; SIGNALING PATHWAYS; MURINE FIBROBLASTS; CELLS; MEMBRANE; PHOSPHORYLATION; THAPSIGARGIN; STIMULATION; 3T3-CELLS; BINDING AB Although a pathway that requires sequential activation of Ras, Raf, and MAP kinase kinase has been proposed as the major mechanism for stimulation of mitogen-activated protein kinase (MAP kinase), alternative pathways also exist. A wide variety of extracellular stimuli have been shown to activate MAP kinase; however, the precise mechanisms by which these stimuli mediate the signaling events have not been elucidated. Using a Balb/c-derived cell line expressing a dominant-negative mutant of Raf, we determined whether Raf is required for the activation of MAP kinase by growth factors, phorbol esters, and calcium. Insulin-like growth factor I (IGF-I), epidermal growth factor (EGF), and phorbol 12,13-dibutyrate activated Ras in both mutant and control cells. However, stimulation of MAP kinase by IGF-I was nearly abolished in the dominant-negative Raf mutant. Stimulation of MAP kinase by the Ca2+ mobilizer thapsigargin was also inhibited in the presence of the Raf mutant. In contrast, EGF and phorbol 12,13-dibutyrate remained potent stimulators of MAP kinase in the dominant-negative Raf cells. The activation of MAP kinase by these stimuli can be further distinguished by differential requirements for Ca2+ and protein kinase C. These results suggest that Raf is required for the activation of MAP kinase by IGF-I and calcium, whereas EGF and possibly phorbol eaters may employ alternative Raf-independent pathways for MAP kinase activation. 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. NCI,VIRAL CARCINOGENESIS LAB,FREDERICK,MD 21702. FU NCI NIH HHS [CA35541, CA46677] NR 39 TC 130 Z9 130 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 11 PY 1994 VL 269 IS 10 BP 7337 EP 7341 PG 5 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA NA032 UT WOS:A1994NA03200049 PM 8125950 ER PT J AU KELMAN, DJ DEGRAY, JA MASON, RP AF KELMAN, DJ DEGRAY, JA MASON, RP TI REACTION OF MYOGLOBIN WITH HYDROGEN-PEROXIDE FORMS A PEROXYL RADICAL WHICH OXIDIZES SUBSTRATES SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID SPERM WHALE MYOGLOBIN; METMYOGLOBIN; RESONANCE; FERRYLMYOGLOBIN; TYR-151; SYSTEMS AB Evidence is presented that the radical observed upon reaction of myoglobin with hydrogen peroxide is a peroxyl radical. Simulation of this spectrum gives principal values for the g tenser of g(x) = 2.0357, g(y) = 2.0082, and g(z) = 2.0016, which are consistent with those of a peroxyl radical. Use of molecular oxygen isotopically labeled with O-17 confirmed that the radical observed was a peroxyl radical. Removal of oxygen from the incubation by use of glucose and glucose oxidase revealed two radicals, one at g(iso) = 2.0028 and the other at g(iso) = 2.0073. Addition of various amounts of the spin trap 5,5-dimethyl-1-pyrroline N-oxide revealed that the spin trap and oxygen compete for the same radical site. Four model substrates, glutathione, styrene, arachidonic acid and linoleic acid, were individually added to both the aerobic and anoxic systems. Glutathione reacted with the peroxyl radical, reducing its intensity by 98%, and entirely eliminated the g(iso) = 2.0028 line from the spectrum of the anoxic incubation. Styrene, arachidonic acid and linoleic acid reacted with the peroxyl radical, reducing its amplitude by 84, 57, and 35%, respectively, but did not decrease the amplitude of either radical species in the anoxic incubation. The g(iso) = 2.0028 species detected in the anoxic incubation appears to be the original radical site to which molecular oxygen binds to form the peroxyl radical. This myoglobin-derived peroxyl radical species is responsible for the advent of lipid peroxidation as proposed in ischemia/repurfusion injury, as well as other reactions, as exemplified by the O-2-dependent epoxidation of styrene. C1 UNIV N CAROLINA,CURRICULUM TOXICOL,CHAPEL HILL,NC 27599. RP KELMAN, DJ (reprint author), NIEHS,MOLEC BIOPHYS LAB,RES TRIANGLE PK,NC 27709, USA. NR 31 TC 134 Z9 134 U1 0 U2 6 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD MAR 11 PY 1994 VL 269 IS 10 BP 7458 EP 7463 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA NA032 UT WOS:A1994NA03200068 PM 8125965 ER PT J AU AHN, BY GERSHON, PD MOSS, B AF AHN, BY GERSHON, PD MOSS, B TI RNA POLYMERASE-ASSOCIATED PROTEIN RAP94 CONFERS PROMOTER SPECIFICITY FOR INITIATING TRANSCRIPTION OF VACCINIA VIRUS EARLY-STAGE GENES SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID TEMPERATURE-SENSITIVE MUTANTS; FACTOR-IIF; 2ND-LARGEST SUBUNIT; INTERMEDIATE GENE; TERNARY COMPLEXES; DNA; EXPRESSION; GENOME; IDENTIFICATION; COMPONENT AB The association of a 94,000-Da viral polypeptide, called Rap94, with 30-40% of the multisubunit DNA-dependent RNA polymerase molecules purified from infectious vaccinia virus particles was established by immunoaffinity chromatography. The submolar amount of Rap94, relative to RNA polymerase, was confirmed by quantitative immunoblotting of total virion extracts. Only the RNA polymerase molecules containing Rap94 could functionally interact with VETF, the vaccinia virus early transcription factor, to transcribe a double-stranded DNA template regulated by a viral early stage promoter. Rap94 was required for the synthesis of short oligoribonucleotides and for the formation of stable ter nary transcription complexes. With a nonspecific single stranded DNA template, however, the Rap94-deficient polymerase had greater catalytic activity than the Rap94-containing polymerase. These data support a model in which Rap94 confers specificity to the RNA polymerase for promoters of early stage genes. C1 NIAID,VIRAL DIS LAB,BETHESDA,MD 20892. NR 48 TC 41 Z9 42 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 11 PY 1994 VL 269 IS 10 BP 7552 EP 7557 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA NA032 UT WOS:A1994NA03200082 PM 8125977 ER PT J AU WERTHEIMER, E BARBETTI, F MUGGEO, M ROTH, J TAYLOR, SI AF WERTHEIMER, E BARBETTI, F MUGGEO, M ROTH, J TAYLOR, SI TI 2 MUTATIONS IN A CONSERVED STRUCTURAL MOTIF IN THE INSULIN-RECEPTOR INHIBIT NORMAL FOLDING AND INTRACELLULAR-TRANSPORT OF THE RECEPTOR SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID DEPENDENT PROTEIN-KINASE; GROWTH-FACTOR; CELL-SURFACE; EXTRACELLULAR DOMAIN; CATALYTIC SUBUNIT; IMPAIRS TRANSPORT; PROLINE MUTATION; MUTANT ALLELES; ALPHA-SUBUNIT; RESISTANCE AB Insulin initiates its biological response by binding to the extracellular domain of the insulin receptor. The N-terminal half of the alpha-subunit contains several repeats of a loosely conserved motif consisting of a central glycine plus several hydrophobic amino acid residues upstream from the glycine, Hy phi Xaa-Xaa-Hy phi-Xaa-Hy phi Hy phi-Xaa-Gly (where Hy phi represents a hydrophobic amino acid residue). This structural motif has been proposed to be important in determining the three-dimensional structure of the insulin binding domain. We have identified two naturally occurring mutant alleles of the insulin receptor gene in an insulin-resistant patient, substitution of Ala for Val(28) and Arg for Gly(366). The mu- tations alter conserved amino acid residues in two distinct repeats of the structural motif described above, When mutant cDNAs were expressed in NIH-3T3 cells, both mutations severely impaired proteolytic processing of the proreceptor to mature alpha and beta-subunits. Transport of mutant receptors to the plasma membrane was also impaired. However, the minority (<1O%) of receptors that were eventually transported to the plasma membrane retained the ability to bind insulin with nor- mal affinity and to undergo insulin-stimulated phosphorylation. In conclusion, the effects of these naturally occurring mutations provide experimental support for the importance of the conserved glycine-containing structural motifs described above. By interrupting these structural motifs, the Ala(28) and Arg(366) mutations prevent normal folding of the insulin receptor alpha-subunit, thereby inhibiting post-translational processing and intracellular transport of the mutant receptors. C1 NIDDKD,DIABET BRANCH,BETHESDA,MD 20892. OSPED POLICLIN UNIV VERONA,DEPT METAB DIS,I-37134 VERONA,ITALY. NR 31 TC 20 Z9 21 U1 0 U2 1 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD MAR 11 PY 1994 VL 269 IS 10 BP 7587 EP 7592 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA NA032 UT WOS:A1994NA03200087 PM 8125981 ER PT J AU KUAN, CT WANG, QC PASTAN, I AF KUAN, CT WANG, QC PASTAN, I TI PSEUDOMONAS EXOTOXIN-A MUTANTS - REPLACEMENT OF SURFACE-EXPOSED RESIDUES IN DOMAIN-II WITH CYSTEINE RESIDUES THAT CAN BE MODIFIED WITH POLYETHYLENE-GLYCOL IN A SITE-SPECIFIC MANNER SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID RECOMBINANT INTERLEUKIN-2; NUCLEOTIDE-SEQUENCE; ESCHERICHIA-COLI; AERUGINOSA; PROTEIN; TOXIN; GENE; CONJUGATION; MUTAGENESIS; EXPRESSION AB Pseudomonas exotoxin A (PE) is a three-domain protein in which domain Ia is involved in recognition of receptors on eukaryotic target cells, domain II promotes translocation of PE into the cytosol, and domain III en- zymatically ADP-ribosylates elongation factor 2. Modification of proteins with polyethylene glycol (PEG) has been shown to prolong circulating plasma lifetime and may reduce or eliminate immunogenicity. However, in the case of toxins, PEG may interfere with or block toxin activity. To investigate the effect of polyethylene glycolation on specific residues located on the surface of PE domain II, we substituted cysteine, for each of the five most exposed surface amino acids (H276, E282, N306, R313, and E327) in domain II. These cysteines can serve as unique sites for PEG modification. The PE-Cys proteins retained most of their cytotoxicity even when the free sulfhydryl group was blocked by 5,5'-dithiobis(nitrobenzoic acid) or glutathione. When the PE-Cys proteins were conjugated with ovalbumin using a cleavable disulfide linkage, cytotoxicity was retained, but it was lost with a non-cleavable thioether linkage. In contrast, cytotoxicity was maintained when PE-Cys mutants were coupled to 5- or 20-kDa mPEG, using either a disulfide or a thioether linkage. Unexpectedly in some cases, the thioether conjugate was more active than the disulfide linkage. Pharmacokinetic studies on one of the polyethylene glycolated molecules (R313C) showed that the mean residence time (t(1/2) was prolonged to 72 min, compared to 20 min for unpolyethylene glycolated PECys(R313C). These studies show it is possible to derivatize PE at specific residues in domain II, maintain significant cytotoxic activity, and alter pharmacokinetics. These studies also suggest that large mPEG molecules can be translocated to the cytosol while still attached to domain II of PE. C1 NCI,DIV CANC BIOL DIAG & CTR,MOLEC BIOL LAB,BETHESDA,MD 20892. NR 36 TC 53 Z9 55 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 11 PY 1994 VL 269 IS 10 BP 7610 EP 7616 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA NA032 UT WOS:A1994NA03200091 PM 8125985 ER PT J AU SHIPLEY, DS ROSS, AM MOHAN, RS WHALEN, DL SAYER, JM SERVE, PM JERINA, DM AF SHIPLEY, DS ROSS, AM MOHAN, RS WHALEN, DL SAYER, JM SERVE, PM JERINA, DM TI SOLVOLYSIS OF (4-NITROPHENOXY)ETHYLENE OXIDES SO JOURNAL OF ORGANIC CHEMISTRY LA English DT Article ID EPOXIDE HYDRASE ACTIVITY; GENERAL ACID CATALYSIS; CHLORIDE-ION; HYDROLYSIS; ACETALS; MECHANISM; INTERMEDIATE; METHANOLYSIS; NAPHTHALENE; ASSAY AB (4-Nitrophenoxy)ethylene oxide (1a) (2-chloro-4-nitrophenoxy)ethylene oxide (1b), and (4-phenylphenoxy) ethylene oxide (1c) were synthesized. Rates of acid-catalyzed, noncatalyzed, and hydroxide ion-catalyzed reactions for is and Ib and rates of acid-catalyzed and noncatalyzed hydrolysis of 1c were measured in 0.1 M NaClO4 solutions. Acid-catalyzed hydrolysis of 1a is ca. 6200 times faster than that of 4-nitrostyrene oxide, and that of 1c is 57 times faster than that of styrene oxide. These increased rates are attributed to stabilization of developing positive charge on the acetal carbon by the phenoxy oxygen that is present in the substituted phenoxyethylene oxides but not in the styrene oxides. The pH-rate profiles for reaction of 1a and 1b in 1.0 M KCl solutions over the pH range 2-14 were determined. At intermediate pH, the rates of reaction of 1a and 1b in 1.0 M KCl solutions are ca. 6-8 times faster than the corresponding rates in 0.1 M NaClO4 solutions. From rate and product studies, these increased reaction rates in KCl solutions were attributed to bimolecular attack of chloride ion at the methylene carbon of the epoxide moiety, The reactivity of 1a is greater than that of 1b toward acid-catalyzed hydrolysis but less than that of 1b in both noncatalyzed and hydroxide ion-catalyzed hydrolysis. Compound 1c reacts about 73-fold faster than 1a in acid and about 11-fold faster in the noncatalyzed reaction. From reactivity considerations, it is proposed that H2O and HO- also add as nucleophiles to the methylene carbon of the epoxide moieties of 1a and 1b, whereas H2O adds to the acetal carbon of 1c. C1 UNIV MARYLAND,DEPT CHEM & BIOCHEM,CHEM DYNAM LAB,CATONSVILLE,MD 21228. NIDDK,BIOORGAN CHEM LAB,BETHESDA,MD 20892. NR 45 TC 3 Z9 3 U1 2 U2 4 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0022-3263 J9 J ORG CHEM JI J. Org. Chem. PD MAR 11 PY 1994 VL 59 IS 5 BP 977 EP 983 DI 10.1021/jo00084a012 PG 7 WC Chemistry, Organic SC Chemistry GA NB443 UT WOS:A1994NB44300012 ER PT J AU BOYD, DR DAVIES, RJH HAMILTON, L MCCULLOUGH, JJ MALONE, JF PORTER, HP SMITH, A CARL, JM SAYER, JM JERINA, DM AF BOYD, DR DAVIES, RJH HAMILTON, L MCCULLOUGH, JJ MALONE, JF PORTER, HP SMITH, A CARL, JM SAYER, JM JERINA, DM TI SYNTHESIS AND SOLVOLYSIS OF ACRIDINE 1,2-OXIDE AND 3,4-OXIDE - CRYSTAL-STRUCTURE OF ACRIDINE 1,2-OXIDE SO JOURNAL OF ORGANIC CHEMISTRY LA English DT Article ID REGION ARENE OXIDES; METABOLISM AB Acridine 1,2- and 3,4-oxides were synthesized from 3,4- and 1,2-dihydroacridine, respectively, via intermediate bromohydrin acetates. Crystals of acridine 1,2-oxide were sufficiently stable to allow the first determination of X-ray crystallographic structural features of a non-K-region arene oxide. Aqueous alkaline hydrolysis of the acridine 1,2- and 3,4-oxides produced trans-1,2-dihydrorxy-1,2-dihydroacridine and trans-3,4-dihydroxy-3,4-dihydroacridine, respectively. The former dihydrodiol was also obtained by a six-step synthesis from 3,4-dihydroacridine. Acid-catalyzed hydrolysis of acridine 1,2-oxide yielded the corresponding cis- and trans-1,2-dihydrodiols (20%) in addition to 1-hydroxy- (12%) and 2-hydroxyacridine (68%). By contrast, solvolysis of acridine 3,4-oxide under acid conditions gave 4-hydroxyacridine as the exclusive product. pH-rate profiles for hydrolysis of the acridine oxides in 1:9 dioxane-water at 25 degrees C were compared with those for anthracene 1,2-oxide, naphthalene 1,2-oxide, and quinoline 5,6- and 7,8-oxides. Second-order rate constants for the hydronium ion-catalyzed ring opening of anthracene 1,2-, acridine 3,4-, and acridine 1,2-oxide are 585, 7.81, and 0.45 M(-1) s(-2), respectively, and are 3-5 times larger than the rate constants for the corresponding naphthalene 1,2-, quinoline 7,8-, and quinoline 5,6-oxides. Rate constants for uncatalyzed ring opening of anthracene 1,2- and acridine 3,4-oxides (117 x 10(-5) s(-1) and 2.4 X 10(-5) s(-1), respectively) are about two to three times larger than the corresponding rate constants for naphthalene 1,2- and quinoline 7,8-oxides, whereas the rate of nucleophilic ring opening by hydroxide ion to give the trans-dihydrodiols is accelerated by less than a factor of 2 for the acridine oxides as compared with their quinoline analogs. The pH-rate profiles for solvolysis of the acridine oxides, like those of the quinoline oxides, exhibit a pH-independent region at pH values below the pK(a) of the ring nitrogen that is attributed to formation of an unreactive N-protonated species. C1 QUEENS UNIV BELFAST,SCH BIOCHEM,BELFAST BT9 5AG,ANTRIM,NORTH IRELAND. NIDDK,BIOORGAN CHEM LAB,BETHESDA,MD 20892. RP BOYD, DR (reprint author), QUEENS UNIV BELFAST,SCH CHEM & BIOL,BELFAST BT9 5AG,ANTRIM,NORTH IRELAND. NR 29 TC 11 Z9 11 U1 1 U2 2 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 11 PY 1994 VL 59 IS 5 BP 984 EP 990 DI 10.1021/jo00084a013 PG 7 WC Chemistry, Organic SC Chemistry GA NB443 UT WOS:A1994NB44300013 ER PT J AU DRISCOLL, CT DARLINGTON, GJ MARAIA, RJ AF DRISCOLL, CT DARLINGTON, GJ MARAIA, RJ TI THE CONSERVED 7SK SNRNA GENE LOCALIZES TO HUMAN CHROMOSOME-6 BY HOMOLOG EXCLUSION PROBING OF SOMATIC-CELL HYBRID RNA SO NUCLEIC ACIDS RESEARCH LA English DT Article ID POLYMERASE-III; PSEUDOGENES; SEQUENCES; UPSTREAM; TRANSCRIPTION; ELEMENTS; REGION; GENOME; SNRPN; DNA AB Many small RNAs contribute essential activities to eukaryotic cells. In mammalian genomes dispersed repetitive sequences which exhibit homology to small RNAs often exist as pseudogenes which can complicate identification, localization, and analysis of the authentic gene. We mapped a productive human 7SK small nuclear RNA gene to human chromosome 6 by analyzing Northern blots derived from a panel of somatic cell hybrids that contain single human chromosomes. In order to avoid crossreactivity of the probe with rodent 7SK RNA, which is 98% identical to human 7SK, a method termed homolog exclusion probing was developed. This method uses an excess of non-labelled rodent-specific oligodeoxynucleotide to block the rodent 7SK RNA from hybridizing with the human-specific oligodeoxynucleotide probe. The effectiveness of this method to enhance the human 7SK RNA signal is demonstrated. The potential to map and subsequently isolate other small RNA genes by this approach and the use of homolog exclusion probing to discriminate among family members of highly related RNAs and DNAs in a single species is discussed. C1 NICHHD,MOLEC GROWTH REGULAT LAB,BLDG 6,ROOM 416,9000 ROCKVILLE PIKE,BETHESDA,MD 20892. TEXAS CHILDRENS HOSP,DEPT PATHOL,HOUSTON,TX 77030. NR 24 TC 4 Z9 4 U1 0 U2 1 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 MAR 11 PY 1994 VL 22 IS 5 BP 722 EP 725 DI 10.1093/nar/22.5.722 PG 4 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA NB375 UT WOS:A1994NB37500003 PM 8139910 ER PT J AU MURTAGH, JJ MOSS, J VAUGHAN, M AF MURTAGH, JJ MOSS, J VAUGHAN, M TI ALTERNATIVE SPLICING OF THE GUANINE-NUCLEOTIDE-BINDING REGULATORY PROTEIN-G(O-ALPHA) GENERATES 4 DISTINCT MESSENGER-RNAS SO NUCLEIC ACIDS RESEARCH LA English DT Article ID BOVINE BRAIN MEMBRANES; POLYMERASE CHAIN-REACTION; AMINO-ACID-SEQUENCE; ALPHA-SUBUNIT; MOLECULAR-CLONING; GO-ALPHA; ADENYLATE-CYCLASE; G-PROTEINS; RAT-BRAIN; SIGNAL-TRANSDUCTION AB G(oalpha) a guanine nucleotide-binding (G) protein abundant in brain and other neural tissues, has been implicated in ion channel regulation. Concerted efforts in several laboratories have revealed multiple G(oalpha), mRNAs and protein isoforms in different contexts. G(oalpha) is a single copy gene in mammalian species, although the structure, number and tissue localization of G(oalpha) mRNAs reported by investigators are inconsistent. To define the cell-specific expression of alternatively spliced variants of G(oalpha) mRNA, we employed several strategies, including Northern hybridizations with sequence-specific oligonucleotides, selective digestions of G(oalpha) mRNA using RNase H, and adaptations of the polymerase chain reaction. Four distinct alternatively spliced variants were identified, a 5.7-kb G(oalpha)2 mRNA and three G(oalpha)1 mRNAs with different 3' UTRs. The UTRs of the three G(oalpha1s) are composed of different combinations of what have been referred to as UTR-A and UTR-B. The sequences of the spliced segments are well conserved among mammalian species, suggesting a functional role for these alternatively spliced 3' UTRs in post-transcriptional and/or tissue-specific regulation of G(oalpha) expression. The position of the intron - exon splice boundary at nucleotide 31 following T of the TGA stop codon is conserved in the G(ialpha)2 and Gi(ialpha)3 genes, consistent with the notion that similar alternative splicing of 3' UTRs occurs in products of these related genes. RP MURTAGH, JJ (reprint author), NHLBI,CELLULAR METAB LAB,ROOM 5N307,BLDG 10,BETHESDA,MD 20892, USA. NR 62 TC 16 Z9 16 U1 0 U2 2 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 MAR 11 PY 1994 VL 22 IS 5 BP 842 EP 849 DI 10.1093/nar/22.5.842 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA NB375 UT WOS:A1994NB37500020 PM 8139926 ER PT J AU ZHOU, H FISHER, RJ PAPAS, TS AF ZHOU, H FISHER, RJ PAPAS, TS TI OPTIMIZATION OF PRIMER SEQUENCES FOR MOUSE SCFV REPERTOIRE DISPLAY LIBRARY CONSTRUCTION SO NUCLEIC ACIDS RESEARCH LA English DT Article ID PHAGE; GENERATION; PROTEIN C1 PRI DYNCORP,CELLULAR BIOCHEM LAB,FREDERICK,MD 21702. NCI,FCRDC,MOLEC ONCOL LAB,FREDERICK,MD 21702. RI Fisher, Robert/B-1431-2009 FU NCI NIH HHS [CP05667, NCI NO1-CO-74102] NR 9 TC 55 Z9 60 U1 0 U2 3 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 MAR 11 PY 1994 VL 22 IS 5 BP 888 EP 889 DI 10.1093/nar/22.5.888 PG 2 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA NB375 UT WOS:A1994NB37500029 PM 8139934 ER PT J AU LONG, SR ZAKIAN, V ALLEN, NS ARVIN, AM BAKKEN, A BEEMON, K BELFORT, M BENNETT, KL BISSELL, MJ BLACKBURN, E BLAU, H CARLSON, M CHANDLER, V CHILTON, MD CLARKE, AE COLEMAN, MS CORUZZI, G CRAIG, EA DAVIS, TN DUTCHER, SK ECKHARDT, LA ELGIN, SCR ENRIETTO, PJ ESPOSITO, RE FLINT, J FULLER, MT GALLOWAY, D GOODENOUGH, U GRAVES, B GREENWALD, I GROSS, CA HANSON, MR HENRY, SA HUANG, AS KIMBLE, J KLINMAN, JP LIDSTROM, ME LINDQUIST, S LINIAL, M WONGSTAAL, F MARTIN, NC OLMSTED, JB PRAKASH, L PRIVES, C PUKKILA, PJ RAIKHEL, N ROBINSON, HL ROSENBERG, N ROTHMANDENES, LB ROWLEY, JD RUDNER, R SCHAAL, BA SCHUPBACH, T SHAPIRO, L SIBLEY, CH SINGER, MF SKALKA, AM SOLLNERWEBB, B SPECTOR, DH STEITZ, JA STROME, S TILGHMAN, SM TOBIN, EM WALL, JD WESSLER, S HOPPER, AK AF LONG, SR ZAKIAN, V ALLEN, NS ARVIN, AM BAKKEN, A BEEMON, K BELFORT, M BENNETT, KL BISSELL, MJ BLACKBURN, E BLAU, H CARLSON, M CHANDLER, V CHILTON, MD CLARKE, AE COLEMAN, MS CORUZZI, G CRAIG, EA DAVIS, TN DUTCHER, SK ECKHARDT, LA ELGIN, SCR ENRIETTO, PJ ESPOSITO, RE FLINT, J FULLER, MT GALLOWAY, D GOODENOUGH, U GRAVES, B GREENWALD, I GROSS, CA HANSON, MR HENRY, SA HUANG, AS KIMBLE, J KLINMAN, JP LIDSTROM, ME LINDQUIST, S LINIAL, M WONGSTAAL, F MARTIN, NC OLMSTED, JB PRAKASH, L PRIVES, C PUKKILA, PJ RAIKHEL, N ROBINSON, HL ROSENBERG, N ROTHMANDENES, LB ROWLEY, JD RUDNER, R SCHAAL, BA SCHUPBACH, T SHAPIRO, L SIBLEY, CH SINGER, MF SKALKA, AM SOLLNERWEBB, B SPECTOR, DH STEITZ, JA STROME, S TILGHMAN, SM TOBIN, EM WALL, JD WESSLER, S HOPPER, AK TI WOMEN IN BIOMEDICINE - ENCOURAGEMENT SO SCIENCE LA English DT Letter C1 UNIV WASHINGTON,FRED HUTCHINSON CANC RES CTR,SEATTLE,WA 98104. WAKE FOREST UNIV,WINSTON SALEM,NC 27109. SUNY ALBANY,BIOCHEM MOLEC BIOL & GENET PROGRAM,ALBANY,NY. NEW YORK STATE DEPT HLTH,ALBANY,NY 12201. UNIV MISSOURI,COLUMBIA,MO. LAWRENCE BERKELEY LAB,DIV LIFE SCI,BERKELEY,CA. UNIV CALIF BERKELEY,COMPARAT BIOCHEM & MOLEC BIOL GRP,BERKELEY,CA. UNIV CALIF SAN FRANCISCO,SAN FRANCISCO,CA 94143. COLUMBIA UNIV,NEW YORK,NY. UNIV OREGON,EUGENE,OR 97403. CIBA GEIGY CORP,AGR BIOTECHNOL,RES TRIANGLE PK,NC. UNIV MELBOURNE,SCH BOT,PARKVILLE,VIC 3052,AUSTRALIA. PLANT CELL BIOL RES CTR,PARKVILLE,VIC,AUSTRALIA. UNIV NEW MEXICO,ALBUQUERQUE,NM 87131. NYU,NEW YORK,NY 10003. UNIV WISCONSIN,MADISON,WI. UNIV COLORADO,BOULDER,CO 80309. CUNY HUNTER COLL,NEW YORK,NY 10021. WASHINGTON UNIV,ST LOUIS,MO. SUNY STONY BROOK,STONY BROOK,NY 11794. STANFORD UNIV,DEPT PEDIAT,ASSOCIATE CHAIR ACAD AFFAIRS,STANFORD,CA 94305. UNIV CHICAGO,COMM GENET,CHICAGO,IL 60637. UNIV WASHINGTON,SEATTLE,WA 98195. CSIRO,SYDNEY,NSW,AUSTRALIA. UNIV UTAH,SALT LAKE CITY,UT. CORNELL UNIV,ITHACA,NY. CARNEGIE MELLON UNIV,PITTSBURGH,PA 15213. MELLON COLL SCI,PITTSBURGH,PA. PENN STATE UNIV,MILTON S HERSHEY MED CTR,HERSHEY,PA 17033. CALTECH,PASADENA,CA 91125. UNIV CHICAGO,HOWARD HUGHES MED INST,CHICAGO,IL 60637. UNIV LOUISVILLE,SCH MED,LOUISVILLE,KY 40292. UNIV ROCHESTER,ROCHESTER,NY. UNIV TEXAS,MED BRANCH,SEALY CTR MOLEC SCI,GALVESTON,TX. UNIV N CAROLINA,CHAPEL HILL,NC. MICHIGAN STATE UNIV,PLANT RES LAB,E LANSING,MI. UNIV MASSACHUSETTS,AMHERST,MA 01003. TUFTS UNIV,MEDFORD,MA 02155. CARNEGIE INST WASHINGTON,WASHINGTON,DC. NIH,BETHESDA,MD 20892. FOX CHASE CANC CTR,INST CANC RES,PHILADELPHIA,PA 19111. JOHNS HOPKINS UNIV,HUMAN GENET PROGRAM,BALTIMORE,MD. UNIV CALIF SAN DIEGO,SAN DIEGO,CA 92103. YALE UNIV,NEW HAVEN,CT. HUTCHINSON CANC RES CTR,SEATTLE,WA. INDIANA UNIV,BLOOMINGTON,IN. PRINCETON UNIV,SCI & TECHNOL COUNCIL,PRINCETON,NJ. UNIV CALIF LOS ANGELES,LOS ANGELES,CA 90024. UNIV GEORGIA,CTR PLANT CELLULAR & MOLEC BIOL,ATHENS,GA. RP LONG, SR (reprint author), STANFORD UNIV,DEPT BIOL SCI,STANFORD,CA 94305, USA. RI Prakash, Louise/C-7891-2012; Henry, Susan/K-5464-2014 NR 1 TC 0 Z9 0 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 MAR 11 PY 1994 VL 263 IS 5152 BP 1357 EP 1358 PG 2 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA MZ927 UT WOS:A1994MZ92700002 PM 8128213 ER PT J AU DIODATI, JG CANNON, RO QUYYUMI, AA AF DIODATI, JG CANNON, RO QUYYUMI, AA TI PLATELET ACTIVATION IN STABLE CORONARY-ARTERY DISEASE SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article; Proceedings Paper CT Symposium on Myocardial Ischemia: Mechanisms, Risk Reduction, and Management, at the 7th Annual Meeting of the Council-on-Myocardial-Ischemia CY DEC 04-05, 1992 CL AVENTURA, FL SP COUNCIL MYOCARDIAL ISCHEMIA, MEDED ID ACUTE MYOCARDIAL-INFARCTION; SUBSTANCE PROSTAGLANDIN-X; PACING-INDUCED ANGINA; RELAXING FACTOR; CLINICAL IMPLICATIONS; THROMBOXANE RELEASE; TACHYCARDIA STRESS; MORNING INCREASE; PROSTACYCLIN PGX; UNSTABLE ANGINA AB To elucidate the role of physical activity in the pathogenesis of acute ischemic syndromes in patients with coronary artery disease (CAD), we hypothesized that platelet activation occurs when coronary blood flew velocity and shear stress increase across an atherosclerotic vascular bed. We measured platelet aggregation by using angiologic catheterization to obtain simultaneous samples of whole blood from the coronary sinus and the aorta while at rest, 2 minutes after the onset of rapid atrial pacing and 10 minutes after termination of pacing. Of 82 consecutive patients included in our study, 36 had stenosis of the left coronary artery, 12 had stenosis of the right coronary artery only, and 34 had no evidence of CAD. Samples taken at rest revealed no arteriovenous difference in platelet aggregation between patients with CAD and those without CAD. In patients with significant stenosis (greater than or equal to 80%) of the left coronary artery, atrial pacing caused platelet aggregation to increase in samples from the coronary sinus (64 +/- 9% increase; p <0.01) but not in blood from the aorta (2 +/- 8% decrease; difference not significant). This increase was transient, with aggregation returning almost to resting values 10 minutes after pacing ended. Atrial pacing elicited no change in platelet aggregation in samples from either the coronary sinus or aorta of patients with nonsignificant stenosis (<50%) of the left coronary artery, patients with significant stenosis of the right coronary artery only, and patients free of CAD. Thus, under resting conditions, no evidence of platelet activation across the coronary bed was seen regardless of CAD status. However, significant stenosis was associated with heightened platelet activation and aggregation when coronary blood flow was increased with atrial pacing. C1 NHLBI,CARDIOL BRANCH,BETHESDA,MD 20892. NR 48 TC 9 Z9 9 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 10 PY 1994 VL 73 IS 6 BP B8 EP B11 DI 10.1016/0002-9149(94)90258-5 PG 4 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA NB417 UT WOS:A1994NB41700003 PM 8141080 ER PT J AU ABRAMS, DI GOLDMAN, AI LAUNER, C KORVICK, JA NEATON, JD CRANE, LR GRODESKY, M WAKEFIELD, S MUTH, K KORNEGAY, S COHN, DL HARRIS, A LUSKINHAWK, R MARKOWITZ, N SAMPSON, JH THOMPSON, M DEYTON, L AF ABRAMS, DI GOLDMAN, AI LAUNER, C KORVICK, JA NEATON, JD CRANE, LR GRODESKY, M WAKEFIELD, S MUTH, K KORNEGAY, S COHN, DL HARRIS, A LUSKINHAWK, R MARKOWITZ, N SAMPSON, JH THOMPSON, M DEYTON, L TI A COMPARATIVE TRIAL OF DIDANOSINE OR ZALCITABINE AFTER TREATMENT WITH ZIDOVUDINE IN PATIENTS WITH HUMAN-IMMUNODEFICIENCY-VIRUS INFECTION SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID AIDS-RELATED COMPLEX; PHASE-I TRIAL; 2',3'-DIDEOXYINOSINE DDI; HIV; DIDEOXYCYTIDINE; MODELS AB Background. Both didanosine and zalcitabine are commonly used to treat patients with human immunodeficiency virus (HIV) infection who cannot tolerate zidovudine treatment or who have had disease progression despite it. The relative efficacy and safety of these second-line therapies are not well defined. Methods. In this multicenter, open-label trial we randomly assigned 467 patients who previously received zidovudine and had 300 or fewer CD4 cells per cubic millimeter or a diagnosis of the acquired immunodeficiency syndrome (AIDS) to treatment with either didanosine (500 mg per day) or zalcitabine (2.25 mg per day). Results. After a median follow-up of 16 months, disease progression or death occurred in 157 of 230 patients assigned to didanosine and 152 of 237 patients assigned to zalcitabine, for a relative risk of 0.93 for the zalcitabine group as compared with the didanosine group (P = 0.56), which decreased to 0.84 (P = 0.15) after adjustment for the CD4 count, Karnofsky score, and presence of AIDS at base line. There were 100 deaths in the didanosine group and 88 in the zalcitabine group, for a relative risk of 0.78 (P = 0.09) and an adjusted relative risk of 0.63 (P = 0.003). A majority of patients in each group (66 percent) had at least one adverse event during treatment (153 patients taking didanosine and 157 taking zalcitabine). Peripheral neuropathy and stomatitis occurred more often with zalcitabine and diarrhea and abdominal pain more frequently with didanosine. Conclusions. For patients with HIV infection who have not responded to treatment with zidovudine, zalcitabine is at least as efficacious as didanosine in delaying disease progression and death. C1 NIAID,DIV AIDS,BETHESDA,MD 20892. UNIV CALIF SAN FRANCISCO,SAN FRANCISCO COMMUNITY CONSORTIUM AIDS,SAN FRANCISCO,CA. UNIV MINNESOTA,DIV BIOSTAT,MINNEAPOLIS,MN. HARPER GRACE HOSP,COMPREHENS AIDS ALLIANCE DETROIT,DETROIT,MI 48201. CHICAGO COMMUNITY PROGRAMS CLIN RES AIDS,CHICAGO,IL. ROW SCI,ROCKVILLE,MD. ST JOSEPH HOSP & HLTH CARE CTR,DEPT MED,CHICAGO,IL 60657. HENRY FORD HOSP,DIV INFECT DIS,DETROIT,MI 48202. RES & EDUC GRP,PORTLAND,OR. AIDS RES CONSORTIUM ATLANTA,ATLANTA,GA. NR 16 TC 170 Z9 170 U1 1 U2 5 PU MASS MEDICAL SOC PI BOSTON PA 10 SHATTUCK, BOSTON, MA 02115 SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD MAR 10 PY 1994 VL 330 IS 10 BP 657 EP 662 DI 10.1056/NEJM199403103301001 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA MY575 UT WOS:A1994MY57500001 PM 7906384 ER PT J AU LENFANT, C AF LENFANT, C TI REDUCING THE DELAYS SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Editorial Material RP LENFANT, C (reprint author), NHLBI,BETHESDA,MD 20892, USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD MAR 9 PY 1994 VL 271 IS 10 BP 738 EP 738 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA MY288 UT WOS:A1994MY28800009 PM 8114202 ER PT J AU LENFANT, C AF LENFANT, C TI SPEED URGED FOR THROMBOLYTIC THERAPY IN ACUTE MYOCARDIAL-INFARCTION SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Editorial Material RP LENFANT, C (reprint author), NHLBI,BETHESDA,MD 20892, USA. NR 2 TC 2 Z9 2 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD MAR 9 PY 1994 VL 271 IS 10 BP 738 EP 738 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA MY288 UT WOS:A1994MY28800007 PM 8114202 ER PT J AU LENFANT, C AF LENFANT, C TI HOSPITAL DELAYS COMPOUND PATIENT AND TRANSPORT DELAYS SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Editorial Material RP LENFANT, C (reprint author), NHLBI,BETHESDA,MD 20892, USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD MAR 9 PY 1994 VL 271 IS 10 BP 738 EP 738 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA MY288 UT WOS:A1994MY28800008 PM 8114202 ER PT J AU COLLINS, FS BENJAMIN, LJ BOTSTEIN, D COX, JR DAVIDSON, N GRAY, JW HOLTZMAN, N HOUSMAN, DE JAMISON, KR NELKIN, D ROTHSTEIN, R SMITH, DC SMITH, LM SPENCE, MA TILGHMAN, SM AF COLLINS, FS BENJAMIN, LJ BOTSTEIN, D COX, JR DAVIDSON, N GRAY, JW HOLTZMAN, N HOUSMAN, DE JAMISON, KR NELKIN, D ROTHSTEIN, R SMITH, DC SMITH, LM SPENCE, MA TILGHMAN, SM TI STATEMENT ON USE OF DNA TESTING FOR PRESYMPTOMATIC IDENTIFICATION OF CANCER RISK SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Editorial Material C1 MONTEFIORE MED HOSP CTR,BRONX,NY. STANFORD UNIV,STANFORD,CA. WASHINGTON UNIV,ST LOUIS,MO. CALTECH,PASADENA,CA 91125. UNIV CALIF SAN FRANCISCO,SAN FRANCISCO,CA 94143. JOHNS HOPKINS UNIV,BALTIMORE,MD. MIT,CAMBRIDGE,MA 02139. NYU,NEW YORK,NY 10003. COLUMBIA UNIV,NEW YORK,NY. BULL INFORMAT SYST,BILLERICA,MA. UNIV WISCONSIN,MADISON,WI. UNIV CALIF IRVINE,IRVINE,CA 92717. PRINCETON UNIV,PRINCETON,NJ. RP COLLINS, FS (reprint author), NIH,NATL CTR HUMAN GENOME RES,BLDG 38A,ROOM 617,BETHESDA,MD 20892, USA. NR 7 TC 74 Z9 74 U1 0 U2 2 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 9 PY 1994 VL 271 IS 10 BP 785 EP 785 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA MY288 UT WOS:A1994MY28800035 ER PT J AU KOLEY, AP ROBINSON, RC MARKOWITZ, A FRIEDMAN, FK AF KOLEY, AP ROBINSON, RC MARKOWITZ, A FRIEDMAN, FK TI KINETICS OF CO BINDING TO CYTOCHROMES P450 IN THE ENDOPLASMIC-RETICULUM SO BIOCHEMISTRY LA English DT Article ID PSEUDOMONAS-PUTIDA CYTOCHROME-P-450; 7-ETHOXYRESORUFIN O-DEETHYLASE; ARYL-HYDROCARBON HYDROXYLASE; CARBON-MONOXIDE BINDING; RAT-LIVER MICROSOMES; MONOCLONAL-ANTIBODIES; CRYSTAL-STRUCTURE; PURIFICATION; COMPLEX; BENZOPYRENE AB The kinetics of CO binding to cytochromes P450 in rat liver microsomes were examined using the flash photolysis technique. Modulation of the kinetics by P450 form-specific effecters such as anti-P450 monoclonal antibodies and substrates was used to elucidate the kinetic behavior of individual P450s within the endoplasmic reticulum. The problem of attributing a kinetic parameter to a single P450 in the presence of multiple microsomal P450s was overcome with a difference method that employs the difference of the kinetic profiles obtained in the presence and absence of a P450 effector. Applying this approach to study the conformation/dynamics of P450 2B1 in microsomes from phenobarbital-treated rats revealed that the substrate benzphetamine enhances while testosterone inhibits the rate of CO binding to this P450. Similar experiments with P450 1A1 in microsomes from 3-methylcholanthrene-treated rats showed that the substrate benzo[alpha]pyrene accelerates CO binding. These results show that the access channel between solvent and heme in the P450 interior can be altered in a substrate- and P450-dependent manner to either hinder or facilitate CO diffusion to the heme iron. These results also demonstrate that analytical difference methods may be employed to characterize the conformation of individual P450s in their native membrane environment in the endoplasmic reticulum. C1 NCI,MOLEC CARCINOGENESIS LAB,BETHESDA,MD 20892. NIH,BIOMED INSTRUMENTAT & ENGN PROGRAM,BETHESDA,MD 20892. RI Friedman, Fred/D-4208-2016 NR 46 TC 16 Z9 16 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 8 PY 1994 VL 33 IS 9 BP 2484 EP 2489 DI 10.1021/bi00175a017 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA MZ697 UT WOS:A1994MZ69700017 PM 8117709 ER PT J AU KLEINBERG, ME MALECH, HL MITAL, DA LETO, TL AF KLEINBERG, ME MALECH, HL MITAL, DA LETO, TL TI P21RAC DOES NOT PARTICIPATE IN THE EARLY INTERACTION BETWEEN P47-PHOX AND CYTOCHROME B(558) THAT LEADS TO PHAGOCYTE NADPH OXIDASE ACTIVATION IN-VITRO SO BIOCHEMISTRY LA English DT Article ID RESPIRATORY BURST OXIDASE; CHRONIC GRANULOMATOUS-DISEASE; GTP-BINDING PROTEIN; CELL-FREE SYSTEM; HUMAN-NEUTROPHILS; PLASMA-MEMBRANE; CYTOSOLIC COMPONENTS; MICROBICIDAL OXIDASE; 2 FORMS; TRANSLOCATION AB The phagocyte superoxide-generating NADPH oxidase, a multicomponent, membrane-bound electron transport chain, consists of cytochrome b(558), p47-phox, p67-phox, and p21rac2 or p21rac2. The mechanisms of oxidase assembly are poorly understood. In previous studies using a cell-free NADPH oxidase system, we showed that preincubation of neutrophil membrane with neutrophil cytosol containing p47-phox, but not p67-phox, led to formation of a long-lived NADPH oxidase intermediate. This suggested that p47-phox interacted with cytochrome b(558) in the early stages of oxidase assembly while p67-phox participated in a later stage. Peptides containing the sequence RGVHFIF (corresponding to amino acids 559-565 of the 91-kDa subunit of cytochrome b(558)) inhibit NADPH oxidase activity by blocking the early interaction between p47-phox and cytochrome b(558) In the present study, we examined whether p21rac facilitated the interaction between p47-phox and cytochrome b(558) We preincubated pure recombinant p47-phox with neutrophil membrane containing cytochrome b(558) in the cell-free system. Superoxide-generating activity was subsequently reconstituted by adding pure rp67-phox and partially purified p21rac. RGVHFIF inhibited superoxide production if added to the cell-free system during preincubation of rp47-phox with membrane. RGVHFIF was markedly less inhibitory if added to the cell-free system after membrane was preincubated with pure rp47-phox. In contrast to p47-phox, preincubation of membrane with either p21rac or rp67-phox conferred no protection from inhibition of superoxide-generating activity by RGVHFIF added after preincubation. We conclude that p21rac does not facilitate interaction of p47-phox with cytochrome b(558) and that p47-phox is the first cytosol protein to associate with cytochrome b(558) during oxidase assembly. C1 UNIV MARYLAND,SCH MED,DEPT MED,BALTIMORE,MD 21201. NIAID,HOST DEF LAB,BETHESDA,MD 20892. RP KLEINBERG, ME (reprint author), VET AFFAIRS MED CTR,RES SERV,ROOM 3A125,10 N GREENE ST,BALTIMORE,MD 21201, USA. FU NIAID NIH HHS [AI-32220] NR 33 TC 27 Z9 27 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 8 PY 1994 VL 33 IS 9 BP 2490 EP 2495 DI 10.1021/bi00175a018 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA MZ697 UT WOS:A1994MZ69700018 PM 8117710 ER PT J AU MATSUNAGA, T WATANABE, K YAMAMOTO, I NEGISHI, M GONZALEZ, FJ YOSHIMURA, H AF MATSUNAGA, T WATANABE, K YAMAMOTO, I NEGISHI, M GONZALEZ, FJ YOSHIMURA, H TI CDNA CLONING AND SEQUENCE OF CYP2C29 ENCODING P-450-MUT-2, A MICROSOMAL ALDEHYDE OXYGENASE SO BIOCHIMICA ET BIOPHYSICA ACTA-BIOENERGETICS LA English DT Note DE CDNA CLONING; CYTOCHROME P-450 (P-450 MUT-2); CYP2C29; MICROSOMAL ALDEHYDE OXYGENASE; (MOUSE) ID LIVER MESSENGER-RNA; CARBOXYLIC-ACID; RAT LIVERS; CYTOCHROME-P-450; MECHANISM; DNA AB A cDNA clone encoding a cytochrome P-450 (P-450) isozyme was isolated from a mouse liver cDNA library. This P-450, designated CYP2C29, the first member of the mouse CYP2C subfamily to be reported, contained the complete coding region of 490 amino acid residues. The deduced amino acid sequence of CYP2C29 exhibited 83% identity with that of the rat CYP2C7 and had an N-terminal sequence identical to that of P-450 MUT-2, a microsomal aldehyde oxygenase. Two peptides, derived from BrCN cleavage of P-450 MUT-2, were also identical to the cDNA deduced protein of CYP2C29. These results indicate that CYP2C29 cDNA encodes P-450 MUT-2. C1 HOKURIKU UNIV,FAC PHARMACEUT SCI,DEPT HYG CHEM,KANAZAWA,ISHIKAWA 92011,JAPAN. NIEHS,PHARMACOGENET SECT,RES TRIANGLE PK,NC 27709. NCI,MOLEC CARCINOGENESIS LAB,BETHESDA,MD 20892. NAKAMURA GAKUEN COLL,DEPT FOOD & NUTR,JOHNEN KU,FUKUOKA 81401,JAPAN. NR 18 TC 22 Z9 25 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0005-2728 J9 BBA-BIOENERGETICS JI Biochim. Biophys. Acta-Bioenerg. PD MAR 8 PY 1994 VL 1184 IS 2-3 BP 299 EP 301 DI 10.1016/0005-2728(94)90237-2 PG 3 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA NA917 UT WOS:A1994NA91700018 PM 8130255 ER PT J AU ADACHI, Y PAVLAKIS, GN COPELAND, TD AF ADACHI, Y PAVLAKIS, GN COPELAND, TD TI IDENTIFICATION OF IN-VIVO PHOSPHORYLATION SITES OF SET, A NUCLEAR PHOSPHOPROTEIN ENCODED BY THE TRANSLOCATION BREAKPOINT IN ACUTE UNDIFFERENTIATED LEUKEMIA SO FEBS LETTERS LA English DT Article DE SET; NUCLEAR PROTEIN; PROTEIN PHOSPHORYLATION; TRANSLOCATION; ACUTE UNDIFFERENTIATED LEUKEMIA ID MESSENGER-RNA; PROTEIN; FUSION; GENES; CELLS AB SET, the translocation breakpoint-encoded protein in acute undifferentiated leukemia (AUL), is identified as a 39-kDa phosphoprotein found predominantly in the cell nuclei [1994, J. Biol. Chem. 269, 2258-2262]. SET is fused to a putative oncoprotein, CAN, in AUL and is thought to regulate the transformation potential of SET-CAN by its nuclear localization and phosphorylation. We investigated in detail the in vivo phosphorylation of SET. Phosphorylation of SET occurred in all human cell lines examined in vivo, primarily on serine residues. Endoproteinase Glu-C digestion of phosphorylated SET yielded two phosphopeptides. By radiosequencing, we identified the in vivo phosphorylation sites of SET as Ser(9) and Se-24. The surrounding sequences of Se-9 and Ser(24) contained an apparent consensus site sequence for protein kinase C. C1 NCI,FREDERICK CANC RES & DEV CTR,ABL BASIC RES PROGRAM,HUMAN RETROVIRUS SECT,FREDERICK,MD 21702. FU NCI NIH HHS [N01-CO-74101] NR 28 TC 34 Z9 35 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 7 PY 1994 VL 340 IS 3 BP 231 EP 235 DI 10.1016/0014-5793(94)80144-4 PG 5 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA NB037 UT WOS:A1994NB03700018 PM 8131851 ER PT J AU LUSSO, P GALLO, RC AF LUSSO, P GALLO, RC TI HUMAN HERPESVIRUS-6 IN AIDS SO LANCET LA English DT Editorial Material ID VIRUS RP LUSSO, P (reprint author), NCI,TUMOR CELL BIOL LAB,BLDG 37,BETHESDA,MD 20892, USA. NR 6 TC 28 Z9 28 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 MAR 5 PY 1994 VL 343 IS 8897 BP 555 EP 556 DI 10.1016/S0140-6736(94)91515-6 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA MY843 UT WOS:A1994MY84300003 PM 7906323 ER PT J AU DAWID, IB AF DAWID, IB TI INTERCELLULAR SIGNALING AND GENE-REGULATION DURING EARLY EMBRYOGENESIS OF XENOPUS-LAEVIS SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Review ID ERYTHROID-DIFFERENTIATION FACTOR; BONE MORPHOGENETIC PROTEIN-4; MATERNAL MESSENGER-RNA; MESODERM INDUCTION; GROWTH-FACTORS; ACTIVIN-A; AMPHIBIAN DEVELOPMENT; VENTRALIZING FACTOR; FROG EMBRYOS; TGF-BETA RP DAWID, IB (reprint author), NICHHD,MOLEC GENET LAB,BETHESDA,MD 20892, USA. NR 77 TC 63 Z9 63 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 4 PY 1994 VL 269 IS 9 BP 6259 EP 6262 PG 4 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA MZ503 UT WOS:A1994MZ50300001 PM 8119971 ER PT J AU OSIFCHIN, NE JIANG, D OHTANIFUJITA, N FUJITA, T CARROZA, M KIM, SJ SAKAI, T ROBBINS, PD AF OSIFCHIN, NE JIANG, D OHTANIFUJITA, N FUJITA, T CARROZA, M KIM, SJ SAKAI, T ROBBINS, PD TI IDENTIFICATION OF A P53 BINDING-SITE IN THE HUMAN RETINOBLASTOMA SUSCEPTIBILITY GENE PROMOTER SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID WILD-TYPE P53; LARGE T-ANTIGEN; CELL-CYCLE; MUTANT P53; TRANSCRIPTIONAL ACTIVATION; PROTEINS BIND; DNA-SEQUENCE; SV40 ORIGIN; RB GENE; PRODUCT AB p53 is a tumor suppressor gene-found to be mutated in a wide variety of tumors. The encoded p53 protein has properties of a classical transcription factor, but the promoter targets for its regulation are largely unknown. We have investigated the ability of p53 to regulate activity of the human retinoblastoma susceptibility gene (Rb) promoter using a cotransfection assay in CCL-64 and Saos-2 cells, p53 was able to stimulate transcription from the Rb promoter at low input doses of p53 expression plasmid, whereas transcription was repressed at high input doses. The stimulatory effect of p53 on Rb promoter activity mapped to a region between 4 and 92 base pairs upstream from the start site of translation, whereas the region controlling repression by p53 mapped to the basal transcriptional control region of the promoter between -207 and -185. Moreover, an oligonucleotide containing Rb promoter sequences between -63 and -88 was sufficient to confer stimulation by p53 when inserted upstream from a minimal heterologous promoter. Gel mobility shift analysis was used to demonstrate that p53 can bind to a sequence within the -63 to -88 oligonucleotide with homology to a p53 binding site. The presence of a functional p53 binding site in the human retinoblastoma tumor suppressor gene promoter suggests that p53 can regulate Rb promoter activity. C1 UNIV PITTSBURGH,SCH MED,DEPT MOLEC GENET & BIOCHEM,PITTSBURGH,PA 15261. UNIV PITTSBURGH,SCH MED,DEPT MED,PITTSBURGH,PA 15261. KYOTO PREFECTURAL UNIV MED,DEPT PREVENT MED,KAMIKYO KU,KYOTO 602,JAPAN. NATL CANC INST,CHEMOPREVENT LAB,BETHESDA,MD 20892. FU NCI NIH HHS [CA-55227]; NIDDK NIH HHS [5 T32 DK07458] NR 54 TC 42 Z9 44 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 4 PY 1994 VL 269 IS 9 BP 6383 EP 6389 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA MZ503 UT WOS:A1994MZ50300022 PM 8119988 ER PT J AU NAKANISHI, S CATT, KJ BALLA, T AF NAKANISHI, S CATT, KJ BALLA, T TI INHIBITION OF AGONIST-STIMULATED INOSITOL 1,4,5-TRISPHOSPHATE PRODUCTION AND CALCIUM SIGNALING BY THE MYOSIN LIGHT-CHAIN KINASE INHIBITOR, WORTMANNIN SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID ADRENAL GLOMERULOSA CELLS; PLASMA-MEMBRANE; ANGIOTENSIN-II; HUMAN NEUTROPHIL; PHOSPHOLIPASE-C; RECEPTOR; ACTIVATION; ENTRY; MECHANISM; RELEASE AB The myosin light chain kinase inhibitor, wortmannin (WT), caused dose dependent inhibition of the sustained increases but not the initial spikes of inositol 1,4,5-trisphosphate (Ins-1,4,5-P-3) and cytoplasmic Ca2+ concentration ([Ca2+](i)) in angiotensin II (AII)-stimulated adrenal glomerulosa cells. In contrast, WT did not affect the [Ca2+](i) increases evoked by K+-induced depolarization or by depletion of intracellular Ca2+ stores with ionomycin or thapsigargin, suggesting that its inhibitory effects on Ins-1,4,5-P-3 and [Ca2+](i) responses are closely related. The inhibitory effect of WT on the lns-1,4,5-P-3 response was not secondary to its reduction of Ca2+ entry, since ionomycin induced elevation of [Ca2+](i) did not restore Ins-1,4,5-P-3 formation. Also, WT inhibited agonist- and GTP gamma S-stimulated Ins 1,4,5-P-3 formation in permeabilized cells maintained at fixed Ca2+ concentrations. Thus, inhibition of Ca2+ influx by WT is a consequence of reduced Ins-1,4,5-P-3 formation and could reflect the resultant refilling of the agonist-sensitive Ca2+ pool. Indeed, AII-depleted Ca2+ pools were found to refill by a thapsigargin-sensitive mechanism in WT-treated cells. Other structurally unrelated inhibitors of myosin light chain kinase (MS-347a, KT5926, and ML-9) also inhibited AII-induced inositol phosphate formation, albeit with lower potencies than WT. MS-347a, like WT, inhibited only the second phase of the inositol phosphate and [Ca2+](i) responses to AII. These findings demonstrate that WT is a potent inhibitor of the Ins-1,4,5-P-3-Ca2+ signaling pathway and acts primarily on a mechanism that promotes Ins-1,4,5-P-3 formation and is sensitive to inhibitors of myosin light chain kinase activity. C1 NIH,ENDOCRINOL & REPROD RES BRANCH,BETHESDA,MD 20892. OI Balla, Tamas/0000-0002-9077-3335 NR 43 TC 54 Z9 54 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 4 PY 1994 VL 269 IS 9 BP 6528 EP 6535 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA MZ503 UT WOS:A1994MZ50300043 PM 8120005 ER PT J AU DE, SK MARSH, JW AF DE, SK MARSH, JW TI HIV-1 NEF INHIBITS A COMMON ACTIVATION PATHWAY IN NIH-3T3 CELLS SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; INOSITOL 1,4,5-TRISPHOSPHATE RECEPTOR; PHOSPHOLIPASE-C; MESSENGER-RNA; CALCIUM POOLS; T-CELLS; TYPE-1; EXPRESSION; GENE; INDUCTION AB The human immunodeficiency virus type 1 (HlV-1) Nef is a myristylated 27-kDa, cytoplasmic protein. It is attributed to have suppressive effects on LTR-based expression and T cell activation. Additionally, SIV nef has been shown to possess an essential in vivo function in the development of immunodeficiency. To define the bio chemical activity of HIV-1 Nef in a signal transduction pathway, we have transduced murine NIH-3T3 cells with a retroviral nef expression system, In nef-expressing cells, but not in controls, the proliferative response to bombesin and platelet-derived growth factor (PDGF) was eliminated. Analysis of an early signal pathway metabolite, inositol l,4,5-trisphosphate following bombesin and PDGF treatment to quiscent cells, revealed that both control and nef-transformed cells displayed similar kinetics of signal formation. Normally, inositol 1,4,5-trisphosphate mediates increase in the cytosolic free Ca2+ ([Ca2+](i)). Upon stimulation with bombesin or PDGF, control cells displayed a 2-4-fold increase of [Ca2+](i) over the basal level, while the [Ca2+](i) response in nef-expressing NIH-3T3 cells was lacking or highly diminished. However, the release of [Ca2+](i) from the intracellular store of the nef-expressing cells by an endomembrane Ca2+ ATPase inhibitor, thapsigargin, revealed that these cells contained normal Ca2+ stores. These results suggest a specific, definable biochemical activity for the HIV-1 Nef protein in the context of a well characterized cellular activation pathway. Our results thus define, for the first time, a unique function of Nef that is not limited to an alteration of T cell function or of expression of a T cell surface antigen. RP DE, SK (reprint author), NIMH,MOLEC BIOL LAB,BLDG 36,RM 1B08,BETHESDA,MD 20892, USA. NR 38 TC 57 Z9 57 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 4 PY 1994 VL 269 IS 9 BP 6656 EP 6660 PG 5 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA MZ503 UT WOS:A1994MZ50300063 PM 8120020 ER PT J AU ANOUAR, Y MACARTHUR, L COHEN, J IACANGELO, AL EIDEN, LE AF ANOUAR, Y MACARTHUR, L COHEN, J IACANGELO, AL EIDEN, LE TI IDENTIFICATION OF A TPA-RESPONSIVE ELEMENT MEDIATING PREFERENTIAL TRANSACTIVATION OF THE GALANIN GENE PROMOTER IN CHROMAFFIN CELLS SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID PROTEIN KINASE-C; SIGNAL TRANSDUCTION PATHWAYS; NUCLEOTIDE-SEQUENCE ANALYSIS; PHORBOL ESTER TREATMENT; TRANSCRIPTION FACTORS; BINDING-PROTEINS; ADRENAL-MEDULLA; ANTERIOR-PITUITARY; ENHANCER ELEMENTS; INDUCIBLE GENES AB The gene encoding the neuropeptide galanin is upregulated by second messenger signal transduction pathways in bovine chromaffin cells. To identify its transcriptional regulatory elements, 5'-flanking sequences of the galanin gene were transiently transfected into primary cultures of bovine chromaffin cells within reporter gene constructs. Multiple regions of the galanin 5' flank seem to be necessary for basal activity. The most promoter-proximal of these regions contains a sequence (TGACG) -66 to -62 nucleotides upstream from the transcriptional start site which mediates stimulation by 12-O-tetradecanoylphorbol- 13 acetate (TPA), as demonstrated by site-directed mutagenesis and cis-activation experiments. This cis-regulatory element mediates preferential TPA stimulation of transcription from the galanin promoter in chromaffin cells compared with bovine endothelial or HeLa cells, DNA-protein binding assays indicate that an oligonucleotide that includes the galanin TPA-responsive element (GTRE) binds specifically to proteins from nuclear extracts of chromaffin cells. TPA treatment persistently increases this binding activity in chromaffin but not in endothelial cells. Mutation of the galanin promoter within the -66 to -62 region renders it unresponsive to transcriptional stimulation by TPA, and a correspondingly mutated oligonucleotide fails to bind chromaffin cell nuclear proteins in a gel-shift assay. Chromaffin cell nuclear extracts also contain proteins that bind consensus TPA-responsive (TRE) and cyclic AMP-responsive (CRE) elements. GTRE, TRE, and CRE oligonucleotides all compete more efficiently for protein binding to their labeled congeners than for protein binding to either of the other labeled oligonucleotides, suggesting that the GTRE, TRE, and CRE oligo nucleotides each bind unique as well as common proteins, likely to be members of the Jun/Fos and cAMP-responsive element-binding protein/activating transcription factors (CREB/ATF) families of transcription factors, in chromaffin cells. RP ANOUAR, Y (reprint author), NIMH,CELL BIOL LAB,MOLEC NEUROSCI SECT,BLDG 36,RM 3A-17,BETHESDA,MD 20892, USA. OI Eiden, Lee/0000-0001-7524-944X NR 53 TC 41 Z9 42 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 4 PY 1994 VL 269 IS 9 BP 6823 EP 6831 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA MZ503 UT WOS:A1994MZ50300089 PM 7509811 ER PT J AU PRASAD, K HEUSER, J EISENBERG, E GREENE, L AF PRASAD, K HEUSER, J EISENBERG, E GREENE, L TI COMPLEX-FORMATION BETWEEN CLATHRIN AND UNCOATING ATPASE SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID COATED VESICLES; HEAT-SHOCK; STRESS PROTEINS; TRANSLOCATION; DISSOCIATION; BINDING; HSP70; CAGES AB The bovine brain uncoating ATPase, a constitutive 70-kDa heat shock protein, uncoats clathrin coated vesicles in an ATP dependent reaction. The uncoating ATPase-clathrin complex formed from the uncoating reaction was compared to the complex formed by directly binding free clathrin to uncoating ATPase. The amount of the latter complex shows a simple hyperbolic dependence on either free clathrin or free uncoating ATPase concentration, whichever is in excess, with a binding stoichiometry of one uncoating ATPase per clathrin heavy chain. ATP markedly increases the rates of formation and dissociation of this complex while ADP profoundly inhibits these rates. At low uncoating ATPase concentrations, much more complex is formed by uncoating than by directly binding clathrin to enzyme. However, during column chromatography or dilution for electron microscopy, both types of complex dissociate in ATP but not ADP, and electron microscopy of both types of complex diluted into ADP shows binding only to the vertex of the clathrin triskelion. We conclude that the uncoating ATPase forms only one type of complex with clathrin and has only one site for nucleotide; ADP at this site prevents either formation or dissociation of complex, whereas ATP at this site allows both processes to occur rapidly. C1 NHLBI,CELL BIOL LAB,BETHESDA,MD 20892. WASHINGTON UNIV,SCH MED,DEPT CELL BIOL & PHYSIOL,ST LOUIS,MO 63110. NR 25 TC 43 Z9 43 U1 2 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 4 PY 1994 VL 269 IS 9 BP 6931 EP 6939 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA MZ503 UT WOS:A1994MZ50300103 PM 8120055 ER PT J AU GALLORODRIGUEZ, C JI, XD MELMAN, N SIEGMAN, BD SANDERS, LH ORLINA, J FISCHER, B PU, QL OLAH, ME VANGALEN, PJM STILES, GL JACOBSON, KA AF GALLORODRIGUEZ, C JI, XD MELMAN, N SIEGMAN, BD SANDERS, LH ORLINA, J FISCHER, B PU, QL OLAH, ME VANGALEN, PJM STILES, GL JACOBSON, KA TI STRUCTURE-ACTIVITY-RELATIONSHIPS OF N-6-BENZYLADENOSINE-5'-URONAMIDES AS A(3)-SELECTIVE ADENOSINE AGONISTS SO JOURNAL OF MEDICINAL CHEMISTRY LA English DT Article ID MOLECULAR-CLONING; ADENYLATE-CYCLASE; RAT-BRAIN; RECEPTORS; ANALOGS; A1; A2-RECEPTORS; DERIVATIVES AB Adenosine analogues modified at the 5'-position as uronamides and/or as N-6-benzyl derivatives were synthesized. These derivatives were examined for affinity in radioligand binding assays at the newly discovered rat brain A(3) adenosine receptor and at rat brain A(1) and Az, receptors. 5'Uronamide substituents favored AS selectivity in the order N-methyl > N-ethyl approximate to unsubstituted carboxamide > N-cyclopropyl. 5'-(N-Methylcarboxamido)-N-6-benzyladenosine was 37-56-fold more selective for Ag receptors. Potency at A(3) receptors was enhanced upon substitution of the benzyl substituent with nitro and other groups. 5'-N-Methyluronamides and N-6-(3-substituted-benzyl) adenosines are optimal for potency and selectivity at A(3) receptors. A series of 3-(halobenzyl)5'-N-ethyluronamide derivatives showed the order of potency at A(1) and A(2)a receptors of I similar to Br > Cl > F. At A(3) receptors the 3-F derivative was weaker than the other halo derivatives. 5'-N-Methyl-N-6- (3-iodobenzyl) adenosine displayed a K-i value of 1.1 nM at A(3) receptors and selectivity versus A(1) and A(2a), receptors of 50-fold. A series of methoxybenzyl derivatives showed that a C-methoxy group best favored A(3) selectivity. A 4-sulfobenzyl derivative was a specific ligand at A(3) receptors of moderate potency. An aryl amino derivative was prepared as a probe for radioiodination and receptor cross-linking. C1 NIDDK,BIOORGAN CHEM LAB,BETHESDA,MD 20892. DUKE UNIV,MED CTR,DEPT MED,DURHAM,NC 27710. RI Gallo-Rodriguez, Carola/E-1732-2012; Jacobson, Kenneth/A-1530-2009 OI Jacobson, Kenneth/0000-0001-8104-1493 FU Intramural NIH HHS [Z01 DK031117-20, Z99 DK999999] NR 30 TC 204 Z9 204 U1 0 U2 1 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 4 PY 1994 VL 37 IS 5 BP 636 EP 646 DI 10.1021/jm00031a014 PG 11 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA MZ388 UT WOS:A1994MZ38800014 PM 8126704 ER PT J AU HARRIS, JW KATKI, A ANDERSON, LW CHMURNY, GN PAUKSTELIS, JV COLLINS, JM AF HARRIS, JW KATKI, A ANDERSON, LW CHMURNY, GN PAUKSTELIS, JV COLLINS, JM TI ISOLATION, STRUCTURAL DETERMINATION, AND BIOLOGICAL-ACTIVITY OF 6-ALPHA-HYDROXYTAXOL, THE PRINCIPAL HUMAN METABOLITE OF TAXOL SO JOURNAL OF MEDICINAL CHEMISTRY LA English DT Note ID ESTABLISHMENT; INVITRO AB The principal biotransformation product of taxol was found to be identical for human hepatic microsomes, human liver slices, and patient bile samples. We have isolated this metabolite from the bile of a patient given taxol, and we report its structure and its cytotoxicity relative to taxol. The NMR and SIMS data presented here indicate that, in humans, taxol is regiospecifically hydroxylated at the 6-position on the taxane ring and that this hydroxyl is stereospecifically placed trans to the hydroxyl at position 7, yielding 6(alpha-hydroxytaxol. This metabolite is apparently not formed in rats. Tests of the growth inhibition potential of 6 alpha-hydroxytaxol versus taxol in two human tumor cell lines showed that the metabolite was approximately 30-fold less cytotoxic than taxol. Thus the cytochrome P-450-mediated biotransformation of taxol to 6 alpha-hydroxytaxol can be classified as a detoxification reaction. C1 US FDA,CTR DRUG EVALUAT & RES,DIV CLIN PHARMACOL,ROCKVILLE,MD 20857. NCI,FREDERICK CANC RES & DEV CTR,PRI DYNCORP INC,CHEM SYNTH & ANAL LAB,FREDERICK,MD 21702. NR 18 TC 79 Z9 81 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0022-2623 J9 J MED CHEM JI J. Med. Chem. PD MAR 4 PY 1994 VL 37 IS 5 BP 706 EP 709 DI 10.1021/jm00031a022 PG 4 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA MZ388 UT WOS:A1994MZ38800022 PM 7907372 ER PT J AU BENEDETTIDOCTOROVICH, V BURGESS, EM LAMBROPOULOS, J LEDNICER, D VANDERVEER, D ZALKOW, LH AF BENEDETTIDOCTOROVICH, V BURGESS, EM LAMBROPOULOS, J LEDNICER, D VANDERVEER, D ZALKOW, LH TI SYNTHESIS OF 2-METHYL-(Z)-4-(PHENYLIMINO)NAPHTH[2,3-D]OXAZOL-9-ONE, A MONOIMINE QUINONE WITH SELECTIVE CYTOTOXICITY TOWARD CANCER-CELLS SO JOURNAL OF MEDICINAL CHEMISTRY LA English DT Note ID LINES AB A regio and stereospecific synthesis of 2-methyl-(Z)-4-(phenylimino)naphth[2,3-d]oxazol-9-one (1) was achieved by using titanium tetrachloride in methylene chloride in the preparation of the imine. The regiochemistry was assigned by single-crystal X-ray analysis. In vitro tests showed that this diastereomer is selectively active for some solid cancer tumors. C1 GEORGIA INST TECHNOL,SCH CHEM & BIOCHEM,ATLANTA,GA 30332. NCI,PHARMACEUT RESOURCES BRANCH,BETHESDA,MD 20892. FU NCI NIH HHS [NCI NO1-CM-17570] NR 12 TC 14 Z9 14 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0022-2623 J9 J MED CHEM JI J. Med. Chem. PD MAR 4 PY 1994 VL 37 IS 5 BP 710 EP 712 DI 10.1021/jm00031a023 PG 3 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA MZ388 UT WOS:A1994MZ38800023 PM 8126711 ER PT J AU PASCUALLEONE, A GRAFMAN, J HALLETT, M AF PASCUALLEONE, A GRAFMAN, J HALLETT, M TI MODULATION OF CORTICAL MOTOR OUTPUT MAPS DURING DEVELOPMENT OF IMPLICIT AND EXPLICIT KNOWLEDGE SO SCIENCE LA English DT Article ID FREQUENCY-DISCRIMINATION TASK; FOCAL MAGNETIC STIMULATION; ADULT OWL MONKEYS; FUNCTIONAL REORGANIZATION; MEMORY; CORTEX; BRAIN; SYSTEM; DEAFFERENTATION; REPRESENTATION AB The excitability of the human motor cortex during the development of implicit and declarative knowledge of a motor task was examined. During a serial reaction time test, subjects developed implicit knowledge of the test sequence, which was reflected by diminishing response times. Motor cortical mapping with transcranial magnetic stimulation revealed that the cortical output maps to the muscles involved in the task became progressively larger until explicit knowledge was achieved, after which they returned to their baseline topography. These results illustrate the rapid functional plasticity of cortical outputs associated with learning and with the transfer of knowledge from an implicit to explicit state. C1 NINCDS,MED NEUROL BRANCH,COGNIT NEUROSCI SECT,BETHESDA,MD 20892. NINCDS,MED NEUROL BRANCH,HUMAN MOTOR CONTROL SECT,BETHESDA,MD 20892. UNIV VALENCIA,DEPT FISIOL,UNIDAD NEUROBIOL,VALENCIA,SPAIN. RI Pascual-Leone, Alvaro/G-6566-2011; OI Grafman, Jordan H./0000-0001-8645-4457 NR 42 TC 415 Z9 419 U1 0 U2 30 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 SN 0036-8075 J9 SCIENCE JI Science PD MAR 4 PY 1994 VL 263 IS 5151 BP 1287 EP 1289 DI 10.1126/science.8122113 PG 3 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA MY570 UT WOS:A1994MY57000039 PM 8122113 ER PT J AU HADA, T HAGIYA, H SUZUKI, H ARAKAWA, T NAKAMURA, M MATSUDA, S YOSHIMOTO, T YAMAMOTO, S AZEKAWA, T MORITA, Y ISHIMURA, K KIM, HY AF HADA, T HAGIYA, H SUZUKI, H ARAKAWA, T NAKAMURA, M MATSUDA, S YOSHIMOTO, T YAMAMOTO, S AZEKAWA, T MORITA, Y ISHIMURA, K KIM, HY TI ARACHIDONATE 12-LIPOXYGENASE OF RAT PINEAL GLANDS - CATALYTIC PROPERTIES AND PRIMARY STRUCTURE DEDUCED FROM ITS CDNA SO BIOCHIMICA ET BIOPHYSICA ACTA-LIPIDS AND LIPID METABOLISM LA English DT Article DE LIPOXYGENASE; PRIMARY STRUCTURE; PINEAL GLAND; (RAT) ID MOLECULAR-CLONING; ANTERIOR-PITUITARY; PORCINE LEUKOCYTES; ACID; LIPOXYGENASE; EXPRESSION; PLATELETS; 15-LIPOXYGENASE; LOCALIZATION; SEQUENCE AB When a crude extract of rat pineal glands (the 1000 x g supernatant of a homogenate) was incubated with arachidonic acid, 12-hydroxy-5,8,10,14-eicosatetraenoic acid was found as a major product. The 12-lipoxygenase of rat pineal gland also reacted with linoleic and cr-linolenic acids at 35% and 101% the rate of arachidonate 12-oxygenation, respectively. Upon Western blot analysis using polyclonal antibody against: porcine leukocyte 12-lipoxygenase, the cytosol fraction of rat pineal gland showed a positive band with a molecular weight of approx. 74 kDa. A full-length cDNA for this enzyme was cloned from a cDNA library of rat pineal gland and the identity of the 12-lipoxygenase cDNA was confirmed by its expression in E. coli. The amino acid sequence of the enzyme was deduced from the nucleotide sequence of the cDNA, encoding 663 amino acids with a calculated molecular weight of 75 305. The enzyme showed 72% identity of amino acid sequence with porcine leukocyte 12-lipoxygenase and 73% with bovine tracheal 12-lipoxygenase, but only 59% with human platelet 12-lipoxygenase. Taken together, the high reactivity with C-18 fatty acids, the immunoreactivity and the amino acid homology data indicate that the rat pineal 12-lipoxygenase is more closely related to leukocyte 12-lipoxygenase than to platelet 12-lipoxygenase. Upon RNA blot analysis, by far the highest content of 12-lipoxygenase mRNA was observed in the pineal gland and negligible amounts of mRNA were detected in other parts of the brain. The predominant presence of 12-lipoxygenase mRNA in pineal gland was confirmed by in situ hybridization of rat brain. Significant amounts of 12-lipoxygenase mRNA were also detected in rat spleen, aorta, lung and leukocytes. C1 UNIV TOKUSHIMA,SCH MED,DEPT BIOCHEM,TOKUSHIMA 770,JAPAN. UNIV TOKUSHIMA,SCH MED,DEPT PHYSIOL,TOKUSHIMA 770,JAPAN. UNIV TOKUSHIMA,SCH MED,DEPT ANAT,TOKUSHIMA 770,JAPAN. NIAAA,BETHESDA,MD 20892. NR 30 TC 42 Z9 43 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0005-2760 J9 BBA-LIPID LIPID MET JI Biochim. Biophys. Acta-Lipids Lipid Metab. PD MAR 3 PY 1994 VL 1211 IS 2 BP 221 EP 228 DI 10.1016/0005-2760(94)90272-0 PG 8 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA MZ859 UT WOS:A1994MZ85900011 PM 8117750 ER PT J AU GALLO, RC AF GALLO, RC TI TEMIN,HOWARD,M. (1934-94) - OBITUARY SO NATURE LA English DT Item About an Individual RP GALLO, RC (reprint author), NCI,BETHESDA,MD 20892, USA. NR 2 TC 0 Z9 0 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 3 PY 1994 VL 368 IS 6466 BP 17 EP 17 DI 10.1038/368017a0 PG 1 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA MY569 UT WOS:A1994MY56900031 PM 7509045 ER PT J AU BRACKETT, LE DALY, JW AF BRACKETT, LE DALY, JW TI FUNCTIONAL-CHARACTERIZATION OF THE A(2B) ADENOSINE RECEPTOR IN NIH 3T3 FIBROBLASTS SO BIOCHEMICAL PHARMACOLOGY LA English DT Article DE ADENOSINE RECEPTORS; XANTHINES; ADENYLATE CYCLASE; PHEOCHROMOCYTOMA CELLS; FIBROBLASTS; CYCLIC AMP ID ADENYLATE-CYCLASE; MOLECULAR-CLONING; RAT-BRAIN; SELECTIVE AGONISTS; CAMP FORMATION; CYCLIC-AMP; CGS 21680; ANTAGONISTS; POTENT; ANALOGS AB The adenosine (ADO) receptor in NIH 3T3 fibroblasts was characterized using a series of adenosine agonists and selected xanthine and non-xanthine antagonists. The ADO receptor elicited accumulations of cyclic AMP in intact NIH 3T3 fibroblasts and caused activation of adenylate cyclase in membrane preparations. The receptor had characteristics of the A(2b) subtype of adenosine receptor. ADO analogs had relatively high EC(50) values at the receptor and were antagonized competitively by xanthines. The rank order of potency for adenosine analogs in NIH 3T3 fibroblasts for cyclic AMP accumulation was: NECA > 2-ClADO > R-PIA much greater than CV1808, CGS 21680. The EC(50) for 2-ClADO was 4.3 mu M in intact cells and 15 mu M in membrane preparations. All ADO analogs were more potent at the A(2a) receptor of pheochromocytoma PC12 membranes than at the A(2b) receptor of fibroblast NIH 3T3 membranes. Structure-activity relationships suggested that the regions of interaction with 5'- and N-6-substituents of ADO were similar for both the PC12 A(2a) and NIH 3T3 A(2b) receptor. However, ADO analogs with large substituents in the 2'-position, such as 2-cyclohexylethoxyADO and CGS 21680, were highly selective for the A(2a) receptor. All ADO analogs tested were stimulatory to adenylate cyclase at the NIH 3T3 A(2b) receptor, including 5'-methylthioADO, which was a weak partial agonist. A series of xanthine antagonists were not selective for the NIH 3T3 A(2b) versus the PC12 A(2a) receptor. In all cases, xanthines were more potent as antagonists in the intact NIH 3T3 cells than in NIH 3T3 membranes. In a series of non-xanthine antagonists, most compounds were equipotent or slightly more potent at the A(2a) receptor except for alloxazine, which was approximately 9-fold selective for the A(2b) receptor. C1 NIDDKD,BIOORGAN CHEM LAB,BETHESDA,MD 20892. NR 45 TC 116 Z9 117 U1 0 U2 2 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0006-2952 J9 BIOCHEM PHARMACOL JI Biochem. Pharmacol. PD MAR 2 PY 1994 VL 47 IS 5 BP 801 EP 814 PG 14 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA NA068 UT WOS:A1994NA06800008 PM 8135856 ER PT J AU HAASCH, ML GRAF, WK QUARDOKUS, EM MAYER, RT LECH, JJ AF HAASCH, ML GRAF, WK QUARDOKUS, EM MAYER, RT LECH, JJ TI USE OF 7-ALKOXYPHENOXAZONES, 7-ALKOXYCOUMARINS AND 7-ALKOXYQUINOLINES AS FLUORESCENT SUBSTRATES FOR RAINBOW-TROUT HEPATIC MICROSOMES AFTER TREATMENT WITH VARIOUS INDUCERS SO BIOCHEMICAL PHARMACOLOGY LA English DT Article DE CYTOCHROME P450; FLUORESCENT SUBSTRATES; TROUT; MICROSOMES; INDUCTION; HEPATIC ID O-DEALKYLASE ACTIVITIES; CYTOCHROME-P-450; INDUCTION; LIVER; RAT; 3-METHYLCHOLANTHRENE; METABOLISM; ASSAY; FISH; XENOBIOTICS AB Various fluorescent substrates have been used as specific indicators of induction or activity of different cytochrome P450 isozymes in both fish and mammalian species. In an attempt to identify additional definitive fluorescent substrates for use in fish, we examined a series of 7-alkoxyphenoxazones, 7-alkoxycoumarins and 7-alkoxyquinolines as substrates in O-dealkylation assays with hepatic microsomes from rainbow trout (Oncorhynchus mykiss). Microsomes were prepared after 48 hr of treatment with beta-naphthoflavone (beta-NF), pregnenolone-16 alpha-carbonitrile (PCN), phenobarbital (PB), isosafrole (ISF), or dexamethasone (DEX). Total P450 spectra were obtained, and spectral binding studies were performed. Microsomal O-dealkylation rates were greater after ISF treatment than after beta-NF treatment for 7-methoxy-, 7-ethoxy-, 7-propoxy- and 7-benzyloxyphenoxazones but not for 7-butoxyphenoxazone. DEX treatment resulted in a significant elevation of pentoxyphenoxazone metabolism (about a 144-fold increase) compared with microsomes induced by beta-NF (11-fold) and ISF (37-fold). The rates of dealkylation of the alkoxyphenoxazones by ISF-treated microsomes occurred in the following order: methoxy > ethoxy > propoxy > benzxyloxy > butoxy > pentoxy. When beta-NF-treated microsomes were used, the 7-alkoxyphenoxazones were metabolized as follows: methoxy > ethoxy > propoxy > butoxy > benzyloxy approximate to pentoxy, while the order of metabolism of the 7-alkoxycoumarins was: ethoxy much greater than butoxy > propoxy approximate to methoxy > benzyloxy > pentoxy. None of the other treatments significantly increased the rate of metabolism of any of the alkoxycoumarins. Treatment with beta-NF did not significantly elevate the rate of metabolism of any of the alkoxyquinolines. DEX treatment produced significant elevations in the rate of metabolism of benzyloxy-, ethoxy-, and butoxy- approximate to pentoxy- approximate to propoxyquinoline, in that order. ISF treatment significantly elevated the rate of metabolism of benzyloxy-, methoxy- and butoxyquinoline, in that order. These results suggest that some of these new fluorescent substrates can be used to characterize induction of rainbow trout hepatic microsomal monooxygenase activity by ISF and DEX, in addition to the commonly used ethoxyphenoxazone and ethoxycoumarin for the characterization of induction by beta-NF or other 3-methylcholanthrene-type P450 inducers. Distinction between ISF-type and beta-NF-type inducers in rainbow trout hepatic microsomes may best be made using 7-methoxycoumarin as a substrate. Distinction between ISF-type and DEX-type inducers and between beta-NF-type and DEX-type inducers may best be made using 7-methoxyphenoxazone as a substrate. With beta-NF induction 7-methoxycoumarin, with ISF induction 7-methoxy- phenoxazone, and with DEX induction 7-ethoxyquinoline were metabolized to the greatest extent compared with controls and all other substrates tested. C1 UNIV WISCONSIN,NIEHS,MARINE & FRESHWATER BIOMED RES CORE CTR,MILWAUKEE GREAT LAKES RES FACIL,MILWAUKEE,WI 53204. USDA ARS,HORT RES LAB,ORLANDO,FL 32803. RP HAASCH, ML (reprint author), MED COLL WISCONSIN,DEPT PHARMACOL & TOXICOL,8701 WATERTOWN PLANK RD,MILWAUKEE,WI 53226, USA. FU NIEHS NIH HHS [ES04184, R01 ES01080, ES05773] NR 40 TC 36 Z9 38 U1 1 U2 4 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 2 PY 1994 VL 47 IS 5 BP 893 EP 903 DI 10.1016/0006-2952(94)90490-1 PG 11 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA NA068 UT WOS:A1994NA06800018 PM 8135865 ER PT J AU KOHLI, M LEWIS, DJ LUCK, RL SILVERTON, JV SYLLA, K AF KOHLI, M LEWIS, DJ LUCK, RL SILVERTON, JV SYLLA, K TI RHENIUM DIHYDROGEN COMPLEXES AND LONG H-H INTERACTIONS - X-RAY-DETERMINED SINGLE-CRYSTAL STRUCTURES OF RECL(ETA(2)-H2)(PH2PCH2CH2PPH2)2 THF AND [REO2(PH2PCHCHPPH2)2][REO4] SO INORGANIC CHEMISTRY LA English DT Article ID NEUTRON-DIFFRACTION; LIGANDS; RECL(H2)(PMEPH2)4; POLYHYDRIDES; HYDRIDE; CONTAIN AB Reduction of ReCl5 in tetrahydrofuran under Ar with 4 equiv of Na in the presence of bidentate tertiary phosphines (L2) yields complexes of the form ReCl(eta2-H-2)(L2)2, L2 = PPh2CH2CH2PPh2 (1), and L2 = PPh2CHCHPPh2 (2). A similar reduction of ReCl5 in the presence of the monodentate ligand PMe2Ph affords mixtures of ReH3(PMe2Ph)4 and the cation [ReH4(PMe2Ph)4]+. The metal-bonded H atoms in complexes 1 and 2 display T1 (min) times of 43 (5) and 29(4) ms, respectively, at 200 MHz. This suggests a long H-H interaction. The single-crystal X-ray structures of complexes 1.THF and [ReO2(PPh2CHCHPPh2)2][ReO4] (3) are reported. Crystal data: compound 1.THF, monoclinic, space group P2(1)/c, a = 11.472(4) angstrom, b = 13.468(2) angstrom, c = 17.339(5) angstrom, beta = 96.02(1)-degrees, V = 2664.1(4) angstrom3, Z - 2, R - 0.041 (R(w) = 0.058) for 288 parameters and 2323 unique data having F(o) > 3sigma(F(o)2); compound 3, triclinic, space group, P1BAR, a = 9.946(1) angstrom, b = 11.744(3) angstrom, c = 12.506(2) angstrom, alpha = 70.59(2)-degrees, beta = 73.46(1)-degrees, gamma = 65.72(1)-degrees, V - 1237.0(3) angstrom3, Z = 1, R = 0.038 (R(w) = 0.055) for 310 parameters and 2582 unique data having F(o) > 3sigma(F(o)2). The geometries of 2 and the cation in 3 are those of distorted octahedra with the Re atoms situated on inversion points. In 1, there is 50% disorder between the trans Cl- and the eta2-H-2 (not located) ligands. Important distances for 1: Re-Cl at 2.574(6) angstrom and, Re-P(1) and Re-P(2) at 2.388(5) and 2.399(3) angstrom, respectively, with a P(1)-Re-P(2) angle of 80.3(1)-degrees. Core distances for 3: Re-O(101) at 1.788(6) angstrom and Re-P(1) and Re-P(2) at 2.476(2) and 2.473(2) angstrom, respectively, with a P(1)-Re-P(2) angle at 81.18(8)-degrees. The tetrahedral anion in 3, [ReO4]-, is located near an inversion point and was refined at 50% occupancy. Here Re-O bond distances range from 1.60(7) to 1.77(2) angstrom. C1 AMERICAN UNIV,DEPT CHEM,WASHINGTON,DC 20016. NHLBI,BIOPHYS CHEM LAB,BETHESDA,MD 20892. NR 22 TC 12 Z9 12 U1 0 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0020-1669 J9 INORG CHEM JI Inorg. Chem. PD MAR 2 PY 1994 VL 33 IS 5 BP 879 EP 883 DI 10.1021/ic00083a009 PG 5 WC Chemistry, Inorganic & Nuclear SC Chemistry GA NC475 UT WOS:A1994NC47500009 ER PT J AU SCHIFFMAN, M FREEDMAN, LS AF SCHIFFMAN, M FREEDMAN, LS TI EPIDEMIOLOGIC EVIDENCE SHOWING THAT HUMAN PAPILLOMAVIRUS INFECTION CAUSES MOST CERVICAL INTRAEPITHELIAL NEOPLASIA - RESPONSE SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Letter RP SCHIFFMAN, M (reprint author), NCI,ENVIRONM EPIDEMIOL BRANCH,EXECUT PLAZA N,RM 443,6130 EXECUT BLVD,BETHESDA,MD 20892, USA. NR 3 TC 0 Z9 0 U1 0 U2 0 PU NATL CANCER INSTITUTE PI BETHESDA PA 9030 OLD GEORGETOWN RD, BETHESDA, MD 20814 SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD MAR 2 PY 1994 VL 86 IS 5 BP 392 EP 393 DI 10.1093/jnci/86.5.392-a PG 2 WC Oncology SC Oncology GA MX572 UT WOS:A1994MX57200021 ER PT J AU DAWSEY, SM YU, Y TAYLOR, PR LI, JY SHEN, Q SHU, YJ LIU, SF ZHAO, HZ CAO, SG WANG, GQ LIU, FS BLOT, WJ LI, B AF DAWSEY, SM YU, Y TAYLOR, PR LI, JY SHEN, Q SHU, YJ LIU, SF ZHAO, HZ CAO, SG WANG, GQ LIU, FS BLOT, WJ LI, B TI ESOPHAGEAL CYTOLOGY AND SUBSEQUENT RISK OF ESOPHAGEAL CANCER - A PROSPECTIVE FOLLOW-UP-STUDY FROM LINXIAN, CHINA SO ACTA CYTOLOGICA LA English DT Article DE BALLOON CYTOLOGY; ESOPHAGEAL DYSPLASIA; ESOPHAGEAL NEOPLASMS AB This paper reports a 15-year follow-up study of 12,693 persons in Linxian, China, who were originally screened by esophageal balloon cytology in 1974. The purpose of the study was to evaluate the ability of esophageal balloon cytology to identify individuals at increased risk for developing esophageal cancer. Age, sex and cytologic,aic diagnoses were obtained from the original 1974 records, and information on vital status, cancer experience and potential confounding risk factors was collected from interviews and medical abstracts in 1989. A total of 1,162 incident cases of esophageal cancer and 993 deaths due to esophageal cancer were identified and used in this analysis. The follow-up study showed that the risk of esophageal cancer incidence and mortality increased in parallel with the presumed severity of the 1974 Chinese cytologic diagnoses. After adjusting for potential confounding factors, the relative risks (and 95% confidence intervals) for esophageal cancer incidence, by cytologic diagnosis, were: normal, 1.00; esophagitis, 1.52 (1.07-2.14); hyperplasia, 1.17 (1.02-1.33); dysplasia 1, 1.53 (1.20-2.14); dysplasia 2, 1.89 (1.47-2.41); and suspicious for cancer, 5.77 (3.79-8.80). These results suggest that esophageal balloon cytology, as performed and interpreted in Linxian in 1974, successfully identified individuals at increased risk for esophageal cancer. C1 NCI,DIV CANC ETIOL,BIOSTAT BRANCH,BETHESDA,MD. CHINESE ACAD MED SCI,CANC INST & HOSP,DEPT EPIDEMIOL,BEIJING,PEOPLES R CHINA. CHINESE ACAD MED SCI,CANC INST & HOSP,DEPT CYTOL,BEIJING,PEOPLES R CHINA. CHINESE ACAD MED SCI,CANC INST & HOSP,DEPT CHEST SURG & PATHOL,BEIJING,PEOPLES R CHINA. HENAN MED UNIV,DEPT PRECANCEROUS STUDIES,ZHENGZHOU,PEOPLES R CHINA. ESOPHAGEAL CANC INST,LINXIAN,PEOPLES R CHINA. CHINA CANC RES FDN,BEIJING,PEOPLES R CHINA. RP DAWSEY, SM (reprint author), NCI,DIV CANC PREVENT & CONTROL,CANC PREVENT STUDIES BRANCH,EXECUT PLAZA N,ROOM 211,BETHESDA,MD 20892, USA. FU NCI NIH HHS [N01-CP-95616, N01-CP-05634] NR 17 TC 27 Z9 28 U1 0 U2 0 PU SCI PRINTERS & PUBL INC PI ST LOUIS PA P.O. DRAWER 12425 8342 OLIVE BLVD, ST LOUIS, MO 63132 SN 0001-5547 J9 ACTA CYTOL JI Acta Cytol. PD MAR-APR PY 1994 VL 38 IS 2 BP 183 EP 192 PG 10 WC Pathology SC Pathology GA NE710 UT WOS:A1994NE71000010 PM 8147209 ER PT J AU MCNEIL, TF CANTORGRAAE, E TORREY, EF SJOSTROM, K BOWLER, A TAYLOR, E RAWLINGS, R HIGGINS, ES AF MCNEIL, TF CANTORGRAAE, E TORREY, EF SJOSTROM, K BOWLER, A TAYLOR, E RAWLINGS, R HIGGINS, ES TI OBSTETRIC COMPLICATIONS IN HISTORIES OF MONOZYGOTIC TWINS DISCORDANT AND CONCORDANT FOR SCHIZOPHRENIA SO ACTA PSYCHIATRICA SCANDINAVICA LA English DT Article DE SCHIZOPHRENIA; TWINS; OBSTETRIC COMPLICATIONS; BIRTH ID BIRTH-WEIGHT; RISK; CLASSIFICATION; PREGNANCY; PSYCHOSIS; SAMPLE AB Histories of obstetric complications (OCs) during pregnancy, labor-delivery and the neonatal period were investigated by detailed maternal report for 23 monozygotic (MZ) twin pairs discordant for schizophrenia, 10 MZ twin pairs concordant for schizophrenia and 7 normal MZ control pairs. Statistically significant differences in OC rates were found across these 3 groups, OCs being most frequent in discordant pairs and least frequent in normal control pairs. Labor complications were significantly more frequent in discordant than concordant pairs. OC rates were equivalent in sick and well discordant twins. The results provide evidence for the role of OCs in the development of schizophrenia, complications at the time of birth being especially associated with the development of schizophrenia in discordant twins. C1 LUND UNIV,DEPT PSYCHIAT,S-21401 MALMO,SWEDEN. UNIV N CAROLINA,DEPT PSYCHIAT,CHAPEL HILL,NC 27514. ST ELIZABETH HOSP,NIMH,CTR NEUROSCI,TWIN STUDIES UNIT,WASHINGTON,DC 20032. NIAAA,DIV BIOMETRY & EPIDEMIOL,BETHESDA,MD. RP MCNEIL, TF (reprint author), MED UNIV S CAROLINA,DEPT PSYCHIAT,CHARLESTON,SC 29425, USA. FU NIMH NIH HHS [NIMH MH41176] NR 43 TC 59 Z9 59 U1 0 U2 5 PU MUNKSGAARD INT PUBL LTD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0001-690X J9 ACTA PSYCHIAT SCAND JI Acta Psychiatr. Scand. PD MAR PY 1994 VL 89 IS 3 BP 196 EP 204 DI 10.1111/j.1600-0447.1994.tb08092.x PG 9 WC Psychiatry SC Psychiatry GA MY032 UT WOS:A1994MY03200009 PM 8178679 ER PT J AU BALL, JC AF BALL, JC TI WHY HAS IT PROVED SO DIFFICULT TO MATCH DRUG-ABUSE PATIENTS TO APPROPRIATE TREATMENT SO ADDICTION LA English DT Article AB Why has it proved so difficult to match drug abuse patients to appropriate treatment? In seeking answers to this dilemma, attention is directed to the conceptual, semantic, substantive, methodological, political and cultural issues which need to be resolved In particular, the lack of knowledge about the treatment domain as well as the corresponding dearth of instruments to measure program characteristics and the delivery of treatment services is noted Although the importance of demographic and cultural determinants of both patient and treatment characteristics seems evident, numerous conceptual issues persist. Is matching patients to treatment and rehabilitation a one-time event or a process? Is matching a simplistic concept? It is suggested that the principal questions to be resolved about matching drug abuse patients to treatment and rehabilitation are conceptual, or theoretical. C1 NIH,CTR ADDICT RES,BETHESDA,MD 20892. NR 0 TC 11 Z9 11 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 1994 VL 89 IS 3 BP 263 EP 265 DI 10.1111/j.1360-0443.1994.tb00888.x PG 3 WC Substance Abuse; Psychiatry SC Substance Abuse; Psychiatry GA MX983 UT WOS:A1994MX98300002 PM 8173492 ER PT J AU DAWSON, DA AF DAWSON, DA TI CONSUMPTION INDICATORS OF ALCOHOL DEPENDENCE SO ADDICTION LA English DT Article AB This Data Note evaluates various dichotomous measures of alcohol consumption as screeners for past-year alcohol dependence. The analysis is based on data from 22 102 current drinkers interviewed in the 1988 US National Health Interview Survey. The consumption indicators include measures of average daily intake, frequency of heavy drinking, usual quantity and frequency of drinking and various combinations of these measures. The measures based on frequency of heavy drinking are the most strongly correlated with dependence, but none of the consumption indicators have the sensitivity or specificity of screeners based on alcohol-related problems. Most of the consumption items considered in this analysis screen for dependence more successfully among men than among women. RP DAWSON, DA (reprint author), NIAAA,DIV BIOMETRY & EPIDEMIOL,6000 EXECUT BLVD,ROCKVILLE,MD 20892, USA. NR 8 TC 39 Z9 39 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 1994 VL 89 IS 3 BP 345 EP 350 DI 10.1111/j.1360-0443.1994.tb00901.x PG 6 WC Substance Abuse; Psychiatry SC Substance Abuse; Psychiatry GA MX983 UT WOS:A1994MX98300014 PM 8173504 ER PT J AU SPECKER, BL VIEIRA, NE OBRIEN, KO HO, ML HEUBI, JE ABRAMS, SA YERGEY, AL AF SPECKER, BL VIEIRA, NE OBRIEN, KO HO, ML HEUBI, JE ABRAMS, SA YERGEY, AL TI CALCIUM KINETICS IN LACTATING WOMEN WITH LOW AND HIGH-CALCIUM INTAKES SO AMERICAN JOURNAL OF CLINICAL NUTRITION LA English DT Article DE LACTATION; CALCIUM; BONE; INTESTINAL ABSORPTION ID 1,25-DIHYDROXYVITAMIN-D CONCENTRATIONS; ISOTOPIC TRACERS; ABSORPTION; METABOLISM; PREGNANCY; INFANTS; ASSAY AB Absorption of calcium and its mobilization from bone during lactation are important for delivery of calcium to breast-feeding infants; whether calcium intake offsets bone resorption is not known. We hypothesized that calcium absorption is increased in lactation and greater in women on low calcium diets, resulting in similar rates of bone resorption and accretion. Calcium absorption and kinetic indexes were calculated by using two stable isotopic tracers in 8 women; 6 were studied both during lactation and nonlactation. Women consumed low calcium diets, with half receiving supplemental calcium. Intestinal absorption was related to serum 1,25-dihydroxyvitamin D and did not increase during lactation. Despite decreased urinary calcium excretion during lactation, especially in women with low calcium intake, net balance tended to be lower during lactation. Mean residence time decreased and bone resorption exceeded accretion in almost all lactating women. Calcium need for milk production appears to be met by decreased urinary excretion and increased bone resorption, and not by increased intestinal absorption. C1 CHILDRENS HOSP MED CTR,CINCINNATI,OH. NICHHD,BETHESDA,MD 20892. BAYLOR MED CTR,DEPT PEDIAT,HOUSTON,TX. USDA ARS,CHILDRENS NUTR RES CTR,HOUSTON,TX. RP SPECKER, BL (reprint author), UNIV CINCINNATI,MED CTR,DEPT PEDIAT,CINCINNATI,OH 45267, USA. OI Abrams, Steven/0000-0003-4972-9233 FU NIAMS NIH HHS [AR41366] NR 25 TC 60 Z9 62 U1 0 U2 2 PU AMER SOC CLINICAL NUTRITION PI BETHESDA PA 9650 ROCKVILLE PIKE, SUBSCRIPTIONS, RM L-2310, BETHESDA, MD 20814-3998 SN 0002-9165 J9 AM J CLIN NUTR JI Am. J. Clin. Nutr. PD MAR PY 1994 VL 59 IS 3 BP 593 EP 599 PG 7 WC Nutrition & Dietetics SC Nutrition & Dietetics GA MZ669 UT WOS:A1994MZ66900008 PM 8116535 ER PT J AU FLAGG, EW COATES, RJ JONES, DP BYERS, TE GREENBERG, RS GRIDLEY, G MCLAUGHLIN, JK BLOT, WJ HABER, M PRESTONMARTIN, S SCHOENBERG, JB AUSTIN, DF FRAUMENI, JF AF FLAGG, EW COATES, RJ JONES, DP BYERS, TE GREENBERG, RS GRIDLEY, G MCLAUGHLIN, JK BLOT, WJ HABER, M PRESTONMARTIN, S SCHOENBERG, JB AUSTIN, DF FRAUMENI, JF TI DIETARY GLUTATHIONE INTAKE AND THE RISK OF ORAL AND PHARYNGEAL CANCER SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Article DE DIET; GLUTATHIONE; MOUTH NEOPLASMS; NEOPLASMS; PHARYNGEAL NEOPLASMS; RETROSPECTIVE STUDIES; RISK FACTORS ID UNITED-STATES; VITAMIN-C; CARCINOGENESIS; INJURY; FIBER; CELLS AB Glutathione, a tripeptide found in a variety of foods, may function as an anticarcinogen by acting as an antioxidant and by binding with cellular mutagens. The association between dietary glutathione intake and risk of oral and pharyngeal cancer was investigated using data from 1,830 white participants (855 cases and 975 controls) in a population-based case-control study conducted in New Jersey; metropolitan Atlanta, Georgia; Los Angeles County, California; and Santa Clara and San Mateo counties, south of San Francisco-Oakland, California, during 1984-1985. The estimated relative risk of cancer among people with the highest quartile of glutathione intake from all sources was 0.5 (95% confidence interval 0.3-0.7). When analyzed by dietary source, however, glutathione intakes derived from all vegetables and from meat were not related to risk of cancer. Only glutathione derived from fruit and from vegetables commonly consumed raw was associated with reduced oral cancer risk. Relative to the lowest level of combined intake of fruit and of fruit-derived glutathione, risk of cancer decreased slightly with increasing intake of fruit glutathione. This analysis was limited, however, by the small numbers of subjects with extreme combinations of intakes. Further studies are needed to distinguish the potential effect of glutathione from that of fruit and raw vegetables per se or from the influence of other constituents in these foods. C1 EMORY UNIV,SCH MED,DEPT BIOCHEM,ATLANTA,GA 30322. CTR DIS CONTROL,NATL CTR CHRON DIS PREVENT & HLTH PROMOT,DIV NUTR,CHRON DIS BRANCH,ATLANTA,GA 30333. NCI,DIV CANC ETIOL,BETHESDA,MD 20892. EMORY UNIV,SCH PUBL HLTH,DIV BIOSTAT,ATLANTA,GA 30322. UNIV SO CALIF,SCH MED,LOS ANGELES,CA. NEW JERSEY STATE DEPT HLTH,TRENTON,NJ. CALIF DEPT HLTH SERV,EMERYVILLE,CA. RP FLAGG, EW (reprint author), EMORY UNIV,SCH PUBL HLTH,DIV EPIDEMIOL,1599 CLIFTON RD,ATLANTA,GA 30329, USA. FU NCI NIH HHS [CA17998-15, N01-CP-31041-01] NR 48 TC 40 Z9 41 U1 1 U2 2 PU JOHNS HOPKINS UNIV SCHOOL HYGIENE PUB HEALTH PI BALTIMORE PA 111 MARKET PLACE, STE 840, BALTIMORE, MD 21202-6709 SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD MAR 1 PY 1994 VL 139 IS 5 BP 453 EP 465 PG 13 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA NF164 UT WOS:A1994NF16400001 PM 8154469 ER PT J AU POWERS, WF KIELY, JL AF POWERS, WF KIELY, JL TI HOW TO FIND A WOMBMATE - VALIDATION OF AN ALGORITHM TO IDENTIFY TWIN PAIRS IN LINKED BIRTH INFANT DEATH FILES SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Article DE INFANT MORTALITY; RISK FACTORS; TWINS ID INFANT-MORTALITY; UNITED-STATES AB Linked Birth/infant Death Files available from the National Center for Health Statistics identify an infant as a twin, but do not identify twin pairs. An algorithm based on maternal, paternal, and infant characteristics has been used to identify twin pairs, but the validity of this algorithm has never been tested. The Missouri linked birth/infant death file from 1980 to 1990 identifies twin pairs by a sequence number. The authors tested the rate and accuracy with which the algorithm identified true pairs in the Missouri file and whether estimates of risk and possible risk factors calculated from pairs of twins identified by the algorithm agreed with these characteristics as calculated from known twin pairs. The algorithm identified 96% (8,273 of 8,620) of true pairs and one false pair. Despite incomplete pair identification, and even identification of a false pair, estimates from the subset identified by the algorithm generally agreed well with characteristics measured from all twin pairs. Nonetheless, incorporation of a multiple birth sequence number into Linked Birth/infant Death Files would enhance their utility. C1 NICHHD,DIV EPIDEMIOL STAT & PREVENT RES,EPIDEMIOL BRANCH,BETHESDA,MD. CTR DIS CONTROL & PREVENT,NATL CTR HLTH STAT,OFF ANAL & EPIDEMIOL,HYATTSVILLE,MD 20782. RP POWERS, WF (reprint author), WINCHESTER HOSP,JOINT PROGRAM NEONATOL SPECIAL CARE NURSERY,41 HIGHLAND AVE,WINCHESTER,MA 01890, USA. NR 9 TC 4 Z9 4 U1 0 U2 0 PU JOHNS HOPKINS UNIV SCHOOL HYGIENE PUB HEALTH PI BALTIMORE PA 111 MARKET PLACE, STE 840, BALTIMORE, MD 21202-6709 SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD MAR 1 PY 1994 VL 139 IS 5 BP 535 EP 540 PG 6 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA NF164 UT WOS:A1994NF16400011 PM 8154478 ER PT J AU PURUCKER, ME COTTLERFOX, M AF PURUCKER, ME COTTLERFOX, M TI GOOD RESPONSE TO HIGH-DOSE INTRAVENOUS IMMUNOGLOBULIN IN PATIENTS WITH ALVEOLAR HEMORRHAGE REFRACTORY TO PLATELET TRANSFUSION SO AMERICAN JOURNAL OF HEMATOLOGY LA English DT Letter ID IMMUNE GLOBULIN; THERAPY C1 NIH,WARREN GRANT MAGNUSON CLIN CTR,DEPT TRANSFUS MED,BETHESDA,MD 20892. RP PURUCKER, ME (reprint author), NIH,WARREN G MAGNUSON CLIN CTR,DEPT CRIT CARE MED,BETHESDA,MD 20892, USA. NR 10 TC 1 Z9 1 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0361-8609 J9 AM J HEMATOL JI Am. J. Hematol. PD MAR PY 1994 VL 45 IS 3 BP 269 EP 270 DI 10.1002/ajh.2830450318 PG 2 WC Hematology SC Hematology GA MT449 UT WOS:A1994MT44900017 PM 8296803 ER PT J AU GOLDSTEIN, AM DRACOPOLI, NC ENGELSTEIN, M FRASER, MC CLARK, WH TUCKER, MA AF GOLDSTEIN, AM DRACOPOLI, NC ENGELSTEIN, M FRASER, MC CLARK, WH TUCKER, MA TI LINKAGE OF CUTANEOUS MALIGNANT-MELANOMA DYSPLASTIC NEVI TO CHROMOSOME 9P, AND EVIDENCE FOR GENETIC-HETEROGENEITY SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Article ID TUMOR PROGRESSION; DYSPLASTIC NEVI; MELANOMA; CANCER; LOCUS AB We examined the relationship between cutaneous malignant melanoma/dysplastic nevi (CMM/DN) and chromosome 9p in 13 pedigrees with two or more living cases of invasive melanoma. We used two highly informative (CA)(n) repeats, D9S126 and IFNA, previously implicated in familial malignant melanoma (MLM), to conduct linkage analysis. Three analyses were performed: (1) CMM alone-all individuals without either confirmed melanoma or borderline lesions were considered unaffected (model A); (2) CMM/DN with both variable age at onset and sporadics (model B); and (3) CMM affecteds only-all individuals either without confirmed melanoma or with borderline lesions were designated ''unknown'' (model C). There was significant evidence for linkage to IFNA in all three models. For CMM alone, the maximum lod score (Z(max)) was 4.36 at theta =.10 for model A and 3.39 at theta =.10 for model C. For CMM/DN (model B), Z(max) = 3.05 at theta =.20. There was no significant evidence for linkage between CMM alone or CMM/DN and chromosome 9p marker D9S126. In addition, there was significant evidence for heterogeneity when a homogeneity test allowing for linkage to chromosome 9p or chromosome 3p or neither region was used. These results suggest that there is an MLM susceptibility locus on chromosome 9p but that familial melanoma is heterogeneous and not all families with CMM/DN are linked to a locus in this region. C1 MIT,DEPT BIOL,CAMBRIDGE,MA. UNIV PENN,SCH MED,PIGMENTED LES STUDY GRP,PHILADELPHIA,PA. UNIV PENN,SCH MED,DEPT DERMATOL,PHILADELPHIA,PA 19104. RP GOLDSTEIN, AM (reprint author), NCI,GENET EPIDEMIOL BRANCH,EXECUT PLAZA N,ROOM 439,6130 EXECUT BLVD,BETHESDA,MD 20892, USA. RI Tucker, Margaret/B-4297-2015 NR 30 TC 109 Z9 109 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 S WOODLAWN AVE, CHICAGO, IL 60637 SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD MAR PY 1994 VL 54 IS 3 BP 489 EP 496 PG 8 WC Genetics & Heredity SC Genetics & Heredity GA MZ158 UT WOS:A1994MZ15800012 PM 8116618 ER PT J AU AMOS, CI AF AMOS, CI TI ROBUST VARIANCE-COMPONENTS APPROACH FOR ASSESSING GENETIC-LINKAGE IN PEDIGREES SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Article ID QUANTITATIVE TRAITS; LINEAR-MODELS; MARKER LOCUS; IDENTITY AB To assess evidence for genetic linkage from pedigrees, I developed a limited variance-components approach. In this method, variability among trait observations from individuals within pedigrees is expressed in terms of fixed effects from covariates and effects due to an unobservable trait-affecting major locus, random polygenic effects, and residual nongenetic variance. The effect attributable to a locus linked to a marker is a function of the additive and dominance components of variance of the locus, the recombination fraction, and the proportion of genes identical by descent at the marker locus for each pair of sibs. For unlinked loci, the polygenic variance component depends only on the relationship between the relative pair. Parameters can be estimated by either maximum-likelihood methods or quasi-likelihood methods. The forms of quasi-likelihood estimators are provided. Hypothesis tests derived from the maximum-likelihood approach are constructed by appeal to asymptotic theory. A simulation study showed that the size of likelihood-ratio tests was appropriate but that the monogenic component of variance was generally underestimated by the likelihood approach. C1 NIAMS,GENET STUDIES SECT,BETHESDA,MD. RP AMOS, CI (reprint author), UNIV TEXAS,MD ANDERSON CANC CTR,DEPT EPIDEMIOL,1515 HOLCOMBE BLVD,BOX 189,HOUSTON,TX 77030, USA. NR 27 TC 587 Z9 599 U1 0 U2 4 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 S WOODLAWN AVE, CHICAGO, IL 60637 SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD MAR PY 1994 VL 54 IS 3 BP 535 EP 543 PG 9 WC Genetics & Heredity SC Genetics & Heredity GA MZ158 UT WOS:A1994MZ15800017 PM 8116623 ER PT J AU MACLEAN, CJ SHAM, PC PLOUGHMAN, LM DIEHL, SR KENDLER, KS AF MACLEAN, CJ SHAM, PC PLOUGHMAN, LM DIEHL, SR KENDLER, KS TI TESTING FOR LINKAGE UNDER HETEROGENEITY - A-TEST VERSUS C-TEST - REPLY SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Letter C1 VIRGINIA COMMONWEALTH UNIV,MED COLL VIRGINIA,DEPT HUMAN GENET,RICHMOND,VA 23298. INST PSYCHIAT,DEPT PSYCHOL MED,LONDON SE5 8AF,ENGLAND. INST PSYCHIAT,DEPT BIOSTAT & COMP,LONDON,ENGLAND. NIDR,EODPP,MOLEC EPIDEMIOL & DIS INDICATORS BRANCH,BETHESDA,MD. RP MACLEAN, CJ (reprint author), VIRGINIA COMMONWEALTH UNIV,MED COLL VIRGINIA,DEPT PSYCHIAT,RICHMOND,VA 23298, USA. NR 3 TC 2 Z9 2 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 S WOODLAWN AVE, CHICAGO, IL 60637 SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD MAR PY 1994 VL 54 IS 3 BP 564 EP 567 PG 4 WC Genetics & Heredity SC Genetics & Heredity GA MZ158 UT WOS:A1994MZ15800025 ER PT J AU MANOLIO, TA BURKE, GL SAVAGE, PJ SIDNEY, S GARDIN, JM OBERMAN, A AF MANOLIO, TA BURKE, GL SAVAGE, PJ SIDNEY, S GARDIN, JM OBERMAN, A TI EXERCISE BLOOD-PRESSURE RESPONSE AND 5-YEAR RISK OF ELEVATED BLOOD-PRESSURE IN A COHORT OF YOUNG-ADULTS - THE CARDIA STUDY SO AMERICAN JOURNAL OF HYPERTENSION LA English DT Article DE EXERCISE TEST; BLOOD PRESSURE; HYPERTENSION; POPULATION STUDIES AB Systolic blood pressure response to exercise has been shown to predict development of hypertension in men, but this association has not been examined in population-based samples of men, or in women or non-whites. This relationship was explored in 3741 normotensive black and white young adults undergoing treadmill testing in the CARDIA study and examined 5 years later for development of hypertension. Exaggerated response to exercise (systolic pressure greater than or equal to 210 mm Hg in men and greater than or equal to 190 mm Hg in women) was detected in 687 subjects (18%) at baseline, and incident hypertension (blood pressure greater than or equal to 140/90 mm Hg or on medication) was detected in 184 subjects (4.9%) at followup. Persons with exaggerated response to exercise at baseline had 5 mm Hg higher systolic and 1 mm Hg higher diastolic pressures at follow-up (P < .005) and were 1.70 times more likely to have developed hypertension than were persons with normal response (P <.001). After adjustment for age, race, sex, clinic, resting systolic pressure, body mass index, heavy activity score, exercise duration, and preexercise systolic pressure, exaggerated response was associated with a 2.14 mm Hg increase in year 5 systolic pressure (P <.0001). These associations did not differ by race or sex. Although the increment in systolic pressure associated with exaggerated exercise response was small (1 to 3 mm Hg), this small increment sustained over time could lead to a substantially increased incidence of hypertension and hypertension-related target organ damage. Determination of factors associated with exaggerated response may provide further insights into the development of hypertension in young adults. RP MANOLIO, TA (reprint author), NHLBI,DIV EPIDEMIOL & CLIN APPLICAT,CLIN & GENET EPIDEMIOL BRANCH,EBP,FED BLDG,ROOM 301,BETHESDA,MD 20892, USA. FU NHLBI NIH HHS [N01-HC-48048, N01-HC-48047, N01-HC-48049] NR 0 TC 116 Z9 117 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0895-7061 J9 AM J HYPERTENS JI Am. J. Hypertens. PD MAR PY 1994 VL 7 IS 3 BP 234 EP 241 PG 8 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA NB216 UT WOS:A1994NB21600004 PM 8003274 ER PT J AU BOCK, GH NEU, L LONG, C PATTERSON, LT KORB, S GELPI, J NELSON, DL AF BOCK, GH NEU, L LONG, C PATTERSON, LT KORB, S GELPI, J NELSON, DL TI AN ASSESSMENT OF SERUM AND URINE SOLUBLE INTERLEUKIN-2 RECEPTOR CONCENTRATIONS DURING RENAL-TRANSPLANT REJECTION SO AMERICAN JOURNAL OF KIDNEY DISEASES LA English DT Article DE RENAL TRANSPLANTATION; REJECTION; INTERLEUKIN 9 RECEPTORS; CELLULAR IMMUNITY; MONITORING ID CARDIAC ALLOGRAFT SURVIVAL; MONOCLONAL-ANTIBODY; RECIPIENTS; IL-2 C1 CHILDRENS NATL MED CTR,DEPT NEPHROL,WASHINGTON,DC. NCI,DCBDC,METAB BRANCH,BETHESDA,MD 20892. WASHINGTON HOSP CTR,DEPT TRANSPLANTAT,WASHINGTON,DC. NR 27 TC 21 Z9 22 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0272-6386 J9 AM J KIDNEY DIS JI Am. J. Kidney Dis. PD MAR PY 1994 VL 23 IS 3 BP 421 EP 426 PG 6 WC Urology & Nephrology SC Urology & Nephrology GA NA087 UT WOS:A1994NA08700012 PM 8128944 ER PT J AU SMITH, RJH BERLIN, CI HEJTMANCIK, JF KEATS, BJB KIMBERLING, WJ LEWIS, RA MOLLER, CG PELIAS, MZ TRANEBJAERG, L AF SMITH, RJH BERLIN, CI HEJTMANCIK, JF KEATS, BJB KIMBERLING, WJ LEWIS, RA MOLLER, CG PELIAS, MZ TRANEBJAERG, L TI CLINICAL-DIAGNOSIS OF THE USHER SYNDROMES SO AMERICAN JOURNAL OF MEDICAL GENETICS LA English DT Article DE USHER SYNDROME TYPE I; USHER SYNDROME TYPE II ID SYNDROME TYPE-II; RETINITIS-PIGMENTOSA; GENETIC-HETEROGENEITY; ELECTRICAL RESPONSE; CHROMOSOME-1Q; CILIA AB The Usher syndromes are genetically distinct disorders which share specific phenotypic characteristics. This paper describes a set of clinical criteria recommended for the diagnosis of Usher syndrome type I and Usher syndrome type II. These criteria have been adopted by the Usher Syndrome Consortium and are used in studies reported by members of this Consortium. (C) 1994 Wiley-Liss, Inc. C1 LOUISIANA STATE UNIV,SCH MED,NEW ORLEANS,LA. NEI,BETHESDA,MD 20892. BOYS TOWN NATL RES HOSP,OMAHA,NE 68131. LINKOPING UNIV,LINKOPING,SWEDEN. BAYLOR COLL MED,HOUSTON,TX. UNIV TROMSO,TROMSO,NORWAY. RP SMITH, RJH (reprint author), UNIV IOWA,DEPT OTOLARYNGOL,MOLEC OTOLARYNGOL RES LABS,IOWA CITY,IA 52242, USA. NR 34 TC 198 Z9 205 U1 2 U2 14 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0148-7299 J9 AM J MED GENET JI Am. J. Med. Genet. PD MAR 1 PY 1994 VL 50 IS 1 BP 32 EP 38 DI 10.1002/ajmg.1320500107 PG 7 WC Genetics & Heredity SC Genetics & Heredity GA MZ339 UT WOS:A1994MZ33900006 PM 8160750 ER PT J AU HORNSBY, PP WILCOX, AJ WEINBERG, CR HERBST, AL AF HORNSBY, PP WILCOX, AJ WEINBERG, CR HERBST, AL TI EFFECTS ON THE MENSTRUAL-CYCLE OF IN-UTERO EXPOSURE TO DIETHYLSTILBESTROL SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Article DE DIETHYLSTILBESTROL; MENSTRUAL CYCLE; MENSTRUATION DISORDERS; DYSMENORRHEA ID BLOOD-LOSS; FOLLOW-UP; WOMEN; PREGNANCY; INFERTILITY; STILBESTROL; DAUGHTERS; HISTORY; MOTHERS AB OBJECTIVES: The purpose of this study was to determine the effects of in utero exposure to diethylstilbestrol on the menstrual cycle. STUDY DESIGN: This was a prospective cohort study of 198 diethylstilbestrol-exposed women and 162 unexposed controls, recruited from women whose mothers participated in a randomized trial of diethylstilbestrol in pregnancy at the Chicago Lying-in Hospital from 1950 to 1952. Women with severe menstrual abnormality were excluded from the study. RESULTS: Diethylstilbestrol exposure was associated with a statistically significantly decreased duration of menstrual bleeding of approximately one half day and a lower average daily bleeding score (self-reported). We found no evidence for effects of diethylstilbestrol exposure on cycle length or variability of cycle length. Exposure was not related to symptoms of dysmenorrhea. CONCLUSIONS: The decreased duration and amount of menstrual bleeding among diethylstilbestrol-exposed women could be due to direct effects on the uterus. The lack of an effect on cycle length and variability appears to indicate that endocrine function is not grossly disturbed in those women studied. C1 NIEHS,EPIDEMIOL BRANCH,RES TRIANGLE PK,NC 27709. NIEHS,STAT & BIOMATH BRANCH,RES TRIANGLE PK,NC 27709. UNIV CHICAGO,DEPT OBSTET & GYNECOL,CHICAGO,IL 60637. OI Wilcox, Allen/0000-0002-3376-1311 NR 25 TC 25 Z9 26 U1 0 U2 1 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD MAR PY 1994 VL 170 IS 3 BP 709 EP 715 PG 7 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA NC566 UT WOS:A1994NC56600002 PM 8141188 ER PT J AU MCNELLIS, D MEDEARIS, AL FOWLER, S ROMERO, R SIBAI, BM CARITIS, SN PAUL, RH DEPP, R WITTER, F HOBBINS, JC HORENSTEIN, J CEFALO, RC GORDON, T YAFFE, S KLEBANOFF, M BERENDES, H CATZ, C WALLA, C COTRONEO, P TANNENBAUM, S BRAY, E SABO, G ROCCO, L PORTALE, A GREEN, L GREEN, JD AF MCNELLIS, D MEDEARIS, AL FOWLER, S ROMERO, R SIBAI, BM CARITIS, SN PAUL, RH DEPP, R WITTER, F HOBBINS, JC HORENSTEIN, J CEFALO, RC GORDON, T YAFFE, S KLEBANOFF, M BERENDES, H CATZ, C WALLA, C COTRONEO, P TANNENBAUM, S BRAY, E SABO, G ROCCO, L PORTALE, A GREEN, L GREEN, JD TI A CLINICAL-TRIAL OF INDUCTION OF LABOR VERSUS EXPECTANT MANAGEMENT IN POSTTERM PREGNANCY SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Article DE POSTTERM PREGNANCY; PROSTAGLANDIN-E2 GEL ID PROSTAGLANDIN-E2 GEL; PROLONGED PREGNANCY; FETAL SURVEILLANCE; TERM PREGNANCY AB OBJECTIVE: Management of the uncomplicated pregnancy prolonged beyond the estimated date of confinement is controversial, particularly when the cervix is unfavorable for induction. The benefit of reducing potential fetal risk with induction of labor must be balanced against the morbidity associated with this procedure. The objective of this study was to compare two strategies for managing postterm pregnancy (i.e., immediate induction and expectant mangement). STUDY DESIGN: Four hundred forty patients with uncomplicated pregnancies at 41 weeks' gestation were randomized to either immediate induction of labor (n = 265) or expectant management (n = 175). Patients with expectant management underwent nonstress testing and amnioic fluid volume assesment twice per week. Patients in the induction group underwent induction within 24 hours of randomization. To evaluate the efficacy of intracervical prostaglandin E2 gel, patients in the induction group were randomized in a 2:1 scheme to receive either 0.5 mg prostaglandin E2 gel or placebo gel intracervically 12 hours before induction of labor with oxytocin. RESULTS: The incidence of adverse perinatal outcome (neonatal seizures, intracranial hemorrhage, the need for mechanical ventilation, or nerve injury) was 1.5% in the induction group and 1% in the expectant management group (p > 0.05). There were no fetal deaths in either group. There were no differences in mean birth weight or the frequency of macrosomia (birth weight a 4000 gm) between the two groups (p > 0.05). Regardless of parity, prostaglandin E2 intracervical gel was not more effective than placebo in ripening the cervix. The cesarean delivery rate was not significantly different in the expectant (18%), prostaglandin E2 gel (23%), or placebo gel (18%) groups. CONCLUSIONS: Adverse perinatal outcome in otherwise uncomplicated pregnancies of greater-than-or-equal-to 41 weeks is very low with either of the management schemes described. Thus from the perspective of perinatal morbidity or mortality either management scheme is acceptable. C1 COLUMBIA UNIV,NEW YORK,NY 10027. GEORGE WASHINGTON UNIV,CTR BIOSTAT,WASHINGTON,DC 20052. JOHNS HOPKINS UNIV,BALTIMORE,MD 21218. THOMAS JEFFERSON UNIV,PHILADELPHIA,PA 19107. UNIV N CAROLINA,CHAPEL HILL,NC 27514. UNIV PITTSBURGH,MAGEE WOMENS HOSP,PITTSBURGH,PA 15213. UNIV SO CALIF,LOS ANGELES,CA 90089. UNIV TENNESSEE,KNOXVILLE,TN 37996. YALE UNIV,NEW HAVEN,CT 06520. RP MCNELLIS, D (reprint author), NICHHD,EPN BLDG,ROOM 643,BETHESDA,MD 20892, USA. NR 17 TC 55 Z9 56 U1 1 U2 5 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 1994 VL 170 IS 3 BP 716 EP 723 PG 8 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA NC566 UT WOS:A1994NC56600003 ER PT J AU HURTEAU, JA SIMON, HU KURMAN, C RUBIN, L MILLS, GB AF HURTEAU, JA SIMON, HU KURMAN, C RUBIN, L MILLS, GB TI LEVELS OF SOLUBLE INTERLEUKIN-2 RECEPTOR-ALPHA ARE ELEVATED IN SERUM AND ASCITIC FLUID FROM EPITHELIAL OVARIAN-CANCER PATIENTS SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Article DE SOLUBLE INTERLEUKIN-2 RECEPTOR-ALPHA; OVARIAN; EPITHELIAL ID COLONY-STIMULATING FACTOR; BREAST-CANCER; TUMOR-CELLS; MESSENGER AB OBJECTIVE: The purpose of the study was to determine whether ovarian cancer patients have activated lymphocytes as indicated by the presence of soluble interleukin-2 receptor-alpha and to compare soluble interleukin-2 receptor-alpha with other markers in ovarian cancer. STUDY DESIGN: Ascites and serum from patients with advanced active ovarian cancer was tested for the presence of elevated levels of soluble interleukin-2 receptor-alpha and compared with normal controls. Levels of soluble interleukin-2 receptor-alpha were also compared with levels of CA 125 and macrophage colony-stimulating factor in the same patients, to evaluate the correlation between different markers. RESULTS: Elevated levels of soluble interleukin-2 receptor-alpha were detected in 86 of 86 (100%) ascites samples and 67 of 85 (79%) serum samples from patients with advanced epithelial ovarian cancer. In contrast, only 12 of 25 (48%) benign ascites samples and one of 88 (1%) serum samples from controls had elevated levels. There was no obvious correlation between levels of soluble interleukin-2 receptor-alpha and levels of CA 125; however, levels of soluble interleukin-2 receptor-alpha did correlate with levels of macrophage colony-stimulating factor. Concurrent measurement of serum-soluble interleukin-2alpha and CA 125 levels detected 100% of patients with epithelial ovarian cancer. CONCLUSION: The detection of elevated levels of soluble interleukin-2 receptor-alpha in serum and ascites indicates the presence of activated lymphocytes in patients with epithelial ovarian cancer. Ascites and serum levels of soluble interleukin-2 receptor-alpha are elevated in patients with advanced ovarian cancer and warrant assessment as a potential complementary marker to CA 125 for early detection of ovarian cancer and management of patients with advanced ovarian cancer. C1 TORONTO GEN HOSP,200 ELIZABETH ST,TORONTO M5G 2C4,ON,CANADA. UNIV TORONTO,DEPT OBSTET & GYNECOL,TORONTO M5S 1A1,ONTARIO,CANADA. UNIV TORONTO,DEPT MED & IMMUNOL,TORONTO M5S 1A1,ONTARIO,CANADA. NIH,BETHESDA,MD 20892. NR 34 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 1994 VL 170 IS 3 BP 918 EP 928 PG 11 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA NC566 UT WOS:A1994NC56600042 PM 8141226 ER PT J AU SNOW, JB AF SNOW, JB TI NEWS FROM THE NATIONAL-INSTITUTE-ON-DEAFNESS-AND-OTHER-COMMUNICATION-DISORDERS SO AMERICAN JOURNAL OF OTOLOGY LA English DT Editorial Material RP SNOW, JB (reprint author), NIDCD,BETHESDA,MD, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0192-9763 J9 AM J OTOL JI Am. J. Otol. PD MAR PY 1994 VL 15 IS 2 BP 132 EP 136 PG 5 WC Otorhinolaryngology SC Otorhinolaryngology GA MZ141 UT WOS:A1994MZ14100003 PM 8172291 ER PT J AU TAKAHASHI, T UEDA, S TAKAHASHI, K SCOW, RO AF TAKAHASHI, T UEDA, S TAKAHASHI, K SCOW, RO TI PH-DEPENDENT MULTILAMELLAR STRUCTURES IN FETAL MOUSE BONE - POSSIBLE INVOLVEMENT OF FATTY-ACIDS IN BONE MINERALIZATION SO AMERICAN JOURNAL OF PHYSIOLOGY LA English DT Article DE OSTEOBLASTS; MEMBRANE BONE; FATTY ACIDS; TANNIC ACID; ELECTRON MICROSCOPY ID WHITE ADIPOSE-TISSUE; YOUNG-RATS; ELECTRON-MICROSCOPE; LIPOLYTIC PRODUCTS; FREEZE-FRACTURE; TANNIC-ACID; MEMBRANES; ULTRASTRUCTURE; PRESERVATION; COMPLEXES AB Multilamellar structures (MLS) were found inside and outside osteoblasts in cultured and uncultured fetal mouse parietal bone fixed at pH 7.3 with glutaraldehyde solution containing tannic acid (TA). Electron-lucent areas (up to 1.5 mu m in diameter) surrounded by thin lamellar structures were found in place of MLS in bone and bone cell cultures fixed at pH 6.0 in the presence of TA. Large lipid droplets were found, in place of electron-lucent areas and MLS, in specimens fixed at pH 7.4 in the absence of TA and dehydrated with a procedure that did not extract neutral lipid. Freeze-fracture studies showed phosphatidylcholine formed MLS at both pH 8.1 and pH 6.0, whereas oleic acid formed MLS at pH 8.1 and lipid droplets at pH 6.0. Thus fatty acids probably formed the pH-dependent MLS found in bone. The data suggest that osteoblasts synthesize and secrete fatty acids, as droplets, into the extracellular space. The close association of MLS with calcifying osteoid in specimens processed with TA suggests that fatty acids are directly involved in bone mineralization. C1 NIHON UNIV,SCH SCI & TECHNOL,CHIYODA KU,TOKYO 101,JAPAN. NIDDK,CELLULAR & DEV BIOL LAB,ENDOCRINOL SECT,BETHESDA,MD 20892. RP TAKAHASHI, T (reprint author), KANAGAWA DENT COLL,DEPT ORAL ANAT,82 INAOKA CHO,YOKOSUKA,KANAGAWA 238,JAPAN. NR 29 TC 6 Z9 6 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 1994 VL 266 IS 3 BP C590 EP C600 PN 1 PG 11 WC Physiology SC Physiology GA NF859 UT WOS:A1994NF85900002 PM 8166222 ER PT J AU KNUDSEN, GM PETTIGREW, KD PATLAK, CS PAULSON, OB AF KNUDSEN, GM PETTIGREW, KD PATLAK, CS PAULSON, OB TI BLOOD-BRAIN-BARRIER PERMEABILITY MEASUREMENTS BY DOUBLE-INDICATOR METHOD USING INTRAVENOUS-INJECTION SO AMERICAN JOURNAL OF PHYSIOLOGY LA English DT Article DE BLOOD-BRAIN BARRIER; HUMANS; GLUCOSE; PHENYLALANINE; WATER ID AMINO-ACID-TRANSPORT; HETEROGENEITY; ERYTHROCYTES; GLUCOSE AB The double-indicator technique with intracarotid bolus injection is useful for the estimation of transfer rates across the human blood-brain barrier. A method using intravenous tracer injection is developed whereby the input is measured at a peripheral artery and the output is measured at the jugular vein. To correct for differences in the brain input of test and reference substances, a five-parameter Dirac impulse response for passage through the cerebrovascular bed is computed from the input and output of the reference substance. This response is then combined with a capillary model of the brain. This is then convoluted with the arterial input curve of the test substance to yield a theoretical test output curve, which is compared with the actual test output curve. On the basis of these two curves and an appropriate mathematical model for the brain, estimates of blood-brain barrier permeability are obtained. In the present study, the techniques are compared in 13 patients in whom alternating intracarotid and intravenous bolus injections were given. For D-glucose, the two techniques yielded similar results. This was also the case for L-phenylalanine, provided that the erythrocyte compartment was taken into account. Data obtained after intravenous injection of leucine and water yielded similar results compared with previous intracarotid data. C1 NIMH, DIV APPL & SERV RES, BETHESDA, MD 20892 USA. SUNY STONY BROOK, HLTH SCI CTR, DEPT NEUROL SURG, STONY BROOK, NY 11794 USA. RP KNUDSEN, GM (reprint author), UNIV CLIN COPENHAGEN, RIGSHOSP, DEPT NEUROL N2082, 9 BLEGDAMSVEJ, DK-2100 COPENHAGEN, DENMARK. RI Knudsen, Gitte/C-1368-2013 OI Knudsen, Gitte/0000-0003-1508-6866 NR 25 TC 14 Z9 14 U1 0 U2 3 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0002-9513 J9 AM J PHYSIOL JI Am. J. Physiol. PD MAR PY 1994 VL 266 IS 3 BP H987 EP H999 PN 2 PG 13 WC Physiology SC Physiology GA NF861 UT WOS:A1994NF86100021 PM 8160848 ER PT J AU LIU, JY NETTESHEIM, P RANDELL, SH AF LIU, JY NETTESHEIM, P RANDELL, SH TI GROWTH AND DIFFERENTIATION OF TRACHEAL EPITHELIAL PROGENITOR CELLS SO AMERICAN JOURNAL OF PHYSIOLOGY LA English DT Article DE BASAL CELLS; SECRETORY CELLS; CILIATED CELLS ID BASAL CELLS; MONOCLONAL-ANTIBODY; RAT TRACHEA; MARKERS; REGENERATION; KERATIN-7; KINETICS; TISSUE; BREAST; FETUS AB The purpose of these studies was to determine whether both basal and secretory rat tracheal epithelial (RTE) cells served as multipotent epithelial progenitors and whether both cell types gave rise to a similar ''poorly differentiated'' cell during the early phase of epithelial regeneration in denuded tracheal grafts. Griffonia simplicifolia I (GSI) lectin and flow cytometry were used for cell sorting. More than 98% of GSI-positive cells expressed plasma membrane alpha 1-3 terminal galactose (Gal), and 95% contained keratin 14 (K14), phenotypic markers for basal cells; <1% were secretory or ciliated cells. Less than 2% of the GSI-negative cells expressed Gal or K14, but this fraction contained 16% ciliated cells and 54-79% secretory cells, dependent on whether periodic acid-Schiff staining or binding of an antisecretory cell monoclonal antibody (RTE 12) was used as the criterion. Equal numbers of viable cells from either fraction were inoculated into denuded tracheal grafts, which were studied on days 1-14. At 24 h, greater numbers of GSI-negative than -positive cells were found attached to the graft wall; the keratin staining pattern of the attached cells was similar to that of the parent cell populations, but monoclonal antibody-detectable secretory and ciliated cell epitopes, originally present in the GSI-negative fraction, were lost. 5-Bromo-2'-deoxyuridine uptake was not seen at 24 h, but by 48 h all epithelial cells from both fractions entered the cell cycle. From 48 to 96 h, cells derived from either fraction were ultrastructurally indistinguishable; they were poorly differentiated and highly proliferative, and all expressed Gal and K14. A mature epithelium evolved from the poorly differentiated cells in both sets of grafts, but secretory and ciliated cells appeared earlier in grafts inoculated with GSI-negative cells. The results strongly suggest that in this model of tracheal epithelial regeneration both basal and secretory cells ''dedifferentiated'' into a similar highly proliferative phenotype from which a mucociliary epithelium ''redifferentiated.'' C1 NIEHS,PULM PATHOBIOL LAB,RES TRIANGLE PK,NC 27709. NR 29 TC 47 Z9 47 U1 0 U2 1 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 1994 VL 266 IS 3 BP L296 EP L307 PN 1 PG 12 WC Physiology SC Physiology GA NF859 UT WOS:A1994NF85900094 PM 8166299 ER PT J AU LAUNAY, G COSTA, JL DAPRADA, M LAUNAY, JM AF LAUNAY, G COSTA, JL DAPRADA, M LAUNAY, JM TI ESTIMATION OF RATE CONSTANTS FOR SEROTONIN UPTAKE AND COMPARTMENTATION IN NORMAL HUMAN PLATELETS SO AMERICAN JOURNAL OF PHYSIOLOGY LA English DT Article DE STRUCTURAL IDENTIFICATION; NONLINEAR OPTIMIZATION; 5-HYDROXYTRYPTAMINE; BLOOD PLATELET ID INTACT HUMAN-PLATELETS; BOVINE PLATELETS; 5-HYDROXYTRYPTAMINE; GRANULES; RELEASE; STORAGE; BINDING; MODELS AB Biochemical and pharmacological experiments led to a model describing a thrombin-releasable (vesicular) compartment and two non-thrombin-releasable compartments for 5-hydroxytryptamine (5-HT, serotonin) in normal human platelets (J. L. Costa, K. L. Kirk, D. L. Murphy, and H. Stark. Br. J. Pharmacol. 72: 449-459, 1981). With tritiated 5-HT as substrate, the amounts of total and nonreleasable intraplatelet tritiated material were measured. Moreover, in the last set of experiments, the amounts of extraplatelet tritiated material and extraplatelet tritiated 5-HT were also measured. With these data, identification of the kinetic constants for movement between the various compartments was possible. A recent extension of the similarity transformation approach to nonlinear compartmental models was used to carry out the a priori identifiability analysis. Then numerical identification was performed by implementing and achieving: efficient methods from optimal control theory. Under owl experimental conditions, the main results are as follows: 1) the vesicular compartment corresponds to the platelet storage 5-HT compartment, 2) instead of pools I and II proposed previously, only a single nonreleasable thrombin-resistant pool could be detected, and 3) the optimized model computed to suit the first set of experiments fits homologous intraplatelet results obtained under similar experimental conditions in the last set of experiments and also fits one of the two supplementary extraplatelet investigations. C1 HOP ST LOUIS,FORMAT RECH ASSOCIEE C BERNARD NEUROCHIM COMMUNIC,F-75010 PARIS,FRANCE. NIMH,CLIN NEUROPHARMACOL BRANCH,BETHESDA,MD 20892. F HOFFMANN LA ROCHE & CO LTD,DEPT PHARMACEUT RES,CH-4002 BASEL,SWITZERLAND. RP LAUNAY, G (reprint author), INRIA,DOMAINE VOLUCEAU,BP 105 ROCQUENCOURT,F-78153 LE CHESNAY,FRANCE. NR 32 TC 8 Z9 8 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 1994 VL 266 IS 3 BP R1061 EP R1075 PN 2 PG 15 WC Physiology SC Physiology GA NF861 UT WOS:A1994NF86100106 ER PT J AU SUBAR, AF ZIEGLER, RG PATTERSON, BH URSIN, G GRAUBARD, B AF SUBAR, AF ZIEGLER, RG PATTERSON, BH URSIN, G GRAUBARD, B TI US DIETARY PATTERNS ASSOCIATED WITH FAT INTAKE - THE 1987 NATIONAL-HEALTH INTERVIEW SURVEY SO AMERICAN JOURNAL OF PUBLIC HEALTH LA English DT Article ID FOOD FREQUENCY QUESTIONNAIRE; NHANES-II SURVEY; QUANTITATIVE DATA; NUTRIENT SOURCES; AMERICAN DIET; INTERVENTION; VALIDATION; RECORDS; WOMEN AB Objectives. This research used food frequency data to investigate dietary patterns associated with fat intake. Methods. Data from the 1987 National Health Interview Survey of 20 143 adults were used to determine correlations between fat (adjusted for kilocalories) and both nutrient and food group intakes. Median food and nutrient intakes were determined within quartiles of percentage of kilocalories from fat. Results. Intakes of vegetables, fruits, cereals, fish/chicken, low-fat milk, alcoholic beverages, vitamin C, percentage of kilocalories from carbohydrates, carotenoids, folate, dietary fiber, carbohydrates, and vitamin A decreased as percentage of kilocalories from fat increased. Intakes of salty snacks, peanuts, processed and red meats, whole milk and cheese, desserts, eggs, fried potatoes, table fats, cholesterol, vitamin E, sodium, protein, and energy increased with percentage of kilocalories from fat. Results by demographic subgroups showed few differences from those found in the total population. Conclusions. Fat intake is consistently associated with specific dietary patterns. Such patterns need to be evaluated concurrently in studies of diet and chronic disease. C1 NCI,DIV CANC ETIOL,BETHESDA,MD 20892. UNIV SO CALIF,SCH MED,DEPT PREVENT MED,LOS ANGELES,CA 90033. RP SUBAR, AF (reprint author), NCI,DIV CANC PREVENT & CONTROL,APPL RES BRANCH,SURVEILLANCE PROGRAM,9000 ROCKVILLE PIKE,EPN 313,BETHESDA,MD 20892, USA. NR 26 TC 41 Z9 41 U1 1 U2 5 PU AMER PUBLIC HEALTH ASSOC INC PI WASHINGTON PA 1015 FIFTEENTH ST NW, WASHINGTON, DC 20005 SN 0090-0036 J9 AM J PUBLIC HEALTH JI Am. J. Public Health PD MAR PY 1994 VL 84 IS 3 BP 359 EP 366 DI 10.2105/AJPH.84.3.359 PG 8 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA NM618 UT WOS:A1994NM61800005 PM 8129050 ER PT J AU CHEN, YCJ YU, MLM ROGAN, WJ GLADEN, BC HSU, CC AF CHEN, YCJ YU, MLM ROGAN, WJ GLADEN, BC HSU, CC TI A 6-YEAR FOLLOW-UP OF BEHAVIOR AND ACTIVITY DISORDERS IN THE TAIWAN YU-CHENG CHILDREN SO AMERICAN JOURNAL OF PUBLIC HEALTH LA English DT Article ID POLYCHLORINATED-BIPHENYLS; PCBS; EXPOSURE; MONKEYS; MICE; INFANTS; MOTHERS AB Objectives. The relationship of behavior and activity levels to the interval between outbreak and year of birth and to age of the children is explored in Taiwanese children exposed in utero to heat-degraded polychlorinated biphenyls (PCBs)-the Yu-cheng children. Additionally, the relationship of the scores to chemical, physical, and cognitive findings is described. Methods. With Rutter's Child Behavior Scale A and a modified Werry-Weiss-Peters Activity Scale, 118 Yu-cheng children and matched controls were followed biannually from 1985 to 1991. Results. At each year, the Yu-cheng children scored 7% to 43% worse (mean = 23%) than control children on the Rutter scale. At any fixed age, the Yu-cheng children scored 11% to 63% (mean = 28%) worse. The effect for children born later did not differ from that for those born earlier; neither was there any improvement as the children aged. A similar but weaker picture was seen for the activity score. These behavioral findings were not related to physical or cognitive findings or to serum PCB levels. Conclusions. Inutero exposure to heat-degraded PCBs appears to cause mildly disordered behavior and increased activity level; the effect persists over time and is similar in children born up to 6 years after the mothers were exposed. C1 NIEHS,DIV INTRAMURAL RES,RES TRIANGLE PK,NC 27709. NATL CHENG KUNG UNIV,COLL MED,DEPT PSYCHIAT,TAINAN,TAIWAN. RI Rogan, Walter/I-6034-2012 OI Rogan, Walter/0000-0002-9302-0160 NR 46 TC 83 Z9 85 U1 3 U2 6 PU AMER PUBLIC HEALTH ASSOC INC PI WASHINGTON PA 1015 FIFTEENTH ST NW, WASHINGTON, DC 20005 SN 0090-0036 J9 AM J PUBLIC HEALTH JI Am. J. Public Health PD MAR PY 1994 VL 84 IS 3 BP 415 EP 421 DI 10.2105/AJPH.84.3.415 PG 7 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA NM618 UT WOS:A1994NM61800014 PM 8129058 ER PT J AU LYNCH, CF LOGSDENSACKETT, N EDWARDS, SL CANTOR, KP AF LYNCH, CF LOGSDENSACKETT, N EDWARDS, SL CANTOR, KP TI THE DRIVERS LICENSE LIST AS A POPULATION-BASED SAMPLING FRAME IN IOWA SO AMERICAN JOURNAL OF PUBLIC HEALTH LA English DT Note ID TELEPHONE; DIRECTORIES AB Driver's license lists are infrequently used for population-based sampling, presumably because of suspicions of poor population coverage. The 1990 Iowa driver's license list was compared with the 1990 census to evaluate coverage by 5-year age group, sex, resident county, and urbanicity. Coverage exceeded 90% among 15- to 74-year-old men and 15- to 64-year-old women, with uniform coverage by county and county urbanicity group in these age ranges. In Iowa, these lists are convenient and cost-effective and appear to be representative for 25- to 64-year-olds. The representativeness of driver lists in regard to other factors and in other geographic regions deserves further evaluation. C1 UNIV UTAH,DEPT FAMILY & PREVENT MED,SALT LAKE CITY,UT. NCI,ENVIRONM EPIDEMIOL BRANCH,BETHESDA,MD 20892. RP LYNCH, CF (reprint author), UNIV IOWA,DEPT PREVENT MED & ENVIRONM HLTH,2800 STEINDLER BLDG,IOWA CITY,IA 52242, USA. FU NCI NIH HHS [5 KO7 CA01181-05] NR 22 TC 36 Z9 36 U1 0 U2 0 PU AMER PUBLIC HEALTH ASSOC INC PI WASHINGTON PA 1015 FIFTEENTH ST NW, WASHINGTON, DC 20005 SN 0090-0036 J9 AM J PUBLIC HEALTH JI Am. J. Public Health PD MAR PY 1994 VL 84 IS 3 BP 469 EP 472 DI 10.2105/AJPH.84.3.469 PG 4 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA NM618 UT WOS:A1994NM61800025 PM 8129069 ER PT J AU BERNARD, GR ARTIGAS, A BRIGHAM, KL CARLET, J FALKE, K HUDSON, L LAMY, M LEGALL, JR MORRIS, A SPRAGG, R COCHIN, B LANKEN, PN LEEPER, KV MARINI, J MURRAY, JF OPPENHEIMER, L PESENTI, A REID, L RINALDO, J VILLAR, J VANASBECK, BS DHAINAUT, JF MANCEBO, J MATTHAY, M MEYRICK, B PAYEN, D PERRET, C FOWLER, AA SCHALLER, MD HUDSON, LD HYERS, T KNAUS, W MATTHAY, R PINSKY, M BONE, RC BOSKEN, C JOHANSON, WG LEWANDOWSKI, K REPINE, J RODRIGUEZROISIN, R ROUSSOS, C ANTONELLI, MA BELOUCIF, S BIHARI, D BURCHARDI, H LEMAIRE, F MONTRAVERS, P PETTY, TL ROBOTHAM, J ZAPOL, W AF BERNARD, GR ARTIGAS, A BRIGHAM, KL CARLET, J FALKE, K HUDSON, L LAMY, M LEGALL, JR MORRIS, A SPRAGG, R COCHIN, B LANKEN, PN LEEPER, KV MARINI, J MURRAY, JF OPPENHEIMER, L PESENTI, A REID, L RINALDO, J VILLAR, J VANASBECK, BS DHAINAUT, JF MANCEBO, J MATTHAY, M MEYRICK, B PAYEN, D PERRET, C FOWLER, AA SCHALLER, MD HUDSON, LD HYERS, T KNAUS, W MATTHAY, R PINSKY, M BONE, RC BOSKEN, C JOHANSON, WG LEWANDOWSKI, K REPINE, J RODRIGUEZROISIN, R ROUSSOS, C ANTONELLI, MA BELOUCIF, S BIHARI, D BURCHARDI, H LEMAIRE, F MONTRAVERS, P PETTY, TL ROBOTHAM, J ZAPOL, W TI THE AMERICAN-EUROPEAN CONSENSUS CONFERENCE ON ARDS - DEFINITIONS, MECHANISMS, RELEVANT OUTCOMES, AND CLINICAL-TRIAL COORDINATION SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Editorial Material ID RESPIRATORY-DISTRESS SYNDROME; ICU PATIENTS; FAILURE; SYSTEM; PHYSIOLOGY; MORTALITY; SURVIVAL AB The acute respiratory distress syndrome (ARDS), a process of nonhydrostatic pulmonary edema and hypoxemia associated with a variety of etiologies, carries a high morbidity, mortality (10 to 90%), and financial cost. The reported annual incidence in the United States is 150,000 cases, but this figure has been challenged, and it may be different in Europe. Part of the reason for these uncertainties are the heterogeneity of diseases underlying ARDS and the lack of uniform definitions for ARDS. Thus, those who wish to know the true incidence and outcome of this clinical syndrome are stymied. The American-European Consensus Committee on ARDS was formed to focus on these issues and on the pathophysiologic mechanisms of the process. It was felt that international coordination between North America and Europe in clinical studies of ARDS was becoming increasingly important in order to address the recent plethora of potential therapeutic agents for the prevention and treatment of ARDS. C1 LATTER DAY ST HOSP,SALT LAKE CITY,UT. ST JOSEPHS HOSP,PARIS,FRANCE. HOSP PARIS,PARIS,FRANCE. UNIV PENN,PHILADELPHIA,PA. UNIV TENNESSEE,MEMPHIS,TN. UNIV MINNESOTA,MINNEAPOLIS,MN. UNIV CALIF SAN FRANCISCO,SAN FRANCISCO,CA. UNIV MANITOBA,WINNIPEG R3T 2N2,MB,CANADA. UNIV MILAN,MONZA,ITALY. HARVARD UNIV,CHILDRENS HOSP,SCH MED,BOSTON,MA 02115. UNIV TORONTO,TORONTO,ON,CANADA. VANDERBILT UNIV,SCH MED,NASHVILLE,TN 37212. UNIV LIEGE,LIEGE,BELGIUM. UNIV UTRECHT,UTRECHT,NETHERLANDS. HOP COCHIN,PARIS,FRANCE. VIRGINIA COMMONWEALTH UNIV,MED COLL VIRGINIA,RICHMOND,VA 23298. UNIV LAUSANNE,LAUSANNE,SWITZERLAND. UNIV WASHINGTON,SEATTLE,WA. ST LOUIS UNIV,ST LOUIS,MO. GEORGE WASHINGTON UNIV,WASHINGTON,DC. UNIV PITTSBURGH,PITTSBURGH,PA. UNIV CALIF SAN DIEGO,SAN DIEGO,CA. RUSH MED COLL,CHICAGO,IL. NHLBI,DIV LUNG DIS,BETHESDA,MD. UNIV MED & DENT NEW JERSEY,NEW JERSEY MED SCH,NEWARK,NJ 07103. UNIV COLORADO,HLTH SCI CTR,WEBB WARING INST BIOMED RES,DENVER,CO. HOSP CLIN BARCELONA,BARCELONA,SPAIN. EVANGELISMOS MED CTR,ATHENS,GREECE. UNIV ROME,ROME,ITALY. GUYS HOSP,LONDON,ENGLAND. UNIV GOTTINGEN,GOTTINGEN,GERMANY. MASSACHUSETTS GEN HOSP,BOSTON,MA. RP BERNARD, GR (reprint author), VANDERBILT UNIV,T-1219 MCN,NASHVILLE,TN, USA. FU NHLBI NIH HHS [NHLBI HL19153, NHLBI HL43167] NR 27 TC 3647 Z9 3962 U1 12 U2 75 PU AMER LUNG ASSOC PI NEW YORK PA 1740 BROADWAY, NEW YORK, NY 10019 SN 1073-449X J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PD MAR PY 1994 VL 149 IS 3 BP 818 EP 824 PG 7 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA NP719 UT WOS:A1994NP71900042 PM 7509706 ER PT J AU FISHMAN, AP HURD, SS FUHRER, MJ AF FISHMAN, AP HURD, SS FUHRER, MJ TI PULMONARY REHABILITATION RESEARCH SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Editorial Material C1 NHLBI,DLD,BETHESDA,MD 20892. NICHHD,NCMRR,BETHESDA,MD 20892. NR 2 TC 63 Z9 64 U1 0 U2 0 PU AMER LUNG ASSOC PI NEW YORK PA 1740 BROADWAY, NEW YORK, NY 10019 SN 1073-449X J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PD MAR PY 1994 VL 149 IS 3 BP 825 EP 833 PG 9 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA NP719 UT WOS:A1994NP71900043 PM 8118655 ER PT J AU SNOW, JB AF SNOW, JB TI NIDCD RESEARCH IN HUMAN-COMMUNICATION - PRESENTED TO THE XII INTERNATIONAL-SYMPOSIUM ON INFECTION AND ALLERGY OF THE NOSE, OCTOBER 8, 1993 SO AMERICAN JOURNAL OF RHINOLOGY LA English DT Article AB The mission of the National Institute on Deafness and Other Communication Disorders (NIDCD) is to support and conduct biomedical and behavioral research and research training on normal mechanisms as well as diseases and disorders of hearing, balance, smell, taste, voice, speech, and language. The National Strategic Research Plan, developed in 1989, guides the research supported and conducted by the Institute in each of its seven areas of interest. Each year two sections of the plan are updated. The chemical senses section of the plan was updated in January 1993. Some of the research goals, opportunities, and priorities in olfaction recommended by the panel are presented. Several examples of NIDCD-supported olfactory research are also highlighted. Research opportunities for foreign scientists in the Institute's intramural laboratories are outlined along with opportunities for international collaborations through the NIDCD. NIDCD funding for chemosensory research is provided. RP SNOW, JB (reprint author), NIDOCD,BLDG 31,ROOM 3C-02,BETHESDA,MD 20892, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OCEAN SIDE PUBLICATIONS INC PI PROVIDENCE PA 95 PITMAN ST, PROVIDENCE, RI 02906 SN 1050-6586 J9 AM J RHINOL JI Am. J. Rhinol. PD MAR-APR PY 1994 VL 8 IS 2 BP 97 EP 100 DI 10.2500/105065894781874467 PG 4 WC Otorhinolaryngology SC Otorhinolaryngology GA NL354 UT WOS:A1994NL35400007 ER PT J AU CHEEVER, AW MOSIMANN, JE DEB, S CHEEVER, EA DUVALL, RH AF CHEEVER, AW MOSIMANN, JE DEB, S CHEEVER, EA DUVALL, RH TI NATURAL-HISTORY OF SCHISTOSOMA-MANSONI INFECTION IN MICE - EGG-PRODUCTION, EGG PASSAGE IN THE FECES, AND CONTRIBUTION OF HOST AND PARASITE DEATH TO CHANGES IN WORM NUMBERS SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE LA English DT Article ID INTENSITY; FECUNDITY AB Mice, C57B1/6N (B6) and BALB/cAnN (BALB), infected with Schistosoma mansoni were examined 8-26 weeks postinfection (PI) to estimate the fecundity of the worms and the contribution of death of worms and the death of heavily infected mice to the decrease in worm numbers in chronic infections. Portal worms were recovered by perfusion and the lungs were examined for parasites shunted from the portal circulation. Animals that died were more heavily infected than those that survived. Between eight and 12 weeks PI, this loss of worms resulted in a net decrease of approximately 19% of worm Fairs in surviving BALB mice, but of only 4% in B6 mice. Loss of portal worms to the lungs after the eighth week of infection was 9-13% of portal worms in BALB mice and 3-4% in B6 mice. The estimated rates of egg production by S. mansoni decreased slightly with time in both strains of mice. At 12 and 20 weeks PI, tissue eggs per worm pair and eggs passed in the feces per worm pair often decreased as the intensity of infection increased. We do not consider the loss of worms in the murine host relevant to most infections in humans because of the high intensity of infection relative to body size in mice and the high frequency of severe portal obstruction in murine infections. C1 SWARTHMORE COLL,DEPT ENGN,SWARTHMORE,PA 19081. RP CHEEVER, AW (reprint author), NIAID,PARASIT DIS LAB,BLDG 4,BETHESDA,MD 20892, USA. NR 23 TC 19 Z9 21 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 1994 VL 50 IS 3 BP 269 EP 280 PG 12 WC Public, Environmental & Occupational Health; Tropical Medicine SC Public, Environmental & Occupational Health; Tropical Medicine GA NE918 UT WOS:A1994NE91800002 PM 8147486 ER PT J AU CHEEVER, AW MACEDONIA, JG MOSIMANN, JE CHEEVER, EA AF CHEEVER, AW MACEDONIA, JG MOSIMANN, JE CHEEVER, EA TI KINETICS OF EGG-PRODUCTION AND EGG EXCRETION BY SCHISTOSOMA-MANSONI AND SCHISTOSOMA-JAPONICUM IN MICE INFECTED WITH A SINGLE PAIR OF WORMS SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE LA English DT Article ID HEPATIC-FIBROSIS; INTENSITY; FECUNDITY; BABOONS; PERSISTENCE AB Individual male and female schistosomes approximately three weeks of age were implanted into the portal venous system of C57Bl/6 mice to produce infections with a single pair of Schistosoma mansoni or S. japonicum. Mice were killed between seven and 53 weeks after infection. Worm fecundity was measured by counting eggs accumulating in the tissues and eggs passed in the feces. Schistosoma mansoni worm pairs laid approximately 350 eggs per day with no change in the apparent rate of egg laying between eight and 52 weeks after infection and approximately one-third of the eggs were passed in the feces. Schistosoma japonicum worm pairs laid approximately 2,200 eggs per day initially and this decreased to 1,000 eggs per day by the end of the experiment, with one-third to one-half of the eggs being passed in the feces. Then was marked variability in the fecundity of individual worm pairs, but the number of eggs passed in the feces of individual mice correlated well with the number of eggs in the intestines at all time points in S. mansoni-infected mice and at the seventh and tenth week of S. japonicum infection. C1 NIH,BETHESDA,MD 20892. SWARTHMORE COLL,DEPT ENGN,SWARTHMORE,PA 19081. RP CHEEVER, AW (reprint author), NIAID,PARASIT DIS LAB,BLDG 4,ROOM 126,BETHESDA,MD 20892, USA. NR 32 TC 43 Z9 45 U1 1 U2 5 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 1994 VL 50 IS 3 BP 281 EP 295 PG 15 WC Public, Environmental & Occupational Health; Tropical Medicine SC Public, Environmental & Occupational Health; Tropical Medicine GA NE918 UT WOS:A1994NE91800003 PM 8147487 ER PT J AU COUTINHO, AD DREYER, G MEDEIROS, Z LOPES, E MACHADO, G GALDINO, E RIZZO, JA ANDRADE, LD ROCHA, A MOURA, I GODOY, J OTTESEN, EA AF COUTINHO, AD DREYER, G MEDEIROS, Z LOPES, E MACHADO, G GALDINO, E RIZZO, JA ANDRADE, LD ROCHA, A MOURA, I GODOY, J OTTESEN, EA TI IVERMECTIN TREATMENT OF BANCROFTIAN FILARIASIS IN RECIFE, BRAZIL SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE LA English DT Article ID HIGH-DOSE IVERMECTIN; WUCHERERIA-BANCROFTI; HUMAN ONCHOCERCIASIS; LYMPHATIC FILARIASIS; FRENCH-POLYNESIA; DIETHYLCARBAMAZINE; EFFICACY; SAFETY; CHEMOTHERAPY; TOLERANCE AB To determine the effectiveness of single oral dosages of ivermectin ranging between 20 and 200 mu g/kg and to make detailed observations of both the kinetics of parasite killing and the adverse reactions induced by treatment, the present double-blind study on ivermectin treatment of lymphatic filariasis caused by Wuchereria bancrofti was undertaken with 43 microfilaremic patients in Recife, Brazil. Follow-up at one year indicated equivalent efficacy for the 20-, 100-, and 200-mu g/kg drug dosages in reducing microfilaremia to geometric means of 13-25% of pretreatment levels. Adverse clinical reactions (predominantly fever, headache, weakness, and myalgia) occurred to some degree in almost all patients but generally lasted only 24-48 hr and were easily managed symptomatically. Adverse reactions were significantly milder in those receiving the lowest (20 mu g/kg) ivermectin dose, and they were significantly correlated with individuals' pretreatment microfilaremia levers in all groups. Posttreatment eosinophilia was a regular feature of the response to treatment, with the magnitude and kinetics also proportional to pretreatment microfilarial levels. Transient pulmonary function abnormalities (16 of 42, 38%), liver enzyme elevations (10 of 43, 23%), and hematuria (9 of 42, 22%) developed posttreatment, but air cleared without significant complications. The results indicate that W. bancrofti from Brazil is similar to strains of the parasites studied elsewhere in susceptibility to ivermectin, that the drug's systemic adverse reactions are essentially those resulting from parasite clearance, and that the intensity of these reactions can be significantly reduced by using the low (20 mu g/kg) dose of ivermectin. This detailed dose-finding study provides information necessary for developing optimal regimens to treat bancroftian filariasis with ivermectin either alone or in combination with other medications. C1 UNIV FED PERNAMBUCO,HOSP CLIN,RECIFE,PE,BRAZIL. NIAID,PARASIT DIS LAB,BETHESDA,MD 20892. RP COUTINHO, AD (reprint author), CTR PESQUISAS AGGEU MAGALHAES,AV MORAES REGO S-N,CAMPUS UNIV,CIDADE UNIV,BR-52020020 RECIFE,PE,BRAZIL. NR 30 TC 22 Z9 24 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 1994 VL 50 IS 3 BP 339 EP 348 PG 10 WC Public, Environmental & Occupational Health; Tropical Medicine SC Public, Environmental & Occupational Health; Tropical Medicine GA NE918 UT WOS:A1994NE91800008 PM 8147492 ER PT J AU KOLOBOW, T POWERS, T MANDAVA, S APRIGLIANO, M KAWAGUCHI, A TSUNO, K MUELLER, E AF KOLOBOW, T POWERS, T MANDAVA, S APRIGLIANO, M KAWAGUCHI, A TSUNO, K MUELLER, E TI INTRATRACHEAL PULMONARY VENTILATION (ITPV) - CONTROL OF POSITIVE END-EXPIRATORY PRESSURE AT THE LEVEL OF THE CARINA THROUGH THE USE OF A NOVEL ITPV CATHETER DESIGN SO ANESTHESIA AND ANALGESIA LA English DT Article ID JET VENTILATION; CONSTANT-FLOW; FREQUENCY; LUNGS; DOGS AB A new mode of pulmonary ventilation called intratracheal pulmonary ventilation (ITPV) was studied. Briefly, a continuous flow of air/oxygen is introduced through a small catheter, the tip of which is positioned at the carina, with a diffuser mounted at its distal end. A timed expiration valve, when closed, provides for inspiration; when open, it provides for expiration. The system as first described had a potential for significant back pressure at the level of the carina, which was more at rapid gas flows and with smaller endotracheal tubes. We have now mounted a venturi on the tip of the catheter (reverse thrust catheter [RTC]) that avoids back pressure, and which facilitates expiration. At respiratory rates from 10 to 120/min, the ITPV system with the RTC maintained end-expiratory pressure at the level of the carina at, or near 0 cm H2O. Compared to conventional mechanical ventilation, at identical respiratory rates, this system reduced tidal volume by one half at the lowest respiratory rates, and by as much as two thirds at the highest respiratory rates, with a proportional decrease in peak inspiratory pressure. ITPV has the smallest minute volume ventilation of any conventional or nonconventional mode of pulmonary ventilation. RP KOLOBOW, T (reprint author), NHLBI,CELL BIOL LAB,PULM & CARDIAC ASSIST DEVICES SECT,BLDG 10,ROOM 5D17,BETHESDA,MD 20892, USA. NR 23 TC 39 Z9 39 U1 0 U2 1 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0003-2999 J9 ANESTH ANALG JI Anesth. Analg. PD MAR PY 1994 VL 78 IS 3 BP 455 EP 461 PG 7 WC Anesthesiology SC Anesthesiology GA NA403 UT WOS:A1994NA40300006 PM 8109760 ER PT J AU WILLOUGHBY, A AF WILLOUGHBY, A TI EPIDEMIOLOGY OF HUMAN-IMMUNODEFICIENCY-VIRUS INFECTION IN CHILDREN SO ANNALS OF ALLERGY LA English DT Review ID HIV-1 INFECTION; CHILDBEARING WOMEN; TRANSMISSION; PREVALENCE; SURVIVAL; SAMPLES; BLOOD; RISK RP WILLOUGHBY, A (reprint author), NICHHD,CTR RES MOTHERS & CHILDREN,PEDIAT ADOLESCENT & MATERNAL AIDS BRANCH,6100 EXECUT BLVD,ROCKVILLE,MD 20852, USA. NR 37 TC 4 Z9 5 U1 0 U2 0 PU AMER COLL ALLERGY ASTHMA IMMUNOLOGY PI ARLINGTON HTS PA 85 WEST ALGONQUIN RD SUITE 550, ARLINGTON HTS, IL 60005 SN 0003-4738 J9 ANN ALLERGY JI Ann. Allergy PD MAR PY 1994 VL 72 IS 3 BP 185 EP 195 PG 11 WC Allergy SC Allergy GA NB245 UT WOS:A1994NB24500002 PM 8129210 ER PT J AU VANPELT, F LUDLOW, CL SMITH, PJ AF VANPELT, F LUDLOW, CL SMITH, PJ TI COMPARISON OF MUSCLE ACTIVATION PATTERNS IN ADDUCTOR AND ABDUCTOR SPASMODIC DYSPHONIA SO ANNALS OF OTOLOGY RHINOLOGY AND LARYNGOLOGY LA English DT Article DE LARYNGEAL MUSCLES; SPASMODIC DYSPHONIA; SPEECH ID BOTULINUM TOXIN INJECTIONS; FOCAL LARYNGEAL DYSTONIA; SPASTIC DYSPHONIA AB Patients with adductor and abductor spasmodic dysphonia were compared with normal controls on speech items particularly difficult for the two patient groups. Intrinsic and extrinsic laryngeal muscles were measured during adduction for voicing and for a glottal stop, and during abduction after a vowel and after a glottal stop. Muscle activity was measured while the patients attempted the speech items, with considerable difficulty, but not during periods of complete voice loss. Muscle activity at rest, activity increases for speech, and percent changes for adduction and abduction did not differ from normal in either patient group. The results demonstrated normal muscle activation levels and changes for speech in the patients, and suggested that symptoms occur when spasmodic bursts intrude on an otherwise normal pattern. C1 NIDOCD,VOICE & SPEECH SECT,BETHESDA,MD 20892. UNIV MARYLAND,DEPT MATH,STAT PROGRAM,COLL PK,MD. OI Ludlow, Christy/0000-0002-2015-6171 NR 17 TC 17 Z9 17 U1 0 U2 0 PU ANNALS PUBL CO PI ST LOUIS PA 4507 LACLEDE AVE, ST LOUIS, MO 63108 SN 0003-4894 J9 ANN OTO RHINOL LARYN JI Ann. Otol. Rhinol. Laryngol. PD MAR PY 1994 VL 103 IS 3 BP 192 EP 200 PG 9 WC Otorhinolaryngology SC Otorhinolaryngology GA NA446 UT WOS:A1994NA44600005 PM 8122835 ER PT J AU ALLENDE, MC LEE, JW FRANCIS, P GARRETT, K DOLLENBERG, H BERENGUER, J LYMAN, CA PIZZO, PA WALSH, TJ AF ALLENDE, MC LEE, JW FRANCIS, P GARRETT, K DOLLENBERG, H BERENGUER, J LYMAN, CA PIZZO, PA WALSH, TJ TI DOSE-DEPENDENT ANTIFUNGAL ACTIVITY AND NEPHROTOXICITY OF AMPHOTERICIN-B COLLOIDAL DISPERSION IN EXPERIMENTAL PULMONARY ASPERGILLOSIS SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY LA English DT Article ID FUNGAL-INFECTIONS; INVASIVE ASPERGILLOSIS; DELIVERY; PHARMACOKINETICS; GRANULOCYTOPENIA; DIAGNOSIS AB We investigated the safety and efficacy of amphotericin B colloidal dispersion (ABCD) for the treatment of invasive pulmonary aspergillosis in persistently granulocytopenic rabbits. Treatment groups included ABCD in dosages of 1, 5, and 10 mg/kg/day intravenously or conventional desoxycholate amphotericin B (DAmB) at 1 mg/kg/day intravenously. Antifungal activity was directly related to increasing dosage of ABCD as determined by the concentration of Aspergillus fumigatus organisms in lungs and the frequency of hemorrhagic pulmonary lesions. At 5 and 10 mg/kg/day, there was a significant reduction in the tissue burden of A. fumigatus as measured by percent culture-positive lobes and CFU per gram of tissue (P less than or equal to 0.001), whereas at 1 mg/kg/day the tissue burden of A. fumigatus was not significantly different from that in untreated controls. Microbiological clearance was significantly greater at 1 mg of DAmB per kg per day than at 1 mg of ABCD per kg per day (P less than or equal to 0.001). There was no difference in microbiological clearance of bronchoalveolar lavage fluid among the treatment groups as measured by CFU per milliliter. As determined by survival, ABCD at 5.0 mg/kg/day was more effective than DAmB at 1.0 mg/kg/day and ABCD at 10 mg/kg/day. ABCD at 10 mg/kg/day was more nephrotoxic than the lower dosages of ABCD and resulted in higher mortality. Impairment of glomerular filtration developed as a direct function increasing the ABCD dosage (r = 0.77; P < 0.001). In summary, this study found dose-dependent antifungal activity and nephrotoxicity of ABCD against invasive pulmonary aspergillosis in persistently granulocytopenic rabbits and showed that the optimal dosage of ABCD for antifungal activity and safety was 5 mg/kg/day. C1 NCI,PEDIAT BRANCH,INFECT DIS SECT,BETHESDA,MD 20892. OI Berenguer, Juan/0000-0001-8541-8200 NR 24 TC 56 Z9 57 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 1994 VL 38 IS 3 BP 518 EP 522 PG 5 WC Microbiology; Pharmacology & Pharmacy SC Microbiology; Pharmacology & Pharmacy GA MZ312 UT WOS:A1994MZ31200020 PM 8203848 ER PT J AU LORANGER, AW SARTORIUS, N ANDREOLI, A BERGER, P BUCHHEIM, P CHANNABASAVANNA, SM COID, B DAHL, A DIEKSTRA, RFW FERGUSON, B JACOBSBERG, LB MOMBOUR, W PULL, C ONO, Y REGIER, DA AF LORANGER, AW SARTORIUS, N ANDREOLI, A BERGER, P BUCHHEIM, P CHANNABASAVANNA, SM COID, B DAHL, A DIEKSTRA, RFW FERGUSON, B JACOBSBERG, LB MOMBOUR, W PULL, C ONO, Y REGIER, DA TI THE INTERNATIONAL PERSONALITY-DISORDER EXAMINATION - THE WORLD-HEALTH-ORGANIZATION ALCOHOL, DRUG-ABUSE, AND MENTAL-HEALTH ADMINISTRATION INTERNATIONAL PILOT-STUDY OF PERSONALITY-DISORDERS SO ARCHIVES OF GENERAL PSYCHIATRY LA English DT Article ID TEST-RETEST RELIABILITY; DIAGNOSTIC INTERVIEW; MAJOR DEPRESSION; STABILITY; CLASSIFICATION; SYSTEMS AB Background: One of the aims of the World Health Organization/Alcohol, Drug Abuse, and Mental Health Administration joint program on psychiatric diagnosis and classification is the development and standardization of diagnostic assessment instruments for use in clinical research worldwide. The International Personality Disorder Examination (IPDE) is a semistructured clinical interview compatible with the International Classification of Diseases, Tenth Revision, and the DMS-III-R classification systems. This is the first report of the results of a field trial to investigate the feasibility of using the IPDE to assess personality disorders worldwide. Methods: The IPDE was administered by 58 psychiatrists and clinical psychologists to 716 patients enrolled in clinical facilities at 14 participating centers in 11 countries in North America, Europe, Africa, and Asia. To determine interrater reliability, 141 of the IPDEs (20%) were independently rated by a silent observer. To determine temporal stability, 243 patients (34%) were reexamined after an average interval of 6 months. Results: The IPDE proved acceptable to clinicians and demonstrated an interrater reliability and temporal stability roughly similar to instruments used to diagnose the psychoses, mood, anxiety, and substance use disorders. Conclusion: It is possible to assess personality disorders with reasonably good reliability in different nations, languages, and cultures using a semistructured clinical interview that experienced clinicians find relevant, meaningful, and user-friendly. C1 STONEBRIDGE RES CTR,NOTTINGHAM,ENGLAND. LEIDEN UNIV,2300 RA LEIDEN,NETHERLANDS. MAX PLANCK INST PHYS & ASTROPHYS,W-8000 MUNICH 40,GERMANY. KEIO UNIV,SCH MED,TOKYO 108,JAPAN. NATL INST MENTAL HLTH & NEUROSCI,BANGALORE 560029,KARNATAKA,INDIA. INST PSYCHIAT,LONDON SE5 8AF,ENGLAND. UNIV OSLO,INST PSYCHIAT,OSLO 3,NORWAY. CTR HOSP LUXEMBOURG,LUXEMBOURG,LUXEMBOURG. NIMH,BETHESDA,MD 20892. CORNELL UNIV,DEPT PSYCHIAT,ITHACA,NY 14853. WHO,CH-1211 GENEVA 27,SWITZERLAND. UNIV GENEVA,INST PSYCHIAT,CH-1211 GENEVA 4,SWITZERLAND. UNIV VIENNA,NERVEN KLIN,A-1010 VIENNA,AUSTRIA. NR 33 TC 533 Z9 534 U1 4 U2 29 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0003-990X J9 ARCH GEN PSYCHIAT JI Arch. Gen. Psychiatry PD MAR PY 1994 VL 51 IS 3 BP 215 EP 224 PG 10 WC Psychiatry SC Psychiatry GA NC030 UT WOS:A1994NC03000005 PM 8122958 ER PT J AU SURGUCHOV, AP BOERWINKLE, E SHARETT, AR PATSCH, WP AF SURGUCHOV, AP BOERWINKLE, E SHARETT, AR PATSCH, WP TI APOLIPOPROTEIN-E GENOTYPE AND LIPID TRANSPORT - INSIGHT INTO THE ROLE OF THE EPSILON-4 ALLELE SO ATHEROSCLEROSIS LA English DT Letter DE APOLIPOPROTEIN E POLYMORPHISM; CHOLESTEROL; TRIGLYCERIDES; ATHEROSCLEROSIS ID E POLYMORPHISM; CHOLESTEROL; HOMOZYGOSITY; PHENOTYPES; POPULATION; DISEASE; SAMPLE C1 UNIV TEXAS,CTR GENET,HOUSTON,TX 77030. NHLBI,EPIDEMIOL & BIOMETRY PROGRAM,BETHESDA,MD 20892. RP SURGUCHOV, AP (reprint author), BAYLOR COLL MED,DEPT MED,HOUSTON,TX 77030, USA. NR 17 TC 3 Z9 3 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 1994 VL 106 IS 1 BP 119 EP 121 DI 10.1016/0021-9150(94)90088-4 PG 3 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA NE048 UT WOS:A1994NE04800012 PM 8018103 ER PT J AU MATHIS, C PAUL, SM CRAWLEY, JN AF MATHIS, C PAUL, SM CRAWLEY, JN TI CHARACTERIZATION OF BENZODIAZEPINE-SENSITIVE BEHAVIORS IN THE A/J AND C57BL/6J INBRED STRAINS OF MICE SO BEHAVIOR GENETICS LA English DT Article DE ANXIETY; EXPLORATORY ACTIVITY; SEIZURES; MEMORY; GAMMA-AMINOBUTYRIC ACID(A)(GABA)(A)) BENZODIAZEPINE RECEPTOR ID BETA-CARBOLINE; MOUSE STRAINS; GENETIC-ANALYSIS; RESPONSES; PERFORMANCE; DIAZEPAM; ANXIETY; MODEL; PATTERNS; BRAIN AB Exploratory behaviors as well as pharmacological actions of gamma-aminobutyric acid(A) (GABA(A))/benzodiazepine receptor agonists and inverse agonists were characterized in C57BL/6J and A/J strains of mice. C57BL/6J mice displayed higher levels of exploratory behavior than A/J mice in the light half arrow left over half arrow right dark exploration model of anxiety and in an open-field test, suggesting that C57BL/6J mice are less ''emotional'' and more active than A/J mice, respectively. However, C57BL/6J mice were more sensitive than A/J mice to the anxiolytic effects of diazepam in the light half arrow left over half arrow right dark exploration model. In contrast, A/J mice were more sensitive than C57BL/6J mice to the convulsant effects of methyl-beta-carboline-3-carboxylate. C57BL/6J mice showed no evidence of acquisition of a passive avoidance task, while A/J readily acquired this memory task at low levels of footshock. C57BL/6J and A/J mice should be useful parental strains in recombinant inbred lines for investigating the genetic determinants of benzodiazepine-sensitive behaviors and sensitivity to drugs acting on the GABA(A)/benzodiazepine receptor complex. C1 NIMH,EXPTL THERAPEUT BRANCH,BEHAV NEUROPHARMACOL SECT,BETHESDA,MD 20892. NIMH,CLIN NEUROSCI BRANCH,MOLEC PHARMACOL SECT,BETHESDA,MD 20892. RI MATHIS, CHANTAL/B-6399-2013 NR 45 TC 90 Z9 91 U1 0 U2 5 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 1994 VL 24 IS 2 BP 171 EP 176 DI 10.1007/BF01067821 PG 6 WC Behavioral Sciences; Genetics & Heredity; Psychology, Multidisciplinary SC Behavioral Sciences; Genetics & Heredity; Psychology GA ND465 UT WOS:A1994ND46500007 PM 8024534 ER PT J AU NADIV, O SHINITZKY, M MANU, H HECHT, D ROBERTS, CT LEROITH, D ZICK, Y AF NADIV, O SHINITZKY, M MANU, H HECHT, D ROBERTS, CT LEROITH, D ZICK, Y TI ELEVATED PROTEIN-TYROSINE-PHOSPHATASE ACTIVITY AND INCREASED MEMBRANE VISCOSITY ARE ASSOCIATED WITH IMPAIRED ACTIVATION OF THE INSULIN-RECEPTOR KINASE IN OLD RATS SO BIOCHEMICAL JOURNAL LA English DT Article ID GROWTH-FACTOR RECEPTORS; AGE-RELATED-CHANGES; PHOSPHOTYROSINE PHOSPHATASE; STIMULATED PHOSPHORYLATION; PLASMA-MEMBRANES; DIABETIC RATS; INTACT-CELLS; RESISTANCE; FLUIDITY; DEPHOSPHORYLATION AB Insulin resistance is very common in the elderly, and may be associated with glucose intolerance or frank diabetes. In previous studies we demonstrated that insulin resistance in old Wistar rats is associated with decreased autophosphorylation and activation of the hepatic insulin receptor kinase (IRK) in vivo. We now show that this defect can be reproduced in vitro, where the extent of insulin-induced activation of IRK in liver membranes of old rats was decreased by similar to 50% compared with young controls. The defect could be largely abolished after solubilization of the membranes with Triton X-100. We also show that: (a) the viscosity of membranes from the old rats was significantly (P < 0.001, n = 4) higher (by 15%) compared with young controls; (b) incubation of plasma membranes from old animals with lecithin liposomes, which lowered their cholesterol levels, partially abolished the defect in IRK activation; and (c) Triton extracts of liver membranes prepared from old rats did not interfere with the activation of IRK derived from young controls. Additionally, non-membrane components did contribute to the development of this defect. We observed a significant (similar to 30%) (P < 0.001, n = 18) elevation of cytosolic protein tyrosine phosphatase (PTP) activity directed against the P subunit of the insulin receptor in livers of old rats. No such elevation of PTP activity could be demonstrated with synthetic substrates. Our findings are consistent with a model in which increased membrane viscosity as well as enhancement of a cytosolic PTP activity both markedly inhibit the activation in vivo of the hepatic IRK in old animals. C1 WEIZMANN INST SCI,DEPT CHEM IMMUNOL,IL-76100 REHOVOT,ISRAEL. WEIZMANN INST SCI,DEPT MEMBRANE RES & BIOPHYS,IL-76100 REHOVOT,ISRAEL. NIH,DIABET BRANCH,BETHESDA,MD. OI Roberts, Charles/0000-0003-1756-5772 NR 57 TC 58 Z9 58 U1 1 U2 5 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 1994 VL 298 BP 443 EP 450 PN 2 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA NA073 UT WOS:A1994NA07300029 PM 8135754 ER PT J AU GAO, BC GREENE, L EISENBERG, E AF GAO, BC GREENE, L EISENBERG, E TI CHARACTERIZATION OF NUCLEOTIDE-FREE UNCOATING ATPASE AND ITS BINDING TO ATP, ADP, AND ATP ANALOGS SO BIOCHEMISTRY LA English DT Article ID SHOCK COGNATE PROTEIN; COATED VESICLES; PEPTIDE BINDING; UNFOLDED PROTEINS; CLATHRIN COATS; HSP70; ACTIN; TRANSLOCATION; DISSOCIATION AB The interactions of the 70-kDa heat-shock proteins (hsp70s) with their protein substrates appear to be regulated by bound nucleotide. Previous work has shown that the nucleotide binding site of the bovine brain uncoating ATPase, a constitutive member of the hsp70 family, crystallographically resembles the nucleotide binding site of actin and, like actin, the uncoating ATPase has a strongly bound ADP which cannot be removed by dialysis or treatment with ethylenediaminetetraacetic acid (EDTA). This suggests that, like the bound nucleotide of actin, it may be required for the enzyme to retain its native structure. In this study, the strongly bound ADP was removed by first replacing it with 5'-adenylyl imidodiphosphate (AMP-PNP) and then removing the bound AMP-PNP by dialysis. Following this treatment, more than 95% of the uncoating ATPase becomes nucleotide-free. The nucleotide-free uncoating ATPase retains its ability to bind and hydrolyze ATP and to uncoat clathrin-coated vesicles, even after 10 days of storage at 4 degrees C. Therefore, in contrast to actin, the bound nucleotide of the uncoating ATPase is not required to prevent denaturation of the enzyme. Using nucleotide-free uncoating ATPase, we were able to accurately measure the dissociation constants of ATP, ADP, and the nucleotide analogues AMP-PNP and 2'-deoxyadenosine 5'-triphosphate (dATP). The dissociation constants of both ATP and ADP are about 10(-8) M, more than 1-2 orders of magnitude stronger than previously reported, while AMP-PNP and dATP bind 2-3 orders of magnitude more weakly than ATP. RP GAO, BC (reprint author), NHLBI,CELL BIOL LAB,BLDG 3,ROOM B1-23,BETHESDA,MD 20892, USA. NR 30 TC 55 Z9 55 U1 2 U2 4 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD MAR 1 PY 1994 VL 33 IS 8 BP 2048 EP 2054 DI 10.1021/bi00174a010 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA MZ093 UT WOS:A1994MZ09300010 PM 8117662 ER PT J AU RIVAS, G INGHAM, KC MINTON, AP AF RIVAS, G INGHAM, KC MINTON, AP TI CA2+-LINKED ASSOCIATION OF HUMAN-COMPLEMENT C1(S)OVER-BAR AND C1(R)OVER-BAR SO BIOCHEMISTRY LA English DT Article ID 1ST COMPONENT; BINDING-PROPERTIES; CATALYTIC DOMAINS; FUNCTIONAL-MODEL; PROENZYME FORM; C1S; CLR; ACTIVATION; SUBCOMPONENTS; CENTRIFUGE AB The weight-average molecular weight of Cl (r) over bar, an activated serine protease subcomponent of complement Cl, was measured in the presence of widely varying concentrations of Ca2+ and the other serine protease subcomponent, Cl (s) over bar, by utilizing the technique of tracer sedimentation equilibrium. A quantitative model for heteroassociation between the two subcomponents, which takes into account the previously observed Ca2+-dependent self-association of Cl (s) over bar s, was fit to the combined data at each Ca2+ concentration. The results indicate that Cl (r) over bar, which exists as a dimer under all of the conditions explored in this work, can bind up to two molecules of Cl (s) over bar at both low and high Ca2+ concentrations, but the association constant for binding a single molecule of Cl (s) over bar to dimeric Cl (r) over bar is estimated to increase on the order of a 1000-fold as [Ca2+] increases from 1 nM to 1.0 mM. Heteroassociation of Cl (r) over bar and Cl (s) over bar is favored over self-association of Cl (s) over bar at all conditions. The results clearly indicate the necessity of taking into account a multiplicity of states of association when attempting to understand the equilibrium average properties of a mixture of the two subcomponents and their binding Clq in solution. C1 NIDDKD,BIOCHEM PHARMACOL LAB,BETHESDA,MD 20892. AMER RED CROSS,HOLLAND LAB,DEPT BIOCHEM,ROCKVILLE,MD 20855. OI Rivas, German/0000-0003-3450-7478 FU NHLBI NIH HHS [HL21791] NR 34 TC 24 Z9 24 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 1 PY 1994 VL 33 IS 8 BP 2341 EP 2348 DI 10.1021/bi00174a048 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA MZ093 UT WOS:A1994MZ09300048 PM 8117692 ER PT J AU HOU, EW KAWAI, Y MIYASAKA, H LI, SSL AF HOU, EW KAWAI, Y MIYASAKA, H LI, SSL TI MOLECULAR-CLONING AND EXPRESSION OF CDNAS ENCODING 2 ISOFORMS OF PROTEIN PHOSPHATASE 2C-BETA FROM MOUSE TESTIS SO BIOCHEMISTRY AND MOLECULAR BIOLOGY INTERNATIONAL LA English DT Article C1 NIEHS,GENET LAB,RES TRIANGLE PK,NC 27709. NR 14 TC 17 Z9 18 U1 0 U2 0 PU ACADEMIC PRESS AUST PI MARRICKVILLE PA LOCKED BAG 16, MARRICKVILLE NSW 2204, AUSTRALIA SN 1039-9712 J9 BIOCHEM MOL BIOL INT JI Biochem. Mol. Biol. Int. PD MAR PY 1994 VL 32 IS 4 BP 773 EP 780 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA NF509 UT WOS:A1994NF50900021 PM 8038726 ER PT J AU SHI, YB LIANG, VCT AF SHI, YB LIANG, VCT TI CLONING AND CHARACTERIZATION OF THE RIBOSOMAL-PROTEIN L8 GENE FROM XENOPUS-LAEVIS SO BIOCHIMICA ET BIOPHYSICA ACTA-GENE STRUCTURE AND EXPRESSION LA English DT Note DE RIBOSOMAL PROTEIN; CDNA; METAMORPHOSIS; (XENOPUS LAEVIS) ID EXPRESSION; SEQUENCE AB A full-length cDNA clone encoding the Xenopus laevis ribosomal protein L8 has been isolated and sequenced. The cDNA has an open reading frame of 257 amino acids. The deduced amino acid sequence is rich in basic residues and extremely homologous to the rat L8 protein. The Xenopus gene is ubiquitously expressed at fairly constant levels during development, consistent with its role as a house-keeping gene. RP SHI, YB (reprint author), NICHHD,MOLEC EMBRYOL LAB,BLDG 6,RM B1A02,BETHESDA,MD 20892, USA. NR 13 TC 101 Z9 103 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0167-4781 J9 BBA-GENE STRUCT EXPR JI Biochim. Biophys. Acta-Gene Struct. Expression PD MAR 1 PY 1994 VL 1217 IS 2 BP 227 EP 228 DI 10.1016/0167-4781(94)90042-6 PG 2 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA MZ657 UT WOS:A1994MZ65700018 PM 8110841 ER PT J AU DUNCAN, WC SCHULL, J AF DUNCAN, WC SCHULL, J TI THE INTERACTION OF THYROID STATE, MAOI DRUG-TREATMENT, AND LIGHT ON THE LEVEL AND CIRCADIAN PATTERN OF WHEEL-RUNNING IN RATS SO BIOLOGICAL PSYCHIATRY LA English DT Article DE HYPOTHYROIDISM; CIRCADIAN RHYTHM; LIGHT; MAOI; DEPRESSION; MOTOR ACTIVITY ID DOPAMINE RECEPTOR SENSITIVITY; SEASONAL AFFECTIVE-DISORDER; MONOAMINE-OXIDASE; CLORGYLINE TREATMENT; SLEEP-DEPRIVATION; HYPOTHYROID RATS; SYRIAN-HAMSTERS; SEROTONIN; BRAIN; RESPONSES AB In order to examine the relationship between thyroid status, the circadian system, and antidepressant drug response, the antidepressant drug clorgyline, a monoamine oxidase inhibitor (MAOI), was administered chronically to sham-operated or thyroparathyroidectomized rats. Wheel-running was monitored continuously in a light-dark (LD) cycle, and then in constant dim light. In LD, MAOI treatment increased levels of running. This effect was delayed in hypothyroid rats relative to euthyroid rats. In constant light, the MAOI-induced increase in running was diminished in euthyroid but not hypothyroid animals. Hypothyroid animals were less responsive to the change in lighting than were euthyroid animals, and this was more apparent in hypothyroid rats given MAOI. The daily pattern of running differed with lighting condition as well as with treatment group. MAOI-treatment of hypothyroid animals phase-advanced the pattern of wheel-running. MAOI-treatment of control animals increased the amplitude of wheel-running particularly in the LD cycle. These results indicate that thyroid status, lighting, and MAOI treatment interact to alter the behavioral response to chronic drug treatment. C1 HAVERFORD COLL,DEPT PSYCHOL,HAVERFORD,PA 19041. RP DUNCAN, WC (reprint author), NIMH,CLIN PSYCHOBIOL BRANCH,RM 4S239,BLDG 10,BETHESDA,MD 20892, USA. NR 72 TC 2 Z9 2 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAR 1 PY 1994 VL 35 IS 5 BP 324 EP 334 DI 10.1016/0006-3223(94)90036-1 PG 11 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA ND189 UT WOS:A1994ND18900007 PM 8011801 ER PT J AU ROY, BF BENKELFAT, C HILL, JL PIERCE, PF DAUPHIN, MM KELLY, TM SUNDERLAND, T WEINBERGER, DR BRESLIN, N AF ROY, BF BENKELFAT, C HILL, JL PIERCE, PF DAUPHIN, MM KELLY, TM SUNDERLAND, T WEINBERGER, DR BRESLIN, N TI SERUM ANTIBODY FOR SOMATOSTATIN-14 AND PRODYNORPHIN-209-240 IN PATIENTS WITH OBSESSIVE-COMPULSIVE DISORDER, SCHIZOPHRENIA, ALZHEIMERS-DISEASE, MULTIPLE-SCLEROSIS, AND ADVANCED HIV-INFECTION SO BIOLOGICAL PSYCHIATRY LA English DT Article DE SOMATOSTATIN; DYNORPHIN; AUTOIMMUNITY; OBSESSIVE-COMPULSIVE DISORDER ID SYSTEMIC LUPUS-ERYTHEMATOSUS; GROWTH-HORMONE SECRETION; AIDS DEMENTIA COMPLEX; MYELIN BASIC-PROTEIN; CEREBROSPINAL-FLUID; BETA-ENDORPHIN; NEUROPSYCHIATRIC MANIFESTATIONS; TOURETTES SYNDROME; ENDOTHELIAL-CELLS; SEQUENCE-ANALYSIS AB Patients with obsessive-compulsive disorder (OCD) demonstrated significant levels of antibody for somatostatin-28, its C-terminal fragment somatostatin-14, and prodynorphin. In contrast there were lower levels of reactivity for somatostatin-28(1-14) (the N-terminal fragment of somatostatin-28) and negligible reactivity for several other peptides including beta-endorphin and corticotropin. Healthy volunteers and disease controls [schizophrenia, Alzheimer's disease, multiple sclerosis, and subjects with advanced human immunodeficiency virus (HIV) infection] exhibited negligible reactivity. These data raise the consideration of an autoimmune mechanism for some OCD. C1 ALBANY MED COLL,ALBANY,NY 12208. MCGILL UNIV,DEPT PSYCHIAT,MONTREAL H3A 2T5,QUEBEC,CANADA. NIMH,CLIN SCI LAB,BETHESDA,MD 20892. HOWARD UNIV,COLL MED,DEPT PSYCHIAT & PSYCHOL,WASHINGTON,DC 20001. GEORGETOWN UNIV,SCH MED,DEPT MED,WASHINGTON,DC 20057. NIMH,CLIN BRAIN DISORDERS BRANCH,BETHESDA,MD 20892. RP ROY, BF (reprint author), VET AFFAIRS MED CTR,PSYCHIAT SERV 116A,113 HOLLAND AVE,ALBANY,NY 12208, USA. FU NIMH NIH HHS [NIMH MH43781-02] NR 71 TC 29 Z9 29 U1 1 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAR 1 PY 1994 VL 35 IS 5 BP 335 EP 344 DI 10.1016/0006-3223(94)90037-X PG 10 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA ND189 UT WOS:A1994ND18900008 PM 7912113 ER PT J AU RIGATTO, H FITZGERALD, SF WILLIS, MA YU, C AF RIGATTO, H FITZGERALD, SF WILLIS, MA YU, C TI IN SEARCH OF THE REAL RESPIRATORY NEURONS - CULTURE OF MEDULLARY FETAL CELLS SENSITIVE TO CO2 AND LOW PH SO BIOLOGY OF THE NEONATE LA English DT Article; Proceedings Paper CT Research Colloquium on Control of Breathing during Development: Apnea of the Newborn and in Sudden Infant Death Syndrome CY SEP 07-09, 1992 CL NANCY PONT MOUSSON, FRANCE SP INSERM, NIH NICHHHD DE RESPIRATORY NEURONS; RESPIRATORY RHYTHM; CENTRAL RESPIRATORY CONTROL ID MOUSE SPINAL-CORD; VENTRAL MEDULLA; RAT; MAMMALS; INVITRO; CALCIUM; RHYTHM; DORSAL AB Although extensively pursued, the real respiratory neurons have remained elusive. We departed from the more conventional physiologic and morphologic methods of system and tissue examination and cultured dissociated fetal rat cells from the areas of the nucleus ambiguus and the nucleus tractus solitarius located within the 2 mm rostral to the obex. Pacemaker-like cells, with a regular single or bursting activity, studied at 3-5 weeks of age, responded to very small pulses of CO2 (50 ms) and low pH with an increase in spike frequency and a decrease in amplitude. Other irregularly beating or silent cells did not respond or else required very large pulses (>200 ms) to do so. The pacemaker cells also responded to hypoxia induced by administration of sodium hydrosulfite with an increase in spike frequency and amplitude; high oxygen (>600 Torr) and adenosine produced a decrease in electrical activity. Most of these cells were multipolar after staining with antibodies to neuron-specific enolase and fragment C of tetanus toxin. They did not stain for choline acetyltransferase. The results suggest that these cultured cells, expressing a phenotype inherently responsive to CO2 and low pH, have the characteristics of central respiratory chemoreceptors, and may be involved in the generation of the respiratory rhythm. C1 UNIV MANITOBA,DEPT PEDIAT PHYSIOL & REPROD MED,WINNIPEG,MB,CANADA. NICHHD,DEV NEUROBIOL LAB,BETHESDA,MD. NR 29 TC 16 Z9 16 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0006-3126 J9 BIOL NEONATE JI Biol. Neonate PD MAR-APR PY 1994 VL 65 IS 3-4 BP 149 EP 155 PG 7 WC Pediatrics SC Pediatrics GA NH182 UT WOS:A1994NH18200005 PM 8038275 ER PT J AU ALBERT, PS AF ALBERT, PS TI A MARKOV MODEL FOR SEQUENCES OF ORDINAL DATA FROM A RELAPSING-REMITTING DISEASE SO BIOMETRICS LA English DT Article DE FINITE MARKOV CHAINS; RELAPSING-REMITTING DISEASES; REPEATED MEASURES; STOCHASTIC PROCESSES ID EXPERIMENTAL ALLERGIC ENCEPHALOMYELITIS AB Many chronic diseases follow a course with multiple relapses into periods with severe symptoms alternating with periods of remission; experimental allergic encephalomyelitis, the animal model for multiple sclerosis, is an example of such a disease. A finite Markov chain is proposed as a model for analyzing sequences of ordinal data from a relapsing-remitting disease. The proposed model is one in which the state space is expanded to include information about the relapsing-remitting status as well as the ordinal severity score, and a reparameterization is suggested that reduces the number of parameters needed to be estimated. The Markov model allows for a wide range of relapsing-remitting behavior, provides an understanding of the stochastic nature of the disease process, and allows for efficient estimation of important characteristics of the disease course (such as mean first passage times, occupation times, and steady-state probabilities). These methods are applied to data from a study of the effect of a treatment (transforming growth factor-beta(1)) on experimental allergic encephalomyelitis. RP ALBERT, PS (reprint author), NATL INST NEUROL DISORDERS & STROKE,BIOMETRY & FIELD STUDIES BRANCH,FED BLDG,ROOM 7C06,BETHESDA,MD 20892, USA. NR 13 TC 20 Z9 20 U1 0 U2 1 PU INTERNATIONAL BIOMETRIC SOC PI WASHINGTON PA 808 17TH ST NW SUITE 200, WASHINGTON, DC 20006-3910 SN 0006-341X J9 BIOMETRICS JI Biometrics PD MAR PY 1994 VL 50 IS 1 BP 51 EP 60 DI 10.2307/2533196 PG 10 WC Biology; Mathematical & Computational Biology; Statistics & Probability SC Life Sciences & Biomedicine - Other Topics; Mathematical & Computational Biology; Mathematics GA NH265 UT WOS:A1994NH26500005 PM 8086615 ER PT J AU LINK, CJ BICHER, A KOHN, EC CHRISTIAN, MC DAVIS, PA ADAMO, DO REED, E SAROSY, GA AF LINK, CJ BICHER, A KOHN, EC CHRISTIAN, MC DAVIS, PA ADAMO, DO REED, E SAROSY, GA TI FLEXIBLE GRANULOCYTE-COLONY-STIMULATING FACTOR DOSING IN OVARIAN-CANCER PATIENTS WHO RECEIVE DOSE-INTENSE TAXOL THERAPY SO BLOOD LA English DT Article ID PHASE-I; G-CSF; CHEMOTHERAPY; NEUTROPENIA; CARCINOMA C1 NCI,MED BRANCH,MED OVARIAN CANC SECT,BETHESDA,MD 20892. NR 22 TC 13 Z9 13 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 1994 VL 83 IS 5 BP 1188 EP 1192 PG 5 WC Hematology SC Hematology GA MZ289 UT WOS:A1994MZ28900005 PM 7509652 ER PT J AU SAELMAN, EUM NIEUWENHUIS, HK HESE, KM DEGROOT, PG HEIJNEN, HFG SAGE, EH WILLIAMS, S MCKEOWN, L GRALNICK, HR SIXMA, JJ AF SAELMAN, EUM NIEUWENHUIS, HK HESE, KM DEGROOT, PG HEIJNEN, HFG SAGE, EH WILLIAMS, S MCKEOWN, L GRALNICK, HR SIXMA, JJ TI PLATELET-ADHESION TO COLLAGEN TYPE-I THROUGH TYPE-VIII UNDER CONDITIONS OF STASIS AND FLOW IS MEDIATED BY GPIA/IIA (ALPHA(2)BETA(1)-INTEGRIN) SO BLOOD LA English DT Article ID CHICK CARTILAGE COLLAGEN; GLYCOPROTEIN-IA; EXTRACELLULAR-MATRIX; VONWILLEBRAND-FACTOR; DEPENDENT ADHESION; BLOOD-PLATELETS; VESSEL WALL; AGGREGATION; SUBENDOTHELIUM; IDENTIFICATION C1 UNIV HOSP UTRECHT,DEPT HAEMATOL G03647,3508 GA UTRECHT,NETHERLANDS. NIH,CTR CLIN,HEMATOL SERV,BETHESDA,MD. UNIV WASHINGTON,DEPT BIOL STRUCT,SEATTLE,WA 98195. NR 48 TC 199 Z9 201 U1 0 U2 11 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 1994 VL 83 IS 5 BP 1244 EP 1250 PG 7 WC Hematology SC Hematology GA MZ289 UT WOS:A1994MZ28900012 PM 8118028 ER PT J AU MUSSO, T GUSELLA, GL BROOKS, A LONGO, DL VARESIO, L AF MUSSO, T GUSELLA, GL BROOKS, A LONGO, DL VARESIO, L TI INTERLEUKIN-4 INHIBITS INDOLEAMINE 2,3-DIOXYGENASE EXPRESSION IN HUMAN MONOCYTES SO BLOOD LA English DT Article ID PERIPHERAL-BLOOD MONOCYTES; STIMULATORY FACTOR-I; INTERFERON-GAMMA; IFN-GAMMA; DEGRADE TRYPTOPHAN; HUMAN MACROPHAGES; PICOLINIC-ACID; IL-4; INDUCTION; LIPOPOLYSACCHARIDE C1 NCI,FREDERICK CANC RES & DEV CTR,MOLEC IMMUNOL LAB,FREDERICK,MD 21702. UNIV TURIN,INST MICROBIOL,PRI DYNCORP,BIOL CARCINOGENESIS & DEV PROGRAM,TURIN,ITALY. RP MUSSO, T (reprint author), NCI,FREDERICK CANC RES & DEV CTR,DIV CANC TREATMENT,FREDERICK,MD 21702, USA. RI varesio, luigi/J-8261-2016 OI varesio, luigi/0000-0001-5659-2218 NR 35 TC 88 Z9 93 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 1994 VL 83 IS 5 BP 1408 EP 1411 PG 4 WC Hematology SC Hematology GA MZ289 UT WOS:A1994MZ28900030 PM 8118042 ER PT J AU GITTERMAN, M WEISS, GH AF GITTERMAN, M WEISS, GH TI GENERALIZED THEORY OF THE KINETICS OF TRACERS IN BIOLOGICAL-SYSTEMS SO BULLETIN OF MATHEMATICAL BIOLOGY LA English DT Article ID TRANSPORT AB Most theoretical analyses of tracer kinetics in capillaries contain an implicit assumption that the tissues to which they are connected have homogeneous material properties. The microscopic description of the exchange of tracer molecules and tissues is then modeled in terms of first-order kinetics. We consider a class of more general models allowing us to assess the robustness of simplifying assumptions made above. It is shown that when amorphous properties are important the kinetics of the system may differ considerably from those predicted by standard theories. C1 BAR ILAN UNIV,DEPT PHYS,IL-52100 RAMAT GAN,ISRAEL. RP GITTERMAN, M (reprint author), NIH,DIV COMP RES & TECHNOL,PHYS SCI LAB,BETHESDA,MD 20892, USA. NR 18 TC 6 Z9 6 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0092-8240 J9 B MATH BIOL JI Bull. Math. Biol. PD MAR PY 1994 VL 56 IS 2 BP 171 EP 186 DI 10.1007/BF02460638 PG 16 WC Biology; Mathematical & Computational Biology SC Life Sciences & Biomedicine - Other Topics; Mathematical & Computational Biology GA ND918 UT WOS:A1994ND91800001 PM 8186752 ER PT J AU KAUFMAN, D AF KAUFMAN, D TI CANCER-THERAPY AND THE RANDOMIZED CLINICAL-TRIAL - GOOD MEDICINE SO CA-A CANCER JOURNAL FOR CLINICIANS LA English DT Article AB True improvements in the treatment of cancer-by the introduction of new drugs or novel drug combinations, new therapeutic modalities, or technologic improvements of old modalities-result in higher response rates and prolonged survival when compared with existing therapies. When a new treatment convincingly meets the test of improving survival rates or, at worst, improving patients' quality of life, it becomes the accepted standard of care if its side effects are acceptable and its cost is not prohibitive. Improved therapeutic results can be demonstrated only by clinical trials with an adequate numbers of patients, appropriate control subjects, and a sufficient duration of follow-up. Therapeutic breakthroughs are revolutionary advances in treatment, usually rapidly and dramatically obvious in comparison with historic controls; demonstration of benefit in these cases does not usually require randomized trials. Much more common, however, are new therapies that represent modest, incremental advances over existing treatment and that usually require randomized comparison trials to demonstrate convincingly statistically significant improvement. A randomized clinical trial should test an important hypothesis. It must be carefully designed to ensure that both groups of patients are comparable in terms of various prognostic variables and to minimize subtle sources of bias. An honest belief that both arms of the trial are a priori equal must be maintained. Meeting these criteria, the randomized clinical trial offers to the individual cancer patient treatment that should be at least equal to the best available nonexperimental therapy. This equates with Good Medicine. RP KAUFMAN, D (reprint author), NCI,DIV CANC TREATMENT,BETHESDA,MD 20892, USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU AMER CANCER SOC PI NEW YORK PA C/O JB LIPPINCOTT CO 1180 AVE OF THE AMERICAS 6TH FLOOR, NEW YORK, NY 10036 SN 0007-9235 J9 CA-CANCER J CLIN JI CA-Cancer J. Clin. PD MAR-APR PY 1994 VL 44 IS 2 BP 109 EP 114 DI 10.3322/canjclin.44.2.109 PG 6 WC Oncology SC Oncology GA NA820 UT WOS:A1994NA82000006 PM 8124603 ER PT J AU COCEANI, F KELSEY, L ACKERLEY, C RABINOVITCH, M GELBOIN, H AF COCEANI, F KELSEY, L ACKERLEY, C RABINOVITCH, M GELBOIN, H TI CYTOCHROME-P450 DURING ONTOGENIC DEVELOPMENT - OCCURRENCE IN THE DUCTUS-ARTERIOSUS AND OTHER TISSUES SO CANADIAN JOURNAL OF PHYSIOLOGY AND PHARMACOLOGY LA English DT Article DE DUCTUS ARTERIOSUS CLOSURE; OXYGEN; CYTOCHROME P450 ID SMOOTH-MUSCLE CELLS; DRUG-METABOLIZING-ENZYMES; MONOCLONAL-ANTIBODIES; N-DEMETHYLATION; COLLOIDAL GOLD; FEMALE SHEEP; RAT; LIVER; GLUCOCORTICOIDS; DEXAMETHASONE AB Our previous investigations have implicated a cytochrome P450 mechanism in the oxygen contraction of the ductus arteriosus and, by extension, in the closure of the vessel at birth. This study was undertaken in fetal and newborn sheep to characterize the ductal cytochrome and gather insight into its operation. Other tissues, vascular and extravascular, were used as a reference. Benzo[a]pyrene hydroxylation (a marker for the 3-methylcholanthrene-inducible isozyme) and aminopyrine N-demethylation (a marker for the glucocorticoid-inducible isozyme) had insignificant activity in the ductus and aorta from fetal sheep, and no increase was noted after exposing the animal in utero to beta-naphthoflavone or dexamethasone, both alone and in combination with phenobarbital. However, dexamethasone and, particularly, dexamethasone plus phenobarbital produced a variable constriction of the fetal ductus. No monooxygenase activity was found in the naturally closing ductus of the newborn. Conversely, both enzyme reactions were measurable in the fetal liver, and they became more active after treatment with the inducers or at birth. Scanning immunoelectron microscopy of cultured endothelial and muscle cells from both ductus and aorta showed specific gold labelling for the glucocorticoid-inducible cytochrome P450 only in ductal muscle. By transmission electron microscopy, this immunoreactivity was located along the sarcolemma and in the sarcoplasmic reticulum. These findings indicate the presence in the ductus arteriosus of a cytochrome P450 belonging to the 3A subfamily. However, considering the uneven action of the inducers on enzyme activity in ductal tissue and muscle tone, the role of this cytochrome in closure of the vessel at birth remains to be ascertained. C1 HOSP SICK CHILDREN,DEPT PATHOL,TORONTO M5G 1X8,ON,CANADA. NCI,MOLEC CARCINOGENESIS LAB,BETHESDA,MD 20892. RP COCEANI, F (reprint author), HOSP SICK CHILDREN,RES INST,555 UNIV AVE,TORONTO M5G 1X8,ON,CANADA. NR 51 TC 15 Z9 15 U1 0 U2 0 PU NATL RESEARCH COUNCIL CANADA PI OTTAWA PA RESEARCH JOURNALS, MONTREAL RD, OTTAWA ON K1A 0R6, CANADA SN 0008-4212 J9 CAN J PHYSIOL PHARM JI Can. J. Physiol. Pharmacol. PD MAR PY 1994 VL 72 IS 3 BP 217 EP 226 PG 10 WC Pharmacology & Pharmacy; Physiology SC Pharmacology & Pharmacy; Physiology GA NM239 UT WOS:A1994NM23900005 PM 8069768 ER PT J AU COLE, K KOHN, E AF COLE, K KOHN, E TI CALCIUM-MEDIATED SIGNAL-TRANSDUCTION - BIOLOGY, BIOCHEMISTRY, AND THERAPY SO CANCER AND METASTASIS REVIEWS LA English DT Review DE SIGNAL TRANSDUCTION; CALCIUM; G-PROTEIN; INVASION; METASTASIS ID AUTOCRINE MOTILITY FACTOR; EPIDERMAL GROWTH-FACTOR; HUMAN-MELANOMA CELLS; PROTEIN-KINASE-C; INOSITOL PHOSPHATES; TYROSINE PHOSPHORYLATION; METASTATIC PHENOTYPE; PHOSPHOLIPASE-C; 2ND MESSENGERS; RECEPTOR GENES AB The process of proliferation, invasion and metastasis is a complex one which involves both the autonomy of the malignant cells and their interaction with the cellular and extracellular environments. The way in which the tumor cells respond to cellular and extracellular stimuli is regulated through transduction of those signals and translation into cellular activity. Transmembrane signal transduction involves three major categories of events: ion channel activation, transmission through guanine nucleotide binding protein intermediates with production of second messengers, and phosphorylation events. A frequent common denominator of these different pathways is a cellular calcium homeostasis. Calcium may be both a result of and a regulator of many of these signal transduction pathways and has been shown to have a role in the regulation of proliferation, invasion, and metastatic potential. The understanding and application of the basic tenets of these pathways to tumor cell proliferation, invasion, and metastases opens a new target for therapeutic intervention. We have identified a novel agent, CAI, which through inhibition of stimulated calcium influx inhibits proliferation and migration in vitro, and growth and dissemination in human cancer xenografts in vivo. CAI offers a new a approach to cancer therapy, signal transduction therapy. C1 NCI,PATHOL LAB,SIGNAL TRANSDUCT & PREVENT UNIT,BLDG 10,ROOM 2A33,BETHESDA,MD 20892. RI Cole, Kristina/M-3922-2015 NR 94 TC 72 Z9 75 U1 0 U2 2 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA SPUIBOULEVARD 50, PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS SN 0167-7659 J9 CANCER METAST REV JI Cancer Metastasis Rev. PD MAR PY 1994 VL 13 IS 1 BP 31 EP 44 DI 10.1007/BF00690417 PG 14 WC Oncology SC Oncology GA MN723 UT WOS:A1994MN72300004 PM 8143344 ER PT J AU LUBIN, JH LIANG, ZH HRUBEC, Z PERSHAGEN, G SCHOENBERG, JB BLOT, WJ KLOTZ, JB XU, ZY BOICE, JD AF LUBIN, JH LIANG, ZH HRUBEC, Z PERSHAGEN, G SCHOENBERG, JB BLOT, WJ KLOTZ, JB XU, ZY BOICE, JD TI RADON EXPOSURE IN RESIDENCES AND LUNG-CANCER AMONG WOMEN - COMBINED ANALYSIS OF 3 STUDIES SO CANCER CAUSES & CONTROL LA English DT Article DE CIGARETTE SMOKING; FEMALES; LUNG CANCER; PEOPLES-REPUBLIC-OF-CHINA; RADON; SWEDEN; UNITED-STATES AB Lung cancer risk in relation to indoor radon was examined in three case-control studies in Stockholm (Sweden), New Jersey (United States), and Shenyang (People's Republic of China). Year-long measurements of radon gas were made in current and past homes of 966 women who developed lung cancer and of 1,158 control women, included in the combined analysis. Nearly 14 percent of the participants were estimated to have a time-weighted, mean, radon concentration in their homes of more than 4 pCi/l (150 Bq/m3) during the period from five to 35 years prior to the date of lung cancer diagnosis (or comparable date for controls). There was a tendency for risk to increase with increasing levels of radon in NJ and Stockholm, but the trends for individual studies and overall were not statistically significant. The estimates of the excess relative risk for indoor exposure per pCi/l were 0.18 (95 percent [CI] = - 0.04-0.70) in NJ, 0.06 (CI = - 0.05-0.34) in Stockholm, and - 0.02 (CI = - infinity-0.03) for Shenyang; these estimates did not differ significantly from each other. The overall excess RR per pCi/l was 0.00 (CI = - 0.05-0.07); the confidence limits were sufficiently broad, however, that the overall estimate was still compatible with extrapolations of risks from miners. Cigarette smoking was the predominant cause of lung cancer with the RR significantly elevated in all studies. Within smoking categories, the trend in risk with increasing mean radon concentration was inconsistent. Analyses of data from several studies are complicated by the possibility that there may exist important differences in study bases which might affect results, and which may be controlled only partially through adjustment procedures. Future efforts to combine various residential studies will need to be attentive to the intrinsic limitations of studies to detect low levels of risk as well as the unique uncertainties associated with estimating, accurately, cumulative exposure to indoor radon. RP LUBIN, JH (reprint author), NCI,BIOSTAT BRANCH,EXECUTIVE PL N,ROOM 403,6130 EXECUT BLVD,ROCKVILLE,MD 20852, USA. FU NCI NIH HHS [N01-CP-51021, N01-CP-61031, R01-CA-37744] NR 0 TC 36 Z9 37 U1 0 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 1994 VL 5 IS 2 BP 114 EP 128 DI 10.1007/BF01830257 PG 15 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA NA760 UT WOS:A1994NA76000003 PM 8167258 ER PT J AU HSING, AW MCLAUGHLIN, JK ZHENG, W GAO, YT BLOT, WJ AF HSING, AW MCLAUGHLIN, JK ZHENG, W GAO, YT BLOT, WJ TI OCCUPATION, PHYSICAL-ACTIVITY, AND RISK OF PROSTATE-CANCER IN SHANGHAI, PEOPLES-REPUBLIC-OF-CHINA SO CANCER CAUSES & CONTROL LA English DT Article DE OCCUPATION; PEOPLES-REPUBLIC-OF-CHINA; PHYSICAL ACTIVITY; PROSTATE CANCER AB Based on occupational data for all (n = 264) prostate cancer cases diagnosed during 1980-84 in urban Shanghai and on employment information from the 1982 census, standardized incidence ratios (SIR) were calculated for occupational groups classified by job type and physical activity level. White-collar workers (professionals, government officials, clerical workers, salespersons) had an elevated incidence of prostate cancer, although the excesses were not significant. In addition, when jobs were classified by time spent sitting or energy expenditure, men employed in occupations with low physical activity levels tended to have moderately elevated risks of prostate cancer. Findings from this study in an area with one of the world's lowest incidence rates of prostate cancer add to the accumulating evidence that jobs with a low level of physical activity are associated with an increased prostate-cancer risk. RP HSING, AW (reprint author), NCI,DIV CANC ETIOL,EPIDEMIOL & BIOSTAT PROGRAM,EPN 415,BETHESDA,MD 20892, USA. NR 0 TC 52 Z9 52 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 1994 VL 5 IS 2 BP 136 EP 140 DI 10.1007/BF01830259 PG 5 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA NA760 UT WOS:A1994NA76000005 PM 8167260 ER PT J AU LAND, CE HAYAKAWA, N MACHADO, SG YAMADA, Y PIKE, MC AKIBA, S TOKUNAGA, M AF LAND, CE HAYAKAWA, N MACHADO, SG YAMADA, Y PIKE, MC AKIBA, S TOKUNAGA, M TI A CASE-CONTROL INTERVIEW STUDY OF BREAST-CANCER AMONG JAPANESE A-BOMB SURVIVORS .1. MAIN EFFECTS SO CANCER CAUSES & CONTROL LA English DT Article DE ATOMIC BOMB SURVIVORS; BREAST CANCER; JAPAN; REPRODUCTIVE HISTORY AB Women with breast cancer (cases = 196) and without the disease (controls = 566), selected from the Life Span Study sample of A-bomb survivors and nonexposed residents of Hiroshima and Nagasaki, Japan, and matched on age at the time of the bombings, city, and estimated radiation dose, were interviewed about reproductive and medical history. A primary purpose of the study was to identify strong breast cancer risk factors that could be investigated further for possible interactions with radiation dose. As expected, age at first full-term pregnancy was strongly and positively related to risk. Inverse associations were observed with number of births and total, cumulative period of breast feeding, even after adjustment for age at first full-term pregnancy. Histories of treatment for dysmenorrhea and for uterine or ovarian surgery were associated positively and significantly with risk at ages 55 or older, a finding that requires additional study. Other factors related to risk at older ages were the Quetelet index (weight [kg]/height [cm]2) at age 50, history of thyroid disease, and hypertension. Neither age at menarche nor age at menopause was associated significantly with risk. Subjects appeared to be poorly informed about history of breast cancer or other cancer in themselves or in their close relatives; this finding suggests that innovative strategies may be required when studying familial cancer patterns in Japanese populations. RP LAND, CE (reprint author), NCI,RADIAT EPIDEMIOL BRANCH,6130 ROCKVILLE PIKE,EPN 408,ROCKVILLE,MD 20852, USA. NR 0 TC 27 Z9 28 U1 0 U2 2 PU RAPID SCIENCE PUBLISHERS PI LONDON PA 2-6 BOUNDARY ROW, LONDON, ENGLAND SE1 8NH SN 0957-5243 J9 CANCER CAUSE CONTROL JI Cancer Causes Control PD MAR PY 1994 VL 5 IS 2 BP 157 EP 165 DI 10.1007/BF01830262 PG 9 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA NA760 UT WOS:A1994NA76000008 PM 8167263 ER PT J AU LAND, CE HAYAKAWA, N MACHADO, SG YAMADA, Y PIKE, MC AKIBA, S TOKUNAGA, M AF LAND, CE HAYAKAWA, N MACHADO, SG YAMADA, Y PIKE, MC AKIBA, S TOKUNAGA, M TI A CASE-CONTROL INTERVIEW STUDY OF BREAST-CANCER AMONG JAPANESE A-BOMB SURVIVORS .2. INTERACTIONS WITH RADIATION-DOSE SO CANCER CAUSES & CONTROL LA English DT Article DE A-BOMB SURVIVORS; BREAST CANCER; IONIZING RADIATION; JAPAN; REPRODUCTIVE HISTORY AB Three breast cancer risk factors were evaluated in terms of their interactions with radiation dose in a case-control interview study of Japanese A-bomb survivors. Cases and controls were matched on age at the time of the bombings and radiation dose, and dose-related risk was estimated from cohort rather than case-control data. Each factor-age at first full-term pregnancy, number of deliveries, and cumulative lactation period summed over births-conformed reasonably well to a multiplicative interaction model with radiation dose (the additive interactive model, in which the absolute excess risk associated with a factor is assumed to be independent of radiation dose, was rejected). An important implication of the finding is that early age at first full-term pregnancy, multiple births, and lengthy cumulative lactation are all protective against radiation-related, as well as baseline, breast cancer. Analyses by age at exposure to radiation suggest that, among women exposed to radiation in childhood or adolescence, a first full-term pregnancy at an early age following exposure may be protective against radiation-related risk. RP LAND, CE (reprint author), NCI,RADIAT EPIDEMIOL BRANCH,6130 ROCKVILLE PIKE,EPN 408,ROCKVILLE,MD 20852, USA. NR 0 TC 58 Z9 59 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 1994 VL 5 IS 2 BP 167 EP 176 DI 10.1007/BF01830263 PG 10 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA NA760 UT WOS:A1994NA76000009 PM 8167264 ER PT J AU CHEN, VW CORREA, P KURMAN, RJ WU, XC ELEY, JW AUSTIN, D MUSS, H HUNTER, CP REDMOND, C SOBHAN, M COATES, R REYNOLDS, P HERMAN, AA EDWARDS, BK AF CHEN, VW CORREA, P KURMAN, RJ WU, XC ELEY, JW AUSTIN, D MUSS, H HUNTER, CP REDMOND, C SOBHAN, M COATES, R REYNOLDS, P HERMAN, AA EDWARDS, BK TI HISTOLOGICAL CHARACTERISTICS OF BREAST-CARCINOMA IN BLACKS AND WHITES SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID CANCER-PATIENTS; LUNG-CANCER; RACIAL-DIFFERENCES; SURVIVAL; PROGNOSIS; DIFFERENTIATION; PHENOTYPE; ESTROGEN; RECEPTOR; WOMEN AB Tumor characteristics of 963 newly diagnosed invasive breast cancer cases from the population-based Black/White Cancer Survival Study were evaluated. Representative slides of the tumors were requested from all participating hospitals of three metropolitan areas and reviewed by one expert pathologist, blinded in regard to the age and race of patients. Nine tumor characteristics were evaluated for black and white patients. After adjusting for age, stage, and metropolitan area, blacks were significantly more likely to have high grade nuclear atypia [odds ratio (OR) = 1.97, 95% confidence interval (CI) = 1.27-3.04]; high mitotic activity (OR = 2.05, 95% CI = 1.34-3.14), grade 3 tumors (OR = 1.58, 95% CI = 1.02-2.45), and more necrosis (OR = 1.51, 95% CI = 1.16-1.98); and less likely to have well defined tubular formation (OR = 0.57, 95% CI = 0.42-0.77), marked fibrosis (OR 0.65, 95% CI = 0.45-0.94), and positive estrogen receptor status (OR = 0.78, 95% CI = 0.58-1.05). These black/white differences remained after controlling for socioeconomic status (SES), body mass index, use of alcohol and tobacco, reproductive experience, and health care access and utilization. No significant racial differences were found for blood vessel invasion and lymphatic invasion. Although white women of high SES had more favorable tumors than those of low SES, the same pattern was not observed for blacks. High SES black women had statistically nonsignificant elevated ORs of a high mitotic index and tumor grade. These racial differences in tumor biology may have etiological and clinical implications. C1 NIH,OFF RES WOMENS HLTH,BETHESDA,MD 20892. UNIV PITTSBURGH,DEPT BIOSTAT,PITTSBURGH,PA 15261. CALIF DEPT HLTH SERV,EMERYVILLE,CA 94608. NCI,BETHESDA,MD 20892. NCI,DIV CANC PREVENT & CONTROL,BETHESDA,MD 20892. JOHNS HOPKINS UNIV,DEPT GYNECOL OBSTET & PATHOL,BALTIMORE,MD 21205. EMORY UNIV,SCH PUBL HLTH,DIV EPIDEMIOL,ATLANTA,GA 30322. NCI,BETHESDA,MD 20892. WAKE FOREST UNIV,CTR COMPREHENS CANC,WINSTON SALEM,NC 27157. RP CHEN, VW (reprint author), LOUISIANA STATE UNIV,MED CTR,DEPT PATHOL,1901 PERDIDO ST,NEW ORLEANS,LA 70112, USA. FU NCI NIH HHS [N01-CN-45174, N01-CN-45176, N01-CN-45175] NR 46 TC 141 Z9 143 U1 2 U2 2 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA PUBLIC LEDGER BLDG, SUITE 816, 150 S. INDEPENDENCE MALL W., PHILADELPHIA, PA 19106 SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD MAR PY 1994 VL 3 IS 2 BP 127 EP 135 PG 9 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA NA344 UT WOS:A1994NA34400005 PM 7519506 ER PT J AU SHAW, GL FALK, RT DESLAURIERS, J NESBITT, JC MCKNEALLY, MF FRAME, JN FELD, R ISSAQ, HJ RUCKDESCHEL, JC HOOVER, RN AF SHAW, GL FALK, RT DESLAURIERS, J NESBITT, JC MCKNEALLY, MF FRAME, JN FELD, R ISSAQ, HJ RUCKDESCHEL, JC HOOVER, RN TI LUNG-TUMOR RESECTION DOES NOT AFFECT DEBRISOQUINE METABOLISM SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID CANCER RISK; GENETIC-POLYMORPHISM; OXIDATION; HYDROXYLATION; PHENOTYPE; SUSCEPTIBILITY; HUMANS; FAMILY AB Some authors have reported an association of extensive metabolism of debrisoquine with increased lung cancer risk, although others have found no association. Debrisoquine metabolism is controlled by a cytochrome P-450 isozyme encoded at the CYP2D6 locus, which is inducible by antipyrine and rifampicin. Because lung tumors may produce a variety of humoral substances, we wanted to determine whether the tumor induced debrisoquine metabolism. As part of a case-control study of lung cancer, debrisoquine metabolism was measured in patients with histologically confirmed non-small cell lung cancer before and after surgical resection with curative intent. One hundred four incident patients with pathological stage I, II, or IIIA non-small cell lung cancer took debrisoquine (10 mg) orally at 10 p.m. and collected the subsequent 8-h urine both before and after surgery. We compared the values of the metabolic ratio, which is the percentage of the dose excreted as debrisoquine to the percentage of the dose excreted as the principal metabolite. The pre- and postoperative metabolic ratios were highly correlated (Pearson correlation coefficient = 0.96), and did not differ in value significantly (P = 0.88). Using traditional cutpoints (metabolic ratio, 1.0 and 12.6) to categorize the three metabolic phenotypes, the preoperative and postoperative phenotypes were well correlated (kappa = 0.78). These results show that the ability to metabolize debrisoquine is not induced by the presence of a primary lung tumor. C1 ALBANY MED COLL, ALBANY, NY 12208 USA. LAVAL HOSP, ST FOY, PQ, CANADA. NCI, FREDERICK CANC RES FACIL, PROGRAM RESOURCES INC DYNCORP, FREDERICK, MD 21701 USA. NATL NAVAL MED CTR, BETHESDA, MD 20814 USA. PRINCESS MARGARET HOSP, TORONTO M4X 1K9, ONTARIO, CANADA. UNIV TORONTO, DIV THORAC SURG, TORONTO M5S 1A1, ONTARIO, CANADA. RP SHAW, GL (reprint author), NCI, BETHESDA, MD 20892 USA. FU NCI NIH HHS [NCI NO1-CP0-5684, NCI NO1-CP1-5672] NR 26 TC 5 Z9 5 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 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD MAR PY 1994 VL 3 IS 2 BP 141 EP 144 PG 4 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA NA344 UT WOS:A1994NA34400007 PM 8049635 ER PT J AU WANG, GQ DAWSEY, SM LI, JY TAYLOR, PR LI, B BLOT, WJ WEINSTEIN, WM LIU, FS LEWIN, KJ WANG, H WIGGETT, S GAIL, MH YANG, CS AF WANG, GQ DAWSEY, SM LI, JY TAYLOR, PR LI, B BLOT, WJ WEINSTEIN, WM LIU, FS LEWIN, KJ WANG, H WIGGETT, S GAIL, MH YANG, CS TI EFFECTS OF VITAMIN MINERAL SUPPLEMENTATION ON THE PREVALENCE OF HISTOLOGICAL DYSPLASIA AND EARLY CANCER OF THE ESOPHAGUS AND STOMACH - RESULTS FROM THE GENERAL-POPULATION TRIAL IN LINXIAN, CHINA SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article AB A randomized nutrition intervention trial was conducted among 29,584 adult residents of Linxian, China, to examine the effects of vitamin/mineral supplementation on the occurrence of esophageal/gastric cardia cancer in this high-risk population. A fractional factorial study design allowed evaluations of four different combinations of nutrients: (A) retinol and zinc; (B) riboflavin and niacin; (C) vitamin C and molybdenum; and (D) beta-carotene, vitamin E, and selenium. During the 5.25-year intervention, significant reductions in total mortality, total cancer mortality, and stomach cancer mortality occurred among those receiving beta-carotene, vitamin E, and selenium. At the end of intervention, an endoscopic survey was carried out in a sample of subjects to see if the nutritional supplements had affected the prevalence of clinically silent precancerous lesions and early invasive cancers of the esophagus or stomach. Endoscopy was performed on 391 individuals from two study villages. The prevalences of esophageal and gastric dysplasia and cancer were compared by nutrient factor. Cancer or dysplasia was diagnosed in 15% of the participants. No statistically significant reductions in the prevalence of esophageal or gastric dysplasia or cancer were seen for any of the four vitamin/mineral combinations. The greatest reduction in risk (odds ratio, 0.38; P = 0.09) was seen for the effect of retinol and zinc on the prevalence of gastric cancer. Although no significant protective effects were seen in this endoscopic survey, there was a suggestion that supplementation with retinol and zinc may protect against the development of gastric neoplasia in this high-risk population. Additional studies with larger numbers of endpoints will be needed to further evaluate this possibility. C1 NCI,BETHESDA,MD 20892. UNIV CALIF LOS ANGELES,LOS ANGELES,CA 90024. RUTGERS STATE UNIV,PISCATAWAY,NJ 08855. FU NCI NIH HHS [N01-CP-05634, N01-CP-41019, N01-CP-95616] NR 11 TC 65 Z9 65 U1 0 U2 3 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA PUBLIC LEDGER BLDG, SUITE 816, 150 S. INDEPENDENCE MALL W., PHILADELPHIA, PA 19106 SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD MAR PY 1994 VL 3 IS 2 BP 161 EP 166 PG 6 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA NA344 UT WOS:A1994NA34400011 PM 8049638 ER PT J AU DAWSEY, SM WANG, GQ TAYLOR, PR LI, JY BLOT, WJ LI, B LEWIN, KJ LIU, FS WEINSTEIN, WM WIGGETT, S WANG, H MARK, SD YU, Y YANG, CS AF DAWSEY, SM WANG, GQ TAYLOR, PR LI, JY BLOT, WJ LI, B LEWIN, KJ LIU, FS WEINSTEIN, WM WIGGETT, S WANG, H MARK, SD YU, Y YANG, CS TI EFFECTS OF VITAMIN MINERAL SUPPLEMENTATION ON THE PREVALENCE OF HISTOLOGICAL DYSPLASIA AND EARLY CANCER OF THE ESOPHAGUS AND STOMACH - RESULTS FROM THE DYSPLASIA TRIAL IN LINXIAN, CHINA SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article AB Linxian, China has some of the highest rates of esophageal/gastric cardia cancer in the world, and epidemiological evidence suggests that chronically low intake of micronutrients may contribute to these high cancer rates. To examine whether supplementation with multiple vitamins and minerals can affect the occurrence of esophageal/gastric cardia cancer in this population, a two-arm randomized nutrition intervention trial was conducted among 3318 Linxian residents with cytological evidence of esophageal dysplasia. During the 6-year intervention, esophageal/gastric cardia cancer mortality was 8% lower among those receiving the active supplements. After 30 and 72 months of intervention, endoscopic surveys were carried out to see if the nutritional supplements had affected the prevalence of clinically silent precancerous lesions and early invasive cancers of the esophagus and stomach. In the first survey, in 1987, 833 subjects were endoscoped; in the second survey, in 1991, 396 subjects were examined. The histological diagnoses from each survey were compared by treatment group. Cancer or dysplasia was diagnosed in 28% of the subjects endoscoped in 1987 and 24% of those examined in 1991. The odds ratio for subjects in the treatment group (versus those in the placebo group) having esophageal or gastric dysplasia or cancer was 0.84 (95% confidence interval, 0.61-1.15) in 1987 and 0.86 (0.54-1.38) in 1991. Although modest protective effects on worst overall diagnosis were seen in the supplemented group in both surveys, none of the results was statistically significant, and the findings must be considered inconclusive. It is likely that longer interventions and larger numbers of endoscoped subjects will be required to fully investigate the effects of micronutrient supplementation in this population. C1 UNIV CALIF LOS ANGELES,LOS ANGELES,CA 90024. RUTGERS STATE UNIV,PISCATAWAY,NJ 08855. CHINESE ACAD MED SCI,CANC INST & HOSP,BEIJING,PEOPLES R CHINA. RP DAWSEY, SM (reprint author), NCI,BETHESDA,MD 20892, USA. FU NCI NIH HHS [N01-CP-05634, N01-CP-41019, N01-CP-95616] NR 13 TC 46 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 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD MAR PY 1994 VL 3 IS 2 BP 167 EP 172 PG 6 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA NA344 UT WOS:A1994NA34400012 PM 8049639 ER PT J AU BRAWLEY, OW FORD, LG THOMPSON, I PERLMAN, JA KRAMER, BS AF BRAWLEY, OW FORD, LG THOMPSON, I PERLMAN, JA KRAMER, BS TI 5-ALPHA-REDUCTASE INHIBITION AND PROSTATE-CANCER PREVENTION SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Review ID MALE PSEUDOHERMAPHRODITISM; FINASTERIDE MK-906; ANDROGEN RECEPTOR; CARCINOMA; SERUM; ADENOCARCINOMA; TESTOSTERONE; MEN; DIHYDROTESTOSTERONE; CASTRATION AB Studies of prostate biology support the concept that dihydrotestosterone is the principal androgen responsible for normal and hyperplastic growth of the prostate gland. Cancer is a process of malignant transformation evolving over time, involving cellular growth and division. Therefore, an altered endocrine state, such as suppression of dihydrotestosterone activity, may have an impact on prostate cells inhibiting carcinogenic transformation. In vitro and in vivo preclinical observations support this hypothesis. A placebo-controlled randomized trial using finasteride, an inhibitor of the enzyme that converts testosterone to dihydrotestosterone, is planned. The endpoint of this trial will be reduction of prostate cancer incidence. C1 BROOKE ARMY MED CTR,DEPT SURG,RADIOL SERV,FT SAM HOUSTON,TX 78234. RP BRAWLEY, OW (reprint author), NCI,DIV CANC PREVENT & CONTROL,COMMUNITY ONCOL & REHABIL BRANCH,EPN,BETHESDA,MD 20892, USA. NR 59 TC 64 Z9 65 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 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD MAR PY 1994 VL 3 IS 2 BP 177 EP 182 PG 6 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA NA344 UT WOS:A1994NA34400014 PM 8049641 ER PT J AU SUN, Y HEGAMYER, G COLBURN, NH AF SUN, Y HEGAMYER, G COLBURN, NH TI MOLECULAR-CLONING OF 5 MESSENGER-RNAS DIFFERENTIALLY EXPRESSED IN PRENEOPLASTIC OR NEOPLASTIC JB6 MOUSE EPIDERMAL-CELLS - ONE IS HOMOLOGOUS TO HUMAN TISSUE INHIBITOR OF METALLOPROTEINASES-3 SO CANCER RESEARCH LA English DT Note ID RESISTANT; DISPLAY; GROWTH; MEMBER; FAMILY AB To better understand the molecular mechanism of multistage carcinogenesis, we have attempted to identify putative oncogenes and/or tumor suppressor genes involved in preneoplastic-to-neoplastic progression of mouse epidermal JB6 variants. The JB6 variants consist of P- (promotion resistant), P+ (promotion sensitive), and Tx [transformed; both apoptosis-sensitive (A(5)) and apoptosis-resistant (A(r))] cells, representing progression from early to late stages of carcinogenesis. By using the newly developed differential mRNA display technique, we have isolated five clones from these JB6 variants. The isolated clones were uniquely expressed either in P-/P+ cells or in Tx (A(s)/A(r)) cells or showed highly differential expression among the variants. The expression pattern shown by differential mRNA display was confirmed by Northern blot analysis. DNA sequencing followed by computer search against Genbank and EMBL DNA databases indicates that three clones are novel and two have high homology with recorded genes. One of the clones (Cl.14), which detects expression in preneoplastic not neoplastic JB6 cells, was used as a probe for complementary DNA library screening. The corresponding gene, named sun for specifically unexpressed in neoplastic JB6 cells, was isolated and sequenced. The longest open reading frame of the sun clone predicts a peptide showing 96% amino acid sequence identity to the recorded sequence of human tissue inhibitor of metalloproteinases-3, one of a family of genes implicated in tumorigenesis and tumor invasion. This is the first report, to our knowledge, of the simultaneous display of mRNAs of four phenotypically distinct cell variants and of the isolation of five clones which may be associated with specific stages of tumor promotion and/or progression and apoptosis. RP SUN, Y (reprint author), NCI,FREDERICK CANC RES & DEV CTR,CELLBIOL SECT,VIRAL CARCINOGENESIS LAB,FREDERICK,MD 21702, USA. NR 22 TC 132 Z9 150 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 1994 VL 54 IS 5 BP 1139 EP 1144 PG 6 WC Oncology SC Oncology GA MZ092 UT WOS:A1994MZ09200003 PM 8118794 ER PT J AU CONRY, RM LOBUGLIO, AF KANTOR, J SCHLOM, J LOECHEL, F MOORE, SE SUMEREL, LA BARLOW, DL ABRAMS, S CURIEL, DT AF CONRY, RM LOBUGLIO, AF KANTOR, J SCHLOM, J LOECHEL, F MOORE, SE SUMEREL, LA BARLOW, DL ABRAMS, S CURIEL, DT TI IMMUNE-RESPONSE TO A CARCINOEMBRYONIC ANTIGEN POLYNUCLEOTIDE VACCINE SO CANCER RESEARCH LA English DT Note ID DELAYED-TYPE HYPERSENSITIVITY; T-CELL MEMORY; MOLECULAR-BIOLOGY; VIRUS-VACCINE; MOUSE MUSCLE; GENE; EXPRESSION; EPITOPES; ANTIBODY; HUMANS AB We have constructed a DNA plasmid encoding the full length complementary DNA for human carcinoembryonic antigen (CEA) driven by the cytomegalovirus early promoter/enhancer (plasmid DNA encoding human CEA) and demonstrated that this plasmid can function as a polynucleotide vaccine. This polynucleotide vaccine induced humoral and/or cellular immune responses specific for human CEA in all 5 immunized mice. Lymphoblastic transformation data with the use of enriched T-cell populations detected the presence of CEA-specific memory T-cells in 3 of 5 mice. Lymphocytes from 2 of 5 mice had interleukin 2/interleukin 4 release in response to CEA. CEA specificity was confirmed by the absence of reactivity to a control antigen and lack of CEA reactivity among mice vaccinated with a control plasmid encoding chloramphenicol acetyltransferase. Four of 5 mice vaccinated with plasmid DNA encoding human CEA demonstrated anti-CEA antibody responses. This immune response compared favorably with a positive control group of mice immunized with vaccinia-CEA by a dose and schedule previously shown to induce immunoprotection and therapy against a human CEA expressing syngeneic murine colon carcinoma model. Studies are ongoing to establish the construct, dose, and schedule to elicit optimal CEA-specific immune response as well as immunoprotection and therapy against human CEA expressing syngeneic murine adenocarcinoma models. C1 NATL CANC INST,TUMOR IMMUNOL & BIOL LAB,BETHESDA,MD 20892. RP CONRY, RM (reprint author), UNIV ALABAMA,BIRMINGHAM COMPREHENS CANC CTR,GENE THERAPY PROGRAM,1824 6TH AVE S,BIRMINGHAM,AL 35294, USA. NR 25 TC 129 Z9 133 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 1994 VL 54 IS 5 BP 1164 EP 1168 PG 5 WC Oncology SC Oncology GA MZ092 UT WOS:A1994MZ09200009 PM 8118800 ER PT J AU ELDEIRY, WS HARPER, JW OCONNOR, PM VELCULESCU, VE CANMAN, CE JACKMAN, J PIETENPOL, JA BURRELL, M HILL, DE WANG, YS WIMAN, KG MERCER, WE KASTAN, MB KOHN, KW ELLEDGE, SJ KINZLER, KW VOGELSTEIN, B AF ELDEIRY, WS HARPER, JW OCONNOR, PM VELCULESCU, VE CANMAN, CE JACKMAN, J PIETENPOL, JA BURRELL, M HILL, DE WANG, YS WIMAN, KG MERCER, WE KASTAN, MB KOHN, KW ELLEDGE, SJ KINZLER, KW VOGELSTEIN, B TI WAF1/CIP1 IS INDUCED IN P53-MEDIATED G(1) ARREST AND APOPTOSIS SO CANCER RESEARCH LA English DT Note ID PROGRAMMED CELL-DEATH; AMINO-ACID MIMOSINE; DNA-REPLICATION; P53; PROTEIN; BCL-2; INITIATION; CYCLE AB The tumor growth suppressor WAF1/CIP1 was recently shown to be induced p53 and to be a potent inhibitor of cyclin-dependent kinases. In the present studies, we sought to determine the relationship between the expression of WAF1/CIP1 and endogenous regulation of p53 function. WAF1/CIP1 protein was first localized to the nucleus of cells containing mild-type p53 and undergoing G(1) arrest. WAF1/CIP1 was induced in wild-type p53-containing cells by exposure to DNA damaging agents, but not in mutant p53-containing cells. The induction of WAF1/CIP1 protein occurred in cells undergoing either p53-associated G(1) arrest or apoptosis but not in cells induced to arrest in G(1) or to undergo apoptosis through p53-independent mechanisms. DNA damage Led to increased levels of WAF1/CIP1 in cyclin E-containing complexes and to an associated decrease in cyclin-dependent kinase activity. These results support the idea that WAF1/CIP1 is a critical downstream effector in the p53-specific pathway of growth control in mammalian cells. C1 JOHNS HOPKINS UNIV,SCH MED,PROGRAM HUMAN GENET & MOLEC BIOL,BALTIMORE,MD 21231. NCI,DIV CANC TREATMENT,DEV THERAPEUT PROGRAM,MOLEC PHARMACOL LAB,BETHESDA,MD 20892. ONCOGENE SCI INC,CAMBRIDGE,MA 02142. KAROLINSKA INST,DEPT TUMOR BIOL,S-10401 STOCKHOLM,SWEDEN. HOWARD HUGHES MED INST,HOUSTON,TX 77030. BAYLOR COLL MED,VERNA & MARRS MCLEAN DEPT BIOCHEM,HOUSTON,TX 77030. BAYLOR COLL MED,INST MOLEC GENET,HOUSTON,TX 77030. THOMAS JEFFERSON UNIV,JEFFERSON CANC INST,DEPT MICROBIOL & IMMUNOL,PHILADELPHIA,PA 19107. RP ELDEIRY, WS (reprint author), JOHNS HOPKINS UNIV,SCH MED,CTR ONCOL,BALTIMORE,MD 21231, USA. RI Hill, David/B-6617-2011 FU NIEHS NIH HHS [ES05777]; NIGMS NIH HHS [GM07309, GM07184] NR 31 TC 2050 Z9 2072 U1 1 U2 20 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 1994 VL 54 IS 5 BP 1169 EP 1174 PG 6 WC Oncology SC Oncology GA MZ092 UT WOS:A1994MZ09200010 PM 8118801 ER PT J AU WIEDENFELD, EA FERNANDEZVINA, M BERZOFSKY, JA CARBONE, DP AF WIEDENFELD, EA FERNANDEZVINA, M BERZOFSKY, JA CARBONE, DP TI EVIDENCE FOR SELECTION AGAINST HUMAN LUNG CANCERS BEARING P53 MISSENSE MUTATIONS WHICH OCCUR WITHIN THE HLA A-ASTERISK-0201 PEPTIDE CONSENSUS MOTIF SO CANCER RESEARCH LA English DT Note ID TUMOR SUPPRESSOR GENE; CELL-LINES; ACCUMULATION; PROGNOSIS; PROTEIN; GROWTH AB Short peptide fragments of intracellular proteins that fit a defined sequence moth bind to the most common human major histocompatibility complex class I molecule, HLAA*0201, and mediate killing by cytotoxic T-cells [D.F. Hunt et al., Science (Washington DC), 255: 1261-1263, 1992; K. Falk et al., Nature (Lend.), 351: 290-296, 1991]. The existence of such a motif allows prediction of whether novel peptides derived from mutant oncoproteins might be presented on the surface of cancer cells bearing that HLA allele. Clinical cancer might develop only when these mutations occur outside a major histocompatibility complex binding motif or in those cells that acquire defects in antigen presentation. Here, we find that missense mutations of p53 from a variety of tumors fall within the HLA A*0201 moth less often than would be expected if the location of mutations and motifs were independent. When we analyzed the HLA subtype of lung cancer cell lines with known p53 missense mutations, we found that all of the mutant oncopeptides predicted to be presentable by HLA A*0201 came from tumors that either did not carry the A*0201 allele or had lost that allele in the process of tumorigenesis. Presentation of mutant oncogene peptides on class I major histocompatibility complex might thus represent a physiologically significant selection pressure in the development of human cancer. C1 UNIV TEXAS,SW MED CTR,SIMMONS CANC CTR,DALLAS,TX 75235. NATL CANC INST,METAB BRANCH,BETHESDA,MD 20892. FU NCI NIH HHS [R01 CA57856] NR 14 TC 47 Z9 47 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 1994 VL 54 IS 5 BP 1175 EP 1177 PG 3 WC Oncology SC Oncology GA MZ092 UT WOS:A1994MZ09200011 PM 8118802 ER PT J AU YUSPA, SH AF YUSPA, SH TI THE PATHOGENESIS OF SQUAMOUS-CELL CANCER - LESSONS LEARNED FROM STUDIES OF SKIN CARCINOGENESIS - 33RD GHA-CLOWES-MEMORIAL-AWARD LECTURE SO CANCER RESEARCH LA English DT Article ID PROTEIN-KINASE-C; MOUSE EPIDERMAL-CELLS; TRANSFORMING GROWTH-FACTOR; ESTER TUMOR PROMOTERS; HARVEY-RAS GENE; CALCIUM-REGULATED DIFFERENTIATION; CULTURED MURINE KERATINOCYTES; HA-RAS; TERMINAL DIFFERENTIATION; MALIGNANT CONVERSION AB The multistage nature of cancer pathogenesis was first defined over 50 years ago by the sequential topical application of chemical agents to mouse skin. Since then, the skin model has provided remarkable insights into the biology, biochemistry, pharmacology, and genetics of carcinogenesis. Discoveries from studies of mouse skin have proved to be landmarks in cancer research including: the binding of carcinogens to DNA; the monoclonal origin of benign and malignant tumors; the powerful tumor-promoting action of phorbol esters; the antipromoting potency of retinoids and steroids; the modifying role of age, caloric intake, and specific dietary constituents on cancer induction; the variable risk far benign tumors to progress to cancer; and the requirement for multiple genetic changes in malignant conversion. Many of these concepts are now widely applied to the interpretation of specific molecular discoveries both in simple experimental systems and in human cancers, but the power of this quantitative, multistage skin carcinogenesis model has made these assessments possible. It has also provided the separation of mechanistically distinct stages in cancer pathogenesis: initiation; promotion; premalignant progression; and malignant conversion. This paper will review our current understanding of the genetic, biological, and biochemical alterations that contribute to the evolution of each of these stages in skin carcinogenesis. These new insights provide an opportunity to replace the traditional operational-based schemata defining the process of carcinogenesis with a working model designed around functional alterations in neoplastic cells. RP YUSPA, SH (reprint author), NCI,CELLULAR CARCINOGENESIS & TUMOR PROMOT,BETHESDA,MD 20892, USA. NR 171 TC 268 Z9 268 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 1994 VL 54 IS 5 BP 1178 EP 1189 PG 12 WC Oncology SC Oncology GA MZ092 UT WOS:A1994MZ09200012 PM 8118803 ER PT J AU PENNO, MB AUGUST, JT BAYLIN, SB MABRY, M LINNOILA, RI LEE, VS CROTEAU, D YANG, XL ROSADA, C AF PENNO, MB AUGUST, JT BAYLIN, SB MABRY, M LINNOILA, RI LEE, VS CROTEAU, D YANG, XL ROSADA, C TI EXPRESSION OF CD44 IN HUMAN LUNG-TUMOR SO CANCER RESEARCH LA English DT Article ID CANCER CELL-LINES; MONOCLONAL-ANTIBODIES; HYALURONATE; PROGRESSION; CARCINOMA; RECEPTOR; FAMILY; ESTABLISHMENT; PROTEINS; MOLECULE AB CD44 is an integral membrane glycoprotein that functions as a receptor for the extracellular matrix glycan, hyaluronan. Here we report that CD44 is a novel biomarker for non-small cell lung tumors, squamous metaplasia of the lung, and activated type II pneumocytes. We have examined the expression of CD44 in 12 human lung tumor cell lines and 23 fixed, paraffin-embedded lung cancers. CD44 transcription and translation is consistently high among non-small cell tumors (5 of 5 cell lines, 10 of 14 tumors) but rare in small cell tumors (1 of 6 cell lines, 0 of 9 tumors). In normal lung, CD44 was confined to the surface of bronchial basai cells and alveolar macrophages. Squamous metaplasia of the lung showed strong CD44 immunoreactivity. Resting type II pneumocytes were Largely CD44 negative but rows of active, surfactant-secreting type II cells had significant amounts of CD44 located on lateral surfaces of adjacent cells. The correlation between CD44 and the non-small cell phenotype was further demonstrated in studies of a cultured small cell lung cancer line induced to exhibit characteristics of a non-small lung cancer by infection with v-Ha-ras. Following ras gene insertion, these cells showed a 40-fold increase in CD44 expression. The CD44 detected in lung cancer cells throughout these studies was predominantly the ''standard'' rather than the ''variant'' species. Taken together, these results suggest that CD44 is a protein expressed on non-small cell lung tumors, squamous metaplasia, and activated type II cells. In addition, CD44 in cultured small cell lung cancer cells is transcriptionally activated following differentiation by the ras oncogene. The fact that immunohistochemistry can be used to discriminate among the cell types makes CD44 a valuable new marker for lung neoplasia. C1 JOHNS HOPKINS UNIV,SCH MED,DEPT PHARMACOL & MOLEC SCI,BALTIMORE,MD 21205. JOHNS HOPKINS UNIV,SCH MED,DEPT MED,BALTIMORE,MD 21205. ONCOL CTR,BALTIMORE,MD 21205. NCI,BIOMARKERS & PREVENT RES BRANCH,ROCKVILLE,MD 20850. FU NCI NIH HHS [CA09243, CA58184, P50 CA058184, T32 CA 09243] NR 44 TC 128 Z9 134 U1 0 U2 2 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 1994 VL 54 IS 5 BP 1381 EP 1387 PG 7 WC Oncology SC Oncology GA MZ092 UT WOS:A1994MZ09200043 PM 7509720 ER PT J AU LAVAL, F WINK, DA AF LAVAL, F WINK, DA TI INHIBITION BY NITRIC-OXIDE OF THE REPAIR PROTEIN, O(6)-METHYLGUANINE-DNA-METHYLTRANSFERASE SO CARCINOGENESIS LA English DT Article ID WOODCHUCK HEPATITIS-VIRUS; MARMOTA-MONAX; DNA; CELLS; 1,3-BIS(2-CHLOROETHYL)-1-NITROSOUREA; PEROXYNITRITE; OXIDATION; NITRATE; AGENTS AB Nitric oxide (NO) has been shown to be involved in a number of physiological processes. In the presence of oxygen, this reactive diatomic molecule is capable of generating reactive nitrogen oxide species (NOx) which possess both nitrosating and oxidizing ability for various substrates, including certain biological macromolecules. This report shows the inhibition of the DNA repair protein, O-6-methylguanine-DNA-methyltransferase, by Et(2)N[N(O)NO]Na (DEA/NO), a compound which decomposes with concurrent release of NO. The inhibition of the purified transferase activity by NO was dose- and time-dependent and the extent of inhibition by DEA/NO corresponded to the total quantity of NO released. This inhibitory effect by NO was also demonstrated to be reversible over time. The reaction of the NO released from DEA/NO with cysteine under aerobic conditions resulted in the formation of an S-nitrosothiol adduct, suggesting that a similar adduct could be responsible for the inactivation. C1 FREDERICK CANC RES & DEV CTR,NATL CANC INST,CHEM SECT,COMPARAT CARCINOGENESIS LAB,FREDERICK,MD 21702. RP LAVAL, F (reprint author), INST GUSTAVE ROUSSY,RADIOCHIM ADN GRP,INSERM,U247,F-94805 VILLEJUIF,FRANCE. NR 31 TC 163 Z9 168 U1 0 U2 4 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0143-3334 J9 CARCINOGENESIS JI Carcinogenesis PD MAR PY 1994 VL 15 IS 3 BP 443 EP 447 DI 10.1093/carcin/15.3.443 PG 5 WC Oncology SC Oncology GA NA027 UT WOS:A1994NA02700004 PM 8118926 ER PT J AU YAMAZAKI, H MIMURA, M ODA, Y GONZALEZ, FJ ELBAYOUMY, K CHAE, YH GUENGERICH, FP SHIMADA, T AF YAMAZAKI, H MIMURA, M ODA, Y GONZALEZ, FJ ELBAYOUMY, K CHAE, YH GUENGERICH, FP SHIMADA, T TI ACTIVATION OF TRANS-1,2-DIHYDRO-1,2-DIHYDROXY-6-AMINOCHRYSENE TO GENOTOXIC METABOLITES BY RAT AND HUMAN CYTOCHROMES P450 SO CARCINOGENESIS LA English DT Article ID LIVER MICROSOMAL CYTOCHROME-P-450; OXIDATIVE DRUG-METABOLISM; GENETIC-POLYMORPHISM; CELL-LINE; UMU-GENE; ENZYMES; PURIFICATION; FORMS; 6-NITROCHRYSENE; BIOACTIVATION AB In order to address the hypothesis that 6-aminochrysene (6-AC) is converted to genotoxic products by cytochrome P450 enzymes via two activation pathways (N-hydroxylation and epoxidation), the activation of 6-AC and trans-1,2-dihydro-1,2-dihydroxy-6-aminochrysen (6-AC-diol) to genotoxic metabolites was examined in rat and human liver microsomal cytochrome P450 enzymes using Salmonella typhimurium TA1535/pSK1002 and TA1535/pSK1002/pNM12 (NM2009) as tester strains. The latter bacteria, an O-acetyl-transferase-overexpressing strain, was highly sensitive to metabolites derived from activation of 6-AC, but not those from 6-AC-diol, using liver microsomes from phenobarbital-treated rats or a reconstituted monooxygenase system containing P4502B1 or -2B2, thus suggesting the roles of P450 and acetyltransferase systems in the activation process. 6-AC-diol, on the other hand, was activated very efficiently by liver microsomes prepared from beta-naphthoflavone-treated rats or a reconstituted system containing P4501A1 or -1A2; the activation reaction is considered to proceed through diolepoxide formation. The contribution of rat P4501A enzymes towards activation of 6-AC-diol was confirmed by the inhibitory effects on the activation process of alpha-naphthoflavone, a specific inhibitor of P4501A-related activities, and antibodies raised against purified P4501A1 and -1A2. In humans, P4501A2 was found to be the major enzyme involved in the activation of 6-AC-diol to genotoxic metabolites while the parent compound 6-AC was activated mainly by P4503A4. Experiments using recombinant P450. proteins expressed in human lymphoblastoid cell lines showed that human P4501A1 could also activate 6-AC-diol to reactive metabolites at almost the same rate measured,vith P4501A2. In addition, P4502B6 was found to efficiently catalyze the activation of 6-AC to genotoxic metabolites, and P4503A4 was active in the activation of 6-AC-diol as well as 6-AC. Addition of purified rat epoxide hydrolase to the incubation mixture containing purified rat P4501A1 or microsomes expressing human P4501A1 caused inhibition of activation of 6-AC-diol. These results suggest the existence of different enzymatic activation pathways for 6-AC and 6-AC-diol. The former carcinogen may be N-hydroxylated principally by P4502B enzymes in rats and P4503A4 and -2B6 in humans and activation to its ultimate metabolites may proceed through esterification of the N-hydroxy metabolites by an N-acetyltransferase. The 6-AC-diol is metabolized to its ultimate diolepoxide product by P4501A enzymes in rat and human liver microsomes. P4503A4 (humans) and P4503A2 (rats) may also contribute to some extent in the activation of Q-AC-diol, albeit at lower rates than those of P4501A enzymes. C1 OSAKA PREFECTURAL INST PUBL HLTH,NAKAMICHI HIGASHINARI KU,OSAKA 537,JAPAN. NCI,MOLEC CARCINOGENESIS LAB,BETHESDA,MD 20892. AMER HLTH FDN,DIV CHEM CARCINOGENESIS,VALHALLA,NY 10595. VANDERBILT UNIV,SCH MED,DEPT BIOCHEM,NASHVILLE,TN 37232. VANDERBILT UNIV,SCH MED,CTR MOLEC TOXICOL,NASHVILLE,TN 37232. OI Yamazaki, Hiroshi/0000-0002-1068-4261 FU NCI NIH HHS [CA44353, CA35519]; NIEHS NIH HHS [ES00267] NR 34 TC 14 Z9 14 U1 0 U2 0 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0143-3334 J9 CARCINOGENESIS JI Carcinogenesis PD MAR PY 1994 VL 15 IS 3 BP 465 EP 470 DI 10.1093/carcin/15.3.465 PG 6 WC Oncology SC Oncology GA NA027 UT WOS:A1994NA02700008 PM 8118930 ER PT J AU STRICKLAND, PT KANG, D BOWMAN, ED FITZWILLIAM, A DOWNING, TE ROTHMAN, N GROOPMAN, JD WESTON, A AF STRICKLAND, PT KANG, D BOWMAN, ED FITZWILLIAM, A DOWNING, TE ROTHMAN, N GROOPMAN, JD WESTON, A TI IDENTIFICATION OF 1-HYDROXYPYRENE GLUCURONIDE AS A MAJOR PYRENE METABOLITE IN HUMAN URINE BY SYNCHRONOUS FLUORESCENCE SPECTROSCOPY AND GAS-CHROMATOGRAPHY MASS-SPECTROMETRY SO CARCINOGENESIS LA English DT Article ID POLYCYCLIC AROMATIC-HYDROCARBONS; EXPOSURE; BENZOPYRENE AB Humans are exposed to polycyclic aromatic hydrocarbons (PAHs) from various occupational, environmental, medicinal and dietary sources. The measurement of specific PAH metabolites, particularly 1-hydroxypyrene, in human urine treated with deconjugating enzymes (e.g. beta-glucuronidase) has been extensively used as a means of assessing recent exposure to PAHs. We have examined pyrene metabolites in human urine prior to enzymatic deconjugation in order to determine the relative proportions of conjugated and unconjugated pyrene metabolites. The analytical method utilized immunoaffinity chromatography, high performance liquid chromatography (HPLC) and the complementary techniques of synchronous fluorescence spectroscopy (SFS) and gas chromatography - mass spectrometry (GC-MS) to measure pyrene-containing metabolites. SFS analysis of immunoaffinity-purified urine samples showed fluorescence spectra characteristic of the pyrene moiety (using wavelength differences of 34 nm, 54 nm and 102 nm). These spectra are produced by several PAHs containing the pyrene moiety. HPLC analysis with fluorescence detection indicated that the major fluorescent metabolite in immunoaffinity-purified urine was much more polar than simple hydroxylated metabolites of pyrene (1-hydroxypyrene) or benzo[a]pyrene (benzo[a] pyrene-diols or -tetrols), Following digestion with beta-glucuronidase, this metabolite co-chromatographed with authentic 1-hydroxypyrene and exhibited fluorescence spectra characteristic of 1-hydroxypyrene, suggesting that the major metabolite was a glucuronide conjugate of 1-hydroxypyrene. This was subsequently confirmed by GC-MS analysis of trimethylsilyl derivatives of the major metabolite; both 1-hydroxypyrene and glucuronic acid were detected independently as derivatized products. Since 1-hydroxypyrene glucuronide is approximately 5-fold more fluorescent than 1-hydroxypyrene, it may provide a more sensitive biomarker for assessing exposure to pyrene in mixtures of PAHs. C1 NCI,DIV CANC ETIOL,BETHESDA,MD 20892. RP STRICKLAND, PT (reprint author), JOHNS HOPKINS SCH HYG & PUBL HLTH,DEPT ENVIRONM HLTH SCI,BALTIMORE,MD 21205, USA. RI Kang, Dae Hee/E-8631-2012 FU NIEHS NIH HHS [P30-ES03819, P01-ES06052] NR 21 TC 85 Z9 91 U1 1 U2 8 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0143-3334 J9 CARCINOGENESIS JI Carcinogenesis PD MAR PY 1994 VL 15 IS 3 BP 483 EP 487 DI 10.1093/carcin/15.3.483 PG 5 WC Oncology SC Oncology GA NA027 UT WOS:A1994NA02700011 PM 8118933 ER PT J AU GRAY, TE ZHU, SJ NETTESHEIM, P AF GRAY, TE ZHU, SJ NETTESHEIM, P TI REGULATION OF TRANSFORMATION FREQUENCY BY EXOGENOUS AND ENDOGENOUS GROWTH-FACTORS IN RAT TRACHEAL EPITHELIAL-CELLS SO CARCINOGENESIS LA English DT Article ID NEOPLASTIC PROGRESSION; PROLIFERATION; CARCINOGENS; RESPONSES; CULTURE AB The purpose of our studies was to re-evaluate the rat tracheal epithelial (RTE) transformation system and to identify critical variables that affect the development of enhanced growth variants (EGV). The enhanced growth variant colony, which is a preneoplastic cell variant, is the quantifiable transformation endpoint in RTE cultures. Using a standard protocol the frequency of EGV colony formation was shown to be inversely related to the number of clonogenic cells (CFU) seeded per dish in control cultures as well as in cultures treated with the transforming agent 6-nitrochrysene (6-NC). Experiments showed that the major mechanisms that underlie the CFU density-dependent inhibition of EGV colony formation are depletion of growth factors from and accumulation of autocrine TGF-beta in the media. Thus the cells themselves are creating the selection environment, which allows only the EGVs to survive. The effects of agents such as 6-NC, which increase the frequency of EGV colony formation, are to induce a cellular phenotype that is less susceptible to the selection environment. We showed that TGF-beta-neutralizing antibodies added to the selection media significantly increased EGV colony formation in control cultures but not in 6-NC-exposed cultures. In addition we demonstrated that the development of EGV colonies is much less susceptible to inhibition by (exogenous) TGF-beta in 6-NC-exposed than in control cultures. Thus spontaneous and 6-NC EGV colony formation are distinguishable based on TGF-beta sensitivity. To conduct quantitative cell transformation experiments with RTE cells it is essential that the number of surviving CFU per dish is the same in control and treated cultures. Under the conditions used in the studies described here, 350-500 CFU per culture was found to be the optimum CFU density. Besides 6-NC, agents that have been shown to increase EGV colony frequency under conditions similar to those described here are nitrosamines, NNK, nickel compounds and X-rays. C1 MANTECH ENVIRONM,RES TRIANGLE PK,NC 27709. RP GRAY, TE (reprint author), NIEHS,PULM PATHOBIOL LAB,POB 12233,RES TRIANGLE PK,NC 27709, USA. NR 28 TC 1 Z9 1 U1 0 U2 0 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0143-3334 J9 CARCINOGENESIS JI Carcinogenesis PD MAR PY 1994 VL 15 IS 3 BP 549 EP 555 DI 10.1093/carcin/15.3.549 PG 7 WC Oncology SC Oncology GA NA027 UT WOS:A1994NA02700022 PM 8118942 ER PT J AU GAMBASSI, G CERBAI, E PAHOR, M CAPOGROSSI, MC CARBONIN, P MUGELLI, A AF GAMBASSI, G CERBAI, E PAHOR, M CAPOGROSSI, MC CARBONIN, P MUGELLI, A TI TEMPERATURE MODULATES CALCIUM HOMEOSTASIS AND VENTRICULAR ARRHYTHMIAS IN MYOCARDIAL PREPARATIONS SO CARDIOVASCULAR RESEARCH LA English DT Article DE TEMPERATURE; HEART; CA2+; SARCOPLASMIC RETICULUM; DELAYED AFTERDEPOLARIZATIONS; I-TI CURRENT, ARRHYTHMIAS; REOXYGENATION; CARDIAC MYOCYTES ID REPERFUSION-INDUCED ARRHYTHMIAS; TRANSIENT INWARD CURRENT; CARDIAC PURKINJE-FIBERS; ISOLATED RAT-HEART; GUINEA-PIG HEART; CARDIOTONIC STEROIDS; NA+-CA2+ EXCHANGE; IONIC MECHANISMS; MUSCLE-FIBERS; CAFFEINE AB Objective: The aim was to evaluate the effect of temperature on reoxygenation induced ventricular arrhythmias in isolated hearts, on delayed after depolarisations and I-ti current in Purkinje fibres, and on sarcoplasmic reticular function and Ca2+ handling of single cardiac myocytes. Methods: Isolated guinea pig hearts were retrogradely perfused at 37 degrees C with a hypoxic medium for 15 min and reoxygenated for 10 min either at 33 degrees C or at 37 degrees C. Intracellular microelectrodes were used to assess the presence of delayed afterdepolarisations and triggered activity in sheep Purkinje fibres exposed to strophanthidin at different temperatures. I-ti current was evaluated in voltage clamp experiments. In rat cardiomyocytes, loaded with the fluorescent Ca2+ dye, indo-1, the sarcoplasmic reticular Ca2+ content was assessed at 30 degrees C and at 37 degrees C, either by a caffeine spritz puffed onto a cell from a patch pipette or by a post-rest contraction. Results: Hypothermic reoxygenation reduced the incidence of ventricular arrhythmias in isolated hearts (30%, n = 10, at 33 degrees C and 75%, n = 30, at 37 degrees C, p < 0.05). In Purkinje fibres, hypothermia decreased the amplitude of delayed afterdepolarisations. Moreover, at 32 degrees C, the amplitude of I-ti current was decreased to 59.2(SEM 2.6)% of the normothermic value [27.5(6.7) nA, n = 4, p < 0.005] and time to peak increased to 159.7(10.2)% [value at 37 degrees C = 470(41) ms, n = 4, p < 0.01]. In cardiac cells, sarcoplasmic reticular Ca2+ release induced by caffeine spritz or by post-rest contraction was increased at 30 degrees C. However, following a pacing period at 1 Hz, hypothermia prolonged the time to onset of the first spontaneous Ca2+ oscillation [59(14) s at 30 degrees C and 27(9) s at 37 degrees C, n = 5, p < 0.05] and reduced the oscillation frequency [1.1(0.4) min(-1) at 30 degrees C and 3.1(0.9) min(-1) at 37 degrees C, n = 5, p < 0.05]. Conclusions: Mild hypothermia increases sarcoplasmic reticular Ca2+ content but decreases the likelihood of spontaneous Ca release. This may explain the reduction of delayed afterdepolarisations and I-ti current amplitude in Purkinje fibres and it could represent a mechanism for the protection provided by hypothermia against ventricular arrhythmias. C1 NIA, GERONTOL RES CTR, CARDIOVASC SCI LAB, BALTIMORE, MD 21224 USA. UNIV FLORENCE, DIPARTIMENTO FARMACOL, FLORENCE, ITALY. RP GAMBASSI, G (reprint author), UNIV CATTOLICA SACRO CUORE, IST CLIN MED, LARGO A GEMELLI 8, I-00168 ROME, ITALY. OI Cerbai, Elisabetta/0000-0001-7839-1361 NR 50 TC 22 Z9 22 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0008-6363 J9 CARDIOVASC RES JI Cardiovasc. Res. PD MAR PY 1994 VL 28 IS 3 BP 391 EP 399 DI 10.1093/cvr/28.3.391 PG 9 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA NA018 UT WOS:A1994NA01800015 PM 8174161 ER PT J AU HAMANAKA, R MALOID, S SMITH, MR OCONNELL, CD LONGO, DL FERRIS, DK AF HAMANAKA, R MALOID, S SMITH, MR OCONNELL, CD LONGO, DL FERRIS, DK TI CLONING AND CHARACTERIZATION OF HUMAN AND MURINE HOMOLOGS OF THE DROSOPHILA POLO SERINE-THREONINE KINASE SO CELL GROWTH & DIFFERENTIATION LA English DT Article ID CELL-CYCLE AB We have cloned both human and murine complementary DNAs that are homologous to the Drosophila serine/threonine polo kinase and the recently cloned murine polo related kinase (PLK). Both the human and murine clones are about 2.1 kilobases with open reading frames of 1.8 kilobases, encoding proteins of 603 amino acids with a predicted size of 66 kilodaltons and an apparent size of 67 kilodaltons by sodium dodecyl sulfate-polyacrylamide gel electrophoresis analysis. During embryonic development of the mouse, the mRNA was expressed in all tissues examined, whereas in adult tissues, expression was limited to thymus and ovaries. All cell lines examined also expressed mRNAs of similar size. Microinjection of in vitro transcribed sense mRNA into serum-starved murine NIH3T3 cells induced tritiated thymidine incorporation, whereas microinjection of antisense RNA into growing NIH3T3 cells blocked tritiated thymidine incorporation. When PC12 rat cells were induced to differentiate with nerve growth factor, gene expression of PLK was greatly reduced. Together, these results suggest that PLK expression is restricted to, and is perhaps required by, proliferating cells. C1 NCI,FREDERICK CANC RES & DEV CTR,PROGRAM RESOURCES DYNCORP,FREDERICK,MD 21702. RP HAMANAKA, R (reprint author), NCI,FREDERICK CANC RES & DEV CTR,DIV CANC TREATMENT,LEUKOCYTE BIOL LAB,FREDERICK,MD 21702, USA. NR 15 TC 108 Z9 114 U1 0 U2 5 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA PUBLIC LEDGER BLDG, SUITE 816, 150 S. INDEPENDENCE MALL W., PHILADELPHIA, PA 19106 SN 1044-9523 J9 CELL GROWTH DIFFER JI Cell Growth Differ. PD MAR PY 1994 VL 5 IS 3 BP 249 EP 257 PG 9 WC Cell Biology SC Cell Biology GA MZ771 UT WOS:A1994MZ77100002 PM 8018557 ER PT J AU GUDAS, JM OKA, M DIELLA, F TREPEL, J COWAN, KH AF GUDAS, JM OKA, M DIELLA, F TREPEL, J COWAN, KH TI EXPRESSION OF WILD-TYPE P53 DURING THE CELL-CYCLE IN NORMAL HUMAN MAMMARY EPITHELIAL-CELLS SO CELL GROWTH & DIFFERENTIATION LA English DT Article ID HUMAN PAPILLOMAVIRUS TYPE-16; GROWTH ARREST; MONOCLONAL-ANTIBODIES; BREAST-CANCER; NUCLEAR-LOCALIZATION; MESSENGER-RNA; PROTEIN; TUMOR; MUTATIONS; MUTANT AB In this study, we compare the expression patterns of p53 mRNA and protein in normal human mammary epithelial cells following synchronization to different points in the cell cycle using two independent methods. When treated with lovastatin, the cells were blocked in G(1) and appeared to express increased levels of wild-type p53 when examined by immunostaining. Upon reversal of the metabolic block, the number of nuclei that stained positively for p53 declined dramatically during mid-G(1) and increased again concomitant with the entry of cells into S phase. In contrast to the immunostaining results, Northern and Western blot analyses revealed little change in p53 mRNA and protein levels in the lovastatin-synchronized cells. When normal human mammary epithelial cells were made quiescent by removal of growth factors, the mRNA for p53 showed a biphasic distribution. p53 mRNA levels were increased during growth arrest, decreased during the C, phase, and rose again concomitant with the entry of cells into S phase. The immunostaining pattern of p53 also showed a biphasic distribution similar to the pattern of mRNA expression. Despite an increase in p53 mRNA and immunostaining levels, growth factor-arrested cells actually had less total p53 protein. Upon stimulation to proliferate, p53 protein levels remained low throughout G(1) and increased concomitant with the entry of cells into S phase. Taken together, the results from these studies demonstrate that p53 immunostaining patterns do not correlate with the overall levels of p53 protein at different times during the cell cycle. Therefore, the distinct changes observed in p53 immunostaining patterns are likely due to posttranslational modifications, conformational changes, or interactions of p53 with other cellular proteins during the cell cycle. C1 NCI,TUMOR IMMUNOL & BIOL LAB,BETHESDA,MD 20892. NCI,CLIN PHARMACOL BRANCH,BETHESDA,MD 20892. RP GUDAS, JM (reprint author), NCI,DIV CANC TREATMENT,MED BRANCH,MED BREAST CANC SECT,BLDG 10,ROOM 12N226,BETHESDA,MD 20892, USA. NR 71 TC 35 Z9 35 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 1044-9523 J9 CELL GROWTH DIFFER JI Cell Growth Differ. PD MAR PY 1994 VL 5 IS 3 BP 295 EP 304 PG 10 WC Cell Biology SC Cell Biology GA MZ771 UT WOS:A1994MZ77100007 PM 8018562 ER PT J AU KULYNYCH, JJ VLADAR, K JONES, DW WEINBERGER, DR AF KULYNYCH, JJ VLADAR, K JONES, DW WEINBERGER, DR TI GENDER DIFFERENCES IN THE NORMAL LATERALIZATION OF THE SUPRATEMPORAL CORTEX - MRI SURFACE-RENDERING MORPHOMETRY OF HESCHLS GYRUS AND THE PLANUM TEMPORALE SO CEREBRAL CORTEX LA English DT Article ID LEFT-RIGHT ASYMMETRIES; UNILATERAL BRAIN-DAMAGE; HUMAN AUDITORY-CORTEX; SEX-DIFFERENCES; MAGNETIC-RESONANCE; SYLVIAN FISSURE; ORGANIZATION; SPEECH; HANDEDNESS; MORPHOLOGY AB Gender differences in hemispheric asymmetry for language functioning have been reported in the neuropsychological literature, Despite numerous reports of anatomic asymmetries in corresponding cortical regions, the possibility of gender dimorphism in the putative neuroanatomical substrate of language has not been systematically examined in vivo. We assessed asymmetry of the planum temporale (PT), a supratemporal region of auditory association cortex, in 12 normal, right-handed females and 12 age-matched right-handed males with the aid of MRI surface-rendering morphometry. Bilateral areas were also assessed for Heschl's gyrus (HG), a supratemporal region of primary auditory cortex where no asymmetry was anticipated. We found a significant interaction between gender and hemisphere for the PT, with males having significantly larger left versus right PTs. Left-right differences in PT area were not significant among females (10 of 12 males showed leftward lateralization of the PT, vs 5 of 12 females). No main effect of gender was found for total (left + right) PT area, and no asymmetries or gender effects were detected for HG. This finding of gender dimorphism in PT area is consistent with evidence for reduced asymmetry among females in the lateralization of language functions attributable to the supratemporal cortex. The implications for theories about interactions between sex hormones and the development of brain asymmetries are discussed. C1 NIMH,ST ELIZABETHS INTRAMURAL RES PROGRAM,CTR NEUROSCI,CLIN BRAIN DISORDERS BRANCH,WASHINGTON,DC 20032. NR 64 TC 154 Z9 154 U1 1 U2 8 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 SN 1047-3211 J9 CEREB CORTEX JI Cereb. Cortex PD MAR-APR PY 1994 VL 4 IS 2 BP 107 EP 118 DI 10.1093/cercor/4.2.107 PG 12 WC Neurosciences SC Neurosciences & Neurology GA NG695 UT WOS:A1994NG69500001 PM 8038562 ER PT J AU GITTERMAN, M WEISS, GH AF GITTERMAN, M WEISS, GH TI A SINGULAR PERTURBATION-THEORY FOR REACTION-DIFFUSION EQUATIONS SO CHEMICAL PHYSICS LA English DT Article AB A perturbation theory is developed for the probability density for the displacement in reaction-diffusion equations of the form partial derivative(p)/partial derivative tau=epsilon(partial derivative/partial derivative y) [f(y)partial derivative p/partial derivative y] - (partial derivative/partial derivative y) [upsilon(y)p] - kappa(y)p. In this equation f(y), upsilon(y) and kappa(y) are dimensionless functions of y taken to be O(1), and epsilon is a dimensionless parameter which, in the diffusion-dominated regime satisfies epsilon << 1. We briefly also discuss the case in which upsilon(y) is also proportional to epsilson. Our results are then applied to an exactly solvable example. C1 BAR ILAN UNIV,DEPT PHYS,IL-52100 RAMAT GAN,ISRAEL. RP GITTERMAN, M (reprint author), NIH,DIV COMP RES & TECHNOL,BETHESDA,MD 20892, USA. NR 14 TC 8 Z9 8 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0301-0104 J9 CHEM PHYS JI Chem. Phys. PD MAR 1 PY 1994 VL 180 IS 2-3 BP 319 EP 328 DI 10.1016/0301-0104(93)E0428-X PG 10 WC Chemistry, Physical; Physics, Atomic, Molecular & Chemical SC Chemistry; Physics GA MZ424 UT WOS:A1994MZ42400017 ER PT J AU CAROTHRS, AM YUAN, W HINGERTY, BE BROYDE, S GRUNBERGER, D SNYDERWINE, EG AF CAROTHRS, AM YUAN, W HINGERTY, BE BROYDE, S GRUNBERGER, D SNYDERWINE, EG TI MUTATION AND REPAIR INDUCED BY THE CARCINOGEN 2-(HYDROXYAMINO)-1-METHYL-6-PHENYLIMIDAZO[4,5-B]PYRIDINE (N-OH-PHIP) IN THE DIHYDROFOLATE-REDUCTASE GENE OF CHINESE-HAMSTER OVARY CELLS AND CONFORMATIONAL MODELING OF THE DG-C8-PHIP ADDUCT IN DNA SO CHEMICAL RESEARCH IN TOXICOLOGY LA English DT Article ID FOOD MUTAGEN 2-AMINO-1-METHYL-6-PHENYLIMIDAZO<4,5-B>PYRIDINE; CRYSTAL-STRUCTURE; SPLICING MUTATIONS; MAMMALIAN-CELLS; PYRIDINE PHIP; BASE-PAIRS; (+/-)-3-ALPHA,4-BETA-DIHYDROXY-1-ALPHA,2-ALPHA-EPOXY-1,2,3,4-TETRAHYDROB ENZO.; IDENTIFICATION; SEQUENCE; GUANINE AB Three experiments using 20 muM 2-(hydroxyamino)-1-methyl-6-phenylimidazo[4,5-b]pyridine (N-OH-PhIP) were performed to induce mutations in the dihydrofolate reductase (DHFR) gene of a hemizygous Chinese hamster ovary (CHO) cell line (UA21). Metabolized forms of this chemical primarily bind at the C-8 position of guanine in DNA. In total, 21 independent induced mutants were isolated and 20 were characterized. DNA sequencing showed that the preferred mutation type found in 75% of the induced DHFR- clones was G.C --> T.A single and tandem double transversions. In addition to base substitutions, one mutant carried a -1 frameshift and another one had lost the entire locus by deletion. The induced changes affected purine targets on the nontranscribed strand of the gene in nearly all of the mutants sequenced (18/19). At the time that the first two experiments were performed, the initial adduct levels were quantitated in treated cells at the mutagenic dose by P-32-postlabeling. While the induced frequency of mutation was relatively low (approximately 5 X 10(-6)), the adduct levels after a 1-h exposure of UA21 cells to 20 muM N-OH-PhIP were relatively high (13 adducts x 10(-6) nucleotides). This latter method was then employed to learn if the induced mutation frequency correlated with rapid overall genome repair of PhIP-DNA adducts. Total adduct levels, determined using DNA samples from treated cells collected after intervals of time, were reduced by about 50% after 6 h, and about 70% after 24 h. Since overall genome repair in CHO cells is relatively slow compared with preferential gene repair, the removal of dG-C8-PhIP adducts was apparently efficient. In order to better understand the mutational and repair results, we performed computational modeling to determine the lowest energy structure for the major dG-C8-PhIP adduct in a repetitively mutated duplex sequence opposite dA. Results of this analysis indicate that the PhIP-modified base resembles previous structural determinations of (deoxyguanosin-8-yl)-aminofluorene; the carcinogen is in the B-DNA minor groove and it adopts a syn conformation mispaired with an anti A. The implications of this conformational distortion in DNA structure for damage recognition by cellular repair enzymes are discussed. C1 NCI,DIV CANC ETIOL,EXPTL CARCINOGENESIS LAB,BETHESDA,MD 20892. OAK RIDGE NATL LAB,HLTH SCI RES UNIT,OAK RIDGE,TN 37831. NYU,DEPT BIOL,NEW YORK,NY 10003. RP CAROTHRS, AM (reprint author), COLUMBIA UNIV,INST CANC,701 W 168TH ST,ROOM 532,NEW YORK,NY 10027, USA. FU NCI NIH HHS [CA21111, CA28038]; NCRR NIH HHS [RR06458] NR 63 TC 40 Z9 40 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 1994 VL 7 IS 2 BP 209 EP 218 DI 10.1021/tx00038a015 PG 10 WC Chemistry, Medicinal; Chemistry, Multidisciplinary; Toxicology SC Pharmacology & Pharmacy; Chemistry; Toxicology GA ND492 UT WOS:A1994ND49200015 PM 8199311 ER PT J AU LENFANT, C AF LENFANT, C TI TRIAGE AT THE NHLBI - COMMON-SENSE SO CIRCULATION LA English DT Editorial Material RP LENFANT, C (reprint author), NIH,BETHESDA,MD 20892, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD MAR PY 1994 VL 89 IS 3 BP 945 EP 946 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA NA762 UT WOS:A1994NA76200001 PM 8124832 ER PT J AU RAGOSTA, M GIMPLE, LW GERTZ, SD DUNWIDDIE, CT VLASUK, GP HABER, HL POWERS, ER ROBERTS, WC SAREMBOCK, IJ AF RAGOSTA, M GIMPLE, LW GERTZ, SD DUNWIDDIE, CT VLASUK, GP HABER, HL POWERS, ER ROBERTS, WC SAREMBOCK, IJ TI SPECIFIC FACTOR XA INHIBITION REDUCES RESTENOSIS AFTER BALLOON ANGIOPLASTY OF ATHEROSCLEROTIC FEMORAL ARTERIES IN RABBITS SO CIRCULATION LA English DT Article DE THROMBOSIS; ANTISTASIN; PEPTIDES; COAGULATION ID TICK ANTICOAGULANT PEPTIDE; LUMINAL CORONARY ANGIOPLASTY; COAGULATION FACTOR-XA; SMOOTH-MUSCLE CELLS; ACUTE MYOCARDIAL-INFARCTION; RECOMBINANT ANTISTASIN; EXTRACELLULAR-MATRIX; INTIMAL HYPERPLASIA; ENDOTHELIAL-CELLS; POTENT INHIBITOR AB Background Balloon angioplasty of atherosclerotic arteries results in activation of the coagulation cascade. Several coagulation factors, including factor Xa and thrombin, are mitogenic for vascular smooth muscle cells in vitro and thus may play a role in restenosis after balloon angioplasty. Specific inhibition of factor Xa can be achieved with recombinant antistasin (rATS) or tick anticoagulant peptide (rTAP). We hypothesized that inhibition of Xa would limit restenosis after balloon angioplasty in an atherosclerotic rabbit model. Methods and Results Focal femoral atherosclerosis was induced by air desiccation injury and a high-cholesterol diet in 38 New Zealand White rabbits. Recombinant antistasin (n=20 arteries) or rTAP (n=14 arteries) was administered by intravenous bolus at the time of balloon angioplasty and followed by a 2-hour infusion; controls (n=21 arteries) received bolus heparin alone (150 U/kg). Therapeutic prolongation of the activated partial thromboplastin time occurred, and antithrombotic drug levels were achieved in all animals. Luminal diameter in millimeters by quantitative angiography did not differ between treatment groups before (1.1+/-0.2 for controls, 1.1+/-0.2 for rATS, and 1.1+/-0.3 for rTAP) or after balloon angioplasty (1.5+/-0.3 for controls, 1.4+/-0.2 for rATS, and 1.4+/-0.2 for rTAP). At 28 days, treatment with factor Xa inhibitors tended to result in arteries with larger luminal diameter than controls (1.2+/-0.3 for rATS, 1.2+/-0.3 for rTAP versus 1.0+/-0.3 for control, P=.09 by one-way ANOVA). Restenosis, defined as reduction in angiographic luminal diameter (in mm) from 2 hours after angioplasty to 28 days after angioplasty was less in the rATS group than in controls (-0.2+/-0.1versus -0.5+/-0.4, P<.001) and tended to be less in the rTAP group (-0.3+/-0.2 versus -0.5+/-0.4, P=.07). Quantitative histopathological analysis showed less percent cross-sectional area narrowing by plaque in both rATS- and rTAP-treated arteries compared with controls (42+/-21%, 47+/-18%, and 63+/-14%, respectively; P<.01 by one-way ANOVA). Conclusions We conclude that a 2-hour infusion of rATS or rTAP reduced angiographic restenosis and resulted in less luminal cross-sectional narrowing by plaque compared with controls. C1 UNIV VIRGINIA,SCH MED,DEPT MED,DIV CARDIOVASC,CHARLOTTESVILLE,VA 22908. HEBREW UNIV JERUSALEM,HADASSAH MED SCH,DEPT ANAT & EMBRYOL,IL-91010 JERUSALEM,ISRAEL. MERCK SHARP & DOHME LTD,W POINT,PA. CORVAS INT INC,SAN DIEGO,CA. NHLBI,PATHOL BRANCH,BETHESDA,MD 20892. NR 51 TC 93 Z9 93 U1 0 U2 0 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD MAR PY 1994 VL 89 IS 3 BP 1262 EP 1271 PG 10 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA NA762 UT WOS:A1994NA76200041 PM 8124815 ER PT J AU BIRO, S YU, ZX FU, YM SMALE, G SASSE, J SANCHEZ, J FERRANS, VJ CASSCELLS, W AF BIRO, S YU, ZX FU, YM SMALE, G SASSE, J SANCHEZ, J FERRANS, VJ CASSCELLS, W TI EXPRESSION AND SUBCELLULAR-DISTRIBUTION OF BASIC FIBROBLAST GROWTH-FACTOR ARE REGULATED DURING MIGRATION OF ENDOTHELIAL-CELLS SO CIRCULATION RESEARCH LA English DT Article DE ENDOTHELIAL CELLS; REENDOTHELIALIZATION; WOUND HEALING; IMMUNOCYTOCHEMISTRY; BASIC FIBROBLAST; GROWTH FACTOR ID SMOOTH-MUSCLE CELLS; EXTRACELLULAR-MATRIX; STIMULATED ANGIOGENESIS; MONOCLONAL-ANTIBODIES; BIOLOGICAL-ACTIVITY; INVITRO; PROLIFERATION; HEPARIN; CHEMOTAXIS; CULTURE AB Migration of endothelial cells is involved in normal and pathological angiogenesis and in reendothelialization after vascular injury or rupture of atherosclerotic plaques. Several types of endothelial cells are known to synthesize basic fibroblast growth factor (bFGF); in some of these, migration is increased by exogenous bFGF and inhibited by anti-bFGF antibodies. Using immunocytochemical techniques and RNase protection analysis, we studied endothelial cells from bovine coronary arteries and veins as well as from adrenal microvessels. We found that bFGF mRNA and peptide were present in confluent endothelial cells and were upregulated during migration stimulated by removal of some cells from the monolayer. During migration, extracellular matrix stores of bFGF were depleted, and bFGF immunoreactivity began to accumulate in the cytoplasm of endothelial cells between 2 and 6 hours. After migration had begun, but before the initiation of DNA synthesis, bFGF immunoreactivity increased in the nuclei and nucleoli. Exogenous bFGF stimulated endothelial migration, and antibodies to bFGF markedly inhibited migration, suggesting that an intracrine function of nuclear bFGF is not sufficient for cell migration. In all three types of endothelial cells studied, bFGF was identified as an endogenous regulator, but not as the sole regulator, of migration. Moreover, bFGF expression and subcellular localization were found to be regulated during endothelial cell migration. (Circ Res. 1994;74:485-494.) C1 NHLBI,CARDIOL BRANCH,BETHESDA,MD 20892. NHLBI,PATHOL BRANCH,BETHESDA,MD 20892. SHRINERS HOSP CRIPPLED CHILDREN,TAMPA,FL. FU NHLBI NIH HHS [R55HL 60-01] NR 55 TC 52 Z9 52 U1 0 U2 1 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7330 J9 CIRC RES JI Circ.Res. PD MAR PY 1994 VL 74 IS 3 BP 485 EP 494 PG 10 WC Cardiac & Cardiovascular Systems; Hematology; Peripheral Vascular Disease SC Cardiovascular System & Cardiology; Hematology GA MZ583 UT WOS:A1994MZ58300014 PM 8118957 ER PT J AU RUDOLPH, DL COLIGAN, JE LAL, RB AF RUDOLPH, DL COLIGAN, JE LAL, RB TI DETECTION OF ANTIBODIES TO TRANSACTIVATOR PROTEIN (P40(TAXI)) OF HUMAN T-CELL LYMPHOTROPIC VIRUS TYPE-I BY A SYNTHETIC PEPTIDE-BASED ASSAY SO CLINICAL AND DIAGNOSTIC LABORATORY IMMUNOLOGY LA English DT Article ID ANTI-TAX ANTIBODY; HTLV-I; MONOCLONAL-ANTIBODIES; CHILD TRANSMISSION; LEUKEMIA; DISEASES; MYELOPATHY; INFECTION; EPITOPES; CARRIERS AB Antibodies to human T-cell lymphotropic virus type I (HTLV-I) cans-activator protein (p40(taxI)) were determined in serum specimens from individuals infected with HTLV-I (n = 138) and HTLV-II (n = 19). Western blot (immunoblot) analysis using recombinant tax demonstrated the presence of anti-tax antibodies in 96% of patients (25 of 26) with HTLV-I-associated myelopathy, 43% of those (20 of 46) with adult T-cell leukemia, and 61% of asymptomatic HTLV-I blood donors (40 of 66); only one of the HTLV-II specimens reacted with the recombinant tar protein. synthetic peptides (Tax8(106-125), Tax22(316-335), Tax-23(331-3)50, and Tax-24(336-353)) representing the immunodominant epitopes of p40(taxI) detected anti-tax antibodies in 66 (48%), 50 (36%), 66 (48%), and 64 (46%) of 138 HTLV-I-positive specimens, respectively. An enzyme immunoassay using an equimolar ratio of these four peptides allowed sensitive detection of anti-tax antibodies in 96% of patients (25 of 26) with HTLV-I-associated myelopathy,, 52% of adult T-cell leukemia patients (24 of 46), and 62% of asymptomatic HTLV-I-infected donors (41 of 66). The synthetic peptide-based cocktail assay aas HTLV-I specific, since none of the HTLV-II-infected specimens reacted with these peptides. Interestingly, the corresponding regions from the HTLV-II tax protein, Tax8II(106-125), and Tax-22II(312-331) did not react with either HTLV-II or HTLV-I specimens. Thus, a synthetic peptide-based assay composed of immunodominant epitopes located towards the amino terminus and at the C terminus of p40(taxI) provides a reliable and sensitive assay for the detection of anti-tax antibodies in seroepidemiologic studies. C1 CTR DIS CONTROL,NATL CTR INFECT DIS,DIV VIRAL & RICKETTSIAL DIS,RETROVIRUS DIS BRANCH,ATLANTA,GA 30333. NIAID,BIOL RESOURCES BRANCH,BETHESDA,MD 20892. NR 28 TC 6 Z9 6 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 1071-412X J9 CLIN DIAGN LAB IMMUN JI Clin. Diagn. Lab. Immunol. PD MAR PY 1994 VL 1 IS 2 BP 176 EP 181 PG 6 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA PT562 UT WOS:A1994PT56200010 PM 7496941 ER PT J AU CARL, M ISAACS, SN KAUR, M KE, JK TAM, AW YARBOUGH, PO REYES, GR AF CARL, M ISAACS, SN KAUR, M KE, JK TAM, AW YARBOUGH, PO REYES, GR TI EXPRESSION OF HEPATITIS-E VIRUS PUTATIVE STRUCTURAL PROTEINS IN RECOMBINANT VACCINIA VIRUSES SO CLINICAL AND DIAGNOSTIC LABORATORY IMMUNOLOGY LA English DT Note ID NON-B HEPATITIS; DEPENDENT RNA-POLYMERASE; TRANSMITTED NON-A; EPIDEMIC NON-A; IDENTIFICATION; EPITOPES; STRAIN; ASSAY; INDIA; HEV AB Hepatitis E virus (HEV) is a polyadenylated, positive-stranded RNA virus which is a major cause of enterically transmitted non-A, non-B hepatitis in many developing countries. The viral genome contains three different open reading frames (ORFs): ORF1, which is believed to encode nonstructural proteins, and ORF2 and ORF3, which are believed to encode structural proteins. The full-length putative structural proteins encoded by ORF2 and ORF3 of HEV have been cloned and expressed in recombinant vaccinia virus. Proteins encoded by ORF2 and ORF3 when expressed in vaccinia virus are recognized by pooled sera obtained from individuals with acute hepatitis E. Vaccinia expressed viral gene products of HEV will have utility in characterizing the cell-mediated immune response to HEV. C1 USN,MED RES INST,ACCELERATED PROD DEV PROGRAM,BETHESDA,MD. NIAID,BETHESDA,MD 20892. GENELABS INC,DEPT MOLEC VIROL,REDWOOD CITY,CA 94063. NR 33 TC 10 Z9 10 U1 0 U2 3 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 1071-412X J9 CLIN DIAGN LAB IMMUN JI Clin. Diagn. Lab. Immunol. PD MAR PY 1994 VL 1 IS 2 BP 253 EP 256 PG 4 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA PT562 UT WOS:A1994PT56200027 PM 7496958 ER PT J AU KROLL, MH CHESLER, R AF KROLL, MH CHESLER, R TI NONLINEARITY OF HIGH-DENSITY-LIPOPROTEIN CHOLESTEROL DETERMINATIONS IS MATRIX DEPENDENT SO CLINICAL CHEMISTRY LA English DT Article DE VARIATION, SOURCE OF; SAMPLE TREATMENT; INTERMETHOD COMPARISON ID ENZYMATIC METHODS; LYOPHILIZATION; SERUM AB The majority of methods for determining high-density lipoprotein (HDL) cholesterol failed the 1991 College of American Pathologists (CAP) linearity survey (sets LN2-A,B,C). We hypothesized that they failed because of the survey material matrix. We evaluated linearity with dextran sulfate or phosphotungstate as the precipitating reagents for several methods: Ektachem; TDx; Sigma; Dimension; Cobas Fara, with Roche reagents; and the Hitachi 736, with precipitating reagents from Boehringer Mannheim Diagnostics. We tested CAP survey material, Sigma HDL-cholesterol control material, and a fresh serum pool for linearity, using the polynomial method. All of the methods were nonlinear for the CAP material and for the controls precipitated after dilution. Five of eight methods were linear for the control materials precipitated before dilution. All methods but one were linear for the serum pool. These results demonstrate that the source of the nonlinearity is located in the precipitation step and depends on the sample matrix. RP KROLL, MH (reprint author), NIH,CTR CLIN,DEPT CLIN PATHOL,BLDG 10,ROOM 2C-407,BETHESDA,MD 20892, USA. NR 15 TC 8 Z9 8 U1 0 U2 1 PU AMER ASSOC CLINICAL CHEMISTRY PI WASHINGTON PA 2101 L STREET NW, SUITE 202, WASHINGTON, DC 20037-1526 SN 0009-9147 J9 CLIN CHEM JI Clin. Chem. PD MAR PY 1994 VL 40 IS 3 BP 389 EP 394 PG 6 WC Medical Laboratory Technology SC Medical Laboratory Technology GA NC389 UT WOS:A1994NC38900009 PM 8131273 ER PT J AU TOLLERUD, DJ KURMAN, CC NELSON, DL BROWN, LM MALONEY, EM BLATTNER, WA AF TOLLERUD, DJ KURMAN, CC NELSON, DL BROWN, LM MALONEY, EM BLATTNER, WA TI RACIAL VARIATION IN SERUM-SOLUBLE INTERLEUKIN-2 RECEPTOR LEVELS - A POPULATION-BASED STUDY OF HEALTHY SMOKERS AND NONSMOKERS SO CLINICAL IMMUNOLOGY AND IMMUNOPATHOLOGY LA English DT Note ID CIGARETTE SMOKERS; IMMUNOGLOBULIN LEVELS; CELL SUBSETS; SMOKING; DISEASE; HYPERRESPONSIVENESS; ASSOCIATION; ASTHMA; WHITES; IMMUNE AB To investigate the influence of race and cigarette smoking on serum levels of soluble interleukin-2 receptors (sIL-2R), we studied a population-based cohort of 282 white and 173 black adults, ages 20-69 years. Serum sIL-2R concentrations in this healthy population ranged from 146 to 2623 U/ml. Whites had significantly higher sIL-2R levels than blacks (455 versus 365 U/ml; P < 0.001), and cigarette smokers had significantly higher levels than nonsmokers (508 versus 420 U/ml; P = 0.01). White smokers had the highest levels (550 U/ml); white nonsmokers and black smokers had intermediate levels (455 and 450 U/ml, respectively); and black nonsmokers had the lowest levels (365 U/ml). Smoking cessation appeared to normalize sIL-2R levels; exsmokers who had not smoked for at least 2 years had sIL-2R levels similar to those of never smokers. These data demonstrate the wide range of serum sIL-2R concentrations found in normal healthy adults and the significant influence of race and cigarette smoking. Further investigation of this natural heterogeneity may provide insights into the mechanisms underlying genetic and environmental influences on this important immunologic parameter. (C) 1994 Academic Press, Inc. C1 NCI,METAB BRANCH,BETHESDA,MD 20892. NCI,EPIDEMIOL & BIOSTAT PROGRAM,BETHESDA,MD 20892. RP TOLLERUD, DJ (reprint author), UNIV PITTSBURGH,GRAD SCH PUBL HLTH,DEPT ENVIRONM & OCCUPAT HLTH,GSPH A-718,130 DESOTO ST,PITTSBURGH,PA 15261, USA. FU NCI NIH HHS [YO1-CP-30500] NR 32 TC 21 Z9 21 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 0090-1229 J9 CLIN IMMUNOL IMMUNOP JI Clin. Immunol. Immunopathol. PD MAR PY 1994 VL 70 IS 3 BP 274 EP 279 DI 10.1006/clin.1994.1040 PG 6 WC Immunology; Pathology SC Immunology; Pathology GA MY664 UT WOS:A1994MY66400014 PM 8313664 ER PT J AU RANDOLPH, C GOLD, JM KOZORA, E CULLUM, CM HERMANN, BP WYLER, AR AF RANDOLPH, C GOLD, JM KOZORA, E CULLUM, CM HERMANN, BP WYLER, AR TI ESTIMATING MEMORY FUNCTION - DISPARITY OF WECHSLER MEMORY SCALE-REVISED AND CALIFORNIA VERBAL-LEARNING TEST INDEXES IN CLINICAL AND NORMAL SAMPLES SO CLINICAL NEUROPSYCHOLOGIST LA English DT Article AB Although a high degree of convergence has been reported between the California Verbal Learning Test (CVLT) and the Wechsler Memory Scale-Revised (WMS-R), standard scores from these tests may not provide commensurate global estimations of memory function. Data were reviewed from 161 subjects who had taken both tests, including schizophrenic (n=33) and temporal-lobe epilepsy (n=31) patients and 97 normal volunteers. The patient group performed approximately one standard deviation below the normal mean on the WMS-R indexes, but three standard deviations below the normal mean on CVLT indices. The normal volunteers, who were well-educated as a group, performed approximately one standard deviation above the population-based mean on the WMS-R (commensurate with their IQ level), but at the mean of the CVLT reference sample. These findings suggest that the standardization samples for these two tests are not representative of the same population. The CVLT normative reference sample appears to have been higher functioning than the WMS-R sample, and may also have been characterized by a narrower range of memory function. The implications of these findings with respect to the clinical evaluation of memory are discussed. C1 NINCDS,EXPTL THERAPEUT BRANCH,BETHESDA,MD 20892. NIMH,IRP,CLIN & RES SERV BRANCH,WASHINGTON,DC 20032. UNIV COLORADO,HLTH SCI CTR,DENVER,CO 80262. BAPTIST MEM HOSP,CTR EPICARE,MEMPHIS,TN 38146. UNIV MEMPHIS,DEPT PSYCHIAT,MEMPHIS,TN. UNIV MEMPHIS,DEPT NEUROSURG,MEMPHIS,TN. SEMMES MURPHEY CLIN,MEMPHIS,TN. NR 15 TC 26 Z9 26 U1 0 U2 2 PU SWETS ZEITLINGER PUBLISHERS PI LISSE PA P O BOX 825, 2160 SZ LISSE, NETHERLANDS SN 0920-1637 J9 CLIN NEUROPSYCHOL JI Clin. Neuropsychol. PD MAR PY 1994 VL 8 IS 1 BP 99 EP 108 DI 10.1080/13854049408401547 PG 10 WC Psychology, Clinical; Clinical Neurology; Psychology SC Psychology; Neurosciences & Neurology GA NB867 UT WOS:A1994NB86700007 ER PT J AU BONKOVSKY, FO AF BONKOVSKY, FO TI ETHICAL ISSUES IN PERINATAL HIV SO CLINICS IN PERINATOLOGY LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; WOMEN; AIDS; INFECTION; PREGNANCY; RISK RP BONKOVSKY, FO (reprint author), NIH,BIOETH PROGRAM,BLDG 10,ROOM 1C116,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 21 TC 5 Z9 5 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0095-5108 J9 CLIN PERINATOL JI Clin. Perinatol. PD MAR PY 1994 VL 21 IS 1 BP 15 EP 28 PG 14 WC Obstetrics & Gynecology; Pediatrics SC Obstetrics & Gynecology; Pediatrics GA NC958 UT WOS:A1994NC95800003 PM 8013183 ER PT J AU ZEICHNER, SL AF ZEICHNER, SL TI THE MOLECULAR-BIOLOGY OF HIV - INSIGHTS INTO PATHOGENESIS AND TARGETS FOR THERAPY SO CLINICS IN PERINATOLOGY LA English DT Review ID HUMAN-IMMUNODEFICIENCY-VIRUS; LONG TERMINAL REPEAT; NF-KAPPA-B; HTLV-III/LAV ENVELOPE; TRANS-ACTIVATOR GENE; TYPE-1 VPU PROTEIN; PRINCIPAL NEUTRALIZING DETERMINANT; REVERSE-TRANSCRIPTASE INHIBITORS; TAR-INDEPENDENT ACTIVATION; TUMOR NECROSIS FACTOR RP ZEICHNER, SL (reprint author), NCI,PEDIAT BRANCH,BLDG 10,ROOM 13N240,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 250 TC 4 Z9 4 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 1994 VL 21 IS 1 BP 39 EP 73 PG 35 WC Obstetrics & Gynecology; Pediatrics SC Obstetrics & Gynecology; Pediatrics GA NC958 UT WOS:A1994NC95800005 PM 8013186 ER PT J AU SCHUTZ, CG CHILCOAT, HD ANTHONY, JC AF SCHUTZ, CG CHILCOAT, HD ANTHONY, JC TI THE ASSOCIATION BETWEEN SNIFFING INHALANTS AND INJECTING DRUGS SO COMPREHENSIVE PSYCHIATRY LA English DT Article ID SOLVENT USE; ABUSE; ADDICTS; HISTORY C1 JOHNS HOPKINS UNIV,SCH HYG & PUBL HLTH,DEPT MENTAL HYG,BALTIMORE,MD 21218. RP SCHUTZ, CG (reprint author), NIDA,ADDICT RES CTR,ETIOL BRANCH,POB 5180,BALTIMORE,MD 21224, USA. NR 19 TC 42 Z9 42 U1 3 U2 3 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 1994 VL 35 IS 2 BP 99 EP 105 DI 10.1016/0010-440X(94)90053-K PG 7 WC Psychiatry SC Psychiatry GA NB005 UT WOS:A1994NB00500002 PM 8187483 ER PT J AU ROY, M COLLIER, B ROY, A AF ROY, M COLLIER, B ROY, A TI EXCESS OF DEPRESSIVE SYMPTOMS AND LIFE EVENTS AMONG DIABETICS SO COMPREHENSIVE PSYCHIATRY LA English DT Article ID PSYCHIATRIC ASPECTS; MELLITUS; SEX C1 NEI,BETHESDA,MD 20892. NIAAA,BETHESDA,MD. NR 25 TC 13 Z9 13 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 1994 VL 35 IS 2 BP 129 EP 131 DI 10.1016/0010-440X(94)90057-O PG 3 WC Psychiatry SC Psychiatry GA NB005 UT WOS:A1994NB00500006 PM 8187476 ER PT J AU MARTIN, SE AF MARTIN, SE TI WOMEN IN CONTROL - THE ROLE OF WOMEN IN LAW-ENFORCEMENT - HEIDENSOHN,F SO CONTEMPORARY SOCIOLOGY-A JOURNAL OF REVIEWS LA English DT Book Review RP MARTIN, SE (reprint author), NIAAA,ROCKVILLE,MD 20852, USA. NR 1 TC 1 Z9 1 U1 0 U2 1 PU AMER SOCIOLOGICAL ASSOC PI WASHINGTON PA 1722 N ST NW, WASHINGTON, DC 20036-2981 SN 0094-3061 J9 CONTEMP SOCIOL JI Contemp. Sociol.-J. Rev. PD MAR PY 1994 VL 23 IS 2 BP 298 EP 299 DI 10.2307/2075264 PG 2 WC Sociology SC Sociology GA PE004 UT WOS:A1994PE00400110 ER PT J AU AZARI, NP PETTIGREW, KD PIETRINI, P HORWITZ, B SCHAPIRO, MB AF AZARI, NP PETTIGREW, KD PIETRINI, P HORWITZ, B SCHAPIRO, MB TI DETECTION OF AN ALZHEIMER-DISEASE PATTERN OF CEREBRAL METABOLISM IN DOWN-SYNDROME SO DEMENTIA LA English DT Article DE POSITRON EMISSION TOMOGRAPHY; (18)FDG; BRAIN; DOWN SYNDROME; ALZHEIMERS DISEASE; DISCRIMINANT ANALYSIS ID GLUCOSE-UTILIZATION; DOWNS-SYNDROME; TRANSMISSION MEASUREMENTS; PET; DEMENTIA; ADULTS; RATES; INTERCORRELATIONS; STATE; CT AB Correlational analysis of cerebral metabolic (rCMRglc) data obtained with positron emission tomography (PET) assesses group differences and has demonstrated reduced frontal-parietal rCMRglc interdependencies in Alzheimer's disease (AD). A multivariate analysis of rCMRglc data assesses individual differences. We recently identified discriminant functions, reflecting frontal-parietal rCMRglc interdependencies, that separated AD from control subjects. To test if the functions would identify an AD rCMRglc pattern in older Down syndrome (DS) adults with (DS DAT+) or without (DS DAT-) dementia, we applied the functions to longitudinal rCMRglc data in: young DS (n = 15), DS DAT- (n = 10), DS DAT+ (n = 4), and young controls (n = 15). Ah DS DAT+ and some of the later DS DAT- scans were classified as AD. The results provide additional validation of the functions and suggest their utility for the early detection of AD. C1 NIMH,DIV EPIDEMIOL APPL & SERV RES,BETHESDA,MD 20892. RP AZARI, NP (reprint author), NIA,NEUROSCI LAB,BLDG 10,ROOM 6C414,BETHESDA,MD 20892, USA. NR 37 TC 13 Z9 13 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 1994 VL 5 IS 2 BP 69 EP 78 DI 10.1159/000106700 PG 10 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA ND985 UT WOS:A1994ND98500003 PM 8038869 ER PT J AU PEARSON, JL COHN, DA COWAN, PA COWAN, CP AF PEARSON, JL COHN, DA COWAN, PA COWAN, CP TI EARNED-SECURITY AND CONTINUOUS-SECURITY IN ADULT ATTACHMENT - RELATION TO DEPRESSIVE SYMPTOMATOLOGY AND PARENTING STYLE SO DEVELOPMENT AND PSYCHOPATHOLOGY LA English DT Article ID CHILDHOOD ATTACHMENT; WORKING MODELS; EXPERIENCE; MOTHERS; REPRESENTATION; INFANT; CYCLE AB The secure working model classification of adult attachment, as derived from Main and Goldwyn's (in press) Adult Attachment Interview scoring system, was considered in terms of earned-security and continuous-security. Earned-security was a classification given to adults who described difficult, early relationships with parents, but who also had current secure working models as indicated by high coherency scores; continuous-security referred to a classification in which individuals described secure early attachment relationship with parents and current secure working models. Working models of attachment were classified as earned-secure, continuous-secure, or insecure in a sample of 40 parents of preschool children. Comparisons among the classifications were conducted on a measure of depressive symptoms and two sets of ratings of observed parenting styles. Adults with earned-secure classifications had comparable depressive symptomatology to insecures, with 30% of the insecures, 40% of the earned-secures, and only 10% of the continuous-secures having scores exceeding the clinical cut-off. The rate of depressive symptomatology in the earned-secure group suggests that reconstructions of past difficulties may remain emotional liabilities despite a current secure working model. With regard to parenting styles with their preschoolers, the behavior of earned-secure parents was comparable to that of the continuous-secures. This refinement in conceptualizing secure working models suggests ways for understanding variation in pathways to competent parenting as well as a possible perspective on how adults' adverse early experiences may continue to place them and their children at risk. C1 UNIV VIRGINIA,CHARLOTTESVILLE,VA 22903. UNIV CALIF BERKELEY,BERKELEY,CA 94720. RP PEARSON, JL (reprint author), NIMH,ROOM 18-105,5600 FISHERS LANE,ROCKVILLE,MD 20857, USA. NR 63 TC 116 Z9 116 U1 2 U2 12 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 40 WEST 20TH STREET, NEW YORK, NY 10011-4211 SN 0954-5794 J9 DEV PSYCHOPATHOL JI Dev. Psychopathol. PD SPR PY 1994 VL 6 IS 2 BP 359 EP 373 DI 10.1017/S0954579400004636 PG 15 WC Psychology, Developmental SC Psychology GA NJ524 UT WOS:A1994NJ52400008 ER PT J AU NAKASHIMA, M NAGASAWA, H YAMADA, Y REDDI, AH AF NAKASHIMA, M NAGASAWA, H YAMADA, Y REDDI, AH TI REGULATORY ROLE OF TRANSFORMING GROWTH-FACTOR-BETA, BONE MORPHOGENETIC PROTEIN-2, AND PROTEIN-4 ON GENE-EXPRESSION OF EXTRACELLULAR-MATRIX PROTEINS AND DIFFERENTIATION OF DENTAL-PULP CELLS SO DEVELOPMENTAL BIOLOGY LA English DT Article ID ALKALINE-PHOSPHATASE ACTIVITY; OSTEOBLAST-LIKE CELLS; DEVELOPING RAT MOLARS; INSITU HYBRIDIZATION; COLLAGEN-SYNTHESIS; MESENCHYMAL CELLS; RNA EXPRESSION; MESSENGER-RNA; INHIBITS PROLIFERATION; ALLOGENEIC DENTIN AB The expression of developmental stage-specific genes during pulp cell differentiation into preodontoblasts was examined in bovine adult pulp cell culture. When proliferation was down-regulated after 14 days of primary culture, expression of fibronectin and type I and type III collagen mRNAs was increased. Expression of alkaline phosphatase was gradually increased, and mRNA for osteocalcin, a marker of preodontoblast, appeared just before the onset of mineralization. Contrarily, in expanded culture, the expression of mRNA for the extracellular matrix proteins was gradually increased from the beginning of culture up to Day 28. Similarly, mRNA levels of alkaline phosphatase and osteocalcin were also increased gradually. Expression of TGF-beta 1 mRNA disappeared on Day 21 in the primary culture when expression of alkaline phosphatase mRNA Fi;as increased. BMP-4 mRNA was expressed on Day 14 when the expression of the extracellular matrix proteins was increased. BMP-2 mRNA was expressed on Day 28 when osteocalcin appeared. Recombinant TGF-beta 1 inhibited alkaline phosphatase activity, while BMP-2 and BMP-I stimulated it. BMP-I increased expression of alpha 1(I) collagen mRNA, and BMP-2 increased osteocalcin synthesis. These results demonstrate the regulatory role of these TGF-P superfamily members on the gene expression of extracellular matrix proteins and the differentiation of pulp cells into preodontoblasts. (C) 1994 Academic Press, Inc. C1 NIDR,DEV BIOL LAB,BETHESDA,MD 20892. JOHNS HOPKINS UNIV,SCH MED,MUSCULOSKELETAL CELL BIOL LAB,BALTIMORE,MD 21205. RP NAKASHIMA, M (reprint author), KYUSHU UNIV,FAC DENT,DEPT CONSERVAT DENT,FUKUOKA 812,JAPAN. NR 67 TC 150 Z9 158 U1 0 U2 2 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0012-1606 J9 DEV BIOL JI Dev. Biol. PD MAR PY 1994 VL 162 IS 1 BP 18 EP 28 DI 10.1006/dbio.1994.1063 PG 11 WC Developmental Biology SC Developmental Biology GA MZ920 UT WOS:A1994MZ92000003 PM 8125185 ER PT J AU MORASSO, MI JAMRICH, M SARGENT, TD AF MORASSO, MI JAMRICH, M SARGENT, TD TI THE HOMEODOMAIN GENE XENOPUS DISTAL-LESS-LIKE-2 (XDLL-2) IS REGULATED BY A CONSERVED MECHANISM IN AMPHIBIAN AND MAMMALIAN EPIDERMIS SO DEVELOPMENTAL BIOLOGY LA English DT Article ID TRANSCRIPTION FACTOR AP-2; DISTAL-LESS; LIMB DEVELOPMENT; RESTRICTED EXPRESSION; DEVELOPING FOREBRAIN; DROSOPHILA EMBRYO; LAEVIS EMBRYOS; HOMEOBOX GENES; KERATIN GENE; DIFFERENTIATION AB Xenopus Distal-less-like-2 (Xdll-2) is a gene encoding a homeodomain protein expressed predominantly in the epidermis of frog embryos. We report here that this epidermal expression is specified by a regulatory 5' flanking DNA region located within 933 bp of the start of transcription. This regulatory DNA also confers upon a globin reporter gene calcium-inducible expression in cultured murine keratinocytes and induction-dependent repression in frog ectodermal cells treated in vitro with activin A. These results reveal a new example of phylogenetically conserved, tissue-specific transcriptional regulation of a homeodomain gene. (C) 1994 Academic Press, Inc. C1 NICHHD,MOLEC GENET LAB,BETHESDA,MD 20892. US FDA,DIV CELLULAR & GENE THERAPY,DEV BIOL LAB,BETHESDA,MD 20892. NR 71 TC 22 Z9 22 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0012-1606 J9 DEV BIOL JI Dev. Biol. PD MAR PY 1994 VL 162 IS 1 BP 267 EP 276 DI 10.1006/dbio.1994.1084 PG 10 WC Developmental Biology SC Developmental Biology GA MZ920 UT WOS:A1994MZ92000024 PM 7907299 ER PT J AU LITTLE, RR ENGLAND, JD WIEDMEYER, HM MADSEN, RW PETTITT, DJ KNOWLER, WC GOLDSTEIN, DE AF LITTLE, RR ENGLAND, JD WIEDMEYER, HM MADSEN, RW PETTITT, DJ KNOWLER, WC GOLDSTEIN, DE TI GLYCATED HEMOGLOBIN PREDICTS PROGRESSION TO DIABETES-MELLITUS IN PIMA-INDIANS WITH IMPAIRED GLUCOSE-TOLERANCE SO DIABETOLOGIA LA English DT Article DE FOLLOW-UP STUDY; GLYCATED HB; HBA(1C); IGT; PIMA INDIANS ID FASTING PLASMA-GLUCOSE; GLYCOSYLATED HEMOGLOBIN; UTILITY; HBA1 AB Glycated haemoglobin could offer several practical advantages over the OGTT for assessing glucose metabolism. Initial cross-sectional studies (1983-1985) on 381 subjects (mostly Pima Indians) described the relationship between HbA(1c) (a specific glycated Hb) and the OGTT. We performed follow-up OGTTs and HbA(1c) measurements on 257 of these same subjects 1.6-6.1 years later. Subjects were again grouped according to both the result of the OGTT (normal,IGT or diabetes, by WHO criteria) and HbA(1c) result: (normal or elevated based on mean +/- 1.96 SD of normal). Of 66 subjects with IGT at baseline, 47 (71 %) had normal HbA(1c) and 19 (29 %) had elevated HbA(1c). Twenty-six (39 %) of these subjects had diabetes at follow-up. Of these subjects with IGT, a significantly greater percentage of subjects with elevated HbA(1c) at baseline (68 %) showed worsening to diabetes than those with a normal-HbA(1c) (28%); (chi-square=7.8, df=1, p < 0.01). Thus, in subjects with IGT, glycated Hb may be a useful predictor of progression to diabetes. C1 UNIV MISSOURI, SCH MED, DEPT CHILD HLTH, COLUMBIA, MO USA. UNIV MISSOURI, SCH MED, DEPT STAT, COLUMBIA, MO USA. NIDDKD, DIABET & ARTHRITIS EPIDEMIOL SECT, PHOENIX, AZ USA. RP LITTLE, RR (reprint author), UNIV MISSOURI, SCH MED, DEPT PATHOL M263, 1 HOSP DR, COLUMBIA, MO 65212 USA. OI Little, Randie/0000-0001-6450-8012 NR 23 TC 33 Z9 35 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0012-186X EI 1432-0428 J9 DIABETOLOGIA JI Diabetologia PD MAR PY 1994 VL 37 IS 3 BP 252 EP 256 DI 10.1007/BF00398051 PG 5 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA NA160 UT WOS:A1994NA16000005 PM 8174838 ER PT J AU BURNSTOCK, G FISCHER, B HOYLE, CHV MAILLARD, M ZIGANSHIN, AU BRIZZOLARA, AL VONISAKOVICS, A BOYER, JL HARDEN, TK JACOBSON, KA AF BURNSTOCK, G FISCHER, B HOYLE, CHV MAILLARD, M ZIGANSHIN, AU BRIZZOLARA, AL VONISAKOVICS, A BOYER, JL HARDEN, TK JACOBSON, KA TI STRUCTURE-ACTIVITY-RELATIONSHIPS FOR DERIVATIVES OF ADENOSINE-5'-TRIPHOSPHATE AS AGONISTS AT P-2 PURINOCEPTORS - HETEROGENEITY WITHIN P-2X AND P-2Y SUBTYPES SO DRUG DEVELOPMENT RESEARCH LA English DT Article DE ATP; PURINOCEPTORS; SMOOTH MUSCLE; NUCLEOTIDES; PHOSPHOLIPASE C ID PIG TAENIA-COLI; RAT MAST-CELLS; PHOSPHOLIPASE-C; SMOOTH-MUSCLE; VAS-DEFERENS; NERVE-STIMULATION; URINARY-BLADDER; ATP; RECEPTOR; P2-PURINOCEPTOR AB The structure-activity relationships for a variety of adenine nucleotide analogues at P-2X- and P-2Y-purinoceptors were investigated. Compounds formed by structural modifications of the ATP molecule including substitutions of the purine ring (C2, C8, N1, and N-6-substituents, and a uridine base instead of adenine), the ribose moiety (2' and 3'-positions), and the triphosphate group (lower phosphates, bridging oxygen substitution, and cyclization) were prepared. Pharmacological activity at P-2Y-purinoceptors was assayed in the guinea pig taenia coli, endothelial cells of the rabbit aorta, smooth muscle of the rabbit mesenteric artery, and turkey erythrocyte membranes. Activity at P-2X-purinoceptors was assayed in the rabbit saphenous artery and the guinea-pig vas deferens and urinary bladder. Some of the analogues displayed selectivity, or even specificity, for either the P-2X- or the P-2Y-purinoceptors. Certain analogues displayed selectivity or specificity within the P-2X- or P-2Y-purinoceptor superfamilies, giving hints about possible subclasses. For example, 8-(6-aminohexylamino)ATP and 2',3'-isopropylidene-AMP were selective for endothelial P-2Y-purinoceptors over P-2Y-purinoceptors in the guinea pig taenia coli, rabbit aorta, and turkey erythrocytes. These compounds were both inactive at P-2X-purinoceptors. The potent agonist N-6-methyl ATP and the somewhat less potent agonist 2'-deoxy-ATP were selective for P-2Y-purinoceptors in the guinea pig taenia coli, but were inactive at P-2X-purinoceptors and the vascular P-2Y-purinoceptors. 3'-Benzylamino-3'-deoxyATP was very potent at the P-2X-purinoceptors in the guinea pig vas deferens and bladder, but not in the rabbit saphenous artery and was inactive at P-2Y receptors. These data suggest that specific compounds can be developed that can be utilized to activate putative subtypes of the P-2X- and P-2Y-purinoceptor classes. (C) 1994 Wiley-Liss, Inc. C1 NIDDKD, BIOORGAN CHEM LAB, BETHESDA, MD 20892 USA. UCL, DEPT ANAT & DEV BIOL, LONDON, ENGLAND. UNIV N CAROLINA, SCH MED, DEPT PHARMACOL, CHAPEL HILL, NC USA. KAZAN MED INST, KAZAN, RUSSIA. RI Jacobson, Kenneth/A-1530-2009; OI Jacobson, Kenneth/0000-0001-8104-1493; Ziganshin, Ayrat/0000-0002-9087-7927 FU Intramural NIH HHS [Z01 DK031116-20, Z99 DK999999]; NIGMS NIH HHS [R01 GM038213] NR 61 TC 81 Z9 81 U1 0 U2 3 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0272-4391 J9 DRUG DEVELOP RES JI Drug Dev. Res. PD MAR PY 1994 VL 31 IS 3 BP 206 EP 219 DI 10.1002/ddr.430310308 PG 14 WC Chemistry, Medicinal; Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA NA159 UT WOS:A1994NA15900007 PM 22962511 ER PT J AU FORKERT, PG REDZA, ZM MANGOS, S PARK, SS TAM, SP AF FORKERT, PG REDZA, ZM MANGOS, S PARK, SS TAM, SP TI INDUCTION AND REGULATION OF CYP2E1 IN MURINE LIVER AFTER ACUTE AND CHRONIC ACETONE ADMINISTRATION SO DRUG METABOLISM AND DISPOSITION LA English DT Article ID RAT-LIVER; MICROSOMAL CYTOCHROME-P-450; NITROSODIMETHYLAMINE DEMETHYLASE; NITROSAMINE METABOLISM; MONOCLONAL-ANTIBODIES; PARA-NITROPHENOL; ETHANOL; GENE; OXIDATION; P450IIE1 AB The effects of acute and chronic acetone administration on hepatic Cyp2e1 were investigated in mice. Acute treatment consisted of a single dose of acetone (5 ml/kg) given intragastrically, whereas the chronic regimen consisted of 1% acetone in drinking water for 8 days. We examined 1) relative induction of Cyp2e1 protein by immunoblotting, 2) relative induction of enzyme catalytic activity (p-nitrophenol hydroxylation), and 3) Cyp2e1 mRNA levels associated with acute and chronic treatment regimens. Western immunoblotting, using a monoclonal antibody (Mab 1-98-1) specific for rat ethanol-inducible P-450, detected a band of M(r) 51,000 in liver microsomes of both control and acetone-treated mice. Densitometric quantitation showed significant enhancement of the intensity of this band by 4.4- and 5.3-fold after acute and chronic acetone treatments, respectively. Hydroxylation of p-nitrophenol was increased 2.3-fold in microsomes from livers exposed acutely to acetone, as compared with an increase of 3.7-fold in microsomes from livers exposed chroni cally. The induction of Cyp2e1 protein, as well as of catalytic activity, by acetone was not accompanied by significant alterations in the levels of Cyp2e1 mRNA. These results demonstrate a difference in induced increases of Cyp2e1 between acute and chronic acetone treatments: significantly higher induction of both protein and catalytic activity is induced by treatment under chronic vs. acute conditions. C1 QUEENS UNIV,DEPT MED,KINGSTON K7L 3N6,ON,CANADA. QUEENS UNIV,DEPT BIOCHEM,KINGSTON K7L 3N6,ON,CANADA. NCI,FCRF,DIV CANC ETIOL,COMPARAT CARCINOGENESIS LAB,FREDERICK,MD. RP FORKERT, PG (reprint author), QUEENS UNIV,DEPT ANAT & CELL BIOL,KINGSTON K7L 3N6,ON,CANADA. NR 48 TC 38 Z9 38 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0090-9556 J9 DRUG METAB DISPOS JI Drug Metab. Dispos. PD MAR-APR PY 1994 VL 22 IS 2 BP 248 EP 253 PG 6 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA NB520 UT WOS:A1994NB52000011 PM 8013281 ER PT J AU KLECKER, RW JAMISDOW, CA EGORIN, MJ ERKMEN, K PARKER, RJ STEVENS, R COLLIN, JM AF KLECKER, RW JAMISDOW, CA EGORIN, MJ ERKMEN, K PARKER, RJ STEVENS, R COLLIN, JM TI EFFECT OF CIMETIDINE, PROBENECID, AND KETOCONAZOLE ON THE DISTRIBUTION, BILIARY-SECRETION, AND METABOLISM OF [H-3] TAXOL IN THE SPRAGUE-DAWLEY RAT SO DRUG METABOLISM AND DISPOSITION LA English DT Article AB Male Sprague-Dawley rats had their bile ducts cannulated and were dosed with [H-3]taxol (2 mg/kg, 68-77 mu Ci/mg) as a continuous intravenous infusion for 6 hr so that the plasma concentrations, tissue distribution, metabolism, and biliary secretion of taxol could be studied. Defining potential drug-drug interactions of taxol with cimetidine (90 mg/kg), probenecid (360 mg/kg), and ketoconazole (50 mg/kg) was motivated by frequent concomitant clinical use or the potential to reduce clearance of taxol so that lower doses could be used. At 6 hr, rats were killed. Samples of blood (plasma), lung, spleen, liver, kidney, heart, skeletal muscle, brain, testes, and fat were obtained. Taxol and metabolites were measured by total radioactivity counting and HPLC separation using on-line radioactivity detection. Concentrations of taxol in plasma increased to 0.19 mu M in the control rats and did not reach steady-state by 6 hr. Lung, spleen, liver, and kidneys had the greatest tissue taxol concentrations [4.7-5.7 nmol/g (mu M)] and were > 25-fold higher than the simultaneous 6-hr plasma taxol concentration. Taxol concentrations in brain and testes were negligible, 0.06 and 0.07 nmol/g, respectively. Radioactive metabolites were not found in plasma or most tissues. Only liver had appreciable concentrations of taxol and metabolites; however, > 80% of hepatic radioactivity was parent taxol. Through 6 hr of collection, 24% of the dose was secreted in the bile similar to 38% of which was as parent taxol. Cimetidine had no effect on the distribution, metabolism, or elimination of [H-3]taxol. Probenecid did not effect tissue distribution or plasma concentrations of (axel. Probenecid decreased the biliary secretion of taxol and metabolites by 50%. Rats pretreated with ketoconazole had biliary secretion of taxol, and metabolites decreased to 25% of control with a concomitant increase in plasma taxol concentration. C1 NCI, BETHESDA, MD 20892 USA. UNIV MARYLAND, CTR CANC, BALTIMORE, MD 21201 USA. UNIV MARYLAND, SCH MED, DEPT MED, BALTIMORE, MD 21201 USA. RP KLECKER, RW (reprint author), US FDA, 4 RES COURT, ROOM 314, ROCKVILLE, MD 20850 USA. NR 12 TC 34 Z9 36 U1 0 U2 0 PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3995 USA SN 0090-9556 EI 1521-009X J9 DRUG METAB DISPOS JI Drug Metab. Dispos. PD MAR-APR PY 1994 VL 22 IS 2 BP 254 EP 258 PG 5 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA NB520 UT WOS:A1994NB52000012 PM 7912177 ER PT J AU WIRTH, PJ AF WIRTH, PJ TI 2-DIMENSIONAL POLYACRYLAMIDE-GEL ELECTROPHORESIS IN EXPERIMENTAL HEPATOCARCINOGENESIS STUDIES SO ELECTROPHORESIS LA English DT Review ID LIVER EPITHELIAL-CELLS; TUMOR SUPPRESSOR GENES; GLUTATHIONE S-TRANSFERASE; HEPATOMA ASCITES-CELLS; RAT CULTURED-CELLS; CHEMICAL HEPATOCARCINOGENESIS; OVAL CELLS; 2-DIMENSIONAL ELECTROPHORESIS; NEOPLASTIC TRANSFORMATION; SEQUENTIAL-ANALYSIS AB High resolution two-dimensional polyacrylamide gel electrophoresis (2-D PAGE) in combination with computer-assisted densitometry was used to analyze sequential changes in polypeptide expression during chemically (aflatoxin B1; AFB), spontaneously, and oncogene (v-Ha-ras, v-raf, and v-raf/v-myc)-induced experimental rat hepatocarcinogenesis. Two-dimensional mapping of [S-35]methionine and [P-32]orthophosphate-labeled whole cell lysate and nuclear polypeptides revealed subsets of polypeptides specific for each transformation modality in the in vitro rat liver epithelial (RLE) transformation model. Many of the observed changes in whole cell lysate preparations were localized to specific subcellular organelles. Significant alterations in the expression of the extracellular matrix protein, fibronectin, as well as tropomyosin- and intermediate filament-related polypeptides (vimentin, P-tubulin, cytokeratins 8, 14, and 18, and actin) were observed among the various transformant cell lines. Whereas alterations in the tropomyosin isoforms appeared to be transformation specific, concomitant modulation of intermediate filament expression was related more to the differentiation state of the individual cell lines than to the transformed phenotype. To integrate protein and DNA information of polypeptides believed to be critically involved during cellular transformation, N-terminal amino acid microsequencing of selected nuclear polypeptides was performed. Preliminary results suggest that N-terminal blockage of rat liver epithelial nuclear proteins to be minor (similar to 20%) with sequencing sensitivity of one pmol. These studies extend our on-going efforts toward the establishment of computerized database of rat liver epithelial cellular proteins (Wirth et al., Electrophoresis, 1991, 12, 931-954) to aid in the delineation of polypeptides critically involved in cellular growth and differentiation as well as transformation. RP WIRTH, PJ (reprint author), NCI,EXPTL CARCINOGENESIS LAB,BIOPOLYMER CHEM SECT,BLDG 37,ROOM 3C28,BETHESDA,MD 20892, USA. NR 142 TC 10 Z9 10 U1 0 U2 2 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-APR PY 1994 VL 15 IS 3-4 BP 358 EP 371 DI 10.1002/elps.1150150155 PG 14 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA NL211 UT WOS:A1994NL21100004 PM 8055866 ER PT J AU OTTERSON, GA FLYNN, GC KRATZKE, RA COXON, A JOHNSTON, PG KAYE, FJ AF OTTERSON, GA FLYNN, GC KRATZKE, RA COXON, A JOHNSTON, PG KAYE, FJ TI STCH ENCODES THE ATPASE CORE OF A MICROSOMAL STRESS70 PROTEIN SO EMBO JOURNAL LA English DT Article DE ATPASE; CDNA CLONING; MICROSOME; PROTEIN CHAPERONE; STRESS70 ID CHAIN BINDING-PROTEIN; MAJOR HEAT-SHOCK; GLUCOSE-REGULATED PROTEIN; PEPTIDE-BINDING; INTRACELLULAR-TRANSPORT; DROSOPHILA-MELANOGASTER; ESCHERICHIA-COLI; GENE; HSP70; SEQUENCE AB The stress70 protein chaperone family plays a central role in the processing of cytosolic and secretory proteins. We have cloned a human cDNA, designated Stch, that is conserved in rat tissues and which encodes a novel microsome-associated member of the stress70 protein chaperone family. Stch mRNA is constitutively expressed in all human cell types and is induced by incubation with the calcium ionophore A23187, but not by exposure to heat shock. Inspection of the predicted amino acid sequence reveals that the STCH product contains a unique hydrophobic leader sequence and shares homology within the amino terminal domains of the stress70 gene family, but has a 50 residue insertion within the ATP-binding domains and truncates the carboxyl terminal peptide-binding region. Immunofluorescent and subcellular analyses show that STCH migrates predominantly as a 60 kDa species and is enriched in a membrane-bound microsome fraction. In contrast to purified BiP and dnaK, however, STCH demonstrates ATPase activity that is independent of peptide stimulation. Stch, therefore, encodes a calcium-inducible, microsome-associated ATPase activity with properties similar to a proteolytically cleaved N-terminal HSC70/BiP fragment. This truncated stress70 molecule may allow increased diversity in cellular responses to protein processing requirements. C1 NCI,NAVY MED ONCOL BRANCH,BETHESDA,MD 20889. UNIV OREGON,INST MOLEC BIOL,EUGENE,OR 97403. RI kaye, frederic/E-2437-2011 NR 37 TC 35 Z9 40 U1 0 U2 1 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0261-4189 J9 EMBO J JI Embo J. PD MAR 1 PY 1994 VL 13 IS 5 BP 1216 EP 1225 PG 10 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA NA288 UT WOS:A1994NA28800023 PM 8131751 ER PT J AU YANG, NY TENG, CT AF YANG, NY TENG, CT TI IDENTIFICATION OF COUP-TF BINDING-ELEMENT IN THE HUMAN LACTOFERRIN PROMOTER SO ENDOCRINE LA English DT Article ID LONG TERMINAL REPEAT; STEROID-RECEPTOR SUPERFAMILY; RETINOIC ACID RECEPTORS; MOLONEY LEUKEMIA-VIRUS; TRANSCRIPTION FACTOR; THYROID-HORMONE; DNA-BINDING; ESTROGEN-RECEPTOR; LACTOTRANSFERRIN GENE; RESPONSE ELEMENTS AB Human lactoferrin gene contains a functional, estrogen-response element (ERE) that is responsible for the estrogen-stimulation of the gene in uterine endometrium. A DNA fragment (-418 to -340), including the ERE, is selectively protected by nuclear protein of endometrial (RL95) and mammary gland (HBL100) cells from DNAase I digestion. This region was divided into three footprint areas; FP1, FP2 and FP3. FP2 (-373 to -360) contains a potential GATA-3 binding element; FP3 (-355 to -340) houses the ERE. At least three nuclear proteins were involved in binding to the FP1 (-418 to -378) and porduced three protein-DNA complexes in the electrophoresis mobility shift assay (EMSA). One protein-DNA complex was formed with the 5' end and two were formed with the 3' end of FP1. There were three potential transcription factor binding elements located at the 3' end region (5'-ACCTTCAAGGTCATCTG-3'); a palindromic COUP-TF binding element (5'-ACCTTCAAGGT-3'); a consensus ELF (5'-TCAAGGTCA-3') and HLH (5'-CATCTG-3') binding elements. By using the COUP-TF antibody and ov-COUP-TF binding element in EMSA, we demonstrated that one of the protein-DNA complexes (C2) that formed with this DNA fragment involved COUP-TF. It was also shown that COUP-TF bound to a direct repeat of AGGTCA at -363 to -350 (FP2 and FP3 region) of the lactoferrin promoter. The GGTCA at 3' half of the direct repeat overlapped with ERE. Thus, the currently identified two COUP-TF binding elements were both overlapped by a positive transcription factor binding element. The unique organization of overlapping positive and negative transcription factor binding elements in human lactoferrin promoter provides an opportunity to study the complicated regulation that modulates its expression. C1 NIEHS,REPROD & DEV TOXICOL LAB,RES TRIANGLE PK,NC 27709. NR 56 TC 8 Z9 8 U1 0 U2 0 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 SN 0969-711X J9 ENDOCRINE JI Endocrine PD MAR PY 1994 VL 2 IS 3 BP 241 EP 248 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA PL771 UT WOS:A1994PL77100012 ER PT J AU TIMME, TL TRUONG, LD MERZ, VW KREBS, T KADMON, D FLANDERS, KC PARK, SH THOMPSON, TC AF TIMME, TL TRUONG, LD MERZ, VW KREBS, T KADMON, D FLANDERS, KC PARK, SH THOMPSON, TC TI MESENCHYMAL-EPITHELIAL INTERACTIONS AND TRANSFORMING GROWTH-FACTOR-BETA EXPRESSION DURING MOUSE PROSTATE MORPHOGENESIS SO ENDOCRINOLOGY LA English DT Article ID UROGENITAL SINUS MESENCHYME; RAT VENTRAL PROSTATE; ANDROGEN RECEPTOR EXPRESSION; RODENT URINARY-BLADDER; MESSENGER-RNA LEVELS; C-MYC; ADULT TISSUES; INDUCTION; FACTOR-BETA-1; TRACT AB To explore the role of transforming growth factor-beta (TGF beta) isoforms and other growth-related genes during prostate morphogenesis in the mouse, we examined mRNA levels in fetal day 17 urogenital sinus, mesenchyme (UGM), and epithelium (UGE) as well as in the ventral, dorsal, and anterior lobes of the adult prostate. In addition, we used antiserum specific for extracellular TGF beta 1 in immunohistochemical studies to localize accumulation of the TGF beta 1 isozyme in the above tissues as well as those derived from fetal day 19 and neonatal mouse prostate. Differential patterns of expression in fetal and adult tissues were seen. TGF beta 1, -beta 2, and -beta 3 expression was substantially elevated in UGM compared to that in UGE, yet only TGF beta 1, not TGF beta 2 or TGF beta 3, mRNA levels were sustained in adult prostate tissues. High levels of accumulation of TGF beta 1 were demonstrated by immunohistochemistry in the mesenchymal compartment compared to those in the epithelial compartment throughout development. Interestingly, the highest levels of TGF beta 1 appeared in areas of active epithelial duct formation and delineated the mesenchymal architectural changes necessary for ductal network formation. Additional studies revealed that levels of mRNAs for other genes involved in tissue remodeling and growth were also elevated in UGM compared to those in UGE. Tissue plasminogen activator, urokinase plasminogen activator, androgen receptor, and c-myc mRNA levels were also elevated in UGM compared to UGE. Interestingly, whereas tissue plasminogen activator mRNA levels, like those of TGF beta 2 and -beta 3, were barely detectable in adult prostatic tissues, mRNA levels for urokinase plasminogen activator, androgen receptor, and c-myc were readily detected and expressed in a lobe-specific fashion. Overall, these data indicate that expression of TGF beta 1 isoforms and other growth-related genes is associated with mesenchymal cells in areas of active morphogenesis during prostate development and provide objective molecular and cellular information regarding mediators of mesenchymal-epithelial interactions in prostate. C1 BAYLOR COLL MED, SCOTT DEPT UROL, HOUSTON, TX 77030 USA. BAYLOR COLL MED, DEPT CELL BIOL, HOUSTON, TX 77030 USA. BAYLOR COLL MED, DEPT PATHOL, HOUSTON, TX 77030 USA. VET AFFAIRS MED CTR, UROL RES LAB, HOUSTON, TX 77030 USA. NCI, CHEMOPREVENT LAB, BETHESDA, MD 20892 USA. FU NIDDK NIH HHS [DK-43523] NR 34 TC 72 Z9 72 U1 0 U2 0 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0013-7227 EI 1945-7170 J9 ENDOCRINOLOGY JI Endocrinology PD MAR PY 1994 VL 134 IS 3 BP 1039 EP 1045 DI 10.1210/en.134.3.1039 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA MZ443 UT WOS:A1994MZ44300007 PM 8119140 ER PT J AU KLEIN, KO MUNSON, PJ BACHER, JD CUTLER, GB BARON, J AF KLEIN, KO MUNSON, PJ BACHER, JD CUTLER, GB BARON, J TI LINEAR GROWTH IN THE RABBIT IS CONTINUOUS, NOT SALTATORY SO ENDOCRINOLOGY LA English DT Article ID LONGITUDINAL BONE-GROWTH; DEXAMETHASONE; PLATE; RAT AB A recent report in Science suggests that human growth occurs in brief bursts, up to 1.65 cm in a single day, separated by extended periods of stasis, lasting up to 63 days. Thus, the organism is proposed to alternate between two states, one with a growth velocity of zero, the other with a mean annualized growth velocity greater than 350 cm/yr. These observations, if correct, suggest the existence of a previously unsuspected hormonal mechanism capable of abruptly switching growth plate cell division on and off and of synchronizing cellular growth not only throughout the growth plate, but presumably throughout all the growth plates in the organism. However, the experimental assessment of short-term growth velocity in the human faces the formidable obstacle of a technical error of measurement that exceeds the mean daily growth rate. Accordingly, we tested the saltatory growth hypothesis by measuring proximal tibial growth in the rabbit, a model in which daily growth rate could be measured more than 15 times more accurately than in the human. The model of saltation and stasis predicts a majority of daily growth velocities clustered around zero, and a minority of high growth velocities, that is, a bimodal distribution. The frequency distribution of observed daily growth velocities instead approximated a single Gaussian distribution, indicating continuous growth. We conclude that linear growth, in the most accurate mammalian system yet studied, is continuous, not saltatory. C1 NICHHD,DEV ENDOCRINOL BRANCH,BETHESDA,MD 20892. NIH,DIV COMP RES & TECHNOL,ANALYT BIOSTAT BRANCH,BETHESDA,MD 20892. NIH,NATL CTR RES RESOURCES,VET RESOURCES PROGRAN,SURG RADIOL & PHARM SECT,BETHESDA,MD 20892. NR 15 TC 12 Z9 12 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 1994 VL 134 IS 3 BP 1317 EP 1320 DI 10.1210/en.134.3.1317 PG 4 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA MZ443 UT WOS:A1994MZ44300045 PM 8119172 ER PT J AU GOSIEWSKA, A WILSON, S KWON, D PETERKOFSKY, B AF GOSIEWSKA, A WILSON, S KWON, D PETERKOFSKY, B TI EVIDENCE FOR AN IN-VIVO ROLE OF INSULIN-LIKE GROWTH FACTOR-BINDING PROTEIN-1 AND PROTEIN-2 AS INHIBITORS OF COLLAGEN GENE-EXPRESSION IN VITAMIN-C-DEFICIENT AND FASTED GUINEA-PIGS SO ENDOCRINOLOGY LA English DT Article ID MESSENGER RIBONUCLEIC-ACID; HUMAN-SKIN FIBROBLASTS; FACTOR-I; RNA; RAT; CARTILAGE; SERUM; PROTEOGLYCAN; STIMULATION; INVITRO AB Acutely scorbutic and fasted (vitamin C-supplemented) guinea pigs exhibit decreased collagen gene expression associated with weight loss. We recently demonstrated that circulating insulin-like growth factor-binding protein-1 and -2 (IGFBP-1 and -2) are induced in these deficiencies, and that removal of IGFBP-1 and -2 from serum of such animals by specific antibodies reverses inhibition of cellular IGF-I-dependent functions, including collagen and DNA synthesis. Here we investigated the kinetics of induction of IGFBP-1 and -2 relative to suppression of collagen gene expression. Guinea pigs were fasted for 10-96 h, with 3-24% weight loss, or received an ascorbate-free diet for up to 4 weeks, with 5-28% weight loss during the third and fourth weeks (phase II of scurvy). In both deficiencies, there was noncoordinate regulation of collagen mRNA expression in tissues. Type I collagen mRNA concentrations in skin decreased rapidly after 5-10% weight loss and reached about 10% of normal levels, whereas in bone, there was a later, and not as extensive, decrease. The concentration of cartilage type II collagen mRNA decreased rapidly initially, but then remained at 40-50% of normal. Circulating IGF-I concentrations remained normal during the period when collagen gene expression was initially suppressed, although there was a later decrease. In contrast, mRNAs for IGFBP-1 and -2 and the circulating proteins were induced before or concomitantly with the suppression of collagen gene expression. The ability of fasted or scorbutic guinea pig sera to inhibit IGF-I action in cells increased in parallel with IGFBP activity ([I-125]IGF-I binding), which, in turn, mainly reflected the concentration of IGFBP-1 in sera. Serum insulin may be the primary regulator of the IGFBPs. Its levels were decreased to 10-13% of normal when weight loss commenced, whereas cortisol levels, although increased, did not correlate with the induction of IGFBPs. The overall results taken together with our recent findings from cell culture experiments are compatible with circulating IGFBP-1 and -2 acting as inhibitors of collagen gene expression by blocking IGF-I action during fasting and phase II of vitamin C deficiency. C1 NCI, BIOCHEM LAB, BETHESDA, MD 20892 USA. NR 44 TC 39 Z9 39 U1 0 U2 2 PU ENDOCRINE SOC PI WASHINGTON PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA SN 0013-7227 EI 1945-7170 J9 ENDOCRINOLOGY JI Endocrinology PD MAR PY 1994 VL 134 IS 3 BP 1329 EP 1339 DI 10.1210/en.134.3.1329 PG 11 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA MZ443 UT WOS:A1994MZ44300047 PM 7509738 ER PT J AU ZHENG, LX STOJILKOVIC, SS HUNYADY, L KRSMANOVIC, LZ CATT, KJ AF ZHENG, LX STOJILKOVIC, SS HUNYADY, L KRSMANOVIC, LZ CATT, KJ TI SEQUENTIAL ACTIVATION OF PHOSPHOLIPASE-C AND PHOSPHOLIPASE-D IN AGONIST-STIMULATED GONADOTROPHS SO ENDOCRINOLOGY LA English DT Article ID PROTEIN-KINASE-C; ADRENAL GLOMERULOSA CELLS; SIGNAL TRANSDUCTION; PITUITARY-CELLS; PHOSPHATIDYLCHOLINE HYDROLYSIS; SECRETORY RESPONSES; HORMONE RECEPTOR; ANGIOTENSIN-II; CALCIUM; DIACYLGLYCEROL AB The contributions of phospholipase-C and -D to diacylglycerol (DG) formation during agonist-induced cell signaling were investigated in rat pituitary cells and alpha T3-1 gonadotrophs. In both cell types, GnRH caused a biphasic increase in DG formation, with an initial spike within 60 sec, followed by a larger and sustained rise to reach a second peak after 15 min of stimulation. Both phases of DG production were temporally correlated with inositol 1,4,5-trisphosphate [Ins(1,4,5)P-3] formation, consistent with the dependence of DG formation on phospholipase-C-mediated phosphoinositide hydrolysis. However, the ability of GnRH to stimulate phosphatidylethanol (PEt) in the presence of ethanol suggested that phospholipase-D may also participate in DG formation. Two inhibitors of phospholipase-C-dependent phosphoinositide hydrolysis, U73122 and neomycin sulfate, reduced the PEt as well as the Ins(1,4,5)P-3 response to GnRH, indicating that phospholipase-D is activated during phospholipase-C-dependent signaling in pituitary gonadotrophs. The production of both DG and PEt was increased by treatment with the active phorbol ester phorbol 12-myristate 13-acetate (PMA), but not with inactive 4 alpha-phorbol 13-didecanoate, indicating that stimulation of protein kinase-C leads to activation of phospholipase-D. In accord with this, GnRH- and PMA-induced elevations of DG and PEt production were attenuated or abolished in protein kinase-C-depleted cells. In contrast, short and long term stimulation with PMA had no effect on basal inositol phosphate production. Also, GnRH-induced inositol phosphate production was not affected by protein kinase-C depletion. Finally, U73122 and neomycin sulfate did not inhibit PMA-induced PEt formation. These data indicate that GnRH activates a dual phospholipase pathway in a sequential and synchronized manner; phospholipase-C initiates the biphasic increase in Ins(1,4,5)P-3 and DG formation, and protein kinase-C mediates the integration of phospholipase-D into the signaling response during the sustained phase of agonist stimulation. C1 NICHHD, ENDOCRINOL & REPROD RES BRANCH, BETHESDA, MD 20892 USA. NR 34 TC 51 Z9 51 U1 0 U2 0 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0013-7227 EI 1945-7170 J9 ENDOCRINOLOGY JI Endocrinology PD MAR PY 1994 VL 134 IS 3 BP 1446 EP 1454 DI 10.1210/en.134.3.1446 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA MZ443 UT WOS:A1994MZ44300062 PM 8119185 ER PT J AU RAJAN, AS LUO, ZT KAHN, BB COMSTOCK, JP CUSHMAN, SW BOYD, AE AF RAJAN, AS LUO, ZT KAHN, BB COMSTOCK, JP CUSHMAN, SW BOYD, AE TI DO ADIPOCYTES CONTAIN HIGH-AFFINITY SULFONYLUREA RECEPTORS SO ENDOCRINOLOGY LA English DT Article ID INSULIN-STIMULATED TRANSLOCATION; GLUCOSE-TRANSPORT ACTIVITY; ISOLATED RAT ADIPOCYTES; 3T3-L1 ADIPOCYTES; BETA-CELLS; DIFFERENTIAL REGULATION; HEXOSE-TRANSPORT; PLASMA-MEMBRANE; ADIPOSE-CELLS; FREE CALCIUM AB Sulfonylureas interact with specific, high affinity receptors on the pancreatic P-cell to close ATP-sensitive K+ channels, depolarize the cell, activate Ca2+ influx through voltage-dependent Ca2+ channels, and trigger insulin secretion. We tested the hypothesis that sulfonylureas promote glucose uptake into 3T3-L1 cells or isolated rat adipocytes by similar mechanisms. Using I-125-labeled 5-iodo-2-hydroxyglyburide and either equilibrium binding or photoaffinity labeling, a high affinity sulfonylurea receptor was not found on plasma membranes of either the 3T3-L1 cells or rat adipocytes. Furthermore, glyburide did not inhibit Rb-86(+) efflux (a marker for ATP-sensitive K+ channel conductance), increase free cytosolic calcium in adipocytes or 3T3-L1 cells, or increase basal or insulin-stimulated glucose uptake into 3T3-L1 cells or rat adipocytes. Parallel studies using a hamster insulin-secreting tumor cell line (HIT cells) easily demonstrated both the receptor and biological effects of glyburide on free cytosolic calcium and insulin secretion. Thus, rat adipocytes and 3T3-L1 cells do not possess the high affinity sulfonylurea receptor or respond to glyburide alone. We conclude that the antidiabetogenic effects of sulfonylureas are not mediated by a direct action of sulfonylureas to increase glucose uptake into adipose tissue and suggest that the major locus for sulfonylurea action is the beta-cell. C1 BAYLOR COLL MED,DEPT MED,DIV ENDOCRINOL,HOUSTON,TX 77030. BETH ISRAEL HOSP,DIABET UNIT,BOSTON,MA 02215. HARVARD UNIV,SCH MED,BOSTON,MA 02115. NIDDKD,DIABET BRANCH,EXPTL DIABET METAB & NUTR SECT,BETHESDA,MD 20892. TUFTS UNIV NEW ENGLAND MED CTR,DIV ENDOCRINOL METAB DIABET & MOLEC MED,BOSTON,MA 02111. FU NIDDK NIH HHS [DK-34447, DK-27635, DK-41898] NR 42 TC 10 Z9 11 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 1994 VL 134 IS 3 BP 1581 EP 1588 DI 10.1210/en.134.3.1581 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA MZ443 UT WOS:A1994MZ44300079 PM 8119201 ER PT J AU RAO, GN AF RAO, GN TI DIET FOR FISCHER-344 RATS IN LONG-TERM STUDIES SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Note RP RAO, GN (reprint author), NIEHS,MD A0-01,POB 12233,RES TRIANGLE PK,NC 27709, USA. NR 9 TC 4 Z9 4 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 1994 VL 102 IS 3 BP 314 EP 315 PG 2 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA NJ416 UT WOS:A1994NJ41600014 PM 8033874 ER PT J AU SHY, C GREENBERG, R WINN, D AF SHY, C GREENBERG, R WINN, D TI SENTINEL HEALTH EVENTS OF ENVIRONMENTAL CONTAMINATION - A CONSENSUS STATEMENT SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Note ID UNITED-STATES; SURVEILLANCE C1 UNIV N CAROLINA,CHAPEL HILL,NC 27599. EMORY UNIV,SCH PUBL HLTH,ATLANTA,GA 30329. NIDR,BETHESDA,MD 20892. NR 17 TC 9 Z9 9 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 1994 VL 102 IS 3 BP 316 EP 317 PG 2 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA NJ416 UT WOS:A1994NJ41600015 PM 8033875 ER PT J AU BOORMAN, GA AF BOORMAN, GA TI NASAL TOXICITY AND DOSIMETRY OF INHALED XENOBIOTICS - IMPLICATIONS FOR HUMAN HEALTH SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Note RP BOORMAN, GA (reprint author), NIEHS,POB 12233,RES TRIANGLE PK,NC 27709, USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU NATL INST ENVIRON HEALTH SCI PI RES TRIANGLE PK PA PO BOX 12233, RES TRIANGLE PK, NC 27709 SN 0091-6765 J9 ENVIRON HEALTH PERSP JI Environ. Health Perspect. PD MAR PY 1994 VL 102 IS 3 BP 318 EP 319 PG 2 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA NJ416 UT WOS:A1994NJ41600016 PM 7913439 ER PT J AU STURGEON, SR HARTGE, P SILVERMAN, DT KANTOR, AF LINEHAN, WM LYNCH, C HOOVER, RN AF STURGEON, SR HARTGE, P SILVERMAN, DT KANTOR, AF LINEHAN, WM LYNCH, C HOOVER, RN TI ASSOCIATIONS BETWEEN BLADDER-CANCER RISK-FACTORS AND TUMOR STAGE AND GRADE AT DIAGNOSIS SO EPIDEMIOLOGY LA English DT Article DE GRADE; STAGE; BLADDER NEOPLASMS; SMOKING; COFFEE; RACE; OCCUPATION; EDUCATION; CASE-CONTROL STUDY AB Using data on 1,860 bladder cancer cases and 3,934 population-based controls from the National Bladder Cancer Study, we examined associations between suspected bladder cancer risk factors and tumor stage and grade. Employment in a high-risk occupation was associated-with the entire clinical spectrum of bladder cancer rather than a particular tumor stage or grade. For example,relative risks (RR) were similar for noninvasive and invasive disease (1.5 and 1.6, respectively). Cigarette smoking also increased risk of the entire clinical spectrum of bladder cancer, but the more advanced the stage, the stronger the effect. For example, relative risks of noninvasive and invasive bladder cancer for current heavy smokers were 3.0 and 5.2, respectively. Cigarette Smoking was associated with higher risk of low-grade than high-grade tumors, once stage of disease was taken into account. Compared with whites, nonwhites were at a lower risk of noninvasive bladder cancer (RR = 0.4) but at similar risk of invasive bladder cancer (RR = 1.1), a pattern indicating racial differences in health practices related to bladder cancer detection. History Of urinary tract infections and bladder stones was associated with increasing relative risks for advanced tumor stage. Heavy artificial sweetener Use was associated with higher-grade, poorly differentiated tumors. Coffee consumption and family history of bladder cancer were not consist entry associated with tumor stage or grade. Overall, different clinical presentations of bladder cancer share most suspected bladder cancer risk factors, including employment in a high-risk occupation and cigarette smoking. RP STURGEON, SR (reprint author), NCI,ENVIRONM EPIDEMIOL BRANCH,EXECUT PLAZA N,ROOM 443,BETHESDA,MD 20892, USA. NR 0 TC 66 Z9 68 U1 1 U2 5 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 1044-3983 J9 EPIDEMIOLOGY JI Epidemiology PD MAR PY 1994 VL 5 IS 2 BP 218 EP 225 DI 10.1097/00001648-199403000-00012 PG 8 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA MZ613 UT WOS:A1994MZ61300012 PM 8172997 ER PT J AU SUBAR, AF FREY, CM HARLAN, LC KAHLE, L AF SUBAR, AF FREY, CM HARLAN, LC KAHLE, L TI DIFFERENCES IN REPORTED FOOD FREQUENCY BY SEASON OF QUESTIONNAIRE ADMINISTRATION - THE 1987 NATIONAL-HEALTH INTERVIEW SURVEY SO EPIDEMIOLOGY LA English DT Article DE DIETARY ASSESSMENT; DIET; SEASONALITY; FOOD INTAKE; DATA COLLECTION; BIAS; MISCLASSIFICATION AB We assessed seasonal reporting bias in a 59-item food frequency questionnaire (FFQ) administered throughout 1 year using data from the 1987 National Health Interview Survey (N = 20,143 adults). Few meaningful differences were found in the proportion of individuals reporting rarely or-never consuming a: food by season of questionnaire administration. Seasonal reporting bias is evident in FFQs, however, and appears to be due to reporting most recent consumption Using gender-specific median servings per week, an analysis using logistic regression showed that the estimated proportion of individuals reporting food intake at greater than the yearly: median differed:between any two seasons by at least 5% of the population for 22 foods. We compared gender-specific quintiles of selected nutrients/food groups for the whole year and each season; these showed that quintile assignment never varied by mere than one adjacent quintile. The most frequent shift in quintile assignment, involving as many as 18.5 % of women in the summer, occurred for citrus fruits. The intake biases are small and do not greatly affect population estimates if the FFQ is administered in all seasons, but they may somewhat affect classification of individuals into quantiles for some foods/nutrients. RP SUBAR, AF (reprint author), NCI,DIV CANC PREVENT & CONTROL,900 ROCKVILLE PIKE,EPN 313,BETHESDA,MD 20892, USA. NR 0 TC 37 Z9 38 U1 0 U2 9 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 1044-3983 J9 EPIDEMIOLOGY JI Epidemiology PD MAR PY 1994 VL 5 IS 2 BP 226 EP 233 DI 10.1097/00001648-199403000-00013 PG 8 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA MZ613 UT WOS:A1994MZ61300013 PM 8172998 ER PT J AU HEYES, MP SAITO, K DEVINSKY, O NADI, NS AF HEYES, MP SAITO, K DEVINSKY, O NADI, NS TI KYNURENINE PATHWAY METABOLITES IN CEREBROSPINAL-FLUID AND SERUM IN COMPLEX PARTIAL SEIZURES SO EPILEPSIA LA English DT Article DE KYNURENIC ACID; QUINOLINIC ACID; 3-HYDROXYKYNURENINE; CEREBROSPINAL FLUID; SEIZURES; HUMAN ID QUINOLINIC ACID CONCENTRATIONS; HUMAN-BRAIN TISSUE; AMINO-ACIDS; CEREBRAL-CORTEX; L-TRYPTOPHAN; RAT-BRAIN; QUANTIFICATION; CHROMATOGRAPHY; INCREASES; INJECTION AB The kynurenine pathway metabolites, quinolinic acid (QUIN) and L-kynurenine are convulsants, whereas kynurenic acid (KYNA) is an antagonist of excitatory amino acid receptors. Imbalances in the concentrations of these metabolites have been implicated in the etiology of human seizure disorders. In the present study, L-kynurenine and QUIN concentrations in both cerebrospinal fluid (CSF) and serum were reduced in patients with intractable complex partial seizures (CPS) in both the postictal period (15-75 min after a seizure) and the interictal period (absence of seizure for >24 h) as compared with neurologically normal control subjects. Linear regression analyses and analysis of covariance showed that the reductions in serum QUIN and L-kynurenine were correlated to blood antiepileptic medication. L-Tryptophan (L-TRP) levels also tended to be lower in both CSF and serum of the seizure patients. CSF KYNA and serum 3-hydroxykynurenine concentrations were not affected in seizure patients, whereas serum levels of KYNA were reduced. 3-Hydroxykynurenine was not detected in the CSF of either control or seizure patients. The results do not support a role for a generalized reduction in KYNA concentrations or an increased ratio of QUIN:KYNA, or increases in CSF L-kynurenine in initiation and maintenance of intractable CPS humans. C1 NYU,HOSP JOINT DIS,SCH MED,DEPT NEUROL,NEW YORK,NY 10003. NINCDS,NEURONAL EXCITABIL SECT,BETHESDA,MD 20892. RP HEYES, MP (reprint author), NIMH,CLIN SCI LAB,ANALYT BIOCHEM SECT,BLDG 10,ROOM 3D40,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 41 TC 34 Z9 34 U1 1 U2 3 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0013-9580 J9 EPILEPSIA JI Epilepsia PD MAR-APR PY 1994 VL 35 IS 2 BP 251 EP 257 DI 10.1111/j.1528-1157.1994.tb02428.x PG 7 WC Clinical Neurology SC Neurosciences & Neurology GA NH701 UT WOS:A1994NH70100001 PM 8156942 ER PT J AU DEMARIA, A COLOMBINI, S SCHNITTMAN, SM MORETTA, L AF DEMARIA, A COLOMBINI, S SCHNITTMAN, SM MORETTA, L TI CD8(+) CYTOLYTIC T-LYMPHOCYTES BECOME INFECTED IN-VITRO IN THE PROCESS OF KILLING HIV-1-INFECTED TARGET-CELLS SO EUROPEAN JOURNAL OF IMMUNOLOGY LA English DT Article DE HIV; TRANSMISSION; ANTIGEN-SPECIFIC; CYTOTOXIC; T LYMPHOCYTES ID HUMAN-IMMUNODEFICIENCY-VIRUS; HUMAN PERIPHERAL-BLOOD; HIV; AIDS; SUSCEPTIBILITY; EXPRESSION; INDUCTION; INVITRO; CD4 AB In the present study the requirements for in vitro infection of antigen-specific CD8(+) cytotoxic T lymphocytes (CTL) with human immunodeficiency virus -1 (HIV-1) were investigated. CD3(+)CD8(+)CD4(-) HIV-1 nef-specific CTL become infected with HIV-1 after short-term co-culture with HLA-matched HIV-1-infected CD20(+) B lymphoblastoid cells (B-LCL) which are specifically killed. Similar results were observed with an allospecific CD8(+) CTL population. In addition, co-culture experiments showed that once infected with HIV-1, these CD8(+) CTL could spread the infection further to uninfected CD4(+) lymphocytes. In contrast, CD8(+) CTL did not become infected with HIV-1 when co-cultured with HLA-mismatched HIV-1-infected B-LCL which are not killed. These observations in vitro could have relevance in peripheral lymphoid organs contributing to the progressive decrease of HIV-specific CD8(+) CTL activity that is associated with the progression to AIDS. C1 OSPED SAN MARTINO GENOVA,DEPT INFECT DIS,GENOA,ITALY. NIAID,MED BRANCH,BETHESDA,MD 20892. NCI,TUMOR CELL BIOL LAB,BETHESDA,MD 20892. UNIV TURIN,DEPT EXPTL MED,NOVARA,ITALY. IST NAZL RIC CANC,I-16132 GENOA,ITALY. RI de maria, andrea/F-7116-2016 OI de maria, andrea/0000-0001-5782-333X NR 26 TC 28 Z9 28 U1 0 U2 0 PU VCH PUBLISHERS INC PI DEERFIELD BEACH PA 303 NW 12TH AVE, DEERFIELD BEACH, FL 33442-1788 SN 0014-2980 J9 EUR J IMMUNOL JI Eur. J. Immunol. PD MAR PY 1994 VL 24 IS 3 BP 531 EP 536 DI 10.1002/eji.1830240306 PG 6 WC Immunology SC Immunology GA NB718 UT WOS:A1994NB71800005 PM 7907291 ER PT J AU STEINHOFF, U BURKHART, C ARNHEITER, H HENGARTNER, H ZINKERNAGEL, R AF STEINHOFF, U BURKHART, C ARNHEITER, H HENGARTNER, H ZINKERNAGEL, R TI VIRUS OR A HAPTEN-CARRIER COMPLEX CAN ACTIVATE AUTOREACTIVE B-CELLS BY PROVIDING LINKED T-HELP SO EUROPEAN JOURNAL OF IMMUNOLOGY LA English DT Note DE TRANSGENIC MICE; AUTOANTIBODIES; T HELP ID REACTIVE LYMPHOCYTES-B; MONOCLONAL-ANTIBODIES; TRANSGENIC MICE; SELF ANTIGEN; TOLERANCE; ELIMINATION; INDUCTION; ARTHRITIS; DELETION; THERAPY AB We investigated the mechanism leading to an IgG autoantibody response in two transgenic mouse lines expressing the glycoprotein of vesicular stomatitis virus (VSV-G). Previous experiments have shown that these animals do not mount a transgene-specific IgG response upon stimulation with purified VSV-G or infection with recombinant vaccinia virus expressing VSV-G. However, infection of VSV-G transgenic animals with wild-type vesicular stomatitis virus, serotype Indiana, readily induced VSV-G-specific, neutralizing IgG autoantibodies. We have tested whether this labile state of tolerance reflected differential availability of VSV-G-specific T help. For this, we immunized transgenic mice with the self-antigen VSV-G covalently coupled to sperm-whale myoglobulin (VSV-G-SWM), to provide new T helper epitopes that are linked to the B cell epitope; co-injected uncoupled VSV-G and SWM served as control. High titers of VSV-G specific IgG autoantibodies were detected in serum of mice immunized with VSV-G-SWM but not after co-injection of uncoupled VSV-G and SWM. Transgenic animals depleted of CD4(+) T cells prior to injection of VSV-G-SWM failed to mount an IgG response. Priming of transgenic mice with the foreign carrier did not accelerate the IgG autoantibody response to VSV-G-SWM, suggesting that B cells were limiting the rate of the response. Thus, self-reactive B cells could be triggered to produce IgG, if they received linked T help specific for a foreign carrier determinant provided either by a classical carrier determinant or a virus. C1 NIH,VIRAL & MOLEC PATHOGENESIS LAB,BETHESDA,MD. NIH,MOLEC GENET LAB,BETHESDA,MD. RP STEINHOFF, U (reprint author), INST EXPTL PATHOL,DEPT PATHOL,SCHMELZBERGSTR 12,CH-8091 ZURICH,SWITZERLAND. NR 24 TC 33 Z9 33 U1 0 U2 0 PU VCH PUBLISHERS INC PI DEERFIELD BEACH PA 303 NW 12TH AVE, DEERFIELD BEACH, FL 33442-1788 SN 0014-2980 J9 EUR J IMMUNOL JI Eur. J. Immunol. PD MAR PY 1994 VL 24 IS 3 BP 773 EP 776 DI 10.1002/eji.1830240343 PG 4 WC Immunology SC Immunology GA NB718 UT WOS:A1994NB71800042 PM 7907298 ER PT J AU LOGAN, A BERRY, M GONZALEZ, AM FRAUTSCHY, SA SPORN, MB BAIRD, A AF LOGAN, A BERRY, M GONZALEZ, AM FRAUTSCHY, SA SPORN, MB BAIRD, A TI EFFECTS OF TRANSFORMING GROWTH FACTOR-BETA(1) ON SCAR PRODUCTION IN THE INJURED CENTRAL-NERVOUS-SYSTEM OF THE RAT SO EUROPEAN JOURNAL OF NEUROSCIENCE LA English DT Article DE TRANSFORMING GROWTH FACTOR-BETA(1); CENTRAL NERVOUS SYSTEM; GLIAL SCARRING; CNS INJURY; FIBROSIS; ASTROCYTES; MESSENGER RNA ID FACTOR-BETA; EXTRACELLULAR-MATRIX; MESSENGER-RNA; TGF-BETA; EXPRESSION; BRAIN; PROLIFERATION; FIBROBLASTS; LOCALIZATION; FIBRONECTIN AB In the central nervous system (CNS), nerve regeneration after traumatic injury fails. The formation of a dense fibrous scar is thought to restrict in part the growth of axonal projections, providing one of the many reasons that complete lesions of neural pathways in the adult mammalian CNS are rarely followed by significant functional recovery. In order to determine which mechanisms mediate scar formation in the CNS and to investigate whether they can be modulated in vivo, we have attempted to define the potential role of trophic factors. Our previous studies have shown the focal elevation of transforming growth factor beta1 (TGFbeta1) expression in lesioned CNS tissue. In the studies described here, we demonstrate that TGFbeta1 participates in the scarring response in the rat brain. First, the elevated protein levels of TGFbeta1 are localized to specific populations of injury-responsive cells in the traumatized CNS. Furthermore, the injection of TGFbeta1 into the brains of injured rats causes a dramatic increase in the scarring response. Conversely, when neutralizing TGFbeta1 antibodies are administered, the deposition of fibrous scar tissue and the formation of a limiting glial membrane that borders the lesion is significantly attenuated, thus establishing a role for the endogenous growth factor in regulation of the non-glial component of the scar. In implicating TGFbeta1 in the scarring response in the CNS, the potential use for TGFbeta1 antagonists as inhibitors of scar formation in the injured mammalian CNS is self-evident. C1 WHITTIER INST DIABET & ENDOCRINOL,DEPT MOLEC & CELLULAR GROWTH BIOL,LA JOLLA,CA 92037. UNIV BIRMINGHAM,DEPT CLIN CHEM,BIRMINGHAM B15 2TT,W MIDLANDS,ENGLAND. NIH,CHEMOPREVENT LAB,BETHESDA,MD 20892. UNITED MED & DENT SCH GUYS & ST THOMAS HOSP,DEPT ANAT & CELL BIOL,LONDON SE1 9RT,ENGLAND. FU NIA NIH HHS [AG10685, R01 AG010685]; NIDDK NIH HHS [DK18811]; NINDS NIH HHS [NS28121, P01 NS028121]; Wellcome Trust NR 38 TC 232 Z9 238 U1 0 U2 2 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0953-816X J9 EUR J NEUROSCI JI Eur. J. Neurosci. PD MAR 1 PY 1994 VL 6 IS 3 BP 355 EP 363 DI 10.1111/j.1460-9568.1994.tb00278.x PG 9 WC Neurosciences SC Neurosciences & Neurology GA ND226 UT WOS:A1994ND22600007 PM 8019673 ER PT J AU TUMMINIA, SJ QIN, C ZIGLER, JS RUSSELL, P AF TUMMINIA, SJ QIN, C ZIGLER, JS RUSSELL, P TI THE INTEGRITY OF MAMMALIAN LENSES IN ORGAN-CULTURE SO EXPERIMENTAL EYE RESEARCH LA English DT Article DE LENS; CRYSTALLINS; ORGAN CULTURE; OXIDATIVE STRESS; PROTEIN LEAKAGE ID MODELING CORTICAL CATARACTOGENESIS; HYDROGEN-PEROXIDE; ALPHA-CRYSTALLIN; NUCLEAR CATARACT; DIABETIC RATS; PROTEIN; LEAKAGE; METABOLISM; EXPRESSION; TISSUES RP TUMMINIA, SJ (reprint author), NEI,MECHANISMS OCULAR DIS LAB,9000 ROCKVILLE PIKE,BLDG 6,RM 228,BETHESDA,MD 20892, USA. NR 43 TC 45 Z9 45 U1 0 U2 0 PU ACADEMIC PRESS LTD PI LONDON PA 24-28 OVAL RD, LONDON, ENGLAND NW1 7DX SN 0014-4835 J9 EXP EYE RES JI Exp. Eye Res. PD MAR PY 1994 VL 58 IS 3 BP 367 EP 374 DI 10.1006/exer.1994.1027 PG 8 WC Ophthalmology SC Ophthalmology GA NF524 UT WOS:A1994NF52400012 PM 8174656 ER PT J AU NAKAMURA, E LANE, MA ROTH, GS CUTLER, RG INGRAM, DK AF NAKAMURA, E LANE, MA ROTH, GS CUTLER, RG INGRAM, DK TI EVALUATING MEASURES OF HEMATOLOGY AND BLOOD-CHEMISTRY IN MALE RHESUS-MONKEYS AS BIOMARKERS OF AGING SO EXPERIMENTAL GERONTOLOGY LA English DT Article DE PRIMATES; NUTRITION; DIET RESTRICTION; CLINICAL PHYSIOLOGY; VALIDITY ID BIOLOGICAL AGE; PIGTAILED MACAQUES; MACACA-NEMESTRINA; RESTRICTION AB Reliable and valid biomarkers of aging can provide valuable tools for examining the effectiveness of interventions that may influence the rate of aging processes. However, a standardized method for identifying biomarkers of aging has yet to be developed. The current analysis focused on hematology and blood chemistry variables obtained from a 5-year longitudinal study of male rhesus monkeys (N = 29) on a diet restriction regime known to retard aging processes and extend lifespan in laboratory rodents (70% of the diet intake of controls). For the current analysis, the major screening criteria for identifying candidate biomarkers of aging were cross-sectional and longitudinal correlation with chronological age (CA) and stability of individual differences. Six potential variables from the battery of blood chemistry tests were identified: 1) serum glutamic oxalacetic transaminase; 2) alkaline phosphatase; 3) total protein; 4) globulin; 5) blood urea nitrogen to creatinine ratio; and 6) phosphates. When submitted to principle component analysis, these variables loaded onto a single component that accounted for over 50% of the total variance to indicate marked covariance among them. By applying the factor score coefficients from the first principle component, an equation was derived for estimating a biological age score (BAS) for each individual monkey. A comparison of BAS between control and diet-restricted monkeys revealed no statistically significant difference at present; however, the slope of the regression of BAS onto CA appeared steeper for the control group compared to the experimental group. Thus, while demonstration of the validity of the candidate biomarkers awaits further evidence, a strategy by which additional biomarkers of aging can be identified is proposed as an improvement over past approaches. C1 NIA,NATHAN W SHOCK LABS,MOLEC PHYSIOL & GENET SECT,BAYVIEW RES CAMPUS,BALTIMORE,MD 21224. NIA,GERONTOL RES CTR,BALTIMORE,MD 21224. NR 42 TC 39 Z9 39 U1 0 U2 2 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0531-5565 J9 EXP GERONTOL JI Exp. Gerontol. PD MAR-APR PY 1994 VL 29 IS 2 BP 151 EP 177 DI 10.1016/0531-5565(94)90048-5 PG 27 WC Geriatrics & Gerontology SC Geriatrics & Gerontology GA ND217 UT WOS:A1994ND21700003 PM 8026568 ER PT J AU LIANG, CT BARNES, J IMANAKA, S DELUCA, HF AF LIANG, CT BARNES, J IMANAKA, S DELUCA, HF TI ALTERATIONS IN MESSENGER-RNA EXPRESSION OF DUODENAL 1,25-DIHYDROXYVITAMIN-D(3) RECEPTOR AND VITAMIN-D-DEPENDENT CALCIUM-BINDING PROTEIN IN AGED WISTAR RATS SO EXPERIMENTAL GERONTOLOGY LA English DT Article DE AGING; CALCIUM BINDING PROTEIN; 1,25-(OH)2D(3) RECEPTOR; GENE EXPRESSION; DUODENUM; RAT ID MOLECULAR-CLONING; DIETARY CALCIUM; GENE-EXPRESSION; ABSORPTION; INTESTINE; TRANSPORT; CDNA AB Previously, we reported that uptake of calcium into isolated duodenal cells and duodenal brush border membrane vesicles decreased in senescence. Decreases in duodenal 1,25-dihydroxyvitamin D3 [1,25-(OH)2D3] receptor number and 9k vitamin D-dependent calcium binding protein (CaBP) were also observed in aged rats. In this study, we examined the steady state mRNA levels of duodenal 1,25-(OH)2D3 receptor and CaBP in both adult (6-month-old) and old (24-month-old) rats. We identified one major band of 4.4 kb for 1,25-(OH)2D3 receptor mRNA. The size of the transcript was not affected by age. The content of 1,25-(OH)2D3 receptor mRNA (normalized with poly(A)+RNA) decreased 23% in the aged rat as compared to the adult rat. The expression of CaBP was also examined. A single band of 0.6 kb was observed for CaBP mRNA. The size of CaBP mRNA was not altered with age. However, the abundance of CaBP mRNA (normalized with poly(A)+RNA) was reduced 20% in the senescent rat. Thus, the results in the present study were consistent with our previous findings that the number of 1,25-(OH)2D3 receptors and the level of CaBP declined in the aged rat. However, the precise mechanism leading to the age-related deficit in mRNA expression remains to be elucidated. C1 UNIV WISCONSIN,DEPT BIOCHEM,MADISON,WI 53706. RP LIANG, CT (reprint author), NIA,GERONTOL RES CTR,4940 EASTERN AVE,BALTIMORE,MD 21224, USA. NR 27 TC 25 Z9 25 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0531-5565 J9 EXP GERONTOL JI Exp. Gerontol. PD MAR-APR PY 1994 VL 29 IS 2 BP 179 EP 186 DI 10.1016/0531-5565(94)90049-3 PG 8 WC Geriatrics & Gerontology SC Geriatrics & Gerontology GA ND217 UT WOS:A1994ND21700004 PM 8026569 ER PT J AU RAY, PE MCCUNE, B GOMEZ, RA BRUGGEMAN, LA KLOTMAN, PE AF RAY, PE MCCUNE, B GOMEZ, RA BRUGGEMAN, LA KLOTMAN, PE TI INDUCTION OF TRANSFORMING GROWTH FACTOR-BETA(2-3) IN THE JUXTAGLOMERULAR APPARATUS AND RENAL VASCULAR SMOOTH-MUSCLE CELLS OF YOUNG-RATS AND INFANTS SO EXPERIMENTAL NEPHROLOGY LA English DT Note C1 NIDR,DEV BIOL LAB,BETHESDA,MD 20892. JOHNS HOPKINS UNIV,DEPT PATHOL,BALTIMORE,MD. UNIV VIRGINIA,SCH MED,DEPT NEPHROL,CHARLOTTESVILLE,VA 22908. RP RAY, PE (reprint author), CHILDRENS NATL MED CTR,CHILDRENS RES INST,WASHINGTON,DC 20010, USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1018-7782 J9 EXP NEPHROL JI Exp. Nephrol. PD MAR-APR PY 1994 VL 2 IS 2 BP 129 EP 129 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA NH188 UT WOS:A1994NH18800016 PM 8082006 ER PT J AU GAZZINELLI, RT BREZIN, A LI, Q NUSSENBLATT, RB CHAN, CC AF GAZZINELLI, RT BREZIN, A LI, Q NUSSENBLATT, RB CHAN, CC TI TOXOPLASMA-GONDII - ACQUIRED OCULAR TOXOPLASMOSIS IN THE MURINE MODEL, PROTECTIVE ROLE OF TNF-ALPHA AND IFN-GAMMA SO EXPERIMENTAL PARASITOLOGY LA English DT Article DE TOXOPLASMA-GONDII STRAIN; RETINAL PIGMENT EPITHELIUM; TACHYZOITE SURFACE ANTIGEN-1; POLYMERASE CHAIN REACTION; REVERSE TRANSCRIPTASE POLYMERASE CHAIN REACTION; MOUSE STRAIN C57BL/6; MONOCLONAL ANTIBODY; DEOXYRIBONUCLEIC ACID; RIBONUCLEIC ACID; MESSAGE RIBONUCLEIC ACID ID POLYMERASE CHAIN-REACTION; TUMOR-NECROSIS-FACTOR; L-ARGININE; MICE; ENCEPHALITIS; ANTIBODY; RETINOCHOROIDITIS; MACROPHAGES; INFECTION; UVEITIS AB DNA and mRNA amplification by the polymerase chain reaction (PCR), immunohistochemical, and histopathology were performed in the eyes and brains from C57BL/6 mice infected with an avirulent strain of Toxoplasma gondii (ME49). Focal ocular inflammation and retinal pigment epithelial involvement were commonly observed after 15 days of infection. Four weeks after infection a stable number of cysts was observed in the brain but rarely in the eye, and they did not elicit an inflammatory response. In most of the ocular lesions the presence of the parasite could not be demonstrated even with the PCR technique. B1 DNA fragments of T. gondii were detected in only 4 of 11 eyes tested by PCR and Southern blot hybridization. Treatment of mice with mAbs against T cells (CD4 plus CD8) or cytokines (IFN-gamma or TNF-alpha) resulted in a marked increase of ocular lesions, more often associated with the presence of the parasite and the severity of inflammatory response. This model and the techniques utilized here can improve our understanding of the respective roles of parasite proliferation and immune mechanisms involved in the pathogenesis of acquired ocular totoplasmosis. (C) 1994 Academic Press, Inc. C1 NEI,IMMUNOL LAB,BETHESDA,MD 20892. RP GAZZINELLI, RT (reprint author), NIAID,PARASIT DIS LAB,BETHESDA,MD 20892, USA. NR 35 TC 85 Z9 89 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0014-4894 J9 EXP PARASITOL JI Exp. Parasitol. PD MAR PY 1994 VL 78 IS 2 BP 217 EP 229 DI 10.1006/expr.1994.1022 PG 13 WC Parasitology SC Parasitology GA NB117 UT WOS:A1994NB11700010 PM 8119376 ER PT J AU LAMB, ME AF LAMB, ME TI THE INVESTIGATION OF CHILD SEXUAL ABUSE - AN INTERNATIONAL, INTERDISCIPLINARY CONSENSUS STATEMENT SO FAMILY LAW QUARTERLY LA English DT Article RP LAMB, ME (reprint author), NICHHD,SOCIAL & EMOT DEV SECT,9190 ROCKVILLE PIKE,BETHESDA,MD 20814, USA. NR 8 TC 5 Z9 5 U1 0 U2 0 PU AMER BAR ASSOC PI CHICAGO PA 750 N LAKE SHORE DR ATTN:ORDER FULFILLMENT, CHICAGO, IL 60611 SN 0014-729X J9 FAM LAW QUART JI Fam. Law Q. PD SPR PY 1994 VL 28 IS 1 BP 151 EP 162 PG 12 WC Family Studies; Law SC Family Studies; Government & Law GA NW615 UT WOS:A1994NW61500008 ER PT J AU BADOLATO, R WANG, JM MURPHY, WJ LLOYD, AR MICHIEL, DF BAUSSERMAN, LL OPPENHEIM, JJ KELVIN, DJ AF BADOLATO, R WANG, JM MURPHY, WJ LLOYD, AR MICHIEL, DF BAUSSERMAN, LL OPPENHEIM, JJ KELVIN, DJ TI SERUM AMYLOID-A HAS CHEMOATTRACTANT ACTIVITY FOR MONOCYTES AND POLYMORPHONUCLEAR CELLS SO FASEB JOURNAL LA English DT Meeting Abstract C1 NCI,BRMP,LMI,FREDERICK,MD 21702. NCI,PRI DYNCORP,BCDP,FREDERICK,MD 21702. RI Badolato, Raffaele/A-8081-2010 OI Badolato, Raffaele/0000-0001-7375-5410 NR 0 TC 2 Z9 2 U1 1 U2 1 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR PY 1994 VL 8 IS 4 BP A234 EP A234 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA ND196 UT WOS:A1994ND19601350 ER PT J AU BEDFORD, JJ BURG, MB LEADER, JP PETERS, E SMITH, RAJ AF BEDFORD, JJ BURG, MB LEADER, JP PETERS, E SMITH, RAJ TI OSMOLYTES IN THE KIDNEY OF THE AUSTRALIAN BRUSH-TAILED OPOSSUM, TRICHOSURUS-VULPECULA SO FASEB JOURNAL LA English DT Meeting Abstract C1 NIH,LKEM,BETHESDA,MD 20892. UNIV OTAGO,DEPT PHYSIOL,DUNEDIN,NEW ZEALAND. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR PY 1994 VL 8 IS 4 BP A575 EP A575 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA ND196 UT WOS:A1994ND19603329 ER PT J AU BERN, C AF BERN, C TI THE USE OF RETROSPECTIVE DIET ASSESSMENT IN A FIELD INVESTIGATION OF EPIDEMIC NEUROPATHY SO FASEB JOURNAL LA English DT Meeting Abstract C1 CTR DIS CONTROL,ATLANTA,GA 30333. MINIST SALUD PUBL,HAVANA,CUBA. PAN AMER HLTH ORG,WASHINGTON,DC 20037. NIH,BETHESDA,MD 20892. US FDA,WASHINGTON,DC 20204. EMORY UNIV,ATLANTA,GA 30322. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR PY 1994 VL 8 IS 4 BP A441 EP A441 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA ND196 UT WOS:A1994ND19602553 ER PT J AU BERNARD, C HENRION, D SPORN, MB TEDGUL, A AF BERNARD, C HENRION, D SPORN, MB TEDGUL, A TI PROTECTIVE ROLE OF TGF-BETA AGAINST LPS ACTIVATED MACROPHAGE-INDUCED HYPOCONTRACTILITY OF RABBIT AORTA SO FASEB JOURNAL LA English DT Meeting Abstract C1 HOP LARIBOISIERE,INSERM,U141,F-75475 PARIS 10,FRANCE. NCI,CHEMOPREVENT LAB,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR PY 1994 VL 8 IS 4 BP A325 EP A325 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA ND196 UT WOS:A1994ND19601874 ER PT J AU BIANCHINE, PJ PAOLINI, R KINET, JP METCALFE, DD AF BIANCHINE, PJ PAOLINI, R KINET, JP METCALFE, DD TI STEM-CELL FACTOR IS SUFFICIENT TO PHOSPHORYLATE MAST-CELL FOCAL ADHESION KINASE SO FASEB JOURNAL LA English DT Meeting Abstract C1 NIAID,BETHESDA,MD 20892. NR 0 TC 1 Z9 1 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR PY 1994 VL 8 IS 4 BP A496 EP A496 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA ND196 UT WOS:A1994ND19602868 ER PT J AU CAMPBELL, K CHO, M YANG, R GILBERT, CW LEE, C SHORR, RGL GINNS, E AF CAMPBELL, K CHO, M YANG, R GILBERT, CW LEE, C SHORR, RGL GINNS, E TI BIOCHEMICAL-CHARACTERIZATION OF POLYETHYLENE-GLYCOL MODIFIED GLUCOCEREBROSIDASE (PEG-GC) SO FASEB JOURNAL LA English DT Meeting Abstract C1 ENZON INC,PISCATAWAY,NJ 08854. NIMH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR PY 1994 VL 8 IS 4 BP A93 EP A93 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA ND196 UT WOS:A1994ND19600541 ER PT J AU CEMAN, S PETERSEN, J PINET, V LONG, EO DEMARS, R AF CEMAN, S PETERSEN, J PINET, V LONG, EO DEMARS, R TI DELETION IN MHC OF HUMAN B-CELL MUTANT-.61 DEFINES LOCATION OF GENE REQUIRED FOR CLASS-II ASSOCIATED ANTIGEN-PROCESSING SO FASEB JOURNAL LA English DT Meeting Abstract C1 UNIV WISCONSIN,MADISON,WI 53706. NIAID,IMMUNOGENET LAB,ROCKVILLE,MD 20852. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR PY 1994 VL 8 IS 4 BP A517 EP A517 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA ND196 UT WOS:A1994ND19602991 ER PT J AU CHO, M GILBERT, CW CAMPBELL, K PSCHENYCZNY, V MARTIN, B GINNS, E SHORR, RGL AF CHO, M GILBERT, CW CAMPBELL, K PSCHENYCZNY, V MARTIN, B GINNS, E SHORR, RGL TI POLYETHYLENE-GLYCOL MODIFIED GLUCOCEREBROSIDASE (PEG-GC) HAS INCREASED CIRCULATING HALF-LIFE AND CAN BE DELIVERED BY 3 ROUTES OF ADMINISTRATION SO FASEB JOURNAL LA English DT Meeting Abstract C1 NIMH,BETHESDA,MD 20892. ENZON INC,PISCATAWAY,NJ 08854. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR PY 1994 VL 8 IS 4 BP A94 EP A94 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA ND196 UT WOS:A1994ND19600547 ER PT J AU CHULUYAN, HE SCHALL, T YOSHIMURA, T ISSEKUTZ, AC AF CHULUYAN, HE SCHALL, T YOSHIMURA, T ISSEKUTZ, AC TI IL-1 ACTIVATION OF ENDOTHELIUM RESULTS IN VLA-4 MEDIATED MONOCYTE TRANSENDOTHELIAL MIGRATION TO C5A, MIP-1-ALPHA, RANTES AND PAF, BUT INHIBITS MIGRATION TO MCP-1 SO FASEB JOURNAL LA English DT Meeting Abstract C1 GENENTECH INC,S SAN FRANCISCO,CA 94080. NCI,BETHESDA,MD 20892. DALHOUSIE UNIV,DEPT PEDIAT,HALIFAX B3H 4H2,NS,CANADA. 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 MAR PY 1994 VL 8 IS 4 BP A234 EP A234 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA ND196 UT WOS:A1994ND19601353 ER PT J AU COX, GW MELILLO, G SHEFFLER, LA WILLIS, JD VARESIO, L AF COX, GW MELILLO, G SHEFFLER, LA WILLIS, JD VARESIO, L TI INHIBITION OF PROLIFERATION OF IMMORTALIZED MOUSE MACROPHAGES BY CYTOKINES AND NITRIC-OXIDE SO FASEB JOURNAL LA English DT Meeting Abstract C1 NCI,FCRDC,BRMP,EXPTL IMMUNOL LAB,FREDERICK,MD 21702. RI varesio, luigi/J-8261-2016 OI varesio, luigi/0000-0001-5659-2218 NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR PY 1994 VL 8 IS 4 BP A510 EP A510 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA ND196 UT WOS:A1994ND19602953 ER PT J AU DEFILIPPI, R PRETE, SP GIULIANI, A BEI, R YAMAUE, H GREINER, JW DEVECCHIS, L BONMASSAR, E AF DEFILIPPI, R PRETE, SP GIULIANI, A BEI, R YAMAUE, H GREINER, JW DEVECCHIS, L BONMASSAR, E TI COMBINED EFFECTS OF INTERFERON-ALPHA AND 5-FLUOROURACIL ON NORMAL LYMPHOCYTES OR COLON-CANCER CELLS SO FASEB JOURNAL LA English DT Meeting Abstract C1 UNIV ROMA TOR VERGATA,I-00173 ROME,ITALY. NCI,LTIB,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR PY 1994 VL 8 IS 4 BP A96 EP A96 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA ND196 UT WOS:A1994ND19600557 ER PT J AU FENTON, RG LUSTER, DG MURPHY, W TAUB, DD AF FENTON, RG LUSTER, DG MURPHY, W TAUB, DD TI HUMAN-MELANOMA CELLS EXPRESSING B7 SIGNIFICANTLY ENHANCES T-CELL RESPONSES TO HUMAN TUMOR-CELLS SO FASEB JOURNAL LA English DT Meeting Abstract C1 NCI,FREDERICK CANC RES & DEV CTR,BIOL RESPONSE MODIFIERS PROGRAM,FREDERICK,MD 21702. USDA ARS,FREDERICK,MD 21702. NCI,FREDERICK CANC RES & DEV CTR,PROGRAM RESOURCES INC DYNCORP,FREDERICK,MD 21701. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR PY 1994 VL 8 IS 4 BP A201 EP A201 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA ND196 UT WOS:A1994ND19601160 ER PT J AU FITTS, MG ALEXANDER, CB YOUNGCOOPER, GO MAGE, RG AF FITTS, MG ALEXANDER, CB YOUNGCOOPER, GO MAGE, RG TI THE RELATIVE FREQUENCY OF REARRANGEMENT TO THE IMMUNOGLOBULIN J(H) LOCUS - PREFERENTIAL REARRANGEMENT TO J(H)2 AND J(H)4 BUT SUPPRESSION OF JH2 UTILIZATION IN RABBIT BONE-MARROW SO FASEB JOURNAL LA English DT Meeting Abstract C1 NIAID,LI,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR PY 1994 VL 8 IS 4 BP A466 EP A466 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA ND196 UT WOS:A1994ND19602697 ER PT J AU FOGLER, WE PILARO, AM TAUB, DD MCCORMICK, KL SAYERS, TJ ORTALDO, JR WILTROUT, RH AF FOGLER, WE PILARO, AM TAUB, DD MCCORMICK, KL SAYERS, TJ ORTALDO, JR WILTROUT, RH TI TUMOR-NECROSIS-FACTOR-ALPHA (TNF-ALPHA) IS A PRINCIPAL CYTOKINE INVOLVED IN THE RECRUITMENT OF NATURAL-KILLER (NK) CELLS TO LIVER PARENCHYMA SO FASEB JOURNAL LA English DT Meeting Abstract C1 NCI,FCRDC,BRMP,LEI,EXPTL THERAPEUT SECT,FREDERICK,MD 21702. NCI,FCRDC,CSP,BETHESDA,MD 21702. NCI,FCRDC,PRI DYNCORP,BCDP,BETHESDA,MD 21702. RI Sayers, Thomas/G-4859-2015 NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR PY 1994 VL 8 IS 4 BP A224 EP A224 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA ND196 UT WOS:A1994ND19601293 ER PT J AU FORMAN, MR LANZA, E BEECHER, G YONG, LC REICHMAN, ME JUDD, JT CAMPBELL, WS TAYLOR, PR AF FORMAN, MR LANZA, E BEECHER, G YONG, LC REICHMAN, ME JUDD, JT CAMPBELL, WS TAYLOR, PR TI THE EFFECT OF ALCOHOL INTAKE ON PLASMA CAROTENOID LEVELS - A CONTROLLED DIET STUDY SO FASEB JOURNAL LA English DT Meeting Abstract C1 NCI,DIV CANC PREVENT & CONTROL,BETHESDA,MD 20892. USDA ARS,BELTSVILLE AGR RES CTR,BHNRC,BELTSVILLE,MD 20705. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR PY 1994 VL 8 IS 4 BP A193 EP A193 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA ND196 UT WOS:A1994ND19601119 ER PT J AU FREDERIKSE, P PIATIGORSKY, J AF FREDERIKSE, P PIATIGORSKY, J TI NOVEL AND HEAT INDUCIBLE BINDING OF HSF PROTEINS TO CRYSTALLIN REGULATORY SEQUENCES SO FASEB JOURNAL LA English DT Meeting Abstract C1 NEI,LMDB,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR PY 1994 VL 8 IS 4 BP A124 EP A124 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA ND196 UT WOS:A1994ND19600721 ER PT J AU GALLAGHER, D SEPULVEDA, D WANG, J PIERSON, RN HARRIS, T HEYMSFIELD, SB AF GALLAGHER, D SEPULVEDA, D WANG, J PIERSON, RN HARRIS, T HEYMSFIELD, SB TI PREDICTION OF TOTAL-BODY WATER FROM HEIGHT, WEIGHT, AGE, AND RACE SO FASEB JOURNAL LA English DT Meeting Abstract C1 COLUMBIA UNIV,ST LUKES ROOSEVELT HOSP,OBES RES CTR,NEW YORK,NY 10025. NIA,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR PY 1994 VL 8 IS 4 BP A164 EP A164 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA ND196 UT WOS:A1994ND19600950 ER PT J AU GERMANO, P KAZANIETZ, MG BLUMBERG, PM RIVERA, J AF GERMANO, P KAZANIETZ, MG BLUMBERG, PM RIVERA, J TI PROTEIN-KINASE-C PARTICIPATES IN THE PHOSPHORYLATION OF THE FC-EPSILON-RI GAMMA-SUBUNIT SO FASEB JOURNAL LA English DT Meeting Abstract C1 NCI,MOLEC MECH TUMOR PROMOT SECT,BETHESDA,MD 20892. NIAMS,CHEM IMMUNOL 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 MAR PY 1994 VL 8 IS 4 BP A238 EP A238 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA ND196 UT WOS:A1994ND19601378 ER PT J AU GIARDINA, SL COFFMAN, JD YOUNG, HA POTTER, SJ FREY, JL ORTALDO, JR ANDERSON, SK AF GIARDINA, SL COFFMAN, JD YOUNG, HA POTTER, SJ FREY, JL ORTALDO, JR ANDERSON, SK TI ASSOCIATION OF THE EXPRESSION OF A NOVEL CYCLOPHILIN WITH MYELOID CELL-DIFFERENTIATION SO FASEB JOURNAL LA English DT Meeting Abstract C1 PRI DYNCORP,BCDP,FREDERICK,MD 21702. NCI,FCRDC,LEI,BRMP,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR PY 1994 VL 8 IS 4 BP A215 EP A215 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA ND196 UT WOS:A1994ND19601239 ER PT J AU GRIMM, SW PHILPOT, RM BEND, JR HALPERT, JR AF GRIMM, SW PHILPOT, RM BEND, JR HALPERT, JR TI DIFFERENTIAL SUBSTRATE-SPECIFICITY AND MECHANISM-BASED INACTIVATION OF RABBIT CYTOCHROME-P450-2B4 AND CYTOCHROME-P450-2B5 SO FASEB JOURNAL LA English DT Meeting Abstract C1 UNIV ARIZONA,DEPT PHARMACOL & TOXICOL,TUCSON,AZ 85721. NIEHS,CELLULAR & MOLEC PHARMACOL LAB,RES TRIANGLE PK,NC 27709. ZENECA PHARMACEUT GRP,DEPT DRUG DISPOSIT & METAB,WILMINGTON,DE 19897. UNIV WESTERN ONTARIO,DEPT PHARMACOL & TOXICOL,LONDON N6A 5C1,ONTARIO,CANADA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR PY 1994 VL 8 IS 4 BP A100 EP A100 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA ND196 UT WOS:A1994ND19600578 ER PT J AU HAMAWY, MM MINOGUCHI, K SWAIM, WD MERGENHAGEN, SE SIRAGANIAN, RP AF HAMAWY, MM MINOGUCHI, K SWAIM, WD MERGENHAGEN, SE SIRAGANIAN, RP TI AGGREGATING THE HIGH-AFFINITY IGE RECEPTOR (FC-EPSILON-RI) INDUCES TYROSINE PHOSPHORYLATION OF PAXILLIN, A FOCAL ADHESION PROTEIN SO FASEB JOURNAL LA English DT Meeting Abstract C1 NIDR,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR PY 1994 VL 8 IS 4 BP A479 EP A479 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA ND196 UT WOS:A1994ND19602773 ER PT J AU HUNT, RA SAAVEDRA, JM TUCKER, DC AF HUNT, RA SAAVEDRA, JM TUCKER, DC TI SYMPATHETIC INNERVATION MODULATES ANGIOTENSIN-II RECEPTOR-BINDING IN EMBRYONIC MYOCARDIUM GRAFTED INOCULO SO FASEB JOURNAL LA English DT Meeting Abstract C1 UNIV ALABAMA,DEPT PSYCHOL,BIRMINGHAM,AL 35294. NIMH,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 MAR PY 1994 VL 8 IS 4 BP A50 EP A50 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA ND196 UT WOS:A1994ND19600292 ER PT J AU IMAMICHI, T UCHIDA, I MCCARTNEYFRANCIS, N WAHL, SM AF IMAMICHI, T UCHIDA, I MCCARTNEYFRANCIS, N WAHL, SM TI MRP8 AND MRP14 GENE-EXPRESSION IS ASSOCIATED WITH THE TRANSITION FROM ACUTE TO CHRONIC INFLAMMATORY DISEASE SO FASEB JOURNAL LA English DT Meeting Abstract C1 NIDR,IMMUNOL LAB,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR PY 1994 VL 8 IS 4 BP A220 EP A220 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA ND196 UT WOS:A1994ND19601272 ER PT J AU JENKINS, GM CROW, M BILATO, C LI, Z RYU, W NATER, C FROEHLICH, J LAKATTA, E CHENG, L AF JENKINS, GM CROW, M BILATO, C LI, Z RYU, W NATER, C FROEHLICH, J LAKATTA, E CHENG, L TI THE ROLE OF MMP-2 IN NEOINTIMA FORMATION FOLLOWING BALLOON INJURY IN THE RAT SO FASEB JOURNAL LA English DT Meeting Abstract C1 NIA,CARDIOVASC SCI LAB,BALTIMORE,MD 21224. NR 0 TC 3 Z9 3 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 1994 VL 8 IS 4 BP A51 EP A51 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA ND196 UT WOS:A1994ND19600298 ER PT J AU JOHNSTON, JA TAUB, D LLOYD, AR CONLON, K OPPENHEIM, JJ KELVIN, DJ AF JOHNSTON, JA TAUB, D LLOYD, AR CONLON, K OPPENHEIM, JJ KELVIN, DJ TI HUMAN T-LYMPHOCYTE CHEMOTAXIS AND ADHERENCE INDUCED BY VASOACTIVE-INTESTINAL-PEPTIDE SO FASEB JOURNAL LA English DT Meeting Abstract C1 NCI,FCRDC,LMI BRMP,FREDERICK,MD 21702. NCI,FCRDC,BCDP PRI DYNCORP,FREDERICK,MD 21702. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR PY 1994 VL 8 IS 4 BP A479 EP A479 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA ND196 UT WOS:A1994ND19602771 ER PT J AU KANG, V KEHRL, JH AF KANG, V KEHRL, JH TI A B-CELL SPECIFIC PROTEIN IS DISTANTLY RELATED TO HELIX-LOOP-HELIX PROTEINS AND IS LOCALIZED IN GERMINAL CENTER B-CELLS SO FASEB JOURNAL LA English DT Meeting Abstract C1 NIAID,LIR,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR PY 1994 VL 8 IS 4 BP A520 EP A520 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA ND196 UT WOS:A1994ND19603010 ER PT J AU KASHIWAYA, Y TSUCHIYA, N SATO, K VEECH, RL PASSONNEAU, JV AF KASHIWAYA, Y TSUCHIYA, N SATO, K VEECH, RL PASSONNEAU, JV TI FACTORS AFFECTING GLYCOLYTIC FLUX AND PERFORMANCE IN WORKING PERFUSED RAT-HEART SO FASEB JOURNAL LA English DT Meeting Abstract C1 NIAAA,LMMB,ROCKVILLE,MD 20859. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR PY 1994 VL 8 IS 4 BP A534 EP A534 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA ND196 UT WOS:A1994ND19603091 ER PT J AU KELSALL, BL EHRHARDT, RO STROBER, W AF KELSALL, BL EHRHARDT, RO STROBER, W TI INDUCTION OF A PRIMARY IFN-G RESPONSE BY PEYERS PATCH DENDRITIC CELLS IS MEDIATED BY IL-12 AND INHIBITED BY IL-4 SO FASEB JOURNAL LA English DT Meeting Abstract C1 NIH,CLIN INVEST LAB,BETHESDA,MD 20892. NR 0 TC 4 Z9 4 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR PY 1994 VL 8 IS 4 BP A207 EP A207 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA ND196 UT WOS:A1994ND19601192 ER PT J AU KINSELLA, J CHENG, L PAULY, R MONTICONE, R KUZUYA, M JENKINS, G FROEHLICH, J LAKATTA, E SOLLOTT, S AF KINSELLA, J CHENG, L PAULY, R MONTICONE, R KUZUYA, M JENKINS, G FROEHLICH, J LAKATTA, E SOLLOTT, S TI TAXOL INHIBITS NEOINTIMAL GROWTH IN THE RAT CAROTID-ARTERY FOLLOWING BALLOON INJURY SO FASEB JOURNAL LA English DT Meeting Abstract C1 NIA,GRC,BALTIMORE,MD 21224. NR 0 TC 0 Z9 0 U1 0 U2 1 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR PY 1994 VL 8 IS 4 BP A317 EP A317 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA ND196 UT WOS:A1994ND19601832 ER PT J AU KINZER, CA KEEGAN, AD BECKMANN, MP WIDMER, M IDELSON, GH BENSASSON, SZ PAUL, WE AF KINZER, CA KEEGAN, AD BECKMANN, MP WIDMER, M IDELSON, GH BENSASSON, SZ PAUL, WE TI CT.H4S CELLS, A MURINE CELL-LINE EXPRESSING HUMAN IL-4 RECEPTORS AND CAPABLE OF ASSAYING HUMAN IL-4 SO FASEB JOURNAL LA English DT Meeting Abstract C1 NIAID,BETHESDA,MD 20892. IMMUNEX CORP,SEATTLE,WA. HEBREW UNIV JERUSALEM,HADASSAH MED CTR,JERUSALEM,ISRAEL. NR 0 TC 5 Z9 5 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 1994 VL 8 IS 4 BP A506 EP A506 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA ND196 UT WOS:A1994ND19602926 ER PT J AU KOLESNITCHENKO, V LEMPICKI, R DONOGHUE, ET TANI, Y ZOLLAPAZNER, S COHEN, DI AF KOLESNITCHENKO, V LEMPICKI, R DONOGHUE, ET TANI, Y ZOLLAPAZNER, S COHEN, DI TI BINDING OF GP41 TO CELL-SURFACE RECEPTORS - SEARCH OF AUXILIARY RECEPTORS SO FASEB JOURNAL LA English DT Meeting Abstract C1 NIAID,IMMUNOREGULAT LAB,BETHESDA,MD 20892. VET AFFAIRS MED CTR,RES & MED SERV LAB,NEW YORK,NY 10010. RI Lempicki, Richard/E-1844-2012 OI Lempicki, Richard/0000-0002-7059-409X NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR PY 1994 VL 8 IS 4 BP A493 EP A493 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA ND196 UT WOS:A1994ND19602851 ER PT J AU KOMAS, N TAIRA, M MURATA, T MANGANIELLO, V AF KOMAS, N TAIRA, M MURATA, T MANGANIELLO, V TI SIMILAR PHARMACOLOGICAL RESPONSES OF 2 RECOMBINANT CGMP-INHIBITED CYCLIC-NUCLEOTIDE PHOSPHODIESTERASE (CGI PDE) ISOFORMS SO FASEB JOURNAL LA English DT Meeting Abstract C1 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 MAR PY 1994 VL 8 IS 4 BP A82 EP A82 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA ND196 UT WOS:A1994ND19600476 ER PT J AU KWON, TK BUCHHOLZ, MA NORDIN, AA AF KWON, TK BUCHHOLZ, MA NORDIN, AA TI THE EXPRESSION AND PROPERTIES OF CYCLIN-DEPENDENT KINASE-6 (PLSTIRE) IN ANTI-CD-3 ACTIVATED MURINE T-CELLS SO FASEB JOURNAL LA English DT Meeting Abstract C1 NIA,GERONTOL RES CTR,CLIN IMMUNOL SECT,BALTIMORE,MD 21224. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR PY 1994 VL 8 IS 4 BP A523 EP A523 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA ND196 UT WOS:A1994ND19603030 ER PT J AU LAVU, S SRIVASTAVA, M KORNHAUSER, A SRIVASTAVA, S AF LAVU, S SRIVASTAVA, M KORNHAUSER, A SRIVASTAVA, S TI ANALYSIS OF THE TUMOR-SUPPRESSOR GENE P53 IN XERODERMA-PIGMENTOSUM FIBROBLASTS SO FASEB JOURNAL LA English DT Meeting Abstract C1 NIDDKO,BETHESDA,MD 20814. USUHSI,BETHESDA,MD 20814. US FDA,LAUREL,MD 20814. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR PY 1994 VL 8 IS 4 BP A391 EP A391 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA ND196 UT WOS:A1994ND19602263 ER PT J AU LEE, C HSU, H CHANG, D BONIFACIO, A GINNS, E SHORR, RGL AF LEE, C HSU, H CHANG, D BONIFACIO, A GINNS, E SHORR, RGL TI CAN POLYETHYLENE-GLYCOL MODIFIED GLUCOCEREBROSIDASE (PEG-GC) DEGRADE GLUCOCEREBROSIDE FROM PLASMA AND BLOOD OF GAUCHERS PATIENTS SO FASEB JOURNAL LA English DT Meeting Abstract C1 NIMH,BETHESDA,MD 20892. ENZON INC,PISCATAWAY,NJ 08854. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR PY 1994 VL 8 IS 4 BP A94 EP A94 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA ND196 UT WOS:A1994ND19600544 ER PT J AU LEROY, MJ TAIRA, M KOMAS, N DEGERMAN, E MANGANIELLO, V AF LEROY, MJ TAIRA, M KOMAS, N DEGERMAN, E MANGANIELLO, V TI EXPRESSION AND CHARACTERIZATION OF THE ADIPOCYTE CGMP-INHIBITED PHOSPHODIESTERASE (CGI PDE) IN NIH-3T3 CELLS - REGULATION BY INSULIN SO FASEB JOURNAL LA English DT Meeting Abstract C1 NHLBI,BETHESDA,MD 20892. LUND UNIV,S-22101 LUND,SWEDEN. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR PY 1994 VL 8 IS 4 BP A82 EP A82 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA ND196 UT WOS:A1994ND19600474 ER PT J AU MAITY, R CASPI, RR NELSON, LM AF MAITY, R CASPI, RR NELSON, LM TI NEONATAL THYMECTOMY CAUSES PERSISTENCE INTO ADULTHOOD OF THE NEONATAL CAPACITY FOR INCREASED IL-4 PRODUCTION SO FASEB JOURNAL LA English DT Meeting Abstract C1 NEI,LI,BETHESDA,MD 20892. NICHHD,DEB,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR PY 1994 VL 8 IS 4 BP A483 EP A483 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA ND196 UT WOS:A1994ND19602796 ER PT J AU MASON, AC AF MASON, AC TI SELENIUM INCORPORATION INTO SELENOCYSTEINE IN YEAST PROTEINS SO FASEB JOURNAL LA English DT Meeting Abstract C1 PURDUE UNIV,W LAFAYETTE,IN 47907. NHLBI,BETHESDA,MD 20892. NR 0 TC 4 Z9 4 U1 0 U2 1 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR PY 1994 VL 8 IS 4 BP A541 EP A541 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA ND196 UT WOS:A1994ND19603134 ER PT J AU MCADAM, PA MORRIS, VC FORMAN, MR LANZA, E CAMPBELL, W BEECHER, GR LEVANDER, OA AF MCADAM, PA MORRIS, VC FORMAN, MR LANZA, E CAMPBELL, W BEECHER, GR LEVANDER, OA TI DIFFERENCES IN PLASMA SELENIUM (SE) AND GLUTATHIONE-PEROXIDASE (GPX) ACTIVITY DURING 3 PHASES OF THE MENSTRUAL-CYCLE IN NORMAL HEALTHY WOMEN SO FASEB JOURNAL LA English DT Meeting Abstract C1 USDA,BELTSVILLE HUMAN NUTR RES CTR,BELTSVILLE,MD 20705. NCI,DCPC,BETHESDA,MD 20892. NR 1 TC 1 Z9 1 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR PY 1994 VL 8 IS 4 BP A436 EP A436 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA ND196 UT WOS:A1994ND19602522 ER PT J AU MELILLO, G MUSSO, T COX, GW VARESIO, L AF MELILLO, G MUSSO, T COX, GW VARESIO, L TI MULTIPLE REGIONS OF THE NITRIC-OXIDE SYNTHASE (NOS) PROMOTER MEDIATE INTERFERON-GAMMA (IFN-GAMMA) PLUS PICOLINIC-ACID INDUCTION OF NOS TRANSCRIPTION IN MURINE MACROPHAGES SO FASEB JOURNAL LA English DT Meeting Abstract C1 NCI,FCRDC,BRMP,EXPTL IMMUNOL LAB,FREDERICK,MD 21702. RI varesio, luigi/J-8261-2016 OI varesio, luigi/0000-0001-5659-2218 NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR PY 1994 VL 8 IS 4 BP A210 EP A210 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA ND196 UT WOS:A1994ND19601208 ER PT J AU MINOGUCHI, K SWAIM, WD BERENSTEIN, E SIRAGANIAN, RP AF MINOGUCHI, K SWAIM, WD BERENSTEIN, E SIRAGANIAN, RP TI ASSOCIATION OF SRC FAMILY TYROSINE KINASE LYN, A SERINE KINASE, AND FC-EPSILON-RI WITH ALPHA-DERIVATIVES OF GANGLIOSIDE GD1B IN RAT BASOPHILIC LEUKEMIA RBL-2H3 CELLS SO FASEB JOURNAL LA English DT Meeting Abstract C1 NIDR,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR PY 1994 VL 8 IS 4 BP A238 EP A238 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA ND196 UT WOS:A1994ND19601376 ER PT J AU MOORADIAN, DL HUTSELL, T KEEFER, L AF MOORADIAN, DL HUTSELL, T KEEFER, L TI INHIBITION OF HUMAN AORTIC SMOOTH-MUSCLE CELL-PROLIFERATION BY NITRIC OXIDE-RELEASING COMPOUNDS SO FASEB JOURNAL LA English DT Meeting Abstract C1 COMEDICUS INC,LONG LAKE,MN 55356. NCI,FCRDC,COMPARAT CARCINOGENESIS,FREDERICK,MD 21702. UNIV MINNESOTA,DEPT LAB MED & PATHOL,MINNEAPOLIS,MN 55455. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR PY 1994 VL 8 IS 4 BP A319 EP A319 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA ND196 UT WOS:A1994ND19601839 ER PT J AU MUTHUKUMAR, G SUNDARAM, R CZUBA, B SZESKO, D LEE, L SHORR, RGL GINNS, E AF MUTHUKUMAR, G SUNDARAM, R CZUBA, B SZESKO, D LEE, L SHORR, RGL GINNS, E TI PURIFICATION OF RECOMBINANT GLUCOCEREBROSIDASE FROM A BACULOVIRUS EXPRESSION SYSTEM SO FASEB JOURNAL LA English DT Meeting Abstract C1 NIMH,BETHESDA,MD 20892. ENZON INC,PISCATAWAY,NJ 08854. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR PY 1994 VL 8 IS 4 BP A94 EP A94 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA ND196 UT WOS:A1994ND19600546 ER PT J AU NAKAJIMA, H HENKART, P AF NAKAJIMA, H HENKART, P TI LIKE GRANZYME-A, GRANZYME-B CONTRIBUTES TO TARGET LYSIS AND DNA BREAKDOWN IN LYMPHOCYTE-MEDIATED CYTOTOXICITY SO FASEB JOURNAL LA English DT Meeting Abstract C1 NCI,EXPTL IMMUNOL BRANCH,BETHESDA,MD 20892. NR 0 TC 1 Z9 1 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR PY 1994 VL 8 IS 4 BP A206 EP A206 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA ND196 UT WOS:A1994ND19601185 ER PT J AU NASLAVSKY, N IDELSON, GH OR, R PAUL, WE BENSASSON, SZ AF NASLAVSKY, N IDELSON, GH OR, R PAUL, WE BENSASSON, SZ TI HUMAN BASOPHILS PRODUCE IL-4 IN RESPONSE TO IGG4-MEDIATED BUT NOT IGG1-MEDIATED CROSS-LINKAGE OF FC-GAMMA-RII SO FASEB JOURNAL LA English DT Meeting Abstract C1 HEBREW UNIV JERUSALEM,HADASSAH MED CTR,JERUSALEM,ISRAEL. NIAID,BETHESDA,MD 20892. NR 0 TC 1 Z9 1 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR PY 1994 VL 8 IS 4 BP A497 EP A497 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA ND196 UT WOS:A1994ND19602877 ER PT J AU PARK, CS PARDHASARADHI, K KUTTY, RK KRISHNA, G AF PARK, CS PARDHASARADHI, K KUTTY, RK KRISHNA, G TI MOLECULAR-CLONING AND SEQUENCING OF A HEAT-SHOCK FACTOR CDNA FROM HUMAN RETINA SO FASEB JOURNAL LA English DT Meeting Abstract C1 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 MAR PY 1994 VL 8 IS 4 BP A374 EP A374 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA ND196 UT WOS:A1994ND19602163 ER PT J AU PEREIRA, MA BARNES, LH RASSMAN, VL STEELE, VE LUBET, RA AF PEREIRA, MA BARNES, LH RASSMAN, VL STEELE, VE LUBET, RA TI NONSTEROIDAL ANTIINFLAMMATORY DRUGS INHIBITION OF FOCI OF ABERRANT CRYPTS AND CANCER IN RAT COLON SO FASEB JOURNAL LA English DT Meeting Abstract C1 EHRT INC,LEXINGTON,KY 40503. NCI,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR PY 1994 VL 8 IS 4 BP A95 EP A95 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA ND196 UT WOS:A1994ND19600549 ER PT J AU POSPISIL, R YOUNGCOOPER, GO WEINSTEIN, PD MAGE, RG AF POSPISIL, R YOUNGCOOPER, GO WEINSTEIN, PD MAGE, RG TI TRAFFICKING PATTERNS SHOW POSSIBLE FUNCTIONAL DIFFERENCES BETWEEN APPENDIX LYMPHOCYTES FROM NORMAL AND ALICIA MUTANT RABBITS SO FASEB JOURNAL LA English DT Meeting Abstract C1 NIAID,BETHESDA,MD 20892. RI Pospisil, Richard/B-7467-2012 NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR PY 1994 VL 8 IS 4 BP A254 EP A254 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA ND196 UT WOS:A1994ND19601471 ER PT J AU RAZIN, E KAZANIETZ, MG SZALLASI, Z BLUMBERG, P RIVERA, J AF RAZIN, E KAZANIETZ, MG SZALLASI, Z BLUMBERG, P RIVERA, J TI THE ISOZYME PROTEIN KINASE-C-BETA IS A POTENTIAL LINK BETWEEN THE MAST-CELL FC-EPSILON-RI AND THE EXPRESSION OF C-FOS AND C-JUN SO FASEB JOURNAL LA English DT Meeting Abstract C1 HEBREW UNIV JERUSALEM,SCH MED,JERUSALEM,ISRAEL. NIH,TUMOR PROMOT LAB,BETHESDA,MD 20892. NIH,CHEM IMMUNOL SECT,SIGNAL TRANSDUCT GRP,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR PY 1994 VL 8 IS 4 BP A480 EP A480 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA ND196 UT WOS:A1994ND19602778 ER PT J AU RISING, R RAVUSSIN, E AF RISING, R RAVUSSIN, E TI DECREASED RATIO OF FAT TO CARBOHYDRATE OXIDATION WITH AGE IN PIMA-INDIANS SO FASEB JOURNAL LA English DT Meeting Abstract C1 NIDDK,CDNS,PHOENIX,AZ 85016. MAIMONIDES HOSP,DEPT PEDIAT,BROOKLYN,NY 11219. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR PY 1994 VL 8 IS 4 BP A160 EP A160 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA ND196 UT WOS:A1994ND19600927 ER PT J AU RIVOLTINI, L MANCINI, M MARKUS, N MARINCOLA, F ROSENBERG, S TOPALIAN, S AF RIVOLTINI, L MANCINI, M MARKUS, N MARINCOLA, F ROSENBERG, S TOPALIAN, S TI CHARACTERIZATION OF SHARED TUMOR-ANTIGENS RECOGNIZED BY MELANOMA-SPECIFIC CD4+ T-CELLS SO FASEB JOURNAL LA English DT Meeting Abstract C1 NCI,SURG 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 MAR PY 1994 VL 8 IS 4 BP A209 EP A209 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA ND196 UT WOS:A1994ND19601204 ER PT J AU RIZZO, LV MILLERRIVERO, NE CHAN, CC WIGGERT, B NUSSENBLATT, RB CASPI, RR AF RIZZO, LV MILLERRIVERO, NE CHAN, CC WIGGERT, B NUSSENBLATT, RB CASPI, RR TI INTERLEUKIN-2 TREATMENT POTENTIATES INDUCTION OF ORAL TOLERANCE SO FASEB JOURNAL LA English DT Meeting Abstract C1 NEI,BETHESDA,MD 20892. RI Rizzo, Luiz Vicente/B-4458-2009 NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR PY 1994 VL 8 IS 4 BP A476 EP A476 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA ND196 UT WOS:A1994ND19602755 ER PT J AU ROSEBOOM, PH KLEIN, DC AF ROSEBOOM, PH KLEIN, DC TI NOREPINEPHRINE-INDUCED PHOSPHORYLATION OF CREB IN THE PINEAL-GLAND INVOLVES BETA-ADRENERGIC ELEVATION OF CAMP SO FASEB JOURNAL LA English DT Meeting Abstract C1 NICHHD,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR PY 1994 VL 8 IS 4 BP A386 EP A386 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA ND196 UT WOS:A1994ND19602229 ER PT J AU ROSENKRANZWEISS, P SESSA, WC MILSTIEN, S KAUFMAN, S WATSON, CA POBER, JS AF ROSENKRANZWEISS, P SESSA, WC MILSTIEN, S KAUFMAN, S WATSON, CA POBER, JS TI CYTOKINE REGULATION OF NITRIC-OXIDE (NO) SYNTHESIS IN HUMAN ENDOTHELIAL-CELLS SO FASEB JOURNAL LA English DT Meeting Abstract C1 YALE UNIV,MOLEC CARDIOBIOL PROGRAM,NEW HAVEN,CT 06520. NIMH,NEUROCHEM LAB,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 2 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR PY 1994 VL 8 IS 4 BP A393 EP A393 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA ND196 UT WOS:A1994ND19602274 ER PT J AU ROSENSTEIN, DL RYSCHON, TW RUBINOW, DR NIEMELA, JE ELIN, R BALABAN, RS AF ROSENSTEIN, DL RYSCHON, TW RUBINOW, DR NIEMELA, JE ELIN, R BALABAN, RS TI INTRACELLULAR FREE MAGNESIUM MEASURES BY P-31-NMR SPECTROSCOPY ACROSS THE MENSTRUAL-CYCLE SO FASEB JOURNAL LA English DT Meeting Abstract C1 NIMH,BETHESDA,MD 20892. 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 MAR PY 1994 VL 8 IS 4 BP A433 EP A433 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA ND196 UT WOS:A1994ND19602503 ER PT J AU ROWE, M RAVUSSIN, E OLSEN, R PAUL, A BROYLES, A GRAFF, M AF ROWE, M RAVUSSIN, E OLSEN, R PAUL, A BROYLES, A GRAFF, M TI MITOCHONDRIAL-DNA TYPE AFFECTS RMR SO FASEB JOURNAL LA English DT Meeting Abstract C1 BRIGHAM YOUNG UNIV,PROVO,UT 84602. 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 MAR PY 1994 VL 8 IS 4 BP A160 EP A160 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA ND196 UT WOS:A1994ND19600928 ER PT J AU RYSCHON, TW ROSENSTEIN, DL RUBINOW, DR NIEMELA, JE ELIN, RJ BALABAN, RS AF RYSCHON, TW ROSENSTEIN, DL RUBINOW, DR NIEMELA, JE ELIN, RJ BALABAN, RS TI RELATIONSHIP BETWEEN INTRACELLULAR FREE MAGNESIUM AND BLOOD TOTAL MAGNESIUM MEASURES SO FASEB JOURNAL LA English DT Meeting Abstract C1 NIMH,CTR CLIN,BETHESDA,MD 20892. 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 MAR PY 1994 VL 8 IS 4 BP A433 EP A433 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA ND196 UT WOS:A1994ND19602506 ER PT J AU SCONOCCHIA, G TITUS, JA SEGAL, DM AF SCONOCCHIA, G TITUS, JA SEGAL, DM TI CD44 IS A TRIGGER MOLECULE IN HUMAN NATURAL-KILLER-CELLS SO FASEB JOURNAL LA English DT Meeting Abstract C1 NCI,EXPTL IMMUNOL 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 MAR PY 1994 VL 8 IS 4 BP A199 EP A199 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA ND196 UT WOS:A1994ND19601149 ER PT J AU SENTERRELESENFANTS, S ALAG, A HOLLISTER, S SOBEL, ME AF SENTERRELESENFANTS, S ALAG, A HOLLISTER, S SOBEL, ME TI POTENTIAL ROLE OF ADENINE RICH ELEMENTS IN THE DIFFERENTIAL EXPRESSION OF 2 CALMODULIN-I MESSENGER-RNA TRANSCRIPTS IN HUMAN-CELLS SO FASEB JOURNAL LA English DT Meeting Abstract C1 NCI,PATHOL LAB,MOLEC PATHOL 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 MAR PY 1994 VL 8 IS 4 BP A397 EP A397 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA ND196 UT WOS:A1994ND19602299 ER PT J AU SEPULVEDA, D GALLAGHER, D PIERSON, RN HARRIS, T HEYMSFIELD, SB AF SEPULVEDA, D GALLAGHER, D PIERSON, RN HARRIS, T HEYMSFIELD, SB TI BMI AS ESTIMATE OF FATNESS ACROSS AGE, GENDER, AND ETHNIC-GROUPS SO FASEB JOURNAL LA English DT Meeting Abstract C1 ST LUKES ROOSEVELT HOSP,OBES RES CTR,NEW YORK,NY 10025. NIA,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR PY 1994 VL 8 IS 4 BP A164 EP A164 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA ND196 UT WOS:A1994ND19600949 ER PT J AU SHAIKH, N RIVERA, J STEAD, RH MARSHALL, JS AF SHAIKH, N RIVERA, J STEAD, RH MARSHALL, JS TI FC-EPSILON-RI BETA-CHAIN EXPRESSION DURING NIPPOSTRONGYLUS-BRASILIENSIS (NB) INFECTION SO FASEB JOURNAL LA English DT Meeting Abstract C1 MCMASTER UNIV,HAMILTON L8N 3Z5,ONTARIO,CANADA. NIAMS,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR PY 1994 VL 8 IS 4 BP A497 EP A497 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA ND196 UT WOS:A1994ND19602876 ER PT J AU SITKOVSKY, MV SMITH, P REDEGELD, FA AF SITKOVSKY, MV SMITH, P REDEGELD, FA TI IDENTIFICATION OF THE TYROSINE AND OF SERINE THREONINE PROTEIN-KINASE ACTIVITY ON THE SURFACE OF THE T-LYMPHOCYTES - POSSIBLE FUNCTIONAL INVOLVEMENT OF ECTOPROTEIN KINASE(S) IN THE T-LYMPHOCYTE EFFECTOR FUNCTIONS SO FASEB JOURNAL LA English DT Meeting Abstract C1 NIAID,IMMUNOL LAB,BETHESDA,MD 20892. RI Redegeld, Frank/O-6534-2016 OI Redegeld, Frank/0000-0001-8830-7960 NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR PY 1994 VL 8 IS 4 BP A206 EP A206 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA ND196 UT WOS:A1994ND19601189 ER PT J AU SMITH, P REDEGELD, F SITKOVSKY, MV AF SMITH, P REDEGELD, F SITKOVSKY, MV TI IDENTIFICATION, ISOLATION AND PURIFICATION OF THE PLASMA MEMBRANE-ASSOCIATED PROTEIN-KINASES FROM THE T-CELLS SO FASEB JOURNAL LA English DT Meeting Abstract C1 NIAID,IMMUNOL LAB,BETHESDA,MD 20892. RI Redegeld, Frank/O-6534-2016 OI Redegeld, Frank/0000-0001-8830-7960 NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR PY 1994 VL 8 IS 4 BP A85 EP A85 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA ND196 UT WOS:A1994ND19600492 ER PT J AU SOWELL, A AF SOWELL, A TI NUTRITIONAL-STATUS IN THE CUBA OPTIC NEUROPATHY STUDY SO FASEB JOURNAL LA English DT Meeting Abstract C1 CTR DIS CONTROL,ATLANTA,GA 30333. MINIST SALUD PUBL,HAVANA,CUBA. PAN AMER HLTH ORG,WASHINGTON,DC 20037. EMORY UNIV,ATLANTA,GA 30322. US FDA,WASHINGTON,DC 20204. NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR PY 1994 VL 8 IS 4 BP A441 EP A441 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA ND196 UT WOS:A1994ND19602550 ER PT J AU SVERDLOV, V SITKOVSKY, MV AF SVERDLOV, V SITKOVSKY, MV TI DEVELOPMENT OF THE PROCEDURE FOR THE CLONING OF ATP-BINDING PROTEINS FROM T-CELL CDNA LIBRARY SO FASEB JOURNAL LA English DT Meeting Abstract C1 NIAID,IMMUNOL LAB,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR PY 1994 VL 8 IS 4 BP A85 EP A85 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA ND196 UT WOS:A1994ND19600495 ER PT J AU TAUB, DD MASON, A CARTER, C SAYERS, T ORTALDO, JR AF TAUB, DD MASON, A CARTER, C SAYERS, T ORTALDO, JR TI MULTIPLE EFFECTS OF CHEMOKINES ON NATURAL-KILLER-CELL MIGRATION AND CYTOLYTIC ACTIVITY SO FASEB JOURNAL LA English DT Meeting Abstract C1 NCI,FREDERICK CANC RES & DEV CTR,EXPTL IMMUNOL LAB,BIOL RESPONSE MODIFIER PROGRAM,FREDERICK,MD 21702. DYNCORP,PRI INC,CLIN SERV PROGRAM,FREDERICK,MD 21702. RI Sayers, Thomas/G-4859-2015 NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR PY 1994 VL 8 IS 4 BP A512 EP A512 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA ND196 UT WOS:A1994ND19602964 ER PT J AU TSUCHIDA, T BIDDISON, W COLIGAN, J PARKER, K AF TSUCHIDA, T BIDDISON, W COLIGAN, J PARKER, K TI SYNTHETIC SELF PEPTIDES DERIVED FROM SEQUENCES OF HUMAN MYELIN PROTEINS CAN BIND TO HLA-A2 AND INDUCE AUTOREACTIVE CD8+ T-CELL RESPONSES SO FASEB JOURNAL LA English DT Meeting Abstract C1 NINCDS,NEUROIMMUNOL BRANCH,BETHESDA,MD 20892. NIAID,BIOL RESOURCES BRANCH,BETHESDA,MD 20892. NR 0 TC 1 Z9 1 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR PY 1994 VL 8 IS 4 BP A468 EP A468 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA ND196 UT WOS:A1994ND19602709 ER PT J AU WANG, MH YOSHIMURA, T SKEEL, A LEONARD, EJ AF WANG, MH YOSHIMURA, T SKEEL, A LEONARD, EJ TI MACROPHAGE STIMULATING PROTEIN (MSP) - CLEAVAGE OF SINGLE-CHAIN PRO-MSP TO THE BIOLOGICALLY-ACTIVE DISULFIDE-LINKED HETERODIMER SO FASEB JOURNAL LA English DT Meeting Abstract C1 NCI,FCRDC,IMMUNOBIOL LAB,FREDERICK,MD 21702. NR 0 TC 0 Z9 0 U1 0 U2 1 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR PY 1994 VL 8 IS 4 BP A503 EP A503 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA ND196 UT WOS:A1994ND19602911 ER PT J AU WEINSTEIN, PD ANDERSON, AO MAGE, RG AF WEINSTEIN, PD ANDERSON, AO MAGE, RG TI PRODUCTION OF A HIGHLY DIVERSE PRIMARY ANTIBODY REPERTOIRE OCCURS IN RABBIT APPENDIX GERMINAL-CENTERS BY GENE CONVERSION AND SOMATIC HYPERMUTATION SO FASEB JOURNAL LA English DT Meeting Abstract C1 NIAID,LI,BETHESDA,MD 20892. USAMRIID,ARD,FI DETRICK,FREDERICK,MD 21702. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR PY 1994 VL 8 IS 4 BP A525 EP A525 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA ND196 UT WOS:A1994ND19603040 ER PT J AU WELCH, R WANG, Y CROSSMAN, A KIRK, K LEVINE, M AF WELCH, R WANG, Y CROSSMAN, A KIRK, K LEVINE, M TI SEPARATE TRANSPORT ACTIVITIES FOR ASCORBIC AND DEHYDROASCORBIC ACIDS FROM 2 TISSUES SO FASEB JOURNAL LA English DT Meeting Abstract C1 NIDDK,BETHESDA,MD 20877. NR 3 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR PY 1994 VL 8 IS 4 BP A446 EP A446 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA ND196 UT WOS:A1994ND19602583 ER PT J AU XU, LL WANG, JM KELVIN, DJ OPPENHEIM, JJ AF XU, LL WANG, JM KELVIN, DJ OPPENHEIM, JJ TI EFFECT OF RECEPTOR EXPRESSION ON T-LYMPHOCYTE CHEMOTAXIS TO IL-8 SO FASEB JOURNAL LA English DT Meeting Abstract C1 NCI,FCRDC,LM BRMP,FREDERICK,MD 21702. NCI,FCRDC,BCDP PRI DYNCORP,FREDERICK,MD 21702. 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 MAR PY 1994 VL 8 IS 4 BP A479 EP A479 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA ND196 UT WOS:A1994ND19602768 ER PT J AU LEVINE, JG SCHAAPER, RM DEMARINI, DM AF LEVINE, JG SCHAAPER, RM DEMARINI, DM TI COMPLEX FRAMESHIFT MUTATIONS MEDIATED BY PLASMID PKM101 - MUTATIONAL MECHANISMS DEDUCED FROM 4-AMINOBIPHENYL-INDUCED MUTATION SPECTRA IN SALMONELLA SO GENETICS LA English DT Article ID OLIGODEOXYRIBONUCLEOTIDE COLONY HYBRIDIZATION; HUMAN UROEPITHELIAL CELLS; DNA-SEQUENCE ANALYSIS; ESCHERICHIA-COLI; CARCINOGEN 4-AMINOBIPHENYL; HISD3052 ALLELE; TYPHIMURIUM HISD3052; MUTAGENICITY TEST; TARGET SEQUENCES; 1ST BASE AB We used colony probe hybridization and polymerase chain reaction/DNA sequence analysis to determine the mutations in similar to 2,400 4-aminobiphenyl (4-AB) +S9-induced revertants of the -1 frameshift allele hisD3052 and of the base-substitution allele hisG46 of Salmonella typhimurium. Most of the mutations occurred at sites containing guanine, which is the primary base at which 4-AB forms DNA adducts. A hotspot mutation involving the deletion of a CG or GC within the sequence CGCGCGCG accounted for 100 and 99.9%, respectively, of the reversion events at the hisD3052 allele in the pKM101 plasmid-minus strains TA1978 (uvr(+)) and TA1538 (Delta uvrB). In strain TA98 (Delta uvrB, pKM101), which contained the SOS DNA repair system provided by the pKM101 plasmid, similar to 85% of the revertants also contained the hotspot deletion; the remaining similar to 15 % contained one of two types pes of mutations: (1) complex frameshifts that can be described as a -2 or +1 frameshift and an associated base substitution and (2) deletions of the CC or GG sequences that flank the hotspot site (CCGCGCGCGG). We propose a misincorporation/slippage model to account for these mutations in which (1) pKM101-mediated misincorporation and translesion synthesis occurs across a 4-AB-adducted guanine; (2) the instability of such a mispairing and/or the presence of the adduct leads to strand slippage in a run of repeated bases adjacent to the adducted guanine; and (3) continued DNA synthesis from the slipped intermediate produces a frameshift associated with a base substitution. This model readily accounts for the deletion of the CC or GG sequences flanking the hotspot site, indicating that these mutations are, in fact, complex mutations in disguise (i.e., cryptic complex frameshifts). The inferred base-substitution specificity associated with the complex frameshifts at the hisD3052 allele (primarily G.C --> T.A transversions) is consistent with the finding that 4-AB induced primarily G.C --> T.A transversions at the hisG4G base-substitution allele. The model also provides a framework for understanding the different relative mutagenic potencies of 4-AB at the two alleles in the various DNA repair backgrounds of Salmonella. C1 US EPA,DIV GENET TOXICOL,RES TRIANGLE PK,NC 27711. UNIV N CAROLINA,DEPT ENVIRONM SCI & ENGN,CHAPEL HILL,NC 27599. NIEHS,MOLEC GENET LAB,RES TRIANGLE PK,NC 27709. NR 80 TC 45 Z9 45 U1 1 U2 1 PU GENETICS PI BALTIMORE PA 428 EAST PRESTON ST, BALTIMORE, MD 21202 SN 0016-6731 J9 GENETICS JI Genetics PD MAR PY 1994 VL 136 IS 3 BP 731 EP 746 PG 16 WC Genetics & Heredity SC Genetics & Heredity GA MZ474 UT WOS:A1994MZ47400004 PM 8005429 ER PT J AU LEE, JE BECK, TW BRENNSCHEIDT, U DEGENNARO, LJ RAPP, UR AF LEE, JE BECK, TW BRENNSCHEIDT, U DEGENNARO, LJ RAPP, UR TI THE COMPLETE SEQUENCE AND PROMOTER ACTIVITY OF THE HUMAN A-RAF-1 GENE (ARAF1) SO GENOMICS LA English DT Article ID COMPLETE CODING SEQUENCE; HUMAN X-CHROMOSOME; PROTEIN-KINASE; V-RAF; B-RAF; TRANSCRIPTION FACTORS; SIGNAL TRANSDUCTION; BIOLOGICAL-ACTIVITY; ONCOGENE; EXPRESSION AB The raf proto-oncogenes encode cytoplasmic protein serine/threonine kinases, which play a critical role in cell growth and development. One of these, A-raf-1 (human gene symbol, ARAF1), which is predominantly expressed in mouse urogenital tissues, has been mapped to an evolutionarily conserved linkage group composed of ARAF1, SYN1, TIMP, and properdin located at human chromosome Xp11.2. We have isolated human genomic DNA clones containing the expressed gene (ARAF1) on the X chromosome and a pseudogene (ARAF2) on chromosome 7p12-q11.21. Analysis of the nucleotide sequence from the ARAF1 genomic clones demonstrated that it consists of 16 exons encoded by minimally 10,776 nucleotides. The major transcriptional start site (+1) was determined by RNase protection and primer extension assays. Promoter activity was confirmed by functional assays using DNA fragments fused to a CAT reporter gene. The ARAF1 minimal promoter, located between nucleotides -59 and +93, has a low G + C content and lacks consensus TATA and Inr sequences but shows sequence similarity at position -1 to the E box that is known to interact with USF and TFII-I transcription factors. (C) 1994 Academic Press, Inc. C1 NCI,FREDERICK CANC RES & DEV CTR,VIRAL CARCINOGENESIS LAB,FREDERICK,MD 21702. NCI,FREDERICK CANC RES & DEV CTR,PROGRAM RESOURCES INC DYNCORP,FREDERICK,MD 21702. GEORGE WASHINGTON UNIV,DEPT GENET,WASHINGTON,DC. UNIV MASSACHUSETTS,SCH MED,DEPT NEUROL,WORCESTER,MA 01655. UNIV MASSACHUSETTS,SCH MED,DEPT CELL BIOL,WORCESTER,MA 01655. NR 64 TC 16 Z9 19 U1 0 U2 1 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0888-7543 J9 GENOMICS JI Genomics PD MAR 1 PY 1994 VL 20 IS 1 BP 43 EP 55 DI 10.1006/geno.1994.1125 PG 13 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA NB193 UT WOS:A1994NB19300007 PM 8020955 ER PT J AU ARONS, BS FRANK, RG GOLDMAN, HH MCGUIRE, TG STEPHENS, S AF ARONS, BS FRANK, RG GOLDMAN, HH MCGUIRE, TG STEPHENS, S TI MENTAL-HEALTH AND SUBSTANCE-ABUSE COVERAGE UNDER HEALTH REFORM SO HEALTH AFFAIRS LA English DT Article ID SERVICES AB President Clinton's health care reform proposal articulates a complete vision for the mental health and substance abuse care system that includes a place for those traditionally served by both the public and the private sectors. Mental health and substance abuse services are to be fully integrated into health alliances under the president's proposal. If this is to occur, we must come to grips with both the history and the insurance-related problems of financing mental health/substance abuse' care: (1) the ability of health plans to manage die benefit so as to alter patterns of use; (2) a payment system for health plans that addresses biased selection; and (3) preservation of the existing public investment while accommodating in a fair manner differences in funding across the fifty states. C1 JOHNS HOPKINS UNIV,SCH HYG & PUBL HLTH,DEPT HLTH POLICY & MANAGEMENT,BALTIMORE,MD 21218. UNIV MARYLAND,COLL PK,MD 20742. BOSTON UNIV,BOSTON,MA 02215. NIMH,BETHESDA,MD 20892. RP ARONS, BS (reprint author), US DEPT HHS,CTR MENTAL HLTH SERV,WASHINGTON,DC 20201, USA. NR 26 TC 27 Z9 27 U1 1 U2 2 PU PROJECT HOPE-HEALTH AFFAIRS PI SYRACUSE PA PO BOX 8015, SYRACUSE, NY 13217 SN 0278-2715 J9 HEALTH AFFAIR JI Health Aff. PD SPR PY 1994 VL 13 IS 1 BP 192 EP 205 DI 10.1377/hlthaff.13.1.192 PG 14 WC Health Care Sciences & Services; Health Policy & Services SC Health Care Sciences & Services GA MX788 UT WOS:A1994MX78800019 PM 8188135 ER PT J AU FRANK, RG MCGUIRE, TG REGIER, DA MANDERSCHEID, R WOODWARD, A AF FRANK, RG MCGUIRE, TG REGIER, DA MANDERSCHEID, R WOODWARD, A TI PAYING FOR MENTAL-HEALTH AND SUBSTANCE-ABUSE CARE SO HEALTH AFFAIRS LA English DT Article AB Fifty-four billion dollars was spent on alcohol/drug abuse and mental health treatment in 1990. These expenditures were concentrated in the area of inpatient psychiatric care and on persons with severe mental health and substance abuse problems. The data on expenditure patters for mental health and substance abuse care suggest that successful health care reform in this area must implement mechanisms for controlling inpatient utilization and managing the care of persons with the most severe disorders. C1 BOSTON UNIV,DEPT ECON,BOSTON,MA 02215. NIMH,DIV EPIDEMIOL & SERV RES,BETHESDA,MD 20892. RP FRANK, RG (reprint author), JOHNS HOPKINS UNIV,SCH PUBL HLTH,BALTIMORE,MD 21218, USA. NR 9 TC 17 Z9 17 U1 0 U2 0 PU PROJECT HOPE-HEALTH AFFAIRS PI SYRACUSE PA PO BOX 8015, SYRACUSE, NY 13217 SN 0278-2715 J9 HEALTH AFFAIR JI Health Aff. PD SPR PY 1994 VL 13 IS 1 BP 337 EP 342 DI 10.1377/hlthaff.13.1.337 PG 6 WC Health Care Sciences & Services; Health Policy & Services SC Health Care Sciences & Services GA MX788 UT WOS:A1994MX78800036 PM 8188153 ER PT J AU PIRIE, PL STONE, EJ ASSAF, AR FLORA, JA MASCHEWSKYSCHNEIDER, U AF PIRIE, PL STONE, EJ ASSAF, AR FLORA, JA MASCHEWSKYSCHNEIDER, U TI PROGRAM-EVALUATION STRATEGIES FOR COMMUNITY-BASED HEALTH PROMOTION PROGRAMS - PERSPECTIVES FROM THE CARDIOVASCULAR-DISEASE COMMUNITY RESEARCH AND DEMONSTRATION STUDIES SO HEALTH EDUCATION RESEARCH LA English DT Article ID STANFORD 5-CITY PROJECT; WIDE SMOKING CESSATION; EDUCATION-PROGRAM; PHYSICIAN PRACTICE; INTERVENTION; PREVENTION; DESIGN; ATTITUDES; PAWTUCKET; REDUCTION AB Community-based programs are being widely adopted in the struggle to prevent chronic disease. Program evaluation of community-based programs involves a particular set of problems stemming from the variety of activities being undertaken simultaneously, the multiple intermediate goals of the programs and the rapidity with which the programs evolve. An analysis of the experience of four large community-based cardiovascular disease research and demonstration studies (Stanford Five-City Project, Minnesota Heart Health Program, Pawtucket Heart Health Program and the German Cardiovascular Prevention Project) provides valuable models, methodologies and strategies for planning and conducting evaluations of public health programs or community studies. By comparing and combining their experiences, the four programs have identified eight categories of evaluation for community studies, including formative evaluation, quality assurance, assessment of delivered dose, assessment of received dose, component program impact, intermediate outcomes, community impact and cost analysis. This paper presents information on the strategies by which each of the four programs addressed these evaluation categories. C1 NHLBI,BETHESDA,MD 20892. MEM HOSP,PAWTUCKET HEART HLTH PROGRAM,DIV HLTH EDUC,PAWTUCKET,RI 02860. STANFORD UNIV,STANFORD HEART DIS PREVENT PROGRAM,STANFORD,CA 94305. BREMEN INST PREVENT RES & SOC MED,DIV EPIDEMIOL,GRUENEN STR 120,W-2800 BREMEN,GERMANY. RP PIRIE, PL (reprint author), UNIV MINNESOTA,SCH PUBL HLTH,DIV EPIDEMIOL,MINNEAPOLIS,MN 55455, USA. FU NHLBI NIH HHS [HL-21906, HL-23639, HL-25523] NR 51 TC 18 Z9 18 U1 0 U2 0 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 1994 VL 9 IS 1 BP 23 EP 36 DI 10.1093/her/9.1.23 PG 14 WC Education & Educational Research; Public, Environmental & Occupational Health SC Education & Educational Research; Public, Environmental & Occupational Health GA NA277 UT WOS:A1994NA27700003 PM 10146732 ER PT J AU ADAMS, DH BURRA, P HUBSCHER, SG ELIAS, E NEWMAN, W AF ADAMS, DH BURRA, P HUBSCHER, SG ELIAS, E NEWMAN, W TI ENDOTHELIAL ACTIVATION AND CIRCULATING VASCULAR ADHESION MOLECULES IN ALCOHOLIC LIVER-DISEASE SO HEPATOLOGY LA English DT Article ID TUMOR-NECROSIS-FACTOR; LYMPHOCYTES-T; HEPATITIS; CELLS; EXPRESSION; ANTIGEN; VCAM-1; ICAM-1; INDUCTION; SELECTIN AB Alcoholic hepatitis is characterized by hepatocyte necrosis associated with infiltration of the liver parenchyma by neutrophils. The mechanisms responsible for recruiting neutrophils to the liver are unknown. We report high circulating levels and tissue expression of the endothelial adhesion molecule E-selectin in alcoholic hepatitis. Because expression of E-selectin is involved in neutrophil transmigration into inflamed tissue, it may play a crucial role in the recruitment of neutrophils to the liver in alcoholic hepatitis. By contrast, we detected high levels of vascular cell adhesion molecule-1, the endothelial counter-receptor for the lymphocyte adhesion molecule very late antigen-4, in alcoholic cirrhosis, which is associated with a predominantly mononuclear cell infiltrate. Both diseases were associated with high levels of circulating intercellular adhesion molecule-1, which is released by activated lymphocytes, providing further evidence of immune activation in alcoholic liver disease. C1 NCI, EXPTL IMMUNOL BRANCH, BETHESDA, MD 20892 USA. UNIV PADUA, INST INTERNAL MED, DEPT GASTROENTEROL, PADUA, ITALY. UNIV BIRMINGHAM, SCH MED, DEPT PATHOL, BIRMINGHAM B15 2TH, W MIDLANDS, ENGLAND. OTSUKA PHARMACEUT INC, MARYLAND RES LABS, ROCKVILLE, MD 20850 USA. RP QUEEN ELIZABETH HOSP, LIVER RES LABS, LIVER UNIT, BIRMINGHAM B15 2TH, W MIDLANDS, ENGLAND. RI Adams, David/C-9092-2009 NR 39 TC 83 Z9 86 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0270-9139 EI 1527-3350 J9 HEPATOLOGY JI Hepatology PD MAR PY 1994 VL 19 IS 3 BP 588 EP 594 DI 10.1002/hep.1840190308 PG 7 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA MY449 UT WOS:A1994MY44900007 PM 7509770 ER PT J AU ROSENFELD, MA CHU, CS SETH, P DANEL, C BANKS, T YONEYAMA, K YOSHIMURA, K CRYSTAL, RG AF ROSENFELD, MA CHU, CS SETH, P DANEL, C BANKS, T YONEYAMA, K YOSHIMURA, K CRYSTAL, RG TI GENE-TRANSFER TO FRESHLY ISOLATED HUMAN RESPIRATORY EPITHELIAL-CELLS IN-VITRO USING A REPLICATION-DEFICIENT ADENOVIRUS CONTAINING THE HUMAN CYSTIC-FIBROSIS TRANSMEMBRANE CONDUCTANCE REGULATOR CDNA SO HUMAN GENE THERAPY LA English DT Article ID DEPENDENT PROTEIN-KINASE; RAT EMBRYO CELLS; INSITU HYBRIDIZATION; CHLORIDE CHANNELS; AIRWAY EPITHELIUM; EXPRESSION; IDENTIFICATION; CFTR; LOCALIZATION; INDIVIDUALS AB Cystic fibrosis (CF) results from mutations of the CF transmembrane conductance regulator (CFTR) gene and subsequent defective regulation of cAMP-stimulated chloride (CI-) permeability across the apical membrane of epithelial cells. In vitro transfer of normal CFTR cDNA corrects this defect, and studies in experimental animals have shown successful gene transfer to airway epithelium in vivo using a recombinant adenoviral vector containing the human CFTR cDNA (AdCFTR), supporting the feasibility of in vivo AdCFTR-mediated gene therapy for the respiratory manifestations of CF. One step in applying this therapy to CF patients is to evaluate the safety and efficacy of AdCFTR-mediated gene transfer in the actual target for human gene therapy, human airway epithelium. The present study demonstrates that AdCFTR restores cAMP-stimulated Cl- permeability in human CF bronchial epithelial cells. In addition, the study utilizes freshly isolated human airway epithelial cells from the nose and/or bronchi of normal individuals and/or individuals with CF to demonstrate that after in vitro AdCFTR-mediated gene transfer: (i) AdCFTR DNA does not replicate as a function of dose and time; (ii) CF epithelial cells express AdCFTR-mediated normal human CFTR mRNA; and (iii) CF epithelial cells, including terminally differentiated ciliated cells (the most common airway epithelial cell type), express the normal human CFTR protein. Together, these data support the use of AdCFTR in human gene therapy trials and suggest that biologic efficacy should be achievable in vivo. C1 CORNELL UNIV,MED CTR,COLL MED,DIV PULM & CRIT CARE MED,NEW YORK,NY 10021. RP ROSENFELD, MA (reprint author), NHLBI,PULM BRANCH,ROOM 6D03,BLDG 10,BETHESDA,MD 20892, USA. NR 56 TC 44 Z9 44 U1 0 U2 1 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 SN 1043-0342 J9 HUM GENE THER JI Hum. Gene Ther. PD MAR PY 1994 VL 5 IS 3 BP 331 EP 342 DI 10.1089/hum.1994.5.3-331 PG 12 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA NB818 UT WOS:A1994NB81800007 PM 7517189 ER PT J AU CULVER, KW VANGILDER, J LINK, CJ CARLSTROM, T BUROKER, T YUH, W KOCH, K SCHABOLD, K DOORNBAS, S WETJEN, B BLAESE, RM AF CULVER, KW VANGILDER, J LINK, CJ CARLSTROM, T BUROKER, T YUH, W KOCH, K SCHABOLD, K DOORNBAS, S WETJEN, B BLAESE, RM TI GENE-THERAPY FOR THE TREATMENT OF MALIGNANT BRAIN-TUMORS WITH IN-VIVO TUMOR TRANSDUCTION WITH THE HERPES-SIMPLEX THYMIDINE KINASE GENE GANCICLOVIR SYSTEM SO HUMAN GENE THERAPY LA English DT Article ID RETROVIRAL VECTORS; GLIOMAS; RECOMBINATION; REOPERATION; METASTASES; DEFICIENCY; TRIAL AB Murine retroviral vectors can infect a wide variety of proliferating mammalian cell types (e.g. lymphocytes). Non-proliferating tissues (e.g. neurons) are not transduced by murine retroviral vectors. These findings suggest that this type of vector may be useful for the selective introduction of genes into growing tumors in the brain, since the tumor is essentially the only tissue that will integrate and express the vector genes. We have investigated the possibility of direct in vivo gene transfer into growing brain tumors in animals. Rats with a malignant brain tumor were given an intratumoral stereotaxic injection of murine retroviral vector-producer cells (VPC) that were producing vectors containing the Herpes Simplex-thymidine kinase (HS-tk) gene or a control VPC line containing the beta-galactosidase gene. The animals were rested 5 days to allow time for the HS-tk retroviral vectors that were produced in situ to transduce the neighboring proliferating gliosarcoma. The animals were then treated with the anti-herpes drug ganciclovir (GCV). Tumors injected with the HS-tk VPC regressed completely with GCV therapy while the tumors injected with beta-galactosidase VPC developed large tumors. Staining for beta-galactosidase (+) cells in control animal brain revealed transduction of 10-50% of the tumor cells without evidence of transduction of the surrounding normal brain tissue. No significant toxicity was observed in toxicity studies in mice, rats and non-human primates. Based upon these findings, we have proposed a human clinical trial to determine if the direct implantation of the G1TkSvNa VPC line into growing human brain tumors will induce regression with GCV therapy. The patient population primarily consists of individuals with recurrent malignant tumors who are currently considered ineligible for the approved NIH trial due to the size of the tumor. The RAC has previously approved an initial trial at NIH involving the stereotaxic injection of brain tumors. In this protocol, patients will undergo surgical debulking of the tumor followed by repeated treatments of HS-tk VPC into the tumor bed in an attempt to induce complete regression of the tumor with GCV therapy. These are patients who have failed standard therapy for their tumor and are expected to survive for several weeks to a few months. C1 UNIV IOWA,DIV NEUROSURG,IOWA CITY,IA 52242. UNIV IOWA,DEPT RADIOL,IOWA CITY,IA 52242. UNIV IOWA,COLL MED,DEPT RADIOL,IOWA CITY,IA 52242. IMMC,DEPT NEUROSURG,DES MOINES,IA. IMMC,DEPT RADIOL,DES MOINES,IA. NCI,GENET THERAPY INC,CELLULAR IMMUNOL SECT,GAITHERSBURG,MD. RP CULVER, KW (reprint author), IMMC,HUMAN GENE THERAPY RES INST,DES MOINES,IA, USA. NR 27 TC 96 Z9 97 U1 0 U2 0 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 SN 1043-0342 J9 HUM GENE THER JI Hum. Gene Ther. PD MAR PY 1994 VL 5 IS 3 BP 343 EP 379 DI 10.1089/hum.1994.5.3-343 PG 37 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA NB818 UT WOS:A1994NB81800008 PM 8018748 ER PT J AU PORTER, JC PUCK, JM AF PORTER, JC PUCK, JM TI 7 CHROMOSOME-22 STR POLYMORPHISMS SO HUMAN MOLECULAR GENETICS LA English DT Article C1 NATL CTR HUMAN GENOME RES,IMMUNOL GENET SECT,BETHESDA,MD 20892. RP PORTER, JC (reprint author), ALBANY MED COLL,DEPT PEDIAT,43 NEW SCOTLAND AVE,ALBANY,NY 12208, USA. FU NCI NIH HHS [CA09615]; NHGRI NIH HHS [R01 HG00233, HGO0425] NR 4 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0964-6906 J9 HUM MOL GENET JI Hum. Mol. Genet. PD MAR PY 1994 VL 3 IS 3 BP 519 EP 519 DI 10.1093/hmg/3.3.519 PG 1 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA NA583 UT WOS:A1994NA58300024 PM 8012367 ER PT J AU KOZAK, D AF KOZAK, D TI REIFYING THE BODY THROUGH THE MEDICALIZATION OF VIOLENT DEATH SO HUMAN ORGANIZATION LA English DT Article DE CRITICAL THEORY; MEDICALIZATION OF DEATH; NATIVE AMERICANS ID NEW-MEXICO; SUICIDE AB This article suggests that the violent deaths of American Indians are being medicalized. The biomedical classification of violent death (suicides, homicides, accidents) subverts the social elements of causality in favor of identifying individual culpability. It is here argued that the biomedical nosology known as the International Classification of Disease (ICD) has entered the everyday, commonsensical discourse of those who investigate these deaths (police, EMTs, medical examiners). After presenting a theoretical framework I offer four ethnographic vignettes to illustrate how death has been medicalized among the Tohono O'odham Indians of southern Arizona. These vignettes, though not statistically significant, reveal how cause is inscribed on the bodies of the deceased. In other words, the classification of violent death reifies the individual body at the expense of the social body. Five recommendations for further research and consideration are then offered. C1 NIH,PHOENIX,AZ. INDIAN HLTH SERV,PHEONIX AREA OFF,PHOENIX,AZ. RP KOZAK, D (reprint author), ARIZONA STATE UNIV,DEPT ANTHROPOL,TEMPE,AZ 85287, USA. NR 30 TC 0 Z9 0 U1 1 U2 1 PU SOC APPLIED ANTHROPOLOGY PI OKLAHOMA CITY PA BUSINESS OFFICE BOX 24083, OKLAHOMA CITY, OK 73124 SN 0018-7259 J9 HUM ORGAN JI Hum. Organ. PD SPR PY 1994 VL 53 IS 1 BP 48 EP 54 PG 7 WC Anthropology; Social Sciences, Interdisciplinary SC Anthropology; Social Sciences - Other Topics GA MX045 UT WOS:A1994MX04500006 ER PT J AU ABATI, A LANDUCCI, D SOLOMON, D AF ABATI, A LANDUCCI, D SOLOMON, D TI DIAGNOSIS OF PULMONARY MICROVASCULAR METASTASES BY CYTOLOGIC EVALUATION OF PULMONARY-ARTERY CATHETER-DERIVED BLOOD SPECIMENS SO HUMAN PATHOLOGY LA English DT Article DE PULMONARY MICROVASCULAR CYTOLOGY; PULMONARY ARTERY CATHETER ID SUBACUTE COR-PULMONALE; LYMPHANGITIC CARCINOMATOSIS; TUMOR EMBOLIZATION; EMBOLISM; CANCER; DYSPNEA; LUNG C1 NIH,DEPT CRIT CARE MED,BETHESDA,MD. RP ABATI, A (reprint author), NCI,CYTOPATHOL SECT,BLDG 10,ROOM 2A19,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 23 TC 17 Z9 17 U1 0 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0046-8177 J9 HUM PATHOL JI Hum. Pathol. PD MAR PY 1994 VL 25 IS 3 BP 257 EP 262 DI 10.1016/0046-8177(94)90197-X PG 6 WC Pathology SC Pathology GA NF072 UT WOS:A1994NF07200008 PM 7512073 ER PT J AU BLACK, HR ALDERMAN, MH COOPER, JK CUTLER, J GOINS, MK HORAN, MJ HUTCHINS, EC MANN, RJ SCHRON, E WHELTON, PK ROCCELLA, EJ AMES, MV ANDERSON, DE BRITO, GT AF BLACK, HR ALDERMAN, MH COOPER, JK CUTLER, J GOINS, MK HORAN, MJ HUTCHINS, EC MANN, RJ SCHRON, E WHELTON, PK ROCCELLA, EJ AMES, MV ANDERSON, DE BRITO, GT TI NATIONAL HIGH BLOOD-PRESSURE EDUCATION-PROGRAM WORKING GROUP-REPORT ON HYPERTENSION IN THE ELDERLY SO HYPERTENSION LA English DT Article DE AGING; HYPERTENSION, SYSTOLIC; EDUCATION; CARDIOVASCULAR DISEASES; ANTIHYPERTENSIVE THERAPY ID QUALITY-OF-LIFE; OSLERS MANEUVER; TRIAL; MORTALITY; MORBIDITY; THERAPY; PATIENT; PARTY AB Raised blood pressures in the elderly and the increased prevalence of hypertension in this population are not benign occurrences and should not be viewed as a normal or inevitable consequence of aging. In fact, the relation of systolic and diastolic blood pressures to cardiovascular events is generally more pronounced in people aged 65 years and older when compared with those aged 35 to 64. The relative risk of cardiovascular disease is greater among the elderly at every level of blood pressure. Furthermore, the absolute likelihood that an older individual will have a cardiovascular event is substantially greater than for someone younger, reflecting the increased prevalence of other cardiovascular disease risk factors in this age group. Thus, equivalent blood pressure reduction is likely to produce a greater benefit in the elderly than in younger patients at every level of blood pressure. This report, an update of the 1985 Working Group Report on Hypertension in the Elderly, has two aims: to guide clinicians in their care of elderly patients with hypertension and to assist health care professionals participating in high blood pressure control programs that serve the elderly. The role of lifestyle modifications-weight loss, dietary sodium restriction, alcohol reduction, and exercise-as definitive or adjunctive therapy to drug treatment is discussed. In addition, the report reviews the relative advantages and disadvantages of the specific classes of antihypertensive medications. C1 NHLBI,NATL HIGH BLOOD PRESSURE EDUC PROGRAM,BETHESDA,MD 20892. RUSH PRESBYTERIAN ST LUKES MED CTR,DEPT PREVENT MED,CHICAGO,IL. ALBERT EINSTEIN COLL MED,DEPT EPIDEMIOL & SOCIAL MED,BRONX,NY. NIA,BETHESDA,MD. NHLBI,DIV EPIDEMIOL & CLIN APPLICAT,BETHESDA,MD 20892. S DADE INC,COMMUNITY HLTH,MIAMI,FL. EMORY UNIV,DEPT MED,DIV HYPERTENS,ATLANTA,GA 30322. NHLBI,DIV HEART & VAC DIS,BETHESDA,MD. VET ADM MED CTR,PHYS MED & REHABIL SERV,FAYETTEVILLE,AR. UNIV ARKANSAS MED SCI HOSP,DEPT FAMILY & COMMUNITY MED,LITTLE ROCK,AR. JOHNS HOPKINS MED INST,WELCH CTR PREVENT EPIDEMIOL & CLIN RES,BALTIMORE,MD. ROW SCI INC,ROCKVILLE,MD. UNIV RES CORP,BETHESDA,MD. NR 49 TC 168 Z9 175 U1 0 U2 3 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0194-911X J9 HYPERTENSION JI Hypertension PD MAR PY 1994 VL 23 IS 3 BP 275 EP 285 PG 11 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA MZ690 UT WOS:A1994MZ69000002 ER PT J AU ROTH, BJ WIKSWO, JP AF ROTH, BJ WIKSWO, JP TI ELECTRICAL-STIMULATION OF CARDIAC TISSUE - A BIDOMAIN MODEL WITH ACTIVE MEMBRANE-PROPERTIES SO IEEE TRANSACTIONS ON BIOMEDICAL ENGINEERING LA English DT Article ID DIMENSIONAL ANISOTROPIC BISYNCYTIA; CYLINDRICAL BUNDLE; MUSCLE; PROPAGATION; SIMULATION; CONDUCTIVITIES; MECHANISM; FIELDS; HEART AB Numerical calculations simulated the response of cardiac muscle to stimulation by electrical current. The bidomain model with unequal anisotropy ratios represented the tissue, and parallel leak and active sodium channels represented the membrane conductance. The speed of the wavefront was faster in the direction parallel to the myocardial fibers than in the direction perpendicular to them. However, for cathodal stimulation well above threshold, the wavefront originated farther from the cathode in the direction perpendicular to the myocardial fibers than in the direction parallel to them, consistent with observations of a dog-bone-shaped virtual cathode made by Wikswo et al., Circ. Res. 68:513-530, 1991. The model showed that the virtual cathode size and shape were dependent upon both membrane and tissue conductivities. Increasing the peak sodium conductance or reducing the transverse intracellular conductivity accentuated the dog-bone shape, while the opposite change caused the virtual cathode to become more elliptical, with the major axis of the ellipse transverse to the fiber direction. A cathodal stimulus created regions of hyperpolarization that slowed conduction of the wavefront propagating parallel to the fibers. An anodal stimulus evoked a wavefront with a complex shape; activation originated from two depolarized regions 1 to 2 mm from the stimulus site along the fiber direction. The threshold current strength (0.5 ms duration pulse) for a cathodal stimulus was 0.048 mA, and for an anodal stimulus was 0.67 mA. When the model was modified to simulate the effect of electropermeabilization, which may be present when the transmembrane potential reaches very large values near the stimulating electrode, our qualitative conclusions remained unchanged. These three-dimensional calculations using an active membrane model are consistent with the results obtained previously using two-dimensional linear models and go further to provide an explanation for anodal excitation. Most importantly, by including the third dimension and a nonlinear membrane, this model provides an important physiologically realistic link between the data recorded in vivo from the canine heart and the theoretical concept that the anisotropic bidomain nature of cardiac tissue can affect cardiac activation and propagation. C1 VANDERBILT UNIV,DEPT PHYS & ASTRON,LIVING STATE PHYS GRP,NASHVILLE,TN 37235. RP ROTH, BJ (reprint author), NIH,BIOMED ENGN & INSTRUMENTAT PROGRAM,BETHESDA,MD 20892, USA. RI Roth, Bradley/A-4920-2008 FU NHLBI NIH HHS [HL 36724, HL 46681] NR 29 TC 79 Z9 80 U1 1 U2 2 PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017-2394 SN 0018-9294 J9 IEEE T BIO-MED ENG JI IEEE Trans. Biomed. Eng. PD MAR PY 1994 VL 41 IS 3 BP 232 EP 240 DI 10.1109/10.284941 PG 9 WC Engineering, Biomedical SC Engineering GA NL828 UT WOS:A1994NL82800003 PM 8045575 ER PT J AU DAY, CE SCHMITT, K ROBINSON, MA AF DAY, CE SCHMITT, K ROBINSON, MA TI FREQUENT RECOMBINATION IN THE HUMAN T-CELL RECEPTOR BETA-GENE COMPLEX SO IMMUNOGENETICS LA English DT Article ID POLYMERASE CHAIN-REACTION; CLASS-II REGION; ALLELIC VARIATIONS; DNA POLYMORPHISMS; HUMAN FAMILIES; LINKAGE MAP; ORGANIZATION; IDENTIFICATION; POPULATIONS; SEGREGATION AB Although individual TCRVBV gene segments exhibit limited polymorphism, human T-cell receptor beta (TCRB) haplotypes are characterized by multiple different combinations of allelic markers. This observation suggests that genetic recombination may have played a role in the generation of these haplotypes. Meiotic recombination in a region spanning approximately 250 kilobases (kb) at the 3' end of the TCRB gene complex was investigated by extended family studies and by analysis of single sperm. Segregation patterns of polymorphic TCRB markers in families allowed the assignment of TCRB alleles to parental haplotypes and detection of recombinants among the offspring. Among the 178 informative paternal meioses, four (approximately 2%) were recombinant, whereas no recombinants were found in the 199 maternal meioses. In addition, segregation of two allelic markers was examined in a total of 1101 individual sperm from two heterozygous donors to detect exchange events in this region. The results revealed a similar rate of recombination, approximately 1.3%, which, along with the family data, suggests that at, least in males, meiotic recombination in this 250 kb region may be six times higher than the ''average'' rate of 1% per 10(6) bases that has been estimated for the human genome. C1 NIAID,IMMUNOGENET LAB,ROCKVILLE,MD 20852. UNIV SO CALIF,DEPT BIOL SCI,DIV MOLEC BIOL,LOS ANGELES,CA 90089. NR 35 TC 11 Z9 11 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 1994 VL 39 IS 5 BP 335 EP 342 PG 8 WC Genetics & Heredity; Immunology SC Genetics & Heredity; Immunology GA ND510 UT WOS:A1994ND51000005 PM 8168851 ER PT J AU RINALDI, MG DIXON, DM AF RINALDI, MG DIXON, DM TI THE EVOLVING ETIOLOGIES OF INVASIVE MYCOSES - INTRODUCTION SO INFECTIOUS DISEASES IN CLINICAL PRACTICE LA English DT Editorial Material ID HOSPITAL-ACQUIRED CANDIDEMIA; RISK-FACTORS C1 NIAID,BETHESDA,MD 20892. RP RINALDI, MG (reprint author), UNIV TEXAS,HLTH SCI CTR,DEPT PATHOL,7703 FLOYD CURL DR,SAN ANTONIO,TX 78284, USA. NR 4 TC 1 Z9 1 U1 0 U2 0 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 1994 VL 3 SU 2 BP S47 EP S49 DI 10.1097/00019048-199403002-00001 PG 3 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA NF874 UT WOS:A1994NF87400001 ER PT J AU WALSH, TJ AF WALSH, TJ TI EVOLVING PATTERNS OF NOSOCOMIAL AND COMMUNITY-ACQUIRED DEEP MYCOSES - ANALOGIES TO OTHER INFECTIONS AND IMPLICATIONS FOR PRACTITIONERS SO INFECTIOUS DISEASES IN CLINICAL PRACTICE LA English DT Review ID INVASIVE PULMONARY ASPERGILLOSIS; IMMUNODEFICIENCY-VIRUS-INFECTION; AMPHOTERICIN-B; FUNGAL-INFECTIONS; CANCER-PATIENTS; CANDIDA-KRUSEI; DISSEMINATED HISTOPLASMOSIS; MYCOBACTERIUM-TUBERCULOSIS; PARENTERAL-NUTRITION; ORAL CANDIDIASIS RP WALSH, TJ (reprint author), NCI,ORGAN CHEM SECT,BLDG 10,ROOM 13N-240,BETHESDA,MD 20892, USA. NR 104 TC 3 Z9 3 U1 0 U2 0 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 1994 VL 3 SU 2 BP S103 EP S112 PG 10 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA NF874 UT WOS:A1994NF87400010 ER PT J AU WILBUR, WJ COFFEE, L AF WILBUR, WJ COFFEE, L TI THE EFFECTIVENESS OF DOCUMENT NEIGHBORING IN SEARCH ENHANCEMENT SO INFORMATION PROCESSING & MANAGEMENT LA English DT Article ID RETRIEVAL PERFORMANCE; RELEVANCE FEEDBACK; INFORMATION AB We consider two kinds of queries that may be applied to a database. The first is a query written by a searcher to express an information need. The second is a request for documents most similar to a document already judged relevant by the searcher. We examine the effectiveness of these two procedures and show that in important cases the latter query type is more effective than the former. This provides a new view of the cluster hypothesis and a justification for document neighboring procedures (precomputation of closely related documents). If all the documents in a database have readily available precomputed nearest neighbors, a new search algorithm, which we call parallel neighborhood searching, is conveniently used. We show that this feedback-based method provides significant improvement in recall over traditional linear searching methods, and even appears superior to traditional feedback methods in overall performance. RP WILBUR, WJ (reprint author), NIH,NATL LIB MED,NATL CTR BIOTECHNOL INFORMAT,BLDG 38A,RM 8S806,8600 ROCKVILLE PIKE,BETHESDA,MD 20894, USA. NR 22 TC 34 Z9 35 U1 0 U2 2 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0306-4573 J9 INFORM PROCESS MANAG JI Inf. Process. Manage. PD MAR-APR PY 1994 VL 30 IS 2 BP 253 EP 266 DI 10.1016/0306-4573(94)90068-X PG 14 WC Computer Science, Information Systems; Information Science & Library Science SC Computer Science; Information Science & Library Science GA MP710 UT WOS:A1994MP71000007 ER PT J AU BENSON, JM BARR, EB BECHTOLD, WE CHENG, YS DUNNICK, JK EASTIN, WE HOBBS, CH KENNEDY, CH MAPLES, KR AF BENSON, JM BARR, EB BECHTOLD, WE CHENG, YS DUNNICK, JK EASTIN, WE HOBBS, CH KENNEDY, CH MAPLES, KR TI FATE OF INHALED NICKEL-OXIDE AND NICKEL SUBSULFIDE IN F344/N RATS SO INHALATION TOXICOLOGY LA English DT Article ID INHALATION EXPOSURE; B6C3F1 MICE; LUNG; CLEARANCE; RESPIRATION; TOXICITY; AEROSOL AB The fates of inhaled nickel oxide (NiO, green oxide calcined at 1200 degrees C) and nickel subsulfide (Ni3S2), two occupationally relevant nickel compounds, have been studied in male F344/N rats. Croups of rats underwent pernasal exposure to 9.9 mg NiO/m(3) or to 5.7 mg Ni3S2/m(3) for 70 and 120 min, respectively. The activity median aerodynamic diameters (geomeiric standard deviation) of the NiO and Ni3S2 aerosols were 1.3 mu m (2.0) and 1.3 mu m (1.5), respectively. End points evaluated included total and regional respiratory tract deposition oi the aerosols, lung clearance of deposited material, distribution of solubilized material to extrarespiratory tract tissue, and pathways of Ni excretion from the body. The fractions oi the inhaled NiO and Ni3S2 aerosols that deposited in the respiratory tract were 0.11 and 0.13, respectively. The fractions of the inhaled aerosol that deposited in the lungs were 0.05 for both aerosols. Inhaled NiO cleared slowly from the lungs, with a half-life of approximately 120 days. Following NiO exposures, Ni was not distributed to the extrarespiratory tract tissue, and the material was excreted only in the feces during the first few days after the exposure. Inhaled Ni3S2 cleared rapidly from the lungs, with a clearance half-time of approximately 4 days. Nickel was detected in several extrarespiratory tract tissues of Ni3S2-exposed rats within a few hours after the end of the exposure, and was detected in lung and kidneys up to 16 days postexposure. Results of this study indicate that two occupationally relevant Ni compounds formed during the refining of Ni ore have significantly different lung retention and tissue distribution patterns. As expected, the high-temperature NiO behaves as a relatively insoluble particle and is retained in lung, while Ni3S2 behaves as a relatively soluble particle, with fairly rapid dissolution in lung and distribution of Ni to extrarespiratory tract tissues. C1 NIEHS,NATL TOXICOL PROGRAM,RES TRIANGLE PK,NC 27709. INHALAT TOXICOL RES INST,ALBUQUERQUE,NM 87185. RP BENSON, JM (reprint author), INHALAT TOXICOL RES INST,POB 5890,ALBUQUERQUE,NM 87185, USA. NR 24 TC 23 Z9 23 U1 0 U2 6 PU TAYLOR & FRANCIS PI BRISTOL PA 1900 FROST ROAD, SUITE 101, BRISTOL, PA 19007-1598 SN 0895-8378 J9 INHAL TOXICOL JI Inhal. Toxicol. PD MAR-APR PY 1994 VL 6 IS 2 BP 167 EP 183 DI 10.3109/08958379409029703 PG 17 WC Toxicology SC Toxicology GA NJ195 UT WOS:A1994NJ19500006 ER PT J AU ZHANG, L BLOT, WJ YOU, WC CHANG, YS LIU, XQ KNELLER, RW ZHAO, L LIU, WD LI, JY JIN, ML XU, GW FRAUMENI, JF YANG, CS AF ZHANG, L BLOT, WJ YOU, WC CHANG, YS LIU, XQ KNELLER, RW ZHAO, L LIU, WD LI, JY JIN, ML XU, GW FRAUMENI, JF YANG, CS TI SERUM MICRONUTRIENTS IN RELATION TO PRECANCEROUS GASTRIC-LESIONS SO INTERNATIONAL JOURNAL OF CANCER LA English DT Article ID SUBSEQUENT CANCER; STOMACH-CANCER; ASCORBIC-ACID; RISK; FERRITIN; SELENIUM; POPULATION; ETIOLOGY; RETINOL; ASSAY AB Serum levels of retinol, beta-carotene, ascorbic acid, alpha-tocopherol, selenium, ferritin, copper, and zinc were assayed for approximately 600 adults aged 35 to 64 with pre-cancerous gastric lesions in an area of China with one of the world's highest rates of stomach cancer. Previous studies have shown that the cancers generally are preceded by chronic atropic gastritis (CAG), intestinal metaplasia (IM) and dysplasia. Concentrations of beta-carotene and ascorbic acid were significantly lower among individuals with IM than among those whose most severe lesion was superficial gastritis or CAG. The associations with IM for these nutrients were strong and independent. In combination, the odds of CAG progressing to IM were only 1/6 as high among those with upper tertile levels of beta-carotene and ascorbic acid as among those with lower tertile levels of both nutrients. The serum levels of beta-carotene and ascorbic acid were similar for individuals having IM with or without accompanying dysplasia. Risk of IM was also somewhat increased among those with low serum ferritin, but no significant effects were observed in multivariate analyses for the other nutrients assayed. The findings point to a major influence of specific nutrient deficits in the mechanisms of gastric carcinogenesis in this high-risk area. (C) 1994 Wiley-Liss, Inc.* C1 NCI,BETHESDA,MD 20892. BEIJING INST CANC RES,BEIJING 100034,PEOPLES R CHINA. WEIFANG MED INST,WEIFANG 261041,PEOPLES R CHINA. LINQU PUBL HLTH BUR,LINQU 262600,PEOPLES R CHINA. RUTGERS STATE UNIV,CANC RES LAB,PISCATAWAY,NJ 08855. FU NCI NIH HHS [N01-CP-05631, N01-CP-15620, N01-CP-95660] NR 31 TC 52 Z9 61 U1 0 U2 2 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0020-7136 J9 INT J CANCER JI Int. J. Cancer PD MAR 1 PY 1994 VL 56 IS 5 BP 650 EP 654 DI 10.1002/ijc.2910560508 PG 5 WC Oncology SC Oncology GA MY950 UT WOS:A1994MY95000007 PM 8314341 ER PT J AU YANOVSKI, SZ SEBRING, NG AF YANOVSKI, SZ SEBRING, NG TI RECORDED FOOD-INTAKE OF OBESE WOMEN WITH BINGE-EATING DISORDER BEFORE AND AFTER WEIGHT-LOSS SO INTERNATIONAL JOURNAL OF EATING DISORDERS LA English DT Article ID COGNITIVE-BEHAVIORAL TREATMENT; BULIMIA-NERVOSA; DIAGNOSTIC-CRITERIA; ENERGY-EXPENDITURE; DIETARY RESTRAINT; EATERS; SELECTION; PATTERNS AB Because binge eating in obese individuals has been postulated to be a reaction to dietary restriction, we examined the recorded food intake of 17 obese women with and 16 obese women without binge eating disorder (BED) during 1-week periods before and 3 months after a very low calorie diet program in order to determine the effects of dietary restriction on binge eating frequency and severity. Before weight loss, rather than reporting severe caloric restriction, women with BED reported greater average energy intake than nonbinge eaters on both a total (2707 vs. 1869 kcal/day, p < .01) and weight-adjusted (25.1 vs. 18.1 kcal/kg, p < .01) basis, with both higher intake on nonbinge days and an increased frequency of binge days. After weight loss, there was no significant difference in energy intake, on either a total or weight-adjusted basis, between subjects with and without BED. Although average daily energy intake fell for both groups after weight loss, only subjects with BED reported significantly decreased energy intake when adjusted for change in body weight. This resulted from decreased intake on nonbinge days and a decreased frequency of binge days. Before weight loss, subjects with BED reported an average energy intake equivalent to 94% of their predicted energy expenditure. Whereas subjects without BED reported intake only 64% of predicted (p = .002). After weight loss, there was no significant difference between subjects with and without BED in the percentage of predicted energy expenditure reported as intake (64% vs. 58%). Restraint was similar in both groups before weight loss, but those with BED reported greater hunger and disinhibition. After weight loss treatment, restraint increased significantly, whereas disinhibition and hunger remained elevated in subjects with BED. Disinhibition, rather than restraint, appears to be a major contributor to the disordered eating of these individuals. Unlike normal-weight women with bulimia nervosa dietary restriction does not appear to worsen symptoms of binge C1 NIMH,CLIN NEUROENDOCRINOL BRANCH,BETHESDA,MD 20892. NIH,CTR CLIN,NUTR SERV,BETHESDA,MD 20892. RP YANOVSKI, SZ (reprint author), NIDDKD,DIV DIGEST DIS & NUTR,BLDG 10,3S231,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. RI Gomez Gonzalez, Adela/D-2863-2012 NR 41 TC 77 Z9 78 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 1994 VL 15 IS 2 BP 135 EP 150 DI 10.1002/1098-108X(199403)15:2<135::AID-EAT2260150205>3.0.CO;2-I PG 16 WC Psychology, Clinical; Nutrition & Dietetics; Psychiatry; Psychology SC Psychology; Nutrition & Dietetics; Psychiatry GA MZ262 UT WOS:A1994MZ26200004 PM 8173559 ER PT J AU KRISHNA, MC DEWHIRST, MW FRIEDMAN, HS COOK, JA DEGRAFF, W SAMUNI, A RUSSO, A MITCHELL, JB AF KRISHNA, MC DEWHIRST, MW FRIEDMAN, HS COOK, JA DEGRAFF, W SAMUNI, A RUSSO, A MITCHELL, JB TI HYPERTHERMIC SENSITIZATION BY THE RADICAL INITIATOR 2,2'-AZOBIS-(2-AMIDINOPROPANE) DIHYDROCHLORIDE (AAPH) .1. IN-VITRO STUDIES SO INTERNATIONAL JOURNAL OF HYPERTHERMIA LA English DT Article ID HAMSTER OVARY CELLS; GLUTATHIONE ELEVATION; LOCAL-CONTROL; ENHANCEMENT; DEPLETION; THERMOTOLERANCE; RADIATION; OXYGEN AB AAPH (2,2'-azobis-(2-amidinopropane dihydrochloride)) is a water-soluble, heat-labire azo compound which undergoes thermal decomposition to produce carbon-centred free radicals. These carbon-centred radicals might be directly cytotoxic or may react with oxygen to produce potentially cytotoxic alkoxyl and peroxyl radicals. The rate of free radical production as a result of AAPK thermal decomposition increases with increasing temperature. We have evaluated the efficacy of AAPH as a heat sensitizer for Chinese hamster V79 cells by the clonogenic assay. AAPH (50 mM) was not cytotoxic to V79 cells at 37 degrees C for exposures up to 3 h. In contrast, AAPH (50 mM) was found to markedly sensitize cells exposed to 42, 43 and 45 degrees C. For a 75 min exposure to 42 degrees C alone? cell survival was reduced to 9x10(-1) however, a 75 min exposure at 42 degrees C+AAPH resulted in survival of 5.5x10(-4). For 43 and 45.5 degrees C heating, cell survival was potentiated by AAPH at the 1% survival level by 4.1 and 1.4-fold, respectively. AAPH was also found to sensitize both hypoxic cells and thermotolerant cells. These findings would encourage in vivo evaluation of AAPH (or analogues) as a temperature-dependent heat sensitizer. AAPH represents a new class of heat sensitizers which may have use in unravelling the mechanism(s) of heat killing and may have utility in local hyperthermia treatment. C1 DUKE UNIV,MED CTR,DEPT RADIAT ONCOL,DURHAM,NC. HEBREW UNIV JERUSALEM,JERUSALEM,ISRAEL. RP KRISHNA, MC (reprint author), NCI,RADIAT BIOL BRANCH,BLDG 10,ROOM B3-B69,BETHESDA,MD 20892, USA. NR 29 TC 17 Z9 17 U1 1 U2 1 PU TAYLOR & FRANCIS LTD PI LONDON PA ONE GUNDPOWDER SQUARE, LONDON, ENGLAND EC4A 3DE SN 0265-6736 J9 INT J HYPERTHER JI Int. J. Hyperthermia PD MAR-APR PY 1994 VL 10 IS 2 BP 271 EP 281 DI 10.3109/02656739409009348 PG 11 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA NK139 UT WOS:A1994NK13900009 PM 8064185 ER PT J AU RUMPEL, C INGRAM, DD HARRIS, TB MADANS, J AF RUMPEL, C INGRAM, DD HARRIS, TB MADANS, J TI THE ASSOCIATION BETWEEN WEIGHT CHANGE AND PSYCHOLOGICAL WELL-BEING IN WOMEN SO INTERNATIONAL JOURNAL OF OBESITY LA English DT Article DE WEIGHT GAIN; WEIGHT LOSS; WELL-BEING ID SEVERE OBESITY; DEPRESSION; RESPONSES; REDUCTION; ADULTS; BYPASS AB Previous studies on the effects of weight change on psychological well-being in clinical samples have yielded inconsistent results. We examined the relationship between weight change and psychological wellbeing as measured by the General Well-Being (GWB) scale in 3747 women aged 50 years or less at baseline using data from the NHANES I Epidemiologic Follow-up Study. Multiple logistic regression was used to estimate odds ratios while adjusting for potential confounders. Recent weight gain was associated with poorer wellbeing in both overweight and non-overweight women and recent weight loss with poorer well-being in non-overweight women. These findings were unchanged by controlling for age, race, marital status, employment status, education, physical activity level, number of medical conditions, alcohol use and extroversion. Thus, maintenance of stable weight may contribute to psychological well-being in women. C1 NATL CTR HLTH STAT,DIV ANAL,HYATTSVILLE,MD 20782. NIA,EPIDEMIOL DEMOG & BIOMETRY PROGRAM,BETHESDA,MD 20816. NR 30 TC 31 Z9 31 U1 1 U2 3 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE, HAMPSHIRE, ENGLAND RG21 6XS SN 0307-0565 J9 INT J OBESITY JI Int. J. Obes. PD MAR PY 1994 VL 18 IS 3 BP 179 EP 183 PG 5 WC Endocrinology & Metabolism; Nutrition & Dietetics SC Endocrinology & Metabolism; Nutrition & Dietetics GA MY403 UT WOS:A1994MY40300008 PM 8186816 ER PT J AU ROMANOSPICA, V SUZUKI, H GEORGIOU, P CHEN, SL ASCIONE, R PAPAS, TS BHAT, NK AF ROMANOSPICA, V SUZUKI, H GEORGIOU, P CHEN, SL ASCIONE, R PAPAS, TS BHAT, NK TI EXPRESSION OF ETS FAMILY GENES IN HEMATOPOIETIC-CELLS SO INTERNATIONAL JOURNAL OF ONCOLOGY LA English DT Article DE DIFFERENTIATION; LEUKEMIA; MITOGENS; DNA BINDING PROTEIN; HL-60 CELLS; PHORBOL ESTERS; T-CELL ACTIVATION ID TRANSCRIPTION FACTORS; C-ETS; PROMOTER; DIFFERENTIATION; IDENTIFICATION; PROTEIN; BINDING; PROTOONCOGENE; ENHANCER; CLONING AB We have examined the expression of the ets family of transcription factors in different types of hematopoietic cells. Our results demonstrate that several members of the ets gene family are expressed differentially in hematopoietic cells. During phorbol ester induced differentiation of HL60 cells, ETS2, PEA3, as well as GABPalpha and GABPbeta mRNAs are coordinately induced. During the activation of T-cells, ETS2 proteins are induced; however, the expression of the ETS1 and ERGB gene products are reduced. These results demonstrate that the regulation of ets family of genes is complex and depends on cell type. This observation leads to the conclusion that the regulation of ets target genes, will be dependent, in part, upon the type of ets genes expressed in each particular cell type. C1 NCI,MOLEC ONCOL LAB,POB B,FREDERICK,MD 21702. MED UNIV S CAROLINA,HOLLINGS CANC CTR,CTR MOLEC & STRUCT BIOL,CHARLESTON,SC 29425. FREDERICK CANC RES & DEV CTR,DYNCORP,PROGRAM RESOURCES INC,FREDERICK,MD 21702. NR 44 TC 20 Z9 20 U1 1 U2 2 PU INT JOURNAL ONCOLOGY PI ATHENS PA C/O PROFESSOR D A SPANDIDOS, EDITORIAL OFFICE, 1, S MERKOURI ST, ATHENS 116 35, GREECE SN 1019-6439 J9 INT J ONCOL JI Int. J. Oncol. PD MAR PY 1994 VL 4 IS 3 BP 521 EP 531 PG 11 WC Oncology SC Oncology GA MX334 UT WOS:A1994MX33400001 PM 21566954 ER PT J AU LEONE, A CORREALE, M DRAGONE, CD PARADISO, A DELENA, M STETLERSTEVENSON, WG LIOTTA, LA MASIERO, L GARBISA, S AF LEONE, A CORREALE, M DRAGONE, CD PARADISO, A DELENA, M STETLERSTEVENSON, WG LIOTTA, LA MASIERO, L GARBISA, S TI GELATINASE-A/MMP-2 SERUM LEVELS AND NEOPLASTIC PROGRESSION IN BREAST-CANCER PATIENTS SO INTERNATIONAL JOURNAL OF ONCOLOGY LA English DT Article DE GELATINASE-A; BREAST CANCER; METASTASES ID IV COLLAGENASE; METASTASIS; CARCINOMA; INVASION AB The metastatic potential of cancer cells has been associated to their ability to elaborate and secrete basement membrane degradative enzymes. In this process a major role appears to be played by a protease known as gelatinase A (72 kDa type IV collagenase, MMP-2). In an effort to assess the significance of these findings to breast cancer progression, we have evaluated the gelatinase A/MMP-2 serum levels in a cohort of 80 breast cancer patients, 27 subjects affected by benign breast disease and 27 healthy controls. Although differences between the three groups were observed, with the highest values monitored in benign breast disease, they were not statistically significant. On the contrary, within the breast cancer cohort, the patients presenting clinical evidence of distant metastases (M+, n=40) had statistically elevated enzyme serum levels (p<0.03) compared to those without nodal involvement and distant metastases (N-M-, n=20). The statistical significance was still evident when considering the overall M- cohort (including N+ and N- patients, n=40) compared to the M+. Although indicating that, in general, gelatinase A/MMP-2 is not a useful serum marker for breast cancer screening and diagnosis, the findings point toward its involvement in the breast cancer metastatic process and suggest a possible value in monitoring the outcome of the disease. C1 NCI,PATHOL LAB,BETHESDA,MD 20892. MED SCH PADUA,INST HISTOL & GEN EMBRYOL,PADUA,ITALY. RP LEONE, A (reprint author), INST BARI,EXPTL ONCOL LAB,I-70126 BARI,ITALY. RI Stetler-Stevenson, William/H-6956-2012; Leone, Alvaro/K-6410-2016 OI Stetler-Stevenson, William/0000-0002-5500-5808; Leone, Alvaro/0000-0003-3815-9052 NR 20 TC 3 Z9 3 U1 0 U2 0 PU INT JOURNAL ONCOLOGY PI ATHENS PA C/O PROFESSOR D A SPANDIDOS, EDITORIAL OFFICE, 1, S MERKOURI ST, ATHENS 116 35, GREECE SN 1019-6439 J9 INT J ONCOL JI Int. J. Oncol. PD MAR PY 1994 VL 4 IS 3 BP 551 EP 554 PG 4 WC Oncology SC Oncology GA MX334 UT WOS:A1994MX33400004 PM 21566957 ER PT J AU GUTIERREZ, MI BHATIA, K DIEZ, B MURIEL, FS EPELMAN, S DEANDREAS, ML HUPPI, K MAGRATH, I AF GUTIERREZ, MI BHATIA, K DIEZ, B MURIEL, FS EPELMAN, S DEANDREAS, ML HUPPI, K MAGRATH, I TI PROGNOSTIC-SIGNIFICANCE OF P53 MUTATIONS IN SMALL NON-CLEAVED CELL LYMPHOMAS SO INTERNATIONAL JOURNAL OF ONCOLOGY LA English DT Article DE P53 MUTATIONS; NON-HODGKINS LYMPHOMA; BURKITTS LYMPHOMA; PROGNOSIS; PROGRESSION; RELAPSE; CHEMOTHERAPY ID BURKITT-LYMPHOMA; GENE; ASSOCIATION; TUMORS; RAS AB We have assessed the prognostic significance of mutations in the p53 tumor suppressor gene in patients with small non-cleaved cell lymphomas. In this retrospective pilot study we have, been able to evaluate the response to therapy of 21 previously untreated patients. Seven of these patients (33%) had tumors which contained a p53 mutation at presentation. Five of the 7 patients with mutant p53 relapsed and 4 died of progressive disease whereas none of the patients with wild type p53 relapsed and none died of progressive disease. These preliminary results strongly suggest that the presence of a mutated p53 gene is an unfavorable prognostic factor. p53 mutations could be used as a parameter in risk-adapted therapy protocols, or could even provide an appropiate target for therapy. C1 NCI,PEDIAT BRANCH,LYMPHOMA BIOL SECT,BLDG 10,ROOM 13N240,BETHESDA,MD 20892. HOSP PEDIAT PROF DR JUAN P GARRAHAN,DEPT HEMATOL ONCOL,RA-1245 BUENOS AIRES,ARGENTINA. HOSP NINOS DR RICARDO GUTIERREZ,DEPT ONCOL,RA-1425 BUENOS AIRES,ARGENTINA. HOSP AC CARMARGO FUNDACAO ANTONIO PRUDENTE,BR-01509 SAO PAULO,BRAZIL. NCI,MOLEC GENET SECT,BETHESDA,MD 20892. NR 22 TC 13 Z9 14 U1 1 U2 1 PU INT JOURNAL ONCOLOGY PI ATHENS PA C/O PROFESSOR D A SPANDIDOS, EDITORIAL OFFICE, 1, S MERKOURI ST, ATHENS 116 35, GREECE SN 1019-6439 J9 INT J ONCOL JI Int. J. Oncol. PD MAR PY 1994 VL 4 IS 3 BP 567 EP 571 PG 5 WC Oncology SC Oncology GA MX334 UT WOS:A1994MX33400007 PM 21566960 ER PT J AU MOON, RC RAO, KVN DETRISAC, CJ KELLOFF, GJ STEELE, VE DOODY, LA AF MOON, RC RAO, KVN DETRISAC, CJ KELLOFF, GJ STEELE, VE DOODY, LA TI CHEMOPREVENTION OF RESPIRATORY-TRACT NEOPLASIA IN THE HAMSTER BY OLTIPRAZ, ALONE AND IN COMBINATION SO INTERNATIONAL JOURNAL OF ONCOLOGY LA English DT Article DE CHEMOPREVENTION; CANCER; LUNG; TRACHEA; HAMSTER; DEN; BETA-CAROTENE; DFMO; 4-HPR; OLTIPRAZ ID MAMMARY-TUMOR INDUCTION; METHYL-N-NITROSOUREA; ORNITHINE DECARBOXYLASE; ALPHA-DIFLUOROMETHYLORNITHINE; 5-(2-PYRAZINYL)-4-METHYL-1,2-DITHIOL-3-THIONE OLTIPRAZ; PULMONARY CARCINOGENESIS; ANALOGS RETINOIDS; MOUSE SKIN; VITAMIN-A; INHIBITION AB Two doses of oltipraz (300, 600 mg/kg diet) and alpha-difluoromethylornithine DFMO; 1600, 3200 mg/kg diet), alone and in combinations with N-(4-hydroxyphenyl) retinamide (4-HPR; 98, 196 mg/kg diet) and/or beta-carotene (3, 1.5 mg; sc, 2x/week), were investigated for prevention of hamster respiratory carcinogenesis. After 25 weeks, only high dose oltipraz (-100%) inhibited the incidence of DEN-induced (17.8 mg/kg BW, sc, 2x/week, 20 weeks) bronchial carcinomas when given alone. Low dose oltipraz (-34%, n.s.) synergistically decreased carcinoma incidence in combinations with 4-HPR (-80%), beta-carotene (-90%) or both (-100%). Other effective combinations were low dose DFMO + beta-carotene (-64%) and high dose DFMO with 4-HPR (-56%), beta-carotene (-63%) or both (-67%). C1 IIT,CHICAGO,IL 60616. NCI,CHEMOPREVENT INVEST STUDIES BRANCH,BETHESDA,MD 20892. CSS ASSOCIATES,PALO ALTO,CA 94301. NR 50 TC 21 Z9 21 U1 0 U2 0 PU INT JOURNAL ONCOLOGY PI ATHENS PA C/O PROFESSOR D A SPANDIDOS, EDITORIAL OFFICE, 1, S MERKOURI ST, ATHENS 116 35, GREECE SN 1019-6439 J9 INT J ONCOL JI Int. J. Oncol. PD MAR PY 1994 VL 4 IS 3 BP 661 EP 667 PG 7 WC Oncology SC Oncology GA MX334 UT WOS:A1994MX33400021 PM 21566974 ER PT J AU CACHAU, RE GUSSIO, R BEUTLER, JA CHMURNY, GN HILTON, BD MUSCHIK, GM ERICKSON, JW AF CACHAU, RE GUSSIO, R BEUTLER, JA CHMURNY, GN HILTON, BD MUSCHIK, GM ERICKSON, JW TI SOLUTION STRUCTURE OF TAXOL DETERMINED USING A NOVEL FEEDBACK-SCALING PROCEDURE FOR NOE-RESTRAINED MOLECULAR-DYNAMICS SO INTERNATIONAL JOURNAL OF SUPERCOMPUTER APPLICATIONS AND HIGH PERFORMANCE COMPUTING LA English DT Article ID NMR; SPECTROSCOPY; CHEMISTRY; ANALOGS; AGENT AB The increasing availability of high-performance computers makes it possible to treat larger systems in shorter computing times. However, a more challenging aspect of the availability of larger and faster computers is the exploration of alternative algorithms. This is especially important in view of new computer architectures. In this work we describe a novel technique for feedback-scaling individual NOE distance restraints during molecular-dynamics-simulated annealing experiments. C1 NCI,FREDERICK CANC RES & DEV CTR,DIV CANC TREATMENT,DEV THERAPEUT PROGRAM,FREDERICK,MD 21702. NCI,FREDERICK CANC RES & DEV CTR,PRI DYNCORP,CHEM SNTH & ANAL LAB,FREDERICK,MD 21702. RP CACHAU, RE (reprint author), NCI,FREDERICK CANC RES & DEV CTR,PRI DYNCORP,FREDERICK BIOMED SUPERCOMP CTR,STRUCT BIOCHEM LAB,FREDERICK,MD 21702, USA. RI Beutler, John/B-1141-2009 OI Beutler, John/0000-0002-4646-1924 NR 25 TC 24 Z9 24 U1 0 U2 2 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 SN 1078-3482 J9 INT J SUPERCOMPUT AP JI Int. J. Supercomput. Appl. High Perform. Comput. PD SPR PY 1994 VL 8 IS 1 BP 24 EP 34 DI 10.1177/109434209400800104 PG 11 WC Computer Science, Hardware & Architecture; Computer Science, Interdisciplinary Applications SC Computer Science GA NW587 UT WOS:A1994NW58700003 ER PT J AU CRAGG, GM AF CRAGG, GM TI BIOPROSPECTING SO ISSUES IN SCIENCE AND TECHNOLOGY LA English DT Letter RP CRAGG, GM (reprint author), NCI,DIV CANC TREATMENT,NAT PROD BRANCH,DEV THERAPEUT PROGRAM,BETHESDA,MD 20892, USA. NR 0 TC 0 Z9 0 U1 0 U2 1 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 1994 VL 10 IS 3 BP 20 EP 20 PG 1 WC Engineering, Multidisciplinary; Engineering, Industrial; Multidisciplinary Sciences; Social Issues SC Engineering; Science & Technology - Other Topics; Social Issues GA NF115 UT WOS:A1994NF11500020 ER PT J AU LIJINSKY, W PEGG, AE ANVER, MR MOSCHEL, RC AF LIJINSKY, W PEGG, AE ANVER, MR MOSCHEL, RC TI EFFECTS OF INHIBITION OF O-6-ALKYLGUANINE-DNA ALKYLTRANSFERASE IN RATS ON CARCINOGENESIS BY METHYLNITROSOUREA AND ETHYLNITROSOUREA SO JAPANESE JOURNAL OF CANCER RESEARCH LA English DT Article DE O-6-ALKYLGUANINE-DNA ALKYLTRANSFERASE; CARCINOGENESIS; METHYLNITROSOUREA; ETHYLNITROSOUREA ID AGENTS; GAVAGE; DNA AB Many alkylating agents are potent carcinogens and there is considerable evidence that the formation of O6-alkylguanine in DNA can lead to mutations and the initiation of neoplastic growth. The repair of O6-methyl- or O6-ethylguanine in DNA is known to be brought about by the action of a protein termed 06-alkylguanine-DNA alkyltransferase. In order to investigate the role of this activity in the carcinogenic action of methylnitrosourea and ethylnitrosourea, O6-benzylguanine, a potent inhibitor of the alkyltransferase, was used. Groups of 20 female F344 rats were treated with the nitrosourea (0.2 mmol) by gavage in 10 weekly doses and a parallel group was also treated with 4 mg of 06 -benzylguanine, 2 h prior to each dose of the nitrosourea. This dose of O6-benzylguanine was sufficient to reduce the alkyltransferase activity to zero in the liver for at least 8 h but activity had returned to about 60% of normal within 24 h. Animals were maintained until they became moribund, when they were killed, or until death related to tumors. The median week of death in the animals receiving methylnitrosourea was reduced from 60 wk to 52 wk by co-treatment with O6-benzylguanine. There was a smaller reduction from 55 to 50 wk in the rats receiving ethylnitrosourea. The treatment with O6-benzylguanine caused no significant change in the incidence of the principal tumors induced by the alkylnitrosoureas and there were no liver tumors produced by the combined treatments. These results show that the level of inactivation of alkyltransferase produced by this dose of O6-benzylguanine was not sufficient to greatly alter the potent carcinogenic effect of these doses of alkylnitrosoureas in this system. C1 NCI,FREDERICK CANC RES & DEV CTR,ABL BASIC RES PROGRAM,CHEM CARCINOGENESIS LAB,FREDERICK,MD 21702. NCI,FREDERICK CANC RES & DEV CTR,DYNCORP,PROGRAM RESOURCES INC,PATHOL HISTOTECHNOL LAB,FREDERICK,MD 21702. PENN STATE UNIV,MILTON S HERSHEY MED CTR,COLL MED,DEPT CELLULAR & MOLEC PHYSIOL,HERSHEY,PA 17033. FU NCI NIH HHS [N01-CO-72102, N01-CO-74101, CA19137] NR 19 TC 10 Z9 11 U1 0 U2 2 PU JAPANESE CANCER ASSOCIATION PI TOKYO PA EDITORIAL OFFICE 7TH FLOOR, JOHKOH BLDG 2-23-11, KOISHIKAWA, TOKYO 112, JAPAN SN 0910-5050 J9 JPN J CANCER RES JI Jpn. J. Cancer Res. PD MAR PY 1994 VL 85 IS 3 BP 226 EP 230 PG 5 WC Oncology SC Oncology GA NB995 UT WOS:A1994NB99500002 PM 8188519 ER PT J AU KRONER, BL ROSENBERG, PS ALEDORT, LM ALVORD, WG GOEDERT, JJ AF KRONER, BL ROSENBERG, PS ALEDORT, LM ALVORD, WG GOEDERT, JJ TI HIV-1 INFECTION INCIDENCE AMONG PERSONS WITH HEMOPHILIA IN THE UNITED-STATES AND WESTERN-EUROPE, 1978-1990 SO JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES AND HUMAN RETROVIROLOGY LA English DT Article DE HIV-1 INFECTION INCIDENCE; HEMOPHILIA; RISK FACTORS FOR INFECTION ID LYMPHADENOPATHY-ASSOCIATED VIRUS; FACTOR-VIII CONCENTRATE; HTLV-III; NATURAL-HISTORY; AIDS EPIDEMIC; SEROCONVERSION; ANTIBODIES; HEAT; SEROPREVALENCE; INACTIVATION AB We studied human immunodeficiency virus type 1 (HIV-1) infection incidence over time in a 16-center cohort of hemophiliacs in the United States and Europe and estimated the most likely date of seroconversion for all sero-positive subjects. Five U.S. centers enrolled subjects independent of HIV-1 status, whereas 11 centers preferentially included seropositive subjects. We obtained unbiased estimates of HIV-1 infection incidence rates from the five centers and estimated dates of seroconversion from the distribution seen among seropositives from all centers. In the five-center cohort, infection incidence began in 1978, peaked in October 1982 at 22 infections per 100 person-years at risk, and declined to 4 per 100 person-years by July 1984. Few infections occurred after 1987, and by that time, 50% of the cohort had become infected. Median seroconversion dates for subgroups of all seropositives ranged from July 1980 to December 1983, depending on the dose and type of factor concentrate. Median dates in Europe ranged from September 1981 to March 1983 and reflected the use of products manufactured from American plasma. Infection incidence apparently peaked about the same time that public health interventions were introduced to reduce transmission. These interventions, including heat treatment of factor concentrates and deferral of high-risk donors, have prevented HIV-1 infection from becoming endemic among younger birth cohorts of persons with hemophilia. C1 NCI,BIOSTAT BRANCH,ROCKVILLE,MD. MT SINAI MED CTR,NEW YORK,NY. DATA MANAGEMENT SERV,FREDERICK,MD. NCI,VIRAL EPIDEMIOL BRANCH,ROCKVILLE,MD. RP KRONER, BL (reprint author), NCI,RES TRIANGLE INST,6101 EXECUT BLVD,SUITE 363,ROCKVILLE,MD, USA. FU NCI NIH HHS [N01-CP-85649] NR 46 TC 103 Z9 103 U1 1 U2 2 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 1994 VL 7 IS 3 BP 279 EP 286 PG 8 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA MY532 UT WOS:A1994MY53200010 PM 8106967 ER PT J AU SAAH, AJ HOOVER, DR HE, YH KINGSLEY, LA PHAIR, JP AF SAAH, AJ HOOVER, DR HE, YH KINGSLEY, LA PHAIR, JP TI FACTORS INFLUENCING SURVIVAL AFTER AIDS - REPORT FROM THE MULTICENTER-AIDS-COHORT-STUDY (MACS) SO JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES AND HUMAN RETROVIROLOGY LA English DT Article DE PROGNOSIS; MULTICENTER AIDS COHORT STUDY; ANTIRETROVIRAL THERAPY; PNEUMOCYSTIS CARINII PNEUMONIA ID IMMUNODEFICIENCY-VIRUS TYPE-1; CONTROLLED TRIAL; HOMOSEXUAL MEN; INFECTION; ZIDOVUDINE; PREDICTORS; RISK AB The objective of this study was to determine if clinical signs, symptoms, laboratory variables, and use of therapeutic or prophylactic agents have prognostic associations with survival after diagnosis of clinical AIDS. A total of 2,168 homosexual men, seropositive for human immunodeficiency virus type 1 (HIV-1) participated in a longitudinal cohort study of the greater metropolitan areas of Baltimore, Maryland, Washington, D.C., Chicago, Illinois, Pittsburgh, Pennsylvania, and Los Angeles, California, U.S.A.-the Multicenter AIDS Cohort Study (MACS). Variables within 6 months prior to AIDS diagnosis included age, CD4(+) lymphocyte counts, hemoglobin, and self-reported thrush, fever, anti-retroviral therapy (ART) beginning prior to AIDS onset, and ART beginning after AIDS (as a time-dependent covariate) were analyzed as mutually exclusive categories, as was prophylaxis for Pneumocystis carinii pneumonia (PCP). Univariate and multivariate survival models of time from AIDS to death were fit. In univariate analysis, younger age, higher counts of CD4(+) lymphocytes, hemoglobin, and absence of thrush or fever prior to AIDS onset were associated with longer survival after AIDS. Those who began ART within 3 months after AIDS onset had longer median survival (1.75 years), from 3 months after AIDS, when compared with those who began ART prior to AIDS (1.18 years). This comparison is not influenced by the bias that those who survive longer have a greater likelihood to subsequently receive ART, Prophylaxis for PCP beginning after AIDS onset was also associated with longer post-AIDS survival when compared with beginning prophylaxis prior to AIDS or never using prophylaxis. In multivariate analysis, age <37 years at AIDS onset, higher hemoglobin level, and higher CD4(+) lymphocyte count remained prognostically beneficial for survival after AIDS (relative hazards 0.78, 0.91 per g/dL and 0.80 per 100 cells x 10(6)/L, respectively). When PCP prophylaxis and ART were started only after AIDS onset (considered as time-dependent covariates, they reduced the hazard of death by 40% and 50%, respectively. The hazard of death after AIDS was 26% lower in those using ART prior to AIDS than in those never using ART (p = 0.095). Clinical variables such as younger age, higher hemoglobin level, and higher CD4(+) count are prognostically beneficial for survival after AIDS. Pre-AIDS ART and pneumocystis prophylaxis are presently the standard of care in treating those with HIV-1 infection and have been shown to delay the onset of AIDS. Survival after AIDS onset was longer for men who received pre-AIDS ART compared with those who never received ART, but it was shorter in the former group than in those initiating ART after AIDS, This finding suggests a transient beneficial effect from ART that is not completely attenuated at AIDS in the pre-AIDS ART recipient. C1 NIAID,BETHESDA,MD. NORTHWESTERN UNIV,SCH MED,CHICAGO,IL. UNIV PITTSBURGH,GRAD SCH PUBL HLTH,PITTSBURGH,PA. UNIV PITTSBURGH,SCH MED,PITTSBURGH,PA. RP SAAH, AJ (reprint author), JOHNS HOPKINS UNIV,SCH HYG & PUBL HLTH,624 N BROADWAY,SUITE 896,BALTIMORE,MD 21205, USA. FU NIAID NIH HHS [N01-AI-72632, N01-AI-72634, N01-AI-72631] NR 17 TC 129 Z9 133 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 1994 VL 7 IS 3 BP 287 EP 295 PG 9 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA MY532 UT WOS:A1994MY53200011 PM 8106968 ER PT J AU FIGUEROA, JP BRATHWAITE, A MORRIS, J WARD, E PERUGA, A BLATTNER, W VERMUND, SH HAYES, R AF FIGUEROA, JP BRATHWAITE, A MORRIS, J WARD, E PERUGA, A BLATTNER, W VERMUND, SH HAYES, R TI RISING HIV-1 PREVALENCE AMONG SEXUALLY-TRANSMITTED DISEASE CLINIC ATTENDERS IN JAMAICA - TRAUMATIC SEX AND GENITAL ULCERS AS RISK-FACTORS SO JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES AND HUMAN RETROVIROLOGY LA English DT Article DE HUMAN IMMUNODEFICIENCY VIRUS; SEXUALLY TRANSMITTED DISEASE; RISK FACTORS; HETEROSEXUAL TRANSMISSION; JAMAICA ID HUMAN-IMMUNODEFICIENCY-VIRUS; MALE TRANSMISSION; INFECTION; FEMALE; TYPE-1; MEN AB Between November 1990 and January 1991, status of human immunodeficiency virus (HIV) infection was assessed for 522 men and 484 women attending the Comprehensive Health Centre in Kingston, Jamaica, for a new sexually transmitted disease (STD) complaint. Prevalence of HIV type 1 (HIV-1) infection was 3.1% (31 of 1,006), a tenfold rise in seroprevalence in 4.5 years. Nineteen of 517 (3.7%) heterosexual men, 3 of 5 (60%) homosexual/bisexual men, and 9 of 484 (1.9%) women were infected with HIV. In heterosexual men, factors associated with HIV infection after age adjustment included present complaint of genital ulcer [odds ratio (OR) 7.3; 95% confidence interval (CI) 1.4-72], past history of genital ulcer (OR, 4.3; CI, 1.4-12), positive MHATP syphilis serology (OR, 3.4; CI, 1.1-10), sex with a prostitute in the past month (OR, 3.8; CI, 1.1-11). Three or more sex partners in the month prior to complaint (OR, 3.6; CI, 1.0-12), and bruising during sex (OR, 4.0; CI, 1.4-13). On multiple logistic regression analysis, independent associations with HIV infection were shown for bruising during sex (OR, 3.0; CI, 1.1-8.3), positive MHATP syphilis serology (OR, 3.2; CI, 1.1-9.5), and history of genital ulcer (OR, 2.9; Ct, 1.0 8.0). Among women, history of ''bad blood'' (syphilis) (OR, 6.6; CI, 1.4-30), self-perception of high risk for acquired immune deficiency syndrome (AIDS) (OR, 8.6; CI, 0.9-108), positive gonorrhea culture (OR 12; CI 2.1-72), HTLV-1 seropositivity (OR, 5.7; CI, 0.9-29), history of stillbirth (OR, 7.6; CI, 1.3-43), and current abnormality of the cervix (OR, infinity; CI, 1.7-infinity) were associated with HIV infection. Conditions giving rise to a disruption of the genital epithelium in men such as bruising (trauma) with sex and genital ulcers may facilitate HIV transmission from women to men while inflammation of the cervix (e.g., gonorrhea) may facilitate male-to-female HIV transmission. C1 LONDON SCH HYG & TROP MED,LONDON,ENGLAND. PAN AMER HLTH ORG,WASHINGTON,DC. NCI,BETHESDA,MD 20892. NIAID,DIV AIDS,BETHESDA,MD 20892. RP FIGUEROA, JP (reprint author), MINIST HLTH,EPIDEMIOL UNIT,30-34 HALF WAY TREE RD,KINGSTON 5,JAMAICA. OI Hayes, Richard/0000-0002-1729-9892; Vermund, Sten/0000-0001-7289-8698 NR 21 TC 33 Z9 34 U1 1 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 1994 VL 7 IS 3 BP 310 EP 316 PG 7 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA MY532 UT WOS:A1994MY53200014 PM 8106971 ER PT J AU DICKLER, HB ALBRIGHT, JF AF DICKLER, HB ALBRIGHT, JF TI IMMUNOSUPPRESSION IN THE TREATMENT OF DISEASE SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Editorial Material ID EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS; RHEUMATOID-ARTHRITIS; METHOTREXATE; INHIBITION; THERAPY; INSULIN; ASTHMA; AUTOANTIBODIES; CYCLOSPORINE; SUPPRESSION RP DICKLER, HB (reprint author), NIAID,DIV ALLERGY IMMUNOL & TRANSPLANTAT,SOLAR BLDG,ROOM 4A-19,BETHESDA,MD 20892, USA. NR 30 TC 2 Z9 2 U1 0 U2 0 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 SN 0091-6749 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD MAR PY 1994 VL 93 IS 3 BP 669 EP 676 DI 10.1016/S0091-6749(94)70079-6 PG 8 WC Allergy; Immunology SC Allergy; Immunology GA ND140 UT WOS:A1994ND14000014 PM 8151066 ER PT J AU BARR, RA JOHNSON, KW MIRANDA, M AF BARR, RA JOHNSON, KW MIRANDA, M TI RESEARCH TRANSLATION IN GERONTOLOGY - A BEHAVIORAL AND SOCIAL-PERSPECTIVE INTRODUCTION TO THE SPECIAL ISSUE SO JOURNAL OF APPLIED GERONTOLOGY LA English DT Editorial Material RP BARR, RA (reprint author), NIA,GATEWAY BLDG,ROOM 26234,7201 WISCONSIN AVE,BETHESDA,MD 20892, USA. NR 5 TC 7 Z9 7 U1 0 U2 0 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 SN 0733-4648 J9 J APPL GERONTOL JI J. Appl. Gerontol. PD MAR PY 1994 VL 13 IS 1 BP 3 EP 6 DI 10.1177/073346489401300101 PG 4 WC Gerontology SC Geriatrics & Gerontology GA PR770 UT WOS:A1994PR77000001 ER PT J AU ANGOV, E CAMERINIOTERO, RD AF ANGOV, E CAMERINIOTERO, RD TI THE RECA GENE FROM THE THERMOPHILE THERMUS-AQUATICUS YT-1 - CLONING, EXPRESSION, AND CHARACTERIZATION SO JOURNAL OF BACTERIOLOGY LA English DT Article ID DNA STRAND EXCHANGE; ESCHERICHIA-COLI; EXTREME THERMOPHILE; NUCLEOTIDE-SEQUENCE; MOLECULAR-CLONING; RIBONUCLEASE-H; PROTEIN; RECOMBINATION; HB8; PURIFICATION AB We have cloned, expressed, and purified the RecA analog from the thermophilic eubacterium Thermus aquaticus YT-1. Analysis of the deduced amino acid sequence indicates that the T. aquaticas RecA is structurally similar to the Escherichia coli RecA and suggests that RecA-like function has been conserved in thermophilic organisms. Preliminary biochemical analysis indicates that the protein has an ATP-dependent single-stranded DNA binding activity and can pair and carry out strand exchange to form a heteroduplex DNA under reaction conditions previously described for E. coli RecA, but at 55 to 65 degrees C. Further characterization of a thermophilically derived RecA protein should yield important information concerning DNA-protein interactions at high temperatures. In addition, a thermostable RecA protein may have some general applicability in stabilizing DNA-protein interactions in reactions which occur at high temperatures by increasing the specificity (stringency) of annealing reactions. C1 NIDDKD,GENET & BIOCHEM BRANCH,BETHESDA,MD 20892. NR 40 TC 18 Z9 19 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0021-9193 J9 J BACTERIOL JI J. Bacteriol. PD MAR PY 1994 VL 176 IS 5 BP 1405 EP 1412 PG 8 WC Microbiology SC Microbiology GA MY351 UT WOS:A1994MY35100026 PM 8113181 ER PT J AU LOBOCKA, M HENNIG, J WILD, J KLOPOTOWSKI, T AF LOBOCKA, M HENNIG, J WILD, J KLOPOTOWSKI, T TI ORGANIZATION AND EXPRESSION OF THE ESCHERICHIA-COLI K-12 DAD OPERON ENCODING THE SMALLER SUBUNIT OF D-AMINO-ACID DEHYDROGENASE AND THE CATABOLIC ALANINE RACEMASE SO JOURNAL OF BACTERIOLOGY LA English DT Article ID PROTEIN-SEQUENCE DETERMINATION; GENE ACTIVATOR PROTEIN; AMP RECEPTOR PROTEIN; SALMONELLA-TYPHIMURIUM; CYCLIC-AMP; DNA-SEQUENCE; MOLECULAR-CLONING; OXIDASE; KIDNEY; RNA AB A fragment of the Escherichia call K-12 chromosome complementing the D-amino acid dehydrogenase and catabolic alanine racemase deficiency of a dad operon deletion mutant was cloned in a mini-Mu plasmid. The dadA and dadX genes were localized to a 3.5-kb part of the plasmid insert. The nucleotide sequence of this fragment revealed two open reading frames encoding 432- and 356-amino-acid-long proteins. We show here that they correspond to the dadA and dadX genes. The dadA gene can encode only the smaller of the two subunits of D-amino acid dehydrogenase. A computer search revealed the presence of a flavin adenine dinucleotide-binding motif in the N-terminal domain of the deduced DadA protein sequence. This is in agreement with biochemical data showing that the D-amino acid dehydrogenase contains flavin adenine dinucleotide in its active center. The predicted dadX gene product appeared to be 85% identical to a dadB-encoded catabolic alanine racemase of Salmonella typhimurium. The organization of the dadA and dadX genes confirmed our previous conclusion based on the genetic data (J. Wild, J. Hennig, M. Lobocka, W. Walczak, and T. Klopotowski, Mol. Gen. Genet. 198:315-322, 1985) that these genes form an operon. The main transcription start points of the dad operon were determined by primer extension. They are preceded by a putative sigma(70) promoter sequence and two cyclic AMP-cyclic AMP receptor protein (cAMP-CRP) binding sites, one of higher and one of lower affinity to CRP. We propose that the high-affinity site, centered 59.5 bp upstream of the main transcription start point, plays a role in cAMP-CRP-mediated activation of dad operon expression in the absence of glucose. C1 POLISH ACAD SCI,INST BIOCHEM & BIOPHYS,DEPT MICROBIAL BIOCHEM,PL-02532 WARSAW,POLAND. RP LOBOCKA, M (reprint author), NCI,BIOCHEM LAB,BLDG 37,ROOM 4D-15,BETHESDA,MD 20892, USA. NR 65 TC 58 Z9 64 U1 0 U2 8 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0021-9193 J9 J BACTERIOL JI J. Bacteriol. PD MAR PY 1994 VL 176 IS 5 BP 1500 EP 1510 PG 11 WC Microbiology SC Microbiology GA MY351 UT WOS:A1994MY35100038 PM 7906689 ER PT J AU SMALL, P BLANKENHORN, D WELTY, D ZINSER, E SLONCZEWSKI, JL AF SMALL, P BLANKENHORN, D WELTY, D ZINSER, E SLONCZEWSKI, JL TI ACID AND BASE RESISTANCE IN ESCHERICHIA-COLI AND SHIGELLA-FLEXNERI - ROLE OF RPOS AND GROWTH PH SO JOURNAL OF BACTERIOLOGY LA English DT Article ID SALMONELLA-TYPHIMURIUM; NUCLEOTIDE-SEQUENCE; TOLERANCE RESPONSE; GENE-EXPRESSION; CAD OPERON; KATF; TRANSCRIPTION; HOMEOSTASIS; CLONING; IDENTIFICATION AB Escherichia coli K-12 strains and Shigella flexneri grown to stationary phase can sun ive several hours at pH 2 to 3, which is considerably lower than the acid limit for growth (about pH 4.5). A 1.3-kb fragment cloned from S. flexneri conferred acid resistance on acid-sensitive E. coli HB101; sequence data identified the fragment as a homolog of rpoS, the growth phase-dependent sigma factor sigma(38). The clone also conferred acid resistance on S. flexneri rpoS::Tn10 but not on Salmonella typhimurium. E. coli and S. flexneri strains containing wild-type rpoS maintained greater internal pH in the face of a low external pH than strains lacking functional rpoS, but the ability to sun ive at low pH did not require maintenance of a high transmembrane pH difference. Aerobic stationary-phase cultures of E. coli MC4100 and S. flexneri 3136, grown initially at an external pH range of 5 to 8, were 100% acid resistant (surviving 2 h at pH 2.5). Aerobic log-phase cultures grown at pH 5.0 were acid resistant; survival decreased 10- to 100-fold as the pH of growth th was increased to pH 8.0. Extended growth in log phase also decreased acid resistance substantially. Strains containing rpoS::Tn10 showed ed partial acid resistance when grown at pH 5 to stationary phase; log-phase cultures showed <0.01% acid resistance. When grown anaerobically at low pH, however, the rpoS::Tn10 strains were acid resistant. E. coli MC4100 also showed resistance at alkaline pH outside the growth range (base resistance). Significant base resistance was observed up to pH 10.2. Base resistance was diminished by rpoS::Tn10 and by the presence of Na+. Base resistance was increased by an order of magnitude for stationary-phase cultures grown in moderate base (pH 8) compared with those grown in moderate acid (pH 5). Anaerobic growth partly restored base resistance in cultures grown at pH 5 but not in those grown at pH 8. Thus, both acid resistance and base resistance show dependence on growth pH and are regulated by rpoS under certain conditions. For acid resistance, and in part for base resistance, the rpoS requirement can be overcome by anaerobic growth in moderate acid. C1 KENYON COLL,DEPT BIOL,GAMBIER,OH 43022. NIAID,ROCKY MT LABS,VECTORS & PATHOGENS LAB,HAMILTON,MT 59840. FU NIAID NIH HHS [R15 AI32708-01] NR 49 TC 282 Z9 295 U1 3 U2 25 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0021-9193 J9 J BACTERIOL JI J. Bacteriol. PD MAR PY 1994 VL 176 IS 6 BP 1729 EP 1737 PG 9 WC Microbiology SC Microbiology GA NB994 UT WOS:A1994NB99400023 PM 8132468 ER PT J AU TREPTOW, R ROSENFELD, R YARMOLINSKY, M AF TREPTOW, R ROSENFELD, R YARMOLINSKY, M TI PARTITION OF NONREPLICATING DNA BY THE PAR SYSTEM OF BACTERIOPHAGE-P1 SO JOURNAL OF BACTERIOLOGY LA English DT Note ID UNIT-COPY MINIPLASMIDS; BACTERIAL PLASMIDS; ESCHERICHIA-COLI; DAUGHTER CELLS; REGION; LAMBDA; INCOMPATIBILITY; EQUIPARTITION; MAINTENANCE; REPLICATION AB P1 plasmid encodes a cis-acting centromere analog, parS, and two Par proteins that together stabilize plasmids by partitioning them to daughter bacteria. We infected immune bacteria with bacteriophage X into which parS had been inserted. The presence of P1 Par proteins in the infected cells,vas found to delay the appearance of cells cured of the nonreplicating, extrachromosomal lambda-parS DNA. This stabilization of lambda-parS, approximated in a computer simulation, demonstrates that active partition by the P1 par system does not require the act of plasmid replication and can be studied in its absence. C1 NCI,BIOCHEM LAB,BETHESDA,MD 20892. HEBREW UNIV JERUSALEM,FAC MED,DEPT MOLEC GENET,IL-91010 JERUSALEM,ISRAEL. NR 40 TC 14 Z9 14 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0021-9193 J9 J BACTERIOL JI J. Bacteriol. PD MAR PY 1994 VL 176 IS 6 BP 1782 EP 1786 PG 5 WC Microbiology SC Microbiology GA NB994 UT WOS:A1994NB99400032 ER PT J AU KEPPLE, TM ARNOLD, AS STANHOPE, SJ SIEGEL, KL AF KEPPLE, TM ARNOLD, AS STANHOPE, SJ SIEGEL, KL TI ASSESSMENT OF A METHOD TO ESTIMATE MUSCLE ATTACHMENTS FROM SURFACE LANDMARKS - A 3D COMPUTER-GRAPHICS APPROACH SO JOURNAL OF BIOMECHANICS LA English DT Note ID ANTHROPOMETRIC SCALING METHOD; HUMAN LOWER-EXTREMITY; MUSCULOSKELETAL MODEL; KNEE-JOINT; ANATOMY; GAIT; HIP AB A method for estimating the locations of muscle origins and insertions from the measurement of surface landmarks was evaluated using two indirect accuracy tests and a three-dimensional computer graphics program. For each of four lower extremity anatomical segments, a least-squares technique was used to map the measured locations of three landmark targets to their anatomically based locations. The residual errors, obtained from the applications of the least squares, supplied the first indirect accuracy test. These residual errors were between 6 and 12 mm for the four anatomical segments when averaged over ten subjects. The second indirect accuracy test was conducted by comparing the predicted locations of end points on two adjacent segments forming a joint. Errors in aligning adjacent end points were between 12 and 29 mm for three anatomical joints when averaged over ten subjects. A three-dimensional computer graphics program was developed by the authors and demonstrated that the static testing techniques alone were insufficient to evaluate the quality of the muscle origin and insertion estimates. Any evaluation of muscle lengths, velocities and lines-of-action from surface landmarks should examine the estimates made from motion data, and should address both the ability of the model to fit the subjects as well as model's ability to represent the geometry of the musculoskeletal system. C1 MIT,DEPT MECH ENGN,CAMBRIDGE,MA 02139. RP KEPPLE, TM (reprint author), NIH,WARREN G MAGNUSON CLIN CTR,DEPT REHABIL MED,MIOMECH LAB,BLDG 10,ROOM 6S235,BETHESDA,MD 20892, USA. RI Siegel, Karen Lohmann/B-5898-2008 NR 16 TC 21 Z9 22 U1 0 U2 2 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0021-9290 J9 J BIOMECH JI J. Biomech. PD MAR PY 1994 VL 27 IS 3 BP 365 EP 371 DI 10.1016/0021-9290(94)90012-4 PG 7 WC Biophysics; Engineering, Biomedical SC Biophysics; Engineering GA MX060 UT WOS:A1994MX06000012 PM 8051196 ER PT J AU VUISTER, GW BAX, A AF VUISTER, GW BAX, A TI MEASUREMENT OF 4-BOND H(N)-H-ALPHA J-COUPLINGS IN STAPHYLOCOCCAL NUCLEASE SO JOURNAL OF BIOMOLECULAR NMR LA English DT Article DE 4-BOND J-COUPLING; ECOSY; QUANTITATIVE J-CORRELATION; STAPHYLOCOCCAL NUCLEASE ID TWO-DIMENSIONAL NMR; CONSTANTS; PROTEINS; SPECTROSCOPY; CONFORMATION; POLYPEPTIDES; SPECTRA; PHASE AB Quantitative J-correlation and triple-resonance ECOSY-type experiments are used to unambiguously establish the presence of four-bond sequential H(N)-H(alpha) J-couplings in the protein staphylococcal nuclease. Substantially negative 4J(HalphaHN) values, ranging from -0.8 to -2.3 Hz, are observed when the psi angle is near +120-degrees, and the following phi angle near +60-degrees. For other conformations, the four-bond H(N)-H(alpha) J-couplings fall between -0.5 and +0.5 Hz. RP VUISTER, GW (reprint author), NIDDKD,CHEM PHYS LAB,BETHESDA,MD 20892, USA. NR 29 TC 42 Z9 42 U1 0 U2 2 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 1994 VL 4 IS 2 BP 193 EP 200 PG 8 WC Biochemistry & Molecular Biology; Spectroscopy SC Biochemistry & Molecular Biology; Spectroscopy GA NC390 UT WOS:A1994NC39000004 PM 8019134 ER PT J AU CHENU, C IBARAKI, K ROBEY, PG DELMAS, PD YOUNG, MF AF CHENU, C IBARAKI, K ROBEY, PG DELMAS, PD YOUNG, MF TI CLONING AND SEQUENCE-ANALYSIS OF BOVINE BONE SIALOPROTEIN CDNA - CONSERVATION OF ACIDIC DOMAINS, TYROSINE SULFATION CONSENSUS REPEATS, AND RGD CELL ATTACHMENT DOMAIN SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Article ID MESSENGER-RNA; RAT OSTEOCLASTS; EXPRESSION; OSTEOPONTIN; TISSUES; MATRIX; LOCALIZATION; OSTEOBLASTS; FIBRONECTIN; BSP AB We isolated and sequenced a cDNA encoding bovine bone sialoprotein (BSP) using a bovine cDNA library made from mRNA isolated from bone-derived cell cultures and ligated to a phage lambda gt11. One of the cDNA clones isolated from this library had a 1800 base pair long insert and was found to contain the entire protein-encoding region. The deduced protein sequence revealed a 310 amino acid protein containing a signal peptide sequence of 16 hydrophobic amino acids. The protein sequence shows remarkable conservation with previously published human and rat sequences (more than 80% similarity for both species). The potential functional domains of BSP, including three acid amino acid-rich sequences, tyrosine sulfation consensus repeats, and the RGD cell binding sequence, are all present in the bovine sequence. Northern analysis of RNA from different bovine tissues indicated the presence of BSP message in bone but not in other nonmineralized tissues, confirming that bone is the major site of BSP message production. C1 NIDR,BONE RES BRANCH,BETHESDA,MD 20892. RP CHENU, C (reprint author), HOP EDOUARD HERRIOT,INSERM,U234,PAVILLON F,F-69437 LYON 03,FRANCE. RI Robey, Pamela/H-1429-2011 OI Robey, Pamela/0000-0002-5316-5576 NR 27 TC 13 Z9 16 U1 0 U2 1 PU BLACKWELL SCIENCE INC PI CAMBRIDGE PA 238 MAIN ST, CAMBRIDGE, MA 02142 SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD MAR PY 1994 VL 9 IS 3 BP 417 EP 421 PG 5 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA MX225 UT WOS:A1994MX22500017 PM 7514841 ER PT J AU VOGEL, T GUO, NH GUY, R DREZLICH, N KRUTZSCH, HC BLAKE, DA PANET, A ROBERTS, DD AF VOGEL, T GUO, NH GUY, R DREZLICH, N KRUTZSCH, HC BLAKE, DA PANET, A ROBERTS, DD TI APOLIPOPROTEIN-E - A POTENT INHIBITOR OF ENDOTHELIAL AND TUMOR-CELL PROLIFERATION SO JOURNAL OF CELLULAR BIOCHEMISTRY LA English DT Article DE DNA; HEPARIN-BINDING GROWTH FACTORS; BASIC FIBROBLAST GROWTH FACTOR; CARCINOMA CELLS; ANGIOGENESIS ID FIBROBLAST GROWTH-FACTOR; HERITABLE HYPERLIPIDEMIC RABBITS; HEPARIN-LIKE MOLECULES; PLASMA-LIPOPROTEINS; CHOLESTEROL TRANSPORT; EXTRACELLULAR-MATRIX; THROMBOSPONDIN; BINDING; ANGIOGENESIS; RECEPTOR AB Recombinant human apolipoprotein E3 (apoE), purified from E. coli, inhibited the proliferation of several cell types, including endothelial cells and tumor cells in a dose- and time-dependent manner. ApoE inhibited both de novo DNA synthesis and proliferation as assessed by an increase in cell number. Maximal inhibition of cell growth by apoE was achieved under conditions where proliferation was dependent on heparin-binding growth factors. Thus, at low serum concentrations (0-2.5%) basic fibroblast growth factor (bFGF) stimulated the proliferation of bovine aortic endothelial (BAE) cells severalfold. The bFGF-dependent proliferation was dramatically inhibited by apoE with an IC50 approximate to 50 nM. Under conditions where cell proliferation was mainly serum-dependent, apoE also suppressed growth but required higher concentrations to be effective (IC50 approximate to 500 nM). ApoE also inhibited growth of bovine corneal endothelial cells, human melanoma cells, and human breast carcinoma cells. The IC50 values obtained with these cells were generally 3-5 times higher than with BAE cells. Inhibition of cell proliferation by apoE was reversible and dependent on the time of apoE addition to the culture. In addition, apoE inhibited the chemotactic response of endothelial cells that were induced to migrate by a gradient of soluble bFGF. Inhibition of cell proliferation by apoE may be mediated both by competition for growth factor binding to proteoglycans and by an antiadhesive activity of apoE. The present results demonstrate that apoE is a potent inhibitor of proliferation of several cell types and suggest that apoE may be effective in modulating angiogenesis, tumor cell growth, and metastasis. (C) 1994 Wiley-Liss, Inc.* C1 NCI,PATHOL LAB,BETHESDA,MD 20892. MEHARRY MED COLL,DEPT BIOCHEM,NASHVILLE,TN 37208. BIOTECHNOL GEN LTD,REHOVOT,ISRAEL. RI Roberts, David/A-9699-2008 OI Roberts, David/0000-0002-2481-2981 FU NEI NIH HHS [R01 EY09092] NR 48 TC 101 Z9 104 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 0730-2312 J9 J CELL BIOCHEM JI J. Cell. Biochem. PD MAR PY 1994 VL 54 IS 3 BP 299 EP 308 DI 10.1002/jcb.240540306 PG 10 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA MY540 UT WOS:A1994MY54000005 PM 8200910 ER PT J AU FRERICHS, KU KENNEDY, C SOKOLOFF, L HALLENBECK, JM AF FRERICHS, KU KENNEDY, C SOKOLOFF, L HALLENBECK, JM TI LOCAL CEREBRAL BLOOD-FLOW DURING HIBERNATION, A MODEL OF NATURAL TOLERANCE TO CEREBRAL-ISCHEMIA SO JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM LA English DT Article DE CEREBRAL ISCHEMIA; GROUND SQUIRREL; HIBERNATION; IODOANTIPYRINE ID TRAUMATIC BRAIN INJURY; MODERATE HYPOTHERMIA; INTERPEDUNCULAR NUCLEUS; MAMMALIAN HIBERNATION; PROFOUND HYPOTHERMIA; CIRCULATORY ARREST; NEURONAL INJURY; TEMPERATURE; METABOLISM; DAMAGE AB The breakdown of cellular homeostasis and progressive neuronal destruction in cerebral ischemia appears to be mediated by a complex network of causes that are intricately interrelated. We have investigated a physiological state existing normally in nature in which mammals appear to tolerate the ordinarily detrimental effects of ischemia with reduced oxygen availability and to resist activation of self-destructive processes, i.e., mammalian hibernation. Ground squirrels (Spermophilus tridecemlineatus) were chronically implanted with arterial and ve nous catheters and telemetry devices for electroencephalography, electrocardiography, and monitoring of body temperature. The animals were placed in an environmental chamber at an ambient temperature of 5 degrees C. Entrance into hibernation was characterized by a drop in heart rate followed by a gradual decline in body temperature and an isoelectric electroencephalogram. Cold-adapted active animals that were not hibernating served as controls. Cerebral blood flow (CBF) was measured in both groups with the autoradiographic [C-14]iodoantipyrine method. Mean (+/- SD) mass-weighted CBF in the brain as a whole was 62 +/- 16 ml/100 g/min (n = 4) in the control group but was reduced to ischemic levels, 7 +/- 4 ml/100 g/min (n = 4), in the hibernating animals (p < 0.001). No neuropathological changes were found in similarly hibernating animals aroused from hibernation. Hibernation appears to be actively regulated, and hormonal factors may be involved. The identification and characterization of such factors and of the mechanisms used by hibernating species to increase ischemic tolerance and to blunt the destructive effects of ischemia may enable us to prevent or minimize the loss of homeostatic control during and after cerebral ischemia in other species. C1 NIMH,CEREBRAL METAB LAB,BETHESDA,MD 20892. RP FRERICHS, KU (reprint author), NINCDS,STROKE BRANCH,BLDG 36,ROOM 4D04,BETHESDA,MD 20892, USA. NR 64 TC 149 Z9 154 U1 0 U2 8 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 1994 VL 14 IS 2 BP 193 EP 205 PG 13 WC Endocrinology & Metabolism; Hematology; Neurosciences SC Endocrinology & Metabolism; Hematology; Neurosciences & Neurology GA MX608 UT WOS:A1994MX60800002 PM 8113316 ER PT J AU WAKABAYASHI, S FREED, LM BELL, JM RAPOPORT, SI AF WAKABAYASHI, S FREED, LM BELL, JM RAPOPORT, SI TI IN-VIVO CEREBRAL INCORPORATION OF RADIOLABELED FATTY-ACIDS AFTER ACUTE UNILATERAL ORBITAL ENUCLEATION IN ADULT HOODED LONG-EVANS RATS SO JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM LA English DT Article DE ARACHIDONATE; DEOXYGLUCOSE; FATTY ACIDS; LIPIDS; ORBITAL ENUCLEATION; QUANTITATIVE AUTORADIOGRAPHY; VISUAL SYSTEM ID CENTRAL-NERVOUS-SYSTEM; LATERAL GENICULATE-NUCLEUS; UNANESTHETIZED RATS; METABOLIC-ACTIVITY; ARACHIDONIC-ACID; VISUAL-CORTEX; CHOLINERGIC STIMULATION; EXTRASTRIATE CORTEX; BRAIN INCORPORATION; FISCHER-344 RATS AB We examined effects of acute unilateral enucleation on incorporation from blood of intravenously injected unsaturated [1-C-14]arachidonic acid ([C-14]AA) and [1-C-14]docosahexaenoic acid ([C-14]DHA), and of saturated [9,10-H-3]palmitic acid ([H-3]PA), into visual and nonvisual brain areas of awake adult Long-Evans hooded rats. Regional cerebral metabolic rate for glucose (rCMR(glc)) values also were assessed with 2-deoxy-D-[C-14]glucose ([C-14]DG). One day after unilateral enucleation, an awake rat was placed in a brightly lit visual stimulation box with black and white striped walls, and a radiolabeled fatty acid was infused for 5 min or [C-14]DG was injected as a bolus. [C-14]DG also was injected in a group of rats kept in the dark for 4 h. Fifteen minutes after starting an infusion of a radiolabeled fatty acid, or 45 min after injecting [C-14]DG, the rat was killed and the brain was prepared for quantitative autoradiography. Incorporation coefficients k* of fatty acids, or rCMR(glc) values, were calculated in homologous brain regions contralateral and ipsilateral to enucleation. As compared with ipsilateral regions, rCMR(glc), was reduced significantly (by as much as -39%) in contralateral visual areas, including the superior colliculus, lateral geniculate body, and layers I, IV, and V of the primary (striate) and secondary (association, extrastriate) visual cortices. Enucleation did not affect incorporation of [H-3]PA into contralateral visual regions, but reduced incorporation of [C-14]AA and of [C-14]DHA by -18.5 to -2.1%. Percent reductions were correlated with percent reductions in rCMR(glc) in most but not all regions. No effects were noted at any of nine nonvisual structures that were examined. These results indicate that enucleation acutely reduces neuronal activity in contralateral visual areas of the awake rat and that the reductions are coupled to reduced incorporation of unsaturated fatty acids into sn-2 regions of phosphatidylcholine, phosphatidylinositol, and phosphatidylethanolamine. Reduced fatty acid incorporation likely reflects reduced activity of phospholipases A(2) and/or phospholipase C. C1 NIA, NEUROSCI LAB, BETHESDA, MD 20892 USA. NR 65 TC 26 Z9 27 U1 0 U2 0 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0271-678X EI 1559-7016 J9 J CEREBR BLOOD F MET JI J. Cereb. Blood Flow Metab. PD MAR PY 1994 VL 14 IS 2 BP 312 EP 323 PG 12 WC Endocrinology & Metabolism; Hematology; Neurosciences SC Endocrinology & Metabolism; Hematology; Neurosciences & Neurology GA MX608 UT WOS:A1994MX60800014 PM 8113326 ER PT J AU LIU, Y JACOBOWITZ, DM BARONE, F MCCARRON, R SPATZ, M FEUERSTEIN, G HALLENBECK, JM SIREN, AL AF LIU, Y JACOBOWITZ, DM BARONE, F MCCARRON, R SPATZ, M FEUERSTEIN, G HALLENBECK, JM SIREN, AL TI QUANTITATION OF PERIVASCULAR MONOCYTES AND MACROPHAGES AROUND CEREBRAL BLOOD-VESSELS OF HYPERTENSIVE AND AGED RATS SO JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM LA English DT Note DE IMMUNOFLUORESCENCE; ED2; VON WILLEBRAND FACTOR; RATS; BRAIN ID TUMOR-NECROSIS-FACTOR; MICROGLIAL CELLS; RISK-FACTORS; BRAIN; TISSUE; INTERLEUKIN-1; EXPRESSION; CYTOKINES; INDUCTION; CULTURE AB The numbers of monocytes and macrophages in the walls of cerebral blood vessels were counted on perfusion-fixed frozen brain sections (16 mu m) of spontaneously hypertensive rats (SHR), stroke-prone SHR (SHR-SP), normotensive Wistar-Kyoto (WKY) rats, and young (16-week-old) and old (2-year-old) normotensive Sprague-Dawley rats (SD-16w and SD-2y, respectively) using monoclonal antibodies against rat macrophages (ED2). The staining was visualized with fluorescein-labeled second antibodies. The ED2-specific staining in brain sections was restricted to macrophages in a perivascular location. The number of perivascular cells per square millimeter of high-power field was significantly greater in SHR-SP (8.6 +/- 2.1; n = 4) and SHR (6.7 +/- 0.9; n = 6) than in normotensive WKY (4.0 +/- 0.5; n = 6; p < 0.01). The number of perivascular macrophages was also greater in SD-2y (7.5 +/- 2.7; n = 9) than in SD-16w (2.9 +/- 1.8; n = 8; p < 0.01). No ED2 staining was found in the resident microglia or in the endothelial cells, which were identified by double staining with rhodamine-labeled anti-factor VIII-related antigen antibodies. The results suggest that the stroke risk factors hypertension and advanced age are associated with increased subendothelial accumulation of monocytes and macrophages. This accumulation could increase the tendency for the endothelium to convert from an anticoaulant to a procoagulant surface in response to mediators released from these subendothelial cells. C1 UNIFORMED SERV UNIV HLTH SCI,DEPT NEUROL,BETHESDA,MD 20814. NIMH,CLIN SCI LAB,BETHESDA,MD 20892. SMITHKLINE BEECHAM LABS,DEPT PHARMACOL,KING OF PRUSSIA,PA. NINCDS,STROKE BRANCH,BETHESDA,MD. OI Siren, Anna-Leena/0000-0002-2217-0081 FU NINDS NIH HHS [NS-28225] NR 31 TC 32 Z9 34 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0271-678X J9 J CEREBR BLOOD F MET JI J. Cereb. Blood Flow Metab. PD MAR PY 1994 VL 14 IS 2 BP 348 EP 352 PG 5 WC Endocrinology & Metabolism; Hematology; Neurosciences SC Endocrinology & Metabolism; Hematology; Neurosciences & Neurology GA MX608 UT WOS:A1994MX60800019 PM 8113330 ER PT J AU ZHOU, HX SZABO, A DOUGLAS, JF HUBBARD, JB AF ZHOU, HX SZABO, A DOUGLAS, JF HUBBARD, JB TI A BROWNIAN DYNAMICS ALGORITHM FOR CALCULATING THE HYDRODYNAMIC FRICTION AND THE ELECTROSTATIC CAPACITANCE OF AN ARBITRARILY-SHAPED OBJECT SO JOURNAL OF CHEMICAL PHYSICS LA English DT Article ID ELLIPSOIDS AB An algorithm originally devised for calculating the diffusion-controlled reaction rate toward an arbitrarily shaped object is adapted to calculate the scalar translational hydrodynamic friction and the electrostatic capacitance of the object. In this algorithm Brownian particles are launched from a spherical surface enclosing the object. Each particle is propagated until it either hits the enclosed object or crosses the starting surface. In the latter case the particle is allowed to escape to infinity with an analytically known probability. If the particle does not escape to infinity, it is ;put-back on the starting surface with the correct distribution density and the process is repeated. The scalar friction or capacitance of the ''probed'' object is proportional to the fraction of particles that hit the object. This algorithm is illustrated on a dumbbell made of two equal-size spheres, a cube, and a phantom spherical shell having random distributed beads embedded in its surface. C1 NATL INST STAND & TECHNOL,DIV POLYMERS,GAITHERSBURG,MD 20899. NATL INST STAND & TECHNOL,DIV BIOTECHNOL,GAITHERSBURG,MD 20899. RP ZHOU, HX (reprint author), NIDDKD,BETHESDA,MD 20892, USA. RI Szabo, Attila/H-3867-2012; Zhou, Huan-Xiang/M-5170-2016 OI Zhou, Huan-Xiang/0000-0001-9020-0302 NR 29 TC 69 Z9 69 U1 0 U2 12 PU AMER INST PHYSICS PI WOODBURY PA CIRCULATION FULFILLMENT DIV, 500 SUNNYSIDE BLVD, WOODBURY, NY 11797-2999 SN 0021-9606 J9 J CHEM PHYS JI J. Chem. Phys. PD MAR 1 PY 1994 VL 100 IS 5 BP 3821 EP 3826 DI 10.1063/1.466371 PG 6 WC Chemistry, Physical; Physics, Atomic, Molecular & Chemical SC Chemistry; Physics GA MY349 UT WOS:A1994MY34900046 ER PT J AU RAPOPORT, JL AF RAPOPORT, JL TI CLOZAPINE AND CHILD-PSYCHIATRY SO JOURNAL OF CHILD AND ADOLESCENT PSYCHOPHARMACOLOGY LA English DT Editorial Material RP RAPOPORT, JL (reprint author), NIMH,BETHESDA,MD 20892, USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 SN 1044-5463 J9 J CHILD ADOL PSYCHOP JI J. Child Adolesc. Psychopharmacol. PD SPR PY 1994 VL 4 IS 1 BP 1 EP 3 DI 10.1089/cap.1994.4.1 PG 3 WC Pediatrics; Pharmacology & Pharmacy; Psychiatry SC Pediatrics; Pharmacology & Pharmacy; Psychiatry GA NE990 UT WOS:A1994NE99000001 ER PT J AU FRIEDMAN, E ADAMS, EF HOOG, A GEJMAN, PV CARSON, E LARSSON, C DEMARCO, L WERNER, S FAHLBUSCH, R NORDENSKJOLD, M AF FRIEDMAN, E ADAMS, EF HOOG, A GEJMAN, PV CARSON, E LARSSON, C DEMARCO, L WERNER, S FAHLBUSCH, R NORDENSKJOLD, M TI NORMAL STRUCTURAL DOPAMINE TYPE-2 RECEPTOR GENE IN PROLACTIN-SECRETING AND OTHER PITUITARY-TUMORS SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID GRADIENT GEL-ELECTROPHORESIS; ENDOCRINE NEOPLASIA TYPE-1; SINGLE-BASE CHANGES; ADENYLATE-CYCLASE; GC-CLAMP; D2-DOPAMINE RECEPTOR; INHIBITORY-ACTION; DNA FRAGMENTS; ALLELIC LOSS; CHROMOSOME-11 AB Dopamine, acting via its specific receptor (DRD2) in the anterior pituitary, tonically inhibits pituitary prolactin secretion and lactotroph proliferation. In addition, dopamine agonist therapy for pituitary prolactinomas results in reduction of prolactin secretion and tumor regression. These observations lead to the speculation that functional dopamine uncoupling may release lactotrophs from the inhibitory effects of dopamine and contribute to the development of prolactin (PRL)secreting pituitary tumors. We hypothesized that such an uncoupling may occur by inactivating mutation(s) of the DRD2. To test our hypothesis, we examined 79 pituitary tumors, mostly prolactinomas and mixed GH/PRL-secreting, for mutations in the coding exons of the DRD2 gene. We used the polymerase chain reaction and analyzed the fragments for migration abnormalities on denaturing gradient gel electrophoresis, complemented by direct DNA sequencing. No mutations were demonstrated, and all migration abnormalities detected by denaturing gradient gel electrophoresis were due to polymorphisms within the DRD2 gene. In addition, allelic losses in the multiple endocrine neoplasia type 1 region in 11q13 could not be demonstrated in all five informative prolactinomas. We conclude that mutations in the DRD2 gene do not occur in PRL or GH/PRL-secreting pituitary tumors and that allelic loss of 11q13 is uncommon in prolactinomas. C1 KAROLINSKA HOSP, DEPT ENDOCRINOL & DIABETOL, S-17176 STOCKHOLM, SWEDEN. KOPFKLINIKUM, DEPT NEUROSURG, W-8520 ERLANGEN, GERMANY. NIMH, CLIN NEUROGENET BRANCH, BETHESDA, MD 20892 USA. UNIV FED MINAS GERAIS, DEPT PHARMACOL, BR-31270 BELO HORIZONTE, MG, BRAZIL. KAROLINSKA HOSP, DEPT PATHOL, S-17176 STOCKHOLM, SWEDEN. RP FRIEDMAN, E (reprint author), KAROLINSKA HOSP, DEPT CLIN GENET, POB 60500, S-17176 STOCKHOLM, SWEDEN. RI De Marco, Luiz /H-6275-2012 NR 54 TC 56 Z9 59 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 EI 1945-7197 J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD MAR PY 1994 VL 78 IS 3 BP 568 EP 574 DI 10.1210/jc.78.3.568 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA MZ307 UT WOS:A1994MZ30700011 PM 7907340 ER PT J AU ANASTI, JN ADAMS, S KIMZEY, LM DEFENSOR, RA ZACHARY, AA NELSON, LM AF ANASTI, JN ADAMS, S KIMZEY, LM DEFENSOR, RA ZACHARY, AA NELSON, LM TI KARYOTYPICALLY NORMAL SPONTANEOUS PREMATURE OVARIAN FAILURE - EVALUATION OF ASSOCIATION WITH THE CLASS-II MAJOR HISTOCOMPATIBILITY COMPLEX SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID AUTOIMMUNE AB Patients with premature ovarian failure (POF) have been reported to have an increased frequency of the major histocompatibily class (MHC) class II antigen HLA-DR3. Here we attempt to confirm this association. We performed MHC class II immunophenotyping of HLA-DR antigens 1-10 on 102 North American caucasians with confirmed POF and 102 control caucasian women. All patients had experienced amenorrhea before the age of 40 yr and had elevated serum gonadotropins on repeated study. We found no significant increase in HLA-DR3 frequency in patients with POF when compared to our control group (P = 0.52) or even when compared to a large reference population (n = 1927) that did not differ significantly from our control group (P = 0.47). Our patients did have an increased frequency of HLA DR4 compared to this large reference population (41% vs. 23%; P < 0.001), but we were unable to demostrate increased HLA DR4 frequency using our control group (31%; P = 0.14). In conclusion, despite a power of 99%, we were unable to confirm a significant increase in MHC class II HLA-DR3 frequency in patients with POF. C1 NIAID, CTR CLIN, DEPT TRANSFUS MED, DIV HLA, BETHESDA, MD 20892 USA. NIAID, CTR CLIN, DEPT NURSING, BETHESDA, MD 20892 USA. NIAID, DIV ALLERGY IMMUNOL & TRANSPLANTAT, BETHESDA, MD 20892 USA. RP ANASTI, JN (reprint author), NICHHD, DEV ENDOCRINOL BRANCH, GYNECOL RES SECT, BLDG 10, ROOM 10N-262, BETHESDA, MD 20892 USA. NR 14 TC 28 Z9 29 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 1994 VL 78 IS 3 BP 722 EP 723 DI 10.1210/jc.78.3.722 PG 2 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA MZ307 UT WOS:A1994MZ30700036 PM 8126148 ER PT J AU REINCKE, M KARL, M TRAVIS, WH MASTORAKOS, G ALLOLIO, B LINEHAN, HM CHROUSOS, GP AF REINCKE, M KARL, M TRAVIS, WH MASTORAKOS, G ALLOLIO, B LINEHAN, HM CHROUSOS, GP TI P53 MUTATIONS IN HUMAN ADRENOCORTICAL NEOPLASMS - IMMUNOHISTOCHEMICAL AND MOLECULAR STUDIES SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID GENE; TRANSFORMATION; TUMORIGENESIS; CARCINOMAS; POLYMERASE; PROTEIN; CANCER; LINE; DNA AB The mechanisms of tumorigenesis of adrenocortical neoplasms have not been elucidated as yet. However, loss of heterozygosity at chromosomal locus 17p has been consistently observed in adrenocortical cancer. p53 is a recessive tumor suppressor gene located on chromosome 17p. Mutations in the p53 gene play an important role in the tumorigenesis of diverse types of human neoplasms including breast and colon cancers. More than 90% of all mutations discovered in such tumors have been detected in 4 hot spot areas that lie between exons 5 and 8. In contrast to wild-type p53, mutant p53 accumulates intracellularly and can be easily detected by immunohistochemistry. We therefore investigated the frequency of p53 mutations in human adrenocortical neoplasms using molecular biology and immunohistochemistry techniques. Five patients with adrenocortical adenomas (5 female; ages 39-72 yr), 11 patients with adrenocortical carcinomas (8 female, 3 male; ages 15-50 yr), and two adrenocortical tumor cell lines were studied. After DNA extraction from frozen tumor tissue or paraffin-embedded material, exons 5 through 8 were amplified using the polymerase chain reaction and directly sequenced by the dideoxy termination method. Immunohistochemistry was performed on paraffin-embedded tumor specimens obtained during adrenalectomy using a monoclonal antibody reacting with both wild-type and mutant p53. Prevalence of mutations was adenomas, 0/5, carcinomas, 3/11, and adrenocortical cell lines, 2/2. Single point mutations were detected in 3 cases (exons 5, 6, and 7, respectively), and rearrangements of exon 7/8 and 8 were found in 2 cases. Immunohistochemistry detected strong nuclear and/or cytoplasmic p53 immunoreactivity in all adrenocortical carcinomas with point mutations of the p53 gene but not in adenomas and carcinomas with the wild-type sequence or with deletion/rearrangement of the p53 gene. We conclude that p53 plays a role in the tumorigenesis of adrenocortical carcinomas but is of less importance to benign adenomas. C1 NICHHD, DEV ENDOCRINOL BRANCH, BETHESDA, MD 20892 USA. UNIV WURZBURG, MED KLIN, W-8700 WURZBURG, GERMANY. NICHHD, DEPT CLIN PATHOL, BETHESDA, MD 20892 USA. NICHHD, SURG BRANCH, BETHESDA, MD 20892 USA. NR 27 TC 164 Z9 165 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 1994 VL 78 IS 3 BP 790 EP 794 DI 10.1210/jc.78.3.790 PG 5 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA MZ307 UT WOS:A1994MZ30700048 PM 8126158 ER PT J AU PUCK, JM AF PUCK, JM TI MOLECULAR AND GENETIC-BASIS OF X-LINKED IMMUNODEFICIENCY DISORDERS SO JOURNAL OF CLINICAL IMMUNOLOGY LA English DT Article DE MOLECULAR CLONING; HUMAN X-LINKED IMMUNODEFICIENCY (X-LINKED SEVERE COMBINED IMMUNODEFICIENCY); AGAMMAGLOBULINEMIA; HYPER-IGM SYNDROME; INTERLEUKIN-2 RECEPTOR GAMMA CHAIN; CYTOKINE RECEPTOR; B-CELL TYROSINE KINASE; CD40 LIGAND; GP39 ID CHROMOSOME INACTIVATION; CARRIER DETECTION; HUMAN DNA; T-CELLS; AGAMMAGLOBULINEMIA; DEFECT; POLYMORPHISMS; INTERLEUKIN-2; EXPRESSION; DXS178 C1 CHILDRENS HOSP PHILADELPHIA,PHILADELPHIA,PA. UNIV PENN,SCH MED,DEPT PEDIAT,PHILADELPHIA,PA 19104. RP PUCK, JM (reprint author), NIH,NATL CTR HUMAN GEN RES,GENE TRANSFER LAB,IMMUNOL GENET SECT,BETHESDA,MD 20892, USA. FU NHGRI NIH HHS [R01 HG00233]; NICHD NIH HHS [R01 HD23679] NR 51 TC 34 Z9 34 U1 0 U2 3 PU PLENUM PUBL CORP PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 SN 0271-9142 J9 J CLIN IMMUNOL JI J. Clin. Immunol. PD MAR PY 1994 VL 14 IS 2 BP 81 EP 89 DI 10.1007/BF01541340 PG 9 WC Immunology SC Immunology GA ND034 UT WOS:A1994ND03400001 PM 8195317 ER PT J AU SIGOUNAS, G HARINDRANATH, N DONADEL, G NOTKINS, AL AF SIGOUNAS, G HARINDRANATH, N DONADEL, G NOTKINS, AL TI HALF-LIFE OF POLYREACTIVE ANTIBODIES SO JOURNAL OF CLINICAL IMMUNOLOGY LA English DT Article DE HALF-LIFE; HUMAN; POLYREACTIVE ANTIBODIES ID B-CELL REPERTOIRE; SYSTEMIC LUPUS-ERYTHEMATOSUS; MONOREACTIVE HIGH-AFFINITY; MONOCLONAL AUTOANTIBODIES; RHEUMATOID-FACTOR; NATURAL ANTIBODIES; IMMUNE-COMPLEXES; MULTIPLE ORGANS; SERUM; IGG AB Monoclonal polyreactive antibodies bind to a variety of self and foreign antigens. In contrast, monoclonal monoreactive antibodies bind to a single or restricted number of known antigens. The rate at which polyreactive antibodies are removed from the circulation compared to monoreactive antibodies has not been determined. In the present experiments, human monoclonal polyreactive and monoreactive antibodies of different isotypes were injected intravenously into mice and the clearance from the circulation was determined. The half-life of polyreactive IgM, IgA, and IgG antibodies was 8.0, 8.2, and 9.8 hr, respectively, compared to 35.4, 26.6, and 280 hr for monoreactive IgM, IgA, and IgG antibodies, respectively. Examination of tissue sections from animals given intravenous antibody showed substantial deposition of polyreactive, but not monoreactive, antibodies in several organs, the liver being the principal site of deposition. It is concluded that polyreactive antibodies are cleared from the circulation substantially faster than monoreactive antibodies. RP SIGOUNAS, G (reprint author), NIDR,ORAL MED LAB,BLDG 30,ROOM 121,BETHESDA,MD 20892, USA. NR 39 TC 30 Z9 31 U1 0 U2 7 PU PLENUM PUBL CORP PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 SN 0271-9142 J9 J CLIN IMMUNOL JI J. Clin. Immunol. PD MAR PY 1994 VL 14 IS 2 BP 134 EP 140 DI 10.1007/BF01541346 PG 7 WC Immunology SC Immunology GA ND034 UT WOS:A1994ND03400007 PM 8195315 ER PT J AU SMITH, PD SUFFREDINI, AF ALLEN, JB WAHL, LM PARRILLO, JE WAHL, SM AF SMITH, PD SUFFREDINI, AF ALLEN, JB WAHL, LM PARRILLO, JE WAHL, SM TI ENDOTOXIN ADMINISTRATION TO HUMANS PRIMES ALVEOLAR MACROPHAGES FOR INCREASED PRODUCTION OF INFLAMMATORY MEDIATORS SO JOURNAL OF CLINICAL IMMUNOLOGY LA English DT Article DE ALVEOLAR MACROPHAGE; SHOCK; ENDOTOXIN; TUMOR NECROSIS FACTOR; INTERLEUKIN-1 ID TUMOR-NECROSIS-FACTOR; PERIPHERAL-BLOOD MONOCYTES; FACTOR-ALPHA; ENDOTHELIAL-CELLS; GENE-EXPRESSION; INTERLEUKIN-1; LIPOPOLYSACCHARIDE; RELEASE; CACHECTIN; RECEPTORS AB To elucidate potential mechanisms of the acute lung injury associated with endotoxemia, we evaluated the effect of intravenously administered endotoxin on the ability of alveolar macrophages isolated by bronchoalveolar lavage from normal subjects to produce inflammatory mediators. Within 1 hr of endotoxin (4 ng/kg body weight) administration, all 12 study subjects developed constitutional symptoms and leukopenia, and within 3 hr, low-grade fever. Resolution of symptoms and fever by 6 hr was accompanied by systemic granulocytosis. Although intravenously administered endotoxin appeared to activate a subset of circulating monocytes, it did not alter the bronchoalveolar lavage cell number, phenotype (95% macrophages), or constitutively expressed high levels of surface HLA-DR and O2-. In contrast, intravenous endotoxin primed the alveolar macrophages for enhanced lipopolysaccharide-induced secretion of interleukin-1 (11.8 to 25.8 U/ml; P = 0.04), tumor necrosis factor-alpha (titer, 6.8 to 13.6; P = 0.20), and prostaglandin E2 (38.4 to 116.3 ng/ml; P = 0.035). These results demonstrate that low-dose intravenous endotoxin primes human alveolar macrophages, which are already differentiated in situ, for enhanced secretion of inflammatory mediators. Such mediators may contribute to the pulmonary changes associated with endotoxemia and acute lung injury. C1 NIDR,IMMUNOL LAB,BETHESDA,MD 20892. NIH,CTR CLIN,DEPT CRIT CARE MED,BETHESDA,MD 20892. NR 39 TC 37 Z9 37 U1 0 U2 3 PU PLENUM PUBL CORP PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 SN 0271-9142 J9 J CLIN IMMUNOL JI J. Clin. Immunol. PD MAR PY 1994 VL 14 IS 2 BP 141 EP 148 DI 10.1007/BF01541347 PG 8 WC Immunology SC Immunology GA ND034 UT WOS:A1994ND03400008 PM 8195316 ER PT J AU BONDY, CA ZHOU, J CHIN, E REINHARDT, RR DING, L ROTH, RA AF BONDY, CA ZHOU, J CHIN, E REINHARDT, RR DING, L ROTH, RA TI CELLULAR-DISTRIBUTION OF INSULIN-DEGRADING ENZYME GENE-EXPRESSION - COMPARISON WITH INSULIN AND INSULIN-LIKE GROWTH-FACTOR RECEPTORS SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article DE PROTEOLYSIS; IN SITU HYBRIDIZATION; SPERMATOCYTE; OOCYTE; MESSENGER-RNA ID I-125 INSULIN; FACTOR-II; DEGRADATION; PROTEASE; CELLS; METALLOENDOPROTEASE; MECHANISMS; INHIBITION; PRODUCTS; INVIVO AB Insulin-degrading enzyme (IDE) hydrolyzes both insulin and IGFs and has been proposed to play a role in signal termination after binding of these peptides to their receptors. In situ hybridization was used to investigate the cellular distribution of IDE mRNA and to compare it with insulin receptor (IR) and IGF-I receptor (IGFR) gene expression in serial thin sections from a variety of tissues in embryonic and adult rats. IDE mRNA is highly abundant in kidney and liver, tissues known to play a role in insulin degradation. IDE and IR mRNAS are highly coexpressed in brown fat and liver. The highest level IDE gene expression, on a per cell basis, is found in germinal epithelium. IDE and IGFR mRNAs are colocalized in oocytes, while IDE is colocalized with the IGF-II receptor in spermatocytes, suggesting that IDE may be involved with degradation of IGF-II in the testis. In summary, IDE expression demonstrates significant anatomical correlation with insulin/IGF receptors. These data are compatible with a role for IDE in degrading insulin and IGFs after they bind to and are internalized with their respective receptors and may also suggest a novel role for IDE in germ cells. C1 STANFORD UNIV,DEPT MOLEC PHARMACOL,STANFORD,CA 94305. RP BONDY, CA (reprint author), NICHHD,DEV ENDOCRINOL BRANCH,BLDG 10,ROOM 10N262,BETHESDA,MD 20892, USA. FU NIDDK NIH HHS [DK-34926] NR 35 TC 28 Z9 28 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 1994 VL 93 IS 3 BP 966 EP 973 DI 10.1172/JCI117103 PG 8 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA NB195 UT WOS:A1994NB19500010 PM 8132782 ER PT J AU MAURAS, N HAYMOND, MW DARMAUN, D VIEIRA, NE ABRAMS, SA YERGEY, AL AF MAURAS, N HAYMOND, MW DARMAUN, D VIEIRA, NE ABRAMS, SA YERGEY, AL TI CALCIUM AND PROTEIN KINETICS IN PREPUBERTAL BOYS - POSITIVE EFFECTS OF TESTOSTERONE SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article DE TESTOSTERONE; PUBERTY; GROWTH; LEUCINE METABOLISM; CALCIUM METABOLISM ID RAT SKELETAL-MUSCLE; GROWTH-HORMONE; GLUTAMINE CONCENTRATION; CONSTITUTIONAL DELAY; ISOTOPIC TRACERS; BONE LOSS; METABOLISM; PUBERTY; HUMANS; MASS AB We investigated the effects of 4-6-wk administration of testesterone on calcium and protein metabolism in six healthy prepubertal short boys (mean age+/-SE = 12.9+/-0.6 yr). At baseline, subjects received a 4-h infusion of L-[1-C-13]leucine and L-[2-N-15]glutamine, and were given Ca-42 intravenously, and Ca-44 PO. Testosterone enanthate (similar to 3 mg/kg) was given I.M. 2 wk apart (two doses n = 5, three doses n = 1), and the study was repeated 4-5 d after the last injection. After testosterone therapy, there were significant increases in serum testosterone and mean peak and total growth hormone concentrations. Net calcium absorption (Va) and retention (Vbal) also increased (Va 13.3+/-2.3 vs 21.5+/-2.3; mg.kg(-1).d(-)1, Vbal 8.0+/-2.1 vs 16.6+/-2.5, mg.kg(-1).d(-1), P<.05 both), as well as Ca's net forward flow into bone and total exchangeable pool (16 and 20%, respectively). The rate of appearance of leucine (an indicator of proteolysis) increased by 17.6+/-5.9%, P = 0.036. Leucine oxidation decreased by 48.6+/-8.0%, P = 0.004; thus, nonoxidative leucine disappearance, which estimates protein synthesis, increased significantly by 34.4+/-7.7%, P = 0.009. Glutamine's rate of appearance also increased (+32%), mostly through enhanced glutamine de novo synthesis (+42%). In conclusion, short term testosterone administration significantly increases calcium's retention and net forward flow into bone in prepubertal humans, as well as whole body estimates of protein and calcium anabolism. These effects may represent a pure androgen effect, an amplification of growth hormone's action or some combination of these factors. C1 NICHHD,BETHESDA,MD 20842. CHILDRENS NUTR RES CTR,HOUSTON,TX 77096. RP MAURAS, N (reprint author), NEMOURS CHILDRENS CLIN,807 NIRA ST,JACKSONVILLE,FL 32207, USA. OI Abrams, Steven/0000-0003-4972-9233 FU PHS HHS [R01 26989] NR 42 TC 77 Z9 77 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 1994 VL 93 IS 3 BP 1014 EP 1019 DI 10.1172/JCI117049 PG 6 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA NB195 UT WOS:A1994NB19500016 PM 8132741 ER PT J AU CROFFORD, LJ WILDER, RL RISTIMAKI, AP SANO, H REMMERS, EF EPPS, HR HLA, T AF CROFFORD, LJ WILDER, RL RISTIMAKI, AP SANO, H REMMERS, EF EPPS, HR HLA, T TI CYCLOOXYGENASE-1 AND CYCLOOXYGENASE-2 EXPRESSION IN RHEUMATOID SYNOVIAL TISSUES - EFFECTS OF INTERLEUKIN-1-BETA, PHORBOL ESTER, AND CORTICOSTEROIDS SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article DE RHEUMATOID ARTHRITIS; INFLAMMATION; GLUCOCORTICOID; INTERLEUKIN-1; PROSTAGLANDIN ID CORTICOTROPIN-RELEASING FACTOR; PROSTAGLANDIN-H SYNTHASE; ADRENAL AXIS ACTIVATION; CELL-WALL ARTHRITIS; INDUCIBLE CYCLOOXYGENASE; ALVEOLAR MACROPHAGES; LIPOPOLYSACCHARIDE; GENE; MECHANISMS; INDUCTION AB High levels of immunoreactive cyclooxygenase (Cox; prostaglandin H synthase) are present in synovia from patients with rheumatoid arthritis (RA). We now show that the recently identified inducible isoform of Cox, Cox-2, is expressed in synovia from patients with RA. To further explore modulation of the Cox isoforms in RA synovial tissues, we examined the expression and modulation of Cox-1 and -2 in rheumatoid synovial explant cultures and cultured rheumatoid synovial fibroblastlike cells (synoviocytes). Immunoprecipitation of in vitro labeled proteins and Western blot analysis demonstrated the presence of both Cox-1 and -2 under basal conditions in freshly explanted rheumatoid synovial tissues. De novo synthesis of Cox-2 polypeptide was enhanced by IL-1 beta or PMA, and dramatically suppressed by dexamethasone (dex). Cox-1 expression, under the same conditions, showed only minor variation. Since mRNA for Cox-2 is highly unstable, we examined the regulation of Cox-2 transcripts in cultured rheumatoid synoviocytes. Under basal conditions both Cox-1 and -2 mRNAs were present at low levels, but Cox-2 mRNA was markedly increased by treatment with IL-1 beta or PMA. dex markedly suppressed the induction of Cox-2 mRNA. In sharp contrast, Cox-1 transcripts were not modulated by IL-1 beta or dex. These data suggest that modulation of Cox-2 expression by IL-1 beta and corticosteroids may be an important component of the inflammatory process in synovial tissues from patients with RA. C1 NIAMSD,ARTHRITIS & RHEUMATISM BRANCH,INFLAMMATORY JOINT DIS SECT,BETHESDA,MD 20892. AMER RED CROSS,JEROME H HOLLAND LAB,DEPT MOLEC BIOL,ROCKVILLE,MD 20855. RI Hla, Timothy/G-5873-2012; Crofford, Leslie/J-8010-2013 OI Hla, Timothy/0000-0001-8355-4065; FU NHLBI NIH HHS [HL-49094] NR 46 TC 595 Z9 609 U1 3 U2 10 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 1994 VL 93 IS 3 BP 1095 EP 1101 DI 10.1172/JCI117060 PG 7 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA NB195 UT WOS:A1994NB19500027 PM 8132748 ER PT J AU POLLAK, MR CHOU, YHW MARX, SJ STEINMANN, B COLE, DEC BRANDI, ML PAPAPOULOS, SE MENKO, FH HENDY, GN BROWN, EM SEIDMAN, CE SEIDMAN, JG AF POLLAK, MR CHOU, YHW MARX, SJ STEINMANN, B COLE, DEC BRANDI, ML PAPAPOULOS, SE MENKO, FH HENDY, GN BROWN, EM SEIDMAN, CE SEIDMAN, JG TI FAMILIAL HYPOCALCIURIC HYPERCALCEMIA AND NEONATAL SEVERE HYPERPARATHYROIDISM - EFFECTS OF MUTANT-GENE DOSAGE ON PHENOTYPE SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article DE GENE DOSAGE; CHROMOSOME 3Q; CONSANGUINITY; HYPERCALCEMIA; HYPERPARATHYROIDISM ID BENIGN HYPERCALCEMIA; KINDREDS; PARENTS; GENE AB Neonatal severe hyperparathyroidism is a rare life-threatening disorder characterized by very high serum calcium concentrations (> 15 mg/dl). Many cases have occurred in families with familial hypocalciuric hypercalcemia, a benign condition transmitted as a dominant trait. Among several hypothesized relationships between the two syndromes is the suggestion that neonatal severe hyperparathyroidism is the homozygous form of familial hypocalciuric hypercalcemia. To test this hypothesis, we refined the map location of the gene responsible for familial hypocalciuric hypercalcemia on chromosome 3q. Analyses in 11 families defined marker loci closely linked to the gene responsible for familial hypocalciuric hypercalcemia. These loci were then analyzed in four families with parental consanguinity and offspring with neonatal severe hyperparathyroidism. Each individual who was homozygous for loci that are closely linked to the gene responsible for familial hypocalciuric hypercalcemia had neonatal severe hyperparathyroidism . The calculated odds of linkage between these disorders of > 350,000:1 (lod score = 5.56). We conclude that dosage of the gene defect accounts for these widely disparate clinical phenotypes; a single defective allele causes familial hypocalciuric hypercalcemia, while two defective alleles causes neonatal severe hyperparathyroidism. C1 HARVARD UNIV,BRIGHAM & WOMENS HOSP,SCH MED,DEPT MED,BOSTON,MA 02115. HARVARD UNIV,SCH MED,HOWARD HUGHES MED INST,BOSTON,MA 02115. NIDDKD,METAB DIS BRANCH,BETHESDA,MD 20892. UNIV ZURICH,DEPT PEDIAT,CH-8032 ZURICH,SWITZERLAND. DALHOUSIE UNIV,DEPT PEDIAT,HALIFAX B3J 3G9,NS,CANADA. DALHOUSIE UNIV,DEPT PATHOL,HALIFAX B3J 3G9,NS,CANADA. UNIV FLORENCE,DEPT CLIN PHYSIOPATHOL,I-50139 FLORENCE,ITALY. LEIDEN UNIV HOSP,DEPT ENDOCRINOL & METAB DIS,2333 AA LEIDEN,NETHERLANDS. MCGILL UNIV,DEPT MED,MONTREAL H3A 1A1,PQ,CANADA. RP POLLAK, MR (reprint author), HARVARD UNIV,SCH MED,DEPT GENET,EQRF ROOM 533,200 LONGWOOD AVE,BOSTON,MA 02115, USA. FU NHLBI NIH HHS [HL-41474]; NIDDK NIH HHS [DK02138, DK36796] NR 26 TC 183 Z9 186 U1 0 U2 4 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 1994 VL 93 IS 3 BP 1108 EP 1112 DI 10.1172/JCI117062 PG 5 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA NB195 UT WOS:A1994NB19500029 PM 8132750 ER PT J AU PANOS, RJ RUBIN, JS CSAKY, KG AARONSON, SA MASON, RJ AF PANOS, RJ RUBIN, JS CSAKY, KG AARONSON, SA MASON, RJ TI KERATINOCYTE GROWTH-FACTOR AND HEPATOCYTE GROWTH FACTOR/SCATTER FACTOR ARE HEPARIN-BINDING GROWTH-FACTORS FOR ALVEOLAR TYPE-II CELLS IN FIBROBLAST-CONDITIONED MEDIUM (VOL 92, PG 969, 1993) SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Correction, Addition C1 NCI,CELLULAR & MOLEC BIOL LAB,BETHESDA,MD 20892. UNIV COLORADO,HLTH SCI CTR,NATL JEWISH CTR IMMUNOL & RESP MED,DIV PULM,DENVER,CO 80206. RP PANOS, RJ (reprint author), NORTHWESTERN UNIV,SCH MED,DEPT MED,DIV PULM,CHICAGO,IL 60611, USA. NR 1 TC 7 Z9 7 U1 0 U2 0 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD MAR PY 1994 VL 93 IS 3 BP 1347 EP 1347 PG 1 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA NB195 UT WOS:A1994NB19500061 ER PT J AU KLEINMAN, SH KAPLAN, JE KHABBAZ, RF CALABRO, MA THOMSON, R BUSCH, M AF KLEINMAN, SH KAPLAN, JE KHABBAZ, RF CALABRO, MA THOMSON, R BUSCH, M TI EVALUATION OF A P21E-SPIKED WESTERN-BLOT (IMMUNOBLOT) IN CONFIRMING HUMAN T-CELL LYMPHOTROPIC VIRUS TYPE-I OR TYPE-II INFECTION IN VOLUNTEER BLOOD-DONORS SO JOURNAL OF CLINICAL MICROBIOLOGY LA English DT Article ID LEUKEMIA-VIRUS; HTLV-I/II; TRANSMISSION; TRANSFUSION; SEROCONVERSION; COMPONENTS; RECIPIENTS AB Current algorithms for the serologic confirmation of human T-cell lymphotropic virus type I or II (HTLV-I/II) antibody reactivity are complicated. We evaluated the performance of an HTLV/I Western blot (immunoblot) spiked with recombinant p21e protein (p21e WB) as an alternative to current confirmatory methods. These methods include the HTLV-I viral lysate Western blot and either a radioimmunoprecipitation assay or a p21e enzyme-linked immunosorbent assay. Five hundred fifty nine blood donations obtained from five U.S. blood centers and classified as HTLV-I/II seropositive (n = 149) or seroindeterminate (n = 410) by routine testing methods were further evaluated by PCR for proviral DNA and by the p21e WB. On the basis of serologic and PCR testing, 155 donations were classified as HTLV-I/II infected. The sensitivity of the p21e WB was 97.4%, slightly exceeding that of routine confirmatory testing. The specificity of the p21e WB was 97.5%, as determined by testing of 404 seroindeterminate samples that were negative in the PCR. The positive predictive value of the p21e WB was 94%. In contrast, the specificity and positive predictive value of routine confirmatory testing were both 100%. follow-up sampling of presumptive p21e WB false-positive donors substantiated the absence of HTLV-I/II infection. Although the p21e WB used in this study has high sensitivity and may be useful as a confirmatory assay in epidemiologic research studies, it may not be ideal as a confirmatory test for the notification of blood donors. C1 SO CALIF REG AMER RED CROSS, BLOOD SERV, LOS ANGELES, CA 90006 USA. CTR DIS CONTROL & PREVENT, NATL CTR INFECT DIS, DIV VIRAL & RICKETTSIAL DIS, RETROVIRUS DIS BRANCH, ATLANTA, GA 30333 USA. SRA TECHNOL INC, ROCKVILLE, MD 20850 USA. WESTAT CORP, ROCKVILLE, MD 20850 USA. IRWIN MEM BLOOD CTR, SAN FRANCISCO, CA 94118 USA. UNIV CALIF SAN FRANCISCO, SAN FRANCISCO, CA 94143 USA. NHLBI, BETHESDA, MD 20892 USA. RP KLEINMAN, SH (reprint author), UNIV CALIF LOS ANGELES, MED CTR, 10833 LECONTE AVE, ROOM A4-239 CHS, LOS ANGELES, CA 90024 USA. FU NHLBI NIH HHS [N0 1 HB 97080] NR 17 TC 18 Z9 18 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0095-1137 EI 1098-660X J9 J CLIN MICROBIOL JI J. Clin. Microbiol. PD MAR PY 1994 VL 32 IS 3 BP 603 EP 607 PG 5 WC Microbiology SC Microbiology GA MW516 UT WOS:A1994MW51600004 PM 8195365 ER PT J AU CUZICK, J STEWART, H RUTQVIST, L HOUGHTON, J EDWARDS, R REDMOND, C PETO, R BAUM, M FISHER, B HOST, H LYTHGOE, J RIBEIRO, G SCHEURLEN, H AF CUZICK, J STEWART, H RUTQVIST, L HOUGHTON, J EDWARDS, R REDMOND, C PETO, R BAUM, M FISHER, B HOST, H LYTHGOE, J RIBEIRO, G SCHEURLEN, H TI CAUSE-SPECIFIC MORTALITY IN LONG-TERM SURVIVORS OF BREAST-CANCER WHO PARTICIPATED IN TRIALS OF RADIOTHERAPY SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID POSTOPERATIVE RADIOTHERAPY; RADIATION-THERAPY; CLINICAL-TRIAL C1 SCOTTISH CANC TRIALS OFF,EDINBURGH,MIDLOTHIAN,SCOTLAND. CANC RES CAMPAIGN,CTR CLIN TRIALS,LONDON,ENGLAND. RADCLIFFE INFIRM,OXFORD,ENGLAND. ROYAL PRESTON HOSP,PRESTON,LANCS,ENGLAND. CHRISTIE HOSP,MANCHESTER,LANCS,ENGLAND. KAROLINSKA HOSP,STOCKHOLM,SWEDEN. UNIV PITTSBURGH,NATL SURG ADJUVANT BREAST & BOWEL PROJECT,PITTSBURGH,PA. NORWEGIAN RADIUM HOSP,OSLO,NORWAY. UNIV HEIDELBERG,HEIDELBERG,GERMANY. RP CUZICK, J (reprint author), IMPERIAL CANC RES FUND,POB 123,LINCOLNS INN FIELDS,LONDON WC2A 3PX,ENGLAND. NR 17 TC 543 Z9 554 U1 0 U2 12 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 1994 VL 12 IS 3 BP 447 EP 453 PG 7 WC Oncology SC Oncology GA MZ763 UT WOS:A1994MZ76300003 PM 8120544 ER PT J AU GREM, JL MCATEE, N MURPHY, RF HAMILTON, JM BALIS, F STEINBERG, S ARBUCK, SG SETSER, A JORDAN, E CHEN, A KOHLER, DR KOTITE, B ALLEGRA, CJ AF GREM, JL MCATEE, N MURPHY, RF HAMILTON, JM BALIS, F STEINBERG, S ARBUCK, SG SETSER, A JORDAN, E CHEN, A KOHLER, DR KOTITE, B ALLEGRA, CJ TI PHASE-I AND PHARMACOKINETIC STUDY OF RECOMBINANT HUMAN GRANULOCYTE-MACROPHAGE COLONY-STIMULATING FACTOR GIVEN IN COMBINATION WITH FLUOROURACIL PLUS CALCIUM LEUCOVORIN IN METASTATIC GASTROINTESTINAL ADENOCARCINOMA SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID HIGH-DOSE LEUCOVORIN; BONE-MARROW TRANSPLANTATION; FOLINIC ACID; BIOCHEMICAL MODULATION; COLORECTAL-CARCINOMA; RANDOMIZED TRIAL; 5-FLUOROURACIL; CHEMOTHERAPY; CANCER; NEUTROPENIA C1 NCI,DIV CANC TREATMENT,CANC THERAPY EVALUAT PROGRAM,BETHESDA,MD 20892. NIH,WARREN GRANT MAGNUSON CLIN CTR,CANC NURSING SERV,BETHESDA,MD 20892. NIH,WARREN GRANT MAGNUSON CLIN CTR,DEPT PHARM,BETHESDA,MD 20892. RP GREM, JL (reprint author), NCI,NATL NAVAL MED CTR,NAVY MED ONCOL BRANCH,CLIN ONCOL PROGRAM,BETHESDA,MD 20889, USA. NR 34 TC 36 Z9 37 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 1994 VL 12 IS 3 BP 560 EP 568 PG 9 WC Oncology SC Oncology GA MZ763 UT WOS:A1994MZ76300018 PM 8120554 ER PT J AU SWEDO, SE LEONARD, HL AF SWEDO, SE LEONARD, HL TI CHILDHOOD MOVEMENT-DISORDERS AND OBSESSIVE-COMPULSIVE DISORDER SO JOURNAL OF CLINICAL PSYCHIATRY LA English DT Article; Proceedings Paper CT 146th Annual Meeting of the American-Psychiatric-Association CY MAY 22-27, 1993 CL SAN FRANCISCO, CA SP Amer Psychiat Assoc ID ACUTE RHEUMATIC-FEVER; DOUBLE-BLIND; CLOMIPRAMINE TREATMENT; TOURETTES-SYNDROME; CHILDREN; ADOLESCENTS; PREVALENCE; PLACEBO; CHOREA; DESIPRAMINE AB Recent investigations of childhood-onset obsessive compulsive disorder (OCD) and pediatric movement disorders such as tics, Tourette's syndrome (TS), and Sydenham's chorea suggest that these disorders may be related. Although comorbid obsessive-compulsive symptoms have long been recognized in individuals with TS, more recent studies have demonstrated that tics and TS are surprisingly common in children with primary OCD, and further, that the two disorders seem to have a common genetic vulnerability. Obsessive-compulsive symptoms are also manifest in Sydenham's chorea, a neurologic variant of rheumatic fever in which antistreptococcal antibodies are thought to cross-react with neuronal tissue, particularly within the basal ganglia, and cause inflammatory changes resulting in neuropsychiatric symptomatology. The frequent comorbidity of OCD and Sydenham's chorea and similar postulates of basal ganglia dysfunction for both disorders suggest that Sydenham's chorea may serve as a medical model for OCD. Of note, however, is that the medications (e.g., neuroleptics) that are effective in treating this and other movement disorders are distinctly different from those that are efficacious for OCD (e.g., serotonin reuptake blockers). Examinations of the similarities and differences among these various neuropsychiatric conditions may lead to greater understanding of the pathophysiology of OCD and offer further insights into the etiology and treatment of this troubling disorder. RP SWEDO, SE (reprint author), NIMH,CHILD PSYCHIAT BRANCH,BEHAV PEDIAT UNIT,BLDG 10,ROOM 6N240,BETHESDA,MD 20892, USA. NR 42 TC 47 Z9 48 U1 3 U2 5 PU PHYSICIANS POSTGRADUATE PRESS PI MEMPHIS PA P O BOX 240008, MEMPHIS, TN 38124 SN 0160-6689 J9 J CLIN PSYCHIAT JI J. Clin. Psychiatry PD MAR PY 1994 VL 55 SU S BP 32 EP 37 PG 6 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA NG369 UT WOS:A1994NG36900006 PM 7915713 ER PT J AU MALKIN, CM LAMB, ME AF MALKIN, CM LAMB, ME TI CHILD MALTREATMENT - A TEST OF SOCIOBIOLOGICAL THEORY SO JOURNAL OF COMPARATIVE FAMILY STUDIES LA English DT Article DE SOCIOBIOLOGY; CHILD MALTREATMENT; INFANTICIDE; STEPPARENTS ID SEX-RATIO; ABUSE; INFANTICIDE; PARENTS AB Five hypotheses regarding child maltreatment were derived from sociobiological theory and tested using data on 69,119 families and 113,748 abused children. It was predicted that: 1) nonbiological parents would engage in more severe types of abuse than would biological parents; 2) in two-biological-parent households, biological fathers would maltreat their progeny more than would biological mothers; 3) biological parents would abuse their progeny while their children were very young, whereas nonbiological parents would not show a predictable age-related pattern of abuse; 4) when biological parents from poorer families abused their progeny, the victims would tend to be male, whereas when biological parents from more affluent families abused their progeny, the victims would tend to be female; and 5) children living with female relatives who were past their reproductive prime would be at low risk for abuse. Only two of these hypotheses were supported: biological parents abused younger rather than older children, whereas nonbiological parents did not show a predictable age-related pattern of abuse; and female relatives past their reproductive prime tended to commit less severe types of abuse than did female relatives still reproductively capable. C1 NICHHD,SOCIAL & EMOT DEV SECT,BETHESDA,MD 20814. RP MALKIN, CM (reprint author), UNIV UTAH,DEPT PSYCHOL,SALT LAKE CITY,UT 84112, USA. NR 49 TC 24 Z9 24 U1 0 U2 4 PU J COMPARATIVE FAMILY STUDIES PI CALGARY PA UNIV CALGARY-DEPT SOCIOLOGY 2500 UNIVERSITY DRIVE NW, CALGARY AB T2N 1N4, CANADA SN 0047-2328 J9 J COMP FAM STUD JI J. Comp. Fam. Stud. PD SPR PY 1994 VL 25 IS 1 BP 121 EP 133 PG 13 WC Family Studies SC Family Studies GA MX835 UT WOS:A1994MX83500008 ER PT J AU CONDE, F LUND, JS JACOBOWITZ, DM BAIMBRIDGE, KG LEWIS, DA AF CONDE, F LUND, JS JACOBOWITZ, DM BAIMBRIDGE, KG LEWIS, DA TI LOCAL CIRCUIT NEURONS IMMUNOREACTIVE FOR CALRETININ, CALBINDIN D-28K OR PARVALBUMIN IN MONKEY PREFRONTAL CORTEX - DISTRIBUTION AND MORPHOLOGY SO JOURNAL OF COMPARATIVE NEUROLOGY LA English DT Article DE CALCIUM-BINDING PROTEINS; NONPYRAMIDAL NEURONS; CYNOMOLGUS MONKEY; RHESUS MONKEY ID CALCIUM-BINDING PROTEIN; PRIMARY AUDITORY-CORTEX; BOUQUET CELL AXONS; HUMAN MOTOR CORTEX; CEREBRAL-CORTEX; VISUAL-CORTEX; IMMUNOHISTOCHEMICAL LOCALIZATION; PRENATAL DEVELOPMENT; RAT-BRAIN; STRUCTURAL ORGANIZATION AB In the cerebral cortex, local circuit neurons provide critical inhibitory control over the activity of pyramidal neurons, the major class of excitatory efferent cortical cells. The calcium-binding proteins, calretinin, calbindin, and parvalbumin, are expressed in a variety of cortical local circuit neurons. However, in the primate prefrontal cortex, relatively little is known, especially with regard to calretinin, about the specific classes or distribution of local circuit neurons that contain these calcium-binding proteins. In this study, we used immunohistochemical techniques to characterize and compare the morphological features and distribution in macaque monkey prefrontal cortex of local circuit neurons that contain each of these calcium-binding proteins. On the basis of the axonal features of the labeled neurons, and correlations with previous Golgi studies, calretinin appeared to be present in double-bouquet neurons, calbindin in neurogliaform neurons and Martinotti cells, and parvalbumin in chandelier and wide arbor (basket) neurons. Calretinin was also found in other cell populations, such as a distinctive group of large neurons in the infragranular layers, but it was not possible to assign these neurons to a known cell class. In addition, although the animals studied were adults, immunoreactivity for both calretinin and calbindin was found in Cajal-Retzius neurons of layer I. Dual labeling studies confirmed that with the exception of the Cajal-Retzius neurons, each calcium-binding protein was expressed in separate populations of prefrontal cortical neurons. Comparisons of the laminar distributions of the labeled neurons also indicated that these calcium-binding proteins were segregated into discrete neuronal populations. Calretinin-positive neurons were present in greatest density in deep layer I and layer II, calbindin-immunoreactive cells were most dense in layers II-superficial III, and parvalbumin-containing neurons were present in greatest density in the middle cortical layers. In addition, the relative density of calretinin-labeled neurons was approximately twice that of the calbindin- and parvalbumin-positive neurons. However, within each group of labeled neurons, their laminar distribution and relative density did not differ substantially across regions of the prefrontal cortex. These findings demonstrate that calretinin, calbindin, and parvalbumin are markers of separate populations of local circuit neurons in monkey prefrontal cortex, and that they may be useful tools in unraveling the intrinsic inhibitory circuitry of the primate prefrontal cortex in both normal and disease states. (C) 1994 Wiley-Liss, Inc. C1 UNIV PITTSBURGH,DEPT PSYCHIAT,PITTSBURGH,PA 15213. UNIV PITTSBURGH,DEPT BEHAV NEUROSCI,PITTSBURGH,PA 15213. UNIV LONDON,DEPT VISUAL SCI,LONDON EC1V 9EL,ENGLAND. NIMH,CLIN SCI LAB,BETHESDA,MD 20892. UNIV BRITISH COLUMBIA,DEPT PHYSIOL,VANCOUVER,BC,CANADA. RI Lewis, David/G-4053-2014 OI Lewis, David/0000-0002-3225-6778 FU NIMH NIH HHS [NIMH MH00519, NIMH MH45156] NR 81 TC 351 Z9 358 U1 0 U2 10 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0021-9967 J9 J COMP NEUROL JI J. Comp. Neurol. PD MAR 1 PY 1994 VL 341 IS 1 BP 95 EP 116 DI 10.1002/cne.903410109 PG 22 WC Neurosciences; Zoology SC Neurosciences & Neurology; Zoology GA MV322 UT WOS:A1994MV32200008 PM 8006226 ER PT J AU VALDEZ, IH PIZZO, PA ATKINSON, JC AF VALDEZ, IH PIZZO, PA ATKINSON, JC TI ORAL HEALTH OF PEDIATRIC AIDS PATIENTS - A HOSPITAL-BASED STUDY SO JOURNAL OF DENTISTRY FOR CHILDREN LA English DT Article ID ACQUIRED IMMUNODEFICIENCY SYNDROME; CHILDREN; DISEASE; CARIES; RISK AB The prevalence of acquired immunodeficiency syndrome (AIDS) is steadily increasing among American children. The dental needs of these patients are significant. This study evaluated the oral health of forty children being treated for HIV-infection at the National Institutes of Health (NIH). Eight of twenty-two patients in primary dentition (36 percent) had baby bottle tooth decay (BBTD). These cases required extensive dental restoration usually under general anesthesia. Tooth development was delayed in 31 percent of patients. Candidiasis was the most common soft tissue abnormality, found in 35 percent of children. Preventive and therapeutic dental programs should be instituted to meet the special needs of pediatric AIDS patients. C1 NCI,BETHESDA,MD 20892. NIDR,BETHESDA,MD 20892. RP VALDEZ, IH (reprint author), UNIV COLORADO,SCH DENT,DENVER,CO 80202, USA. NR 32 TC 25 Z9 25 U1 0 U2 0 PU AMER SOC DENTISTRY CHILD PI CHICAGO PA JOHN HANCOCK CENTER, 875 N MICHIGAN AVE, STE 4040, CHICAGO, IL 60611-1901 SN 0022-0353 J9 J DENT CHILD JI J. Dent. Child. PD MAR-APR PY 1994 VL 61 IS 2 BP 114 EP 118 PG 5 WC Dentistry, Oral Surgery & Medicine; Pediatrics SC Dentistry, Oral Surgery & Medicine; Pediatrics GA NM040 UT WOS:A1994NM04000008 PM 8046089 ER PT J AU MONDER, C VINCZE, I BLYE, RP IOHAN, F AF MONDER, C VINCZE, I BLYE, RP IOHAN, F TI METABOLISM OF TESTOSTERONE TRANS-4-N-BUTYLCYCLOHEXYL CARBOXYLATE, A HIGH POTENCY ANDROGEN, IN RODENTS AND PRIMATES - IN-VITRO STUDIES SO JOURNAL OF ENDOCRINOLOGY LA English DT Article ID ESTER; PHARMACOKINETICS; MEN AB Testosterone trans-4-n-butylcyclohexyl carboxylate releases continuous physiological levels of testosterone into the circulation of men or monkeys over a period of 8 to 10 weeks from an intramuscular depot and may, therefore, be an agent of choice for androgen replacement therapy. The purpose of this study was to investigate the metabolism of the ester and its side chain. The ester was hydrolysed by blood sera of guinea-pig, rabbit and rat, but not horse or man. It was slowly hydrolysed by rat and cynomolgus liver and the testosterone metabolites androstenedione and androstanediol were formed. Bucyclic acid (trans-4-n-butylcyclohexyl carboxylate) was slowly metabolized to two metabolites, M1 and M2, by cynomolgus liver homogenates. The acid metabolites were analysed by chromatography and mass spectrometry after reaction with diazomethylpyrene to form fluorescent pyrenyl esters. When compared with synthetic compounds using the criteria of chromatographic mobility and mass spectral analysis, the polar metabolite was identified as hydroxy-4-n-butylcyclohexyl carboxylate. The less polar metabolite could not be definitively identified. C1 ATTILA JOZSEF UNIV,DEPT ORGAN CHEM,H-6720 SZEGED,HUNGARY. NIH,CONTRACEPT DEV BRANCH,BETHESDA,MD 20892. RP MONDER, C (reprint author), POPULAT COUNCIL,1230 YORK AVE,NEW YORK,NY 10021, USA. NR 11 TC 1 Z9 1 U1 0 U2 0 PU J ENDOCRINOLOGY LTD PI BRISTOL PA 17/18 THE COURTYARD, WOODLANDS, ALMONDSBURY, BRISTOL, ENGLAND BS12 4NQ SN 0022-0795 J9 J ENDOCRINOL JI J. Endocrinol. PD MAR PY 1994 VL 140 IS 3 BP 465 EP 473 DI 10.1677/joe.0.1400465 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA NF891 UT WOS:A1994NF89100018 PM 8182375 ER PT J AU LUJAN, HD NASH, TE AF LUJAN, HD NASH, TE TI THE UPTAKE AND METABOLISM OF CYSTEINE BY GIARDIA-LAMBLIA TROPHOZOITES SO JOURNAL OF EUKARYOTIC MICROBIOLOGY LA English DT Article DE CYSTINE; DIFFUSION; METHIONINE; SULFATE; SULFUR; TRANSPORT ID SACCHAROMYCES-CEREVISIAE; ENTAMOEBA-HISTOLYTICA; SURFACE-PROTEINS; AMINO-ACIDS; BIOCHEMISTRY; ATTACHMENT; CULTURE; GROWTH AB The cysteine, cystine, methionine and sulfate uptake and cysteine metabolism of Giardia lamblia was studied. Initial experiments indicated that bathocuproine sulphonate (20 mu M) added to Keister's modified TYI-S-33 medium supported the growth of G. lamblia at low L-cysteine concentration. This allowed the use of high specific activity radiolabeled L-cysteine for further studies. The analyses of L-cysteine uptake by G. lamblia indicate the presence of at least two different transport systems. The total cysteine uptake was non saturable, with a capacity of 3.7 pmoles per 10(6) cells per min per mu M of cysteine, and probably represent passive diffusion. However, cysteine transport was partially inhibited by L-methionine, D-cysteine and DL-homocysteine, indicating that another system specific for SH-containing amino acids is also present. Cysteine uptake was markedly decreased in medium without serum. In contrast to cysteine, the uptake of L-methionine and sulfate were carried out by saturable systems with apparent K-m of 71 and 72 mu M, respectively, but the V-max of the uptake of sulfate was six orders of magnitude lower than the V-max of methionine uptake. Cystine was not incorporated into trophozoites. [S-35]-labeled L-cysteine and L-methionine, but not [S-35]sulfate, were incorporated into Giardia proteins, indicating that the parasite lacks the capacity to synthesize cysteine or methionine from sulfate. Neither cystathionine gamma lyase nor crystathionine gamma synthase activities was detected in homogenates of Giardia lamblia, suggesting that the transsulfuration pathway is not active and there is no conversion of methionine to cysteine. Our data indicate take up cystine, and b) cannot synthesize cysteine de novo. RP LUJAN, HD (reprint author), NIAID,PARASIT DIS LAB,BLDG 4,BETHESDA,MD 20892, USA. NR 33 TC 24 Z9 24 U1 0 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 1994 VL 41 IS 2 BP 169 EP 175 DI 10.1111/j.1550-7408.1994.tb01491.x PG 7 WC Microbiology SC Microbiology GA NE680 UT WOS:A1994NE68000012 PM 8167619 ER PT J AU KIRSCHNER, R KULHAVI, C BODROGI, I BOKI, M SIKLOS, P BAKACS, T AF KIRSCHNER, R KULHAVI, C BODROGI, I BOKI, M SIKLOS, P BAKACS, T TI ENHANCED ANTIBODY-DEPENDENT CELL-MEDIATED CYTOTOXICITY OF PERIPHERAL-BLOOD MONONUCLEAR-CELLS IN PATIENTS WITH GERMINAL CELL TUMORS SO JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH LA English DT Article DE K-CELL; ADCC; GERMINAL CELL TUMOR; CHEMOTHERAPY AB The antibody-dependent cell mediated cytotoxicity (K-cell activity) of peripheral blood mononuclear cells from 92 patients with germinal cell tumors and 60 healthy male controls was measured against 0,Rh(D) positive human red blood cells sensitized with anti-D antibody. To determine the maximal K-cell activity the enyzme-like kinetic model of cytotoxicity-in which lysis was measured in presence of target cell excess, was utilized. To avoid variations due to the individual sensitivity of target erythrocytes red blood cells were obtained from a single donor. It was demonstrated that the K-cell activity of patients with germinal cell tumors was significantly enhanced compared to the control group. Patients with clinically detectable tumors showed relevant higher activity than those without detectable tumor. Chemotherapy significantly enhanced the activity of patients in the former group. C1 NCI,EXPTL IMMUNOL BRANCH,BLD 10,ROOM 4B-17,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU APSIT ASSOC PROM STUD IMMUNOL TUMOR PI ROME PA VIALE REGINA ELENA 291, 00161 ROME, ITALY SN 0392-9078 J9 J EXP CLIN CANC RES JI J. Exp. Clin. Cancer Res. PD MAR PY 1994 VL 13 IS 1 BP 61 EP 65 PG 5 WC Oncology SC Oncology GA NH273 UT WOS:A1994NH27300009 ER PT J AU BAKKER, ABH SCHREURS, MWJ DEBOER, AJ KAWAKAMI, Y ROSENBERG, SA ADEMA, GJ FIGDOR, CG AF BAKKER, ABH SCHREURS, MWJ DEBOER, AJ KAWAKAMI, Y ROSENBERG, SA ADEMA, GJ FIGDOR, CG TI MELANOCYTE LINEAGE-SPECIFIC ANTIGEN GP100 IS RECOGNIZED BY MELANOMA-DERIVED TUMOR-INFILTRATING LYMPHOCYTES SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Note ID MONOCLONAL-ANTIBODY; METASTATIC MELANOMA; HLA-A2; CELLS AB We recently isolated a cDNA clone that encodes the melanocyte lineage-specific antigen glycoprotein (gp)100. Antibodies directed against gp100 are an important tool in the diagnosis of human melanoma. Since the gp100 antigen is highly expressed in melanocytic cells, we investigated whether this antigen might serve as a target for antimelanoma cytotoxic T lymphocytes (CTL). Here, we demonstrate that cytotoxic tumor-infiltrating lymphocytes (TIL) derived from a melanoma patient (TIL 1200) are directed against gp100. HLA-A2.1(+) melanoma cells are lysed by TIL from this patient. In addition, murine double transfectants, expressing both HLA-A2.1 and gp100, are lysed by TIL 1200, whereas transfectants expressing only HLA-A2.1 are not susceptible to lysis. Furthermore, the HLA-A2.1(+) melanoma cell line BLM, which lacks gp100 expression and is resistant to lysis, becomes susceptible after transfection of gp100 cDNA. Finally, HLA-A2.1(+) normal melanocytes are lysed by TIL 1200. These data demonstrate that the melanocyte differentiation antigen gp100 can be recognized in the context of HLA-A2.1 by CTL from a melanoma patient. Gp100 may therefore constitute a useful target for specific immunotherapy against melanoma, provided that no unacceptable cytotoxicity towards normal tissue is observed. C1 ANTONI VAN LEEUWENHOEK HUIS,NETHERLANDS CANC INST,DIV IMMUNOL,1066 CX AMSTERDAM,NETHERLANDS. NCI,DIV CANC TREATMENT,SURG BRANCH,BETHESDA,MD 20892. RI Figdor, Carl/A-4232-2010; Adema, G.J./H-8007-2014; Kawakami, Yutaka /E-7429-2013; OI Kawakami, Yutaka /0000-0003-4836-2855; Figdor, Carl/0000-0002-2366-9212 NR 26 TC 483 Z9 488 U1 1 U2 11 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 1994 VL 179 IS 3 BP 1005 EP 1009 DI 10.1084/jem.179.3.1005 PG 5 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA MY484 UT WOS:A1994MY48400025 PM 8113668 ER PT J AU BOWSER, AD DIXON, D HASEMAN, JK AF BOWSER, AD DIXON, D HASEMAN, JK TI COMPARISON OF AUTOMATED AND MANUAL IMMUNOHISTOCHEMICAL STAINING OF BROMODEOXYURIDINE (BRDU)-LABELED PULMONARY EPITHELIAL-CELLS IN MICE SO JOURNAL OF HISTOTECHNOLOGY LA English DT Article DE AUTOMATED STAINING; BROMODEOXYURIDINE (BRDU); IMMUNOHISTOCHEMISTRY; LUNG; MICE ID THYMIDINE AB An automated method for 5-bromo-2'-deoxyuridine (BrdU) staining of mouse lung tissue with the Fisher Code-On series is described. BrdU labeling indices (LI) were statistically analyzed to determine the efficacy of automated vs manual staining to detect BrdU incorporation. In the automated method, which utilized capillary gap technology, tissue-tissue and tissue-non-tissue slide pairing were evaluated. The effects of varying trypsin concentrations and the maximum concentration for producing optimal automated BrdU staining were also determined. Comparisons were made between 10% neutral buffered formalin and modified B5 (mercuric chloride) fixed tissues. The automated and manual BrdU staining methods were comparable in overall quality. Analysis of variance procedures revealed no significant differences between the manual and automated procedures for LI in the treated and control animals. In the automated method, no significant difference in the intensity or pattern of staining was found in the variations of slide pairing. A 0.3% trypsin concentration enhanced the intensity of nuclear staining compared to 0.006% trypsin; however, the optimal trypsin concentration in which cellular integrity was maintained was determined to be 0.0375%. Tissues preserved in modified B5 fixative had distorted cellular morphology and decreased intensity of staining compared to tissues fixed in 10% neutral buffered formalin, after trypsin digestion. C1 NIEHS,POB 12233,RES TRIANGLE PK,NC 27709. NR 8 TC 0 Z9 0 U1 0 U2 0 PU NATL SOC HISTOTECHNOLOGY PI BOWIE PA 4201 NORTHVIEW DR, STE 502, BOWIE, MD 20716-1073 SN 0147-8885 J9 J HISTOTECHNOL JI J. Histotechnol. PD MAR PY 1994 VL 17 IS 1 BP 23 EP 27 PG 5 WC Cell Biology SC Cell Biology GA ND278 UT WOS:A1994ND27800003 ER PT J AU CARMELLI, D ROBINETTE, D FABSITZ, R AF CARMELLI, D ROBINETTE, D FABSITZ, R TI CONCORDANCE, DISCORDANCE AND PREVALENCE OF HYPERTENSION IN WORLD-WAR-II MALE VETERAN TWINS SO JOURNAL OF HYPERTENSION LA English DT Article DE HYPERTENSION; ADULT MALE TWINS; CONCORDANCE; DISCORDANCE; OBESITY; WEIGHT GAIN; ALCOHOL CONSUMPTION ID DISEASE RISK-FACTORS; NHLBI TWIN; WEIGHT AB Objective: To determine concordance for hypertension in adult male twins and to examine individual environmental factors associated with the manifestation of the disease in one member but not both members of a twin pair. Methods: The subjects were 1003 monozygotic and 858 dizygotic Caucasian, male, World War II veteran twins born in the USA between 1917 and 1927, who were aged 56-66 years when surveyed by the National Heart, Lung, and Blood Institute for health behaviors and cardiovascular disease status. Hypertensive status was determined by the subjects' diagnostic reports from physicians and the subjects' past or current use of antihypertensive medications. Self-reports were validated in a subsample of 675 individual twins who were participants in a series of cardiovascular examinations and for whom blood pressure measurements were available. Results: The data analyses indicate that in this cohort of adult male twins, 62% of monozygotic and 48% of dizygotic cotwins of the hypertensive twins were hypertensives, compared with a prevalence of 36% in the whole cohort. Among the 281 monozygotic twins discordant for hypertension, hypertensive twins differed significantly from their non-hypertensive cotwins in the weight gain throughout adulthood and in alcohol consumption. They did not differ in weight at induction into the military, or according to smoking, physical activity or demographics. Those pairs that were concordant for hypertension gained significantly more weight throughout adulthood, consumed more alcohol, and were physically less active than concordant-negative pairs. Conclusions: The findings from this study suggest that although genetic factors influence the development of hypertension, non-genetic and potentially modifiable lifestyle behaviors, including adult weight gain, alcohol consumption and physical activity, are closely related to the clinical manifestation of the disease, C1 NATL ACAD SCI, MED FOLLOW UP AGCY, WASHINGTON, DC 20418 USA. NHLBI, BETHESDA, MD 20892 USA. RP SRI INT, HLTH SCI PROGRAM, 333 RAVENSWOOD AVE, MENLO PK, CA 94025 USA. FU NHLBI NIH HHS [HL 46115]; NIAAA NIH HHS [ADAMHA AA08925] NR 31 TC 26 Z9 26 U1 1 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0263-6352 EI 1473-5598 J9 J HYPERTENS JI J. Hypertens. PD MAR PY 1994 VL 12 IS 3 BP 323 EP 328 PG 6 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA NB137 UT WOS:A1994NB13700015 PM 8021487 ER PT J AU APASOV, SG SITKOVSKY, MV AF APASOV, SG SITKOVSKY, MV TI DEVELOPMENT AND ANTIGEN-SPECIFICITY OF CD8(+) CYTOTOXIC T-LYMPHOCYTES IN BETA(2)-MICROGLOBULIN-NEGATIVE, MHC CLASS I-DEFICIENT MICE IN RESPONSE TO IMMUNIZATION WITH TUMOR-CELLS SO JOURNAL OF IMMUNOLOGY LA English DT Article ID BETA-2-MICROGLOBULIN-DEFICIENT MICE; SURFACE EXPRESSION; TRANSGENIC MICE; GRAFT-REJECTION; MOLECULES; PEPTIDE; SELECTION; CLEARANCE; INFECTION; BINDING AB beta(2)-Microglobulin knockout mice (beta(2)-m-/-) with MHC class I expression deficiency are able to develop functional TCR(+)-alpha beta, CD8(+) CTLs in response to tumor cell injection. The i.p. injection of beta(2)-m-/- mice with tumor results in the massive accumulation of highly lytic CD8(+) CTLs in the peritoneum and causes the local recruitment of CD8(+) T cells into lymph nodes and spleens of immune animals. The accumulation of CD8(+) CTLs in peritoneum is accompanied by the rejection of tumor cells and the survival of animals. The deficiency in MHC class I expression in beta(2)-m-/- mice is reflected in the delayed tumor rejection and CD8(+) cell accumulation during the primary anti-tumor response in comparison with normal mice. The secondary response, however, is identical in normal and MHC class I-deficient mice. The rejection of tumor cells appears to be MHC class I directed because no rejection of tumors, no accumulation oi CD8(+) CTLs, and no survival of animals were observed when syngeneic tumor cells were used for injection with the notable exception of anti-minor Ag response. The Ag specificity of CD8(+) CTLs in beta(2)-m-/- mice is demonstrated using a panel of tumor target cells and class I transfectants. Although no substantial differences were found in the number and specificity of peritoneal CD8(+) CTLs in beta(2)-m-/- and normal mice using tumor rejection studies, the analysis of TCR-V beta phenotype using the panel of mAbs revealed the reduction in proportion of TCR-V beta and TCR-V beta 6 used by CD8(+) cell population from beta(2)-m-/- mice. Development of lytic and H-2-directed CD8(+) cells in regional lymph nodes was also observed after footpad immunization of beta(2)-m-/- mice with TNP-labeled C57BL/6 splenocytes, suggesting anti-minor Ag reaction. C1 NIAID,IMMUNOL LAB,BETHESDA,MD 20892. NR 32 TC 46 Z9 46 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 1994 VL 152 IS 5 BP 2087 EP 2097 PG 11 WC Immunology SC Immunology GA NB988 UT WOS:A1994NB98800001 PM 8133027 ER PT J AU KWON, BS KOZAK, CA KIM, KK PICKARD, RT AF KWON, BS KOZAK, CA KIM, KK PICKARD, RT TI GENOMIC ORGANIZATION AND CHROMOSOMAL LOCALIZATION OF THE T-CELL ANTIGEN 4-1BB SO JOURNAL OF IMMUNOLOGY LA English DT Article ID GROWTH-FACTOR RECEPTOR; TUMOR-NECROSIS-FACTOR; MOLECULAR-CLONING; TNF RECEPTOR; EXPRESSION; TRANSCRIPTION; ACTIVATION; GENE; SEQUENCES; PROTEINS AB 4-1BB is an inducible T cell surface receptor which belongs to the nerve growth factor receptor superfamily, a group of cysteine-rich cell-surface proteins. 4-1BB is a 30-kDa glycoprotein and exists as both a monomer and a 55-kDa dimer on the T cell surface. Cross-linking 4-1BB with monoclonal antibody resulted in the 2- to 10-fold enhancement of T cell proliferation. We have isolated and characterized 4-1BB genomic clones and have found that the 4-1BB gene contains two different 5' untranslated regions, which are used alternately to form the 4-1BB mRNA. The two 5' UTRs were encoded in the same chromosome and were separated from one another by an intron of similar to 2.5 kb. The entire gene spans approximately 13 kb of mouse chromosome 4.4-1BB gene consists of 10 exons and 9 introns, in which there are two exons for 5' untranslated regions and 8 exons for coding region. Most of the putative functional domains were encoded by separate exons. 4-1BB extracellular domain contains four potential C6 (CXn C XX C XX CXn C Xn C) motifs, of which the first motif is partial and the third is distinct from those of nerve growth factor receptor or TNF receptor 1. A comparison of exon-intron organization among the genes of the nerve growth factor receptor family indicated that most C6 motif is interrupted by an intron. C1 NIAID,MOLEC MICROBIOL LAB,BETHESDA,MD 20892. RP KWON, BS (reprint author), INDIANA UNIV,SCH MED,WALTHER ONCOL CTR,DEPT MICROBIOL & IMMUNOL,635 BARNHILL DR,INDIANAPOLIS,IN 46202, USA. RI Kim, Kack-Kyun/C-5031-2012 OI Kim, Kack-Kyun/0000-0002-1279-5387 FU NIAID NIH HHS [AI 28175]; NIAMS NIH HHS [AR 40248]; NIDCR NIH HHS [DE 10525] NR 33 TC 25 Z9 28 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 1994 VL 152 IS 5 BP 2256 EP 2262 PG 7 WC Immunology SC Immunology GA NB988 UT WOS:A1994NB98800021 PM 8133039 ER PT J AU POLITIS, AD OZATO, K COLIGAN, JE VOGEL, SN AF POLITIS, AD OZATO, K COLIGAN, JE VOGEL, SN TI REGULATION OF IFN-GAMMA-INDUCED NUCLEAR EXPRESSION OF IFN CONSENSUS SEQUENCE BINDING-PROTEIN IN MURINE PERITONEAL-MACROPHAGES SO JOURNAL OF IMMUNOLOGY LA English DT Article ID INTERFERON-ALPHA; TRANSCRIPTION FACTOR; INDUCIBLE GENES; MESSENGER-RNA; KINASE-C; ACTIVATION; IRF-1; CELLS; BETA; INDUCTION AB IFNs are well characterized macrophage-activating agents. Their varied effects are largely mediated via the induction of many genes, whose products act in concert to induce macrophage differentiation. Homologous DNA sequences have been found upstream of the promoter in many of these IFN-inducible genes and bind a family of trans-acting proteins. Interferon consensus sequence binding protein (ICSBP) is one member of this family of interferon regulatory factors (IRF) and is structurally related within the DNA-binding domain to the other members, IRF-1, IRF-2, and ISCF3 gamma. ISCBP mRNA levels become elevated in response to IFN-gamma; however, little is known about the regulation of ICSBP expression at the protein level. In this study, anti-ICSBP peptide Abs were used to quantify and localize ICSBP in murine peritoneal exudate macrophages. Western blot analysis of cytoplasmic and nuclear extracts from treated and control cells revealed ICSBP to be induced by IFN-gamma and not by IFN-alpha and to exist primarily in the nucleus. The regulation of ICSBP induction by IFN-gamma was consistent with the characteristics found at the mRNA level; inhibition by IFN-alpha or glucocorticoids and the requirement for protein kinase C (as determined pharmacologically). The time course of IFN-gamma-induced ICSBP showed an induction of protein that required similar to 12 h to reach maximal levels. Induced ICSBP was relatively stable, exhibiting a half-life of similar to 48 h. Indirect immunofluorescence also demonstrated ICSBP to be an IFN-gamma-inducible protein that is strongly localized to the nucleus. C1 UNIFORMED SERV UNIV HLTH SCI,DEPT MICROBIOL & IMMUNOL,BETHESDA,MD 20814. NICHHD,DEV & MOLEC IMMUN LAB,BETHESDA,MD 20892. NIAID,BIOL RESOURCES BRANCH,BETHESDA,MD 20892. FU NIAID NIH HHS [AI-18797] NR 42 TC 58 Z9 58 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 1994 VL 152 IS 5 BP 2270 EP 2278 PG 9 WC Immunology SC Immunology GA NB988 UT WOS:A1994NB98800023 PM 8133040 ER PT J AU SAYERS, TJ WILTROUT, TA SMYTH, MJ OTTAWAY, KS PILARO, AM SOWDER, R HENDERSON, LE SPRENGER, H LLOYD, AR AF SAYERS, TJ WILTROUT, TA SMYTH, MJ OTTAWAY, KS PILARO, AM SOWDER, R HENDERSON, LE SPRENGER, H LLOYD, AR TI PURIFICATION AND CLONING OF A NOVEL SERINE-PROTEASE, RNK-TRYP-2, FROM THE GRANULES OF A RAT NK CELL LEUKEMIA SO JOURNAL OF IMMUNOLOGY LA English DT Article ID CYTOLYTIC LYMPHOCYTES-T; NATURAL-KILLER ACTIVITY; PORE-FORMING PROTEIN; GRANZYME-A; CYTOPLASMIC GRANULES; MEDIATED LYSIS; INHIBITORS; ESTERASES; SUBSTRATE; PERFORIN AB We have biochemically purified a 27-kDa serine protease (designated RNK-Tryp-2) from the granules of the rat large granular lymphocyte leukemia cell line (RNK-16) which has tryptase activity. Utilizing molecular sieve chromatography and reverse-phase HPLC, we purified RNK-Tryp-2 to homogeneity and sequenced 33 NH2 terminal amino acids. Oligonucleotide primers were used in the PCR to generate a 528-bp cDNA clone encoding a novel serine protease from RNK-16 mRNA. This cDNA clone was used to isolate an 884-bp RN K-Tryp-2 cDNA from an RNK-16 lambda-gt11 library. The open reading frame predicts a mature protein of 233 amino acids which does not have potential sites for N-linked glycosylation. The cDNA encodes a leader peptide of at least 25 amino acids. The characteristic Ile-Ile-Gly-Gly amino acids of the N-terminus, and the His, Asp, and Ser amino acids that form the catalytic triad of serine proteases, are conserved. The amino acid sequence has less than 45% identity with any other member of the serine protease family, indicating that RNK-Tryp-2 is distinct protease. Southern blot analysis suggests the existence of one or more related genes. A single 1.3-kb mRNA transcript was detected by Northern blot analysis of total cellular RNA from the in vivo passaged RNK-16, rat splenocytes, lung and liver nonparenchymal cells, as well as in highly purified rat LGL and T cells. RNK-Tryp-2 is a novel serine protease that is expressed in the granules of large granular lymphocytes. C1 NCI,FREDERICK CANC RES & DEV CTR,PRI DYNCORP,AIDS VACCINE DEV PROGRAM,FREDERICK,MD 21702. NCI,FREDERICK CANC RES & DEV CTR,PRI DYNCORP,CLIN SERV PROGRAM,FREDERICK,MD 21702. NCI,FREDERICK CANC RES & DEV CTR,BIOL RESPONSE MODIFIERS PROGRAM,FREDERICK,MD 21702. AUSTIN HOSP,AUSTIN RES INST,CELLULAR CYTOTOX LAB,HEIDELBERG,VIC,AUSTRALIA. RP SAYERS, TJ (reprint author), NCI,FREDERICK CANC RES & DEV CTR,PRI DYNCORP,FREDERICK,MD 21702, USA. RI Sayers, Thomas/G-4859-2015; Smyth, Mark/H-8709-2014 OI Smyth, Mark/0000-0001-7098-7240 NR 43 TC 30 Z9 31 U1 0 U2 1 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD MAR 1 PY 1994 VL 152 IS 5 BP 2289 EP 2297 PG 9 WC Immunology SC Immunology GA NB988 UT WOS:A1994NB98800025 PM 8133042 ER PT J AU OHANLON, TP DALAKAS, MC PLOTZ, PH MILLER, FW AF OHANLON, TP DALAKAS, MC PLOTZ, PH MILLER, FW TI PREDOMINANT TCR-ALPHA-BETA VARIABLE AND JOINING GENE-EXPRESSION BY MUSCLE-INFILTRATING LYMPHOCYTES IN THE IDIOPATHIC INFLAMMATORY MYOPATHIES SO JOURNAL OF IMMUNOLOGY LA English DT Article ID T-CELL-RECEPTOR; MYELIN BASIC-PROTEIN; TRANSFER-RNA-SYNTHETASE; MONOCLONAL-ANTIBODY ANALYSIS; SIGNAL RECOGNITION PARTICLE; V-BETA; RHEUMATOID-ARTHRITIS; MULTIPLE-SCLEROSIS; MONONUCLEAR-CELLS; ANTIGEN RECOGNITION AB The idiopathic inflammatory myopathies (IIM) are a heterogeneous group of diseases in which autoreactive T cells are thought to play a pathogenetic role. We have determined the pattern of TCR-alpha beta gene expression by muscle-infiltrating lymphocytes within clinically and serologically defined groups of IIM patients. We utilized the PCR to study TCR V gene expression in muscle biopsies from nine polymyositis (PM) and eight dermatomyositis (DM) patients, all of whom had autoantibodies directed against histidyl-transfer RNA synthetase (anti-Jo-1 autoantibodies). While the TCR repertoire in DM patients was generally polyclonal, an oligoclonal profile characterized PM patients. Certain V gene families were predominantly expressed; V alpha 1 and V beta 6 gene families were detected in 82 and 91% of PM biopsies, respectively. TCR expression was characterized further by analyzing J gene usage from four PM patients expressing the V beta 6 gene. Sequence analysis of 40 independent recombinants (10 per patient) identified only seven V beta 6 clonotypes and restricted usage of the related J beta 2.1, -2.3, and -2.7 genes. These data, describing predominant TCR V and I gene usage by muscle-infiltrating lymphocytes in myositis patients, suggest that Ag-driven T cell responses may play a primary role in mediating some forms of the IIM. C1 US FDA,CTR BIOL EVALUAT & RES,MOLEC IMMUNOL LAB,BETHESDA,MD 20892. NINCDS,BETHESDA,MD 20892. NIAMSD,BETHESDA,MD 20892. NR 54 TC 71 Z9 72 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 1994 VL 152 IS 5 BP 2569 EP 2576 PG 8 WC Immunology SC Immunology GA NB988 UT WOS:A1994NB98800057 PM 8133064 ER PT J AU PETRI, WA CLARK, CG DIAMOND, LS AF PETRI, WA CLARK, CG DIAMOND, LS TI HOST-PARASITE RELATIONSHIPS IN AMEBIASIS - CONFERENCE REPORT SO JOURNAL OF INFECTIOUS DISEASES LA English DT Editorial Material AB Entamoeba histolytica has been redescribed as the separate species E. histolytica and Entamoeba dispar. E. dispar is apparently never invasive in humans, while E. histolytica is the etiologic agent of amebic colitis and liver abscess. Virulence factors that may enable E. histolytica to invade include a galactose-specific adhesin, secreted proteases, extracellular matrix receptors, and a cell surface lipophosphoglycan. Progress in vaccine development includes the identification of the cysteine-rich domain of the adhesin and the serine-rich surface protein as protective antigens. C1 UNIV VIRGINIA,HLTH SCI CTR,DEPT MICROBIOL,CHARLOTTESVILLE,VA 22908. NIAID,PARASIT DIS LAB,BETHESDA,MD 20892. RP PETRI, WA (reprint author), UNIV VIRGINIA,HLTH SCI CTR,DEPT MED,2115 MR4 BLDG,CHARLOTTESVILLE,VA 22908, USA. RI Clark, C Graham/H-3683-2011 OI Clark, C Graham/0000-0002-0521-0977 NR 0 TC 12 Z9 13 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 1994 VL 169 IS 3 BP 483 EP 484 PG 2 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA NP109 UT WOS:A1994NP10900001 PM 7908923 ER PT J AU LAL, RB GIAM, CZ COLIGAN, JE RUDOLPH, DL AF LAL, RB GIAM, CZ COLIGAN, JE RUDOLPH, DL TI DIFFERENTIAL IMMUNE RESPONSIVENESS TO THE IMMUNODOMINANT EPITOPES OF REGULATORY PROTEINS (TAX AND REX) IN HUMAN T-CELL LYMPHOTROPIC VIRUS TYPE I-ASSOCIATED MYELOPATHY SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article ID TROPICAL SPASTIC PARAPARESIS; BLOOD MONONUCLEAR-CELLS; CYTOTOXIC LYMPHOCYTES-T; PROVIRAL DNA LOAD; HTLV-I; LEUKEMIA-VIRUS; MESSENGER-RNA; HAM-TSP; ANTIBODIES; EXPRESSION AB Infection by human T cell lymphotropic virus type I (HTLV-I) is etiologically linked with HTLV-I-associated myelopathy (HAM) or adult T cell leukemia (ATL). To evaluate the contribution of the viral regulatory proteins tax and rex during the development of disease, antibody responses to these proteins were analyzed in patients with HAM (n = 28) or ATL (n = 48) and in asymptomatic carriers (n = 69). Epitope mapping analysis identified immunodominant epitopes towards the amino terminus (Tax8(106-125)) and at the carboxyl terminus (Tax22(316-335) Tax23(331-350), and Tax24(336-353)) Of tax and the amino terminus (Rex1(1-20), Rex2(16-35), Rex4(46-65) and Rex6(76-95)) of rex. Analysis fanatically reactivity to these immunodominant epitopes demonstrated preferential reactivity to Tax8, Tax22, Tax23, and Tax24 (71%-93%) and to Rex4 and Rex6 (52%) in p8tients with HAM when compared with reactivities in ATL patients (4%-31% for tax and 19%-24% for rex) or asymptomatic carriers (27%-37% for tax and 7%-23% for rex). In contrast, antibody responses to the immunodominant epitopes of the env proteins of HTLV-I (MTA, Env1, Env5) were similar in all of three clinical groups. Thus, differential immune responsiveness to the immunodominant epitopes of tax and rex in patients with HAM may play a role in disease pathogenesis in HTLV-I-infected persons. C1 CASE WESTERN RESERVE UNIV,SCH MED,DEPT MED & MOLEC BIOL,DIV INFECT DIS,CLEVELAND,OH. NIAID,BIOL RESOURCES BRANCH,BETHESDA,MD 20892. RP LAL, RB (reprint author), CTR DIS CONTROL & PREVENT,DIV VIRAL & RICKETTSIAL DIS,RETROVIRUS DIS BRANCH,MAIL STOP G19,ATLANTA,GA 30329, USA. NR 40 TC 26 Z9 26 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 1994 VL 169 IS 3 BP 496 EP 503 PG 8 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA NP109 UT WOS:A1994NP10900004 PM 8158021 ER PT J AU HOFFMAN, WD POLLACK, M BANKS, SM KOEV, LA SOLOMON, MA DANNER, RL KOLES, N GUELDE, G YATSIV, I MOUGINIS, T ELIN, RJ HOSSEINI, JM BACHER, J PORTER, JC NATANSON, C AF HOFFMAN, WD POLLACK, M BANKS, SM KOEV, LA SOLOMON, MA DANNER, RL KOLES, N GUELDE, G YATSIV, I MOUGINIS, T ELIN, RJ HOSSEINI, JM BACHER, J PORTER, JC NATANSON, C TI DISTINCT FUNCTIONAL ACTIVITIES IN CANINE SEPTIC SHOCK OF MONOCLONAL-ANTIBODIES SPECIFIC FOR THE O-POLYSACCHARIDE AND CORE REGIONS OF ESCHERICHIA-COLI LIPOPOLYSACCHARIDE SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article ID GRAM-NEGATIVE BACTEREMIA; CROSS-REACTIVE ANTIBODIES; COLONY-STIMULATING FACTOR; SALMONELLA-MINNESOTA; BACTERIAL SEPSIS; CONTROLLED TRIAL; ROUGH MUTANTS; IGG ANTIBODY; LIPID-A; ENDOTOXIN AB Monoclonal antibodies (MAbs) specific for O polysaccharide or core oligosaccharide/lipid A of Escherichia coli O111:B4 lipopolysaccharide (LPS) were compared in canine septic shock. Animals received O-specific, core-specific, or control murine IgG2a MAbs (or saline) before intraperitoneal implantation of an E. coli O111:B4-infected clot. Animals were further randomized to ceftriaxone or saline. O-specific MAb significantly reduced bacteremia and endotoxemia but not serum tumor necrosis factor. Core-specific MAb significantly increased mean arterial pressure from day 4 to 28 (P = .02). In dogs not receiving ceftriaxone, survival was enhanced by O-specific MAb (4/5) compared with core-specific MAb (0/5) and control (1/8) (P = .03). Survival rates were similar (P = .22) but survival was prolonged in antibiotic-treated animals also receiving O-specific MAb (P = .02 vs. core-specific MAb and controls) or core-specific MAb (P = .08 vs. controls). These data support the complex role of LPS in sepsis and the discrete functional effects of MAbs specific for different elements of LPS. C1 NIH,CTR CLIN,DEPT LAB MED,BETHESDA,MD 20892. NIH,VET RESOURCES PROGRAM,BETHESDA,MD 20892. UNIFORMED SERV UNIV HLTH SCI,DEPT MED,DIV INFECT DIS,BETHESDA,MD 20814. RP HOFFMAN, WD (reprint author), NIH,DEPT CRIT CARE MED,BLDG 10,ROOM 7D43,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. FU NIAID NIH HHS [AI-22706] NR 60 TC 19 Z9 19 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 1994 VL 169 IS 3 BP 553 EP 561 PG 9 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA NP109 UT WOS:A1994NP10900012 PM 7512609 ER PT J AU ELSON, LH GUDERIAN, RH ARAUJO, E BRADLEY, JE DAYS, A NUTMAN, TB AF ELSON, LH GUDERIAN, RH ARAUJO, E BRADLEY, JE DAYS, A NUTMAN, TB TI IMMUNITY TO ONCHOCERCIASIS - IDENTIFICATION OF A PUTATIVELY IMMUNE POPULATION IN A HYPERENDEMIC AREA OF ECUADOR SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article ID GUATEMALAN HUMAN ONCHOCERCIASIS; PROTECTIVE IMMUNITY; FILARIAL INFECTION; IGE ANTIBODIES; VOLVULUS; ANTIGENS; RESISTANCE; REINFECTION; PARASITE; SUSCEPTIBILITY AB The existence of immunity to Onchocerca volvulus (Ov) infection is suggested by the presence of uninfected persons in hyperendemic areas. A major barrier to the study of immunity has been the correct identification of putatively immune (PI) subjects. To identify a PI group in a hyperendemic area in Ecuador, clinical and epidemiologic information was combined with a polymerase chain reaction (PCR)-based assay identifying Ov DNA in skin snips and a recombinant antigen-based ELISA. Comparison of immune responses revealed that PI subjects had significantly lower levels of Ov-specific IgG, IgG subclasses, and IgE than infected (INF) subjects. Female subjects were significantly more likely to be PI than male subjects, and INF female subjects had significantly lower levels of Ov-specific IgG, IgG1, and IgG3 than Inf male subjects. Thus, the use of molecular-based techniques has helped to define more precisely the PI state in onchocerciasis. C1 HOSP VOZANDES,CLIN INVEST,QUITO,ECUADOR. UNIV LONDON IMPERIAL COLL SCI TECHNOL & MED,DEPT PURE & APPL BIOL,LONDON,ENGLAND. RP ELSON, LH (reprint author), NIAID,PARASIT DIS LAB,9000 ROCKVILLE PIKE,BLDG 4,ROOM 126,BETHESDA,MD 20892, USA. OI Bradley, Janette/0000-0003-3973-7977 NR 36 TC 64 Z9 64 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 1994 VL 169 IS 3 BP 588 EP 594 PG 7 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA NP109 UT WOS:A1994NP10900017 PM 8158031 ER PT J AU KLION, AD OTTESEN, EA NUTMAN, TB AF KLION, AD OTTESEN, EA NUTMAN, TB TI EFFECTIVENESS OF DIETHYLCARBAMAZINE IN TREATING LOIASIS ACQUIRED BY EXPATRIATE VISITORS TO ENDEMIC REGIONS - LONG-TERM FOLLOW-UP SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article ID LOA-LOA; M-PERSTANS; IVERMECTIN; MICROFILARIAE; INFECTION; ONCHOCERCIASIS; MEBENDAZOLE; EFFICACY; TRIAL AB Although successful treatment of loiasis with diethylcarbamazine (DEC) has been reported, little is known about the long-term success rate of therapy or the predisposing factors for treatment failure. To address these questions, 32 patients were followed 2-15 years (median, 4.5) after DEC treatment; all had acquired infection while expatriate visitors to endemic areas of Africa. Using a strict definition of successful treatment, 12 (38%) appeared to be cured after one course of therapy and 5 (16%) after two courses. Of the remaining 15 patients, 3 continued to be symptomatic despite more than four courses of treatment. Although 12 of the 17 patients who relapsed did so within 1 year of treatment, several had relatively long asymptomatic periods (2-8 years). There was no predictive difference in clinical or laboratory parameters (including eosinophilia and specific filarial serology) between patients requiring one or more courses of therapy. C1 NIH,PARASIT DIS LAB,BETHESDA,MD 20892. RP KLION, AD (reprint author), UNIV IOWA HOSP & CLIN,DEPT INTERNAL MED,DIV INFECT DIS,IOWA CITY,IA 52242, USA. OI Klion, Amy/0000-0002-4986-5326 NR 29 TC 25 Z9 25 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 1994 VL 169 IS 3 BP 604 EP 610 PG 7 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA NP109 UT WOS:A1994NP10900019 PM 8158033 ER PT J AU ZIMMERMAN, PA GUDERIAN, RH ARUAJO, E ELSON, L PHADKE, P KUBOFCIK, J NUTMAN, TB AF ZIMMERMAN, PA GUDERIAN, RH ARUAJO, E ELSON, L PHADKE, P KUBOFCIK, J NUTMAN, TB TI POLYMERASE CHAIN REACTION-BASED DIAGNOSIS OF ONCHOCERCA-VOLVULUS INFECTION - IMPROVED DETECTION OF PATIENTS WITH ONCHOCERCIASIS SO JOURNAL OF INFECTIOUS DISEASES LA English DT Note ID DNA PROBES; SEQUENCE; PARASITE AB Definitive diagnosis of Onchocerca volvulus (Ov) infection requires the identification of the parasite in either the skin or subcutaneous nodules. These parasitologic approaches suffer from poor sensitivity. To assess the efficacy and utility of a polymerase chain reaction (PCR)-based diagnosis for Ov infection, skin snips were examined from 94 persons in an Ov-endemic region of Ecuador, and results were compared in a blinded fashion with those of a PCR assay based on the Onchocerca-specific repetitive DNA sequence, O-150. All 60 patients microfilaria-positive on skin snip examination were positive in the PCR-based assay. In addition, 13 of 34 who were microfilaria-negative by skin snips were positive in the PCR assay. This suggests that the PCR-based assay is significantly more sensitive than current methods and overcomes many deficiencies of parasitologic and serologic methodologies in diagnosing active onchocerciasis. C1 HOSP VOZANDES,NATL CTR TROP MED,QUITO,ECUADOR. RP ZIMMERMAN, PA (reprint author), NIAID,PARASIT DIS LAB,9000 ROCKVILLE PIKE,BLDG 4,ROOM 126,BETHESDA,MD 20892, USA. NR 16 TC 79 Z9 80 U1 0 U2 3 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 1994 VL 169 IS 3 BP 686 EP 689 PG 4 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA NP109 UT WOS:A1994NP10900040 PM 8158053 ER PT J AU ROBINSON, RD LINDO, JF NEVA, FA GAM, AA VOGEL, P TERRY, SI COOPER, ES AF ROBINSON, RD LINDO, JF NEVA, FA GAM, AA VOGEL, P TERRY, SI COOPER, ES TI IMMUNOEPIDEMIOLOGIC STUDIES OF STRONGYLOIDES-STERCORALIS AND HUMAN T-LYMPHOTROPIC VIRUS TYPE-I INFECTIONS IN JAMAICA SO JOURNAL OF INFECTIOUS DISEASES LA English DT Note ID HTLV-I; CARRIERS AB Epidemiologic investigations of Strongyloides stercoralis and human T lymphotropic virus type I (HTLV-I) infections were conducted. Of 312 persons contacted, 209 (67%) provided blood and stool samples. Prevalences of S. stercoralis and HTLV-I antibodies were 26.8% and 8.1% (n = 198), respectively, and S. stercoralis larvae were detected in 4%. HTLV-I antibodies were significantly more common in persons positive for S. stercoralis larvae (10 [58.8%] of 17) compared with seropositive larva-negative (4 [8.9%] of 45) or seronegative persons (9 [6.2%] of 145) (P < .002). IgE levels increased with age in S. stercoralis-seropositive persons who were HTLV-I negative (P < .002). However, there was ange-related depression of serum IgE in HTLV-I-positive persons (P < .003) that was sufficient to annul the IgE level-raising effect of S. stercoralis seropositivity. The data provide evidence that HTLV-I infection is associated with increased frequency of larvae in the stool of S. stercoralis-infected persons and suggest that the mechansim may involve suppression of the IgE response. C1 UNIV W INDIES,DEPT MED,KINGSTON 7,JAMAICA. UNIV W INDIES,TROP METAB RES UNIT,KINGSTON 7,JAMAICA. NIAID,BETHESDA,MD. RP ROBINSON, RD (reprint author), UNIV W INDIES,DEPT ZOOL,PARASITE RES LABS,KINGSTON 7,JAMAICA. NR 15 TC 65 Z9 69 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 1994 VL 169 IS 3 BP 692 EP 696 PG 5 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA NP109 UT WOS:A1994NP10900042 PM 8158055 ER PT J AU YUWEN, H BAYLEY, AC CAIRNS, J TABOR, E AF YUWEN, H BAYLEY, AC CAIRNS, J TABOR, E TI HEPATOCELLULAR-CARCINOMA - LACK OF ASSOCIATION WITH A UNIQUE HEPATITIS-C VIRUS NUCLEOTIDE-SEQUENCE SO JOURNAL OF INFECTIOUS DISEASES LA English DT Letter ID 5' NONCODING REGION; DIVERSITY C1 NCI,BETHESDA,MD 20892. UNIV LUSAKA,TEACHING HOSP,LUSAKA,ZAMBIA. ST FRANCIS HOSP,KATETE,ZAMBIA. NR 6 TC 1 Z9 1 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 S WOODLAWN AVE, CHICAGO, IL 60637 SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD MAR PY 1994 VL 169 IS 3 BP 706 EP 707 PG 2 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA NP109 UT WOS:A1994NP10900051 PM 8158061 ER PT J AU OSTERHOFF, B RAPPERSBERGER, K WANG, BH KOSZIK, F OCHIAI, K KINET, JP STINGL, G AF OSTERHOFF, B RAPPERSBERGER, K WANG, BH KOSZIK, F OCHIAI, K KINET, JP STINGL, G TI IMMUNOMORPHOLOGICAL CHARACTERIZATION OF FC-EPSILON-RI-BEARING CELLS WITHIN THE HUMAN DERMIS SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Article ID EPIDERMAL LANGERHANS CELLS; MONOCYTE MACROPHAGE SYSTEM; NORMAL HUMAN SKIN; DENDRITIC CELLS; MONOCLONAL-ANTIBODIES; IGE; PHENOTYPE; EXPRESS AB Recently we reported that the high-affinity receptor for IgE, FcepsilonRI, is constitutively expressed on normal epidermal Langerhans cells (LC) and on certain cells within the dermis. To study the nature of these cells we performed immunofluorescence double-labeling experiments using an anti-FcepsilonRI reagent (MoAb 15-1) as well as monoclonal antibodies (MoAb) against leukocyte differentiation antigens expressed on LC, interdigitating cells and macrophages. Avidin-fluorescein isothiocyanate was used to distinguish mast cells. We found that dermal FcepsilonRI+ cells are bone marrow derived (CD45+). Further, we found that a subset of 15-1+ dermal cells coexpresses antigens present on certain members of the LC/DC family: the majority of FcepsilonRI+ cells reacted with MoAb anti - HLA-DR and RFD1, the latter recognizes an antigenic moiety on interdigitating cells, and a small subpopulation coexpressed CD1a. In reverse fashion, virtually all CD1a+ cells and most RFD1+ cells reacted with the anti-FcepsilonI reagent. Approximately one third of 15-1+ cells represented avidin-FITC+ mast cells whereas FcepsilonRI expression was not detected on FXIIIa+ dermal dendrocytes or CD3+ lymphocytes. By immunoelectronmicroscopy, we found that perivascularly located 15-1-reactive cells exhibited pronounced dendrites, an indented nucleus, numerous mitochondria, and abundant endo-/lysosomal structures. However, Birbeck granules or granules specific for basophils or eosinophils were never detected in these cells. Collectively, our data suggest that the pool of dermal FcepsilonRI+ cells consists mainly of cells of the LC (CD1a+)/FXIIIa+ dermal macrophages. C1 UNIV VIENNA,VIENNA INT RES COOPERAT CTR,SCH MED,DIV GEN DERMATOL,A-1235 VIENNA,AUSTRIA. NIAID,MOLEC ALLERGY & IMMUNOL SECT,ROCKVILLE,MD. RP OSTERHOFF, B (reprint author), UNIV VIENNA,VIENNA INT RES COOPERAT CTR,SCH MED,DEPT DERMATOL,DIV IMMUNOL ALLERGY & INFECT DIS,A-1235 VIENNA,AUSTRIA. NR 26 TC 31 Z9 31 U1 0 U2 3 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 1994 VL 102 IS 3 BP 315 EP 320 DI 10.1111/1523-1747.ep12371789 PG 6 WC Dermatology SC Dermatology GA NB177 UT WOS:A1994NB17700010 PM 8120415 ER PT J AU DIGIOVANNA, JJ BALE, SJ AF DIGIOVANNA, JJ BALE, SJ TI EPIDERMOLYTIC HYPERKERATOSIS - APPLIED MOLECULAR-GENETICS SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Article DE ICHTHYOSIS; KERATIN; GENODERMATOSIS ID STEROID-SULFATASE DEFICIENCY; X-LINKED ICHTHYOSIS; LIPID STORAGE DISEASE; CYTOKERATIN GENES; COMPLETE SEQUENCE; KERATIN GENES; LINKAGE; LOCALIZATION; MUTATIONS; DISORDER AB Epidermolytic hyperkeratosis is an autosomal dominant ichthyosis characterized by blistering, especially at birth and during childhood, and hyperkeratosis. Epidermolytic hyperkeratosis presents striking clinical heterogeneity, particularly between families. Several avenues of research have implicated an abnormality of epidermal differentiation in the pathogenesis of this disease. In a three-generation family with 20 affected individuals, we tested a variety of candidate loci and identified linkage to the type II keratin region on chromosome 12. Further investigation revealed a mutation in the Hl subdomain of the keratin 1 gene as the cause of EHK in this family. Because keratin 10 is the co-expressed partner of keratin 1, it was not surprising when abnormalities in keratin 10 were found in other families with EHK. We have examined 52 patients from 21 families and have identified at least six clinical phenotypes. The most useful distinguishing feature was the presence or absence of severe hyperkeratosis of the palms and soles. We and others are continuing to search for and characterize mutations in keratin 1 and 10 in patients with epidermolytic hyperkeratosis. Correlation of the clinical disease types with the specific mutations should lead to a better understanding of the relationship between keratin structure and function in normal and diseased epidermis. RP DIGIOVANNA, JJ (reprint author), NCI,DIV CANC BIOL DIAGNOSIS & CTR,DERMATOL BRANCH,BLDG 10,ROOM 12N238,BETHESDA,MD 20892, USA. NR 46 TC 27 Z9 27 U1 0 U2 0 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 1994 VL 102 IS 3 BP 390 EP 394 PG 5 WC Dermatology SC Dermatology GA NB177 UT WOS:A1994NB17700022 PM 7509838 ER PT J AU MASON, LH YAGITA, H ORTALDO, JR AF MASON, LH YAGITA, H ORTALDO, JR TI LGL-1 - A POTENTIAL TRIGGERING MOLECULE ON MURINE NK CELLS SO JOURNAL OF LEUKOCYTE BIOLOGY LA English DT Article DE REVERSE ANTIBODY-DEPENDENT CELLULAR CYTOTOXICITY; MONOCLONAL ANTIBODIES; CORYNEBACTERIUM PARVUM ID NATURAL-KILLER-CELLS; ERYTHROCYTE BINDING-PROTEIN; FC-RECEPTOR; MONOCLONAL-ANTIBODIES; NK1.1 ANTIGEN; LYMPHOCYTES-T; MOUSE; ACTIVATION; CD2; INDUCTION AB Natural killer (NK) cells mediate non-major histocompatibility complex-restricted lysis of tumor cells, lymphokine-activated killing (LAK), antibody-dependent cellular cytotoxicity (ADCC), and reverse ADCC (RADCC). LGL-1(+) cells identify a major subset (50%) of murine NK cells. Here we demonstrate that monoclonal antibodies (mAbs) to LGL-1. consistently induce interleukin-2-cultured, and Corynebacterium par vum (in vivo)-activated NK cells to induce RADCC. LGL-1 triggering of activated NK cells coincides with enhanced LGL-1. expression. Testing of murine mAbs to epitopes of CD2 only appears to augment RADCC induced by mAb NK-1.1 on fresh NK cells. Immunoprecipitation of the LGL-1 antigen reveals a highly disulfide-linked 40-kDa homodimer subunit that is N-glycosylated. Therefore, LGL-1 may be similar to other recently characterized NK-associated antigens such as NK-1.1, Ly-49, and NKR-PI. We conclude that although LGL-1 is expressed on ''resting'' NK cells, enhanced surface expression following activation is usually required for it to act as a signaling molecule. C1 JUNTENDO UNIV,SCH MED,DEPT IMMUNOL,BUNKYO KU,TOKYO 113,JAPAN. RP MASON, LH (reprint author), NCI,FCRDC,DCT,BIOL RESPONSE MODIFIERS PROGRAM,EXPTL IMMUNOL LAB,BLDG 560,RM 31-93,FREDERICK,MD 21702, USA. NR 32 TC 21 Z9 21 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0741-5400 J9 J LEUKOCYTE BIOL JI J. Leukoc. Biol. PD MAR PY 1994 VL 55 IS 3 BP 362 EP 370 PG 9 WC Cell Biology; Hematology; Immunology SC Cell Biology; Hematology; Immunology GA MZ645 UT WOS:A1994MZ64500011 PM 7509843 ER PT J AU MCCARTNEYFRANCIS, NL WAHL, SM AF MCCARTNEYFRANCIS, NL WAHL, SM TI TRANSFORMING GROWTH-FACTOR-BETA - A MATTER OF LIFE AND DEATH SO JOURNAL OF LEUKOCYTE BIOLOGY LA English DT Review DE TRANSFORMING GROWTH FACTOR BETA; INFLAMMATION; TRANSGENICS; GENE TARGETING; THERAPY; FIBROSIS; CYTOKINES; LEUKOCYTES; EMBRYOGENESIS ID EXPERIMENTAL ALLERGIC ENCEPHALOMYELITIS; MOLECULAR-WEIGHT COMPLEX; TGF-BETA; FACTOR-BETA-1 GENE; DIFFERENTIAL EXPRESSION; ENDOTHELIAL-CELLS; SEQUENCE-ANALYSIS; CRYSTAL-STRUCTURE; HUMAN-PLATELETS; HUMAN-MONOCYTES AB A wide variety of functions, many of which represent opposing activities, have been attributed to TGF-beta, a molecule implicated in embryogenesis, development, and immune and inflammatory processes. This paradoxical behavior of promoting or inhibiting cell growth and function, while important in normal physiology and homeostasis, can contribute to or interrupt pathologic sequelae, making TGF-beta a particularly intriguing molecule for study. New transgenic mouse models displaying targeted alterations in TGF-beta 1 expression offer novel and unique opportunities to determine the essential function(s) of TGF-beta. C1 NIDR,IMMUNOL LAB,CELLULAR IMMUNOL SECT,BETHESDA,MD 20892. NR 112 TC 265 Z9 268 U1 0 U2 3 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0741-5400 J9 J LEUKOCYTE BIOL JI J. Leukoc. Biol. PD MAR PY 1994 VL 55 IS 3 BP 401 EP 409 PG 9 WC Cell Biology; Hematology; Immunology SC Cell Biology; Hematology; Immunology GA MZ645 UT WOS:A1994MZ64500017 PM 8120457 ER PT J AU BASSER, PJ MATTIELLO, J LEBIHAN, D AF BASSER, PJ MATTIELLO, J LEBIHAN, D TI ESTIMATION OF THE EFFECTIVE SELF-DIFFUSION TENSOR FROM THE NMR SPIN-ECHO SO JOURNAL OF MAGNETIC RESONANCE SERIES B LA English DT Article ID FIELD GRADIENT; COEFFICIENTS; ORIENTATION; INVIVO; SYSTEM; WATER AB The diagonal and off-diagonal elements of the effective self-diffusion tensor, D(eff), are related to the echo intensity in an NMR spin-echo experiment. This relationship is used to design experiments from which D(eff) is estimated. This estimate is validated using isotropic and anisotropic media, i.e., water and skeletal muscle. It is shown that significant errors are made in diffusion NMR spectroscopy and imaging of anisotropic skeletal muscle when off-diagonal elements of D(eff) are ignored, most notably the loss of information needed to determine fiber orientation. Estimation of D(eff) provides the theoretical basis for a new MRI modality, diffusion tensor imaging, which provides information about tissue microstructure and its physiologic state not contained in scalar quantities such as T1, T2, proton density, or the scalar apparent diffusion constant. (C) 1994 Academic Press, Inc. C1 NIH,WARREN G MAGNUSON CLIN CTR,DEPT DIAGNOST RADIOL,BETHESDA,MD 20892. RP BASSER, PJ (reprint author), NIH,NATL CTR RES RESOURCES,BIOMED ENGN & INSTRUMENTAT PROGRAM,BETHESDA,MD 20892, USA. RI Basser, Peter/H-5477-2011 NR 31 TC 2015 Z9 2067 U1 17 U2 92 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 1064-1866 J9 J MAGN RESON SER B JI J. Magn. Reson. Ser. B PD MAR PY 1994 VL 103 IS 3 BP 247 EP 254 DI 10.1006/jmrb.1994.1037 PG 8 WC Physics, Atomic, Molecular & Chemical SC Physics GA ND157 UT WOS:A1994ND15700006 PM 8019776 ER PT J AU VANGELDEREN, P DESPRES, D VANZIJL, PCM MOONEN, CTW AF VANGELDEREN, P DESPRES, D VANZIJL, PCM MOONEN, CTW TI EVALUATION OF RESTRICTED DIFFUSION IN CYLINDERS - PHOSPHOCREATINE IN RABBIT LEG MUSCLE SO JOURNAL OF MAGNETIC RESONANCE SERIES B LA English DT Article ID NMR-DIFFUSION; ECHO AB Interpretation of NMR diffusion data is complicated in the presence of diffusion barriers. In this study, restricted diffusion in cylinders is evaluated. A method is presented to determine the diameter of the cylinder and the unrestricted diffusion coefficient from the dependence of the trace of the diffusion tensor with diffusion time. This method is valid even if the orientation of the cylinders is unknown and varies within the sample. An example is given for the diffusion of phosphocreatine in the cylindrically shaped fibers of rabbit skeletal muscle. (C) 1994 Academic Press, Inc. C1 NIH,NCRR,BEIP,IN VIVO NMR RES CTR,BETHESDA,MD 20892. JOHNS HOPKINS UNIV,SCH MED,DEPT RADIOL,BALTIMORE,MD 21218. DELFT UNIV TECHNOL,FAC APPL PHYS,DELFT,NETHERLANDS. RI van Zijl, Peter/B-8680-2008 FU PHS HHS [R01 N531490-01] NR 13 TC 71 Z9 72 U1 0 U2 6 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 1064-1866 J9 J MAGN RESON SER B JI J. Magn. Reson. Ser. B PD MAR PY 1994 VL 103 IS 3 BP 255 EP 260 DI 10.1006/jmrb.1994.1038 PG 6 WC Physics, Atomic, Molecular & Chemical SC Physics GA ND157 UT WOS:A1994ND15700007 PM 8019777 ER PT J AU SCHAFER, MKH WEIHE, E VAROQUI, H EIDEN, LE ERICKSON, JD AF SCHAFER, MKH WEIHE, E VAROQUI, H EIDEN, LE ERICKSON, JD TI DISTRIBUTION OF THE VESICULAR ACETYLCHOLINE TRANSPORTER (VACHT) IN THE CENTRAL AND PERIPHERAL NERVOUS SYSTEMS OF THE RAT SO JOURNAL OF MOLECULAR NEUROSCIENCE LA English DT Article DE CHOLINERGIC; VESICULAR ACETYLCHOLINE TRANSPORTER; VACHT; MESSENGER-RNA; BRAIN; PARASYMPATHETIC; SPINAL CORD; CEREBRAL CORTEX; BASAL FOREBRAIN ID ACETYLTRANSFERASE MESSENGER-RNA; CENTRAL CHOLINERGIC NEURONS; INSITU HYBRIDIZATION; SPINAL-CORD; IMMUNOCYTOCHEMICAL LOCALIZATION; MONOAMINE TRANSPORTER; CEREBRAL-CORTEX; PROMOTER REGION; GENE-EXPRESSION; SENILE DEMENTIA AB Expression of the acetylcholine biosynthetic enzyme choline acetyltransferase (ChAT), the vesicular acetylcholine transporter (VAChT), and the high-affinity plasma membrane choline transporter uniquely defines the cholinergic phenotype in the mammalian central (CNS) and peripheral (PNS) nervous systems. The distribution of cells expressing the messenger RNA encoding the recently cloned VAChT in the rat CNS and PNS is described here. The pattem of expression of VAChT mRNA is consistent with anatomical, pharmacological, and histochemical information on the distribution of functional cholinergic neurons in the brain and peripheral tissues of the rat. VAChT mRNA-containing cells are present in brain areas, including neocortex and hypothalamus, in which the existence of cholinergic neurons has been the subject of debate. The demonstration that VAChT is a completely adequate marker for cholinergic neurons should allow the systematic delineation of cholinergic synapses in the rat nervous system when antibodies directed to this protein are available. C1 UNIV MAINZ,DEPT ANAT,W-6500 MAINZ,GERMANY. NIMH,CELL BIOL LAB,MOLEC NEUROSCI SECT,BETHESDA,MD 20892. OI Eiden, Lee/0000-0001-7524-944X NR 67 TC 91 Z9 94 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 1994 VL 5 IS 1 BP 1 EP 26 DI 10.1007/BF02736691 PG 26 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA PP525 UT WOS:A1994PP52500001 PM 7857778 ER PT J AU KASHMAN, Y BERNART, MW TISCHLER, M CARDELLINA, JH BOYD, MR AF KASHMAN, Y BERNART, MW TISCHLER, M CARDELLINA, JH BOYD, MR TI KOUMBALONE-A AND KOUMBALONE-B, NEW CASBANE DITERPENES FROM MAPROUNEA-AFRICANA SO JOURNAL OF NATURAL PRODUCTS LA English DT Note ID AGROSTISTACHYS-HOOKERI AB The organic extract of Mapronnea africana yielded koumbalones A [1] and B [2], defined by spectral methods as new variations on the casbane ring system. The gross structures, relative configurations, and solution conformations were determined by a combination of spectral analyses and molecular modeling. Because koumbalone A spontaneously converts to koumbalone B at room temperature, koumbalone B may be an artifact of isolation. C1 NCI,DIV CANC TREATMENT,DEV THERAPEUT PROGRAM,DRUG DISCOVERY RES & DEV LAB,FREDERICK,MD 21702. NR 7 TC 12 Z9 13 U1 0 U2 0 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 1994 VL 57 IS 3 BP 426 EP 430 DI 10.1021/np50105a020 PG 5 WC Plant Sciences; Chemistry, Medicinal; Pharmacology & Pharmacy SC Plant Sciences; Pharmacology & Pharmacy GA NF028 UT WOS:A1994NF02800020 PM 8201318 ER PT J AU GONZALES, JJ AF GONZALES, JJ TI PRIMARY HEALTH-CARE AND PSYCHIATRIC EPIDEMIOLOGY. - COOPER,B, EASTWOOD,R SO JOURNAL OF NERVOUS AND MENTAL DISEASE LA English DT Book Review RP GONZALES, JJ (reprint author), NIMH,BETHESDA,MD 20892, USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0022-3018 J9 J NERV MENT DIS JI J. Nerv. Ment. Dis. PD MAR PY 1994 VL 182 IS 3 BP 192 EP 192 DI 10.1097/00005053-199403000-00021 PG 1 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA NA763 UT WOS:A1994NA76300022 ER PT J AU NELSON, PG FIELDS, RD AF NELSON, PG FIELDS, RD TI CALCIUM AND NEURONAL PLASTICITY SO JOURNAL OF NEUROBIOLOGY LA English DT Editorial Material RP NELSON, PG (reprint author), NICHHD,DEV NEUROBIOL LAB,BETHESDA,MD 20892, USA. NR 0 TC 3 Z9 3 U1 0 U2 0 PU JOHN WILEY & SONS INC PI NEW YORK PA 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0022-3034 J9 J NEUROBIOL JI J. Neurobiol. PD MAR PY 1994 VL 25 IS 3 BP 219 EP 219 DI 10.1002/neu.480250302 PG 1 WC Neurosciences SC Neurosciences & Neurology GA MX658 UT WOS:A1994MX65800001 ER PT J AU YAGODIN, SV HOLTZCLAW, L SHEPPARD, CA RUSSELL, JT AF YAGODIN, SV HOLTZCLAW, L SHEPPARD, CA RUSSELL, JT TI NONLINEAR PROPAGATION OF AGONIST-INDUCED CYTOPLASMIC CALCIUM WAVES IN SINGLE ASTROCYTES SO JOURNAL OF NEUROBIOLOGY LA English DT Article DE NOREPINEPHRINE; GLUTAMATE; SALTATORY WAVE PROPAGATION ID INOSITOL 1,4,5-TRISPHOSPHATE; LAEVIS OOCYTES; OSCILLATIONS; MECHANISMS; RANGE; CA-2+; CELLS AB In astrocytes in primary culture, activation of neurotransmitter receptors results in intracellular calcium signals that propagate as waves across the cell. Similar agonist-induced calcium waves have been observed in astrocytes in organotypic cultures in response to synaptic activation. By using primary cultured astrocytes grown on glass coverslips, in conjunction with fluorescence microscopy we have analyzed agonist-induced Ca2+ wave initiation and propagation in individual cells. Both norepinephrine and glutamate elicited Ca2+ signals which were initiated focally and discretely in one region of the cell, from where the signals spread as waves along the entire length of the cell. Analysis of the wave propagation and the waveform revealed that the propagation was nonlinear with one or more focal loci in the cytoplasm where the wave was regeneratively amplified. These individual loci appear as discrete focal areas 7-15 mu m in diameter and having intrinsic oscillatory properties that differ from each other. The wave initiation locus and the different amplification loci remained invariant in space during the course of the experiment and supported an identical spatiotemporal pattern of signalling in any given cell in response to multiple agonist applications and when stimulated with different agonists which are coupled via InsP(3). Cytoplasmic Ca2+ concentration at rest was consistently higher (17 +/- 4 nM, mean +/- S.E.M.) in the wave initiation locus compared with the rest of the cytoplasm. The nonlinear propagation results from significant changes in signal rise times, amplitudes, and wave velocity in cellular regions of active loci. Analysis of serial slices across the cell revealed that the rise times and amplitudes of local signals were as much as three- to fourfold higher in the loci of amplification. A phenomenon of hierarchy in local amplitudes of the signal in the amplification loci was observed with the wave initiation locus having the smallest and the most distal locus having the largest amplitude. By this mechanism locally very high concentrations of Ca2+ are achieved in strategic locations in the cell in response to receptor activation. While the average wave velocity calculated over the length of the cell was 10-15 mu m/s, in the active loci rates as high as 40 mu m/s were measured. Wave velocity was fivefold lower in regions of the cell separating active loci. The differences in the intrinsic oscillatory periods give rise to local Ca2+ waves that show the properties of collision and annihilation. It is hypothesized that the wave front provokes regenerative Ca2+ release from specialized areas in the cell where the endoplasmic reticulum is endowed with higher density of InsP(3) receptor channels. Thus wave propagation is achieved by a process of diffusion and regenerative Ca2+ release in multiple cellular loci provoked by the advancing wave front; in this way, wave propagation is nonlinear and saltatory. Regenerative Ca2+ wave propagation from distal astrocytic processes to the cell body and neighboring cells is likely to provide an important signalling mechanism in the nervous system. (C) 1994 John Wiley and Sons, Inc. C1 NICHHD,CELLULAR & MOLEC NEUROPHYSIOL,NEURONAL SECRETORY SYST SECT,BETHESDA,MD 20892. NR 27 TC 67 Z9 67 U1 0 U2 1 PU JOHN WILEY & SONS INC PI NEW YORK PA 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0022-3034 J9 J NEUROBIOL JI J. Neurobiol. PD MAR PY 1994 VL 25 IS 3 BP 265 EP 280 DI 10.1002/neu.480250307 PG 16 WC Neurosciences SC Neurosciences & Neurology GA MX658 UT WOS:A1994MX65800006 PM 8195790 ER PT J AU FIELDS, RD NELSON, PG AF FIELDS, RD NELSON, PG TI RESONANT ACTIVATION OF CALCIUM SIGNAL-TRANSDUCTION IN NEURONS SO JOURNAL OF NEUROBIOLOGY LA English DT Article DE SYNAPTIC PLASTICITY; GROWTH CONE COLLAPSE; IMMEDIATE-EARLY GENES; C-FOS; NEURONAL DEVELOPMENT; CALCIUM KINETICS ID LONG-TERM POTENTIATION; IMMEDIATE-EARLY GENES; NEURITE OUTGROWTH; GROWTH CONE; INTRACELLULAR CALCIUM; POSTSYNAPTIC CALCIUM; SENSORY NEURONS; AREA CA1; SYNAPTIC RESPONSES; HIPPOCAMPAL SLICES AB The relevant parameters of calcium fluxes mediating activation of immediate-early genes and the collapse of growth cones in mouse DRG neurons in response to action potentials delivered in different temporal patterns were measured in a multicompartment cell culture preparation using digital fluorescence videomicroscopy. Growth cone collapse was produced by trains of action potentials causing a large rise in [Ca2+](i), but after chronic exposure to patterned stimulation growth cones regenerated and became insensitive to the stimulus-induced increase in [Ca2+](i). Calcium reached similar peak concentrations, but the [Ca2+](i) increased more slowly than in naive growth cones (time constant of 6.0 s versus 1.4 s in naive growth cones). Semiquantitative PCR measurements of gene expression showed that pulsed stimulation delivered at 1-min intervals for 30 min induced expression of c-fos, but the same total number of action potentials delivered at 2-min intervals failed to induce c-fos expression, even though this stimulus induces a larger peak [Ca2+](i) than the effective stimulus pattern. The experiments suggest that the kinetics of calcium fluxes produced by different patterns of stimulation, and changes in the kinetics of calcium flux in neurons under different states of activation, are critical in determining the effects of action potentials on growth cone motility or expression of IE genes during development of neuronal circuits. We propose that differences in kinetics of individual reactions in the stimulus-response pathway may lead to resonance of activation in the neuron, such that certain processes will be selectively activated by particular temporal patterns of stimulation. (C) 1994 John Wiley and Sons, Inc. RP FIELDS, RD (reprint author), NICHHD,DEV NEUROBIOL LAB,BETHESDA,MD 20892, USA. NR 70 TC 15 Z9 15 U1 1 U2 1 PU JOHN WILEY & SONS INC PI NEW YORK PA 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0022-3034 J9 J NEUROBIOL JI J. Neurobiol. PD MAR PY 1994 VL 25 IS 3 BP 281 EP 293 DI 10.1002/neu.480250308 PG 13 WC Neurosciences SC Neurosciences & Neurology GA MX658 UT WOS:A1994MX65800007 PM 8195791 ER PT J AU LIU, Y FIELDS, RD FITZGERALD, S FESTOFF, BW NELSON, PG AF LIU, Y FIELDS, RD FITZGERALD, S FESTOFF, BW NELSON, PG TI PROTEOLYTIC ACTIVITY, SYNAPSE ELIMINATION, AND THE HEBB SYNAPSE SO JOURNAL OF NEUROBIOLOGY LA English DT Article DE HEBB SYNAPSE; PROTEASE INHIBITOR; SYNAPSE PLASTICITY ID LONG-TERM POTENTIATION; MOTOR UNIT SIZE; CENTRAL-NERVOUS-SYSTEM; RAT SOLEUS MUSCLE; NEUROMUSCULAR-JUNCTION; POLYNEURONAL INNERVATION; RECEPTOR ANTAGONIST; PROTEASE INHIBITORS; SKELETAL-MUSCLE; NMDA RECEPTOR AB The Hebb synapse has been postulated to serve as a mechanism subserving both regulation of synaptic strength in the adult nervous system (long-term potentiation and depression) and developmental activity-dependent plasticity. According to this model, pre- and postsynaptic temporal concordance of activity results in strengthening of connections, while discordant activity results in synapse weakening. Evidence is presented that proteases and protease inhibitors may be involved in modification of synaptic strength. This leads to a modification of the Hebb assumptions, namely that postsynaptic activity results in protease elaboration with a consequent general reduction of synaptic connections to the active postsynaptic element. Further, presynaptic activity, if strong enough, induces local release of a protease inhibitor, such as protease nexin I, which neutralizes proteolytic activity and produces a relative preservation of the active input. This formulation produces many of the effects of the classical Hebbian construction, but the protease/inhibitor model suggests additional specific mechanistic features for activity-dependent plasticity. (C) 1994 John Wiley and Sons, Inc. C1 NICHHD,DEV NEUROBIOL LAB,BETHESDA,MD 20892. VET AFFAIRS MED CTR,NEUROBIOL RES LAB,KANSAS CITY,MO 64128. UNIV KANSAS,MED CTR,DEPT NEUROBIOL,KANSAS CITY,KS. NR 74 TC 75 Z9 75 U1 0 U2 0 PU JOHN WILEY & SONS INC PI NEW YORK PA 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0022-3034 J9 J NEUROBIOL JI J. Neurobiol. PD MAR PY 1994 VL 25 IS 3 BP 325 EP 335 DI 10.1002/neu.480250312 PG 11 WC Neurosciences SC Neurosciences & Neurology GA MX658 UT WOS:A1994MX65800011 PM 8195793 ER PT J AU RAUSCH, DM HEYES, MP MURRAY, EA LENDVAY, J SHARER, LR WARD, JM REHM, S NOHR, D WEIHE, E EIDEN, LE AF RAUSCH, DM HEYES, MP MURRAY, EA LENDVAY, J SHARER, LR WARD, JM REHM, S NOHR, D WEIHE, E EIDEN, LE TI CYTOPATHOLOGIC AND NEUROCHEMICAL CORRELATES OF PROGRESSION TO MOTOR/COGNITIVE IMPAIRMENT IN SIV-INFECTED RHESUS-MONKEYS SO JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY LA English DT Article DE AIDS; ASTROGLIOSIS; MOTOR/COGNITIVE DYSFUNCTION; NEUROPATHOLOGY; QUINOLINIC ACID; SIV ID ACQUIRED-IMMUNODEFICIENCY-SYNDROME; AIDS DEMENTIA COMPLEX; QUINOLINIC ACID CONCENTRATIONS; TUMOR-NECROSIS-FACTOR; CEREBROSPINAL-FLUID; HIV-1 INFECTION; KYNURENIC ACID; L-TRYPTOPHAN; VIRUS HIV; RAT-BRAIN AB Neurochemical, pathologic, virologic, and histochemical correlates of simian immunodeficiency virus (SIV)associated central nervous system (CNS) dysfunction were assessed serially or at necropsy in rhesus monkeys that exhibited motor and cognitive deficits after SIV infection. Some infected monkeys presented with signs of acquired immunodeficiency disease (AIDS) at the time of sacrifice. Seven of eight animals exhibited motor skill impairment which was associated with elevated quinolinic acid in cerebrospinal fluid (CSF). Examination of the brains revealed diffuse increases in glial fibrillary acidic protein immunoreactivity in cerebral cortex in all animals, regardless of evidence of immunodeficiency disease. Reactive astrogliosis preceded or was coincident with the onset of neuropsychological impairments. Virus rescue from CSF of six of eight infected animals showed that one of three animals with AIDS and none of three animals without AIDS at necropsy had virus rescue-positive CSF. Multinucleated giant cells were seen in the brain of only one animal with end-stage AIDS and high systemic virus burden at death. Neither systemic nor CNS virus burden was associated with the onset of CNS dysfunction. SIV-associated motor/cognitive impairment is associated with subtle, widespread changes in CNS cytology and neurochemistry, rather than with large increases in brain virus burden or widespread virus-associated brain lesions. C1 NIMH,CLIN SCI LAB,BETHESDA,MD 20892. NIMH,NEUROPSYCHOL LAB,BETHESDA,MD 20892. UMD,NEW JERSEY MED SCH,DEPT LAB MED & PATHOL,NEWARK,NJ. NCI,FREDERICK,MD. UNIV MAINZ,DEPT ANAT,W-6500 MAINZ,GERMANY. RP RAUSCH, DM (reprint author), NIMH,CELL BIOL LAB,MOLEC NEUROSCI SECT,BLDG 36,RM 3A17,BETHESDA,MD 20892, USA. OI Eiden, Lee/0000-0001-7524-944X; Murray, Elisabeth/0000-0003-1450-1642 NR 55 TC 71 Z9 71 U1 0 U2 0 PU AMER ASSN NEUROPATHOLOGISTS INC PI LAWRENCE PA 1041 NEW HAMPSHIRE ST, LAWRENCE, KS 66044 SN 0022-3069 J9 J NEUROPATH EXP NEUR JI J. Neuropathol. Exp. Neurol. PD MAR PY 1994 VL 53 IS 2 BP 165 EP 175 DI 10.1097/00005072-199403000-00008 PG 11 WC Clinical Neurology; Neurosciences; Pathology SC Neurosciences & Neurology; Pathology GA MZ510 UT WOS:A1994MZ51000008 PM 8120538 ER PT J AU TAN, SE WENTHOLD, RJ SODERLING, TR AF TAN, SE WENTHOLD, RJ SODERLING, TR TI PHOSPHORYLATION OF AMPA-TYPE GLUTAMATE RECEPTORS BY CALCIUM/CALMODULIN-DEPENDENT PROTEIN-KINASE-II AND PROTEIN-KINASE-C IN CULTURED HIPPOCAMPAL-NEURONS SO JOURNAL OF NEUROSCIENCE LA English DT Article DE GLUTAMATE RECEPTOR; PROTEIN KINASE; SYNAPTIC PLASTICITY; HIPPOCAMPUS; CALMODULIN-KINASE ID LONG-TERM POTENTIATION; RAT-BRAIN; MUTANT MICE; CALMODULIN; SUBUNIT; KAINATE; ACTIVATION; EXPRESSION; MECHANISM; PEPTIDE AB Phosphorylation of glutamate receptors (GluRs) is emerging as an important regulatory mechanism. In this study P-32 labeling of non-NMDA GluRs was investigated in cultured hippocampal neurons stimulated 2-15 min with agonists that selectively stimulate either Ca2+/calmodulin-dependent protein kinase II (CaM-kinase II), Ca2+/phospholipid-dependent protein kinase C (PKC), or cAMP-dependent protein kinase A (PKA). Treatment of hippocampal neurons with glutamate/ glycine (Glu/Gly), ionomycin, or 12-O-tetradecanoylphorbol 13-acetate (TPA) increased P-32 labeling of immunoprecipitated alpha-amino-3-hydroxy-5-methyl-4-isoxazoleproprionate (AMPA)-type GluRs by 145%, 180%, and 227%, respectively, of control values. This increased phosphorylation of GluRs was predominantly P-32-Ser with little P-32-Thr and no detectable P-32-Tyr. Glu/Gly and ionomycin, but not TPA, also increased P-32 labeling of CaM-kinase II by 175% and 195%, respectively, of control values. Of these three agonists, only TPA stimulated phosphorylation of MARCKS (225% of control), a specific substrate of PKC. Forskolin treatment gave a three- to fourfold increase in the active catalytic subunit of PKA but did not result in the P-32 labeling of AMPA-type GluRs, CaM-kinase II, or MARCKS. Phosphorylation of GluRs in response to Glu/Gly was blocked by a specific NMDA receptor/ion channel antagonist (DL-2-amino-5-phosphonovaleric acid) or by a cell-permeable inhibitor of CaM-kinase II (1-[N,O-bis(1,5-isoquinolinesulfonyl)-N-methyl-L-tyrosyl]-4-phenylpiperazine, KN-62). These results are consistent with the hypothesis that Ca2+ influx through the NMDA-type ion channel can activate CaM-kinase II, which in turn can phosphorylate and regulate AMPA-type GluR ion channels (McGlade-McCulloh et al., 1993). Such a mechanism could contribute to the postsynaptic component of long-term potentiation and other forms of synaptic plasticity. C1 OREGON HLTH SCI UNIV, VOLLUM INST, PORTLAND, OR 97201 USA. NIDOCD, NEUROCHEM LAB, BETHESDA, MD 20892 USA. FU NINDS NIH HHS [NS27037] NR 42 TC 168 Z9 172 U1 0 U2 2 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD MAR PY 1994 VL 14 IS 3 BP 1123 EP 1129 PN 1 PG 7 WC Neurosciences SC Neurosciences & Neurology GA MZ405 UT WOS:A1994MZ40500016 PM 7509863 ER PT J AU POLLI, JW KINCAID, RL AF POLLI, JW KINCAID, RL TI EXPRESSION OF A CALMODULIN-DEPENDENT PHOSPHODIESTERASE ISOFORM (PDE1B1) CORRELATES WITH BRAIN-REGIONS HAVING EXTENSIVE DOPAMINERGIC INNERVATION SO JOURNAL OF NEUROSCIENCE LA English DT Article DE CAMP; CYCLASE; STRIATUM; DOPAMINE; BASAL GANGLIA; DARPP-32 ID CYCLIC-NUCLEOTIDE PHOSPHODIESTERASE; BINDING PROTEIN CAM-BP80; RAT-BRAIN; MOLECULAR-CLONING; BOVINE BRAIN; MESSENGER-RNA; ADENYLATE-CYCLASE; RECEPTOR; CALCINEURIN; GLUTAMATE AB Cyclic nucleotide-dependent protein phosphorylation plays a central role in neuronal signal transduction. Neurotransmitter-elicited increases in cAMP/cGMP brought about by activation of adenylyl and guanylyl cyclases are downregulated by multiple phosphodiesterase (PDE) enzymes. In brain, the calmodulin (CaM)-dependent isozymes are the major degradative activities and represent a unique point of intersection between the cyclic nucleotide- and calcium (Ca2+)-mediated second messenger systems. Here we describe the distribution of the PDE1B1 (63 kDa) CaM-dependent PDE in mouse brain. An anti-peptide antiserum to this isoform immunoprecipitated approximate to 30-40% of cytosolic PDE activity, whereas antiserum to PDE1A2 (61 kDa isoform) removed 60-70%, demonstrating that these isoforms are the major CaM-dependent PDEs in brain. Quantification of PDE1B1 immunoreactivity on immunoblots indicated that striatum contains 3-17-fold higher levels of PDE1B1 than other brain regions, with lowest immunoreactivity in cerebellum. In site hybridization demonstrated high levels of PDE1B1 mRNA in the caudate-putamen, nucleus accumbens, and olfactory tubercle. Moderate mRNA levels were observed in dentate gyrus, cerebral cortex, medial thalamic nuclei, and brainstem, whereas negligible mRNA was detectable in the globus pallidus, islands of Calleja, substantia nigra, and ventral tegmental area. Immunocytochemistry confirmed that the majority of PDE1B1 protein was localized to the caudate-putamen, nucleus accumbens, and olfactory tubercle. Within the caudate-putamen, PDE1B1 immunoreactivity was ubiquitous, while PDE1AS immunostaining was restricted to a minor subset of striatal neurons. The expression of PDE1B1 protein and mRNA correlate strongly with areas of the brain that are richest in dopaminergic innervation; indeed, there are strikingly similar distributions for PDE1B1 and D-1 dopamine receptor mRNAs. Since D-1 receptor binding activates adenylyl cyclase, and striatal neurons lack CaM-sensitive forms of cyclase, the high amount of this PDE implies an important physiological role for Ca2+-regulated attenuation of cAMP-dependent signaling pathways following dopaminergic stimulation. C1 NIAAA, MOLEC & CELLULAR NEUROBIOL LAB, IMMUNOL SECT, ROCKVILLE, MD 20852 USA. NR 46 TC 88 Z9 91 U1 0 U2 0 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD MAR PY 1994 VL 14 IS 3 BP 1251 EP 1261 PN 1 PG 11 WC Neurosciences SC Neurosciences & Neurology GA MZ405 UT WOS:A1994MZ40500027 PM 8120623 ER PT J AU IRWIN, RP LIN, SZ LONG, RT PAUL, SM AF IRWIN, RP LIN, SZ LONG, RT PAUL, SM TI N-METHYL-D-ASPARTATE INDUCES A RAPID, REVERSIBLE, AND CALCIUM-DEPENDENT INTRACELLULAR ACIDOSIS IN CULTURED FETAL-RAT HIPPOCAMPAL-NEURONS SO JOURNAL OF NEUROSCIENCE LA English DT Article DE NMDA; RECEPTOR; INTRACELLULAR PH; ACIDOSIS; CALCIUM; NEUROTOXICITY ID EXCITATORY AMINO-ACIDS; ISCHEMIC DAMAGE; NERVOUS-SYSTEM; SNAIL NEURONS; PH CHANGES; MODULATION; INHIBITION; RECEPTORS; RESPONSES; CHANNEL AB The ability of NMDA to alter intracellular pH (pH(i)) was studied in fetal rat hippocampal neurons and glia using the pH-sensitive fluorescent indicator 2',7'-bis-(2-carboxyethyl)-5-(and-6)-carboxyfluorescein (BCECF). Brief exposure (60 sec) of hippocampal neurons to NMDA (2.5-250 mu M) results in a rapid, and in most cells reversible, reduction in pH(i), with full recovery to baseline pH(i) values taking several minutes following removal of NMDA. In contrast, little or no change in pH(i) was observed in glial cells exposed to these same concentrations of NMDA. The NMDA-induced acidification of neurons was concentration and time dependent, with an EC(50) of 39 mu M and E(max) (Delta pH) of -0.53. More prolonged exposure to NMDA(greater than or equal to 10 min) resulted in a more prolonged reduction in pH(i) values over the ensuing 20 min observation period. The intracellular acidification resulting from NMDA exposure of hippocampal neurons was blocked by the NMDA receptor antagonist 3-((+/-)-2-carboxypiperazi n-4-yl)-propyl-1-phosphonic acid (CPP). Moreover, removal of extracellular Ca2+ eliminated both the selective NMDA-induced elevation in [Ca2+](i) and the reduction in pH(i) indicating that Ca2+ influx may be required for the decrease in pH(i) induced by NMDA receptor activation. Finally, the NMDA-induced reduction in pH(i) was not significantly attenuated when extracellular [H+] was decreased by increasing extracellular pH to 8.0. The latter suggests that an intracellular source of H+ is responsible for the NMDA-induced reduction in neuronal pH(i). The reduction in neuronal pH(i) induced by NMDA receptor activation may mediate some of the physiological and (or) pathophysiological actions of glutamate. C1 NIMH, CLIN NEUROSCI BRANCH, MOLEC PHARMACOL SECT, BETHESDA, MD 20892 USA. NR 34 TC 93 Z9 96 U1 0 U2 0 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD MAR PY 1994 VL 14 IS 3 BP 1352 EP 1357 PN 1 PG 6 WC Neurosciences SC Neurosciences & Neurology GA MZ405 UT WOS:A1994MZ40500035 PM 8120630 ER PT J AU GRADY, CL MAISOG, JM HORWITZ, B UNGERLEIDER, LG MENTIS, MJ SALERNO, JA PIETRINI, P WAGNER, E HAXBY, JV AF GRADY, CL MAISOG, JM HORWITZ, B UNGERLEIDER, LG MENTIS, MJ SALERNO, JA PIETRINI, P WAGNER, E HAXBY, JV TI AGE-RELATED-CHANGES IN CORTICAL BLOOD-FLOW ACTIVATION DURING VISUAL PROCESSING OF FACES AND LOCATION SO JOURNAL OF NEUROSCIENCE LA English DT Article DE CEREBRAL BLOOD FLOW; AGING; NEUROIMAGING; OBJECT VISION; SPATIAL VISION; CORTEX ID POSITRON EMISSION TOMOGRAPHY; POSTERIOR PARIETAL CORTEX; HUMAN EXTRASTRIATE CORTEX; PREFRONTAL CORTEX; MENTAL ROTATION; RHESUS-MONKEY; FRONTAL-LOBE; FUNCTIONAL-ANATOMY; WORKING MEMORY; SPATIAL VISION AB We examined age-related changes in object and spatial visual processing in two separate experiments. Regional cerebral blood flow (rCBF) was measured in young and old subjects with positron emission tomography and H-2 O-15 during tests of face matching, location matching, and a control task. The task demands in the two experiments were identical, but the stimuli in Experiment II were constructed to equalize stimulus complexity across all three tasks. The old subjects performed more slowly than the young subjects in both experiments, and showed significantly slower reaction times during location matching compared to face matching in Experiment II. Both young and old subjects showed occipitotemporal rCBF activation during face matching and occipitoparietal activation during location matching when these conditions were compared to the control task. However, in both experiments and in both tasks, young subjects showed greater activation of prestriate cortex (Brodmann's area 18), and old subjects had larger rCBF increases in occipitotemporal cortex (area 37). Areas in prefrontal cortex, as well as in inferior and medial parietal cortex, were more activated in the old subjects during location matching in both experiments. These results demonstrate that reliable age-related changes during visual processing can be found in rCBF patterns, suggesting more efficient use of occipital visual areas by younger subjects and more reliance by older subjects on one or more cortical networks, particularly for spatial vision, perhaps to compensate for reduced processing efficiency of occipital cortex. Both the differentially increased reaction times and the more widespread prefrontal activation in the old subjects during location matching suggest that spatial vision may be affected to a greater degree by aging than is object vision. C1 NIMH,NEUROPSYCHOL LAB,BETHESDA,MD 20892. RP GRADY, CL (reprint author), NIA,NEUROSCI LAB,BLDG 10,ROOM 6C414,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 73 TC 391 Z9 394 U1 4 U2 16 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 1994 VL 14 IS 3 BP 1450 EP 1462 PN 2 PG 13 WC Neurosciences SC Neurosciences & Neurology GA MZ407 UT WOS:A1994MZ40700007 PM 8126548 ER PT J AU KNUSEL, B RABIN, SJ HEFTI, F KAPLAN, DR AF KNUSEL, B RABIN, SJ HEFTI, F KAPLAN, DR TI REGULATED NEUROTROPHIN RECEPTOR RESPONSIVENESS DURING NEURONAL MIGRATION AND EARLY DIFFERENTIATION SO JOURNAL OF NEUROSCIENCE LA English DT Article DE NGF; BRAIN-DERIVED NEUROTROPHIC FACTOR; NEUROTROPHIN-3; NEUROTROPHIN-4/5; RECEPTOR TYROSINE KINASE; CHOLINERGIC BRAIN NEURONS; ERK 1; PHOSPHOLIPASE C-GAMMA-1; SNT; ALZHEIMERS DISEASE ID NERVE GROWTH-FACTOR; TYROSINE PROTEIN-KINASE; FACTOR MESSENGER-RNA; TRK PROTOONCOGENE PRODUCT; FOREBRAIN CHOLINERGIC NEURONS; RAT BASAL FOREBRAIN; ADULT-RAT; INSITU HYBRIDIZATION; PHOSPHATIDYLINOSITOL 3-KINASE; PHEOCHROMOCYTOMA CELLS AB The response of brain tissue to neurotrophins during rat development was examined using a novel in vitro assay for Trk/neurotrophin receptor activity. In this assay, brain tissues were exposed to neurotrophins and ligand-induced Trk tyrosine phosphorylation was measured. During the perinatal period, Trk tyrosine phosphorylation in all brain areas was induced very similarly by the TrkB and TrkC ligands brain-derived neurotrophic factor (BDNF), neurotrophin-3 (NT-3), and neurotrophin-4/5 (NT-4/5). In the adult brain, minimal signals were observed after treatment with these three factors, despite the continued presence of full-length and truncated TrkB protein. In contrast, responsiveness to the TrkA ligand NGF was absent in the embryo and increased during the first 2 weeks after birth in various brain areas, particularly in striatum, basal forebrain, and hippocampus. Our results, showing maximal responsiveness of brain tissue to BDNF, NT-3, and NT-4/5 during early neuronal differentiation and migration, suggest involvement of TrkB in these events. The lack of a significant response to these neurotrophins in the adult brain indicates effective posttranslational mechanisms that control the response of Trk family receptors. Our findings further demonstrate that neurons of the striatum and basal forebrain remain NGF responsive in the adult, confirming at the molecular level results obtained earlier at the cellular level for the basal forebrain cholinergic neurons. C1 UNIV SO CALIF,DEPT BIOL SCI,LOS ANGELES,CA 90089. NCI,FREDERICK CANC RES & DEV CTR,ABL,BASIC RES PROGRAM,FREDERICK,MD 21702. RP KNUSEL, B (reprint author), UNIV SO CALIF,ANDRUS GERONTOL CTR,DIV NEUROGERONTOL,MC-0191,LOS ANGELES,CA 90089, USA. FU NIA NIH HHS [AG09793, AG10480]; NINDS NIH HHS [NS22933] NR 85 TC 172 Z9 172 U1 0 U2 3 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 1994 VL 14 IS 3 BP 1542 EP 1554 PN 2 PG 13 WC Neurosciences SC Neurosciences & Neurology GA MZ407 UT WOS:A1994MZ40700014 PM 8126554 ER PT J AU ALLENDOERFER, KL CABELLI, RJ ESCANDON, E KAPLAN, DR NIKOLICS, K SHATZ, CJ AF ALLENDOERFER, KL CABELLI, RJ ESCANDON, E KAPLAN, DR NIKOLICS, K SHATZ, CJ TI REGULATION OF NEUROTROPHIN RECEPTORS DURING THE MATURATION OF THE MAMMALIAN VISUAL-SYSTEM SO JOURNAL OF NEUROSCIENCE LA English DT Article DE BRAIN-DERIVED NEUROTROPHIC FACTOR; NT-3; TRKB; TRKC; P75; RETINA; CORTEX; CROSS-LINKING ID NERVE GROWTH-FACTOR; RETINAL GANGLION-CELLS; TYROSINE PROTEIN-KINASE; LATERAL GENICULATE-NUCLEUS; AFFINITY NGF RECEPTOR; TRK PROTOONCOGENE; MOLECULAR-CLONING; GENE-TRANSFER; POSTNATAL-DEVELOPMENT; RAT PHEOCHROMOCYTOMA AB Cell division, cell death, and remodeling of connections are major features of the construction of the mammalian CNS. We have begun to address the role of neurotrophins in these events through characterization of the expression of their receptors in the developing ferret visual system. By use of chemical cross-linking of iodinated neurotrophins, proteins corresponding to trkB, trkC, and p75 were identified as receptors for brain-derived neurotrophic factor (BDNF) and neurotrophin-3 (NT-3) throughout development. BDNF was also cross-linked to a truncated form of trkB that lacks the tyrosine kinase domain (trkB.T 1) in retinal target tissues and in cortex. At the earliest developmental age examined (E24), the ratio of full-length to truncated trkB is much greater than 1 in the retinal target tissues, LGN and superior colliculus. During the ensuing period of retinal ganglion cell death and segregation into eye-specific layers, the amount of truncated trkB increases markedly relative to full-length trkB. By P27, truncated trkB is the predominant receptor for BDNF in the retinal target tissues and this pattern is maintained into adulthood. Within all subdivisions of visual cortex including the ventricular zone (VZ), intermediate zone (IZ), and cortical plate (CP), similar profiles of bands are observed. The developmental increase in abundance of truncated trkB relative to full-length occurs earliest in the VZ, with a major increase between E30 and P3. In the IZ, this shift to a predominance of truncated trkB occurs between P15 and P30, while in the CP the shift is even further delayed, not occurring until after P30. Within each subdivision of cortex, the shift to a predominance of truncated trkB occurs at times that correlate with the onset of cell death and maturation of axonal connections. This study demonstrates that members of the trk family, previously identified in the CNS on the basis of mRNA transcripts, are present as receptors with specific binding affinities for BDNF and NT-3. Moreover, the correspondence between the developmental shift from full-length to truncated trkB and the critical periods for cell fate determination, cell death, and axonal remodeling suggests an important role for neurotrophic factors in the development of the visual system. C1 UNIV CALIF BERKELEY,DEPT MOLEC & CELL BIOL,BERKELEY,CA 94720. STANFORD UNIV,SCH MED,NEUROSCI PROGRAM,STANFORD,CA 94305. GENENTECH INC,DEPT NEUROSCI,S SAN FRANCISCO,CA 94080. NCI,FREDERICK CANC RES & DEV CTR,ABL,BASIC RES PROGRAM,MMCL,FREDERICK,MD 21702. FU NEI NIH HHS [EY02858, EY06327]; NINDS NIH HHS [NS07158] NR 97 TC 207 Z9 207 U1 0 U2 0 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 1994 VL 14 IS 3 BP 1795 EP 1811 PN 2 PG 17 WC Neurosciences SC Neurosciences & Neurology GA MZ407 UT WOS:A1994MZ40700037 PM 8126572 ER PT J AU BANIK, NL CHOU, CH DEIBLER, GE KRUTZCH, HC HOGAN, EL AF BANIK, NL CHOU, CH DEIBLER, GE KRUTZCH, HC HOGAN, EL TI PEPTIDE-BOND SPECIFICITY OF CALPAIN - PROTEOLYSIS OF HUMAN MYELIN BASIC-PROTEIN SO JOURNAL OF NEUROSCIENCE RESEARCH LA English DT Article DE CALCIUM-ACTIVATED PROTEINASE; DEGRADATION OF PROTEIN; SEQUENCE; DEMYELINATION; AUTOIMMUNE ATTACK ID ACTIVATED NEUTRAL PROTEASE; EXPERIMENTAL ALLERGIC ENCEPHALOMYELITIS; AMINO ACID SEQUENCE; BRAIN WHITE MATTER; BOVINE SPINAL-CORD; LIMITED PROTEOLYSIS; DETERMINANT; PURIFICATION; CLEAVAGE; KINASE AB In order to determine the peptide bond specificity of calpain, human myelin basic protein (HMBP) was treated with purified calpain of bovine brain. Upon incubation, HMBP component I (HMBP-I) was degraded into several peptides as demonstrated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Component I was more susceptible to degradation than components II and III. HMBP degradation products were separated by high performance liquid chromatography (HPLC) and the cleavage sites in HMBP molecules were determined by peptide sequence analysis and by N- and C-terminal analyses. The major cleavage site was found to be (94)Val-(95)Thr with several minor cleavages at (49)Arg-(50)Gly, (18)Ala-(19)Ser, (23)His-(24)Ala, (27)Gly-(28)phe, (59)Asp- (60)Ser, (70)Gly-(71)Ser, (97)Arg-(98)Thr, (110)Ser-(111)Leu, (145)Asp-(146)Ala, and (156)Leu-(157)Gly. These results indicate that calpain is involved in the limited proteolysis of human myelin basic protein and prolonged incubation causes further digestion of the large peptides. (C) 1991 Wiley-Liss, Inc. C1 EMORY UNIV,DEPT NEUROL,ATLANTA,GA. NIH,CEREBRAL METAB LAB,BETHESDA,MD. NIH,PATHOL LAB,BETHESDA,MD 20892. RP BANIK, NL (reprint author), MED UNIV S CAROLINA,DEPT NEUROL,171 ASHLEY AVE,CHARLESTON,SC 29425, USA. FU NINDS NIH HHS [NINDS NS-11066] NR 51 TC 34 Z9 34 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 1994 VL 37 IS 4 BP 489 EP 496 DI 10.1002/jnr.490370408 PG 8 WC Neurosciences SC Neurosciences & Neurology GA MY529 UT WOS:A1994MY52900007 PM 7517457 ER PT J AU RAM, Z WALBRIDGE, S HEISS, JD CULVER, KW BLAESE, RM OLDFIELD, EH AF RAM, Z WALBRIDGE, S HEISS, JD CULVER, KW BLAESE, RM OLDFIELD, EH TI IN-VIVO TRANSFER OF THE HUMAN INTERLEUKIN-2 GENE - NEGATIVE TUMORICIDAL RESULTS IN EXPERIMENTAL BRAIN-TUMORS SO JOURNAL OF NEUROSURGERY LA English DT Article DE BRAIN NEOPLASM; CYTOKINE; INTERLEUKIN-2; GENE THERAPY; RETROVIRUS; THYMIDINE KINASE; RAT ID HUMAN RECOMBINANT INTERLEUKIN-2; PRIMARY INTRACRANIAL TUMORS; ACTIVATED KILLER CELLS; MALIGNANT GLIOMA; LAK CELLS; LYMPHOCYTES; IMMUNOTHERAPY; TOXICITY AB The authors have recently shown the feasibility of eradicating brain tumors using in vivo retroviral-mediated transduction of tumors with the herpes simplex thymidine kinase (HStk) gene and ganciclovir therapy. However, thymidine kinase-transduced subcutaneous tumors in immunocompromised (athymic) mice were less responsive to this therapy than in immunocompetent animals, suggesting a role of the immune system in the process of tumor eradication. Broad suppression of humoral and cell-mediated immunity is found inpatients with malignant gliomas. Interleukin-2 (IL-2) production and IL-2 receptor expression are decreased in glioma patients. These findings and the proposed association between lymphocytic infiltration of brain tumors and survival suggest that immune response modifiers may be useful in treating glioma patients. To evaluate the role of local cytokine expression by tumor cells, alone or combined with HStk gene transfer and ganciclovir therapy, the authors investigated the efficacy of tumor (9L gliosarcoma) eradication in Fischer rats by in vitro and in vivo tumor transduction with the IL-2 gene alone or with a combined vector carrying both the HStk and IL-2 genes. Tumors injected with HStk vector-producer cells alone, with or without ganciclovir, and rats inoculated in the brain and subcutaneously with 9L cells that had previously been transduced in vitro served as controls. Murine vector-producer cells (3 x 10(6)/50 mu l) were injected into the brain tumors 7 days after tumor inoculation. Ganciclovir (15 mg/kg) was administered intraperitoneally twice daily for 10 days to animals that received HStk with or without IL-2 vector-producer cells, starting 5 days after producer-cell injection. The experiment was repeated with continuous daily treatment of all rats with oral dexamethasone (0.5 mg/kg). Rats were sacrificed 21 days after tumor inoculation, and the brains were removed for histological and immunohistochemical analysis for IL-2. Within each experimental group, tumors were found in a similar proportion in the dexamethasone-treated and untreated rats. Large brain tumors developed in all 10 rats that had been inoculated with 9L cells which had been pretransduced in vitro with the IL-2 gene, whereas only three of eight rats receiving subcutaneous inoculation of similar cells developed palpable tumors. No enhancement of tumor eradication was observed by adding the IL-2 gene in the HStk vector construct compared to the use of the vector with HStk alone. Lymphocytic infiltration was absent in all dexamethasone-treated rats but was observed in all treatment groups not receiving steroids. The degree of lymphocytic infiltration was not enhanced by intratumoral injection of IL-2 or IL-2/HStk vector-producer cells. The findings suggest a limited role, if any, for immune enhancement by transduction with IL-2 to eradicate brain tumors, either used alone or in combination with HStk. C1 NCI,METAB BRANCH,BETHESDA,MD 20892. RP RAM, Z (reprint author), NINCDS,SURG NEUROL BRANCH,BLDG 10,ROOM 5D-37,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 25 TC 93 Z9 93 U1 0 U2 0 PU AMER ASSOC NEUROLOGICAL SURGEONS PI CHARLOTTESVILLE PA UNIV VIRGINIA, 1224 WEST MAIN ST, STE 450, CHARLOTTESVILLE, VA 22903 SN 0022-3085 J9 J NEUROSURG JI J. Neurosurg. PD MAR PY 1994 VL 80 IS 3 BP 535 EP 540 DI 10.3171/jns.1994.80.3.0535 PG 6 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA MY483 UT WOS:A1994MY48300017 PM 8113867 ER PT J AU AKUNNE, HC DERSCH, CM CADET, JL BAUMANN, MH CHAR, GU PARTILLA, JS DECOSTA, BR RICE, KC CARROLL, FI ROTHMAN, RB AF AKUNNE, HC DERSCH, CM CADET, JL BAUMANN, MH CHAR, GU PARTILLA, JS DECOSTA, BR RICE, KC CARROLL, FI ROTHMAN, RB TI STUDIES OF THE BIOGENIC-AMINE TRANSPORTERS .3. DEMONSTRATION OF 2 BINDING-SITES FOR [H-3] GBR12935 AND [H-3] BTCP IN RAT CAUDATE MEMBRANES SO JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS LA English DT Article ID DOPAMINE UPTAKE COMPLEX; GUINEA-PIG BRAIN; NOREPINEPHRINE UPTAKE SITES; SEROTONIN UPTAKE SITES; H-3 GBR-12935 BINDING; HIGH-AFFINITY BINDING; COCAINE RECEPTORS; GBR-12935 BINDING; NONHUMAN-PRIMATES; LIGAND-BINDING AB The present study addressed the hypothesis that there exist multiple sites/states associated with the dopamine (DA) transporter ligands. The authors used [H-3](1-[2-(diphenylmethoxy) ethyl]-4-(3-phenylpropyl)piperazine) (GBR12935) and [H-3]-N-{1-(2-benzo[b]thiophenyl)cyclohexyl }piperidine ([H-3]BTCP) to label binding sites present in striatal membranes and conducted experiments under nearly identical assay conditions, i.e., 18- to 24-hr incubations at 4 degrees C in 55.2 mM sodium phosphate buffer, pH 7.4, with a protease inhibitor and antioxidant cocktail. To obtain data suitable for quantitative curve fitting, it was necessary to repurify the [H-3]ligands periodically by high-performance liquid chromatography. Under these conditions, greater than 90% specific binding was observed. The method of binding surface analysis was used to characterize the interaction of GBR12935, BTCP, mazindol and 2 beta-carbomethoxy-3 beta-(4-fluorophenyl) tropane with binding sites labeled by the [H-3]ligands. Nonlinear least-squares curve fitting of the data to one- and two-site binding models demonstrated that, for both [H-3]ligands, the two-site model fit the data far better than did the one-site model. The results indicated that [H-3]GBR12935 labeled two binding sites, with higher (GBR site 1) and lower affinity (GBR site 2) for BTCP (K-i values of 5.84 nM and 1394 nM). [H-3]BTCP labeled two sites with high affinity (K-d values of 9.3 nM and 6.3 nM) at which GBR12935 also had high affinity (K-i values of 8.9 nM and 0.98 nM). Intrastriatal 6-hydroxy-DA lesions decreased the density of both [H-3]GBR12935 binding sites but affected site 1 much more than site 2, which indicated that a greater portion of GBR site 1 is localized on striatal nerve terminals. By contrast, the 6-hydroxy-DA lesions decreased BTCP site 2 without significantly decreasing BTCP site 1, which indicated that BTCP site 1 is not located on DA nerve terminals. The i.c.v. administration of 5,7,- dihydroxytryptamine did not decrease GBR site 1 or 2, which indicated that neither is located on serotonin striatal nerve terminals. Viewed collectively with other reports, these data support the hypothesis that DA transporter ligands label multiple binding sites in caudate membranes. The identification of selective agents for these sites may be valuable tools for identifying drugs that might modulate the effects of cocaine. C1 NIDA,ADDICT RES CTR,CLIN PSYCHOPHARMACOL SECT,BALTIMORE,MD 21224. NIDDK,MED CHEM LAB,DRUG DESIGN & SYNTHESIS SECT,BETHESDA,MD. RES TRIANGLE INST,RES TRIANGLE PK,NC 27709. NR 74 TC 31 Z9 31 U1 2 U2 2 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 1994 VL 268 IS 3 BP 1462 EP 1475 PG 14 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA NB406 UT WOS:A1994NB40600051 PM 7908058 ER PT J AU KLING, MA GARDNER, DL CALOGERO, AE COPPOLA, R TRETTAU, J KELLNER, CH LEFTER, L HART, MJ COWDRY, RW POST, RM GOLD, PW AF KLING, MA GARDNER, DL CALOGERO, AE COPPOLA, R TRETTAU, J KELLNER, CH LEFTER, L HART, MJ COWDRY, RW POST, RM GOLD, PW TI EFFECTS OF LOCAL-ANESTHETICS ON EXPERIENTIAL, PHYSIOLOGICAL AND ENDOCRINE MEASURES IN HEALTHY HUMANS AND ON RAT HYPOTHALAMIC CORTICOTROPIN-RELEASING HORMONE-RELEASE IN-VITRO - CLINICAL AND PSYCHOBIOLOGIC IMPLICATIONS SO JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS LA English DT Review ID BENZODIAZEPINE RECEPTOR LIGANDS; MAMMALIAN AXONAL MEMBRANES; GROWTH-HORMONE; ELECTRICAL-STIMULATION; SECRETION INVITRO; LIMBIC SYSTEM; BIOCHEMICAL MANIFESTATIONS; PROLACTIN SECRETION; CUSHINGS-DISEASE; PATHO-PHYSIOLOGY AB Local anesthetics, given i.v. to treat cardiac arrhythmias and for regional anesthesia, exert prominent central nervous system side effects, such as sensory distortions and mood changes. In experimental animals, these drugs activate limbic structures, such as the amygdala, that may coordinately regulate sensory processing, mood and pituitary hormone secretion during stress. Clinically relevant i.v. doses of the short-acting local anesthetic procaine were administered to 17 healthy volunteers and topographic electroencephalographic (EEG) spectra, stress-responsive neuroendocrine and cardiovascular parameters and sensory-cognitive and mood changes were examined. Because corticotropin-releasing hormone (CRH) mimics the behavioral and physiologic responses to stress and activates limbic structures in experimental animals, the effects of procaine and lidocaine on immunoreactive CRH release from rat hypothalami in vitro were also explored. Procaine administration produced a dose-related increase in fast (21-50 Hz) EEG activity, a significant decrease in alpha EEG activity and dose-dependent increases in heart rate, systolic blood pressure and plasma adrenocorticotropic hormone, cortisol and prolactin secretion. Dose-dependent increases in sensory distortions involved virtually all modalities, particularly auditory, visual and somatosensory. Mood changes occurred in most subjects, including anxiety, euphoria and arousal. In vitro, procaine and lidocaine both produced significant dose-related increases in immunoreactive CRH release from rat hypothalami, maximal at 10(-6) M, that were blocked by carbamazepine, a limbic anticonvulsant used in the management of mood disorders. The electrophysiologic effects of procaine in these volunteers were analogous to local anesthetic effects in experimental animals and consistent with the activation of subcortical structures localized within the temporal lobe, such as the amygdala. The effects of procaine on stress-responsive neurohormones were similar to those of amygdala stimulation both in experimental animals and human subjects. The in vitro data suggested that procaine-induced pituitary-adrenal activation involves stimulation of hypothalamic CRH, although additional (e.g., limbic-hypothalamic) mechanisms may contribute in vivo. These data were compatible with a direct action of local anesthetics on limbic structures that might account for many of the central effects seen with the systemic use of these agents in clinical practice. C1 NIMH,CLIN BRAIN DISORDERS BRANCH,BETHESDA,MD 20892. NIMH,BIOL PSYCHIAT BRANCH,BETHESDA,MD 20892. NINCDS,DIV INTRAMURAL RES,BETHESDA,MD 20892. MED UNIV S CAROLINA,DEPT PSYCHIAT & BEHAV SCI,CHARLESTON,SC 29425. RP KLING, MA (reprint author), NIMH,INTRAMURAL RES PROGRAM,CLIN NEUROENDOCRINOL BRANCH,AFFECT DISORDERS UNIT,BLDG 10,BETHESDA,MD 20892, USA. RI Kling, Mitchel/F-4152-2010 OI Kling, Mitchel/0000-0002-2232-1409 NR 119 TC 9 Z9 9 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0022-3565 J9 J PHARMACOL EXP THER JI J. Pharmacol. Exp. Ther. PD MAR PY 1994 VL 268 IS 3 BP 1548 EP 1564 PG 17 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA NB406 UT WOS:A1994NB40600062 PM 8138967 ER PT J AU LYNN, AB HERKENHAM, M AF LYNN, AB HERKENHAM, M TI LOCALIZATION OF CANNABINOID RECEPTORS AND NONSATURABLE HIGH-DENSITY CANNABINOID BINDING-SITES IN PERIPHERAL-TISSUES OF THE RAT - IMPLICATIONS FOR RECEPTOR-MEDIATED IMMUNE MODULATION BY CANNABINOIDS SO JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS LA English DT Article ID SUBSTANCE-P RECEPTORS; MARIHUANA SMOKERS; ADENYLATE-CYCLASE; T-LYMPHOCYTE; DELTA-9-TETRAHYDROCANNABINOL; BRAIN; MARIJUANA; TETRAHYDROCANNABINOL; SUPPRESSION; INVITRO AB [H-3]CP-55,940, a high-affinity cannabinoid receptor ligand, was used for in vitro binding and autoradiography in peripheral tissues in the rat. Specific cannabinoid receptor binding was found to be restricted to components of the immune system, i.e., spleen, lymph nodes and Peyer's patches. Displacement studies showed that this binding is identical (similar K-d and structure-activity profile) to that in brain. Cannabinoid receptors in the immune system are confined to B lymphocyte-enriched areas, i.e., the marginal zone of the spleen, cortex of the lymph nodes and nodular corona of Peyer's patches. Specific binding is absent in T lymphocyte-enriched areas, such as the thymus and periarteriolar lymphatic sheaths of the spleen. Certain macrophage-enriched areas, i.e., liver and lung, lack specific binding. Thus, the single peripheral cell type that may contain cannabinoid receptors is the B lymphocyte. Numerous sites have dense binding that could not be displaced by excess unlabeled drug. These nonspecific sites were found in the liver, adrenal glands and sebaceous glands, which are high in fat content, and in the heart, pancreas, components of the male and female reproductive systems and the epithelium of the esophagus. Thus, the highly lipophilic nature of cannabinoids does not appear to be the sole determinant of nonspecific binding. The data suggest that cannabinoids may exert specific receptor-mediated actions on the immune system of rats. Perhaps, also at high concentrations, cannabinoids exert membrane effects at sites where they are sequestered nonspecifically. C1 NIMH,FUNCT NEUROANAT SECT,BETHESDA,MD 20892. OI Herkenham, Miles/0000-0003-2228-4238 NR 64 TC 199 Z9 200 U1 1 U2 4 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 1994 VL 268 IS 3 BP 1612 EP 1623 PG 12 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA NB406 UT WOS:A1994NB40600069 PM 8138973 ER PT J AU WOLF, SS HYDE, TM WEINBERGER, DR AF WOLF, SS HYDE, TM WEINBERGER, DR TI MALFORMATIONS OF THE SEPTUM-PELLUCIDUM - 2 DISTINCTIVE CASES IN ASSOCIATION WITH SCHIZOPHRENIA SO JOURNAL OF PSYCHIATRY & NEUROSCIENCE LA English DT Note DE SCHIZOPHRENIA; SEPTUM-PELLUCIDUM; PSYCHOSIS ID CORPUS-CALLOSUM; ABNORMALITIES; CONNECTIONS; PSYCHOSIS AB Two patients with schizophrenia had markedly abnormal neuroimaging studies; one was found to have a large, cystic cavum vergae, while the other demonstrated complete agenesis of the septum pellucidum with a monoventricular system. The increased prevalence of developmental abnormalities of midline forebrain structures in patients with schizophrenia suggests that dysgenesis of these structures may be contributory to the neurobiology of schizophrenia and other psychotic disorders. RP WOLF, SS (reprint author), NIMH,CTR NEUROSCI,WASHINGTON,DC 20032, USA. NR 25 TC 14 Z9 14 U1 0 U2 0 PU CANADIAN PSYCHIATRIC ASSOC PI OTTAWA PA SUITE 200, 237 ARGYLE AVE, OTTAWA ON K2P 1B8, CANADA SN 1180-4882 J9 J PSYCHIATR NEUROSCI JI J. Psychiatry Neurosci. PD MAR PY 1994 VL 19 IS 2 BP 140 EP 144 PG 5 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA ND023 UT WOS:A1994ND02300008 PM 8204566 ER PT J AU ROTTEM, M COTCH, MF FAUCI, AS HOFFMAN, GS AF ROTTEM, M COTCH, MF FAUCI, AS HOFFMAN, GS TI FAMILIAL VASCULITIS - REPORT OF 2 FAMILIES SO JOURNAL OF RHEUMATOLOGY LA English DT Note DE VASCULITIS; POLYARTERITIS NODOSA; WEGENERS GRANULOMATOSIS; HLA ID HLA-ANTIGEN FREQUENCIES; WEGENERS GRANULOMATOSIS; POLYARTERITIS NODOSA; SIBLINGS AB We observed systematic vasculitis (polyarteritis nodosa and Wegener's granulomatosis) in several members of 2 different families. Our experience and a review of the literature suggests that genetic factors are important but not sufficient to express clinical features of these diseases. C1 NIAID,DIV MICROBIOL & INFECT DIS,CLIN INVEST LAB,EPIDEMIOL & BIOMETRY BRANCH,BETHESDA,MD. NIAID,IMMUNOREGULAT LAB,BETHESDA,MD 20892. OI Cotch, Mary Frances/0000-0002-2046-4350 FU Intramural NIH HHS [Z99 EY999999] NR 24 TC 17 Z9 17 U1 0 U2 0 PU J RHEUMATOL PUBL CO PI TORONTO PA 920 YONGE ST, SUITE 115, TORONTO ON M4W 3C7, CANADA SN 0315-162X J9 J RHEUMATOL JI J. Rheumatol. PD MAR PY 1994 VL 21 IS 3 BP 561 EP 563 PG 3 WC Rheumatology SC Rheumatology GA MZ505 UT WOS:A1994MZ50500032 PM 7911836 ER PT J AU CHANG, G ASTRACHAN, BM BRYANT, KJ AF CHANG, G ASTRACHAN, BM BRYANT, KJ TI EMERGENCY PHYSICIANS RATINGS OF ALCOHOLISM TREATERS SO JOURNAL OF SUBSTANCE ABUSE TREATMENT LA English DT Note DE ALCOHOLICS-ANONYMOUS; EMERGENCY PHYSICIANS; EMERGENCY ROOMS; OUTPATIENT TREATMENT AB The purpose of this study is to identify treaters whom emergency physicians perceive to offer effective treatment of alcoholism. A random sample of 2,500 emergency physicians received a questionnaire comparing attitudes toward Alcoholics Anonymous (AA) and professional alcoholism treaters. Physician agreement on the efficacy of alcoholism treaters was greatest for AA (87%), moderate for mental health professionals (including psychiatrists and psychologists, 55%) and least for physicians and surgeons (excluding psychiatrists, 23%; chi-square = 1, 024, p = .000000005, df = 2). Physician education about other alcoholism treaters may be necessary if all types of treatment are to be considered for the emergency room patient. C1 HARVARD UNIV,SCH MED,BOSTON,MA 02115. UNIV ILLINOIS,SCH MED,DEPT PSYCHIAT,CHICAGO,IL 60680. NIAAA,ROCKVILLE,MD 20852. RP CHANG, G (reprint author), BRIGHAM & WOMENS HOSP,DIV PSYCHIAT,75 FRANCAIS ST,BOSTON,MA 02115, USA. FU NCRR NIH HHS [RR05358] NR 25 TC 4 Z9 4 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0740-5472 J9 J SUBST ABUSE TREAT JI J. Subst. Abus. Treat. PD MAR-APR PY 1994 VL 11 IS 2 BP 131 EP 135 DI 10.1016/0740-5472(94)90030-2 PG 5 WC Psychology, Clinical; Substance Abuse SC Psychology; Substance Abuse GA NL650 UT WOS:A1994NL65000011 PM 8040916 ER PT J AU DEBELLIS, MD LEFTER, L TRICKETT, PK PUTNAM, FW AF DEBELLIS, MD LEFTER, L TRICKETT, PK PUTNAM, FW TI URINARY CATECHOLAMINE EXCRETION IN SEXUALLY ABUSED GIRLS SO JOURNAL OF THE AMERICAN ACADEMY OF CHILD AND ADOLESCENT PSYCHIATRY LA English DT Article DE URINARY CATECHOLAMINE AND METABOLITE CONCENTRATIONS; EPINEPHRINE; NOREPINEPHRINE; DOPAMINE; 3-METHOXY-4-HYDROXYPHENYLGLYCOL; METANEPHRINE; NORMETANEPHRINE; HOMOVANILLIC ACID; SEXUAL ABUSE IN GIRLS ID CORTICOTROPIN-RELEASING-FACTOR; STRESS DISORDER; RHESUS-MONKEYS; DEPRESSION; CHILDHOOD; BEHAVIOR; NOREPINEPHRINE; METABOLITES; SYMPTOMS; ACID AB Objective: The objective of this study was to examine urinary catecholamine excretion in a self-selected sample of sexually abused and demographically matched control girls recruited from a prospective, longitudinal study. Method: Twenty-four-hour urinary catecholamine and metabolite concentrations of epinephrine, norepinephrine, dopamine, 3-methoxy-4-hydroxyphenylglycol, metanephrine, normetanephrine, vanillylmandelic acid, 3,4-dihydroxyphenylacetic acid, and homovanillic acid were measured in 12 sexually abused and 9 control girls, aged 8 to 15 years. Psychiatric profiles also were obtained. Results: The abused subjects excreted significantly greater amounts of metanephrine, vanillylmandelic acid, homovanillic acid, and total catecholamine synthesis as measured by the sum of epinephrine, norepinephrine, dopamine, and their metabolites compared to values from control subjects. When the means of all significant biochemical measures were adjusted by the covariate effect of height, only homovanillic acid and group interaction remained significant. There were positive trends toward significantly higher urinary excretion of metanephrine, vanillylmandelic acid, and total catecholamine synthesis. Sexually abused girls also had a greater incidence of suicidal ideation, suicide attempts, and dysthymia than control girls. Conclusions: These findings support the idea that sexually abused girls show evidence of higher catecholamine functional activity compared with controls. The clinical significance of these findings is their similarity to the psychobiology of both post-traumatic stress disorder and major depressive disorder. Results from this pilot study may be of value in understanding the mechanisms of depressive and anxiety disorders and in the clinical treatment of maltreated children. C1 NIMH,CLIN NEUROENDOCRINOL BRANCH,BETHESDA,MD 20892. UNIV SO CALIF,DEPT PSYCHOL,LOS ANGELES,CA 90089. NIMH,DEV PSYCHOL LAB,BETHESDA,MD 20892. RP DEBELLIS, MD (reprint author), UNIV PITTSBURGH,WESTERN PSYCHIAT INST & CLIN,DEPT CHILD & ADOLESCENT PSYCHIAT,3811 OHARA ST,PITTSBURGH,PA 15213, USA. NR 43 TC 137 Z9 139 U1 0 U2 4 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-APR PY 1994 VL 33 IS 3 BP 320 EP 327 DI 10.1097/00004583-199403000-00004 PG 8 WC Psychology, Developmental; Pediatrics; Psychiatry SC Psychology; Pediatrics; Psychiatry GA MY114 UT WOS:A1994MY11400004 PM 8169176 ER PT J AU PERRONEFILARDI, P BACHARACH, SL DILSIZIAN, V MARINNETO, JA MAUREA, S ARRIGHI, JA BONOW, RO AF PERRONEFILARDI, P BACHARACH, SL DILSIZIAN, V MARINNETO, JA MAUREA, S ARRIGHI, JA BONOW, RO TI CLINICAL-SIGNIFICANCE OF REDUCED REGIONAL MYOCARDIAL GLUCOSE-UPTAKE IN REGIONS WITH NORMAL BLOOD-FLOW IN PATIENTS WITH CHRONIC CORONARY-ARTERY DISEASE SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Article ID POSITRON-EMISSION TOMOGRAPHY; LEFT-VENTRICULAR DYSFUNCTION; WALL-MOTION ABNORMALITIES; VIABLE MYOCARDIUM; COMPUTED-TOMOGRAPHY; HEART-DISEASE; PERFUSION; THALLIUM; REINJECTION; METABOLISM AB Objectives. The objective of this study was to assess the clinical significance of reduced regional fluorine-18 F-18- fluorodeoxyglucose uptake with normal flow in patients with chronic coronary artery disease. Background. In patients with ischemic left ventricular dysfunction, F-18-fluorodeoxyglucose uptake may be reduced in some myocardial regions despite normal how. The significance of this finding is unclear and has not been investigated systematically. Methods. Twenty-three patients with coronary artery disease and impaired ventricular function (mean ejection fraction [+/- SD] 28 +/- 10%) underwent positron emission tomography with F-18-fluorodeoxyglucose and oxygen 15-labeled water at rest, exercise thallium-201 tomographic imaging with rest reinjection and gated magnetic resonance imaging to measure end-diastolic wall thickness and systolic wall thickening. Results. Of 168 regions with normal flow (greater than or equal to 0.7 ml/g per min), 125 (74%) had normal F-18-fluorodeoxyglucose uptake (98 +/- 1O%), and the remaining 43 (26%) showed moderately reduced F-18-fluorodeoxyglucose uptake (69 +/- 8%). Systolic wall thickening was absent at rest in 14% of regions with normal F-18-fluorodeoxyglucose uptake compared with 32% of regions with reduced F-18-fluorodeoxyglucose uptake (p < 0.01). Reversible thallium abnormalities were observed in 45 (36%) of 125 regions with normal F-18-fluorodeoxyglucose uptake compared with 27 (63%) of 43 regions with reduced F-18-fluorodeoxyglucose uptake (p < 0.01). This difference was accounted for by a higher proportion of partially reversible defects in regions with reduced F-18-fluorodeoxyglucose uptake compared with regions with normal F-18-fluorodeoxyglucose uptake (42% vs. 18%, respectively, p < 0.01). Conclusions. Thus, regions with moderately reduced F-18-fluorodeoxyglucose uptake with normal flow occur commonly in patients with ischemic left ventricular dysfunction. The majority of these regions show impaired systolic function at rest and exercise induced thallium abnormalities that are only partially reversible. These observations suggest that such regions represent an admixture of fibrotic and reversibly ischemic myocardium. C1 NHLBI,CARDIOL BRANCH,BETHESDA,MD 20892. NIH,CTR CLIN,DIV NUCL MED,BETHESDA,MD 20892. NR 31 TC 44 Z9 44 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 1994 VL 23 IS 3 BP 608 EP 616 PG 9 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA PH369 UT WOS:A1994PH36900010 PM 8113542 ER PT J AU SALIVE, ME GURALNIK, J GLYNN, RJ CHRISTEN, W WALLACE, RB OSTFELD, AM AF SALIVE, ME GURALNIK, J GLYNN, RJ CHRISTEN, W WALLACE, RB OSTFELD, AM TI ASSOCIATION OF VISUAL IMPAIRMENT WITH MOBILITY AND PHYSICAL FUNCTION SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Article ID ELDERLY PEOPLE; HIP FRACTURE; VISION; DISABILITY; RISK; POPULATION; COMMUNITY; DECLINE; IMPACT; LIFE AB Objective: To examine the association of distant vision and physical function in the population of older adults. Design: Cross-sectional and cohort study. Participants: 5143 older residents of three communities (Established Populations for the Epidemiologic Studies of the Elderly) who were interviewed in 1988-89, including residents of two communities who were re-interviewed 15 months later (n = 3133, 97% of those eligible). Measures: Visual acuity screening, self-reported activities of daily living and mobility, and objective physical performance measures of balance, walking, and rising from a chair. Results: Limitations in mobility, activities of daily living, and physical performance were associated with worse visual function. In prospective analyses controlling for potential confounders, participants with severe visual impairment had 3-fold higher odds of incident mobility and activity of daily living limitations than those with acuity of 20/40 or better (P < 0.001). In prospective analyses investigating the relationship of vision with improvement in function, those with poor vision were about half as likely to improve as those with better acuity, but this relationship was only statistically significant for improvement in mobility limitations. Conclusions: Distant visual function appears to play an important role in physical function, particularly for mobility. An intervention to improve vision in at-risk elders might preserve function and prevent disability; this warrants further investigation. C1 HARVARD UNIV,DEPT MED,CHANNING LAB,BOSTON,MA. UNIV IOWA,DEPT PREVENT MED & ENVIRONM HLTH,IOWA CITY,IA 52242. YALE UNIV,SCH MED,DEPT EPIDEMIOL & PUBL HLTH,NEW HAVEN,CT 06510. RP SALIVE, ME (reprint author), NIA,EPIDEMIOL DEMOG & BIOMETRY PROGRAM,GATEWAY BLDG,7201 WISCONSIN AVE,SUITE 3C309,BETHESDA,MD 20892, USA. FU NIA NIH HHS [N01-AG-02106, N01-AG-02105, N01-AG-02107] NR 28 TC 182 Z9 186 U1 2 U2 9 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 1994 VL 42 IS 3 BP 287 EP 292 PG 6 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA NA038 UT WOS:A1994NA03800009 PM 8120313 ER PT J AU BURGIO, LD MCCORMICK, KA SCHEVE, AS ENGEL, BT HAWKINS, A LEAHY, E AF BURGIO, LD MCCORMICK, KA SCHEVE, AS ENGEL, BT HAWKINS, A LEAHY, E TI THE EFFECTS OF CHANGING PROMPTED VOIDING SCHEDULES IN THE TREATMENT OF INCONTINENCE IN NURSING-HOME RESIDENTS SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Article ID URINARY-INCONTINENCE; MANAGEMENT; STAFF AB Objective: To determine the effects of different prompted voiding schedules on urinary incontinence on a continence unit (CU) and the maintenance of benefits on normal nursing units. Design: Multiphase study with both intra- and inter-subject comparisons. Participants: Subjects were 41 consenting incontinent nursing home residents. Based on clinical criteria, subjects were assigned to one of four treatment groups that varied as to the schedule of prompted voiding received. Measurement: The study used chart review, Katz ADL, and MMSE. Urologic status, self-initiated toileting, urine volumes voided, and incontinence assessed by pad/pants checks were measured by research nurses. Baseline pad check data were collected on residents' normal nursing units. Residents were transferred to the CU where baseline measurement was repeated, and the effects of different prompted voiding schedules were then assessed. Indigenous staff were trained to use prompted voiding, and nurse supervisors were instructed in special procedures for enhancing maintenance of the intervention. Residents were returned to their normal units and the maintenance of improvements in continence status was assessed at 2 weeks and 3 months post-CU discharge. Results: One of the four groups showed significant improvement on the CU in response to the 2-hour schedule; two groups improved on the less intensive 3-hour schedule (P < 0.05). Two groups maintained this improvement on their normal nursing units (P < 0.05); one group showed a nonsignificant trend toward improvement. Self-initiated toileting decreased (P < 0.05) and volume voids in an appropriate receptacle increased (P < 0.05) during training. Conclusions: Prompted voiding is an effective treatment for urinary incontinence, and a less intensive S-hour schedule may be superior to the standard 2-hour schedule for some residents. These improvements in dryness can be maintained by normal nursing home staff if formal staff management procedures are utilized by nurse supervisors. C1 NIA,GERONTOL RES CTR,BEHAV SCI LAB,BALTIMORE,MD 21224. FRANCIS SCOTT KEY MED CTR,BALTIMORE,MD. UNIV CINCINNATI,CINCINNATI,OH. CTR AGING,BIRMINGHAM,AL. RP BURGIO, LD (reprint author), UNIV ALABAMA,SCH MED,BEHAV SCI SECT,COMMUNITY HLTH SERV BLDG,933 S 19TH ST,STE 219,BIRMINGHAM,AL 35294, USA. FU NIA NIH HHS [NIA 1K01AG00491] NR 17 TC 30 Z9 30 U1 0 U2 2 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 1994 VL 42 IS 3 BP 315 EP 320 PG 6 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA NA038 UT WOS:A1994NA03800014 PM 8120318 ER PT J AU PARK, T BROWN, MB AF PARK, T BROWN, MB TI MODELS FOR CATEGORICAL-DATA WITH NONIGNORABLE NONRESPONSE SO JOURNAL OF THE AMERICAN STATISTICAL ASSOCIATION LA English DT Article DE BAYESIAN ESTIMATOR; EM ALGORITHM; LOG-LINEAR MODEL; MAXIMUM LIKELIHOOD ESTIMATOR; NONIGNORABLE MISSING DATA; PRIOR DISTRIBUTION; SMOOTHING ID MAXIMUM-LIKELIHOOD ESTIMATION; CONTINGENCY-TABLES; MISSING DATA; CLASSIFIED DATA; REGRESSION; INFERENCE AB When categorical outcomes are subject to nonignorable nonresponse, log-linear models may be used to adjust for the nonresponse. The models are fitted to the data in an augmented frequency table in which one index corresponds to whether or not the subject is a respondent. The likelihood function is maximized over pseudo-observed cell frequencies with respect to this log-linear model using an EM algorithm. Each E step of the EM algorithm determines the pseudo-observed cell frequencies, and the M step yields the maximum likelihood estimators (MLE's) of these pseudo-observed cell frequencies. This approach may produce boundary estimates for the expected cell frequencies of the nonrespondents. In these cases the estimators of the log-linear model parameters are not uniquely determined and may be unstable. Following the approach of Clogg et al., we propose a Bayesian method that uses smoothing constants to adjust the pseudo-observed cell frequencies so that the solution is not on the boundary. The role of smoothing constants is similar to that of the flattening constant k in ridge regression: the use of k is intended to overcome ill-conditioned situations where correlations between the various predictors in the regression model produce unstable parameter estimates. The Bayesian estimation procedure is illustrated using data from a cross-sectional study of obesity in school-age children. Through a simulation study, we show that when fitting nonignorable nonresponse models, the mean squared errors of the expected cell frequencies obtained by the Bayesian procedure can be much smaller than those of the MLE's. C1 UNIV MICHIGAN,DEPT BIOSTAT,ANN ARBOR,MI 48109. NICHHD,BIOMETRY & MATH STAT BRANCH,BETHESDA,MD 20892. RP PARK, T (reprint author), HANKUK UNIV FOREIGN STUDIES,DEPT STAT,KYONGGI DO 449791,SOUTH KOREA. NR 28 TC 51 Z9 52 U1 1 U2 2 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 1994 VL 89 IS 425 BP 44 EP 52 DI 10.2307/2291199 PG 9 WC Statistics & Probability SC Mathematics GA MY546 UT WOS:A1994MY54600005 ER PT J AU ANDERSON, DE AF ANDERSON, DE TI BEHAVIOR ANALYSIS AND THE SEARCH FOR THE ORIGINS OF HYPERTENSION SO JOURNAL OF THE EXPERIMENTAL ANALYSIS OF BEHAVIOR LA English DT Article DE AVOIDANCE CONDITIONING; BLOOD PRESSURE; HYPERCAPNIA; HYPERTENSION; PREAVOIDANCE; RESPIRATION; SODIUM; DOGS ID HIGH SODIUM-INTAKE; BLOOD-PRESSURE; VENTILATION; BABOONS; STRESS; HUMANS; SLEEP AB Hypertension is a disorder of sodium regulation that develops over time in a context of the interactions of the individual with the environment. Experimental hypertension can be induced in laboratory animals and normotensive humans via increases in sodium intake under conditions of aversive behavioral control. Readiness for avoidance contingencies includes a breathing pattern characterized by subnormal rate and normal tidal volume. Studies with humans have shown that this inhibitory breathing pattern is associated with increased plasma acidity, increased renal sodium reabsorption, increased secretion of digitalis-like hormones that inhibit sodium-pump activity, and increased vasoconstriction and blood pressure. Behavioral research is needed that defines the necessary and sufficient conditions for inhibitory breathing and its role in the development of hypertension. RP ANDERSON, DE (reprint author), NIA,GERONTOL RES CTR,BEHAV SCI LAB,494 EASTERN AVE,BALTIMORE,MD 21224, USA. NR 47 TC 5 Z9 5 U1 0 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 1994 VL 61 IS 2 BP 255 EP 261 DI 10.1901/jeab.1994.61-255 PG 7 WC Psychology, Biological; Behavioral Sciences; Psychology, Experimental SC Psychology; Behavioral Sciences GA NB467 UT WOS:A1994NB46700012 PM 8169574 ER PT J AU CHIEN, S OELTGEN, PR DIANA, JN SALLEY, RK SU, TP AF CHIEN, S OELTGEN, PR DIANA, JN SALLEY, RK SU, TP TI EXTENSION OF TISSUE SURVIVAL-TIME IN MULTIORGAN BLOCK PREPARATION WITH A DELTA-OPIOID DADLE ([D-ALA(2),D-LEU(5)]-ENKEPHALIN) SO JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY LA English DT Letter ID HIBERNATION INDUCTION TRIGGER C1 UNIV KENTUCKY,MED CTR,DEPT PATHOL,LEXINGTON,KY 40536. UNIV KENTUCKY,MED CTR,DEPT PHYSIOL & BIOPHYS,LEXINGTON,KY 40536. NIDA,ADDICT RES CTR,ALCOHOL DRUG ABUSE & MENTAL HLTH ADM,BALTIMORE,MD 21224. RP CHIEN, S (reprint author), UNIV KENTUCKY,MED CTR,DEPT SURG,LEXINGTON,KY 40536, USA. NR 6 TC 74 Z9 80 U1 0 U2 1 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 SN 0022-5223 J9 J THORAC CARDIOV SUR JI J. Thorac. Cardiovasc. Surg. PD MAR PY 1994 VL 107 IS 3 BP 964 EP 967 PG 4 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA NA898 UT WOS:A1994NA89800051 PM 8127138 ER PT J AU HENNEMAN, JR FOX, SD LUBET, RA WARD, JM NIMS, RW AF HENNEMAN, JR FOX, SD LUBET, RA WARD, JM NIMS, RW TI INDUCTION OF CYTOCHROME-P-450 IN SIGMODON HISPIDUS (COTTON RATS) EXPOSED TO DIETARY AROCLOR-1254 SO JOURNAL OF TOXICOLOGY AND ENVIRONMENTAL HEALTH LA English DT Article ID ENVIRONMENTAL CONTAMINATION; ALKOXYRESORUFIN METABOLISM; POLYCHLORINATED-BIPHENYLS; O-DEALKYLATION; INDUCERS; 3-METHYLCHOLANTHRENE; LIVER; ASSAY; XENOBIOTICS; INDICATOR AB The induction of immunoreactive cytochrome P-450 protein and associated catalytic activities in 10-wk-old male and female Sigmodon hispidus (cotton rats) exposed for 2 wk to low dietary levels of Aroclor 1254 (0.33, 1.0, 3.3, 10, and 33 ppm), or the prototype P-450 inducers phenobarbital, DDT, clotrimazole, and beta-naphthoflavone was examined. Ethoxy(ETR), methoxy- (MTR), pentoxy- (PTR), and benzyloxyresorufin (BZR) O-dealkylation activities were significantly increased at 0.33 ppm Aroclor for males and 1.0 ppm for females, C1 NCI,FREDERICK CANC RES & DEV CTR,PRI DYNCORP,CHEM SYNTHESIS & ANAL LAB,FREDERICK,MD 21702. NCI,DIV CANC PREVENT & CONTROL,ROCKVILLE,MD. NCI,OFF LAB ANIM SCI,VET & TUMOR PATHOL SECT,FREDERICK,MD. NCI,FREDERICK CANC RES & DEV CTR,COMPARAT CARCINOGENESIS LAB,FREDERICK,MD 21702. RP HENNEMAN, JR (reprint author), NCI,FREDERICK CANC RES & DEV CTR,PRI DYNCORP,BIOL CARCINOGENESIS & DEV PROGRAM,POB 8,BLDG 538,FREDERICK,MD 21702, USA. NR 33 TC 13 Z9 13 U1 0 U2 0 PU TAYLOR & FRANCIS PI BRISTOL PA 1900 FROST ROAD, SUITE 101, BRISTOL, PA 19007-1598 SN 0098-4108 J9 J TOXICOL ENV HEALTH JI J. Toxicol. Environ. Health PD MAR PY 1994 VL 41 IS 3 BP 369 EP 386 PG 18 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA NB944 UT WOS:A1994NB94400009 PM 8126756 ER PT J AU ZBAR, B TORY, K MERINO, M SCHMIDT, L GLENN, G CHOYKE, P WALTHER, MM LERMAN, M LINEHAN, WM AF ZBAR, B TORY, K MERINO, M SCHMIDT, L GLENN, G CHOYKE, P WALTHER, MM LERMAN, M LINEHAN, WM TI HEREDITARY PAPILLARY RENAL-CELL CARCINOMA SO JOURNAL OF UROLOGY LA English DT Article DE CARCINOMA, RENAL CELL; KIDNEY NEOPLASMS; HEREDITARY DISEASES ID VONHIPPEL-LINDAU DISEASE; SHORT ARM; CHROMOSOME-3; REGION; DELETION; TUMORS AB We describe a 3 generation family with members affected with papillary renal cell carcinoma, an uncommon histological type of renal cell carcinoma. Multiple tumors of varying size were present in both kidneys of affected family members. The disorder was not linked to polymorphic markers on chromosome 3p and there was no loss of heterozygosity at loci on 3p in renal tumors. The results suggest the presence of a renal cell carcinoma gene not located on 3p that predisposes to renal cell carcinoma with a distinct histological appearance. The inherited disorder in this family appears to be different from recognized hereditary cancer syndromes. C1 DYNACORP INC,PROGRAM RESOURCES INC,FREDERICK,MD. NIH,CANC DIAG BRANCH,PATHOL LAB,SURG BRANCH,IMMUNOBIOL LAB,BETHESDA,MD. NIH,DEPT DIAGNOST RADIOL,BETHESDA,MD. NR 29 TC 147 Z9 149 U1 1 U2 2 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0022-5347 J9 J UROLOGY JI J. Urol. PD MAR PY 1994 VL 151 IS 3 BP 561 EP 566 PG 6 WC Urology & Nephrology SC Urology & Nephrology GA MW725 UT WOS:A1994MW72500002 PM 8308957 ER PT J AU LOSSEF, SV LUTZ, RJ MUNDORF, J BARTH, KH AF LOSSEF, SV LUTZ, RJ MUNDORF, J BARTH, KH TI COMPARISON OF MECHANICAL DEFORMATION PROPERTIES OF METALLIC STENTS WITH USE OF STRESS-STRAIN ANALYSIS SO JOURNAL OF VASCULAR AND INTERVENTIONAL RADIOLOGY LA English DT Article DE STENTS AND PROSTHESES AB PURPOSE: Elastic and plastic deformation properties of the Wallstent, Palmaz stent, and Strecker stent were evaluated quantitatively with an in vitro model simulating forces exerted by an eccentric lesion. MATERIALS AND METHODS: A miniaturized compression testing device was constructed. Stress-strain graphs were obtained for each stent, and the elastic moduli and yield points were calculated. RESULTS: There is a 21-fold range in the elastic modulus among the Wallstent, Palmaz stent, and Strecker stents. The Palmaz stent was the only device to exhibit permanent plastic deformation. The 10-mm Palmaz stent will undergo 15% focal eccentric narrowing at 0.75 atm of pressure; the ''standard braid'' and ''less shortening braid'' 10-mm Wallstents at 0.55 and 0.25 atm, respectively, and the 10-mm tantalum Strecker stent at 0.08 atm. Overlapping of stents doubles the stiffness of the Wallstent and the Strecker stent and doubles the yield point of the Palmaz stent. The 4-9-mm Palmaz stent is 30% more resistant to deformation than the larger 8-12-mm version when expanded to identical 8-mm diameters CONCLUSIONS: The ''standard braid'' version of the 10-mm Wallstent provides 2.3-fold additional strength for resistant stenoses compared with the ''less shortening braid.'' Overlapping or nesting of stents may permit full expansion should there be incomplete expansion or recoil of a single stent. The 4-9-mm Palmaz stent is preferable from the standpoint of allowing the use of a smaller (7-F instead of 9-F) introducer sheath and also for providing superior resistance to deformation. A purely elastic stent such as the Wallstent is preferable in locations where permanent plastic deformation may occur, such as the thoracic outlet. C1 NIH,BIOMECH ENGN BRANCH,BETHESDA,MD 20892. RP LOSSEF, SV (reprint author), GEORGETOWN UNIV HOSP,DEPT RADIOL,3800 RESERVOIR RD NW,WASHINGTON,DC 20007, USA. NR 6 TC 76 Z9 75 U1 2 U2 14 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 1051-0443 J9 J VASC INTERV RADIOL JI J. Vasc. Interv. Radiol. PD MAR-APR PY 1994 VL 5 IS 2 BP 341 EP 349 DI 10.1016/S1051-0443(94)71499-8 PG 9 WC Radiology, Nuclear Medicine & Medical Imaging; Peripheral Vascular Disease SC Radiology, Nuclear Medicine & Medical Imaging; Cardiovascular System & Cardiology GA PB251 UT WOS:A1994PB25100013 PM 8186605 ER PT J AU JUSTICE, MJ MORSE, HC JENKINS, NA COPELAND, NG AF JUSTICE, MJ MORSE, HC JENKINS, NA COPELAND, NG TI IDENTIFICATION OF EVI-3, A NOVEL COMMON SITE OF RETROVIRAL INTEGRATION IN MOUSE AKXD B-CELL LYMPHOMAS SO JOURNAL OF VIROLOGY LA English DT Article ID GENETIC-LINKAGE MAP; LEUKEMIA-VIRUS DNA; VIRAL INTEGRATION; CPG ISLANDS; EXPRESSION; ONCOGENES; STRAINS; ACTIVATION; GENOMES; LINEAGE AB We have identified a novel common site of ecotropic viral integration called ecotropic viral integration site 3 (Evi-3) in B-cell lineage lymphomas of the AKXD recombinant inbred strains of mice. A number of virally induced pre-B-, B-, myeloid, and T-cell lymphomas were screened for viral rearrangements at Evi-3; rearrangements were found in pre-B- and B-cell lymphomas but not in other hematopoietic tumors. Genetic mapping studies localized Evi-3 to mouse chromosome 18, distinct from proto-oncogene and common viral integration loci identified previously in the mouse. Each proviral integration at Evi-3 is contained within a 200-bp region that lies inside a CpG island. All but one of the proviruses have integrated in the same 5'-to-3' transcriptional orientation. Transcripts from Evi-3 are expressed in a developmentally regulated manner in B cells. Taken together, these data suggest that Evi-3 represents a novel proto-oncogene involved in mouse B-cell lymphomas. C1 NIAID,IMMUNOPATHOL LAB,BETHESDA,MD 20892. NCI,FREDERICK CANC RES & DEV CTR,ABL BASIC RES PROGRAM,MAMMALIAN GENET LAB,FREDERICK,MD 21702. RP JUSTICE, MJ (reprint author), KANSAS STATE UNIV AGR & APPL SCI,DIV BIOL,312 ACKERT HALL,MANHATTAN,KS 66506, USA. OI Morse, Herbert/0000-0002-9331-3705 FU NCI NIH HHS [5F32CA08853-03, N01-CO-74101]; NIAID NIH HHS [N01-AI-72622] NR 50 TC 34 Z9 34 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0022-538X J9 J VIROL JI J. Virol. PD MAR PY 1994 VL 68 IS 3 BP 1293 EP 1300 PG 8 WC Virology SC Virology GA MY596 UT WOS:A1994MY59600004 PM 8107195 ER PT J AU ZHANG, YF AHN, BY MOSS, B AF ZHANG, YF AHN, BY MOSS, B TI TARGETING OF A MULTICOMPONENT TRANSCRIPTION APPARATUS INTO ASSEMBLING VACCINIA VIRUS-PARTICLES REQUIRES RAP94, AN RNA POLYMERASE-ASSOCIATED PROTEIN SO JOURNAL OF VIROLOGY LA English DT Article ID NUCLEOSIDE TRIPHOSPHATE PHOSPHOHYDROLASES; TEMPERATURE-SENSITIVE MUTANTS; ESCHERICHIA-COLI; DOMINANT SELECTION; POLY(A) POLYMERASE; MOLECULAR-CLONING; DNA TOPOISOMERASE; CAPPING ENZYME; LAC REPRESSOR; EARLY GENES AB When expression of the vaccinia virus gene encoding RAP94 (a protein that is associated with the viral multisubunit RNA polymerase and confers transcriptional specificity for early promoters) was repressed, the infectious virus yield was reduced by more than 99%. Nevertheless, intermediate- and late-stage viral gene expression and formation of ultrastructurally mature, membrane-enveloped virions occurred under the nonpermissive conditions. The RAP94-deficient particles contained the viral genome, structural proteins, early transcription factor, and certain enzymes but, unlike normal virions, had low or undetectable amounts of the viral RNA polymerase, capping enzyme/termination factor, poly(A) polymerase, DNA-dependent ATPase, RNA helicase, and topoisomerase. The presence of these viral enzymes in the cytoplasm indicated that RAP94 is required for targeting a complex of functionally related proteins involved in the biosynthesis of mRNA. C1 NIAID,VIRAL DIS LAB,BETHESDA,MD 20892. NR 59 TC 51 Z9 52 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 1994 VL 68 IS 3 BP 1360 EP 1370 PG 11 WC Virology SC Virology GA MY596 UT WOS:A1994MY59600012 PM 8107201 ER PT J AU SHIMIZU, YK HIJIKATA, M IWAMOTO, A ALTER, HJ PURCELL, RH YOSHIKURA, H AF SHIMIZU, YK HIJIKATA, M IWAMOTO, A ALTER, HJ PURCELL, RH YOSHIKURA, H TI NEUTRALIZING ANTIBODIES AGAINST HEPATITIS-C VIRUS AND THE EMERGENCE OF NEUTRALIZATION ESCAPE MUTANT VIRUSES SO JOURNAL OF VIROLOGY LA English DT Article ID NON-B HEPATITIS; NON-A; HYPERVARIABLE REGIONS; ENVELOPE; GLYCOPROTEIN; REPLICATION; SEQUENCE AB We developed an in vitro assay for antibodies to hepatitis C virus (HCV) that bind to virions and prevent initiation of the replication cycle in susceptible cells in vitro. These antibodies therefore appear to be capable of neutralizing the virus. Using this assay and a standard inoculum of HCV of known infectivity, we have measured the antibody in serial serum samples obtained from the same chronically infected patient over 14 years following onset of his hepatitis. Such antibody was found in sera collected within 5 years of onset of hepatitis but not in later sera. In double immunoprecipitation experiments with anti-human immunoglobulin, the same sera that contained neutralizing antibody were found to contain antibody that bound to HCV to form antigen-antibody complexes immunoprecipitable with anti-human globulin. Similarly, plasma collected from this patient in 1990, 13 gears after onset of hepatitis, and which contained HCV that had diverged genetically from the 1977 strain, did not contain antibody capable of neutralizing either the 1977 or the 1990 strain of HCV. However, plasma collected a gear later (1991, 14 years after onset of hepatitis) contained neutralizing antibody to the 1990, but not the 1977, strain of HCV These results suggest that HCV does induce antivirion antibody, as measured by blocking of initiation of the replication cycle of virus in cells and by the formation of immunoprecipitable antigen-antibody complexes but that these antibodies are isolate specific and change over time. Thus, these antivirion antibodies function as neutralizing antibodies and are probably in vitro correlates of the attempt of the host to contain the emergence of neutralization-resistant variants of HCV over time. C1 NATL INST HLTH,DEPT INFECT DIS & VACCINE CONTROL,TOKYO,TOKYO 208,JAPAN. NIH,DEPT TRANSFUS MED,BETHESDA,MD 20892. NIH,INFECT DIS LAB,BETHESDA,MD 20892. RP SHIMIZU, YK (reprint author), UNIV TOKYO,FAC MED,DEPT BACTERIOL,BUNKYO KU,7-3-1 HONGO,TOKYO,TOKYO 113,JAPAN. NR 19 TC 345 Z9 359 U1 0 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0022-538X J9 J VIROL JI J. Virol. PD MAR PY 1994 VL 68 IS 3 BP 1494 EP 1500 PG 7 WC Virology SC Virology GA MY596 UT WOS:A1994MY59600027 PM 8107212 ER PT J AU PALUMBO, GJ BULLER, RM GLASGOW, WC AF PALUMBO, GJ BULLER, RM GLASGOW, WC TI MULTIGENIC EVASION OF INFLAMMATION BY POXVIRUSES SO JOURNAL OF VIROLOGY LA English DT Article ID VACCINIA VIRUS; COWPOX VIRUS; INFLUENZA-VIRUS; PROTEIN-KINASE; MYXOMA VIRUS; RECEPTOR; VIRULENCE; INHIBITION; INFECTION; GENE AB Analyses of different cowpox virus (Brighten Red strain [CPV-BR]) mutants indicate that there is a minimum of three genes encoded by CPV-BR that are nonessential for virus replication in tissue culture but are involved in inhibiting the generation of an inflammatory response in the chicken embryo chorioallantoic membrane (CAM) model. The CPV-BR-encoded anti-inflammatory genes include the gene encoding the 38-kDa protein (also called 38K, crmA, SPI-2, or VV-WR-ORF-B13R), a tumor necrosis factor receptor homolog, and an unidentified gene that maps to the right end of the CPV genome. The kinetics of triggering of an inflammatory response at the site of virus infection as well as the magnitude of the response is dependent on the virus-encoded inhibitor that is deleted. Virus yields recovered from pocks decreased in proportion to the magnitude of the inflammatory response. The deletion of these identified inhibitors of inflammation was associated,vith attenuation of the mutant viruses in mice. These data confirm the existence of multiple poxvirus-encoded host defense modifiers whose function is to block the generation of an inflammatory response at the site of virus infection, which allows enhanced virus replication and potentially facilitates virus transmission. C1 NIEHS,MOLEC BIOPHYS LAB,RES TRIANGLE PK,NC 27709. RP PALUMBO, GJ (reprint author), NIAID,VIRAL DIS LAB,BLDG 4,ROOM 137,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 58 TC 45 Z9 45 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0022-538X J9 J VIROL JI J. Virol. PD MAR PY 1994 VL 68 IS 3 BP 1737 EP 1749 PG 13 WC Virology SC Virology GA MY596 UT WOS:A1994MY59600056 PM 8107235 ER PT J AU REIN, A MIRRO, J HAYNES, JG ERNST, SM NAGASHIMA, K AF REIN, A MIRRO, J HAYNES, JG ERNST, SM NAGASHIMA, K TI FUNCTION OF THE CYTOPLASMIC DOMAIN OF A RETROVIRAL TRANSMEMBRANE PROTEIN - P15E-P2E CLEAVAGE ACTIVATES THE MEMBRANE-FUSION CAPABILITY OF THE MURINE LEUKEMIA-VIRUS ENV PROTEIN SO JOURNAL OF VIROLOGY LA English DT Article ID SIMIAN IMMUNODEFICIENCY VIRUS; ENVELOPE GLYCOPROTEIN; OLIGOMERIC STRUCTURE; INFECTIVITY; SEQUENCE; MATURATION; CELLS; GAG; SEPARATION; MUTATIONS AB In the murine leukemia viruses (MuLVs), the Env complex is initially cleaved by a cellular protease into gp70(SU) and pre15E(TM). After the virus particle is released from the cell, the C-terminal 16 residues are removed from the cytoplasmic domain of pre15E by the viral protease, yielding the mature p15E(TM) and p2E. We have investigated the function of this cleavage by generating a Moloney MuLV mutant, termed p2E(-), in which the Env coding region terminates at the cleavage site. This mutant synthesizes only the truncated, mature form of TM rather than its extended precursor. When cells expressing this truncated Env protein are cocultivated with NIH 3T3 cells, they induce rapid cell-cell fusion. Thus, the truncated form, which is normally found in virions but not in virus-producing cells, is capable of causing membrane fusion. We conclude that the 16-residue p2E tail inhibits this activity of Env until the virus has left the cell. p2E(-) virions were found to be infectious, though with a lower specific infectivity than that of the wild type, showing that p2E does not play an essential role in the process of infection. Fusion was also observed with a chimeric p2E(-) virus in which gp70(SU) and nearly all of p15E(TM) are derived from amphotropic, rather than Moloney, MuLV. In a second mutant, an amino acid at the cleavage site was changed. The pre15E protein in this mutant is not cleaved. While the mutant Env complex is incorporated into virions, these particles have a very low specific infectivity. This result Suggests that the cleavage event is essential for infectivity, in agreement with the idea that removal of p2E activates the membrane fusion capability of the Env complex. C1 NCI,FREDERICK CANC RES & DEV CTR,PROGRAM RESOURCES INC DYNCORP,CELL & MOLEC STRUCT LAB,FREDERICK,MD 21702. RP REIN, A (reprint author), NCI,FREDERICK CANC RES & DEV CTR,ABL BASIC RES PROGRAM,MOLEC VIROL & CARCINOGENESIS LAB,POB B,FREDERICK,MD 21702, USA. FU NCI NIH HHS [N01-CO-74101, N01-CO-74102] NR 50 TC 212 Z9 212 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 1994 VL 68 IS 3 BP 1773 EP 1781 PG 9 WC Virology SC Virology GA MY596 UT WOS:A1994MY59600060 PM 8107239 ER PT J AU SPOUGE, JL AF SPOUGE, JL TI VIRAL MULTIPLICITY OF ATTACHMENT AND ITS IMPLICATIONS FOR HUMAN-IMMUNODEFICIENCY-VIRUS THERAPIES SO JOURNAL OF VIROLOGY LA English DT Article ID RECOMBINANT SOLUBLE CD4; HUMAN MONOCLONAL-ANTIBODY; ENVELOPE GLYCOPROTEIN; CD4-BINDING SITE; CELL RECEPTORS; LOWER AFFINITY; HIV-INFECTION; GP120 BINDING; NEUTRALIZATION; TYPE-1 AB The multiplicity of attachment (MOA) of a virion in any particular time interval is the average number of cellular attachment opportunities that must be blocked to keep the virion in suspension. MOA is usually proportional to incubation time and cell concentration. Low MOA (like low multiplicity of infection) is required for reproducible assay of adsorptive blockers, and high MOA by itself can produce spurious synergies between adsorptive blockers, e.g., soluble CD4 (sCD4) and some antibodies. Poliovirus and human immunodeficiency virus (HIV) data show that viral neutralization conforms quantitatively to MOA and kinetic theory over large ranges of incubation times and target cell concentrations. Extrapolating sCD4 data beyond conditions achievable in vitro to those in vivo predicts that sCD4 concentrations above the strain-specific sCD4-gp120 dissociation constant are required to block lymphoid HIV significantly, in at least semiquantitative agreement with clinical results. The extrapolation is applicable to humoral neutralization data as well. MOA analysis also indicates that although completely stopping the attachment of individual virions to cells may still be an effective therapeutic strategy against established HIV infection, merely retarding attachment probably is not. The concept of MOA holds great promise for improving the therapeutic relevance of in vitro data and can be applied to any infectious agent, to many processes that impair or enhance infection steps, and to many assay end points, not just infection. RP SPOUGE, JL (reprint author), NATL LIB MED, NATL CTR BIOTECHNOL INFORMAT, BLDG 38A, ROOM 8S806, BETHESDA, MD 20894 USA. NR 57 TC 19 Z9 19 U1 2 U2 5 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0022-538X J9 J VIROL JI J. Virol. PD MAR PY 1994 VL 68 IS 3 BP 1782 EP 1789 PG 8 WC Virology SC Virology GA MY596 UT WOS:A1994MY59600061 PM 8107240 ER PT J AU LEHKY, TJ COWAN, EP LAMPSON, LA JACOBSON, S AF LEHKY, TJ COWAN, EP LAMPSON, LA JACOBSON, S TI INDUCTION OF HLA CLASS-I AND CLASS-II EXPRESSION IN HUMAN T-LYMPHOTROPIC VIRUS TYPE I-INFECTED NEUROBLASTOMA-CELLS SO JOURNAL OF VIROLOGY LA English DT Article ID TROPICAL SPASTIC PARAPARESIS; CYTOTOXIC LYMPHOCYTES-T; CENTRAL-NERVOUS-SYSTEM; HTLV-I; GLIAL-CELLS; NEUROLOGICAL DISEASE; CEREBROSPINAL-FLUID; MHC PRODUCTS; SPINAL-CORD; LEUKEMIA AB Human T-lymphotropic virus type I (HTLV-I) is associated with a neurologic disease, HTLV-I-associated myelopathy-tropical spastic paraparesis, in which both pathological and immunological changes are observed within the central nervous system. The pathogenesis of infection in HTLV-I-associated myopathy-tropical spastic paraparesis is not well understood with respect to the cell tropism of HTLV-I and its relationship to the destruction of neural elements. In this study, neuroblastoma cells were infected with HTLV-I by coculturing with HUT-102 cells to demonstrate that cells of neuronal origin are susceptible to this retroviral infection. HTLV-I infection of the neuroblastoma cells was confirmed by verifying the presence of HTLV-I gp46 surface antigens by flow cytometry and by verifying the presence of HTLV-I pX RNA by Northern (RNA) blotting and in situ hybridization techniques. To determine whether HTLV-I infection could potentially lead to changes in cell surface recognition by the immune system, the infected neuroblastoma cells were analyzed for altered HLA expression. The HTLV-I-infected, cocultured neuroblastoma cells were shown, through cell surface antigen expression and RNA transcripts, to express HLA classes I and II. In contrast, cocultured neuroblastoma cells that did not become infected with HTLV-I expressed only HLA class I. HLA class I expression was enhanced by the cytokines tumor necrosis factor alpha and gamma interferon and in the presence of HUT-102 supernatant. In this system, expression of HLA class I and II molecules appeared to be regulated by different mechanisms. HLA class I expression was probably induced by cytokines present in the HUT-102 supernatant and was not dependent on HTLV-I infection. HLA class II expression required HTLV-I infection of the cells. The observation of HTLV-I infection leading to HLA induction in these neuroblastoma cells provides a possible mechanism for immunologic recognition of infected neuronal cells. C1 BRIGHAM & WOMENS HOSP,CTR NEUROL DIS,DEPT MED,DIV NEUROL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT NEUROL,BOSTON,MA 02115. RP LEHKY, TJ (reprint author), NINCDS,NEUROIMMUNOL BRANCH,NIH BLDG,10-5B-16,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 44 TC 26 Z9 27 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0022-538X J9 J VIROL JI J. Virol. PD MAR PY 1994 VL 68 IS 3 BP 1854 EP 1863 PG 10 WC Virology SC Virology GA MY596 UT WOS:A1994MY59600070 PM 7906313 ER PT J AU TANI, Y DONOGHUE, E SHARPE, S BOONE, E LANE, HC ZOLLAPAZNER, S COHEN, DI AF TANI, Y DONOGHUE, E SHARPE, S BOONE, E LANE, HC ZOLLAPAZNER, S COHEN, DI TI ENHANCED IN-VITRO HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 REPLICATION IN B-CELLS EXPRESSING SURFACE ANTIBODY TO THE TM ENV PROTEIN SO JOURNAL OF VIROLOGY LA English DT Article ID HUMAN MONOCLONAL-ANTIBODIES; HIV-1 INFECTION INVITRO; 2 IMMUNODOMINANT DOMAINS; SOLUBLE CD4 BINDING; ENVELOPE GLYCOPROTEIN; MEMBRANE-FUSION; DEPENDENT ENHANCEMENT; TRANSMEMBRANE PROTEIN; GENE-TRANSFER; T4 MOLECULE AB The human immunodeficiency virus type 1 (HIV-1) external envelope glycoprotein gp120 tightly binds CD4 as its principal cellular receptor, explaining the tropism of HIV-1 for CD4(+) cells. Nevertheless, reports documenting HIV infection or HIV binding in cells lacking CD4 surface expression have raised the possibility that cellular receptors in addition to CD4 mag interact with HIV envelope. Moreover, the lymphocyte adhesion molecule LFA-1 appears to play an important role in augmenting HIV-1 viral spread and cytopathicity in vitro, although the mechanism of this function is still not completely defined. In the course of characterizing a human anti-HN gp41 monoclonal antibody, we transfected a CD4-negative, LFA-1-negative B cell line to express an anti-gp41 immunoglobulin receptor (surface immunoglobulin [sIg]/gp41). Despite acquiring the ability to bind HIV envelope, such transfected B cells could not be infected by HIV-1. These cells were not intrinsically defective for supporting HIV-1 infection, because when directed to produce surface CD4 by using retroviral constructs, they acquired the ability to replicate HIV-1. Interestingly, transfected cells expressing both surface CD4 and sIg/gp41 receptors replicated HIV much better than cells expressing only CD4. The enhancement resided specifically in sIg/gp41, because isotype-specific, anti-IgG1 antibodies directed against sIg/gp41 blocked the enhancement. These data directly establish the ability of a cell surface anti-gp41 receptor to enhance HIV-1 replication. C1 NIAID,IMMUNOREGULAT LAB,BETHESDA,MD 20892. NR 58 TC 1 Z9 1 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0022-538X J9 J VIROL JI J. Virol. PD MAR PY 1994 VL 68 IS 3 BP 1942 EP 1950 PG 9 WC Virology SC Virology GA MY596 UT WOS:A1994MY59600078 PM 8107254 ER PT J AU DIMITROV, DS BLUMENTHAL, R AF DIMITROV, DS BLUMENTHAL, R TI PHOTOINACTIVATION AND KINETICS OF MEMBRANE-FUSION MEDIATED BY THE HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 ENVELOPE GLYCOPROTEIN SO JOURNAL OF VIROLOGY LA English DT Article ID CELL-FUSION; SYNCYTIA FORMATION; HIV-1; INACTIVATION; AIDS; INHIBITION; INFECTION AB The fusion kinetics of cells expressing the human immunodeficiency virus type 1 (HIV-1) envelope glycoprotein with CD4 target cells was continuously monitored by image-enhanced Nomarski differential interference contrast optics. The analysis of the videotape recordings showed that (i) cells made contact relatively rapidly (within minutes), in many cases by using microspikes to ''touch'' and adhere to adjoining cells; (ii) the adhered cells fused after a relatively long waiting period, which varied from 15 min to hours; (iii) the morphological changes after membrane fusion, which led to disappearance of the interface separating the two cells, were rapid (less than 1 min); and (iv) the process of syncytium formation involved subsequent fusion with other cells and not simultaneous fusion of many cells. To measure the kinetics of early stages of cell fusion, we used the recently developed very stable membrane-soluble dye, PKH26, which redistributes between labeled and unlabeled membranes after fusion but does not exchange spontaneously between membranes for prolonged periods. We found that photoactivation of this dye by illumination with green light inhibits fusion of cell membranes as indicated by the lack of dye transfer from the labeled HIV-1 envelope-expressing cells to unlabeled CD4 cells. The inhibitory effect was localized in space and time, which allowed us to develop a new assay for measuring the kinetics of membrane fusion by illuminating the cell mixture at different times after coculture. This assay has also been used to monitor the fusion kinetics of HIV-1 and recombinant vaccinia virus. The photoactivation of nonexchangeable membrane-soluble fluorescent dyes may be useful for development of new assays for measuring the kinetics of membrane fusion and could also be important in designing new antiviral approaches. RP DIMITROV, DS (reprint author), NCI,MEMBRANE STRUCT & FUNCT SECT,BLDG 10,RM 4A01,BETHESDA,MD 20892, USA. NR 23 TC 24 Z9 27 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0022-538X J9 J VIROL JI J. Virol. PD MAR PY 1994 VL 68 IS 3 BP 1956 EP 1961 PG 6 WC Virology SC Virology GA MY596 UT WOS:A1994MY59600080 PM 8107256 ER PT J AU GOLDING, H MANISCHEWITZ, J VUJCIC, L BLUMENTHAL, R DIMITROV, DS AF GOLDING, H MANISCHEWITZ, J VUJCIC, L BLUMENTHAL, R DIMITROV, DS TI THE PHORBOL ESTER PHORBOL-MYRISTATE ACETATE INHIBITS HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 ENVELOPE-MEDIATED FUSION BY MODULATING AN ACCESSORY COMPONENT(S) IN CD4-EXPRESSING CELLS SO JOURNAL OF VIROLOGY LA English DT Article ID RECOMBINANT VACCINIA VIRUSES; HTLV-III/LAV ENVELOPE; SYNCYTIUM FORMATION; CD4-MEDIATED FUSION; BINDING-PROTEIN; T-CELLS; GLYCOPROTEIN; HIV-1; CD4; INFECTION AB The phorbol ester phorbol myristate acetate (PMA) strongly inhibits human immunodeficiency virus type 1 (HIV-1)-induced syncytium formation; it has been suggested that this inhibitory effect is due to the transient downmodulation of the surface-associated CD4 receptors by PMA (I. H. Chowdhury, Y. Koyanagi, S. Kobayashi, Y. Hamamoto, H. Yoshiyama, T. Yoshida, and N. Yamamoto, Virology 176:126-132, 1990). Surprisingly, PMA treatment of cells expressing truncated (A2.01.CD4.401) and hybrid (A2.01.CD4.CD8) CD4 molecules, which are not downmodulated (P. Bedinger, A. Moriarty, R. C. von Borstel II, N. J. Donovan, K. S. Steimer, and D. R. Littman, Nature [London] 331:162-165, 1988), inhibited their fusion with CD4(-) (12E1) cells expressing vaccinia virus-encoded HIV-1 envelope glycoprotein (gp120-gp41) and with chronically HIV-1-infected H9 (MN, IIIB, or RF) cells. PMA pretreatment of T (12E1) and non-T (HeLa, U937.3, and Epstein-Barr virus-transformed B) cell lines expressing vaccinia virus-encoded CD4 also blocked fusion with 12E1 cells expressing vaccinia virus-encoded gp120-gp41. Interestingly, pretreatment of the gp120-gp41-expressing 12E1 cells with PMA did not alter their fusion with untreated CD4-expressing cells. Although the inhibitory effect of PMA was rapid and treatment for 1.5 h with 5 ng of PMA per ml was sufficient to reduce fusion by more than 50%, the recovery after treatment was slow and more than 40 h was needed before the cells regained half of their fusion potential. The inhibitory effect of PMA was blocked by staurosporine in a dose-dependent fashion, suggesting that it is mediated by protein kinase C. PMA treatment of A2.01.CD4.401 cells reduced the number of infected cells 6.7-fold, as estimated by a quantitative analysis of the HIV-1 MN infection kinetics, probably by affecting the stage of virus entry into cells. CD26 surface expression was not significantly changed by PMA treatment. We conclude that PMA inhibits the CD4-gp120-gp41-mediated fusion by modulating an accessory component(s), different from CD26, in the target CD4-expressing cells. These findings suggest a novel approach for identification of accessory molecules involved in fusion and may have implications for the development of antiviral agents. C1 NCI,MEMBRANE STRUCT & FUNCT SECT,BETHESDA,MD 20892. US FDA,CBER,DIV VIROL,BETHESDA,MD 20892. NR 31 TC 33 Z9 33 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0022-538X J9 J VIROL JI J. Virol. PD MAR PY 1994 VL 68 IS 3 BP 1962 EP 1969 PG 8 WC Virology SC Virology GA MY596 UT WOS:A1994MY59600081 PM 7906314 ER PT J AU HOSTOMSKY, Z HUGHES, SH GOFF, SP LEGRICE, SFJ AF HOSTOMSKY, Z HUGHES, SH GOFF, SP LEGRICE, SFJ TI REDESIGNATION OF THE RNASE-D ACTIVITY ASSOCIATED WITH RETROVIRAL REVERSE-TRANSCRIPTASE AS RNASE-H SO JOURNAL OF VIROLOGY LA English DT Note ID ESCHERICHIA-COLI; POLYMERASE AB In the presence of Mn2+, reverse transcriptase of both human immunodeficiency virus and murine leukemia virus hydrolyzes duplex RNA. However, designating this novel activity RNase D conflicts with Escherichia coli RNase D, which participates in tRNA processing. On the basis of its location in the RNase H domain, we propose that this novel retroviral activity be redesignated RNase H*. C1 CASE WESTERN RESERVE UNIV,SCH MED,DIV INFECT DIS,CLEVELAND,OH 44106. AGOURON PHARMACEUT INC,SAN DIEGO,CA 92121. NCI,FREDERICK CANC RES & DEV CTR,ABL BASIC RES PROGRAM,FREDERICK,MD 21702. COLUMBIA UNIV,DEPT BIOCHEM,NEW YORK,NY 10032. NR 8 TC 25 Z9 25 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0022-538X J9 J VIROL JI J. Virol. PD MAR PY 1994 VL 68 IS 3 BP 1970 EP 1971 PG 2 WC Virology SC Virology GA MY596 UT WOS:A1994MY59600082 PM 7509004 ER PT J AU MORIUCHI, H MORIUCHI, M SMITH, HA COHEN, JI AF MORIUCHI, H MORIUCHI, M SMITH, HA COHEN, JI TI VARICELLA-ZOSTER VIRUS OPEN READING FRAME-4 PROTEIN IS FUNCTIONALLY DISTINCT FROM AND DOES NOT COMPLEMENT ITS HERPES-SIMPLEX VIRUS TYPE-1 HOMOLOG, ICP27 SO JOURNAL OF VIROLOGY LA English DT Note ID GENE-EXPRESSION; REGULATORY PROTEIN; TRANS-REPRESSOR; MUTANTS; IDENTIFICATION; TRANSCRIPTION; PROMOTER; ACTIVATE; DELETION; RNA AB Varicella-zoster virus (VZV) open reading frame 4 (ORF4) encodes a putative immediate-early protein which is homologous to herpes simplex virus type 1 (HSV-1) ICP27 on the basis of gene location and similarity in amino acid sequence. In transient expression assays, however, ORF4 and ICP27 exhibit different properties. ICP27 alone has little activity on target plasmids, but it acts as a transactivator or a transrepressor in the presence of other HSV-1 transactivators. In contrast, ORF4 directly transactivates plasmids containing homologous or heterologous promoters and has no apparent transrepressing activity. To further illuminate the functional similarities and differences between ORF4 and ICP27, Vero cell lines which express ORF4 under the inducible metallothionein promoter were constructed. Cell lines expressing functionally active ORF4 protein upregulated the expression of transfected VZV target plasmids but were unable to efficiently complement HSV-1 ICP27 mutants. These results indicate that, despite structural similarities, VZV ORF4 and HSV-1 ICP27 behave differently in transient expression assays and may play different roles in virus replication. C1 NIAID,CLIN INVEST LAB,MED VIROL SECT,BETHESDA,MD 20892. NR 31 TC 51 Z9 52 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0022-538X J9 J VIROL JI J. Virol. PD MAR PY 1994 VL 68 IS 3 BP 1987 EP 1992 PG 6 WC Virology SC Virology GA MY596 UT WOS:A1994MY59600086 PM 8107260 ER PT J AU MANCUSO, VA HOPE, TJ ZHU, L DERSE, D PHILLIPS, T PARSLOW, TG AF MANCUSO, VA HOPE, TJ ZHU, L DERSE, D PHILLIPS, T PARSLOW, TG TI POSTTRANSCRIPTIONAL EFFECTOR DOMAINS IN THE REV PROTEINS OF FELINE IMMUNODEFICIENCY VIRUS AND EQUINE INFECTIOUS-ANEMIA VIRUS SO JOURNAL OF VIROLOGY LA English DT Note ID VIRAL MESSENGER-RNA; HIV-1 REV; TYPE-1 REV; TRANS-ACTIVATOR; I REX; TRANSACTIVATOR; IDENTIFICATION; MOTIF; EXPRESSION; PEPTIDE AB By systematically dissecting the Rev proteins of feline immunodeficiency virus (FN) and equine infectious anemia virus (EIAV), we have identified within each a short peptide that is functionally interchangeable with the effector domains found in Rev-like proteins from other retroviruses. The active sequences from FIV and EIAV differ in several respects from other known effectors and may represent a distinct class of effector domain. C1 UNIV CALIF SAN FRANCISCO, DEPT PATHOL, SAN FRANCISCO, CA 94143 USA. UNIV CALIF SAN FRANCISCO, DEPT MICROBIOL & IMMUNOL, SAN FRANCISCO, CA 94143 USA. NCI, FREDERICK CANC RES & DEV CTR, VIRAL CARCINOGENESIS LAB, FREDERICK, MD 21701 USA. SCRIPPS RES INST, DEPT NEUROPHARMACOL, LA JOLLA, CA 92037 USA. FU NIAID NIH HHS [AI29313]; NIGMS NIH HHS [GM43574] NR 23 TC 52 Z9 53 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 1994 VL 68 IS 3 BP 1998 EP 2001 PG 4 WC Virology SC Virology GA MY596 UT WOS:A1994MY59600088 PM 8107262 ER PT J AU HO, DD TOYOSHIMA, T MO, HM KEMPF, DJ NORBECK, D CHEN, CM WIDEBURG, NE BURT, SK ERICKSON, JW SINGH, MK AF HO, DD TOYOSHIMA, T MO, HM KEMPF, DJ NORBECK, D CHEN, CM WIDEBURG, NE BURT, SK ERICKSON, JW SINGH, MK TI CHARACTERIZATION OF HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 VARIANTS WITH INCREASED RESISTANCE TO A C-2-SYMMETRICAL PROTEASE INHIBITOR SO JOURNAL OF VIROLOGY LA English DT Note ID HIV-1 REVERSE-TRANSCRIPTASE; C2 SYMMETRICAL INHIBITORS; HIGH-LEVEL RESISTANCE; CRYSTAL-STRUCTURE; ZIDOVUDINE AZT; PROTEINASE; SENSITIVITY; MUTATIONS; CULTURE AB Inhibitors of the human immunodeficiency virus type 1 protease represent a promising class of antiviral drugs for the treatment of AIDS, and several are now in clinical trials. Here, we report the in vitro selection of viral variants with decreased sensitivity to a C-2-symmetric protease inhibitor (A-77003). We show that a single amino acid substitution (Arg to Gln or Lys) at position 8 of the protease results in a substantial decrease in the inhibitory activity of the drug on the enzyme and a comparable increase in viral resistance. These findings, when analyzed by using the three-dimensional structure of the protease drug complex, provide a strategic guide for the future development of inhibitors of the human immunodeficiency virus type 1 protease. C1 ABBOTT LABS, DIV PHARMACEUT PROD, ABBOTT PK, IL 60064 USA. NCI, FREDERICK CANC RES & DEV CTR, STRUCT BIOL PROGRAM, FREDERICK, MD 21702 USA. RP HO, DD (reprint author), NYU, SCH MED, AARON DIAMOND AIDS RES CTR, 455 1ST AVE, NEW YORK, NY 10016 USA. FU NIAID NIH HHS [AI24030, AI25541, AI27742] NR 30 TC 209 Z9 209 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X EI 1098-5514 J9 J VIROL JI J. Virol. PD MAR PY 1994 VL 68 IS 3 BP 2016 EP 2020 PG 5 WC Virology SC Virology GA MY596 UT WOS:A1994MY59600091 PM 8107264 ER PT J AU GURALNIK, JM SIMONSICK, EM FERRUCCI, L GLYNN, RJ BERKMAN, LF BLAZER, DG SCHERR, PA WALLACE, RB AF GURALNIK, JM SIMONSICK, EM FERRUCCI, L GLYNN, RJ BERKMAN, LF BLAZER, DG SCHERR, PA WALLACE, RB TI A SHORT PHYSICAL PERFORMANCE BATTERY ASSESSING LOWER-EXTREMITY FUNCTION - ASSOCIATION WITH SELF-REPORTED DISABILITY AND PREDICTION OF MORTALITY AND NURSING-HOME ADMISSION SO JOURNALS OF GERONTOLOGY LA English DT Article ID ELDERLY PERSONS; OLDER PERSONS; RISK-FACTORS; COMMUNITY; MOBILITY; CAPACITY; RATINGS; FALLS AB Background. A short battery of physical performance tests was used to assess lower extremity function in more than 5,000 persons age 71 years and older in three communities. Methods. Balance, gait, strength, and endurance were evaluated by examining ability to stand with the feet together in the side-by-side, semi-tandem, and tandem positions, time to walk 8 feet, and time to rise from a chair and return to the seated position 5 times. Results. A wide distribution of performance was observed for each test. Each test and a summary performance scale, created by summing categorical rankings of performance on each test, were strongly associated with self-report of disability. Both self-report items and performance tests were independent predictors of short-term mortality and nursing home admission in multivariate analyses. However, evidence is presented that the performance tests provide information not available from self-report items. Of particular importance is the finding that in those at the high end of the functional spectrum, who reported almost no disability, the performance test Scores distinguished a gradient of risk for mortality and nursing home admission. Additionally, within subgroups with identical self-report profiles, there were systematic differences in physical performance related to age and sex. Conclusion. This study provides evidence that performance measures can validly characterize older persons across a broad spectrum of lower extremity function. Performance and self-report measures may complement each other in providing useful information about functional status. C1 INRCA FLORENCE,HOSP I FRATICINI,DEPT GERIATR,FLORENCE,ITALY. HARVARD UNIV,SCH MED,DEPT MED,CHANNING LAB,BOSTON,MA. YALE UNIV,SCH MED,DEPT EPIDEMIOL,NEW HAVEN,CT 06510. DUKE UNIV,SCH MED,DEPT PSYCHIAT,DURHAM,NC. CTR DIS CONTROL,NATL CTR CHRON DIS PREVENT & HLTH PROMOT,AGING STUDIES BRANCH,ATLANTA,GA 30333. UNIV IOWA,DEPT PREVENT MED & ENVIRONM HLTH,IOWA CITY,IA 52242. RP GURALNIK, JM (reprint author), NIA,EPIDEMIOL DEMOG & BIOMETRY PROGRAM,7201 WISCONSIN AVE,ROOM 3C-309,BETHESDA,MD 20892, USA. FU NIA NIH HHS [N01-AG-0-2105, N01-AG-0-2106, N01-AG-0-2107] NR 30 TC 2089 Z9 2123 U1 30 U2 123 PU GERONTOLOGICAL SOCIETY AMER PI WASHINGTON PA 1275 K STREET NW SUITE 350, WASHINGTON, DC 20005-4006 SN 0022-1422 J9 J GERONTOL JI J. Gerontol. PD MAR PY 1994 VL 49 IS 2 BP M85 EP M94 PG 10 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA NB102 UT WOS:A1994NB10200028 PM 8126356 ER PT J AU RISCO, C ROMERO, C BOSCH, A DASILVA, PP AF RISCO, C ROMERO, C BOSCH, A DASILVA, PP TI TYPE-II PNEUMOCYTES REVISITED - INTRACELLULAR MEMBRANOUS SYSTEMS, SURFACE CHARACTERISTICS, AND LAMELLAR BODY SECRETION SO LABORATORY INVESTIGATION LA English DT Article DE TYPE II PNEUMOCYTES; LAMELLAR BODIES; BAR-LIKE STRUCTURES; CELL SURFACE; SECRETION; ELECTRON MICROSCOPY ID BAR-LIKE STRUCTURE; PULMONARY SURFACTANT; LUNG SURFACTANT; RAT LUNG; IMMUNOCYTOCHEMICAL LOCALIZATION; ALVEOLAR MACROPHAGES; ENDOPLASMIC-RETICULUM; GRANULAR PNEUMOCYTES; ESCHERICHIA-COLI; TUBULAR MYELIN AB BACKGROUND: Type II pneumocytes, the producers of pulmonary surfactant, have been extensively studied during the last 20 years because of the importance of their metabolism in lung function and integrity. The ultrastructural studies of the 1970s and 1980s have shown that these cells present unique elements. EXPERIMENTAL DESIGN: In this work, we used thin-section, freeze-fracture, and fracture-flip electron microscopy techniques to obtain new information on the ultrastructural peculiarities of isolated rat type II pneumocytes, focusing our study on the intracellular membranous systems and their interrelationships and the microanatomy of their plasma membrane during secretory process. RESULTS: In thin-sections of pneumocytes postfixed with osmium tetroxide and potassium ferricyanide, we observed that lamellar bodies (LBs) are usually connected to membranes of the endoplasmic reticulum, and seem to emerge and grow from them. Unusual connections between the endoplasmic reticulum and mitochondria were detected, as well as numerous ''bar-like structures'' (BLSs), most of them in the early stages of development and often generating from the nuclear membrane. Membranes of the smooth endoplasmic reticulum that closely follow the outlines of mitochondria also appear to be the origin of some BLSs. Possible transition forms, BLS --> LB, were also detected, although they were rare. New images of the surface of the pneumocytes and its changes during LB secretion showed a segregation and clearing of membrane particles at the areas of LB extrusion. CONCLUSIONS: We propose that LBs can originate directly from membranes of the endoplasmic reticulum or from BLSs. An indirect participation of mitochondria appears possible. The plasma membrane of pneumocytes displays structural changes associated with the secretion of LBs as visualized by a redistribution of intramembrane and surface particles. C1 NCI,FREDERICK CANC RES & DEV CTR,PROGRAM RESOURCES INC DYNCORP,BIOL CARCINOGENESIS & DEV PROGRAM,FREDERICK,MD 21702. UNIV COMPLUTENSE,FAC CHEM,DEPT BIOCHEM & MOLEC BIOL,MADRID,SPAIN. NCI,FCRDC,MATH BIOL LAB,STRUCT BIOL SECT,FREDERICK,MD 21701. NR 61 TC 23 Z9 24 U1 0 U2 1 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0023-6837 J9 LAB INVEST JI Lab. Invest. PD MAR PY 1994 VL 70 IS 3 BP 407 EP 417 PG 11 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA ND941 UT WOS:A1994ND94100015 PM 8145534 ER PT J AU MORRIS, R LYON, GR ALEXANDER, D GRAY, DB KAVANAGH, J ROURKE, BP SWANSON, HL AF MORRIS, R LYON, GR ALEXANDER, D GRAY, DB KAVANAGH, J ROURKE, BP SWANSON, HL TI PROPOSED GUIDELINES AND CRITERIA FOR DESCRIBING SAMPLES OF PERSONS WITH LEARNING-DISABILITIES SO LEARNING DISABILITY QUARTERLY LA English DT Editorial Material C1 UNIV CALIF RIVERSIDE,RIVERSIDE,CA 92521. UNIV WINDSOR,WINDSOR N9B 3P4,ONTARIO,CANADA. NICHHD,BETHESDA,MD 20892. RP MORRIS, R (reprint author), GEORGIA STATE UNIV,ATLANTA,GA 30303, USA. NR 1 TC 9 Z9 9 U1 0 U2 0 PU COUNC LEARNING DISABILITES KRISTEN MCBRIDE PI OVER LAND PARK PA EXECUTIVE SECRETARY PO BOX 40303, OVER LAND PARK, KS 66204 SN 0731-9487 J9 LEARN DISABILITY Q JI Learn. Disabil. Q. PD SPR PY 1994 VL 17 IS 2 BP 106 EP 109 PG 4 WC Education, Special; Rehabilitation SC Education & Educational Research; Rehabilitation GA PA043 UT WOS:A1994PA04300001 ER PT J AU KREITMAN, RJ PASTAN, I AF KREITMAN, RJ PASTAN, I TI RECOMBINANT SINGLE-CHAIN IMMUNOTOXINS AGAINST T-CELL AND B-CELL LEUKEMIAS SO LEUKEMIA & LYMPHOMA LA English DT Review DE IMMUNOTOXIN; INTERLEUKIN-2 RECEPTOR; TOXIN; FV; PSEUDOMONAS EXOTOXIN; DIPHTHERIA TOXIN; ANTI-TAC; MONOCLONAL ANTIBODY; LEUKEMIA; LYMPHOMA; AUTOIMMUNE DISORDER AB Interleukin 2 (IL2) receptors (IL2R's) are found on malignant cells in many human leukemias and lymphomas and are expressed by activated T cells in many autoimmune disorders. Anti-Tac(Fv), a single-chain protein composed of the variable heavy and light domains of the anti-IL2R monoclonal antibody anti-Tac, can be genetically fused to derivatives of Pseudomonas exotoxin (PE) or diphtheria toxin (DT) to form potent immunotoxins. We have shown that anti-Tac(Fv) binds to low affinity IL2R's on fresh chronic lymphocytic leukemia (CLL) and adult T-cell leukemia (ATL) cells and can target either toxin to kill those cells. Anti-Tac(Fv)-PE40, containing the truncated form of PE without its binding domain, was cytotoxic to malignant cells from 8 of 8 ATL patients tested, with IC50's ranging from 0.11 to 5.5 ng/ ml. Anti-Tac(Fv)-PE40KDEL, a derivative of anti-Tac(Fv)-PE40 which contains the KDEL carboxyl terminus, was more cytotoxic toward cells from all ATL patients and also killed CLL cells from 8 of 16 patients. DT388-anti-Tac(Fv), containing amino acids 1-388 of DT fused to the amino terminus of anti-Tac(Fv), was less cytotoxic than anti-Tac(Fv)-PE40 on ATL cells from 4 of 5 patients, but was cytotoxic toward CLL cells from 12 of 16 patients. DT388-IL2, where IL2 is substituted for anti-Tac(Fv), is similar to DAB(389)IL2, an IL2-toxin currently in clinical trials. DT388-IL2 and DAB(389)IL2 differ by only a few amino acids and have equal cytotoxic activity. DT388-IL2 was cytotoxic toward ATL cells from all patients tested, but usually required much higher concentrations than anti-Tac(Fv)-PE40 and was poorly active against CLL cells. Thus, recombinant toxins containing anti-Tac(Fv) are cytotoxic toward freshly isolated CLL and ATL cells and will be studied further as potential therapy for IL2R-related disorders. C1 NCI,DIAGNOSIS & CTR,DIV CANC BIOL,MOLEC BIOL LAB,BETHESDA,MD 20892. NR 0 TC 50 Z9 51 U1 0 U2 0 PU HARWOOD ACAD PUBL GMBH PI READING PA C/O STBS LTD, PO BOX 90, READING, BERKS, ENGLAND RG1 8JL SN 1042-8194 J9 LEUKEMIA LYMPHOMA JI Leuk. Lymphoma PD MAR PY 1994 VL 13 IS 1-2 BP 1 EP 10 PG 10 WC Oncology; Hematology SC Oncology; Hematology GA NF619 UT WOS:A1994NF61900001 PM 8025511 ER PT J AU BUNN, P ARRIAGADA, R CHOI, N FELD, R GREGOR, A JETT, J JOHNSON, B KOMAKI, R KRISTJANSEN, P MURRAY, N OHNOSHI, T PERRY, M QUOIX, E SAIJO, N SHAW, E AF BUNN, P ARRIAGADA, R CHOI, N FELD, R GREGOR, A JETT, J JOHNSON, B KOMAKI, R KRISTJANSEN, P MURRAY, N OHNOSHI, T PERRY, M QUOIX, E SAIJO, N SHAW, E TI COMBINED-MODALITY THERAPY IN SMALL-CELL LUNG-CANCER SO LUNG CANCER LA English DT Article; Proceedings Paper CT 2nd IASLC Workshop on Combined Radiotherapy and Chemotherapy Modalities in Lung Cancer CY JUN 09-13, 1992 CL FONTAINEBLEAU, FRANCE SP INT ASSOC STUDY LUNG CANC, AMGEN ROCHE, ARIES GRP FITEG, ASSOC RECH THERAPEUT CANC BRONCH, ASTA MEDICA, BRISTOL MYERS SQUIBB US, BRISTOL MYERS SQUIBB FRANCE, CIS BIO INT, FAMITALIA CARLO ERBA, INST RECH INT SERVIER, INST GUSTAVE ROUSSY, LABS SARGET, LABS LEDERLE FRANCE, LABS LILLY FRANCE, LAB PIERRE FABRE ONCOL, LABS ROGER BELLON C1 INST GUSTAVE ROUSSY,DEPT BIOSTAT,F-94805 VILLEJUIF,FRANCE. INST GUSTAVE ROUSSY,DEPT RADIOTHERAPY,F-94805 VILLEJUIF,FRANCE. MASSACHUSETTS GEN HOSP,CTR CANC,DEPT RADIAT ONCOL,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,CTR CANC,MED SERV,PULM UNIT,BOSTON,MA 02114. WESTERN GEN HOSP,DEPT CLIN ONCOL,EDINBURGH EH4 2XU,MIDLOTHIAN,SCOTLAND. PRINCESS MARGARET HOSP,DEPT MED,TORONTO M4X 1K9,ONTARIO,CANADA. UNIV TORONTO,MT SINAI HOSP,DIV HAEMATOL ONCOL,TORONTO M5G 1X5,ONTARIO,CANADA. MAYO CLIN & MAYO FDN,ROCHESTER,MN 55905. NCCTG,OMAHA,NE. NCCTG,DES MOINES,IA. NCCTG,URBANA,IL. NCCTG,CEDAR RAPIDS,IA. NCCTG,ST CLOUD,MN. NCI,NATL NAVAL MED CTR,NAVY MED ONCOL BRANCH,BETHESDA,MD 20889. UNIV TEXAS,MD ANDERSON CANC CTR,DEPT RADIOTHERAPY,HOUSTON,TX 77030. RIGSHOSP,FINSEN INST,DEPT ONCOL,DK-2100 COPENHAGEN,DENMARK. CHR STRASBOURG,F-67005 STRASBOURG,FRANCE. NATL CANC CTR,RES INST,DIV PHARMACOL,TOKYO 104,JAPAN. OKAYAMA UNIV,SCH MED,DEPT MED,OKAYAMA 700,JAPAN. NR 3 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0169-5002 J9 LUNG CANCER-J IASLC JI Lung Cancer PD MAR PY 1994 VL 10 SU 1 BP S25 EP S28 DI 10.1016/0169-5002(94)91664-0 PG 4 WC Oncology; Respiratory System SC Oncology; Respiratory System GA NK637 UT WOS:A1994NK63700007 PM 8087517 ER PT J AU GREEN, M BRODIN, O CHOI, N DRINGS, P GINSBERG, R GRALLA, R JOHNSON, D MULSHINE, J PAYNE, D RUFFIE, P AF GREEN, M BRODIN, O CHOI, N DRINGS, P GINSBERG, R GRALLA, R JOHNSON, D MULSHINE, J PAYNE, D RUFFIE, P TI PREOPERATIVE AND POSTOPERATIVE TREATMENTS IN STAGE-III NSCLC SO LUNG CANCER LA English DT Article; Proceedings Paper CT 2nd IASLC Workshop on Combined Radiotherapy and Chemotherapy Modalities in Lung Cancer CY JUN 09-13, 1992 CL FONTAINEBLEAU, FRANCE SP INT ASSOC STUDY LUNG CANC, AMGEN ROCHE, ARIES GRP FITEG, ASSOC RECH THERAPEUT CANC BRONCH, ASTA MEDICA, BRISTOL MYERS SQUIBB US, BRISTOL MYERS SQUIBB FRANCE, CIS BIO INT, FAMITALIA CARLO ERBA, INST RECH INT SERVIER, INST GUSTAVE ROUSSY, LABS SARGET, LABS LEDERLE FRANCE, LABS LILLY FRANCE, LAB PIERRE FABRE ONCOL, LABS ROGER BELLON C1 UNIV HOSP UPPSALA,DEPT ONCOL,UPPSALA,SWEDEN. MASSACHUSETTS GEN HOSP,CTR CANC,DEPT RADIAT ONCOL,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,CTR CANC,MED SERV,PULM UNIT,BOSTON,MA 02114. CORNELL UNIV,MED CTR,COLL MED,DEPT SURG,THORAC SERV,NEW YORK,NY 10021. THORAXKLIN HEIDELBERG ROHRBACH,DEPT ONCOL,W-6900 HEIDELBERG,GERMANY. VANDERBILT UNIV,MED CTR,SCH MED,DEPT MED,DIV MED ONCOL,NASHVILLE,TN 37232. PRINCESS MARGARET HOSP,DEPT RADIAT ONCOL,TORONTO M4X 1K9,ONTARIO,CANADA. UNIV TORONTO,TORONTO M4X 1K9,ONTARIO,CANADA. INST GUSTAVE ROUSSY,F-94805 VILLEJUIF,FRANCE. CTR HOSP INTERCOMMUNAL CRETEIL,F-94010 CRETEIL,FRANCE. NCI,DIV CANC & CONTROL,BIOMARKERS & PREVENT RES BRANCH,ROCKVILLE,MD 20850. NCI,DIV CANC & CONTROL,EARLY DETECT & COMMUNITY ONCOL PROGRAM,ROCKVILLE,MD 20850. RP GREEN, M (reprint author), UNIV CALIF SAN DIEGO,225 DICKINSON ST,8421,SAN DIEGO,CA 92103, USA. NR 1 TC 4 Z9 4 U1 0 U2 0 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0169-5002 J9 LUNG CANCER-J IASLC JI Lung Cancer PD MAR PY 1994 VL 10 SU 1 BP S15 EP S17 DI 10.1016/0169-5002(94)91662-4 PG 3 WC Oncology; Respiratory System SC Oncology; Respiratory System GA NK637 UT WOS:A1994NK63700005 PM 8087504 ER PT J AU JOHNSON, BE AF JOHNSON, BE TI CONCURRENT APPROACHES TO COMBINED CHEMOTHERAPY AND CHEST RADIOTHERAPY FOR THE TREATMENT OF PATIENTS WITH LIMITED STAGE SMALL-CELL LUNG-CANCER SO LUNG CANCER LA English DT Article; Proceedings Paper CT 2nd IASLC Workshop on Combined Radiotherapy and Chemotherapy Modalities in Lung Cancer CY JUN 09-13, 1992 CL FONTAINEBLEAU, FRANCE SP INT ASSOC STUDY LUNG CANC, AMGEN ROCHE, ARIES GRP FITEG, ASSOC RECH THERAPEUT CANC BRONCH, ASTA MEDICA, BRISTOL MYERS SQUIBB US, BRISTOL MYERS SQUIBB FRANCE, CIS BIO INT, FAMITALIA CARLO ERBA, INST RECH INT SERVIER, INST GUSTAVE ROUSSY, LABS SARGET, LABS LEDERLE FRANCE, LABS LILLY FRANCE, LAB PIERRE FABRE ONCOL, LABS ROGER BELLON DE LUNG NEOPLASM; SMALL CELL LUNG CANCER; RADIATION; SURVIVAL; CHEMOTHERAPY ID THORACIC RADIOTHERAPY; LOCAL-CONTROL; CYCLOPHOSPHAMIDE; VINCRISTINE; CISPLATIN; CARCINOMA; METAANALYSIS; DOXORUBICIN; ALTERNATION; ETOPOSIDE AB The addition of chest radiotherapy to combination chemotherapy has been shown to prolong survival of patients with limited stage small cell lung cancer. Treatment of these patients with concurrent etoposide cisplatin and chest radiotherapy has resulted in a median survival of 18-27 months with a 2-year projected actuarial survival of 36-65%. The alternation of etoposide cisplatin (EP) with vincristine, doxorubicin, and cyclophosphamide (VAC) has been associated with prolonged survival in a single trial of patients with limited stage small cell lung cancer treated with combined modality therapy. Timing of the alternation of the two regimens (EP and VAC) in the first, second, or fourth cycle has not been shown to be an important determinant of survival for patients in single arm studies. Three studies evaluating early (within 1 month of starting chemotherapy) versus late (3-4 months after starting chemotherapy) chest radiotherapy in concurrent regimens, have shown early chest radiotherapy is associated with longer survival in one study while the other two show no difference in survival. Further clinical research will continue to define the appropriate ways to combine chemotherapeutic agents and chest radiotherapy to maximize the survival of patients with small cell lung cancer. RP JOHNSON, BE (reprint author), NCI,NATL NAVAL MED CTR,NAVY MED ONCOL BRANCH,BLDG 8,ROOM 5101,BETHESDA,MD 20889, USA. NR 14 TC 2 Z9 2 U1 0 U2 0 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0169-5002 J9 LUNG CANCER-J IASLC JI Lung Cancer PD MAR PY 1994 VL 10 SU 1 BP S281 EP S287 DI 10.1016/0169-5002(94)91692-6 PG 7 WC Oncology; Respiratory System SC Oncology; Respiratory System GA NK637 UT WOS:A1994NK63700035 PM 8087521 ER PT J AU MULSHINE, JL JOHNSON, BE GAZDAR, AF SHAW, GL KRAMER, BS MITSUDOMI, T MINNA, JD PASS, H PHELPS, R GHOSH, B LINNOILA, RI IHDE, DC AF MULSHINE, JL JOHNSON, BE GAZDAR, AF SHAW, GL KRAMER, BS MITSUDOMI, T MINNA, JD PASS, H PHELPS, R GHOSH, B LINNOILA, RI IHDE, DC TI INTEGRATED CLINICAL AND BASIC STUDIES RELATED TO CIRCUMVENTING NONSMALL CELL LUNG-CANCER DRUG-RESISTANCE SO LUNG CANCER LA English DT Article; Proceedings Paper CT 2nd IASLC Workshop on Combined Radiotherapy and Chemotherapy Modalities in Lung Cancer CY JUN 09-13, 1992 CL FONTAINEBLEAU, FRANCE SP INT ASSOC STUDY LUNG CANC, AMGEN ROCHE, ARIES GRP FITEG, ASSOC RECH THERAPEUT CANC BRONCH, ASTA MEDICA, BRISTOL MYERS SQUIBB US, BRISTOL MYERS SQUIBB FRANCE, CIS BIO INT, FAMITALIA CARLO ERBA, INST RECH INT SERVIER, INST GUSTAVE ROUSSY, LABS SARGET, LABS LEDERLE FRANCE, LABS LILLY FRANCE, LAB PIERRE FABRE ONCOL, LABS ROGER BELLON DE LUNG CANCER; DRUG RESISTANCE; COMBINED MODALITY; TUMOR BIOLOGY ID INDEPENDENT PROGNOSTIC FACTOR; K-RAS ONCOGENE; GENE-MUTATIONS; LINES; CARCINOMA; SURVIVAL; INVITRO; ADENOCARCINOMA; PREVENTION; ACTIVATION AB Consideration of a range of clinical and basic studies conducted at the National Cancer Institute which explore the nature of the tumor biology of lung identify the limitations of using chemotherapy for the treatment of advanced lung cancer. No single mechanistic explanation for lung cancer's chemoresistance is apparent, although considerable information about the biology of lung cancer and some of its clinical consequences have been elucidated. In contrast to previous works from our group, this presentation will focus principally on studies of the nature of drug resistance with non-small cell cancer. An alternative combined modality strategy for lung cancer control is to focus on epithelial progression of lung cancer using local modalities while it is still confined to the bronchial epithelium. Particular high risk populations may be appropriate to determine if local tools such as photodynamic laser therapy can be effective in this application. To deal with the underlying biochemical perturbations resulting from critical exposure of the bronchial epithelium to carcinogens, rational biochemical intervention with 13 cis retinoic acid are being evaluated in several clinical trials. An evolution towards more effective lung cancer control may involve the combined modalities of laser ablation of accessible dysplastic epithelium and chronic administration of intervention agents, such as retinoids, to neutralize cancer promotion dynamics in the more remote areas of the lung epithelium. C1 NCI, NAVY MED ONCOL BRANCH, COMMUNITY ONCOL PROGRAM, DIV CANC TREATMENT, BETHESDA, MD 20895 USA. NCI, DIV CANC TREATMENT, COMMUNITY ONCOL PROGRAM, SURG BRANCH, KENSINGTON, MD 20895 USA. NATL NAVAL MED CTR, DEPT SURG ONCOL, BETHESDA, MD 20898 USA. NCI, DIV CANC & CONTROL, EARLY DETECT & COMMUNITY ONCOL PROGRAM, ROCKVILLE, MD 20850 USA. RP MULSHINE, JL (reprint author), NCI, DIV CANC PREVENT & CONTROL, BIOMARKERS & PREVENT RES BRANCH, C-300, 9610 MED CTR DR, ROCKVILLE, MD 20850 USA. NR 32 TC 2 Z9 2 U1 0 U2 1 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0169-5002 J9 LUNG CANCER-J IASLC JI Lung Cancer PD MAR PY 1994 VL 10 SU 1 BP S73 EP S81 DI 10.1016/0169-5002(94)91669-1 PG 9 WC Oncology; Respiratory System SC Oncology; Respiratory System GA NK637 UT WOS:A1994NK63700012 PM 8087530 ER PT J AU SOUHAMI, RL BRODIN, O DUCHESNE, G GOLDIE, J GREEN, M KIES, M MATTSON, K MULSHINE, J SAIJO, N SAUNDERS, M STAHEL, R TANNOCK, I AF SOUHAMI, RL BRODIN, O DUCHESNE, G GOLDIE, J GREEN, M KIES, M MATTSON, K MULSHINE, J SAIJO, N SAUNDERS, M STAHEL, R TANNOCK, I TI BIOLOGICAL BASIS OF COMBINED THERAPY SO LUNG CANCER LA English DT Article; Proceedings Paper CT 2nd IASLC Workshop on Combined Radiotherapy and Chemotherapy Modalities in Lung Cancer CY JUN 09-13, 1992 CL FONTAINEBLEAU, FRANCE SP INT ASSOC STUDY LUNG CANC, AMGEN ROCHE, ARIES GRP FITEG, ASSOC RECH THERAPEUT CANC BRONCH, ASTA MEDICA, BRISTOL MYERS SQUIBB US, BRISTOL MYERS SQUIBB FRANCE, CIS BIO INT, FAMITALIA CARLO ERBA, INST RECH INT SERVIER, INST GUSTAVE ROUSSY, LABS SARGET, LABS LEDERLE FRANCE, LABS LILLY FRANCE, LAB PIERRE FABRE ONCOL, LABS ROGER BELLON C1 NORTHWESTERN UNIV,SCH MED,CHICAGO,IL 60611. UNIV HOSP UPPSALA,DEPT ONCOL,UPPSALA,SWEDEN. MIDDLESEX HOSP,LONDON W1N 8AA,ENGLAND. BRITISH COLUMBIA CANC AGCY,DIV MED ONCOL,VANCOUVER V5Z 4E6,BC,CANADA. NCI,DIV CANC PREVENT & CONTROL,BIOMARKERS & PREVENT RES BRANCH,ROCKVILLE,MD 20850. NCI,DIV CANC & CONTROL,EARLY DETECT & COMMUNITY ONCOL PROGRAM,ROCKVILLE,MD 20850. UNIV HELSINKI,HOSP CENT,DEPT PULM MED,SF-00290 HELSINKI 29,FINLAND. UNIV HOSP ZURICH,DEPT MED,DIV ONCOL,CH-8091 ZURICH,SWITZERLAND. PRINCESS MARGARET HOSP,DEPT MED,TORONTO M4X 1K9,ONTARIO,CANADA. PRINCESS MARGARET HOSP,DEPT MED BIOPHYS,TORONTO M4X 1K9,ONTARIO,CANADA. UNIV TORONTO,TORONTO M4X 1K9,ONTARIO,CANADA. MT VERNON HOSP,MT VERNON CTR CANC TREATMENT,MARIE CURIE RES WING ONCOL,NORTHWOOD HA6 2RN,MIDDX,ENGLAND. UNIV CALIF SAN DIEGO,SAN DIEGO,CA 92103. NATL CANC CTR,RES INST,DIV PHARMACOL,TOKYO 104,JAPAN. RP SOUHAMI, RL (reprint author), UNIV COLL & MIDDLESEX SCH MED,DEPT ONCOL,91 RIDING HOUSE ST,LONDON W1P 8BT,ENGLAND. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0169-5002 J9 LUNG CANCER-J IASLC JI Lung Cancer PD MAR PY 1994 VL 10 SU 1 BP S3 EP S5 DI 10.1016/0169-5002(94)91659-4 PG 3 WC Oncology; Respiratory System SC Oncology; Respiratory System GA NK637 UT WOS:A1994NK63700002 PM 8087524 ER PT J AU JIANG, X VILLENEUVE, L TURMEL, C KOZAK, CA JOLICOEUR, P AF JIANG, X VILLENEUVE, L TURMEL, C KOZAK, CA JOLICOEUR, P TI THE MYB AND AHI-1 GENES ARE PHYSICALLY VERY CLOSELY LINKED ON MOUSE CHROMOSOME-10 SO MAMMALIAN GENOME LA English DT Article ID MURINE LEUKEMIA-VIRUS; T-CELL LYMPHOMAS; FIELD GEL-ELECTROPHORESIS; ABELSON VIRUS; C-MYB; PROVIRUS INTEGRATION; NUCLEOTIDE-SEQUENCE; VIRAL INTEGRATION; RAT THYMOMAS; DNA AB Ahi-1 has previously been identified as a common helper provirus integration site on mouse Chromosome (Chr) 10 in 16% of Abelson pre-B-cell lymphomas and shown to be closely linked to the Myb protooncogene. By using long-range restriction mapping, we have mapped the Myb and Ahi-1 regions within a 120-kbp DNA fragment. The Ahi-1 region is located approximately 35 kbp downstream of the Myb gene. A further comfirmation of this finding was obtained by screening a mouse YAC library. The three positive clones obtained contained both the Myb and Ahi-1 gene sequences. To test whether provirus integration in the Ahi-1 region enhances the expression of Myb by a cis-acting mechanism, we have also examined Myb gene expression in A-MuLV-induced pre-B-lymphomas. Our data have revealed that there is no clear evidence for such activation in the tumors we have tested, indicating that provirus insertion in the Ahi-1 region is activating a novel gene, apparently involved in tumor formation. C1 CLIN RES INST MONTREAL,MOLEC BIOL LAB,MONTREAL H2W 1R7,PQ,CANADA. XEROX RES CTR CANADA LTD,MISSISSAUGA L5K 2L1,ON,CANADA. NIAID,MOLEC MICROBIOL LAB,BETHESDA,MD 20892. MCGILL UNIV,DEPT EXPTL MED,MONTREAL H3G 1A4,PQ,CANADA. UNIV MONTREAL,DEPT MICROBIOL & IMMUNOL,MONTREAL H3C 3J7,PQ,CANADA. NR 39 TC 19 Z9 19 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0938-8990 J9 MAMM GENOME JI Mamm. Genome PD MAR PY 1994 VL 5 IS 3 BP 142 EP 148 DI 10.1007/BF00352344 PG 7 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity GA NB020 UT WOS:A1994NB02000004 PM 7911043 ER PT J AU MOCK, BA PADLAN, C KOZAK, CA KIDD, V AF MOCK, BA PADLAN, C KOZAK, CA KIDD, V TI THE GENE FOR MOUSE P58(CDC2L1) (CDC2L1) PROTEIN-KINASE MAPS TO DISTAL MOUSE CHROMOSOME-4 SO MAMMALIAN GENOME LA English DT Note ID SHORT ARM; EXPRESSION; COMMITTEE; NEOPLASIA; SEQUENCE; ONCOGENE C1 NCI, BETHESDA, MD 20892 USA. NIAID, MOLEC MICROBIOL LAB, BETHESDA, MD 20892 USA. ST JUDE CHILDRENS RES HOSP, DEPT TUMOR CELL BIOL, MEMPHIS, TN 38105 USA. RP MOCK, BA (reprint author), NIH, GENET LAB, BLDG 37, ROOM 2B-08, BETHESDA, MD 20892 USA. FU NCI NIH HHS [N01-CB-21075]; NIGMS NIH HHS [GM44088-04] NR 17 TC 7 Z9 7 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0938-8990 J9 MAMM GENOME JI Mamm. Genome PD MAR PY 1994 VL 5 IS 3 BP 191 EP 192 DI 10.1007/BF00352357 PG 2 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity GA NB020 UT WOS:A1994NB02000017 PM 8199413 ER PT J AU KOHN, MC HINES, ML KOOTSEY, JM FEEZOR, MD AF KOHN, MC HINES, ML KOOTSEY, JM FEEZOR, MD TI A BLOCK ORGANIZED MODEL BUILDER SO MATHEMATICAL AND COMPUTER MODELLING LA English DT Article DE COMPUTER MODELING; BIOLOGICAL SIMULATION; MODEL-DESCRIPTION LANGUAGE AB A new language has been developed for defining simulation models for biomedical science and implemented as a preprocessor for SCoP (Simulation Control Program) written by the National Biomedical Simulation Resource. The preprocessor creates a C program by translation of statements in a model definition file. The language defines variables and equations in labelled blocks of statements which are either mathematical equations or English phrases. The availability of several kinds of equation definition blocks simplifies the description of the corresponding classes of equations. Sub-blocks are provided for some special operations, such as logical tests. Algebraic logical operators are included. Special statements called directives instruct the preprocessor to create specific variables or generate code to call specific numerical methods routines from SCoP's library. Models may be decomposed into sub-models stored on separate model definition files and automatically assembled by the preprocessor in hierarchical fashion. The model description language has been implemented in the C language by generating machine independent code with the Unix lex and yacc programs. An example of the use of the model description language, including hierarchical assembly, is illustrated by a model of the human ovulatory cycle. RP KOHN, MC (reprint author), NIEHS,STAT & BIOMATH BRANCH,POB 12233,RES TRIANGLE PK,NC 27710, USA. NR 8 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 0895-7177 J9 MATH COMPUT MODEL JI Math. Comput. Model. PD MAR-APR PY 1994 VL 19 IS 6-8 BP 75 EP 97 DI 10.1016/0895-7177(94)90190-2 PG 23 WC Computer Science, Interdisciplinary Applications; Computer Science, Software Engineering; Mathematics, Applied SC Computer Science; Mathematics GA NJ797 UT WOS:A1994NJ79700005 ER PT J AU ROTH, BJ MOMEN, S TURNER, R AF ROTH, BJ MOMEN, S TURNER, R TI ALGORITHM FOR THE DESIGN OF MAGNETIC STIMULATION COILS SO MEDICAL & BIOLOGICAL ENGINEERING & COMPUTING LA English DT Note DE COIL DESIGN; ELECTRIC FIELD; INVERSE PROBLEM; MAGNETIC STIMULATION ID NERVE; BRAIN C1 BALLOU SENIOR HIGH SCH, WASHINGTON, DC USA. NHLBI, CARDIAC ENERGET LAB, BETHESDA, MD 20892 USA. RP ROTH, BJ (reprint author), NIH, BIOMED ENGN & INSTRUMENTAT PROGRAM, BLDG 13, ROOM 3W13, BETHESDA, MD 20892 USA. RI Roth, Bradley/A-4920-2008 NR 9 TC 12 Z9 12 U1 0 U2 2 PU PETER PEREGRINUS LTD PI HERTS PA SOUTHGATE HOUSE STEVENAGE PO BOX 8, HERTS, ENGLAND SG1 1HQ SN 0140-0118 J9 MED BIOL ENG COMPUT JI Med. Biol. Eng. Comput. PD MAR PY 1994 VL 32 IS 2 BP 214 EP 216 DI 10.1007/BF02518921 PG 3 WC Computer Science, Interdisciplinary Applications; Engineering, Biomedical; Mathematical & Computational Biology; Medical Informatics SC Computer Science; Engineering; Mathematical & Computational Biology; Medical Informatics GA NL296 UT WOS:A1994NL29600015 PM 8022220 ER PT J AU WELLS, KB ROGERS, WH DAVIS, LM BENJAMIN, B NORQUIST, G KAHN, K BROOK, R AF WELLS, KB ROGERS, WH DAVIS, LM BENJAMIN, B NORQUIST, G KAHN, K BROOK, R TI QUALITY OF CARE FOR DEPRESSED ELDERLY PRE-POST-PROSPECTIVE PAYMENT SYSTEM - DIFFERENCES IN RESPONSE ACROSS TREATMENT SETTINGS SO MEDICAL CARE LA English DT Article ID MENTAL-HEALTH; PSYCHIATRY AB We evaluated the quality of care for depressed elderly patients (n=2,746) hospitalized in general medical hospitals (n = 297) before or after implementation of Medicare's Prospective Payment System, focusing on whether the response to time period differed for hospitals that in the post-PPS period had no psychiatric unit, an exempt psychiatric unit, or a nonexempt unit, and by ward placement within hospitals with psychiatric units. Quality of care increased over time, and for most measures of quality of care the level of improvement did not differ significantly across different types of hospitals or by ward placement. The intensity of use of therapeutic services, such as rehabilitation, occupation, or recreation therapy, increased over time, particularly in nonexempt psychiatric units and hospitals without psychiatric units, such that these locations caught up some over time in the level of use of these services to the level for exempt psychiatric units. Several outcomes of care improved over time, and the degree of improvement in the rate of inpatient medical and psychiatric complications and other outcomes was significantly greater for psychiatric units that were exempt post-PPS than for nonexempt treatment locations. C1 UNIV CALIF LOS ANGELES,CTR HLTH SCI,DEPT MED,LOS ANGELES,CA 90024. UNIV CALIF LOS ANGELES,CTR HLTH SCI,DEPT HLTH SERV,LOS ANGELES,CA 90024. UNIV CALIF LOS ANGELES,SCH MED,DEPT PSYCHIAT & BIOBEHAV SCI,LOS ANGELES,CA 90024. NIMH,BETHESDA,MD 20892. RP WELLS, KB (reprint author), RAND CORP,1700 MAIN ST,POB 2138,SANTA MONICA,CA 90407, USA. NR 26 TC 7 Z9 7 U1 1 U2 1 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 1994 VL 32 IS 3 BP 257 EP 276 DI 10.1097/00005650-199403000-00006 PG 20 WC Health Care Sciences & Services; Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA MZ654 UT WOS:A1994MZ65400006 PM 8145602 ER PT J AU BROOKS, CM RICHARDS, JM KOHLER, CL SOONG, SJ MARTIN, B WINDSOR, RA BAILEY, WC AF BROOKS, CM RICHARDS, JM KOHLER, CL SOONG, SJ MARTIN, B WINDSOR, RA BAILEY, WC TI ASSESSING ADHERENCE TO ASTHMA MEDICATION AND INHALER REGIMENS - A PSYCHOMETRIC ANALYSIS OF ADULT SELF-REPORT SCALES SO MEDICAL CARE LA English DT Article ID MANAGEMENT; PROGRAM AB Poor adherence to recommended regimens is a substantial problem in the clinical management of adults with asthma and other chronic diseases. Research on adherence assessment is complicated by methodological difficulties including limitations associated with the use of self-report measures. In this study, psychometric techniques were used to analyze two self-report scales for assessing adherence to recommended medication and inhaler use regimens in adults with asthma. Results indicated that the two scales had standard deviations large enough to detect variation adherence, had adequate reliability, and reflected the impact of an intervention designed to improve adherence. The results supported the usefulness of these scales for research on adherence. Additional analyses indicated that the two scales could be combined if the research goal required an overall measure of adherence. C1 UNIV ALABAMA,CTR COMPREHENS CANC,OFF BIOSTAT & BIOMATH,BIRMINGHAM,AL 35294. UNIV ALABAMA,CTR LUNG HLTH,DIV PULM & CRIT CARE MED,BIRMINGHAM,AL 35294. NHLBI,BETHESDA,MD 20892. RP BROOKS, CM (reprint author), UNIV ALABAMA,OFF EDUC DEV,1670 UNIV BLVD,VH700,BIRMINGHAM,AL 35294, USA. FU NHLBI NIH HHS [R01 HL 31481] NR 23 TC 66 Z9 70 U1 1 U2 8 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 1994 VL 32 IS 3 BP 298 EP 307 DI 10.1097/00005650-199403000-00008 PG 10 WC Health Care Sciences & Services; Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA MZ654 UT WOS:A1994MZ65400008 PM 8145604 ER PT J AU FRAKER, DL ALEXANDER, HR AF FRAKER, DL ALEXANDER, HR TI THE USE OF TUMOR-NECROSIS-FACTOR (TNF) IN ISOLATED PERFUSION - RESULTS AND SIDE-EFFECTS - THE NCI RESULTS SO MELANOMA RESEARCH LA English DT Article DE MELANOMA; MELPHALAN; REGIONAL THERAPY; TUMOR NECROSIS FACTOR AB The Surgery Branch of the National Cancer Institute has initiated several clinical trials involving the use of high-dose TNF in isolated limb perfusions. A phase III trial compares the three drug combination of TNF, interferon-gamma (IFN-gamma) and melphalan with a standard melphalan-alone perfusion in a prospective randomized trial. Another protocol escalates the dose of TNF in the perfusate to define the maximally tolerated dose that can be administered in this regional manner. A third protocol adds systemic high-dose interleukin-2 postoperatively to a TNF, IFN, and melphalan limb perfusion for patients with stage IV melanoma with the bulk of the disease in the extremity. This brief review highlights the rationale and study design of these TNF limb perfusion protocols. RP FRAKER, DL (reprint author), NCI,SURG BRANCH,BLDG 10,ROOM 2B07,BETHESDA,MD 20892, USA. FU NCI NIH HHS [CA-37907] NR 0 TC 22 Z9 23 U1 0 U2 1 PU RAPID SCIENCE PUBLISHERS PI LONDON PA 2-6 BOUNDARY ROW, LONDON, ENGLAND SE1 8NH SN 0960-8931 J9 MELANOMA RES JI Melanoma Res. PD MAR PY 1994 VL 4 SU 1 BP 27 EP 29 PG 3 WC Oncology; Dermatology; Medicine, Research & Experimental SC Oncology; Dermatology; Research & Experimental Medicine GA NL502 UT WOS:A1994NL50200006 PM 8038592 ER PT J AU WICKES, BL MOORE, TDE KWONCHUNG, KJ AF WICKES, BL MOORE, TDE KWONCHUNG, KJ TI COMPARISON OF THE ELECTROPHORETIC KARYOTYPES AND CHROMOSOMAL LOCATION OF 10 GENES IN THE 2 VARIETIES OF CRYPTOCOCCUS-NEOFORMANS SO MICROBIOLOGY-UK LA English DT Article DE CRYPTOCOCCUS NEOFORMANS; PULSED-FIELD ELECTROPHORESIS; KARYOTYPE ID VAR GATTII; SACCHAROMYCES-CEREVISIAE; AURINTRICARBOXYLIC ACID; GEL-ELECTROPHORESIS; 2 VARIETIES; FILOBASIDIELLA; SEPARATION; POLYMORPHISM; PROTOPLASTS; SEROTYPES AB We compared multiple isolates of the two varieties of Cryptococcus neoformans, as well as previously characterized representative isolates, for their electrophoretic karyotypes using pulsed-field electrophoresis. The two varieties could be clearly distinguished based upon the size of the smallest chromosome. The smallest chromosome for isolates of the gattii variety (serotypes B and C) was found to be 400-700 kb in size. The smallest chromosome for isolates of the neoformans variety was consistently found to be larger, approximately 770 kb in size. Isolates of the gattii variety averaged 13 chromosomes while the neoformans variety averaged 12. The size of the Cryptococcus genome was found to be approximately 23 megabases. Isolates of C. neoformans var. neoformans tended to be more conserved than those of var. gattii with regard to gene position. C1 NIAID,CLIN INVEST LAB,BETHESDA,MD 20892. UNIV CALIF SAN FRANCISCO,HORMONE RES INST,SAN FRANCISCO,CA 94143. NR 34 TC 84 Z9 84 U1 1 U2 1 PU SOC GENERAL MICROBIOLOGY PI READING PA HARVEST HOUSE 62 LONDON ROAD, READING, BERKS, ENGLAND RG1 5AS SN 1350-0872 J9 MICROBIOL-UK JI Microbiology-(UK) PD MAR PY 1994 VL 140 BP 543 EP 550 PN 3 PG 8 WC Microbiology SC Microbiology GA NN221 UT WOS:A1994NN22100013 PM 8012577 ER PT J AU VARGAS, FF CAVIEDES, PF GRANT, DS AF VARGAS, FF CAVIEDES, PF GRANT, DS TI ELECTROPHYSIOLOGICAL CHARACTERISTICS OF CULTURED HUMAN UMBILICAL VEIN ENDOTHELIAL-CELLS SO MICROVASCULAR RESEARCH LA English DT Article ID ELECTRICAL-PROPERTIES; CALCIUM CURRENTS; IONIC CURRENTS; CHANNELS; POTASSIUM; VESSELS AB Electrophysiological characteristics of cultured human umbilical vein endothelial cells (HUVEC) were determined using the patch-clamp technique in the whole cell configuration. In isolated cells, membrane potential, capacitance, and input resistance were (Mean +/- SD) - 16.3 +/- 12.7 mV, 53.9 +/- 26 pF, and 2.3 +/- 1.3 Gn Omega respectively (N = 26); and in confluent cells - 23.6 +/- 5.5 mV, 127 +/- 59 pF, and 0.254 +/- 0.077 G Omega, respectively (N = 6). The almost 10 times higher input resistance, and smaller capacitance of isolated Versus confluent cells, indicated that the latter were in electrical communication, presumably through open gap junctions, which was confirmed by intercellular diffusion of Lucifer Yellow. Whole-cell currents of isolated cells were made up of at least three components: First, two outward currents, an early transient one with activation-inactivation kinetics and a small delayed sustained component with 6.75 +/- 4.8 and 0.73 +/- 0.089 nS conductance, respectively. Second, an inward component which was rectified and had 1.58 +/- 1.2 nS conductance. In contrast to a reported lack of voltage-gated channels in HUVEC, the above currents were voltage dependent. Inhibition of the whole-cell currents by external Ba-2, internal Cs, and other K+ blockers indicates that the three observed currents are carried by K+. This was confirmed by changes of outside K+ concentrations shifting the I-V curve intercept in the direction expected for K+-selective channels. Voltage-gated Ca2+ currents were not apparent in the whole-cell current records. HUVEC membrane potential was as low as that of microvascular cells, while inward current rectification at normal external K+ was like that in arterial endothelial cells. This mixed phenotypic expression and multipotential behavior suggests that the electrical features of HUVEC may be primarily determined by embryonic origin and the local effect of the microenvironment rather than strictly by vessel size. (C) 1994 Academic Press, Inc. C1 NIDDK,CELL BIOL & GENET LAB,BETHESDA,MD 20892. NIDR,DEV BIOL LAB,BETHESDA,MD 20892. RP VARGAS, FF (reprint author), CDER,ODEI,DIV CARDIORENAL DRUG PROD,ROCKVILLE,MD 20857, USA. NR 42 TC 31 Z9 31 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 0026-2862 J9 MICROVASC RES JI Microvasc. Res. PD MAR PY 1994 VL 47 IS 2 BP 153 EP 165 DI 10.1006/mvre.1994.1012 PG 13 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA NB271 UT WOS:A1994NB27100001 PM 7517490 ER PT J AU DOLAN, SA PROCTOR, JL ALLING, DW OKUBO, Y WELLEMS, TE MILLER, LH AF DOLAN, SA PROCTOR, JL ALLING, DW OKUBO, Y WELLEMS, TE MILLER, LH TI GLYCOPHORIN-B AS AN EBA-175 INDEPENDENT PLASMODIUM-FALCIPARUM RECEPTOR OF HUMAN ERYTHROCYTES SO MOLECULAR AND BIOCHEMICAL PARASITOLOGY LA English DT Article DE ERYTHROCYTE INVASION; LIGAND; PLASMODIUM FALCIPARUM; RECEPTOR ID MALARIA PARASITES; CONTINUOUS CULTURE; BINDING ANTIGEN; INVASION; MEROZOITES; PROTEIN; CLONES; VIVAX; HETEROGENEITY; RESISTANCE AB Invasion of erythrocytes by malaria parasites involves multiple receptor-ligand interactions. To elucidate these pathways, we made use of four parasite clones with differing specificities for invasion, erythrocytes that are mutant for either glycophorin A or B, and enzyme modification of the erythrocyte surface with neuraminidase and trypsin. Neuraminidase alone abolishes invasion of two parasite clones (Dd2, FCR3/A2); these invade after trypsin treatment alone. A third clone (7G8) is unable to invade trypsin-treated erythrocytes. The fourth clone (HB3) can invade after either neuraminidase or trypsin treatment. The receptor for invasion of trypsin-treated erythrocytes was explored in two ways: treatment of trypsin-treated normal cells with neuraminidase, and trypsin treatment of glycophorin B-deficient cells. Both treatments eliminated invasion by all clones, indicating that the trypsin-independent pathway uses sialic acid and glycophorin B. To identify parasite proteins involved in the different pathways, erythrocyte binding assays were performed with soluble parasite proteins from each clone. Based on binding assays using erythrocytes that lack glycophorin A, the parasite protein known as EBA-175 appears to bind predominantly to glycophorin A. In contrast, the glycophorin B pathway does not appear to involve EBA-175, as binding of EBA-175 was similarly reduced to trypsin-treated normal and trypsin-treated glycophorin B-deficient erythrocytes. Thus, the glycophorin B-dependent, sialic acid-dependent invasion of trypsin-treated normal erythrocytes uses a different parasite ligand, indicating two or more sialic-dependent pathways for invasion. Clone 7G8, which cannot invade trypsin-treated erythrocytes, may be missing the ligand for invasion via glycophorin B. Redundancy in the invasion process may give a selective advantage to parasites that must survive in polymorphic human populations. C1 NIAID,MALARIA RES LAB,BETHESDA,MD 20892. NHLBI,OFF DIRECTOR INTRAMURAL RES,BETHESDA,MD 20892. NIH,WARREN GRANT MAGNUSON CLIN CTR,DEPT TRANSFUS MED,BETHESDA,MD 20892. OSAKA RED CROSS,CTR BLOOD,OSAKA,JAPAN. NR 28 TC 152 Z9 154 U1 2 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0166-6851 J9 MOL BIOCHEM PARASIT JI Mol. Biochem. Parasitol. PD MAR PY 1994 VL 64 IS 1 BP 55 EP 63 DI 10.1016/0166-6851(94)90134-1 PG 9 WC Biochemistry & Molecular Biology; Parasitology SC Biochemistry & Molecular Biology; Parasitology GA NH707 UT WOS:A1994NH70700006 PM 8078523 ER EF