FN Thomson Reuters Web of Science™ VR 1.0 PT J AU Sun, SH Silver, PB Du, Y Caspi, RR Wilder, RL Remmers, EF AF Sun, SH Silver, PB Du, Y Caspi, RR Wilder, RL Remmers, EF TI Identification of a locus on rat chromosome 4 associated with EAU susceptibility SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 NEI,IMMUNOL LAB,BETHESDA,MD 20892. NIAMS,ARTHRIT & RHEUMATISM BRANCH,NIH,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 1997 VL 38 IS 4 BP 2058 EP 2058 PN 1 PG 1 WC Ophthalmology SC Ophthalmology GA WN186 UT WOS:A1997WN18602051 ER PT J AU Silver, P Hathcock, K Chan, CC Green, JM Thompson, CB Caspi, R AF Silver, P Hathcock, K Chan, CC Green, JM Thompson, CB Caspi, R TI CD28 costimulation is required for induction of autoimmune uveitis, but not for endotoxin-induced uveitis. SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 NEI,NIH,BETHESDA,MD 20892. NCI,NIH,BETHESDA,MD 20892. UNIV CHICAGO,CHICAGO,IL 60637. 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 1997 VL 38 IS 4 BP 2060 EP 2060 PN 1 PG 1 WC Ophthalmology SC Ophthalmology GA WN186 UT WOS:A1997WN18602053 ER PT J AU Li, Q Matteson, D Nussenblatt, RB Chan, CC AF Li, Q Matteson, D Nussenblatt, RB Chan, CC TI Programmed cell death in experimental autoimmune uveitis (EAU) end experimental melanin induced uveitis (EMIU) SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 NEI,IMMUNOL LAB,NIH,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 1997 VL 38 IS 4 BP 2061 EP 2061 PN 1 PG 1 WC Ophthalmology SC Ophthalmology GA WN186 UT WOS:A1997WN18602054 ER PT J AU Bowers, WE Choudhury, A Haley, S Caspi, RR AF Bowers, WE Choudhury, A Haley, S Caspi, RR TI Antibodies against dendritic cells prevent the induction of experimental auto-immune uveoretinitis SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 UNIV S CAROLINA,SCH MED,DEPT MICROBIOL & IMMUNOL,COLUMBIA,SC 29208. NEI,IMMUNOL 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 1997 VL 38 IS 4 BP 2066 EP 2066 PN 1 PG 1 WC Ophthalmology SC Ophthalmology GA WN186 UT WOS:A1997WN18602059 ER PT J AU Kozhich, AT Whitcup, SM Gery, I AF Kozhich, AT Whitcup, SM Gery, I TI Amelioration of a cell-mediated autoimmune eye disease by targeting the uveitogenic antigen to B cells. SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 NEI,IMMUNOL 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 1997 VL 38 IS 4 BP 2069 EP 2069 PN 1 PG 1 WC Ophthalmology SC Ophthalmology GA WN186 UT WOS:A1997WN18602062 ER PT J AU Xu, H Strassmann, G Chan, CC Silver, PB Wiggert, B Caspi, RR AF Xu, H Strassmann, G Chan, CC Silver, PB Wiggert, B Caspi, RR TI Protective effect of the phosphodiesterase inhibitor rolipram an experimental autoimmune uveoretinitis (EAU) SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 NEI,LRCMB,NIH,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 1997 VL 38 IS 4 BP 2073 EP 2073 PN 1 PG 1 WC Ophthalmology SC Ophthalmology GA WN186 UT WOS:A1997WN18602066 ER PT J AU Fortin, E Anglade, E Chan, CC Csaky, K AF Fortin, E Anglade, E Chan, CC Csaky, K TI Treatment of EAU with adenovirus encoding TGF-beta 1 injected in the subretinal space. SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 NEI,NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 1 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 1997 VL 38 IS 4 BP 2074 EP 2074 PN 1 PG 1 WC Ophthalmology SC Ophthalmology GA WN186 UT WOS:A1997WN18602067 ER PT J AU Russell, P Tumminia, SJ Mitton, KP Arora, J Epstein, DL AF Russell, P Tumminia, SJ Mitton, KP Arora, J Epstein, DL TI Can aqueous humor protein levels activate signal transduction pathways in human trabecular meshwork cells? SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 NEI,BETHESDA,MD 20892. DUKE UNIV,DURHAM,NC. 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 1997 VL 38 IS 4 BP 2120 EP 2120 PN 1 PG 1 WC Ophthalmology SC Ophthalmology GA WN186 UT WOS:A1997WN18602113 ER PT J AU Tamm, ER Russell, P Piatigorsky, J AF Tamm, ER Russell, P Piatigorsky, J TI Initiation and characterization of an immortal, clonal and differentiated murine trabecular meshwork cell line SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 NEI,LMDB,NIH,BETHESDA,MD 20892. NEI,LMOD,NIH,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 1997 VL 38 IS 4 BP 2121 EP 2121 PN 1 PG 1 WC Ophthalmology SC Ophthalmology GA WN186 UT WOS:A1997WN18602114 ER PT J AU Zelenka, PS Gao, C Rampalli, AM He, H AF Zelenka, PS Gao, C Rampalli, AM He, H TI G2 proteins in G1-arrested cells: A possible role for pRb family proteins in the lens SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 NEI,NIH,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 1997 VL 38 IS 4 BP 2182 EP 2182 PN 1 PG 1 WC Ophthalmology SC Ophthalmology GA WN186 UT WOS:A1997WN18602175 ER PT J AU Gery, J Charukamnoetkanok, P Fukushima, A Whitcup, SM Egwuagu, CE AF Gery, J Charukamnoetkanok, P Fukushima, A Whitcup, SM Egwuagu, CE TI Correlation between thymic expression of S-antigen adn resistance to ocular autoimmune disease SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 NEI,NIH,BETHESDA,MD 20892. HOWARD HUGHES MED INST,NIH,RES SCHOLARS PROGRAM,BETHESDA,MD 20817. 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 1997 VL 38 IS 4 BP 2264 EP 2264 PN 1 PG 1 WC Ophthalmology SC Ophthalmology GA WN186 UT WOS:A1997WN18602257 ER PT J AU Charukamnoetkanok, P Brady, JP Wawrousek, EF Qin, C Zigler, JS Egwuagu, CE Whitcup, SM Gery, I AF Charukamnoetkanok, P Brady, JP Wawrousek, EF Qin, C Zigler, JS Egwuagu, CE Whitcup, SM Gery, I TI Selective breakdown of natural immunotolerance to self alpha-crystallin in knockout mice SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 NEI,NIH,BETHESDA,MD 20892. HOWARD HUGHES MED INST,NIH,RES SCHOLARS PROGRAM,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 1997 VL 38 IS 4 BP 2266 EP 2266 PN 1 PG 1 WC Ophthalmology SC Ophthalmology GA WN186 UT WOS:A1997WN18602259 ER PT J AU deVos, AF Fukushima, A Chan, CC Whitcup, SM Gery, I AF deVos, AF Fukushima, A Chan, CC Whitcup, SM Gery, I TI T-cells of transgenic (Tg) mice in which B-cells act as antigen presenting cells (APC) exhibit a unique immune profile and do not induce ocular inflammation SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 NEI,IMMUNOL LAB,NIH,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 1997 VL 38 IS 4 BP 2267 EP 2267 PN 1 PG 1 WC Ophthalmology SC Ophthalmology GA WN186 UT WOS:A1997WN18602260 ER PT J AU Sax, CM Salamon, C Chervenak, M Piatigorsky, J AF Sax, CM Salamon, C Chervenak, M Piatigorsky, J TI The potential role of light and oxidative stress in regulation of the major cornea protein transketolase SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 NEI,MOL & DEV BIOL LAB,NIH,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 1997 VL 38 IS 4 BP 2278 EP 2278 PN 1 PG 1 WC Ophthalmology SC Ophthalmology GA WN186 UT WOS:A1997WN18602271 ER PT J AU Csaky, KG Anglade, E AF Csaky, KG Anglade, E TI Subretinal adenovirus-mediated gene transfer of vascular endothelial growth factor (VEGF(165)) in adult rats results in fibrovascular proliferation. SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 NEI,IMMUNOL LAB,NIH,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 1997 VL 38 IS 4 BP 2309 EP 2309 PN 1 PG 1 WC Ophthalmology SC Ophthalmology GA WN186 UT WOS:A1997WN18602302 ER PT J AU Jacot, JL Jacot, TA Glover, JP Robison, WG AF Jacot, JL Jacot, TA Glover, JP Robison, WG TI Thickness of Descemet's membrane in galactose-fed rats: Roles of matrix metalloproteinases and aldose reductase inhibitors SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 NIDDKD,NIH,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 1997 VL 38 IS 4 BP 2326 EP 2326 PN 1 PG 1 WC Ophthalmology SC Ophthalmology GA WN186 UT WOS:A1997WN18602319 ER PT J AU Glover, JP Jacot, JL Hosotani, H Lois, N Robison, WG AF Glover, JP Jacot, JL Hosotani, H Lois, N Robison, WG TI Diabetic-like loss of corneal sensitivity in galactose-fed rats: Intervention therapy with CT-112, an aldose reductase inhibitor SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 OSAKA PREFECTURAL HOSP,DEPT OPHTHALMOL,OSAKA,JAPAN. NEI,NIH,BETHESDA,MD 20892. WILLS EYE HOSP & RES INST,PHILADELPHIA,PA. 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 1997 VL 38 IS 4 BP 2345 EP 2345 PN 1 PG 1 WC Ophthalmology SC Ophthalmology GA WN186 UT WOS:A1997WN18602338 ER PT J AU Smith, JA Mahdi, RM Whitcup, SM Nussenblatt, RB Egwuagu, CE AF Smith, JA Mahdi, RM Whitcup, SM Nussenblatt, RB Egwuagu, CE TI T cell receptor V delta gene usage in human ocular sarcoidosis SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 NEI,NATL INST HLTH,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 1997 VL 38 IS 4 BP 2434 EP 2434 PN 1 PG 1 WC Ophthalmology SC Ophthalmology GA WN186 UT WOS:A1997WN18602426 ER PT J AU Maraini, G Camparini, M Braccio, L Graziosi, P Ferrigno, L Williams, SL Dondi, P Sperduto, RD AF Maraini, G Camparini, M Braccio, L Graziosi, P Ferrigno, L Williams, SL Dondi, P Sperduto, RD TI An independent evaluation of the AREDS lens opacities classification system SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 UNIV PARMA,I-43100 PARMA,ITALY. NEI,BETHESDA,MD 20892. IST SUPER SANITA,I-00161 ROME,ITALY. 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 1997 VL 38 IS 4 BP 2557 EP 2557 PN 1 PG 1 WC Ophthalmology SC Ophthalmology GA WN186 UT WOS:A1997WN18602549 ER PT J AU OhtakaMaruyama, C Hanaoka, F Chepelinsky, AB AF OhtakaMaruyama, C Hanaoka, F Chepelinsky, AB TI The gene encoding the transcription factor AP2 is expressed in the lens and may regulate MIP gene transcription SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 RIKEN,CELLULAR PHYSIOL LAB,WAKO,SAITAMA,JAPAN. NEI,NIH,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 1997 VL 38 IS 4 BP 2695 EP 2695 PN 1 PG 1 WC Ophthalmology SC Ophthalmology GA WN186 UT WOS:A1997WN18602687 ER PT J AU Wang, X Kim, S OhtakaMaruyama, C Chepelinsky, AB AF Wang, X Kim, S OhtakaMaruyama, C Chepelinsky, AB TI Regulation of the MIP gene promoter by the Sp1 family of transcription factors SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 NEI,MOL & DEV BIOL LAB,NIH,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 1997 VL 38 IS 4 BP 2696 EP 2696 PN 1 PG 1 WC Ophthalmology SC Ophthalmology GA WN186 UT WOS:A1997WN18602688 ER PT J AU Gao, CY Zakeri, Z Zhu, Y He, HY Zelenka, PS AF Gao, CY Zakeri, Z Zhu, Y He, HY Zelenka, PS TI Cyclin dependent kinase activity in developing rat lens SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 NEI,NIH,BETHESDA,MD 20892. CUNY QUEENS COLL,DEPT BIOL,FLUSHING,NY 11367. CUNY QUEENS COLL,GRAD CTR,FLUSHING,NY 11367. 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 1997 VL 38 IS 4 BP 2711 EP 2711 PN 1 PG 1 WC Ophthalmology SC Ophthalmology GA WN186 UT WOS:A1997WN18602703 ER PT J AU Cai, H Arora, JK Zelenka, PS AF Cai, H Arora, JK Zelenka, PS TI Identification of 14-3-3 isoforms in the neonatal rat lens SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 NEI,NIH,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 1997 VL 38 IS 4 BP 2714 EP 2714 PN 1 PG 1 WC Ophthalmology SC Ophthalmology GA WN186 UT WOS:A1997WN18602706 ER PT J AU Li, A Madupu, R Padma, T Ayyagari, R Scott, MH KaiserKupfer, MI Hejtmancik, JF AF Li, A Madupu, R Padma, T Ayyagari, R Scott, MH KaiserKupfer, MI Hejtmancik, JF TI Autosomal dominant congenital cataract with interocular phenotypic variability: Localization to chromosome 2Q and candidate gene analysis of the gamma E-crystallin pseudogene SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 NEI,OGCSB,BETHESDA,MD. UNIV MICHIGAN,DEPT OPHTHALMOL,ANN ARBOR,MI 48109. 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 1997 VL 38 IS 4 BP 2720 EP 2720 PN 1 PG 1 WC Ophthalmology SC Ophthalmology GA WN186 UT WOS:A1997WN18602712 ER PT J AU Janjani, A DuglasTabor, Y Garland, DL AF Janjani, A DuglasTabor, Y Garland, DL TI Lens in Down's syndrome SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 NEI,NIH,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 1997 VL 38 IS 4 BP 2726 EP 2726 PN 1 PG 1 WC Ophthalmology SC Ophthalmology GA WN186 UT WOS:A1997WN18602718 ER PT J AU Mitton, KP Tumminia, SJ Kamiya, T Hess, JL Russell, P AF Mitton, KP Tumminia, SJ Kamiya, T Hess, JL Russell, P TI Cysteine protease activation and loss of calcium homeostasis expression of HIV-1 protease in transgenic mice. SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 NEI,BETHESDA,MD 20892. KYOWA HAKKO KOGYO CO LTD,TOKYO RES LABS,TOKYO 194,JAPAN. VIRGINIA TECH,DEPT BIOCHEM,BLACKSBURG,VA. 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 1997 VL 38 IS 4 BP 2727 EP 2727 PN 1 PG 1 WC Ophthalmology SC Ophthalmology GA WN186 UT WOS:A1997WN18602719 ER PT J AU Egwuagu, CE Nakamura, T Li, W Mahdi, R Chan, CC Chepelinsky, AB AF Egwuagu, CE Nakamura, T Li, W Mahdi, R Chan, CC Chepelinsky, AB TI Gamma interferon mediates lens tumor regression in transgenic mice SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 NEI,NIH,BETHESDA,MD 20892. OSAKA UNIV,SCH MED,DEPT OBSTET & GYNECOL,SUITA,OSAKA 565,JAPAN. 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 1997 VL 38 IS 4 BP 2732 EP 2732 PN 1 PG 1 WC Ophthalmology SC Ophthalmology GA WN186 UT WOS:A1997WN18602724 ER PT J AU Wawrousek, EF Brady, JP AF Wawrousek, EF Brady, JP TI Lens fiber cell inclusion bodies in alpha A-crystallin gene knockout mice are composed predominantly of alpha B-crystallin polypeptides SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 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 1997 VL 38 IS 4 BP 2733 EP 2733 PN 1 PG 1 WC Ophthalmology SC Ophthalmology GA WN186 UT WOS:A1997WN18602725 ER PT J AU Bernstein, SL Russell, P Smith, LEH Wong, P AF Bernstein, SL Russell, P Smith, LEH Wong, P TI A heat shock protein is differentially expressed in the fovea and changes with aging of the retina. SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 UNIV MARYLAND,DEPT OPHTHALMOL,COLLEGE PK,MD 20742. NEI,LAB MECH OCULAR DIS,BETHESDA,MD. HARVARD UNIV,SCH MED,DEPT OPHTHALMOL,CHILDRENS HOSP,CAMBRIDGE,MA 02138. UNIV ALBERTA,DEPT BIOL SCI,EDMONTON,AB,CANADA. 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 1997 VL 38 IS 4 BP 2746 EP 2746 PN 1 PG 1 WC Ophthalmology SC Ophthalmology GA WN186 UT WOS:A1997WN18602738 ER PT J AU Singh, VK Chader, GJ Rodriguez, IR AF Singh, VK Chader, GJ Rodriguez, IR TI Structural analysis of mouse pigment epithelium derived factor gene SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 NEI,RETINAL CELL & MOL BIOL LAB,NIH,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 1997 VL 38 IS 4 BP 2752 EP 2752 PN 1 PG 1 WC Ophthalmology SC Ophthalmology GA WN186 UT WOS:A1997WN18602744 ER PT J AU Feher, J Albedi, FM Formisano, G Perilli, R Scorcia, G Pintucci, S Caiazza, S TombranTink, J AF Feher, J Albedi, FM Formisano, G Perilli, R Scorcia, G Pintucci, S Caiazza, S TombranTink, J TI Pigment epithelium derived factor (PEDF), a candidate for autocrine regulation of retinal pigment epithelial cells. SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 IST SUPER SANITA,I-00161 ROME,ITALY. UNIV CATANZARO,ROME,ITALY. S GIOVANNI HOSP,ROME,ITALY. NEI,NIH,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 1997 VL 38 IS 4 BP 2753 EP 2753 PN 1 PG 1 WC Ophthalmology SC Ophthalmology GA WN186 UT WOS:A1997WN18602745 ER PT J AU Liu, Z Richmond, BJ AF Liu, Z Richmond, BJ TI Generality of stimulus classification from neuronal responses in a memory task SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 NIMH,NEUROPSYCHOL LAB,BETHESDA,MD 20814. 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 1997 VL 38 IS 4 BP 2922 EP 2922 PN 1 PG 1 WC Ophthalmology SC Ophthalmology GA WN186 UT WOS:A1997WN18602914 ER PT J AU Reynolds, J Pasternak, T Desimone, R AF Reynolds, J Pasternak, T Desimone, R TI Attention increases contrast sensitivity of cells in macaque area V4. SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 UNIV ROCHESTER,DEPT NEUROBIOL & ANAT,ROCHESTER,NY 14627. NIMH,NEUROPSYCHOL LAB,BETHESDA,MD. 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 1997 VL 38 IS 4 BP 3206 EP 3206 PN 2 PG 1 WC Ophthalmology SC Ophthalmology GA WN215 UT WOS:A1997WN21500031 ER PT J AU Redmond, TM Yu, S Pfeifer, K AF Redmond, TM Yu, S Pfeifer, K TI An RPE65 knockout: Targeted disruption of the mouse RPE65 SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 NEI,BETHESDA,MD 20892. NICHHD,NIH,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 1997 VL 38 IS 4 BP 3249 EP 3249 PN 2 PG 1 WC Ophthalmology SC Ophthalmology GA WN215 UT WOS:A1997WN21500074 ER PT J AU Mathers, PH Mahon, KA Grinberg, A Jamrich, M AF Mathers, PH Mahon, KA Grinberg, A Jamrich, M TI Misexpression and knockout studies show the Rx homeobox gene is essential for vertebrate eye development SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 W VIRGINIA UNIV,SCH MED,MORGANTOWN,WV 26506. US FDA,BETHESDA,MD 20014. NICHHD,NIH,BETHESDA,MD 20892. BAYLOR COLL MED,HOUSTON,TX 77030. 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 1997 VL 38 IS 4 BP 3250 EP 3250 PN 2 PG 1 WC Ophthalmology SC Ophthalmology GA WN215 UT WOS:A1997WN21500075 ER PT J AU Caspi, RR Silver, PB Rizzo, LV Chan, CC Wiggert, B Tarrant, TK AF Caspi, RR Silver, PB Rizzo, LV Chan, CC Wiggert, B Tarrant, TK TI Administration of IL-12 protects mice from autoimmune uveitis through a mechanism involving IFN-gamma. SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 NEI,LI,BETHESDA,MD 20892. NEI,LRCMB,BETHESDA,MD 20892. NIH,HHMI,RES SCHOLARS PROGRAM,BETHESDA,MD 20892. 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 1997 VL 38 IS 4 BP 3267 EP 3267 PN 2 PG 1 WC Ophthalmology SC Ophthalmology GA WN215 UT WOS:A1997WN21500092 ER PT J AU Sun, B Sun, SH Remmers, EF Rizzo, LV Wilder, RL Caspi, RR AF Sun, B Sun, SH Remmers, EF Rizzo, LV Wilder, RL Caspi, RR TI Kinetic analysis of cytokines in the eyes of EAU-susceptible and resistant rats SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 NEI,NIH,BETHESDA,MD. NIAMS,NIH,BETHESDA,MD. 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 1997 VL 38 IS 4 BP 3268 EP 3268 PN 2 PG 1 WC Ophthalmology SC Ophthalmology GA WN215 UT WOS:A1997WN21500093 ER PT J AU Agarwal, RK Rizzo, LV Chan, CC Wiggert, B Caspi, RR AF Agarwal, RK Rizzo, LV Chan, CC Wiggert, B Caspi, RR TI Pregnancy protects C57BL/6 mice from induction of experimental autoimmune uveoretinitis (EAU) SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 NEI,IMMUNOL LAB,NIH,BETHESDA,MD 20892. 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 1997 VL 38 IS 4 BP 3270 EP 3270 PN 2 PG 1 WC Ophthalmology SC Ophthalmology GA WN215 UT WOS:A1997WN21500095 ER PT J AU Laver, NV Glover, JP Robison, WG McLean, IW AF Laver, NV Glover, JP Robison, WG McLean, IW TI Computer morphometry of the retinal perifoveal vessel changes in human diabetes mellitus. SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 ARMED FORCES INST PATHOL,WASHINGTON,DC 20306. NEI,NIH,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 1997 VL 38 IS 4 BP 3301 EP 3301 PN 2 PG 1 WC Ophthalmology SC Ophthalmology GA WN215 UT WOS:A1997WN21500126 ER PT J AU Spoerri, PE Ellis, EA Hansen, BC Robison, GW Grant, MB AF Spoerri, PE Ellis, EA Hansen, BC Robison, GW Grant, MB TI Plasminogen-activator-inhibitor overexpression in type II noninsulin dependent diabetic retinopathy in monkeys SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 UNIV FLORIDA,GAINESVILLE,FL 32611. UNIV MARYLAND,COLLEGE PK,MD 20742. NEI,BETHESDA,MD. RI Hansen, Barbara/J-8723-2012 OI Hansen, Barbara/0000-0001-9646-3525 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 1997 VL 38 IS 4 BP 3304 EP 3304 PN 2 PG 1 WC Ophthalmology SC Ophthalmology GA WN215 UT WOS:A1997WN21500129 ER PT J AU Robison, WG Jacot, JL Glover, JP Basso, MD Hohman, TC AF Robison, WG Jacot, JL Glover, JP Basso, MD Hohman, TC TI Aldose reductase (AR) inhibitor intervention after significant diabetic-like retinal capillary basement membrane thickening. SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 NEI,NIH,BETHESDA,MD 20892. WYETH AYERST LABS,PRINCETON,NJ. 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 1997 VL 38 IS 4 BP 3305 EP 3305 PN 2 PG 1 WC Ophthalmology SC Ophthalmology GA WN215 UT WOS:A1997WN21500130 ER PT J AU Wong, P Bennett, S Arnold, J Lininger, L Darrow, R Chader, G Tenniswood, M Organisciak, D AF Wong, P Bennett, S Arnold, J Lininger, L Darrow, R Chader, G Tenniswood, M Organisciak, D TI Appearance of an unique isoform of clusterin during light-induced retinal damage in rats. SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 UNIV ALBERTA,DEPT BIOL SCI,EDMONTON,AB T6G 2M7,CANADA. NEI,NIH,BETHESDA,MD 20892. CARLETON UNIV,INST NEUROSCI,OTTAWA,ON K1S 5B6,CANADA. W ALTON JONES CELL SCI CTR,LAKE PLACID,NY 12946. WRIGHT STATE UNIV,DEPT BIOCHEM & MOL BIOL,DAYTON,OH 45435. NATL RETINITIS PIGMENTOSA FDN INC,FDN FIGHTING BLINDNESS,HUNT VALLEY,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 1997 VL 38 IS 4 BP 3321 EP 3321 PN 2 PG 1 WC Ophthalmology SC Ophthalmology GA WN215 UT WOS:A1997WN21500146 ER PT J AU Whitcup, SM Chan, CC Kozhich, AT Magone, MT AF Whitcup, SM Chan, CC Kozhich, AT Magone, MT TI Inhibition of allergic conjunctivitis by blocking ICAM-1 and LFA-1 SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 NEI,NIH,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 1997 VL 38 IS 4 BP 3354 EP 3354 PN 2 PG 1 WC Ophthalmology SC Ophthalmology GA WN215 UT WOS:A1997WN21500179 ER PT J AU Blake, DA Shafiee, A Yu, H Roberts, DD AF Blake, DA Shafiee, A Yu, H Roberts, DD TI Response of human and bovine corneal endothelial cells to peptides derived from thrombospondin (TSP) SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 TULANE UNIV,SCH MED,NEW ORLEANS,LA 70112. NIH,BETHESDA,MD 20892. RI Roberts, David/A-9699-2008 OI Roberts, David/0000-0002-2481-2981 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 1997 VL 38 IS 4 BP 3370 EP 3370 PN 2 PG 1 WC Ophthalmology SC Ophthalmology GA WN215 UT WOS:A1997WN21500195 ER PT J AU Wistow, G Graham, C Ray, M Meltzer, P Trent, J AF Wistow, G Graham, C Ray, M Meltzer, P Trent, J TI Crystallin superfamilies: Insight into the structure and function of crystallins from their non-lens relatives SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 NEI,BETHESDA,MD 20892. NIH,NATL CTR HUMAN GENOME RES,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 3 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 1997 VL 38 IS 4 BP 3378 EP 3378 PN 2 PG 1 WC Ophthalmology SC Ophthalmology GA WN215 UT WOS:A1997WN21500203 ER PT J AU Lertsumitkul, S Polis, MA Whitcup, SM AF Lertsumitkul, S Polis, MA Whitcup, SM TI Sensitivity of CD4+ cell counts and ocular symptoms in screening for cytomegalovirus retinitis SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 NEI,BETHESDA,MD 20892. NIAID,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 1997 VL 38 IS 4 BP 3401 EP 3401 PN 2 PG 1 WC Ophthalmology SC Ophthalmology GA WN215 UT WOS:A1997WN21500226 ER PT J AU Ehren, M Hoffmann, S Jin, ML Kohn, E Hinton, DR Ryan, SJ AF Ehren, M Hoffmann, S Jin, ML Kohn, E Hinton, DR Ryan, SJ TI Inhibition of RPE proliferation, attachment and migration by carboxyamido-triazole (CAI), a drug which acts by modifying calcium mediated signal transduction. SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 UNIV SO CALIF,SCH MED,DEPT OPHTHALMOL,LOS ANGELES,CA 90033. UNIV SO CALIF,SCH MED,DEPT PATHOL,LOS ANGELES,CA 90033. DOHENY EYE INST,LOS ANGELES,CA 90033. NCI,PATHOL LAB,SIGNAL TRANSDUCT UNIT,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 1997 VL 38 IS 4 BP 3486 EP 3486 PN 2 PG 1 WC Ophthalmology SC Ophthalmology GA WN215 UT WOS:A1997WN21500311 ER PT J AU Geller, AM AbdelRahman, AA Peiffer, RL Maguire, R AbouDonia, MB Boyes, WK AF Geller, AM AbdelRahman, AA Peiffer, RL Maguire, R AbouDonia, MB Boyes, WK TI Chlorpyrifos (CPF) interferes with eye growth in experimental myopia. SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 US EPA,NHEERL,RTP,NCI,DURHAM,NC. DUKE UNIV,DURHAM,NC. UNIV N CAROLINA,CHAPEL HILL,NC 27515. 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 1997 VL 38 IS 4 BP 3517 EP 3517 PN 2 PG 1 WC Ophthalmology SC Ophthalmology GA WN215 UT WOS:A1997WN21500342 ER PT J AU Jacot, TA Jacot, JL Glover, JP Robison, WG AF Jacot, TA Jacot, JL Glover, JP Robison, WG TI Expression of VEGF and mRNA is not associated with early diabetic-like retinopathy in the galactose-fed rat model SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 NEI,NIDDKD,NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 1 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 1997 VL 38 IS 4 BP 3530 EP 3530 PN 2 PG 1 WC Ophthalmology SC Ophthalmology GA WN215 UT WOS:A1997WN21500355 ER PT J AU Li, Y Jacot, JL Robison, WG AF Li, Y Jacot, JL Robison, WG TI Cell proliferation associated with microangiopathies of the galactose-fed rat model of diabetic retinopathy. SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 NEI,NIH,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 1997 VL 38 IS 4 BP 3560 EP 3560 PN 2 PG 1 WC Ophthalmology SC Ophthalmology GA WN215 UT WOS:A1997WN21500385 ER PT J AU Ohta, N Sato, S Kador, PF AF Ohta, N Sato, S Kador, PF TI Suppressed neutrophil apoptosis in galactose-fed dogs SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 NEI,LAB OCULAR THERAPEUT,NIH,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 1997 VL 38 IS 4 BP 3568 EP 3568 PN 2 PG 1 WC Ophthalmology SC Ophthalmology GA WN215 UT WOS:A1997WN21500393 ER PT J AU Sato, S Secchi, EF Fukase, S Ohta, N Lizak, MJ Kador, PF AF Sato, S Secchi, EF Fukase, S Ohta, N Lizak, MJ Kador, PF TI Polyol pathway in human leukemia cells - Potential models for investigating lymphocyte and neutrophil interaction in retinal capillaries. SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 NEI,LAB OCULAR THERAPEUT,NIH,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 1997 VL 38 IS 4 BP 3574 EP 3574 PN 2 PG 1 WC Ophthalmology SC Ophthalmology GA WN215 UT WOS:A1997WN21500399 ER PT J AU Lotery, AJ Hughes, AE Silvestri, G TombranTink, J Archer, DB AF Lotery, AJ Hughes, AE Silvestri, G TombranTink, J Archer, DB TI Characterisation of candidate genes for central areolar choroidal dystrophy on chromosome 17p SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 QUEENS UNIV BELFAST,DEPT OPHTHALMOL,BELFAST BT7 1NN,ANTRIM,NORTH IRELAND. QUEENS UNIV BELFAST,DEPT MED GENET,BELFAST BT7 1NN,ANTRIM,NORTH IRELAND. NIH,BETHESDA,MD 20892. RI Hughes, Anne/A-1307-2012 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 1997 VL 38 IS 4 BP 3722 EP 3722 PN 2 PG 1 WC Ophthalmology SC Ophthalmology GA WN215 UT WOS:A1997WN21500546 ER PT J AU Geyer, D Rodriguez, IR Heinzmann, C Kojis, TL Flodman, P Spence, MA Tiller, GE Mazuruk, K Heckenlively, JR Chader, GJ Bateman, JB AF Geyer, D Rodriguez, IR Heinzmann, C Kojis, TL Flodman, P Spence, MA Tiller, GE Mazuruk, K Heckenlively, JR Chader, GJ Bateman, JB TI Map refinement of region 17p13.3 and evaluation of pigment epithelium derived factor (PEDF), a candidate gene in autosomal dominant retinitis pigmentosa SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 ERI,DENVER,CO. NEI,NIH,BETHESDA,MD 20892. UCI,DEPT PEDIAT,IRVINE,CA. VANDERBILT UNIV,SCH MED,DEPT PEDIAT,NASHVILLE,TN 37212. UNIV CALIF LOS ANGELES,JSEI,LOS ANGELES,CA 90024. UCHSC,CHILDRENS HOSP,DENVER,CO. 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 1997 VL 38 IS 4 BP 3723 EP 3723 PN 2 PG 1 WC Ophthalmology SC Ophthalmology GA WN215 UT WOS:A1997WN21500547 ER PT J AU Nemesure, B Leske, MC Hejtmancik, F Connell, AMS Luthra, R AF Nemesure, B Leske, MC Hejtmancik, F Connell, AMS Luthra, R TI Methods to study the potential genetic component of open-angle glaucoma (OAG) in a black population. SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 SUNY STONY BROOK,DEPT PREVENT MED,STONY BROOK,NY 11794. NEI,BETHESDA,MD 20892. MINIST HLTH,BRIDGETOWN,BARBADOS. JOHNS HOPKINS UNIV,SCH MED,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 1997 VL 38 IS 4 BP 3833 EP 3833 PN 2 PG 1 WC Ophthalmology SC Ophthalmology GA WN215 UT WOS:A1997WN21500657 ER PT J AU Ayres, LM Caruso, RC KaiserKupfer, MI AF Ayres, LM Caruso, RC KaiserKupfer, MI TI Analysis of normal limits of the human Ganzfeld electroretinogram (ERG) amplitude SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 NEI,NIH,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 1997 VL 38 IS 4 BP 4093 EP 4093 PN 2 PG 1 WC Ophthalmology SC Ophthalmology GA WN215 UT WOS:A1997WN21500916 ER PT J AU GopalSrivastava, R Cvekl, A Piatigorsky, J AF GopalSrivastava, R Cvekl, A Piatigorsky, J TI Regulation of the murine alpha B-crystallin gene in lens: Involvement of retinoic acid retinoid X receptors SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 NEI,NIH,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 1997 VL 38 IS 4 BP 4288 EP 4288 PN 2 PG 1 WC Ophthalmology SC Ophthalmology GA WN215 UT WOS:A1997WN21501111 ER PT J AU Duncan, MK Haynes, JI Cvekl, A Piatigorsky, J AF Duncan, MK Haynes, JI Cvekl, A Piatigorsky, J TI Pax-6 repression of beta-crystallin expression: A mechanism for lens fiber cell differentiation? 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 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 1997 VL 38 IS 4 BP 4289 EP 4289 PN 2 PG 1 WC Ophthalmology SC Ophthalmology GA WN215 UT WOS:A1997WN21501112 ER PT J AU McGowan, MH Iwata, T Carper, DA AF McGowan, MH Iwata, T Carper, DA TI Characterization of the mouse aldose reductase gene and analysis of transcriptional regulation in a lens epithelial cell line SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 NIH,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 1997 VL 38 IS 4 BP 4290 EP 4290 PN 2 PG 1 WC Ophthalmology SC Ophthalmology GA WN215 UT WOS:A1997WN21501113 ER PT J AU Sheffield, JB Alexander, P StetlerStevenson, W Peng, H AF Sheffield, JB Alexander, P StetlerStevenson, W Peng, H TI Characterization of the immunoreactive forms of the 72 kDa metalloproteinase in developing chick retina. SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 TEMPLE UNIV,DEPT BIOL,PHILADELPHIA,PA 19122. OREGON HLTH SCI UNIV,PORTLAND,OR 97201. NIH,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 1997 VL 38 IS 4 BP 4314 EP 4314 PN 2 PG 1 WC Ophthalmology SC Ophthalmology GA WN215 UT WOS:A1997WN21501137 ER PT J AU Hanna, BW Alexander, P Hawkes, S StetlerStevenson, W Belder, LJ Sheffield, JB AF Hanna, BW Alexander, P Hawkes, S StetlerStevenson, W Belder, LJ Sheffield, JB TI The endogenous protease inhibitor in the embryonic chick retina is TIMP-3. SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 TEMPLE UNIV,DEPT BIOL,PHILADELPHIA,PA 19122. UNIV CALIF SAN FRANCISCO,DEPT PHARMACOL,SAN FRANCISCO,CA 94143. NIH,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 1997 VL 38 IS 4 BP 4315 EP 4315 PN 2 PG 1 WC Ophthalmology SC Ophthalmology GA WN215 UT WOS:A1997WN21501138 ER PT J AU Folk, JC Park, DW Polk, TD Brown, J Nussenblatt, RB Kansupada, K Whitcup, SM AF Folk, JC Park, DW Polk, TD Brown, J Nussenblatt, RB Kansupada, K Whitcup, SM TI Phakic cystoid macular edema with vitreous inflammation SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 UNIV IOWA,DEPT OPHTHALMOL,IOWA CITY,IA 52242. 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 1997 VL 38 IS 4 BP 4319 EP 4319 PN 2 PG 1 WC Ophthalmology SC Ophthalmology GA WN215 UT WOS:A1997WN21501142 ER PT J AU Tomarev, SI Duncan, MX Zinovieva, RD Kos, L AF Tomarev, SI Duncan, MX Zinovieva, RD Kos, L TI Eyes absent genes in eye development SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 NEI,MOL & DEV BIOL LAB,NIH,BETHESDA,MD 20892. NCHGR,LMGD,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 1997 VL 38 IS 4 BP 4332 EP 4332 PN 2 PG 1 WC Ophthalmology SC Ophthalmology GA WN215 UT WOS:A1997WN21501155 ER PT J AU Zivotofsky, AZ Krauzlis, RJ Miles, FA FitzGibbon, EJ AF Zivotofsky, AZ Krauzlis, RJ Miles, FA FitzGibbon, EJ TI Pursuit eye movements and the Duncker illusion with brief time exposures. SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 NEI,SENSORIMOTOR RES LAB,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 1997 VL 38 IS 4 BP 4341 EP 4341 PN 2 PG 1 WC Ophthalmology SC Ophthalmology GA WN215 UT WOS:A1997WN21501164 ER PT J AU Krauzlis, RJ Basso, MA Wurtz, RH AF Krauzlis, RJ Basso, MA Wurtz, RH TI Rostral superior colliculus influences pursuit eye movements in the primate as well as fixation and saccades. SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 NEI,SENSORIMOTOR RES 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 1997 VL 38 IS 4 BP 4343 EP 4343 PN 2 PG 1 WC Ophthalmology SC Ophthalmology GA WN215 UT WOS:A1997WN21501166 ER PT J AU Chepelinsky, AB Sidjanin, DJ ParkerWilson, DM OhtakaMaruyama, C Grimes, P NeuhaeuserKlaus, A Pretsch, W Koeberlein, B Favor, J Stambolian, D AF Chepelinsky, AB Sidjanin, DJ ParkerWilson, DM OhtakaMaruyama, C Grimes, P NeuhaeuserKlaus, A Pretsch, W Koeberlein, B Favor, J Stambolian, D TI Exon 2 deletion in the transcript encoding the lens major intrinsic protein (MIP) results in a mouse genetic cataract SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 NEI,NIH,BETHESDA,MD 20892. UNIV PENN,DEPT HUMAN GENET,PHILADELPHIA,PA 19104. UNIV PENN,DEPT OPHTHALMOL,PHILADELPHIA,PA 19104. GSF MUNICH,INST MAMMALIAN GENET,MUNICH,GERMANY. 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 1997 VL 38 IS 4 BP 4349 EP 4349 PN 2 PG 1 WC Ophthalmology SC Ophthalmology GA WN215 UT WOS:A1997WN21501172 ER PT J AU Brady, JP Wawrousek, EF AF Brady, JP Wawrousek, EF TI Targeted disruption of the mouse alpha beta-crystallin gene SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 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 1997 VL 38 IS 4 BP 4352 EP 4352 PN 2 PG 1 WC Ophthalmology SC Ophthalmology GA WN215 UT WOS:A1997WN21501175 ER PT J AU Kays, WT Cvekl, A Frederikse, P Stepp, MA Duncan, MK Piatigorsky, J AF Kays, WT Cvekl, A Frederikse, P Stepp, MA Duncan, MK Piatigorsky, J TI PAX-6 in the cornea: A role in epithelial proliferation? SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 GEORGE WASHINGTON UNIV,MED CTR,DEPT ANAT,WASHINGTON,DC 20037. NEI,MOL & DEV BIOL LAB,NIH,BETHESDA,MD 20892. NEI,LMOD,NIH,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 1997 VL 38 IS 4 BP 4406 EP 4406 PN 2 PG 1 WC Ophthalmology SC Ophthalmology GA WN215 UT WOS:A1997WN21501228 ER PT J AU Djalilian, AR Aronovich, EL Bradshaw, JJ Cho, WF Obritsch, WF Chan, CC Whitley, CB Krachmer, JH Holland, EJ AF Djalilian, AR Aronovich, EL Bradshaw, JJ Cho, WF Obritsch, WF Chan, CC Whitley, CB Krachmer, JH Holland, EJ TI Subconjunctival-limbal injection of retrovirally transduced fibroblasts: A possible approach for gene delivery to the cornea. SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 NEI,NIH,BETHESDA,MD 20892. UNIV MINNESOTA,MINNEAPOLIS,MN 55455. 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 1997 VL 38 IS 4 BP 4411 EP 4411 PN 2 PG 1 WC Ophthalmology SC Ophthalmology GA WN215 UT WOS:A1997WN21501233 ER PT J AU Vistica, BP Chan, CC Wawrousek, EF Palmer, L Whitcup, SM Gery, I AF Vistica, BP Chan, CC Wawrousek, EF Palmer, L Whitcup, SM Gery, I TI Unique immunopathology in double transgenic mice expressing hen egg lysozyme (HEL) in their lens and HEL-specific receptor by their T-cells. SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 NEI,NIH,BETHESDA,MD 20892. NCI,NIH,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 1997 VL 38 IS 4 BP 4416 EP 4416 PN 2 PG 1 WC Ophthalmology SC Ophthalmology GA WN215 UT WOS:A1997WN21501238 ER PT J AU Shafiee, A Roberts, DD Penn, JS Blake, DA AF Shafiee, A Roberts, DD Penn, JS Blake, DA TI Thrombospondin (TSP) peptides inhibit angiogenesis in retinal explant assay and rat model of retinopathy of prematurity (ROP) SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 UNIV ARKANSAS MED SCI HOSP,LITTLE ROCK,AR 72205. NIH,BETHESDA,MD 20892. TULANE UNIV,SCH MED,NEW ORLEANS,LA 70112. RI Roberts, David/A-9699-2008 OI Roberts, David/0000-0002-2481-2981 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 1997 VL 38 IS 4 BP 4468 EP 4468 PN 2 PG 1 WC Ophthalmology SC Ophthalmology GA WN215 UT WOS:A1997WN21501290 ER PT J AU Haine, CL Caruso, RC AF Haine, CL Caruso, RC TI Reproducibility of measurements of refraction and visual acuity SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 NEI,OPHTHALM GENET & CLIN SERV BRANCH,NIH,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 1997 VL 38 IS 4 BP 4534 EP 4534 PN 2 PG 1 WC Ophthalmology SC Ophthalmology GA WN215 UT WOS:A1997WN21501356 ER PT J AU Miles, FA Masson, GS Busettini, C AF Miles, FA Masson, GS Busettini, C TI Short-latency vergence eye movements to anticorrelated patterns. SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 NEI,SENSORIMOTOR RES LAB,BETHESDA,MD 20892. CRNC,CNRS,MARSEILLE,FRANCE. RI MASSON, Guillaume/G-4615-2012 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 1997 VL 38 IS 4 BP 4585 EP 4585 PN 2 PG 1 WC Ophthalmology SC Ophthalmology GA WN215 UT WOS:A1997WN21501407 ER PT J AU Caruso, RC Ayres, LM Iwata, F Gahl, WA KaiserKupfer, MI AF Caruso, RC Ayres, LM Iwata, F Gahl, WA KaiserKupfer, MI TI Visual evoked potential (VEP) asymmetry in the Hermansky-Pudlak syndrome (HPS) SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 NEI,NIH,BETHESDA,MD 20892. NICHHD,NIH,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 1997 VL 38 IS 4 BP 4630 EP 4630 PN 2 PG 1 WC Ophthalmology SC Ophthalmology GA WN215 UT WOS:A1997WN21501452 ER PT J AU Lizak, MJ Sato, S Kador, PF AF Lizak, MJ Sato, S Kador, PF TI Determination of polyol pathway activity in an intact lens by localized magnetic resonance spectroscopy SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 NEI,LAB OCULAR THERAPEUT,NIH,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 1997 VL 38 IS 4 BP 4762 EP 4762 PN 2 PG 1 WC Ophthalmology SC Ophthalmology GA WN215 UT WOS:A1997WN21501584 ER PT J AU Lee, YS Kador, PF AF Lee, YS Kador, PF TI Mechanism of catalysis and inhibition of aldose reductase SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 NEI,LAB OCULAR THERAPEUT,NIH,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 1997 VL 38 IS 4 BP 4764 EP 4764 PN 2 PG 1 WC Ophthalmology SC Ophthalmology GA WN215 UT WOS:A1997WN21501586 ER PT J AU Jernigan, HM Liu, Y Blum, PS Stimbert, CD Zigler, JS AF Jernigan, HM Liu, Y Blum, PS Stimbert, CD Zigler, JS TI Effects of xylose on cultured monkey lenses: A model for study of sugar cataracts in a primate. SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 UNIV TENNESSEE,CTR HLTH SCI,DEPT BIOCHEM,MEMPHIS,TN 38163. UNIV TENNESSEE,CTR HLTH SCI,DEPT OPHTHALMOL,MEMPHIS,TN 38163. NEI,LAB MECH OCULAR DIS,NIH,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 1997 VL 38 IS 4 BP 4766 EP 4766 PN 2 PG 1 WC Ophthalmology SC Ophthalmology GA WN215 UT WOS:A1997WN21501588 ER PT J AU Lee, JW Sato, S Lizak, MJ Kador, PF AF Lee, JW Sato, S Lizak, MJ Kador, PF TI Glucose dehydrogenase in dog lens and liver SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 NEI,LAB OCULAR THERAPEUT,NIH,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 1997 VL 38 IS 4 BP 4769 EP 4769 PN 2 PG 1 WC Ophthalmology SC Ophthalmology GA WN215 UT WOS:A1997WN21501591 ER PT J AU Lou, MF Wang, GM Robison, WG AF Lou, MF Wang, GM Robison, WG TI Nicotine induced cataract: A new cataract SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 UNIV NEBRASKA,DEPT VET & BIOMED SCI,LINCOLN,NE. UNIV NEBRASKA,DEPT OPHTHALMOL,LINCOLN,NE. NEI,NIH,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 1997 VL 38 IS 4 BP 4783 EP 4783 PN 2 PG 1 WC Ophthalmology SC Ophthalmology GA WN215 UT WOS:A1997WN21501605 ER PT J AU Gomes, JAP Rizzo, L Nishi, M Donoso, LA Dua, HS AF Gomes, JAP Rizzo, L Nishi, M Donoso, LA Dua, HS TI Human mucosal lymphocyte antigen (HML-1) expression on lymphocytes induced by corneal and conjunctival epithelial SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 WILLS EYE HOSP & RES INST,PHILADELPHIA,PA. DEPT OPHTHALMOL,SANTA CASA,SP,BRAZIL. NIH,WASHINGTON,DC. UNIV FED SAO PAULO,SAO PAULO,BRAZIL. UNIV NOTTINGHAM,LARRY A DONOSO LAB EYE RES,NOTTINGHAM NG7 2RD,ENGLAND. 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 1997 VL 38 IS 4 BP 5037 EP 5037 PN 2 PG 1 WC Ophthalmology SC Ophthalmology GA WN215 UT WOS:A1997WN21501858 ER PT J AU Magone, MT Chan, CC Kozhich, AT Rizzo, LV Whitcup, SM AF Magone, MT Chan, CC Kozhich, AT Rizzo, LV Whitcup, SM TI A novel murine model for allergic conjunctivitis SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 NEI,NIH,BETHESDA,MD. 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 1997 VL 38 IS 4 BP 5044 EP 5044 PN 2 PG 1 WC Ophthalmology SC Ophthalmology GA WN215 UT WOS:A1997WN21501865 ER PT J AU Chan, CC Li, Q Matteson, DM Mozes, E Singer, DS AF Chan, CC Li, Q Matteson, DM Mozes, E Singer, DS TI Experimental blepharitis: Adoptive transfer and apoptosis SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 NEI,IMMUNOL LAB,REHOVOT,ISRAEL. WEIZMANN INST SCI,IL-76100 REHOVOT,ISRAEL. NCI,EXPT IMMUNOL BRANCH,NIH,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 1997 VL 38 IS 4 BP 5046 EP 5046 PN 2 PG 1 WC Ophthalmology SC Ophthalmology GA WN215 UT WOS:A1997WN21501867 ER PT J AU Gasch, AT Caruso, RC Schiffman, RM Smith, JA Nussenblatt, RB Mueller, B Whitcup, SM AF Gasch, AT Caruso, RC Schiffman, RM Smith, JA Nussenblatt, RB Mueller, B Whitcup, SM TI Electro-oculography in children with AIDS treated with didanosine SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 NIH,NEI,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 1997 VL 38 IS 4 BP 5155 EP 5155 PN 2 PG 1 WC Ophthalmology SC Ophthalmology GA WN215 UT WOS:A1997WN21501976 ER PT J AU Chesky, L Nagineni, C Detrick, B Hooks, JJ AF Chesky, L Nagineni, C Detrick, B Hooks, JJ TI CMV immediate early (IE) gene expression in human RPE 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 1997 VL 38 IS 4 BP 5158 EP 5158 PN 2 PG 1 WC Ophthalmology SC Ophthalmology GA WN215 UT WOS:A1997WN21501979 ER PT J AU Detrick, B Hooks, JJ Nagineni, C Henry, S Anderson, K AF Detrick, B Hooks, JJ Nagineni, C Henry, S Anderson, K TI Inhibition of CMV replication in human RPE cells following treatment with fomivirsen-sodium (isis 2922) a CMV antisense oligonucleotide. SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 GEORGE WASHINGTON UNIV,MED CTR,WASHINGTON,DC 20037. ISIS PHARMACEUT,CARLSBAD,CA 92008. 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 1997 VL 38 IS 4 BP 5162 EP 5162 PN 2 PG 1 WC Ophthalmology SC Ophthalmology GA WN215 UT WOS:A1997WN21501983 ER PT J AU Iwata, F Caruso, RC Ayres, LM Kuehl, EM McCain, LM Gahl, WA KaiserKupfer, MI AF Iwata, F Caruso, RC Ayres, LM Kuehl, EM McCain, LM Gahl, WA KaiserKupfer, MI TI Ocular manifestations of Hermansky-Pudlak syndrome SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 NICHHD,NIH,BETHESDA,MD 20892. NEI,NIH,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 1997 VL 38 IS 4 BP 5235 EP 5235 PN 2 PG 1 WC Ophthalmology SC Ophthalmology GA WN215 UT WOS:A1997WN21502056 ER PT J AU Li, Y Lee, CH Wiggs, J Jenkins, NA Chew, C Zack, DJ AF Li, Y Lee, CH Wiggs, J Jenkins, NA Chew, C Zack, DJ TI Mouse and human map location and genomic structure of the genes for the small Gtp-binding proteins Rin and Rit SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 JOHNS HOPKINS UNIV,SCH MED,WILMER INST,BALTIMORE,MD 21287. JOHNS HOPKINS UNIV,SCH MED,DEPT NEUROSCI,BALTIMORE,MD 21287. JOHNS HOPKINS UNIV,SCH MED,DEPT MOL BIOL & GENET,BALTIMORE,MD 21287. NEW ENGLAND EYE CTR,BOSTON,MA. NCI,FREDERICK,MD 21702. 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 1997 VL 38 IS 4 BP 5282 EP 5282 PN 2 PG 1 WC Ophthalmology SC Ophthalmology GA WN215 UT WOS:A1997WN21502103 ER PT J AU Rapoport, AL Kozak, C Farber, DB AF Rapoport, AL Kozak, C Farber, DB TI Cloning and characterization of a novel photoreceptor-specific gene SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 UNIV CALIF LOS ANGELES,SCH MED,JULES STEIN EYE INST,LOS ANGELES,CA 90024. NIAID,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 1997 VL 38 IS 4 BP 5283 EP 5283 PN 2 PG 1 WC Ophthalmology SC Ophthalmology GA WN215 UT WOS:A1997WN21502104 ER PT J AU Li, W Nagineni, CN Efiok, B Hooks, JJ Chepelinsky, AB Egwuagu, CE AF Li, W Nagineni, CN Efiok, B Hooks, JJ Chepelinsky, AB Egwuagu, CE TI Differential activation of interferon regulatory factor (IRF) transcription factors in ocular cells SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 NEI,NIH,BETHESDA,MD 20892. NHLBI,NIH,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 1997 VL 38 IS 4 BP 5293 EP 5293 PN 2 PG 1 WC Ophthalmology SC Ophthalmology GA WN215 UT WOS:A1997WN21502114 ER PT J AU Liu, SY Henningsgaard, A Yu, S Lustgarten, EL Redmond, TM AF Liu, SY Henningsgaard, A Yu, S Lustgarten, EL Redmond, TM TI Promoter analysis of the mouse RPE65 gene SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 NIH,HOWARD HUGHES MED INST,MONTGOMERY CTY PUBL SCH INTERNSHIP PROGRAM,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 1997 VL 38 IS 4 BP 5302 EP 5302 PN 2 PG 1 WC Ophthalmology SC Ophthalmology GA WN215 UT WOS:A1997WN21502123 ER PT J AU Salamon, C Piatigorsky, J Sax, CM AF Salamon, C Piatigorsky, J Sax, CM TI Cloning, characterization, and functional promoter analysis of the mouse transketolase gene SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 NEI,MOL & DEV BIOL LAB,NIH,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 1997 VL 38 IS 4 BP 5304 EP 5304 PN 2 PG 1 WC Ophthalmology SC Ophthalmology GA WN215 UT WOS:A1997WN21502125 ER PT J AU Edwards, A Klein, ML Berselli, CB Weleber, RG Rust, K Wirtz, MK Hejtmancik, JF Acott, TS AF Edwards, A Klein, ML Berselli, CB Weleber, RG Rust, K Wirtz, MK Hejtmancik, JF Acott, TS TI Refinement of the locus for malattia leventinese: An autosomal dominant form of macular degeneration with a radial drusen phenotype SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 NEI,BETHESDA,MD 20892. OREGON HLTH SCI UNIV,CASEY EYE INST,PORTLAND,OR 97201. 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 1997 VL 38 IS 4 BP 5342 EP 5342 PN 2 PG 1 WC Ophthalmology SC Ophthalmology GA WN215 UT WOS:A1997WN21502163 ER PT J AU Prendergast, RA Caspi, RR Tarrant, TK Iliff, CE AF Prendergast, RA Caspi, RR Tarrant, TK Iliff, CE TI Class II positive antigen-presenting cells in retina and iris in T cell-induced EAU SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 JOHNS HOPKINS UNIV,BALTIMORE,MD. NEI,NIH,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 1997 VL 38 IS 4 BP 5407 EP 5407 PN 2 PG 1 WC Ophthalmology SC Ophthalmology GA WN215 UT WOS:A1997WN21502228 ER PT J AU Mahdi, RM Charukamnoetkanok, P Li, W Smith, JA Chan, CC Egwuagu, CE AF Mahdi, RM Charukamnoetkanok, P Li, W Smith, JA Chan, CC Egwuagu, CE TI Interferon gamma influences the temporal onset and the severity of experimental autoimmune uveoretinitis (EAU) SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 NEI,NIH,BETHESDA,MD 20892. NIH,HOWARD HUGHES MED INST,RES SCHOLARS PROGRAM,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 1997 VL 38 IS 4 BP 5410 EP 5410 PN 2 PG 1 WC Ophthalmology SC Ophthalmology GA WN215 UT WOS:A1997WN21502231 ER PT J AU Kador, PF Secchi, F Lizak, MJ Sato, S Lin, LR Reddy, VN AF Kador, PF Secchi, F Lizak, MJ Sato, S Lin, LR Reddy, VN TI Metabolism of fluorinated sugars in cultured dog and human lens epithelial cells by F-19-NMR SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 NEI,NIH,LAB OCULAR THERAPEUT,BETHESDA,MD. OAKLAND UNIV,EYE RES INST,ROCHESTER,MI 48063. 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 1997 VL 38 IS 4 BP 5454 EP 5454 PN 2 PG 1 WC Ophthalmology SC Ophthalmology GA WN215 UT WOS:A1997WN21502275 ER PT J AU Gorski, JP Kramer, EA Chen, Y Ryan, S Fullenkamp, C Delviscio, J Jensen, K McKee, MD AF Gorski, JP Kramer, EA Chen, Y Ryan, S Fullenkamp, C Delviscio, J Jensen, K McKee, MD TI Bone acidic glycoprotein-75 self-associates to form macromolecular complexes in vitro and in vivo with the potential to sequester phosphate ions SO JOURNAL OF CELLULAR BIOCHEMISTRY LA English DT Article DE bone acidic glycoprotein-75; self-association; aggregation-dependent neoepitope; macromolecular complexes in vivo and in vitro; sequestration of phosphate ions ID MAJOR 66-KDA PHOSPHOPROTEIN; ULTRASTRUCTURAL IMMUNOLOCALIZATION; HYDROXYAPATITE FORMATION; CRYSTAL-FORMATION; SIALOPROTEIN-II; MATRIX PROTEINS; CHICKEN BONE; RAT BONE; OSTEOPONTIN; TRANSGLUTAMINASE AB Monoclonal antibody HTP IV-#1 specifically recognizes a complexation-dependent neoepitope on bone acidic glycoprotein-75 (BAG-75) and a Mr = 50 kDa fragment. Complexes of BAG-75 exist in situ, as shown by immunofluorescent staining of the primary spongiosa of rat tibial metaphysis and osteosarcoma cell micromass cultures with monoclonal antibody HTP IV-#1. Incorporation of BAG-75 into complexes by newborn growth plate and calvarial tissues was confirmed with a second, anti-BAG-75 peptide antibody (#503). Newly synthesized BAG-75 immunoprecipitated from mineralizing explant cultures of bone was present entirely in large macromolecular complexes, while immunoprecipitates from monolayer cultures of osteoblastic cells were previously shown to contain only monomeric Mr = 75 kDa BAG-75 and a 50 kDa fragment. Purified BAG-75 self-associated in vitro to form large spherical aggregate structures composed of a meshwork of 10 nm diameter fibrils. These structures have the capacity to sequester large amounts of phosphate ions as evidenced by X-ray microanalysis and by the fact that purified BAG-75 preparations, even after extensive dialysis against water, retained phosphate ions in concentrations more than 1,000-fold higher than can be accounted for by exchange calculations or by electrostatic binding. The ultrastructural distribution of immunogold-labeled BAG-75 in the primary spongiosa underlying the rat growth plate is distinct from that for other acidic phosphoproteins, osteopontin and bone sialoprotein. We conclude that BAG-75 self-associates in vitro and in vivo into microfibrillar complexes which are specifically recognized by monoclonal antibody HTP IV-#1. This propensity to self-associate into macromolecular complexes is not shared with acidic phosphoproteins osteopontin and bone sialoprotein. We hypothesize that an extracellular electronegative network of macromolecular BAG-75 complexes could serve an organizational role in forming bone or as a barrier restricting local diffusion of phosphate ions. (C) 1997 Wiley-Liss, Inc. C1 UNIV IOWA,DEPT BIOL,IOWA CITY,IA. UNIV MONTREAL,FAC DENT,DEPT STOMATOL,ELECTRON MICROSCOPY LAB,MONTREAL,PQ,CANADA. UNIV IOWA,NIH,DEV STUDIES HYBRIDOMA BANK,IOWA CITY,IA. RP Gorski, JP (reprint author), UNIV MISSOURI,DIV MOL BIOL & BIOCHEM,SCH BIOL SCI,5100 ROCKHILL RD,KANSAS CITY,MO 64110, USA. FU NIAMS NIH HHS [AR40923, AR37078] NR 53 TC 20 Z9 20 U1 1 U2 2 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0730-2312 J9 J CELL BIOCHEM JI J. Cell. Biochem. PD MAR 15 PY 1997 VL 64 IS 4 BP 547 EP 564 PG 18 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA WQ876 UT WOS:A1997WQ87600003 PM 9093904 ER PT J AU Woitach, JT Conner, EA Wirth, PJ Thorgeirsson, SS AF Woitach, JT Conner, EA Wirth, PJ Thorgeirsson, SS TI Aberrant expression and regulation of hepatic epidermal growth factor receptor in a c-myc transgenic mouse model SO JOURNAL OF CELLULAR BIOCHEMISTRY LA English DT Article DE TGF-alpha; mitogenic signal; tyrosine kinase activity; SP1; transcription ID SIGNAL-TRANSDUCTION; GENE AMPLIFICATION; PROTEIN EXPRESSION; LIVER NEOPLASIA; MESSENGER-RNA; CELL-LINES; HEPATOCARCINOGENESIS; ALPHA; OVEREXPRESSION; TRANSCRIPTION AB In an attempt to elucidate the mechanism by which c-myc and transforming growth factor-alpha (TGF-alpha) cooperate in hepatocyte tumor development, we have analyzed signaling by the epidermal growth factor (EGF) receptor and the consequent regulation of receptor number in transgenic mice bearing the c-myc transgene under the control of the albumin enhancer/promoter. I-125-EGF binding and Scatchard analysis indicated a single class of high affinity receptors with the total number of binding sites of 1.2 x 10(4) +/- 600 and 2.5 x 10(5) +/- 1000 sites/cell in the normal and c-myc hepatocytes in primary culture, respectively. After 72 h of EGF exposure in culture, the number of detectable EGF receptors on the cell surface of the c-myc hepatocytes was not reduced, whereas the number of EGF receptors on normal hepatocytes was reduced to 32% that of untreated hepatocytes. Nuclear run-on experiments done with nuclei isolated from intact livers demonstrated that transcription of the EGF receptor was 4.9-fold higher in c-myc mice. Increased levels of the transcriptional factor SP1 in the c-myc hepatocytes in vivo and in primary culture, suggest a mechanism for the increased transcription of the EGF receptor. c-myc also increases the expression of TGF-alpha; a consequent increase in tyrosine phosphorylation is also detected in vivo. Thus, the increased number of EGF receptors in c-myc expressing hepatocytes, even after prolonged exposure to EGF, or TGF-alpha in vivo, may allow greater triggering of the EGF receptor signaling cascade. (C) 1997 Wiley-Liss Inc. C1 NCI, EXPT CARCINOGENESIS LAB, NATL INST HLTH, BETHESDA, MD 20892 USA. NR 38 TC 3 Z9 3 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0730-2312 EI 1097-4644 J9 J CELL BIOCHEM JI J. Cell. Biochem. PD MAR 15 PY 1997 VL 64 IS 4 BP 651 EP 660 PG 10 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA WQ876 UT WOS:A1997WQ87600013 PM 9093914 ER PT J AU Anton, LC Yewdell, JW Bennink, JR AF Anton, LC Yewdell, JW Bennink, JR TI MHC class I-associated peptides produced from endogenous gene products with vastly different efficiencies SO JOURNAL OF IMMUNOLOGY LA English DT Article ID RESTRICTED ANTIGEN PRESENTATION; TOXIC LYMPHOCYTES-T; ENDOPLASMIC-RETICULUM; MONOCLONAL-ANTIBODIES; TAP TRANSPORTERS; INFECTED-CELLS; MOLECULES; PROTEIN; BINDING; IDENTIFICATION AB We compared the efficiency of generating antigenic peptides from various polypeptide contexts expressed by recombinant vaccinia viruses. These included full-length influenza virus nucleoprotein (NP1-498), two truncated forms, and cytosolic and endoplasmic reticulum-targeted minimal peptides. Two peptides were studied, NP50-57 (K-k-restricted) and NP147-155 (K-d-restricted). The efficiency of peptide generation was measured in cytotoxicity assays by determining 1) the kinetics of presentation following infection using brefeldin A to block additional presentation and 2) the concentration of anti-class I mABs required to block presentation. The two determinants behaved similarly, being presented most efficiently from minigene products, with intermediate efficiency from fragments, and least efficiently from NP1-498. Direct quantitation of HPLC-purified peptides supported the validity of these simple methods to roughly estimate the efficiency of class I Ag presentation. It also surprisingly revealed that 60- to 90-fold more NP50-57 than NP147-155 peptide was present in cells expressing NP1-498 or a rapidly degraded fragment (for NP1-498, 1800 peptides/cell of NP50-57 vs 30 peptides/cell of NP147-155). By contrast, nearly identical (and much greater) amounts of peptides were recovered from cells expressing minigene products (55,000 copies of either peptide/cell). These findings demonstrate 1) that immunodominant peptides from the same protein can be generated with vastly different efficiencies, and 2) that cytosolic or endoplasmic reticulum-targeted minigene products are presented far more efficiently than longer polypeptides. C1 NIAID,VIRAL DIS LAB,BETHESDA,MD 20892. RI yewdell, jyewdell@nih.gov/A-1702-2012; Anton, Luis/C-4740-2013 OI Anton, Luis/0000-0001-9665-011X NR 42 TC 91 Z9 91 U1 0 U2 3 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 1997 VL 158 IS 6 BP 2535 EP 2542 PG 8 WC Immunology SC Immunology GA WM435 UT WOS:A1997WM43500006 PM 9058784 ER PT J AU He, YW Nakajima, H Leonard, WJ Adkins, B Malek, TR AF He, YW Nakajima, H Leonard, WJ Adkins, B Malek, TR TI The common gamma-chain of cytokine receptors regulates intrathymic T cell development at multiple stages SO JOURNAL OF IMMUNOLOGY LA English DT Article ID X-LINKED IMMUNODEFICIENCIES; MICE LACKING JAK3; LYMPHOID DEVELOPMENT; INTERLEUKIN-7 RECEPTOR; DEFICIENT MICE; EXPRESSION; BETA; DIFFERENTIATION; LYMPHOCYTES; MATURATION AB Signaling through the common gamma chain (gamma c), a subunit of the receptors for IL-2, -4, -7, -9, and -15, is critical for lymphocyte development, with the IL-7/IL-7R representing one important interaction. To investigate the stages of intrathymic T cell development that are dependent on gamma c and to determine whether gamma c controls T cell development solely as a component of the IL-7R, intrathymic T tell development was compared in IL-7R alpha-deficient mice and anti-gamma c-treated chimeric mice reconstituted with bone marrow and purified pro-T cells. In the presence of anti-gamma c, each of four phenotypically distinguishable stages of CD4(-)CD8(-) thymocytes failed to reconstitute T cell development, suggesting that each of these subsets of pro-T cells required gamma c for their differentiation and/or growth. Reconstitution of anti-gamma c-treated chimeric mice with bone marrow from IL-7R alpha-deficient mice indicated that IL-7R only partially contributed to intrathymic T cell development. Furthermore, when compared with IL-7R-deficient mice, anti-gamma c chimeric and gamma c-deficient mice exhibited a distinct phenotypic pattern of pro-T cell development. Collectively, these results indicate that several gamma c-sharing cytokines may contribute to T cell development in the thymus and suggest that one of these cytokines may be novel. C1 UNIV MIAMI,SCH MED,DEPT MICROBIOL & IMMUNOL,MIAMI,FL 33101. UNIV MIAMI,SCH MED,DEPT PATHOL,MIAMI,FL 33101. NHLBI,MOL IMMUNOL LAB,NIH,BETHESDA,MD 20892. FU NCI NIH HHS [R01-CA45957] NR 36 TC 42 Z9 42 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 1997 VL 158 IS 6 BP 2592 EP 2599 PG 8 WC Immunology SC Immunology GA WM435 UT WOS:A1997WM43500013 PM 9058791 ER PT J AU Taub, DD Murphy, WJ Asai, O Fenton, RG Peltz, G Key, ML TurcovskiCorrales, S Longo, DL AF Taub, DD Murphy, WJ Asai, O Fenton, RG Peltz, G Key, ML TurcovskiCorrales, S Longo, DL TI Induction of alloantigen-specific T cell tolerance through the treatment of human T lymphocytes with wortmannin SO JOURNAL OF IMMUNOLOGY LA English DT Article ID PHOSPHATIDYLINOSITOL 3-KINASE; MONOCLONAL-ANTIBODY; PHOSPHOLIPASE-D; CYCLOSPORINE-A; CLONAL ANERGY; ACTIVATION; CD28; COSTIMULATION; ASSOCIATION; COMPLEX AB Signaling through the CD28 molecule on T cells by its natural ligand, B7, on APCs has recently been shown to require the presence of an active phosphatidylinositol 3-kinase pathway to mediate some of its costimulatory activities (1-7). Using the phosphatidylinositol 3-kinase inhibitor, wortmannin (WN) (8), on human and murine T cells, we have inhibited B7-1-mediated T cell activation and induced Ag-specific tolerance. The addition of WN and/or the B7-1 antagonist, CTLA4lg, to primary human T cell cultures stimulated with B7-1-transfected allogeneic melanoma cell lines inhibited the generation of alloantigen-specific proliferative and cytolytic responses in vitro. Subsequent examination of these WN- and CTLA4lg-treated primary T cell cultures revealed that these lymphocyte populations were tolerized to rechallenge with the priming alloantigens in secondary cultures in the absence of additional inhibitor(s). However, reactivity to a third party allogeneic stimulator remained intact. This WN-induced tolerance was reversed by the addition of high dose IL-2, but not IL-4 or IL-7, to the primary cultures, indicating that T cell anergy, not deletion, was responsible for this phenomenon. In vivo studies using a murine graft-vs-host disease (GVHD) model demonstrated that WN treatment of allogeneic donor lymphocytes in vitro failed to generate a significant GVHD in irradiated mouse recipients compared with control allogeneic donor lymphocytes. These findings suggest potentially novel therapeutic strategies for the prevention of GVHD. C1 NCI,BIOL CARCINOGENESIS & DEV PROGRAM,SCI APPLICAT INT CORP,FREDERICK CANC RES & DEV CTR,FREDERICK,MD 21702. NIA,OFF SCI DIRECTOR,BALTIMORE,MD 21224. SYNTEX INC,PALO ALTO,CA 94303. RP Taub, DD (reprint author), NCI,CLIN SERV PROGRAM,SCI APPLICAT INT CORP,FREDERICK CANC RES & DEV CTR,BLDG 560,RM 11-23,FREDERICK,MD 21702, USA. NR 42 TC 16 Z9 18 U1 1 U2 1 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD MAR 15 PY 1997 VL 158 IS 6 BP 2745 EP 2755 PG 11 WC Immunology SC Immunology GA WM435 UT WOS:A1997WM43500031 PM 9058809 ER PT J AU Vergelli, M Hemmer, B Muraro, PA Tranquill, L Biddison, WE Sarin, A McFarland, HF Martin, R AF Vergelli, M Hemmer, B Muraro, PA Tranquill, L Biddison, WE Sarin, A McFarland, HF Martin, R TI Human autoreactive CD4(+) T cell clones use perforin- or Fas/Fas ligand-mediated pathways for target cell lysis SO JOURNAL OF IMMUNOLOGY LA English DT Article ID MYELIN BASIC-PROTEIN; FAS ANTIGEN; MULTIPLE-SCLEROSIS; HEPATITIS-C; CYTOTOXICITY; LYMPHOCYTES; CD4+; ACTIVATION; CYTOLYSIS; MECHANISM AB It is well established that target cell lysis by MHC class I-restricted CD8(+) T cells is an important defense mechanism during infections with intracellular pathogens or against tumor targets. On the other hand, little is known about the physiologic role and the mechanisms of cytotoxicity of CD4(+) MHC class II-restricted T cells. We have recently demonstrated that human autoreactive CD4(+) T cells specific for one candidate autoantigen of multiple sclerosis, myelin basic protein, can mediate cytotoxicity. In the present report, we analyze the cytolytic mechanisms employed by these cells, We show that individual T cell clones, regardless of their cytokine phenotype, can be noncytotoxic or lyse target cells via either perforin- or Fas/Fas ligand-mediated cytotoxicity. C1 NINCDS,NEUROIMMUNOL BRANCH,NIH,BETHESDA,MD 20892. NCI,EXPT IMMUNOL BRANCH,NIH,BETHESDA,MD 20892. UNIV TUBINGEN,DEPT NEUROL,SCH MED,D-7400 TUBINGEN,GERMANY. NR 40 TC 79 Z9 80 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 1997 VL 158 IS 6 BP 2756 EP 2761 PG 6 WC Immunology SC Immunology GA WM435 UT WOS:A1997WM43500032 PM 9058810 ER PT J AU Seetharamaiah, GS Dallas, JS Patibandla, SA Thotakura, NR Prabhakar, BS AF Seetharamaiah, GS Dallas, JS Patibandla, SA Thotakura, NR Prabhakar, BS TI Requirement of glycosylation of the human thyrotropin receptor ectodomain for its reactivity with autoantibodies in patients' sera SO JOURNAL OF IMMUNOLOGY LA English DT Article ID RECOMBINANT EXTRACELLULAR DOMAIN; IDIOPATHIC MYXEDEMA PATIENTS; AUTOIMMUNE THYROID-DISEASE; SITE-DIRECTED MUTAGENESIS; HIGH-AFFINITY BINDING; TSH RECEPTOR; GRAVES-DISEASE; SYNTHETIC PEPTIDES; HORMONE-RECEPTOR; INSECT CELLS AB To understand the role of glycosylation on autoantibody reactivity, we expressed cDNA encoding amino acid residues 22 to 416 of the human thyrotropin receptor (TSHR), along with the baculovirus-encoded glycoprotein 67 signal sequence (ETSHR-gp) in insect cells. N-terminal sequence analysis revealed that the signal peptide was cleaved and confirmed the identity of ETSHR-gp protein. The molecular mass of the ETSHR-gp protein was 63 kDa and was higher than the expected molecular mass of 45 kDa, suggesting that the protein was glycosylated. Carbohydrate analysis showed that the protein was glycosylated and that mannose was the major oligosaccharide. A nonglycosylated recombinant ETSHR protein expressed earlier in our laboratory neutralized TSH-binding-inhibitory Ig (TBII) activity in the sera of rabbits immunized with the protein but did not neutralize TBII activity in the sera of patients. In contrast, the glycosylated ETSHR-gp protein neutralized TBII activity in the sera of both experimental animals and patients with autoimmune thyroid disorders. Furthermore, only the ETSHR-gp protein completely neutralized the activities of stimulatory and blocking Abs in the sera of patients with hyperthyroidism and hypothyroidism, respectively. These data clearly show that glycosylated ETSHR-gp, but not the nonglycosylated ETSHR protein, can react with autoantibodies in patients' sera and that it has the epitopes required for the binding of TBII, thyroid stimulatory Abs, and thyroid stimulatory blocking Abs. Moreover, these data suggest that glycosylation might be an important determinant of autoantigenicity of human TSHR. C1 UNIV TEXAS,MED BRANCH,DEPT IMMUNOL & MICROBIOL,GALVESTON,TX 77555. UNIV TEXAS,MED BRANCH,DEPT PEDIAT,GALVESTON,TX 77555. NIDDK,MOL & CELLULAR ENDOCRINOL BRANCH,NIH,BETHESDA,MD 20892. FU NIDDK NIH HHS [DK47417, DK44972] NR 34 TC 35 Z9 37 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 1997 VL 158 IS 6 BP 2798 EP 2804 PG 7 WC Immunology SC Immunology GA WM435 UT WOS:A1997WM43500037 PM 9058815 ER PT J AU Yuhki, N OBrien, SJ AF Yuhki, N OBrien, SJ TI Nature and origin of polymorphism in feline MHC class II DRA and DRB genes SO JOURNAL OF IMMUNOLOGY LA English DT Article ID MAJOR HISTOCOMPATIBILITY COMPLEX; NUCLEOTIDE SUBSTITUTION; OVERDOMINANT SELECTION; SEQUENCE-ANALYSIS; LEUKEMIA-VIRUS; DOMESTIC CAT; DIVERSITY; DNA; ANTIGEN; ALLELES AB Transcripts of the MHC class II DRA and DRB gene homologues of the domestic cat (Felis catus) were cloned and sequenced to compare the pattern and process of DR gene divergence. Homologous DRB exon 2 sequences from 36 feral domestic cats throughout the world plus from three species of Felidae (tiger cat, Iriomote cat, and Geoffroy's cat) were also determined. Limited variation in the domestic cat Feca-DRA gene was observed, but abundant variation in the Feca-DRB gene was seen comprising 61 distinct DRB alleles. Phylogenetic analyses resolved at least five monophyletic feline DRB allelic lineages (DRB*1 to *5), which are clearly distinct from those of human (HLA-DRB1 to 9 lineages), mouse (H-2E beta b, u, f), and dog DRB alleles. Approximately 80% of individual cats contained three to six distinct DRB sequences, indicating that feline MHC maintains two to three DRB loci. Five cats had three DRB sequences in a single allelic lineage, indicating the occurrence of recent gene duplication of feline DRB genes. DRB sequences isolated from three exotic cats demonstrated close association with a particular domestic cat DRB lineage, suggesting that these allelic lineages are derived from common ancestral alleles that existed prior to the divergence of these feline species about 10 to 15 million years ago. Patterns of synonymous and nonsynonymous nucleotide substitution rates that occurred in Ag recognition sites (ARS) and nonrecognition (NAR) sites demonstrated a strong role of natural selection-positive selection for Ag recognition sites and negative selection for nonrecognition sites of feline DRB sequences-in the process of evolution of DR molecules. RP Yuhki, N (reprint author), NCI,GENET SECT,GENOM DIVERS LAB,FREDERICK CANC RES & DEV CTR,BLDG 560,RM 2153,FREDERICK,MD 21702, USA. NR 48 TC 48 Z9 53 U1 1 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 1997 VL 158 IS 6 BP 2822 EP 2833 PG 12 WC Immunology SC Immunology GA WM435 UT WOS:A1997WM43500040 PM 9058818 ER PT J AU Wang, RX Fang, QD Zhang, LY Radvany, L Sharma, A NobenTrauth, N Mills, GB Shi, YF AF Wang, RX Fang, QD Zhang, LY Radvany, L Sharma, A NobenTrauth, N Mills, GB Shi, YF TI CD28 ligation prevents bacterial toxin-induced septic shock in mice by inducing IL-1O expression SO JOURNAL OF IMMUNOLOGY LA English DT Article ID TUMOR-NECROSIS-FACTOR; T-CELL ACTIVATION; INTERFERON-GAMMA; PROLIFERATIVE RESPONSES; PROTECTS MICE; ENDOTOXEMIA; SURVIVAL; ANTIGEN; MACROPHAGES; ANTIBODIES AB The pathogenesis of septic shock is due mainly to bacterial toxin stimulation of the immune system, resulting in an excessive production of proinflammatory cytokines. TNF-alpha has been implicated as a major mediator in septic shock. Coinjection of D-galactosamine and LPS or staphylococcal enterotoxin B induced a rapid-onset, low-dose form of septic shock syndrome and ultimately led to death. We found that both the septic shock syndrome and death could be prevented by administration of anti-CD28 Ab. The protection induced by anti-CD28 Ab was associated with a decrease in TNF-alpha levels in the circulation. In addition, serum from anti-CD28 Ab-treated mice was capable of inhibiting the production of TNF-alpha by bone marrow-derived macrophages following treatment with LPS, indicating that anti-CD28 Ab induced production of soluble factors that subsequently inhibited the production of TNF-alpha. We confirmed that one of the factors present in serum was IL-10, because anti-CD28 Ab treatment stimulated the expression of IL-10, both in splenocytes and in T cell lines. Furthermore, injection of anti-IL-10 Abs could abolish the protective effect of anti-CD28 Ab on septic shock. Anti-IL-10 Ab could also suppress the anti-CD28 Ab-induced inhibition of TNF-alpha production, either in vivo or in vitro. Thus, we conclude that ligation of CD28 induces expression of IL-10, which in turn suppresses TNF-alpha production and prevents septic shock. C1 AMER RED CROSS, JEROME H HOLLAND LAB, DEPT IMMUNOL, ROCKVILLE, MD 20855 USA. PRINCESS MARGARET HOSP, ONTARIO CANC INST, TORONTO, ON M4X 1K9, CANADA. NIAID, IMMUNOL LAB, NIH, ROCKVILLE, MD 20852 USA. UNIV TEXAS, MD ANDERSON CANC CTR, DEPT MOL ONCOL, HOUSTON, TX 77030 USA. NR 33 TC 15 Z9 16 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 1997 VL 158 IS 6 BP 2856 EP 2861 PG 6 WC Immunology SC Immunology GA WM435 UT WOS:A1997WM43500044 PM 9058822 ER PT J AU Segal, R Bermas, BL Dayan, M Kalush, F Shearer, GM Mozes, E AF Segal, R Bermas, BL Dayan, M Kalush, F Shearer, GM Mozes, E TI Kinetics of cytokine production in experimental systemic lupus erythematosus - Involvement of T helper cell 1 T helper cell 2-type cytokines in disease SO JOURNAL OF IMMUNOLOGY LA English DT Article ID TUMOR-NECROSIS-FACTOR; B-LYMPHOCYTE HYPERACTIVITY; GENE-EXPRESSION; RHEUMATOID-ARTHRITIS; MESSENGER-RNA; FACTOR-ALPHA; PRONE MICE; INTERLEUKIN-2; SLE; IL-1 AB We followed cytokine production from induction through disease progression in a murine model of experimental systemic lupus erythematosus (SLE). SLE was induced by immunization with the human monoclonal anti-DNA Ab that bears the common Id designated 16/6 Id. BALB/c and C3H.SW mice that are susceptible to SLE induction and C57BL/6 mice that are resistant were immunized with the 16/6 Id. Cytokine production was tested periodically for 7 mo. Increased production of IL-2 and IFN-gamma, the Th1-type cytokines, was detected in BALB/c and C3H.SW mice 2 to 4 mo following immunization. IL-4 and IL-10, the Th2-type cytokines predominated later in disease course, and peaked 5 mo following disease induction. At this stage the Th1 type cytokines dropped to levels below those observed in controls, IL-4 production also dropped rapidly to very low levels, while IL-10 production decreased but remained above control levels. The ratio of IgG2a/IgG1 of DNA and 16/6 Id-specific Abs peaked at 2 mo following disease induction and decreased later, in concordance with the higher production of Th2-type cytokines. Thus, the development of experimental SLE in mice involves two stages: increased production of Th1-type, followed by increased induction of Th2-type cytokines. High levels of the proinflammatory cytokines, TNF-rw and IL-l, were maintained throughout disease course. No significant changes were detected in the cytokine profile of C57BL/6 immunocytes following immunization with the 16/6 Id, supporting the possible role of the cytokine network in SLE. C1 SHMUEL HAROFEH MED CTR,BEER YAAGOV,ISRAEL. NCI,EXPT IMMUNOL BRANCH,NIH,BETHESDA,MD 20894. RP Segal, R (reprint author), WEIZMANN INST SCI,DEPT IMMUNOL,IL-76100 REHOVOT,ISRAEL. NR 43 TC 95 Z9 101 U1 1 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 1997 VL 158 IS 6 BP 3009 EP 3016 PG 8 WC Immunology SC Immunology GA WM435 UT WOS:A1997WM43500062 PM 9058840 ER PT J AU Chang, DY Newitt, JA Hsu, K Bernstein, HD Maraia, RJ AF Chang, DY Newitt, JA Hsu, K Bernstein, HD Maraia, RJ TI A highly conserved nucleotide in the Alu domain of SRP RNA mediates translation arrest through high affinity binding to SRP9/14 SO NUCLEIC ACIDS RESEARCH LA English DT Article ID SIGNAL RECOGNITION PARTICLE; ENDOPLASMIC-RETICULUM MEMBRANE; COLI 4.5S RNA; PROTEIN TRANSLOCATION; RIBONUCLEOPROTEIN PARTICLE; NASCENT PREPROLACTIN; SECONDARY STRUCTURE; 7SL RNA; SEQUENCE; POLYPEPTIDE AB Binding of the signal recognition particle (SRP) to signal sequences during translation leads to an inhibition of polypeptide elongation known as translation arrest, The arrest activity is mediated by a discrete domain comprised of the Alu portion of SRP RNA and a 9 and 14 kDa polypeptide heterodimer (SRP9/14). Although very few nucleotides in SRP RNA are conserved throughout evolution, the remarkable conservation of G24, which resides in the region of SRP9/14 interaction, suggests that it is essential for translation arrest, To understand the functional significance of the G24 residue, we made single base substitutions in SRP RNA at this position and analyzed the ability of the mutants to bind SRP9/14 and to reconstitute functional SRPs, Mutation of G24 to C reduced binding to SRP9/14 by at least 50-fold, whereas mutation to A and U reduced binding similar to 2- and 5-fold respectively, The mutant RNAs could nevertheless assemble into SRPs at high subunit concentrations, SRPs reconstituted with mutant RNAs were not significantly defective in translation arrest assays, indicating that the conserved guanosine does not interact directly with the translational machinery, Taken together, these results demonstrate that G24 plays an important role in the translation arrest function of SRP by mediating high affinity binding of SRP9/14. C1 NICHHD,LAB MOL GROWTH REGULAT,NIH,BETHESDA,MD 20892. NIDDK,GENET & BIOCHEM BRANCH,NIH,BETHESDA,MD 20892. HOWARD HUGHES MED INST,RES SCHOLARS PROGRAM,NIH,BETHESDA,MD 20892. NR 42 TC 19 Z9 19 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD, ENGLAND OX2 6DP SN 0305-1048 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD MAR 15 PY 1997 VL 25 IS 6 BP 1117 EP 1122 DI 10.1093/nar/25.6.1117 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA WP583 UT WOS:A1997WP58300005 PM 9092618 ER PT J AU Poltorak, M Wright, R Hemperly, JJ Torrey, EF Issa, F Wyatt, RJ Freed, WJ AF Poltorak, M Wright, R Hemperly, JJ Torrey, EF Issa, F Wyatt, RJ Freed, WJ TI Monozygotic twins discordant for schizophrenia are discordant for N-CAM and L1 in CSF SO BRAIN RESEARCH LA English DT Article DE neural cell adhesion molecule; L1 antigen; contactin; cell recognition molecule; cerebrospinal fluid; schizophrenia ID RECOGNITION AB While schizophrenia has a genetic component, its pathogenesis is unknown. Abnormal concentrations of two cell recognition molecules (CRMs), neural-cell adhesion molecule (N-CAM) and L1 antigen have been described in the cerebrospinal fluid (CSF) of patients with schizophrenia. Studies of monozygotic twins discordant for schizophrenia may help separate genetic and environmental contributions to the disease. In the present study of monozygotic twins discordant for schizophrenia, the affected twins had increased N-CAM and decreased L1 antigen in their CSF. Non-affected twins were not different from normals. Although processes related to genetic instability cannot be entirely ruled out, these results suggest that these abnormalities are not a part of the genetic predisposition to become schizophrenic. Thus the changes in N-CAM and L1 antigen may reflect either the events which precipitated the onset of schizophrenia, or events which are associated with the experience of having the disease. (C) 1997 Elsevier Science B.V. C1 BECTON DICKINSON RES CTR,RES TRIANGLE PK,NC 27709. ST ELIZABETH HOSP,NIMH,CTR NEUROSCI,SECT PRECLIN NEUROSCI,WASHINGTON,DC 20032. ST ELIZABETH HOSP,NIMH,CTR NEUROSCI,NEUROPSYCHIAT BRANCH,WASHINGTON,DC 20032. ST ELIZABETH HOSP,NIMH,CTR NEUROSCI,TWIN STUDIES UNIT,WASHINGTON,DC 20032. RP Poltorak, M (reprint author), GEORGE WASHINGTON UNIV,MED CTR,DEPT NEUROL,2150 PENN AVE NW,WASHINGTON,DC 20037, USA. NR 15 TC 35 Z9 36 U1 1 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 1997 VL 751 IS 1 BP 152 EP 154 DI 10.1016/S0006-8993(97)00023-1 PG 3 WC Neurosciences SC Neurosciences & Neurology GA WR178 UT WOS:A1997WR17800019 PM 9098580 ER PT J AU Degerman, E Belfrage, P Manganiello, VC AF Degerman, E Belfrage, P Manganiello, VC TI Structure, localization, and regulation of cGMP-inhibited phosphodiesterase (PDE3) SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Review ID CYCLIC-NUCLEOTIDE PHOSPHODIESTERASES; KM CAMP PHOSPHODIESTERASE; ACTIVATED PROTEIN-KINASE; AMP PHOSPHODIESTERASE; FAT-CELLS; SENSITIVE PHOSPHODIESTERASE; SELECTIVE INHIBITORS; MOLECULAR-CLONING; RAT ADIPOCYTES; INSULIN C1 NHLBI,PULM CRIT CARE MED BRANCH,NIH,BETHESDA,MD 20892. LUND UNIV,SECT MOL SIGNALING,DEPT CELL & MOL BIOL,S-22100 LUND,SWEDEN. NR 61 TC 288 Z9 297 U1 0 U2 4 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD MAR 14 PY 1997 VL 272 IS 11 BP 6823 EP 6826 PG 4 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA WN147 UT WOS:A1997WN14700001 PM 9102399 ER PT J AU Jiang, H StUlme, D Dickens, G Chabuk, A Lavarreda, M Lazarovici, P Guroff, G AF Jiang, H StUlme, D Dickens, G Chabuk, A Lavarreda, M Lazarovici, P Guroff, G TI Both p140(trk) and p75(NGFR) nerve growth factor receptors mediate nerve growth factor-stimulated calcium uptake SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID PROTEIN KINASE-C; FACTOR-INDUCED INCREASE; PC12 CELLS; NEURITE OUTGROWTH; CHROMAFFIN CELLS; FIBER OUTGROWTH; K-252A; RAT; NEURONS; PHOSPHORYLATION AB Human p140(trk) and p75(NGFR) were transfected separately into 3T3 cells. Nerve growth factor stimulates calcium uptake into both transfectants but not into untransfected 3T3 cells. p140(trk) cells were stimulated maximally by 25 ng/ml; 100 ng/ml was submaximal for p75(NGFR) cells. K-252a inhibits the effect of NGF on p140(trk) cells but not on p75(NGFR) cells; brain-derived neurotrophic factor stimulates calcium uptake in p75(NGFR) cells but not in p140(trk) cells. The data suggest that both nerve growth factor receptors could be involved in the nerve growth factor-mediated actions of calcium on its target cells: neuronal survival, neuronal protection, and synaptic plasticity. C1 NICHHD,GROWTH FACTORS SECT,NIH,BETHESDA,MD 20892. HEBREW UNIV JERUSALEM,FAC MED,SCH PHARM,DEPT PHARMACOL,IL-91010 JERUSALEM,ISRAEL. NR 41 TC 25 Z9 25 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD MAR 14 PY 1997 VL 272 IS 11 BP 6835 EP 6837 PG 3 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA WN147 UT WOS:A1997WN14700004 PM 9054365 ER PT J AU Baler, R Covington, S Klein, DC AF Baler, R Covington, S Klein, DC TI The rat arylalkylamine N-acetyltransferase gene promoter - cAMP activation via a cAMP-responsive element-CCAAT complex SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID INDUCIBLE ENHANCER ELEMENTS; TRANSCRIPTION FACTOR; ADRENERGIC REGULATION; BINDING FACTOR; PINEAL-GLAND; CYCLIC-AMP; EXPRESSION; INITIATOR; PROTEINS; RNA AB A 10-100-fold rhythm in the activity of arylalkylamine N-acetyltransferase (AA-NAT; EC 2.3.1.87) controls the rhythm in melatonin synthesis in the pineal gland. In some mammals, including the rat, the high nocturnal level of AA-NAT activity is preceded by an similar to 100-fold increase in AA-NAT mRNA The increase in AA-NAT mRNA is generated by norepinephrine acting through a cAMP mechanism. Indirect evidence has suggested that cAMP enhances AA-NAT gene expression by stimulating phosphorylation of a DNA-binding protein (cAMP-responsive element (CRE)-binding protein) bound to a CRE. The nature of the sites involved in cAMP activation was investigated in this report by analysing the AA-NAT promoter. An similar to 3700-base pair fragment of the 5'-flanking region of the rat AA-NAT gene was isolated, and the major transcription start points were mapped. The results of deletion analysis and site-directed mutagenesis indicate that cAMP activation requires a CRE-CCAAT complex consisting of a near-perfect CRE and an inverted CCAAT box located within two helical turns. C1 NICHHD,SECT NEUROENDOCRINOL,DEV NEUROBIOL LAB,NIH,BETHESDA,MD 20892. NR 44 TC 142 Z9 143 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 14 PY 1997 VL 272 IS 11 BP 6979 EP 6985 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA WN147 UT WOS:A1997WN14700026 PM 9054387 ER PT J AU Taylor, N Candotti, F Smith, S Oakes, SA Jahn, T Isakov, J Puck, JM OShea, JJ Weinberg, K Johnston, JA AF Taylor, N Candotti, F Smith, S Oakes, SA Jahn, T Isakov, J Puck, JM OShea, JJ Weinberg, K Johnston, JA TI Interleukin-4 signaling in B lymphocytes from patients with X-linked severe combined immunodeficiency SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID RECEPTOR-GAMMA-CHAIN; JAK-3 JANUS KINASE; IL-2 RECEPTOR; TYROSINE PHOSPHORYLATION; FUNCTIONAL COMPONENT; STAT PROTEINS; T-CELLS; ACTIVATION; INSULIN; TRANSDUCTION AB Interleukin-4 (IL-4) is an important cytokine for B and T lymphocyte function and mediates its effects via a receptor that contains gamma(c), B cells derived from patients with X-linked severe combined immunodeficiency (X-SCID) are deficient in gamma(c) and provide a useful model in which to dissect the role of this subunit in IL-4-mediated signaling. me found that although IL-4 stimulation of X-SCID B cells did not result in Janus tyrosine kinase-3 (JAK3) phosphorylation, other IL-4 substrates including JAK1 and IRS-1 were phosphorylated, Additionally, we detected signal transducers and activators of transcription 6 (STAT6) tyrosine phosphorylation and DNA binding activity in X-SCID B cells with a wide range of gamma(c) mutations. However, reconstitution of these X-SCID B cells with gamma(c) enhanced IL-4-mediated responses including STAT6 phosphorylation and DNA binding activity and resulted in increased CD23 expression. Thus, gamma(c) is not necessary to trigger IL-4-mediated responses in B cells, but its presence is important for optimal IL-4-signaling, These results suggest that two distinct IL-4 signaling pathways exist. C1 CHILDRENS HOSP LOS ANGELES,DIV RES IMMUNOL & BONE MARROW TRANSPLANTAT,LOS ANGELES,CA 90027. NIH,NATL CTR HUMAN GENOME RES,CLIN GENE THERAPY BRANCH,BETHESDA,MD 20855. NIAMSD,LYMPHOCYTE CELL BIOL SECT,BETHESDA,MD 20855. NIH,NATL CTR HUMAN GENOME RES,IMMUNOL GENET SECT,BETHESDA,MD 20855. RP Taylor, N (reprint author), INST GENET MOL MONTPELLIER,1919 ROUTE MENDE,F-34033 MONTPELLIER 1,FRANCE. RI Taylor, Naomi/H-4016-2014 NR 62 TC 21 Z9 21 U1 1 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 14 PY 1997 VL 272 IS 11 BP 7314 EP 7319 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA WN147 UT WOS:A1997WN14700068 PM 9054429 ER PT J AU Bell, JB Eckert, KA Joyce, CM Kunkel, TA AF Bell, JB Eckert, KA Joyce, CM Kunkel, TA TI Base miscoding and strand misalignment errors by mutator klenow polymerases with amino acid substitutions at tyrosine 766 in the O helix of the fingers subdomain SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID HIV-1 REVERSE-TRANSCRIPTASE; ESCHERICHIA-COLI; FRAMESHIFT FIDELITY; DNA-REPLICATION; TEMPLATE-PRIMER; FRAGMENT; PROCESSIVITY; SITES AB A mutant derivative of Klenow fragment DNA polymerase containing serine substituted for tyrosine at residue 766 has been shown by kinetic analysis to have an increased misinsertion rate relative to wild-type Klenow fragment, but a decreased rate of extension from the resulting mispairs (Carroll, S. S., Cowart, M., and Benkovic, S. J. (1991) Biochemistry 30, 804-813). In the present study we use an M13mp2-based fidelity assay to study the error specificity of this mutator polymerase. Despite its compromised ability to extend mispairs, the Y766S polymerase and a Y766A mutant both have elevated base substitution error fates, The magnitude of the mutator effect is mispair-specific, from no effect for some mispairs to rates elevated by 60-fold for misincorporation of TMP opposite template G. The results with the Y766S mutant are remarkably consistent with the earlier kinetic analysis of misinsertion, demonstrating that either approach can be used to identify and characterize mutator polymerases, Both the Y766S and Y766A mutant polymerases are also frameshift mutators, having elevated rates for two-base deletions and a 276-base deletion between a direct repeat sequence, However, neither mutant polymerase has an increased error rate for single-base frameshifts in repetitive sequences, This error specificity suggests that the deletions generated by the mutator polymerases are initiated by misinsertion rather than by strand slippage. When considered with recent structure-function studies of other polymerases, the data indicate that the nucleotide misinsertion and strand-slippage mechanisms for polymerization infidelity are differentially affected by changes in distinct structural elements of DNA polymerases that share similar subdomain structures. C1 NIEHS,MOL GENET LAB,NIH,RES TRIANGLE PK,NC 27709. YALE UNIV,BASS CTR MOL & STRUCT BIOL,DEPT BIOCHEM & MOL BIOPHYS,NEW HAVEN,CT 06520. NR 34 TC 65 Z9 65 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 14 PY 1997 VL 272 IS 11 BP 7345 EP 7351 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA WN147 UT WOS:A1997WN14700072 PM 9054433 ER PT J AU Sakai, N Vaisman, BL Koch, CA Hoyt, RF Meyn, SM Talley, GD Paiz, JA Brewer, HB SantamarinaFojo, S AF Sakai, N Vaisman, BL Koch, CA Hoyt, RF Meyn, SM Talley, GD Paiz, JA Brewer, HB SantamarinaFojo, S TI Targeted disruption of the mouse lecithin:cholesterol acyltransferase (LCAT) gene - Generation of a new animal model for human LCAT deficiency SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID ESTER TRANSFER PROTEIN; PLASMA-LIPOPROTEINS; A-I; SUBPOPULATIONS; EXPRESSION AB We have established a mouse model for human LCAT deficiency by performing targeted disruption of the LCAT gene in mouse embryonic stem cells, Homozygous LCAT-deficient mice were healthy at birth and fertile, Compared with age-matched wild-type littermates, the LCAT activity in heterozygous and homozygous knockout mice was reduced by 30 and 99%, respectively, LCAT deficiency resulted in significant reductions in the plasma concentrations of total cholesterol, HDL cholesterol, and apoA-I in both LCAT -/- mice (25, 7, and 12%; p < 0.001 of normal) and LCAT +/- mice (65 and 59%;p < 0.001 and 81%; not significant, p = 0.17 of normal), In addition, plasma triglycerides were significantly higher (212% of normal; p < 0.01) in male homozygous knockout mice compared with wild-type animals but remained normal in female knockout LCAT mice, Analyses of plasma lipoproteins by fast protein liquid chromatography and two-dimensional gel electrophoresis demonstrated the presence of heterogenous prep-migrating HDL, as well as triglyceride-enriched very low density lipoprotein, After 3 weeks on a high-fat high-cholesterol diet, LCAT -/- mice had significantly lower plasma concentrations of total cholesterol, reflecting reduced levels of both proatherogenic apoB-containing lipoproteins as well as HDL, compared with controls, Thus, we demonstrate for the first time that the absence of LCAT attenuates the rise of apoB-containing lipoproteins in response to dietary cholesterol, No evidence of corneal opacities or renal insufficiency was detected in 4-month-old homozygous knockout mice, The availability of a homozygous animal model for human LCAT deficiency states will permit further evaluation of the role that LCAT plays in atherosclerosis as well as the feasibility of performing gene transfer in human LCAT deficiency states. C1 NHLBI,LAB ANIM MED & SURG,NIH,BETHESDA,MD 20892. RP Sakai, N (reprint author), NHLBI,MOL DIS BRANCH,NIH,BLDG 10,RM 7N115,10 CTR DR,MSC 1666,BETHESDA,MD 20892, USA. NR 27 TC 83 Z9 83 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 14 PY 1997 VL 272 IS 11 BP 7506 EP 7510 PG 5 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA WN147 UT WOS:A1997WN14700093 PM 9054454 ER PT J AU Kline, RH Izenwasser, S Katz, JL Joseph, DB Bowen, WD Newman, AH AF Kline, RH Izenwasser, S Katz, JL Joseph, DB Bowen, WD Newman, AH TI 3'-chloro-3 alpha-(diphenylmethoxy)tropane but not 4'-chloro-3 alpha-(diphenylmethoxy)tropane produces a cocaine-like behavioral profile SO JOURNAL OF MEDICINAL CHEMISTRY LA English DT Article; Proceedings Paper CT 57th Annual Scientific Meeting of the College-on-Problems-of-Drug-Dependence CY JUN 11-16, 1995 CL SCOTTSDALE, AZ SP Coll Problems Drug Dependence ID DOPAMINE UPTAKE INHIBITORS; RAT-BRAIN; SYNAPTOSOMAL PREPARATIONS; HIGH-AFFINITY; BINDING; ANALOGS; TRANSPORTER; RECEPTOR; POTENT; SITES AB A series of 2'- and 3'-substituted and 3',3''-disubstituted 3 alpha-(diphenylmethoxy)tropane analogs were designed and synthesized as novel probes for the dopamine transporter. All the analogs were evaluated for displacement of [H-3]WIN 35,428 binding at the dopamine transporter and for inhibition of [H-3]dopamine uptake in rat caudate putamen. Compounds were observed to monophasically displace [H-3]WIN 35,428 binding to the dopamine transporter with affinities of 21.6-1836 nM (K-i). Generally, meta-substituted compounds were more potent than benztropine and equipotent to or slightly less potent than their previously reported para-substituted homologs in inhibiting [H-3]WIN 35,428 binding. However, these same meta-substituted analogs were typically less potent than the 4'-substituted analogs in inhibiting [H-3]dopamine uptake. Ortho-substituted analogs were generally less potent in both binding and inhibition of uptake at the dopamine transporter than either benztropine or other aryl-substituted homologs. The analogs were also tested for binding at norepinephrine and serotonin transporters as well as muscarinic m(1) receptors. None of the compounds in the present study bound with high affinity to either the norepinephrine or serotonin transporters, but all bound to muscarinic m(1) receptors with high affinity (K-i = 0.41-2.52 nM). Interestingly, 3'-chloro-3 alpha-(diphenylmethoxy)tropane (5c) produced effects like cocaine in animals trained to discriminate 10 mg/kg cocaine from saline, unlike its 4'-Cl homolog and all of the previously evaluated benztropine analogs. Further evaluation of compound 5c and the other benztropine analogs will undoubtedly prove useful in the elucidation of the role of the dopamine transporter in the reinforcing effects of cocaine and the ultimate identification of a cocaine-abuse treatment. C1 NIDA,PSYCHOBIOL SECT,NIH,DIV INTRAMURAL RES,BALTIMORE,MD 21224. NIDDK,UNIT RECEPTOR BIOCHEM & PHARMACOL,MED CHEM LAB,NATL INST HLTH,BETHESDA,MD 20892. RI Izenwasser, Sari/G-9193-2012 NR 33 TC 44 Z9 44 U1 1 U2 2 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0022-2623 J9 J MED CHEM JI J. Med. Chem. PD MAR 14 PY 1997 VL 40 IS 6 BP 851 EP 857 DI 10.1021/jm950782k PG 7 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA WN195 UT WOS:A1997WN19500005 PM 9083473 ER PT J AU Xu, LF Kelkar, SV Lomenzo, SA Izenwasser, S Katz, JL Kline, RH Trudell, ML AF Xu, LF Kelkar, SV Lomenzo, SA Izenwasser, S Katz, JL Kline, RH Trudell, ML TI Synthesis, dopamine transporter affinity, dopamine uptake inhibition, and locomotor stimulant activity of 2-substituted 3 beta-phenyltropane derivatives SO JOURNAL OF MEDICINAL CHEMISTRY LA English DT Article ID COCAINE RECEPTOR; LIGAND-BINDING; RAT STRIATUM; ANALOGS; SITES; SEROTONIN; DISCOVERY; PROVIDES; POTENT; ESTER AB A series of 2 beta-substituted 3 beta-phenyltropanes were synthesized as analogs of cocaine and tested in vitro for their ability to displace bound [H-3]WIN 35,428 (2b) and inhibit; dopamine uptake in rat caudate-putamen tissue. The analogs bound with high affinity (K-i = 11-22 nM) to the dopamine transporter. Increased lipophilicity at the beta-C(2)-position was found to lead to increased binding affinity and increased dopamine uptake potency. However, a direct correlation between clogP values and binding affinity and potency of uptake inhibition was not observed. The unsaturated ester 7 was found to possess weak dopamine uptake inhibition relative to the high binding affinity (IC50/K-i = 10.2). In vivo measurement of stimulated locomotor activity and drug discrimination against cocaine (10 mg/kg, ip) with selected analogs (4, 6, and 7) demonstrated that the behavioral effects of these drugs were approximately equipotent with those of cocaine, The structure-activity relationships of this series of cocaine analogs supports a pharmacophore model in which lipophilic interactions between the B-C(2)position of 3 beta-phenyltropanes and the cocaine binding site on the dopamine transporter lead to enhanced potency while electrostatic interactions have a nonspecific effect. C1 UNIV NEW ORLEANS,DEPT CHEM,NEW ORLEANS,LA 70148. NIDA,DIV INTRAMURAL RES,BALTIMORE,MD 21224. RI Izenwasser, Sari/G-9193-2012 FU NIDA NIH HHS [R29 DA08055] NR 28 TC 30 Z9 30 U1 1 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 14 PY 1997 VL 40 IS 6 BP 858 EP 863 DI 10.1021/jm960739c PG 6 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA WN195 UT WOS:A1997WN19500006 PM 9083474 ER PT J AU Nicklaus, MC Neamati, N Hong, HX Mazumder, A Sunder, S Chen, J Milne, GWA Pommier, Y AF Nicklaus, MC Neamati, N Hong, HX Mazumder, A Sunder, S Chen, J Milne, GWA Pommier, Y TI HIV-1 integrase pharmacophore: Discovery of inhibitors through three-dimensional database searching SO JOURNAL OF MEDICINAL CHEMISTRY LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; DRUG INFORMATION-SYSTEM; CATION-PI INTERACTIONS; TYPE-1 INTEGRASE; IN-VITRO; RIBONUCLEASE-H; MOLECULAR RECOGNITION; CRYSTAL-STRUCTURE; CATALYTIC DOMAIN; ESCHERICHIA-COLI AB Starting from a known inhibitor of human immunodeficiency virus type 1 (HIV-1) integrase (IN), caffeic acid phenethyl ester (CAFE), a putative three-point pharmacophore for binding of inhibitors to IN was derived. This pharmacophore was used to search the National Cancer Institute three-dimensional (3D) structural database. Out of the open, nonproprietary part of this database, comprising approximately 200 000 compounds, 267 structures were found to match the pharmacophore in at least one conformation, and 60 of those were tested in an in vitro assay against HIV-1 IN. Out of these, 19 were found to inhibit both the 3'-processing and strand transfer of IN at micromolar concentrations. In order to test the validity of this pharmacophore, a small 3D database of 152 published IN inhibitors was built. A search in this database yielded a statistically significant correlation of the presence of this pharmacophore and the potency of the compounds. An automated pharmacophore identification procedure performed on this set of compounds provided additional support for the importance of this pharmacophore for binding of inhibitors to IN and hinted at a possible second pharmacophore. The role of aromatic moieties in the binding of ligands to HIV-1 IN through interactions with divalent metal, cations, which are known to be necessary for activity of the enzyme, was explored in ab initio calculations. C1 NCI,MOL PHARMACOL LAB,DIV BASIC SCI,NIH,BETHESDA,MD 20892. RP Nicklaus, MC (reprint author), NCI,MED CHEM LAB,DIV BASIC SCI,NIH,37 CONVENT DR,BETHESDA,MD 20892, USA. RI Nicklaus, Marc/N-4183-2014 NR 66 TC 153 Z9 158 U1 1 U2 11 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 14 PY 1997 VL 40 IS 6 BP 920 EP 929 DI 10.1021/jm960596u PG 10 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA WN195 UT WOS:A1997WN19500012 PM 9083480 ER PT J AU Hong, HX Neamati, N Wang, SM Nicklaus, MC Mazumder, A Zhao, H Burke, TR Pommier, Y Milne, GWA AF Hong, HX Neamati, N Wang, SM Nicklaus, MC Mazumder, A Zhao, H Burke, TR Pommier, Y Milne, GWA TI Discovery of HIV-1 integrase inhibitors by pharmacophore searching SO JOURNAL OF MEDICINAL CHEMISTRY LA English DT Article ID IMMUNODEFICIENCY-VIRUS TYPE-1; DEFICIENCY SYNDROME AIDS; DRUG INFORMATION-SYSTEM; 3D DATABASE; DESIGN; PROTEASE; INFECTION; ANALOGS; FUTURE AB Based upon a class of known HIV-1 integrase inhibitors, several pharmacophore models were proposed from molecular modeling studies and validated using a 3D database of 152 compounds for which integrase assay data are known. Using the most probable pharmacophore model as the query, the NCI 3D database of 206 876 compounds was searched, and 340 compounds that contain the pharmacophore query were identified. Twenty-nine of these compounds were selected and tested in the HIV-1 integrase assay. This led to the discovery of 10 novel, structurally diverse HIV-1 integrase inhibitors, four of which have an IC50 value less than 30 mu M and are promising lead compounds for further HIV-1 integrase inhibitor development. C1 NCI,MOL PHARMACOL LAB,DIV BASIC SCI,NIH,BETHESDA,MD 20892. RP Hong, HX (reprint author), NCI,MED CHEM LAB,DIV BASIC SCI,NIH,BLDG 37,BETHESDA,MD 20892, USA. RI Wang, Shaomeng/E-9686-2010; Nicklaus, Marc/N-4183-2014; Burke, Terrence/N-2601-2014 NR 46 TC 101 Z9 107 U1 0 U2 5 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 14 PY 1997 VL 40 IS 6 BP 930 EP 936 DI 10.1021/jm960754h PG 7 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA WN195 UT WOS:A1997WN19500013 PM 9083481 ER PT J AU Zhao, H Neamati, N Sunder, S Hong, HX Wang, SM Milne, GWA Pommier, Y Burke, TR AF Zhao, H Neamati, N Sunder, S Hong, HX Wang, SM Milne, GWA Pommier, Y Burke, TR TI Hydrazide-containing inhibitors of HIV-1 integrase SO JOURNAL OF MEDICINAL CHEMISTRY LA English DT Article ID IMMUNODEFICIENCY-VIRUS TYPE-1; DERIVATIVES; PROTEIN; INVITRO AB Inhibitors of HIV integrase are currently being sought as potential new therapeutics for the treatment of AIDS. A large number of inhibitors discovered to date contain the o-bis-hydroxy catechol structure. In an effort to discover structural leads for the development of new HIV integrase inhibitors which do not rely on this potentially cytotoxic catechol substructure, NSC 310217 was identified using a three-point pharmacophore search based on its assigned structure N-(2-hydroxybenzoyl)-N-(2-hydroxy-3-phenoxypropyl)hydrazine (1). When a sample of NSC 310217 was obtained from the NCI repository, it was shown to exhibit potent inhibition of HIV-1 integrase (3'-processing IC50 = 0.6 mu g/mL). In work reported herein, we demonstrate that NSC 310217, rather than containing 1, which has no inhibitory potency against HIV-1 integrase, is comprised of roughly a 1:1 mixture of N-(2-hydroxybenzoyl)-N'-(2-hydroxy-3-phenoxypropyl)hydrazine (6) and N,N'-bis-salicylhydrazine 7, with all inhibitory potency residing with compound 7 (IC50 = 0.7 mu M for strand transfer). In subsequent structure-activity studies on 7, it is shown that removing a single amide carbonyl (compound 14, IC50 = 5.2 mu M) or replacing one aromatic ring system with a naphthyl ring (compound 19, IC50 = 1.1 mu M) can be accomplished with little loss of inhibitory potency. Additionally, replacing a single hydroxyl with a sulfhydryl (compound 23, IC50 = 5.8 mu M) results in only moderate loss of potency. All other modifications examined, including the replacement of a single hydroxyl with an amino group (compound 22), resulted in complete loss of potency. Being potent, structurally simple, and non-catechol-containing, compounds such as 7 and 14 may provide useful leads for the development of a new class of HIV integrase inhibitor. C1 NCI, MED CHEM LAB, DIV BASIC SCI, NIH, BETHESDA, MD 20892 USA. NCI, MOL PHARMACOL LAB, DIV BASIC SCI, NIH, BETHESDA, MD 20892 USA. RI Wang, Shaomeng/E-9686-2010; Burke, Terrence/N-2601-2014 NR 26 TC 95 Z9 96 U1 1 U2 6 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0022-2623 EI 1520-4804 J9 J MED CHEM JI J. Med. Chem. PD MAR 14 PY 1997 VL 40 IS 6 BP 937 EP 941 DI 10.1021/jm960755+ PG 5 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA WN195 UT WOS:A1997WN19500014 PM 9083482 ER PT J AU Neamati, N Hong, HX Mazumder, A Wang, SM Sunder, S Nicklaus, MC Milne, GWA Proksa, B Pommier, Y AF Neamati, N Hong, HX Mazumder, A Wang, SM Sunder, S Nicklaus, MC Milne, GWA Proksa, B Pommier, Y TI Depsides and depsidones as inhibitors of HIV-1 integrase: Discovery of novel inhibitors through 3D database searching SO JOURNAL OF MEDICINAL CHEMISTRY LA English DT Article ID DRUG INFORMATION-SYSTEM; VIRUS TYPE-1 INTEGRASE; DNA CLEAVAGE; ACID; PROTEIN; ANALOGS; POTENT; DESIGN; MODULE AB Seventeen lichen acids comprising depsides, depsidones, and their synthetic derivatives have been examined fur their inhibitory activity against HIV-1 integrase, and two pharmacophores associated with inhibition of this enzyme have been identified. A search of the NCI 3D database of approximately 200 000 structures yielded some 800 compounds which contain one or the other pharmacophore. Forty-two of these compounds were assayed for HIV-1 integrase inhibition, and of these, 27 had inhibitory IC50 values of less than 100 mu M; 15 were below 50 mu M. Several of these compounds were also examined for their activity against HIV-2 integrase and mammalian topoisamerase I. C1 NCI, MOL PHARMACOL LAB, DIV BASIC SCI, NIH, BETHESDA, MD 20892 USA. NCI, MED CHEM LAB, DIV BASIC SCI, NIH, BETHESDA, MD 20892 USA. SLOVAK UNIV TECHNOL BRATISLAVA, DEPT BIOCHEM TECHNOL, BRATISLAVA 81237, SLOVAKIA. RI Wang, Shaomeng/E-9686-2010; Nicklaus, Marc/N-4183-2014 NR 49 TC 164 Z9 171 U1 4 U2 11 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0022-2623 J9 J MED CHEM JI J. Med. Chem. PD MAR 14 PY 1997 VL 40 IS 6 BP 942 EP 951 DI 10.1021/jm960759e PG 10 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA WN195 UT WOS:A1997WN19500015 PM 9083483 ER PT J AU Shi, Q VerdierPinard, P Brossi, A Hamel, E McPhail, AT Lee, KH AF Shi, Q VerdierPinard, P Brossi, A Hamel, E McPhail, AT Lee, KH TI Antitumor agents .172. Synthesis and biological evaluation of novel deacetamidothiocolchicin-7-ols and ester analogs as antitubulin agents SO JOURNAL OF MEDICINAL CHEMISTRY LA English DT Article ID THIOCOLCHICINE ANALOGS; NATURAL COLCHICINOIDS; TUBULIN; BINDING; RING; DERIVATIVES AB A series of novel 7-O-substituted deacetamidothiocolchicine derivatives has been synthesized and evaluated for their inhibitory activity against tubulin polymerization, the binding of [H-3]-colchicine to tubulin, and the growth of human Burkitt lymphoma cells. Of these new derivatives, thiocolchicone (8), wherein an acetamido group in thiocolchicine is replaced by a carbonyl oxygen at C(7), was obtained from deacetylthiocolchicine (6) by Schiffs base equilibration and acid hydrolysis. Reduction of thiocolchicone with sodium borohydride yielded the racemic alcohol 9, the structure of which was verified by X-ray crystallographic analysis. Optically pure alcohols 9a,b were obtained by treatment of 9 with the optically pure reagent (1S)-(-)-camphanic chloride followed by chromatographic separation of the camphanate esters and hydrolysis of the diastereomers. X-ray crystallographic analysis established the aS,7S-configuration of 9a. Racemic and optically active esters 11-15, 11a,b, 12a, 14a, and 15a were obtained by esterification of the corresponding alcohols. The compounds showing activity equivalent to or greater than (-)-thiocolchicine (2a) in all the biological assays were three (-)-aS,7S optically pure enantiomers: the alcohol 9a, the acetate 11a (an oxygen isostere of thiocolchicine), and the isonicotinoate 15a. In addition, the ketone 8 and two (-)-aS,7S enantiomers (12a, 14a) had high activity in the biochemical assays with tubulin but reduced antiproliferative activity. In all cases, optically pure isomers with the (-)-aS,7S configuration exhibited greater biological activity than racemic mixtures or isomers with the (+)-aR,7R configuration. C1 UNIV N CAROLINA,SCH PHARM,DIV MED CHEM & NAT PROD,NAT PROD LAB,CHAPEL HILL,NC 27599. NCI,DIV BASIC SCI,MOL PHARMACOL LAB,NIH,BETHESDA,MD 20892. DUKE UNIV,DEPT CHEM,PAUL M GROSS CHEM LAB,DURHAM,NC 27708. FU NCI NIH HHS [CA 17625, CA 54508] NR 27 TC 47 Z9 50 U1 0 U2 3 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 14 PY 1997 VL 40 IS 6 BP 961 EP 966 DI 10.1021/jm960663k PG 6 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA WN195 UT WOS:A1997WN19500017 PM 9083485 ER PT J AU Yan, XJ Hollis, T Svinth, M Day, P Monzingo, AF Milne, GWA Robertus, JD AF Yan, XJ Hollis, T Svinth, M Day, P Monzingo, AF Milne, GWA Robertus, JD TI Structure-based identification of a ricin inhibitor SO JOURNAL OF MOLECULAR BIOLOGY LA English DT Article DE ricin; inhibitor; X-ray structure; pteroic acid; neopterin ID TOXIN-A CHAIN; ENZYMATIC INACTIVATION; GLUTAMIC ACID-177; ACTIVE-SITE; DESIGN; MECHANISM; RIBOSOMES; PROTEIN; 2.5-A; MUTAGENESIS AB Ricin is a potent cytotoxin which has been used widely in the construction of therapeutic agents such as immunotoxins. Recently it has been used by governments and underground groups as a poison. There is interest in identifying and designing effective inhibitors of the ricin A chain (RTA). In this study computer-assisted searches indicated that pterins might bind in the RTA active site which normally recognizes a specific adenine base on rRNA. Kinetic assays showed that pteroic acid could inhibit RTA activity with an apparent K-i of 0.6 mM. A 2.3 Angstrom crystal structure of the complex revealed the mode of binding. The pterin ring displaces Tyr80 and binds in the adenine pocket making specific hydrogen bonds to active site residues. The benzoate moiety of pteroic acid binds on the opposite side of Tyr80 making van der Waals contact with the Tyr ring and forming a hydrogen bond with Asn78. Neopterin, a propane triol derivative of pterin, also binds to RTA as revealed by the X-ray structure of its complex with RTA. Neither pterin-6-carboxylic acid nor folic acid bind to the crystal or act as inhibitors. The models observed suggest alterations to the pterin moiety which may produce more potent and specific RTA inhibitors. (C) 1997 Academic Press Limited. C1 UNIV TEXAS,DEPT CHEM & BIOCHEM,AUSTIN,TX 78712. NCI,MED CHEM LAB,BETHESDA,MD 20892. FU NIGMS NIH HHS [GM 30048] NR 33 TC 65 Z9 69 U1 2 U2 4 PU ACADEMIC PRESS LTD PI LONDON PA 24-28 OVAL RD, LONDON, ENGLAND NW1 7DX SN 0022-2836 J9 J MOL BIOL JI J. Mol. Biol. PD MAR 14 PY 1997 VL 266 IS 5 BP 1043 EP 1049 DI 10.1006/jmbi.1996.0865 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA WM908 UT WOS:A1997WM90800016 PM 9086280 ER PT J AU Nunez, SB Medin, JA Braissant, O Kemp, L Wahli, W Ozato, K Segars, JH AF Nunez, SB Medin, JA Braissant, O Kemp, L Wahli, W Ozato, K Segars, JH TI Retinoid X receptor and peroxisome proliferator-activated receptor activate an estrogen responsive gene independent of the estrogen receptor SO MOLECULAR AND CELLULAR ENDOCRINOLOGY LA English DT Article DE estrogen receptors; regulate; transcription ID NUCLEAR HORMONE RECEPTORS; BREAST-CANCER CELLS; TRANSCRIPTIONAL ACTIVATION; SIGNALING PATHWAYS; CONFORMATIONAL CHANGE; 9-CIS-RETINOIC ACID; LIPID-METABOLISM; THYROID-HORMONE; CARCINOMA-CELLS; BINDING DOMAIN AB Estrogen receptors regulate transcription of genes essential for sexual development and reproductive function. Since the retinoid X receptor (RXR) is able to modulate estrogen responsive genes and both 9-cis RA and fatty acids influenced development of estrogen responsive tumors, we hypothesized that estrogen responsive genes might be modulated by RXR and the fatty acid receptor (peroxisome proliferator-activated receptor, PPAR). To test this hypothesis, transfection assays in CV-1 cells were performed with an estrogen response element (ERE) coupled to a luciferase reporter construct. Addition of expression vectors for RXR and PPAR resulted in an 11-fold increase in luciferase activity in the presence of 9-cis RA. Furthermore, mobility shift assays demonstrated binding of RXR and PPAR to the vitellogenin A2-ERE and an ERE in the oxytocin promoter. Methylation interference assays demonstrated that specific guanine residues required for RXR/PPAR binding to the ERE were similar to residues required for ER binding. Moreover, RXR domain-deleted constructs in transfection assays showed that activation required RXR since an RXR Delta AF-2 mutant completely abrogated reporter activity. Oligoprecipitation binding studies with biotinylated ERE and S-35-labeled in vitro translated RXR constructs confirmed binding of Delta AF-2 RXR mutant to the ERE in the presence of baculovirus-expressed PPAR. Finally, in situ hybridization confirmed RXR and PPAR mRNA expression in estrogen responsive tissues. Collectively, these data suggest that RXR and PPAR are present in reproductive tissues, are capable of activating estrogen responsive genes and suggest that the mechanism of activation may involve direct binding of the receptors to estrogen response elements. (C) 1997 Elsevier Science Ireland Ltd. C1 NATL INST HLTH,UNIT MOL MECH REPROD,DEV ENDOCRINOL BRANCH,BETHESDA,MD. NICHHD,LAB MOL GROWTH REGULAT,NATL INST HLTH,BETHESDA,MD 20892. UNIV LAUSANNE,INST BIOL ANIM,CH-1015 LAUSANNE,SWITZERLAND. RI Wahli, Walter/B-1398-2009 OI Wahli, Walter/0000-0002-5966-9089 NR 76 TC 81 Z9 83 U1 0 U2 1 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0303-7207 J9 MOL CELL ENDOCRINOL JI Mol. Cell. Endocrinol. PD MAR 14 PY 1997 VL 127 IS 1 BP 27 EP 40 DI 10.1016/S0303-7207(96)03980-9 PG 14 WC Cell Biology; Endocrinology & Metabolism SC Cell Biology; Endocrinology & Metabolism GA WQ319 UT WOS:A1997WQ31900004 PM 9099898 ER PT J AU Lange, N Giedd, JN Castellanos, FX Vaituzis, AC Rapoport, JL AF Lange, N Giedd, JN Castellanos, FX Vaituzis, AC Rapoport, JL TI Variability of human brain structure size: Ages 4-20 years SO PSYCHIATRY RESEARCH-NEUROIMAGING LA English DT Article DE variance; adolescent; child; coefficient of variation; magnetic resonance imaging; measurement error models; morphology; regression calibration ID WEIGHT; SCHIZOPHRENIA; MORPHOLOGY; RATIO AB Understanding variability of human brain structure sizes during development is important for the design and interpretation of pediatric neuroimaging studies. In this study we analyze the effects of hemisphere, sex and age on size variability of the total cerebrum, cerebellum, lateral ventricles, temporal lobe, amygdala, hippocampus, superior temporal gyrus, corpus callosum, caudate, putamen, and globus pallidus in 115 healthy children and adolescents, ages 4-20 years. Variability differed significantly across structures, with the lateral ventricles demonstrating the highest coefficient of variation and the putamen the lowest. Males varied significantly more than females in the left cerebrum and left superior temporal gyrus, whereas females varied more than males in the right caudate and right putamen. Age effects were seen in increased variability after puberty for the lateral ventricles, hippocampus and superior temporal gyrus. These variances are important determinants of minimum sample sizes required to detect group differences in both cross-sectional and longitudinal studies. (C) 1997 Elsevier Science Ireland Ltd. C1 MCLEAN HOSP,BRAIN IMAGING CTR,BELMONT,MA 02178. NIMH,NIH,CHILD PSYCHIAT BRANCH,BETHESDA,MD. RP Lange, N (reprint author), HARVARD UNIV,SCH MED,CONSOLIDATED DEPT PSYCHIAT,115 MILL ST,BELMONT,MA 02178, USA. RI Giedd, Jay/A-3080-2008; Giedd, Jay/B-7302-2012; Giedd, Jay/J-9644-2015 OI Giedd, Jay/0000-0003-0827-3460; Giedd, Jay/0000-0003-2002-8978 NR 35 TC 87 Z9 87 U1 0 U2 6 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0925-4927 J9 PSYCHIAT RES-NEUROIM JI Psychiatry Res. Neuroimaging PD MAR 14 PY 1997 VL 74 IS 1 BP 1 EP 12 DI 10.1016/S0925-4927(96)03054-5 PG 12 WC Clinical Neurology; Neuroimaging; Psychiatry SC Neurosciences & Neurology; Psychiatry GA WT886 UT WOS:A1997WT88600001 PM 10710158 ER PT J AU Irani, K Xia, Y Zweier, JL Sollott, SJ Der, CJ Fearon, ER Sundaresan, M Finkel, T GoldschmidtClermont, PJ AF Irani, K Xia, Y Zweier, JL Sollott, SJ Der, CJ Fearon, ER Sundaresan, M Finkel, T GoldschmidtClermont, PJ TI Mitogenic signaling mediated by oxidants in ras-transformed fibroblasts SO SCIENCE LA English DT Article ID GTP-BINDING PROTEIN; GENERATING NADPH OXIDASE; ACTIN STRESS FIBERS; C-JUN; HYDROGEN-PEROXIDE; ENDOTHELIAL-CELLS; REGULATED KINASES; CDC42 GTPASES; GROWTH; ACTIVATION AB NIH 3T3 fibroblasts stably transformed with a constitutively active isoform of p21(Ras), H-Ras(V12) (v-H-Ras or EJ-Ras), produced large amounts of the reactive oxygen species superoxide (. O-2-). . O-2(-) production was suppressed by the expression of dominant negative isoforms of Ras or Rac1, as well as by treatment with a farnesyltransferase inhibitor or with diphenylene iodonium, a flavoprotein inhibitor, The mitogenic activity of cells expressing H-Ras(V12) was inhibited by treatment with the chemical antioxidant N-acetyl-L-cysteine. Mitogen-activated protein kinase (MAPK) activity was decreased and c-Jun N-terminal kinase (JNK) was not activated in H-Ras(V12)-transformed cells. Thus, H-Ras(V12)-induced transformation can lead to the production of . O-2(-) through one or more pathways involving a flavoprotein and Rac1. The implication of a reactive oxygen species, probably . O-2(-), as a mediator of Ras-induced cell cycle progression independent of MAPK and JNK suggests a possible mechanism for the effects of antioxidants against Ras-induced cellular transformation. C1 JOHNS HOPKINS UNIV,SCH MED,DEPT MED,DIV CARDIOL,BALTIMORE,MD 21205. UNIV N CAROLINA,DEPT PHARMACOL,CHAPEL HILL,NC 27599. UNIV MICHIGAN,MED CTR,ANN ARBOR,MI 48109. NHLBI,CARDIOL BRANCH,NIH,BETHESDA,MD 20892. JOHNS HOPKINS UNIV,SCH MED,DEPT CELL BIOL & ANAT,BALTIMORE,MD 21205. RI Bell, Tiffany/F-4403-2010 FU NHLBI NIH HHS [HL52315] NR 48 TC 1132 Z9 1162 U1 5 U2 31 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 14 PY 1997 VL 275 IS 5306 BP 1649 EP 1652 DI 10.1126/science.275.5306.1649 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA WN123 UT WOS:A1997WN12300047 PM 9054359 ER PT J AU He, X SaintJeannet, JP Wang, YS Nathans, J Dawid, I Varmus, H AF He, X SaintJeannet, JP Wang, YS Nathans, J Dawid, I Varmus, H TI A member of the frizzled protein family mediating axis induction by Wnt-5A SO SCIENCE LA English DT Article ID GLYCOGEN-SYNTHASE KINASE-3; XENOPUS-LAEVIS EMBRYOS; SPEMANN ORGANIZER; EXPRESSION; DOMAINS; HOMOLOG; PATTERN; TISSUE; XWNT-8; GENES AB In Xenopus laevis embryos, the Wingless/Wnt-1 subclass of Wnt molecules induces axis duplication, whereas the Wnt-5A subclass does not. This difference could be explained by distinct signal transduction pathways or by a lack of one or more Wnt-5A receptors during axis formation. Wnt-5A induced axis duplication and an ectopic Spemann organizer in the presence of hFz5, a member of the Frizzled family of seven-transmembrane receptors. Wnt-5A/hFz5 signaling was antagonized by glycogen synthase kinase-3 and by the amino-terminal ectodomain of hFz5. These results identify hFz5 as a receptor for Wnt-5A. C1 NCI,NIH,BETHESDA,MD 20892. NICHHD,NIH,BETHESDA,MD 20892. JOHNS HOPKINS UNIV,SCH MED,DEPT MOL BIOL & GENET,HOWARD HUGHES MED INST,BALTIMORE,MD 21205. NR 29 TC 357 Z9 366 U1 0 U2 5 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 SN 0036-8075 J9 SCIENCE JI Science PD MAR 14 PY 1997 VL 275 IS 5306 BP 1652 EP 1654 DI 10.1126/science.275.5306.1652 PG 3 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA WN123 UT WOS:A1997WN12300048 PM 9054360 ER PT J AU Rightor, EG Hitchcock, AP Ade, H Leapman, RD Urquhart, SG Smith, AP Mitchell, G Fischer, D Shin, HJ Warwick, T AF Rightor, EG Hitchcock, AP Ade, H Leapman, RD Urquhart, SG Smith, AP Mitchell, G Fischer, D Shin, HJ Warwick, T TI Spectromicroscopy of poly(ethylene terephthalate): Comparison of spectra and radiation damage rates in x-ray absorption and electron energy loss SO JOURNAL OF PHYSICAL CHEMISTRY B LA English DT Article ID CORE EXCITATION SPECTROSCOPY; INNER-SHELL SPECTROSCOPY; PHOTOELECTRON-SPECTROSCOPY; MICROSCOPY; POLY(ETHYLENE-TEREPHTHALATE); MICROANALYSIS; ORIENTATION; DEPENDENCE; MOLECULES; POLYMERS AB The C 1s and O 1s X-ray absorption spectra of poly(ethylene terephthalate) (PET) have been recorded using transmission, fluorescence, and electron yield detection. The corresponding electron energy loss spectra (EELS) have been recorded in a scanning transmission electron microscope. These results are compared to the C 1s and O 1s spectra of gas phase 1,4-dimethyl terephthalate (the monomer of PET) recorded using EELS. The comparison of monomer and polymer materials in different phases and with different techniques has aided the understanding of the relative strengths and limitations of each technique as well as assisting the spectral interpretation. Good agreement is found in the overall shape and the energies of the spectral features. Relatively minor differences in intensities can be understood in terms of the properties of the individual spectroscopic techniques. The critical dose for radiation damage by 100 keV electrons incident on PET at 100 K is found to be (1.45 +/- 0.15) x 10(3) eV nm(-3). In contrast, the critical dose for radiation damage by 302 eV X-rays incident on PET at 300 K is (1.2 +/- 0.6) x 10(4) eV nm(-3). A figure of merit involving the product of critical energy dose and spectral efficiency (as expressed by the appropriate G value) is developed. This indicates that, for near-edge studies involving a 20 eV spectral width, there is similar to 500-fold advantage of X-ray absorption studies on room temperature PET relative to electron energy loss studies of cooled PET. C1 MCMASTER UNIV, DEPT CHEM, HAMILTON, ON L8S 4M1, CANADA. DOW CHEM CO USA, FREEPORT, TX 77541 USA. N CAROLINA STATE UNIV, DEPT PHYS, RALEIGH, NC 27695 USA. NIH, BEIP, NCRR, BETHESDA, MD 20892 USA. DOW CHEM CO USA, MIDLAND, MI 48667 USA. NATL INST STAND & TECHNOL, MAT SCI & ENGN LAB, GAITHERSBURG, MD 20899 USA. POHANG LIGHT SOURCE, POHANG, SOUTH KOREA. LAWRENCE BERKELY NATL LAB, BERKELEY, CA 91420 USA. RI Ade, Harald/E-7471-2011; Urquhart, Stephen/A-6237-2014 OI Urquhart, Stephen/0000-0002-6415-6341 NR 66 TC 123 Z9 123 U1 2 U2 23 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1520-6106 J9 J PHYS CHEM B JI J. Phys. Chem. B PD MAR 13 PY 1997 VL 101 IS 11 BP 1950 EP 1960 DI 10.1021/jp9622748 PG 11 WC Chemistry, Physical SC Chemistry GA WM886 UT WOS:A1997WM88600004 ER PT J AU Alter, HJ Nakatsuji, Y Melpolder, J Wages, J Wesley, R Shih, JWK Kim, JP AF Alter, HJ Nakatsuji, Y Melpolder, J Wages, J Wesley, R Shih, JWK Kim, JP TI The incidence of transfusion-associated hepatitis G virus infection and its relation to liver disease SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID NON-B-HEPATITIS; NON-A; C VIRUS; ANTIBODY; BLOOD AB Background The role of hepatitis G virus (HGV) in transfusion-associated infection and its relation to liver disease are not well understood. Methods Serum samples collected between 1972 and 1995 from 357 transfusion recipients, 157 controls who did not receive transfusions, 500 randomly selected volunteer blood donors, and 230 donors of blood received by HGV-infected patients were tested for HGV RNA by qualitative and quantitative polymerase-chain-reaction assays. Samples obtained before transfusion and serially after transfusion from 79 of the 81 transfusion recipients who had transfusion-associated non-A, non-B hepatitis were available for testing. Results Of the 79 patients with transfusion-associated hepatitis, 63 (80 percent) had infections related to the hepatitis C virus (HCV) and 3 had preexisting HCV and the cause of their acute hepatitis could not be determined; of the remaining 13 patients, 3 had acute HGV infection, and 10 were infected with unidentified agents. Six of the 63 patients with HCV infection who were tested (10 percent) were also infected with HGV. The three patients infected only with HGV had mild hepatitis (mean peak alanine aminotransferase level, 198 U per liter; none had jaundice); the levels of alanine aminotransferase and HGV RNA were not well correlated. The combined HCV and HGV infections were no more severe than HCV infections alone; the alanine aminotransferase values paralleled the levels of HCV RNA, but not those of HGV RNA, There were 35 HGV infections among the 357 transfusion recipients; only 3 had hepatitis with HGV as the sole viral marker. One of the 157 controls and 7 of the 500 randomly selected blood donors (1.4 percent) had detectable HGV RNA. In all eight instances in which a transfusion recipient had acute HGV infection after transfusion and samples from all donors could be tested, at least one HGV-positive donor was identified. Conclusions HGV was common in a group of volunteer blood donors, and it can be transmitted by transfusion. Most HGV infections were not associated with hepatitis. HGV did not worsen the course of concurrent HCV infection. No causal relation between HGV and hepatitis has been established. (C) 1997, Massachusetts Medical Society. C1 NIH,WARREN G MAGNUSON CLIN CTR,DEPT INFORMAT SYST,BETHESDA,MD 20892. RP Alter, HJ (reprint author), NIH,WARREN G MAGNUSON CLIN CTR,DEPT TRANSFUS MED,BLDG 10,RM 1C-711,BETHESDA,MD 20892, USA. NR 14 TC 479 Z9 490 U1 1 U2 1 PU MASS MEDICAL SOC PI BOSTON PA 10 SHATTUCK, BOSTON, MA 02115 SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD MAR 13 PY 1997 VL 336 IS 11 BP 747 EP 754 DI 10.1056/NEJM199703133361102 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA WM640 UT WOS:A1997WM64000002 PM 9052652 ER PT J AU Chen, WD Otterson, GA Lipkowitz, S Khleif, SN Coxon, AB Kaye, FJ AF Chen, WD Otterson, GA Lipkowitz, S Khleif, SN Coxon, AB Kaye, FJ TI Apoptosis is associated with cleavage of a 5 kDa fragment from RB which mimics dephosphorylation and modulates E2F binding SO ONCOGENE LA English DT Article DE apoptosis; chemotherapy; cysteine protease; FAS; retinoblastoma protein ID RETINOBLASTOMA GENE-PRODUCT; LUNG-CANCER; GROWTH SUPPRESSION; CELL-LINES; PROTEIN; IDENTIFICATION; DOMAIN; CLONING; MEMBER; FAMILY AB Dephosphorylation of the RE protein has been reported to be associated with apoptosis, In contrast, we show that treatment of HL60 cells with etoposide or cytosine arabinoside or treatment of breast epithelial cells with alpha-FAS is associated with the cleavage of a 5 kDa fragment from the C-terminus of RE, resulting in a truncated product that we have designated as p100cl. This cleavage event coincides with the activation of cysteine proteases at the onset of apoptosis, is blocked by the addition of iodoacetamide to cells prior to the onset of apoptosis, and results in the expression of faster migrating protein species which can mimic dephosphorylated RE. The free 5 kDa fragment is detected only during apoptosis, predicts a cleavage site that we have mapped to a unique CPP32-like recognition sequence which is present at the C-terminus of all reported RE homologues, and results in a truncated RE protein with enhanced E2F binding affinity, While the causality for this cleavage event in the apoptotic process is still under investigation, our findings suggest distinct post-translational pathways for the RE product between cells examined during growth arrest (p105 hypophosphorylated RE) or apoptosis (p100cl). C1 USN,NCI,MED ONCOL BRANCH,DIV CLIN SCI,BETHESDA,MD 20889. RI kaye, frederic/E-2437-2011; CHEN, WEI-DONG/F-4521-2014 OI CHEN, WEI-DONG/0000-0003-2264-5515 NR 24 TC 66 Z9 66 U1 0 U2 0 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE, HAMPSHIRE, ENGLAND RG21 6XS SN 0950-9232 J9 ONCOGENE JI Oncogene PD MAR 13 PY 1997 VL 14 IS 10 BP 1243 EP 1248 DI 10.1038/sj.onc.1201096 PG 6 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA WM782 UT WOS:A1997WM78200015 PM 9121775 ER PT J AU Takenoshita, S Tani, M Nagashima, M Hagiwara, K Bennett, WP Yokota, J Harris, CC AF Takenoshita, S Tani, M Nagashima, M Hagiwara, K Bennett, WP Yokota, J Harris, CC TI Mutation analysis of coding sequences of the entire transforming growth factor beta type II receptor gene in sporadic human colon cancer using genomic DNA and Intron primers SO ONCOGENE LA English DT Article DE transforming growth factor beta type II receptor; colon carcinogenesis; tumor biology ID MICROSATELLITE INSTABILITY; COLORECTAL-CANCER; CARCINOMA-CELLS; TGF-BETA AB Mutations in the transforming growth factor beta type II receptor (TGF beta RII) gene have been detected in several human cancers exhibiting microsatellite instability. To extend analyses of this gene, we previously investigated the exon-intron organization of the TGF beta RII. gene and defined seven exons and flanking intron sequences. In this study, we further determined the nucleotide sequences surrounding these seven exons and designed eight sets of intron-based primers to examine the entire coding region of the TGF beta RII gene. Using these primers, we screened genomic DNA sequences from 30 sporadic colorectal cancers for mutations of the TGF beta RII. gene. TGF beta RII mutations were detected in two of 30 tumors and both displayed microsatellite instability. One had a deletion in a polyadenine tract in exon 3 and the other had a point mutation in the kinase domain located in exon 7. There were no mutations in exons 1, 2, 4, 5 and 6. These results further implicate the polyadenine tract and kinase domain as mutational hotspots in the TGF beta RII gene in cells,vith genomic instability and suggest that TGF beta RII gene mutations occur rarely in cells lacking genomic instability. C1 NCI,HUMAN CARCINOGENESIS LAB,NIH,BETHESDA,MD 20892. NATL CANC CTR,RES INST,DIV BIOL,TOKYO 104,JAPAN. NR 12 TC 53 Z9 56 U1 0 U2 0 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE, HAMPSHIRE, ENGLAND RG21 6XS SN 0950-9232 J9 ONCOGENE JI Oncogene PD MAR 13 PY 1997 VL 14 IS 10 BP 1255 EP 1258 DI 10.1038/sj.onc.1200938 PG 4 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA WM782 UT WOS:A1997WM78200017 PM 9121777 ER PT J AU Ross, GW Abbott, RD Petrovitch, H Masaki, KH Murdaugh, C Trockman, C Curb, JD White, LR AF Ross, GW Abbott, RD Petrovitch, H Masaki, KH Murdaugh, C Trockman, C Curb, JD White, LR TI Frequency and characteristics of silent dementia among elderly Japanese-American men - The Honolulu-Asia aging study SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID ALZHEIMERS-DISEASE CERAD; MULTI-INFARCT DEMENTIA; MILD SENILE DEMENTIA; NEUROPSYCHOLOGICAL ASSESSMENT; INFORMANT QUESTIONNAIRE; COGNITIVE DECLINE; STROKE; CONSORTIUM; DIAGNOSIS; ESTABLISH AB Objective.-To determine the frequency of unrecognized dementia in a group of men found to have dementia by population survey, and to identify factors associated with the failure of a family informant to recognize significant memory impairment. Design and Setting.-The Honolulu-Asia Aging Study, a population-based study of dementia among elderly Japanese-American men living on the island of Oahu, Hawaii, Data for this study were from the dementia prevalence survey, 1991-1993. Study Participants.-A total of 191 noninstitutionalized men with dementia who had a reliable family informant. Main Outcome Measures.-Failure of family informants to recognize a problem with thinking or memory in subjects with dementia, Results.-A total of 21% of family informants failed to recognize a problem with memory among subjects subsequently found to have dementia, Among subjects with very mild dementia, 52% of family informants failed to recognize a significant memory problem compared with 13% among more severely demented subjects. Of the subjects with dementia whose family informants did recognize a memory problem, 53% failed to receive a medical evaluation for this problem. For all family informants, increasing age, fewer years of education, less severe dementia, fewer behavioral complications, fewer functional disabilities, and better performance on certain tests of memory and language were significantly associated with the family informant's failure to recognize a problem with memory, When the family informants were wives living with husbands, less severe dementia, fewer behavioral complications, fewer functional disabilities, and intact remote memory were associated with unrecognized dementia. Conclusions.-Unrecognized dementia was common in our population, especially among mild cases. Cognitive screening programs for the elderly and public education policies designed to increase awareness of early signs of dementia are needed if interventions for individuals with potentially treatable dementias are to be implemented. C1 DEPT VET AFFAIRS,HONOLULU,HI. UNIV VIRGINIA,DIV BIOSTAT,CHARLOTTESVILLE,VA. UNIV HAWAII,JOHN A BURNS SCH MED,DEPT MED,HONOLULU,HI 96822. KUAKINI MED CTR,HONOLULU ASIA AGING STUDY,HONOLULU,HI. NIA,BETHESDA,MD 20892. UNIV ARIZONA,COLL NURSING,TUCSON,AZ 85721. FU NIA NIH HHS [N01-AG-4-2149] NR 42 TC 143 Z9 149 U1 2 U2 4 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 12 PY 1997 VL 277 IS 10 BP 800 EP 805 DI 10.1001/jama.277.10.800 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA WM082 UT WOS:A1997WM08200032 PM 9052709 ER PT J AU MorrisonBogorad, M Phelps, C Buckholtz, N AF MorrisonBogorad, M Phelps, C Buckholtz, N TI Alzheimer disease research comes of age - The pace accelerates SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Editorial Material ID AMYLOID PRECURSOR PROTEIN; APOLIPOPROTEIN-E; ONSET; ALLELE RP MorrisonBogorad, M (reprint author), NIA,GATEWAY BLDG 3C307,7201 WISCONSIN AVE MSC9205,BETHESDA,MD 20892, USA. NR 36 TC 18 Z9 18 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 12 PY 1997 VL 277 IS 10 BP 837 EP 840 DI 10.1001/jama.277.10.837 PG 4 WC Medicine, General & Internal SC General & Internal Medicine GA WM082 UT WOS:A1997WM08200039 PM 9052716 ER PT J AU HamasakiKatagiri, N Tabor, CW Tabor, H AF HamasakiKatagiri, N Tabor, CW Tabor, H TI Spermidine biosynthesis in Saccharomyces cerevisiae: Polyamine requirement of a null mutant of the SPE3 gene (spermidine synthase) SO GENE LA English DT Article; Proceedings Paper CT Annual Meeting of the American-Society-for-Biochemistry-and-Molecular-Biology CY MAY 21-25, 1994 CL WASHINGTON, D.C. SP Amer Soc Biochem Molec Biol DE yeast; spermine; decarboxylated S-adenosylmethionine; S-adenosylmethionine binding motif ID S-ADENOSYLMETHIONINE DECARBOXYLASE; ORNITHINE DECARBOXYLASE; ESCHERICHIA-COLI; PROENZYME FORM; YEAST; DNA; EXPRESSION; TRANSFORMATION; PURIFICATION; PUTRESCINE AB The Saccharomyces cerevisiae SPE3 gene, coding for spermidine synthase, was cloned, sequenced, and localized on the right arm of chromosome XVI. The deduced amino acid sequence has a high similarity to mammalian spermidine synthases, and has putative S-adenosylmethionine binding motifs. To investigate the effect of total loss of the SPE3 gene, we constructed a null mutant of this gene, spe3 Delta, which has no spermidine synthase activity and has an absolute requirement for spermidine or spermine for the growth. This requirement is satisfied by a very low concentration of spermidine (10(-8) M) or a higher concentration of spermine (10(-6) M). C1 NIDDKD, BIOCHEM PHARMACOL LAB, NIH, BETHESDA, MD 20892 USA. NR 51 TC 48 Z9 49 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0378-1119 EI 1879-0038 J9 GENE JI Gene PD MAR 10 PY 1997 VL 187 IS 1 BP 35 EP 43 DI 10.1016/S0378-1119(96)00660-9 PG 9 WC Genetics & Heredity SC Genetics & Heredity GA WN016 UT WOS:A1997WN01600005 PM 9073064 ER PT J AU Kawakami, Y Battles, JK Kobayashi, T Ennis, W Wang, X Tupesis, JP Marincola, FM Robbins, PF Hearing, VJ Gonda, MA Rosenberg, SA AF Kawakami, Y Battles, JK Kobayashi, T Ennis, W Wang, X Tupesis, JP Marincola, FM Robbins, PF Hearing, VJ Gonda, MA Rosenberg, SA TI Production of recombinant MART-1 proteins and specific antiMART-1 polyclonal and monoclonal antibodies: Use in the characterization of the human melanoma antigen MART-1 SO JOURNAL OF IMMUNOLOGICAL METHODS LA English DT Article DE melanoma antigen; MART-1; recombinant protein; baculovirus; monoclonal antibody; immunotherapy ID TUMOR-INFILTRATING LYMPHOCYTES; CYTOLYTIC T-LYMPHOCYTES; AUTOLOGOUS MELANOMA; IN-VIVO; GENE; TYROSINASE; DOPACHROME; IDENTIFICATION; BIOSYNTHESIS; STIMULATION AB Recombinant human MART-1 protein was produced by bacterial and baculoviral-insect cell expression systems. By immunization with bacterial MBP-MART-1 fusion protein or MBP cleaved MART-1 protein, a rabbit polyclonal and two murine monoclonal antibodies specific for MART-1 were produced. These antibodies specifically detected MART-I in immuno-precipitation, Western blotting, flow cytometric assays and in immunohistochemical analysis of tissue sections. They also stained cytoplasmic components in melanocytes and most melanoma cells in frozen or paraffin embedded tissue sections, indicating that these antibodies may be useful for the diagnosis of melanoma, One of the monoclonal antibodies M2-7 C10 recognized only human MART-1, but the other monoclonal antibody M2-9 E3 recognized both human and murine MART-1. The size of the human MART-1 molecule detected by SDS-PAGE with these antibodies was approximately 18 kDa, suggesting possible posttranslational modifications in the MART-1 protein. Subcellular fractionation studies suggested that MART-1 was present in melanosomes and endoplasmic reticulum, although known melanogenic enzymatic activities were not detected in the MART-1 protein. These reagents may be useful for biological studies on melanocytes and melanoma cells as well as for the development and monitoring of immunotherapy for patients with melanoma. (C) 1997 Elsevier Science B.V. C1 NCI,CELL BIOL LAB,NIH,BETHESDA,MD 20892. NCI,FREDERICK CANC RES & DEV CTR,SAIC FREDERICK,LAB CELL & MOL STRUCT,FREDERICK,MD 21702. RP Kawakami, Y (reprint author), NCI,SURG BRANCH,DIV CLIN SCI,NIH,BLDG 10,RM 2B42,10 CTR DR,MSC 1502,ROCKVILLE,MD 20892, USA. RI Kawakami, Yutaka /E-7429-2013 OI Kawakami, Yutaka /0000-0003-4836-2855 NR 29 TC 82 Z9 82 U1 1 U2 4 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0022-1759 J9 J IMMUNOL METHODS JI J. Immunol. Methods PD MAR 10 PY 1997 VL 202 IS 1 BP 13 EP 25 DI 10.1016/S0022-1759(96)00211-6 PG 13 WC Biochemical Research Methods; Immunology SC Biochemistry & Molecular Biology; Immunology GA WN021 UT WOS:A1997WN02100002 PM 9075767 ER PT J AU Anglade, E Sullivan, DM Csaky, KG AF Anglade, E Sullivan, DM Csaky, KG TI Interleukin-10 immunoadhesin production by a replication-defective adenovirus SO JOURNAL OF IMMUNOLOGICAL METHODS LA English DT Article DE immunoadhesin; adenovirus; interleukin ID IGG CHIMERA; RECEPTOR IMMUNOADHESIN; ENDOTOXIC-SHOCK; CTLA4IG; ANTIGEN; BINDING; PROTECTION; INVITRO; LIGANDS; INVIVO AB The present study examined the use of replication-defective adenovirus for in vitro production of an immunoadhesin. A recombinant adenovirus, rendered replication defective by deletion of the El gene, was constructed to contain the murine interleukin-10 gene fused in frame with the hinge, CH2, and CH3 domains of the murine immunoglobulin gamma 1 heavy chain constant region gene under the control of the human cytomegalovirus promoter. The resultant recombinant virus, Ad5.hCMV.mIL-10:HFc, was used to transduce several cell types. The expressed protein, mIL-10:HFc, is secreted as a disulfide-bonded homodimer. In vitro, a murine pro-B-cell line expressing transfected recombinant murine interleukin-10 receptor proliferated in response to purified mIL-10:HFc. The results obtained demonstrate the relative ease of production of an immunoadhesin using replication-defective adenovirus. C1 NEI,IMMUNOL LAB,NIH,BETHESDA,MD 20892. NR 32 TC 2 Z9 2 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0022-1759 J9 J IMMUNOL METHODS JI J. Immunol. Methods PD MAR 10 PY 1997 VL 202 IS 1 BP 41 EP 48 DI 10.1016/S0022-1759(96)00233-5 PG 8 WC Biochemical Research Methods; Immunology SC Biochemistry & Molecular Biology; Immunology GA WN021 UT WOS:A1997WN02100005 PM 9075770 ER PT J AU Sloan, MJ Kirk, KL AF Sloan, MJ Kirk, KL TI Synthesis of a fluorinated analog of 1-aminocyclopropane carboxylic acid SO TETRAHEDRON LETTERS LA English DT Article ID ETHYLENE BIOSYNTHESIS; GLYCINE; INHIBITORS AB A convenient synthesis of 2-fluoro-1-aminocyclopropane-1-carboxylic acid is described. Cyclopropanation of ethyl 2-(3,4-dimethoxyphenyl)-3-fluoroacrylate followed by Curtius rearrangement, oxidative cleavage of the aromatic ring, and deprotection, produced the alpha-amino acid. C1 NIDDKD,BIOORGAN CHEM LAB,NIH,BETHESDA,MD 20892. NR 19 TC 20 Z9 20 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0040-4039 J9 TETRAHEDRON LETT JI Tetrahedron Lett. PD MAR 10 PY 1997 VL 38 IS 10 BP 1677 EP 1680 DI 10.1016/S0040-4039(97)00199-8 PG 4 WC Chemistry, Organic SC Chemistry GA WM040 UT WOS:A1997WM04000005 ER PT J AU Badio, B Garraffo, HM Padgett, WL Greig, NH Daly, JW AF Badio, B Garraffo, HM Padgett, WL Greig, NH Daly, JW TI Pseudophrynaminol: A potent noncompetitive blocker of nicotinic receptor-channels SO BIOCHEMICAL PHARMACOLOGY LA English DT Article DE pseudophyrnamines; nicotinic receptors; physostigmine; noncompetitive blockers; acetylcholinesterase ID ACETYLCHOLINE-RECEPTOR; ION CHANNEL; TORPEDO ELECTROPLAX; PHYSOSTIGMINE; ALKALOIDS; CELLS; MYOBATRACHIDAE; COMPLEX; PROTEIN; BRAIN AB (+/-)-Pseudophrynaminol inhibited carbamylcholine-elicited sodium-22 influx with an IC50 value of about 0.3 mu M in both rat pheochromocytoma PC12 cells (ganglionic-type nicotinic receptor) and human medulloblastoma TE671 cells (neuromuscular-type nicotinic receptor). The inhibition in both cell lines appeared to be noncompetitive in nature. In rat cerebral cortical membranes, pseudophrynaminol had only low affinity (K-i 35 mu M) for the agonist site on central nicotinic receptors at which [H-3]nicotine binds. Pseudophrynaminol, at 10 mu M, had marginal effects on a variety of other central receptors, and even at 100 mu M inhibited batrachotoxin-elicited sodium-22 influx in a synaptoneurosomal preparation by only 40%. It had no effect at 30 mu M on acetylcholinesterase and was a weak inhibitor of butyrylcholinesterase. Thus, pseudophrynaminol appears to be a potent, rather specific, noncompetitive inhibitor of ganglionic and neuromuscular nicotinic receptor-channels. (C) 1997 Elsevier Science Inc. C1 NIDDKD,BIOORGAN CHEM LAB,NIH,BETHESDA,MD 20892. NIA,NEUROSCI LAB,BALTIMORE,MD 21224. NR 26 TC 7 Z9 7 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0006-2952 J9 BIOCHEM PHARMACOL JI Biochem. Pharmacol. PD MAR 7 PY 1997 VL 53 IS 5 BP 671 EP 676 DI 10.1016/S0006-2952(96)00878-7 PG 6 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA WQ351 UT WOS:A1997WQ35100008 PM 9113086 ER PT J AU Fan, H Sakulich, AL Goodier, JL Zhang, XL Qin, J Maraia, RJ AF Fan, H Sakulich, AL Goodier, JL Zhang, XL Qin, J Maraia, RJ TI Phosphorylation of the human La antigen on serine 366 can regulate recycling of RNA polymerase III transcription complexes SO CELL LA English DT Article ID CASEIN KINASE-II; BINDING-PROTEIN; SACCHAROMYCES-CEREVISIAE; EXPRESSION; INVITRO; TFIIIB; GENES; AUTOANTIGEN; TERMINATION; INITIATION AB The human La antigen is an RNA-binding protein that facilitates transcriptional termination and reinitiation by RNA polymerase III. Native La protein fractionates into transcriptionally active and inactive forms that are unphosphorylated and phosphorylated at serine 366, respectively, as determined by enzymatic and mass spectrometric analyses. Serine 366 comprises a casein kinase II phosphorylation site that resides within a conserved region in the La proteins from several species. RNA synthesis from isolated transcription complexes is inhibited by casein kinase Ii-mediated phosphorylation of La serine 366 and is reversible by dephosphorylation. This work demonstrates a novel mechanism of transcriptional control at the level of recycling of stable transcription complexes. C1 NHLBI,BIOPHYS CHEM LAB,NIH,BETHESDA,MD 20892. RP Fan, H (reprint author), NICHHD,LAB MOL GROWTH REGULAT,NIH,BETHESDA,MD 20892, USA. NR 40 TC 87 Z9 88 U1 1 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 7 PY 1997 VL 88 IS 5 BP 707 EP 715 DI 10.1016/S0092-8674(00)81913-3 PG 9 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA WM413 UT WOS:A1997WM41300016 PM 9054510 ER PT J AU Jiang, RF Greener, T Barouch, W Greene, L Eisenberg, E AF Jiang, RF Greener, T Barouch, W Greene, L Eisenberg, E TI Interaction of auxilin with the molecular chaperone, Hsc70 SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID HEAT-SHOCK-PROTEIN; EUKARYOTIC DNAJ HOMOLOG; UNCOATING ATPASE; COATED VESICLES; SUBSTRATE-BINDING; BOVINE BRAIN; HSP70; CLATHRIN; TRANSLOCATION; NUCLEOTIDE AB We have studied the direct interaction of the constitutive isoform of Hsp70 (Hsc70) with the DnaJ homolog, auxilin, a cofactor that binds to clathrin-coated vesicles and is required for their uncoating by Hsc70. Auxilin caused a 5 fold increase in Hsc70 ATPase activity and a corresponding increase in steady-state levels of bound ADP; the dissociation constant for this effect was 0.6 mu M. Auxilin also induced polymerization of Hsc7O and bound to the resulting polymer at a 1:1 molar ratio; here too the dissociation constant was 0.6 mu M. Both this binding and polymerization required ATP; the Hsc70 depolymerized with a 4-min half-life when ATP was completely hydrolyzed to ADP. Although auxilin induces polymerization stoichiometrically and other DnaJ homologs induce polymerization catalytically, these data show that auxilin is similar to other DnaJ homologs in its ability to activate the Hsc70 ATPase activity, to polymerize Hsc70, and in the nucleotide dependence of this polymerization. Furthermore, the 70-amino acid J-domain of auxilin polymerized Hsc76 with the same nucleotide dependence as intact auxilin. Therefore, although only auxilin and not other DnaJ homologs support uncoating, our data suggest that various DnaJ homologs share a common mechanism of interaction with Hsc70, perhaps be cause their J-domains interact similarly with Hsc70. C1 NHLBI,CELL BIOL LAB,NIH,BETHESDA,MD 20892. NR 31 TC 55 Z9 56 U1 1 U2 5 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD MAR 7 PY 1997 VL 272 IS 10 BP 6141 EP 6145 PG 5 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA WM647 UT WOS:A1997WM64700009 PM 9045625 ER PT J AU Schedin, S Sindelar, PJ Pentchev, P Brunk, U Dallner, G AF Schedin, S Sindelar, PJ Pentchev, P Brunk, U Dallner, G TI Peroxisomal impairment in Niemann-Pick type C disease SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID PERFORMANCE LIQUID-CHROMATOGRAPHY; RAT-LIVER PEROXISOMES; STEROL CARRIER; MURINE MODEL; CHOLESTEROL-BIOSYNTHESIS; ISOPRENOID BIOSYNTHESIS; PRENYLTRANSFERASE; SEPARATION; ACTIVATION; DOLICHOL AB Niemann-Pick type C disease (NPC) belongs to the group of lysosomal storage diseases characterized by an accumulation of cholesterol and sphingomyelin. Using a mutant mouse strain, enzymatic markers for lysosomes, mitochondria, microsomes, and peroxisomes were in vestigated in the liver and brain, Aside from lysosomal changes, we found a sizable decrease of peroxisomal beta-oxidation of fatty acids and catalase activity in the brain and liver, Isolated peroxisomes displayed a significant decrease of these enzyme activities, Furthermore, the only phospholipid change in brain was a decreased content of the plasmalogen form of phosphatidylethanolamine, and the dimethylacetal pattern was also modified. The electron microscopical appearance of peroxisomes did not display any large changes, The defect of peroxisomal enzymes was already present 18 days before the onset of the disease, In contrast, the lysosomal marker enzyme increased in activity only 6 days after appearance of the symptoms, The events of the studied process have previously been considered to be elicited by a lysosomal deficiency, but this study demonstrates disturbances similar to those in a number of peroxisomal diseases, It appears that the peroxisomal impair ment is an early event in the process and could be a factor in the development of Niemann-Pick type C disease. C1 KAROLINSKA INST,NOVUM,CLIN RES CTR,S-14186 HUDDINGE,SWEDEN. LINKOPING UNIV,DEPT PATHOL,S-58185 LINKOPING,SWEDEN. NINCDS,NIH,BETHESDA,MD 20892. RP Schedin, S (reprint author), UNIV STOCKHOLM,DEPT BIOCHEM,S-10691 STOCKHOLM,SWEDEN. NR 38 TC 45 Z9 47 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 7 PY 1997 VL 272 IS 10 BP 6245 EP 6251 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA WM647 UT WOS:A1997WM64700025 PM 9045641 ER PT J AU Hao, WH Tan, Z Prasad, K Reddy, KK Chen, J Prestwich, GD Falck, JR Shears, SB Lafer, EM AF Hao, WH Tan, Z Prasad, K Reddy, KK Chen, J Prestwich, GD Falck, JR Shears, SB Lafer, EM TI Regulation of AP-3 function by inositides SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID ASSEMBLY PROTEIN AP-3; SYNAPSE-SPECIFIC PROTEIN; CLATHRIN BINDING; CA2+-ACTIVATED SECRETION; MONOCLONAL-ANTIBODIES; F1-20 PROTEIN; C2B DOMAIN; SYNAPTOTAGMIN; RECEPTOR; NP185 AB As part of the growing effort to understand the role inositol phosphates and inositol lipids play in the regulation of vesicle traffic within nerve terminals, we determined whether or not the synapse-specific clathrin assembly protein AP-3 can interact with inositol lipids. We found that soluble dioctanoyl-phosphatidylinositol 3,4,5-trisphosphate (DiC(8)-PtdIns(3,4,5)P-3) was only 7.5-fold weaker a ligand than D-myo-inositol hexakisphosphate in assays that measured the displacement of D-myo-[H-3]inositol hexakisphosphate. In functional as says we found that both of these ligands inhibited clathrin assembly, but DiC(8)-PtdIns(3,4,5)P-3 was more potent and exhibited a larger maximal effect. We also examined the structural features of DiC(8)-PtdIns(3,4,5)P-3 that establish specificity. Dioctanoyl-phosphatidylinositol 3,4-bisphosphate, which does not have a 5-phosphate, and 4,5-O-bisphosphoryl D-myo-inosityl 1-O-(1,2-O-diundecyl)-sn-3-glycerylphosphate, which does not have a 3-phosphate, were, respectively, a-fold and 4 fold less potent than DiC(8)-PtdIns(3,4,5)P-3 as inhibitors of clathrin assembly. Deacylation of DiC(8)-PtdIns(3,4,5)P-3 reduced its affinity for AP 3 almost 20-fold, and also dramatically lowered its ability to inhibit clathrin assembly. The deacylated products of the soluble derivatives of phosphatidylinositol 3,4-bisphosphate and phosphatidylinositol 4,5-bisphosphate were both not significant inhibitors of clathrin assembly. It therefore appears that the interactions of inositides with AP-3 should not be considered simply in terms of electrostatic effects of the highly charged phosphate groups. Ligand specificity appears also to be mediated by hydrophobic interactions with the fatty-acyl chains of the inositol lipids. C1 UNIV TEXAS,HLTH SCI CTR,INST BIOTECHNOL,DEPT MOL MED,SAN ANTONIO,TX 78245. NIEHS,LAB SIGNAL TRANSDUCT,INOSITOL LIPID SECT,RES TRIANGLE PK,NC 27709. UNIV TEXAS,SW MED CTR,DEPT MOL GENET,DALLAS,TX 75235. UNIV UTAH,DEPT MED CHEM,SALT LAKE CITY,UT 84112. FU NIGMS NIH HHS [GM31278]; NINDS NIH HHS [NS29632, R01 NS029051, NS29051] NR 44 TC 89 Z9 89 U1 1 U2 3 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD MAR 7 PY 1997 VL 272 IS 10 BP 6393 EP 6398 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA WM647 UT WOS:A1997WM64700046 PM 9045662 ER PT J AU Chen, XH Patel, BKR Wang, LM Frankel, M Ellmore, N Flavell, RA LaRochelle, WJ Pierce, JH AF Chen, XH Patel, BKR Wang, LM Frankel, M Ellmore, N Flavell, RA LaRochelle, WJ Pierce, JH TI Jak1 expression is required for mediating interleukin-4 induced tyrosine phosphorylation of insulin receptor substrate and state signaling molecules SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID MYELOID CELLS; HEMATOPOIETIC-CELLS; IL-4 RECEPTOR; GAMMA-CHAIN; FACTOR-I; PROTEIN; MITOGENESIS; INTERFERON; CLONING; KINASE AB The Jak1, Jak2, Jak8, and Fes tyrosine kinases have been demonstrated to undergo tyrosine phosphorylation in response to interleukin (IL)-4 stimulation in different cell systems. However, it is not clear which, if any, of these kinases are responsible for initiating IL-4-induced tyrosine phosphorylation of intracellular substrates in vivo, In the present study, we have utilized a mutant Jak1-deficient HeLa cell line, E1C3, and its parental Jakl-expressing counterpart, 1D4, to analyze the role of Jak1 in mediating IL-8-induced tyrosine phosphorylation events, IL-4 treatment rapidly induced tyrosine phosphorylation of insulin receptor substrate (IRS)-1 and IRS-2 in 1D4 but not in E1C3 cells. IL-4-mediated tyrosine phosphorylation of State was pronounced in 1D4 cells, while no IL-4-induced State phosphorylation was detected in E1C3 cells. IL-4 also induced State DNA binding activity from lysates of 1D4 but not E1C3 cells utilizing a radiolabeled immunoglobulin heavy chain germline epsilon promotor sequence (I epsilon) in an electrophoretic mobility shift assay, Reconstitution of Jak1 expression in E1C3 cells restored the ability of IL-4 to induce IRS and Stat6 tyrosine phosphorylation, These results provide evidence that Jak1 expression is required for mediating tyrosine phosphorylation and activation of crucial molecules involved in IL-4 signal transduction. C1 NCI,MOL & CELLULAR BIOL LAB,NIH,BETHESDA,MD 20892. YALE UNIV,SCH MED,HOWARD HUGHES MED INST,IMMUNOBIOL SECT,NEW HAVEN,CT 06510. YALE UNIV,SCH MED,HOWARD HUGHES MED INST,DEPT BIOL,NEW HAVEN,CT 06510. NR 43 TC 43 Z9 43 U1 0 U2 1 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD MAR 7 PY 1997 VL 272 IS 10 BP 6556 EP 6560 PG 5 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA WM647 UT WOS:A1997WM64700066 PM 9045682 ER PT J AU Goldberg, DE Sharma, V Oksman, A Gluzman, IY Wellems, TE PiwnicaWorms, D AF Goldberg, DE Sharma, V Oksman, A Gluzman, IY Wellems, TE PiwnicaWorms, D TI Probing the chloroquine resistance locus of Plasmodium falciparum with a novel class of multidentate metal(III) coordination complexes SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID MULTIDRUG-RESISTANCE; MALARIA PARASITES; IRON CHELATORS; HEME POLYMERIZATION; DIGESTIVE VACUOLE; RELAXATION AGENTS; MECHANISM; GENE; INVITRO; GALLIUM AB The malaria organism Plasmodium falciparum detoxifies heme released during degradation of host erythrocyte hemoglobin by sequestering it within the parasite digestive vacuole as a polymer called hemozoin, Antimalarial agents such as chloroquine appear to work by interrupting the heme polymerization process, but their efficacy has been impaired by the emergence of drug-resistant organisms, We report here the identification of a new class of antimalarial compounds, hexadentate ethylene diamine-N,N'-bis[propyl(2-hydroxy-(R)-benzylimino)]-metal(III) complexes [(R)-ENBPI-M(III)] and a corresponding ((R)-benzylamino)] analog [(R)-ENBPA-M(III)], a group of lipophilic monocationic leads amenable to metallopharmaceutical development, Racemic mixtures of Al(III), Fe(III), or Ga(III) but not In(III) (R)-ENBPI metallo-complexes killed intraerythrocytic malaria parasites in a stage-specific manner, the R = 4,6-dimethoxy-substituted ENBPI Fe(III) complex being most potent (IC50 similar to 1 mu M), Inhibiting both chloroquine sensitive and -resistant parasites, potency of these imino complexes correlated in a free metal-independent manner with their ability to inhibit heme polymerization in vitro, In contrast, the reduced (amino) 3-MeO-ENBPA Ga(III) complex (MR045) was found to be selectively toxic to chloroquine-resistant parasites in a verapamil-insensitive manner. In 21 independent recombinant progeny of a genetic cross, susceptibility to this agent mapped in perfect linkage with the chloroquine resistance phenotype suggesting that a locus for 3-MeO-ENBPA Ga(III) susceptibility was located on the same 36-kilobase segment of chromosome 7 as the chloroquine resistance determinant, These compounds may be useful as novel probes of chloroquine resistance mechanisms and for antimalarial drug development. C1 WASHINGTON UNIV,SCH MED,MALLINCKRODT INST RADIOL,DEPT RADIOL,ST LOUIS,MO 63110. WASHINGTON UNIV,SCH MED,DEPT MOL BIOL & PHARMACOL,ST LOUIS,MO 63110. WASHINGTON UNIV,SCH MED,HOWARD HUGHES MED INST,DEPT MED,ST LOUIS,MO 63110. WASHINGTON UNIV,SCH MED,HOWARD HUGHES MED INST,DEPT MOL MICROBIOL,ST LOUIS,MO 63110. NIAID,NIH,BETHESDA,MD 20892. FU NCI NIH HHS [CA65735]; NIAID NIH HHS [AI31615] NR 57 TC 55 Z9 57 U1 0 U2 5 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD MAR 7 PY 1997 VL 272 IS 10 BP 6567 EP 6572 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA WM647 UT WOS:A1997WM64700068 PM 9045684 ER PT J AU Montague, JW Hughes, FM Cidlowski, JA AF Montague, JW Hughes, FM Cidlowski, JA TI Native recombinant cyclophilins A, B, and C degrade DNA independently of peptidylprolyl cis-trans-isomerase activity - Potential roles of cyclophilins in apoptosis SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID BINDING-PROTEIN CYCLOPHILIN; CALCIUM-DEPENDENT ENDONUCLEASE; HIGH-MOLECULAR-WEIGHT; ESCHERICHIA-COLI; CYCLOSPORINE-A; THYMOCYTE APOPTOSIS; CARBONIC-ANHYDRASE; PROLYL ISOMERASE; RAT THYMOCYTES; HIV-1 VIRIONS AB Previous work in our laboratory (Montague, J., Gaido, M., Frye, C., and Cidlowski, J. (1994) J. Biol. Chem. 269, 18877-18880) has shown that human recombinant cyclophilins A, B, and C have sequence homology with the apoptotic nuclease NCTC18 and that denatured cyclophilins can degrade DNA. We have now evaluated the nucleolytic activity of recombinant cyclophilins under native conditions. We show that nuclease activity inherent to cyclophilins is distinct from cis-trans-peptidylprolyl isomerase activity and is similar to that described for apoptotic nucleases. Cyclophilin nucleolytic activity is stimulated by Ca2+ and/or Mg2+, with a combination of the two being optimal for cyclophilins A and B. Mg2+ alone is sufficient for cyclophilin C nuclease activity. pH optimums are in the range of pH 7.5-9.5. Cyclophilins can degrade both single-stranded and double-stranded DNA, Additionally, cyclophilins produce 3'-OH termini in linear double-stranded substrates, suggesting the cuts produced are similar to those of apoptotic cells. Cyclophilins also display endonucleolytic activity, demonstrated by their ability to degrade supercoiled DNA. In the absence of ions, cyclophilins bind linearized DNA. When added to nuclei from nonapoptotic cells, cyclophilin C induces 50-kilobase pair DNA fragmentation but not internucleosomal fragmentation. Together, these data suggest that cyclophilins are involved in degradation of the genome during apoptosis. C1 NIEHS,NIH,RES TRIANGLE PK,NC 27709. UNIV N CAROLINA,DEPT BIOCHEM & BIOPHYS,CHAPEL HILL,NC 27599. NR 62 TC 131 Z9 147 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 7 PY 1997 VL 272 IS 10 BP 6677 EP 6684 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA WM647 UT WOS:A1997WM64700083 PM 9045699 ER PT J AU Popova, JS Garrison, JC Rhee, SG Rasenick, MM AF Popova, JS Garrison, JC Rhee, SG Rasenick, MM TI Tubulin, G(q), and phosphatidylinositol 4,5-bisphosphate interact to regulate phospholipase C beta(1) signaling SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID GTP-BINDING PROTEINS; BETA-GAMMA-SUBUNITS; ADENYLYL-CYCLASE; ALPHA-SUBUNITS; C ISOZYMES; GQ CLASS; ACTIVATION; RECEPTOR; TRANSDUCTION; PURIFICATION AB The cytoskeletal protein, tubulin, has been shown to regulate adenylyl cyclase activity through its interaction with the specific G protein alpha subunits, G alpha(s) or G alpha(11). Tubulin activates these G proteins by transferring GTP and stabilizing the active nucleotide-bound G alpha conformation. To study the possibility of tubulin involvement in G alpha(q)-mediated phospholipase C beta(1) (PLC beta(1)) signaling, the m(1) muscarinic receptor, G alpha(q), and PLC beta(1) were expressed in Sf9 cells. A unique ability of tubulin to regulate PLC beta(1) was observed. Low concentrations of tubulin, with guanine nucleotide bound, activated PLC beta(1), whereas higher concentrations inhibited the enzyme. Interaction of tubulin with both G alpha(q) and PLC beta(1), accompanied by guanine nucleotide transfer from tubulin to G alpha(q), is suggested as a mechanism for the enzyme activation. The PLC beta(1) substrate, phosphatidylinositol 4,5-bisphosphate, bound to tubulin and prevented microtubule assembly. This observation suggested a mechanism for the inhibition of PLC beta(1) by tubulin, since high tubulin concentrations might prevent the access of PLC beta(1) to its substrate. Activation of m(1) muscarinic receptors by carbachol relaxed this inhibition, probably by increasing the affinity of G alpha(q) for tubulin. Involvement of tubulin in the articulation between PLC beta(1) signaling and microtubule assembly might prove important for the intracellular governing of a broad range of cellular events. C1 UNIV ILLINOIS, DEPT PHYSIOL & BIOPHYS, COLL MED, CHICAGO, IL 60612 USA. UNIV ILLINOIS, COMM NEUROSCI, COLL MED, CHICAGO, IL 60612 USA. UNIV ILLINOIS, DEPT PSYCHIAT, COLL MED, CHICAGO, IL 60612 USA. UNIV VIRGINIA, DEPT PHARMACOL, CHARLOTTESVILLE, VA 22908 USA. NHLBI, LAB CELL SIGNALING, NIH, BETHESDA, MD 20892 USA. FU NCI NIH HHS [CA 40042]; NIMH NIH HHS [MH 339595] NR 44 TC 77 Z9 77 U1 1 U2 2 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 EI 1083-351X J9 J BIOL CHEM JI J. Biol. Chem. PD MAR 7 PY 1997 VL 272 IS 10 BP 6760 EP 6765 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA WM647 UT WOS:A1997WM64700093 PM 9045709 ER PT J AU Mikhailenko, I Krylov, D Argraves, KM Roberts, DD Liau, G Strickland, DK AF Mikhailenko, I Krylov, D Argraves, KM Roberts, DD Liau, G Strickland, DK TI Cellular internalization and degradation of thrombospondin-1 is mediated by the amino-terminal heparin binding domain (HBD) - High affinity interaction of dimeric HBD with the low density lipoprotein receptor-related protein SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID ALPHA-2-MACROGLOBULIN RECEPTOR; LDL RECEPTOR; PLATELET THROMBOSPONDIN; SURFACE PROTEOGLYCANS; PLASMINOGEN-ACTIVATOR; EXTRACELLULAR-MATRIX; MULTILIGAND RECEPTOR; APOLIPOPROTEIN-E; GENE FAMILY; 2 MEMBERS AB Thrombospondin-1 (TSP-1) is a large modular trimeric protein that has been proposed to play a diverse role in biological processes. Newly synthesized TSP-1 either is incorporated into the matrix or binds to the cell surface where it is rapidly internalized and degraded. TSP-1 catabolism is mediated by the low density lipoprotein receptor-related protein (LRP), a large endocytic receptor that is a member of the low density lipoprotein receptor family. Using adenovirus-mediated gene transfer experiments, we demonstrate that the very low density lipoprotein receptor can also bind and internalize TSP 1. An objective of the current investigation was to identify the portion of TSP-1 that binds to these endocytic receptors. The current studies found that the amino terminal heparin binding domain (HBD, residues 1-214) of mouse TSP-1, when prepared as a fusion protein with glutathione S-transferase (GST), bound to purified LRP with an apparent K-D ranging from 10 to 25 nM. Recombinant HBD (rHBD) purified following proteolytic cleavage of GST-HBD, also bound to purified LRP, but with an apparent K-D of 830 nM. The difference in affinity was attributed to the fact that GST-HBD exists in solution as a dimer, whereas rHBD is a monomer. Like TSP-1, I-125-labeled GST-HBD or I-125-labeled rHBD were internalized and degraded by wild type fibroblasts that express LRP, but not by fibroblasts that are genetically deficient in LRP. The catabolism of both I-125-labeled GST-HBD and rHBD in wild type fibroblast was blocked by the 39-kDa receptor-associated protein, an inhibitor of LRP function. GST-HBD and rHBD both completely blocked catabolism of I-125-labeled TSP-1 in a dose dependent manner, as did antibodies prepared against the HBD. Taken together, these data provide compelling evidence that the amino-terminal domain of TSP-1 binds to LRP and thus the recognition determinants on TSP-1 for both LRP and for cell surface proteoglycans reside within the same TSP-1 domain. Further, high affinity binding of TSP-1 to LRP likely results from the trimeric structure of TSP-1. C1 AMER RED CROSS,HOLLAND LAB,DEPT BIOCHEM,ROCKVILLE,MD 20855. AMER RED CROSS,HOLLAND LAB,DEPT MOL BIOL,ROCKVILLE,MD 20855. NCI,BIOCHEM LAB,NIH,BETHESDA,MD 20892. NCI,PATHOL LAB,NIH,BETHESDA,MD 20892. RI Roberts, David/A-9699-2008 OI Roberts, David/0000-0002-2481-2981 FU NHLBI NIH HHS [HL37510, HL50787]; NIGMS NIH HHS [GM42581] NR 59 TC 74 Z9 76 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 7 PY 1997 VL 272 IS 10 BP 6784 EP 6791 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA WM647 UT WOS:A1997WM64700096 PM 9045712 ER PT J AU Koonin, EV AF Koonin, EV TI Evidence for a family of archaeal ATPases SO SCIENCE LA English DT Article ID PROTEINS; BINDING; SEARCH RP Koonin, EV (reprint author), NATL LIB MED,NATL CTR BIOTECHNOL INFORMAT,NIH,BETHESDA,MD 20894, USA. NR 11 TC 19 Z9 38 U1 0 U2 1 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 7 PY 1997 VL 275 IS 5305 BP 1489 EP 1490 DI 10.1126/science.275.5305.1489 PG 2 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA WM081 UT WOS:A1997WM08100049 PM 9045616 ER PT J AU Pohjalainen, T Cravchik, A Gejman, PV Rinne, J Nagren, K Syvalahti, E Hietala, J AF Pohjalainen, T Cravchik, A Gejman, PV Rinne, J Nagren, K Syvalahti, E Hietala, J TI Antagonist binding characteristics of the Ser(311)->Cys variant of human dopamine D-2 receptor in vivo and in vitro SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article ID GRADIENT GEL-ELECTROPHORESIS; D2 RECEPTOR; STRUCTURAL POLYMORPHISM; STRIATAL D-2; GENE; SCHIZOPHRENIA; DRD2; ASSOCIATION; ALCOHOLISM; EXPRESSION AB We report in vivo and in vitro antagonist binding characteristics of the naturally occurring Ser(311)-->Cys variant of the human D-2 dopamine receptor. Striatal receptor binding characteristics in vivo were measured with positron emission tomography and the D-2 antagonist [C-11]raclopride. The in vitro affinity of raclopride for the Ser(311)-->Cys variant and the wild type receptor was studied in membrane binding assays from stably transfected cell lines. One healthy male carrying the heterozygous Ser(311)-->Cys (TCC->TGC) substitution was identified with denaturing gradient gel electrophoresis and DNA sequencing. The striatal D-2 receptor binding characteristics in vivo in this subject were normal. This was supported by the in vitro data as the Ki values of raclopride for the Ser(311)-->Cys variant and the wild type receptor were identical. Our data suggest that the Ser(311)-->Cys variant of the human D-2 receptor does not influence antagonist-receptor recognition in vivo or in vitro. (C) 1997 Academic Press. C1 UNIV TURKU,DEPT NEUROL,FIN-20014 TURKU,FINLAND. UNIV TURKU,DEPT PSYCHIAT,FIN-20014 TURKU,FINLAND. NIMH,CLIN NEUROGENET BRANCH,CLIN NEUROGENET BRANCH,BETHESDA,MD 20892. TURKU PET CTR,FIN-20520 TURKU,FINLAND. RP Pohjalainen, T (reprint author), UNIV TURKU,DEPT PHARMACOL & CLIN PHARMACOL,FIN-20014 TURKU,FINLAND. NR 28 TC 13 Z9 13 U1 0 U2 1 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD MAR 6 PY 1997 VL 232 IS 1 BP 143 EP 146 DI 10.1006/bbrc.1997.6123 PG 4 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA WN213 UT WOS:A1997WN21300029 PM 9125119 ER PT J AU Lauermann, V AF Lauermann, V TI DNA repair by recycling reverse transcripts SO NATURE LA English DT Letter RP Lauermann, V (reprint author), NCI,FREDERICK CANC RES & DEV CTR,ADV BIOSCI LABS,BLDG 539,POB B,FREDERICK,MD 21702, USA. NR 0 TC 1 Z9 1 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 6 PY 1997 VL 386 IS 6620 BP 31 EP 32 DI 10.1038/386031a0 PG 2 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA WL746 UT WOS:A1997WL74600035 PM 9052778 ER PT J AU Conway, JF Cheng, N Zlotnick, A Wingfield, PT Stahl, SJ Steven, AC AF Conway, JF Cheng, N Zlotnick, A Wingfield, PT Stahl, SJ Steven, AC TI Visualization of a 4-helix bundle in the hepatitis B virus capsid by cryo-electron microscopy SO NATURE LA English DT Article ID 3-DIMENSIONAL STRUCTURE; ANGSTROM RESOLUTION; CRYSTAL-STRUCTURE; ALPHA-HELICES; CORE ANTIGEN; PROTEIN AB Despite the development of vaccines, the hepatitis B virus remains a major cause of human liver disease(1). The virion consists of a lipoprotein envelope surrounding an icosahedral capsid composed of dimers of a 183-residue protein, 'core antigen' (HBcAg)(2). Knowledge of its structure is important for the design of antiviral drugs, but it has yet to be determined. Residues 150-183 are known to form a protamine-like domain required for packaging RNA, and residues 1-149 form the 'assembly domain' that polymerizes into capsids(2) and, unusually for a capsid protein, is highly alpha-helical(3). Density maps calculated from cryo-electron micrographs(4-6) show that the assembly domain dimer is T-shaped: its stem constitutes the dimer interface and the tips of its arms make the polymerization contacts. By refining the procedures used to calculate the map, we have extended the resolution to 9 Angstrom, revealing major elements of secondary structure. In particular, the stem, which protrudes as a spike on the capsid's outer surface, is a 4-helix bundle, formed by the pairing of alpha-helical hairpins from both subunits. C1 NIAMSD,STRUCT BIOL LAB,NIH,BETHESDA,MD 20892. NIAMSD,PROT EXPRESS LAB,NIH,BETHESDA,MD 20892. RI Conway, James/A-2296-2010 OI Conway, James/0000-0002-6581-4748 NR 30 TC 321 Z9 337 U1 3 U2 29 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 6 PY 1997 VL 386 IS 6620 BP 91 EP 94 DI 10.1038/386091a0 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA WL746 UT WOS:A1997WL74600058 PM 9052787 ER PT J AU Koh, KK Mincemoyer, R Bui, MN Csako, G Pucino, F Guetta, V Waclawiw, M Cannon, RO AF Koh, KK Mincemoyer, R Bui, MN Csako, G Pucino, F Guetta, V Waclawiw, M Cannon, RO TI Effects of hormone-replacement therapy on fibrinolysis in postmenopausal women SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID PLASMINOGEN-ACTIVATOR INHIBITOR; LOW-DENSITY-LIPOPROTEIN; PROTEIN ALPHA-2-MACROGLOBULIN RECEPTOR; MYOCARDIAL-INFARCTION; ESTROGEN REPLACEMENT; ENDOTHELIAL-CELLS; HEART-DISEASE; FOLLOW-UP; TYPE-1; PLASMA AB Background Plasma levels of plasminogen-activator inhibitor type 1 (PAI-1), an essential inhibitor of fibrinolysis in humans, increase in women after menopause, and this may contribute to the risk of cardiovascular disease. We studied the effects of hormone-replacement therapy on PAI-1 levels. Methods In a randomized, crossover study, we investigated the effects of oral conjugated estrogen (0.625 mg per day) in 30 postmenopausal women and transdermal estradiol (0.1 mg per day) in 20 postmenopausal women, either alone or in combination with medroxyprogesterone acetate (2.5 mg daily) for one month, on plasma PAI-1 antigen levels. Degradation products of cross-linked fibrin (D-dimer) were measured in serum as an index of fibrinolysis. Results PAI-1 levels were inversely associated with D-dimer levels at base line (r=-0.540, P=0.002). Conjugated estrogen, both alone and in combination with medroxyprogesterone acetate, reduced mean (+/-SD) plasma levels of PAI-1 from 32+/-34 ng per milliliter to 14+/-10 ng per milliliter (P<0.001) and from 31+/-29 ng per milliliter to 15+/-11 ng per milliliter (P=0.003), respectively; there was a significant inverse correlation between pretreatment PAI-1 levels and the degree of reduction in these levels during therapy (r=-0.631, P<0.001 for conjugated estrogen; r=-0.507, P=0.004 for combined therapy). The degree of reduction in PAI-1 levels was associated with increases in D-dimer levels both when conjugated estrogen was given alone (r=-0.572, P=0.001) and when combined hormone therapy was given (r=-0.541, P=0.002). Transdermal estradiol caused no significant changes in PAI-1 levels from base-line values. Conclusions Conjugated estrogen, alone or combined with progestin therapy, reduced PAI-1 levels by approximately 50 percent in postmenopausal women and was associated with enhanced systemic fibrinolysis. These findings may partly explain the protective effect of hormone-replacement therapy with respect to coronary artery disease. (C) 1997, Massachusetts Medical Society. C1 NHLBI,CARDIOL BRANCH,NIH,BETHESDA,MD 20892. NIH,DEPT CLIN PATHOL,CTR CLIN,BETHESDA,MD 20892. NIH,DEPT PHARMACOL,CTR CLIN,BETHESDA,MD 20892. NHLBI,OFF BIOSTAT RES,NIH,BETHESDA,MD 20892. NR 46 TC 309 Z9 313 U1 0 U2 1 PU MASS MEDICAL SOC PI BOSTON PA 10 SHATTUCK, BOSTON, MA 02115 SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD MAR 6 PY 1997 VL 336 IS 10 BP 683 EP 690 DI 10.1056/NEJM199703063361002 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA WL419 UT WOS:A1997WL41900002 PM 9041098 ER PT J AU Goldstein, DS Holmes, C Cannon, RO Eisenhofer, G Kopin, IJ AF Goldstein, DS Holmes, C Cannon, RO Eisenhofer, G Kopin, IJ TI Sympathetic cardioneuropathy in dysautonomias SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID ORTHOSTATIC HYPOTENSION; PLASMA NOREPINEPHRINE; AUTONOMIC FAILURE; INNERVATION; HUMANS; DIHYDROXYPHENYLGLYCOL; NEUROSECRETION; RESPONSES; CATECHOLS; HEART AB Background The classification of dysautonomias has been confusing, and the pathophysiology obscure, We examined sympathetic innervation of the heart in patients with acquired, idiopathic dysautonomias using thoracic positron-emission tomography and assessments of the entry rate of the sympathetic neurotransmitter norepinephrine into the cardiac venous drainage (cardiac norepinephrine spillover). We related the laboratory findings to signs of sympathetic neurocirculatory failure (orthostatic hypotension and abnormal blood-pressure responses associated with the Valsalva maneuver), central neural degeneration, and responsiveness to treatment with levodopa-carbidopa (Sinemet). Methods Cardiac scans were obtained after intravenous administration of 6-[F-18]fluorodopamine in 26 patients with dysautonomia. Fourteen had sympathetic neurocirculatory failure - three with no signs of central neurodegeneration (pure autonomic failure), two with parkinsonism responsive to treatment with levodopa-carbidopa, and nine with central neurodegeneration unresponsive to treatment with levodopa-carbidopa (the Shy-Drager syndrome). The rates of cardiac norepinephrine spillover were estimated on the basis of concentrations of intravenously infused [H-3]norepinephrine during catheterization of the right side of the heart. Results Patients with pure autonomic failure or parkinsonism and sympathetic neurocirculatory failure had no myocardial 6-[F-18]fluorodopamine-derived radioactivity or cardiac norepinephrine spillover, indicating loss of myocardial sympathetic-nerve terminals, whereas patients with the Shy-Drager syndrome had increased levels of 6-[F-18]fluorodopamine-derived radioactivity, indicating intact sympathetic terminals and absent nerve traffic, Patients with dysautonomia who did not have sympathetic neurocirculatory failure had normal levels of 6-[F-18]fluorodopamine-derived radioactivity in myocardium and normal rates of cardiac norepinephrine spillover. Conclusions The results of 6-[F-18]fluorodopamine positron-emission tomography and neurochemical analyses support a new clinical pathophysiologic classification of dysautonomias, based on the occurrence of sympathetic neurocirculatory failure, signs of central neurodegeneration, and responsiveness to levodopa-carbidopa. (C) 1997, Massachusetts Medical Society. C1 NINCDS,CARDIOL BRANCH,NIH,BETHESDA,MD 20892. RP Goldstein, DS (reprint author), NINCDS,CLIN NEUROSCI BRANCH,NIH,BLDG 10,RM 6N252,10 CTR DR,MSC-1424,BETHESDA,MD 20892, USA. NR 32 TC 186 Z9 189 U1 0 U2 0 PU MASS MEDICAL SOC PI BOSTON PA 10 SHATTUCK, BOSTON, MA 02115 SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD MAR 6 PY 1997 VL 336 IS 10 BP 696 EP 702 DI 10.1056/NEJM199703063361004 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA WL419 UT WOS:A1997WL41900004 PM 9041100 ER PT J AU Liao, XB Du, YB Morse, HC Jenkins, NA Copeland, NG AF Liao, XB Du, YB Morse, HC Jenkins, NA Copeland, NG TI Proviral integrations at the Evi5 locus disrupt a novel 90 kDa protein with homology to the Tre2 oncogene and cell-cycle regulatory proteins SO ONCOGENE LA English DT Article DE Evi5; Gfi1; leukemia; oncogene; Tre2 ID GENETIC-LINKAGE MAP; ZINC-FINGER PROTEIN; CHROMOSOMAL LOCALIZATION; SACCHAROMYCES-CEREVISIAE; MOUSE CHROMOSOME-5; MOLECULAR-CLONING; MESSENGER-RNA; LYMPHOMAS; SEQUENCE; FAMILY AB Evi5 is a common site of retroviral integration in T-cell lymphomas of AKXD mice. Mapping studies have localized Evi5 to a region approximately 18 kb upstream of another common viral integration site, Gfi1, on mouse chromosome 5 (Liao X, Jenkins NA and Copeland NG, (1995a). J. Virol., 69, 7132-7137). Gfi1 encodes a zinc finger transcription factor involved in interleukin-2 signaling. To determine if Evi5 encodes a gene separate from Gfi1 that might also be involved in T-cell disease, we have searched within the Evi5 locus for novel transcripts. A 6.0 kb transcript was identified in these studies that spans the Evi5 locus and is disrupted by viral integration at Evi5. This transcript is expressed in all embryonic and adult mouse tissues examined. While blast searches indicated that Evi5 is a novel gene, homologies were detected between Evi5 and a known oncogene, Tre2, as well as mammalian and yeast cell cycle regulatory proteins. Evi5 thus encodes a gene separate from Gfi1 that may also be involved in T-cell disease. C1 NCI,FREDERICK CANC RES & DEV CTR,ABL BASIC RES PROGRAM,MAMMALIAN GENET LAB,FREDERICK,MD 21702. NIAID,IMMUNOPATHOL LAB,BETHESDA,MD 20892. OI Morse, Herbert/0000-0002-9331-3705 NR 49 TC 21 Z9 22 U1 0 U2 0 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE, HAMPSHIRE, ENGLAND RG21 6XS SN 0950-9232 J9 ONCOGENE JI Oncogene PD MAR 6 PY 1997 VL 14 IS 9 BP 1023 EP 1029 DI 10.1038/sj.onc.1200929 PG 7 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA WM070 UT WOS:A1997WM07000003 PM 9070650 ER PT J AU Zhan, QM Bieszczad, CK Bae, I Fornace, AJ Craig, RW AF Zhan, QM Bieszczad, CK Bae, I Fornace, AJ Craig, RW TI Induction of BCL2 family member MCL1 as an early response to DNA damage SO ONCOGENE LA English DT Article DE MCL1; BCL2; radiation; DNA damage ID CYCLE CHECKPOINT PATHWAY; PROGRAMMED CELL-DEATH; TUMOR-SUPPRESSOR P53; LEUKEMIA ML-1 CELLS; ATAXIA-TELANGIECTASIA; GENOTOXIC STRESS; MDM-2 ONCOGENE; HOMOLOG BAK; GENE FAMILY; IN-VIVO AB When ML-1 human myeloid leukemia cells are exposed to DNA damaging agents, they exhibit dramatic changes in the expression of a variety of gene products, This includes an increase in p53 (wild-type), a decrease in BCL2, a p53-dependent increase in the BCL2 family member BAX, and increases in Growth Arrest and DNA Damage-inducible (GADD) genes such as GADD45; these changes occur as early events in a sequence that culminates in DNA damage-induced apoptosis, DNA damaging agents have now been tested for effects on expression of another BCL2 family member, MCL1, a gene expressed during ML-1 cell differentiation, Expression of MCL1 was found to increase upon exposure of ML-1 cells to various types of DNA damaging agents, including ionizing radiation, ultraviolet radiation, and alkylating drugs. The increase in MCL1 occurred rapidly and was transient, levels of the MCL1 mRNA being elevated within 4 h and having returned to near baseline within 24 h. An increase in the Mcl1 protein was also seen, with the maximal increase occurring at an intermediate dose of IR (5 Gray) and lesser increases occurring at either lower or higher doses, The increase in expression of MCL1 was further studied using a panel of human cell lines that includes cells containing or not containing alterations in p53 as well as cells sensitive or insensitive to the apoptosis-inducing effects of DNA damage, The DNA damage-induced increase in MCL1 mRNA did not depend upon p53 as it was seen in cells lacking functional p53, However, the increase did depend upon susceptibility to apoptosis as it was not seen in cells insensitive to apoptosis-induction by DNA damaging agents. These findings demonstrate that cytotoxic DNA damage causes an increase in the expression of MCL1 along with increases in GADD45 and BAX and a decrease in BCL2, Furthermore, while the increase in GADD45 is seen both in cells that undergo growth arrest and in cells that undergo apoptosis in response to DNA damage, alterations in the profile of expression of BCL2 family members occur exclusively in cells that undergo the apoptotic response, with some family members increasing through p53-dependent (BAX) and others through p53-independent (MCL1) pathways, Overall, expression MCL1 can increase during the induction of cell death as well as during the induction of differentiation. C1 DARTMOUTH COLL SCH MED,DEPT PHARMACOL & TOXICOL,HANOVER,NH 03755. NCI,DIV CANC TREATMENT,DEV THERAPEUT PROGRAM,MOL PHARMACOL LAB,BETHESDA,MD 20892. RI Fornace, Albert/A-7407-2008 OI Fornace, Albert/0000-0001-9695-085X FU NCI NIH HHS [CA54385] NR 59 TC 65 Z9 67 U1 1 U2 4 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE, HAMPSHIRE, ENGLAND RG21 6XS SN 0950-9232 J9 ONCOGENE JI Oncogene PD MAR 6 PY 1997 VL 14 IS 9 BP 1031 EP 1039 DI 10.1038/sj.onc.1200927 PG 9 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA WM070 UT WOS:A1997WM07000004 PM 9070651 ER PT J AU Chien, CC Carroll, FI Brown, GP Pan, YX Bowen, W Pasternak, GW AF Chien, CC Carroll, FI Brown, GP Pan, YX Bowen, W Pasternak, GW TI Synthesis and characterization of [I-125]3'-(-)-iodopentazocine, a selective sigma(1) receptor ligand SO EUROPEAN JOURNAL OF PHARMACOLOGY LA English DT Article DE sigma receptor; benzomorphan; affinity label ID GUINEA-PIG BRAIN; HIGH-AFFINITY BINDING; METHYL-D-ASPARTATE; PHARMACOLOGICAL CHARACTERIZATION; AUTORADIOGRAPHIC LOCALIZATION; H-3 (+)-PENTAZOCINE; OPIOID ANALGESIA; OPIATE RECEPTOR; RAT-BRAIN; SITES AB Pentazocine is a potent ligand at both opioid and sigma receptors, but with opposite stereoselectivities. Whereas(-)-pentazocine has high affinity for a number of opioid receptors, (+)-pentazocine labels sigma(1) receptors. Iodination of(-)-pentazocine at the 3'-position reverses its selectivity for opioid and sigma(1) receptors. 3'-(-)-Iodopentazocine competes at sigma(1) receptor binding sites with a K-i value of 8 nM, compared to approximately 40 nM for(-)-pentazocine. 3'-(-)-Iodopentazocine also has lost its affinity for opioid receptors. In contrast, iodination of(+)-pentazocine lowers its affinity at sigma(1) receptors. Synthesis of [I-125]3'-(-)-iodopentazocine is readily performed with incorporations of up to 80%. Binding is of high affinity and shows the selectivity anticipated for a sigma(1) receptor-selective ligand. Exposing membranes prebound with [I-125]3'-(-)-iodopentazocine to ultraviolet light can covalently couple the ligand into the membranes. Polyacrylamide gel electrophoresis reveals a major band at about 25 kDa and a minor one at about 20 kDa, indicating photolabeling of sigma(1) receptors with minor incorporation into sigma(2) sites. C1 MEM SLOAN KETTERING CANC CTR,GEORGE C COTZIAS LAB NEUROONCOL,DEPT NEUROL,NEW YORK,NY 10021. CATHAY GEN HOSP,TAIPEI,TAIWAN. RES TRIANGLE INST,RES TRIANGLE PK,NC 27709. NIH,UNIT RECEPTOR BIOCHEM & PHARMACOL,MED CHEM LAB,BETHESDA,MD. FU NCI NIH HHS [CA08748]; NIDA NIH HHS [DA06241, K01 DA000296, DA000220] NR 56 TC 8 Z9 9 U1 0 U2 1 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 5 PY 1997 VL 321 IS 3 BP 361 EP 368 DI 10.1016/S0014-2999(96)00963-6 PG 8 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA WM978 UT WOS:A1997WM97800014 PM 9085049 ER PT J AU Alderman, EL Andrews, K Brooks, MM Detre, K Kelsey, SF Rosen, AD SuttonTyrrell, K Bourassa, M Chaitman, BR Faxon, DP Follmann, D Sopko, G Frye, RL Schaff, H Hlatky, M Jones, RH Sellers, MA Rogers, WJ Williams, DO AF Alderman, EL Andrews, K Brooks, MM Detre, K Kelsey, SF Rosen, AD SuttonTyrrell, K Bourassa, M Chaitman, BR Faxon, DP Follmann, D Sopko, G Frye, RL Schaff, H Hlatky, M Jones, RH Sellers, MA Rogers, WJ Williams, DO TI Five-year clinical and functional outcome comparing bypass surgery and angioplasty in patients with multivessel coronary disease - A multicenter randomized trial SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID REVASCULARIZATION INVESTIGATION BARI; ARTERY-DISEASE; ANGINA AB Objective.-To compare clinical and functional status in patients who had similar 5-year survival after coronary artery bypass grafting (CABG) and percutaneous transluminal coronary angioplasty (PTCA). Design.-Randomized trial of 1829 patients followed for an average 5.4 years. Participants.-Patients with multivessel coronary artery disease suitable for both CABG and PTCA and not previously revascularized. Intervention.-Coronary artery bypass grafting or PTCA within 2 weeks after randomization. Outcome Measures.-Symptoms, exercise test results, medication use, and quality-of-life measures collected at 4 to 14 weeks, and at 1, 3, and 5 years after randomization. Analysis.-Intention to treat. Results.-Differences in angina-free rates between patients assigned to PTCA and CABG decreased from 73% vs 95% at 4 to 14 weeks (P<.001) to 79% vs 85% at 5 years (P=.007). Similar patterns were observed for exercise-induced angina and ischemia, except 5-year differences were not significant. At follow-up of 1 year and later, quality of life, return to work, modification of smoking and exercise behaviors, and cholesterol levels were similar for the 2 treatments. Compared with patients assigned to CABG, use of anti-ischemic medication was higher in patients assigned to PTCA, while smaller differences were observed for other medications. Among patients angina-free at 5 years, 52% of patients who had PTCA required revascularization after the initial procedure vs 6% of patients who had CABG. Conclusions.-The narrowing of treatment differences in angina and exercise-induced ischemia rates can be attributed to a return of symptoms among patients assigned to CABG and incremental surgical procedures among patients assigned to PTCA. Patients assigned to PTCA apparently were able to tolerate higher rates of residual ischemia as evidenced by comparable quality of life and 5-year survival. C1 UNIV PITTSBURGH,BARI COORDINATING CTR,PITTSBURGH,PA 15261. STANFORD UNIV,CTR MED,CENT RADIOG LAB,STANFORD,CA 94305. MONTREAL HEART INST,MONTREAL,PQ H1T 1C8,CANADA. ST LOUIS UNIV,MED CTR,CENT ELECTROCARDIOG & MYOCARDIAL INFARCT CLASSIFI,ST LOUIS,MO. BOSTON UNIV,BOSTON,MA 02215. NHLBI,BETHESDA,MD 20892. MAYO CLIN & MAYO FDN,ROCHESTER,MN 55905. STANFORD UNIV,SCH MED,STUDY ECON & QUAL LIFE,STANFORD,CA 94305. DUKE UNIV,DURHAM,NC. UNIV ALABAMA,BIRMINGHAM,AL. BROWN UNIV,RHODE ISL HOSP,PROVIDENCE,RI 02903. NR 19 TC 149 Z9 151 U1 0 U2 4 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 5 PY 1997 VL 277 IS 9 BP 715 EP 721 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA WK026 UT WOS:A1997WK02600030 ER PT J AU Ferrucci, L Guralnik, JM Pahor, M Corti, MC Havlik, RJ AF Ferrucci, L Guralnik, JM Pahor, M Corti, MC Havlik, RJ TI Hospital diagnoses, Medicare charges, and nursing home admissions in the year when older persons become severely disabled SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID ACUTE MYOCARDIAL-INFARCTION; ELDERLY PATIENTS; MAINTAINING MOBILITY; CORONARY ANGIOPLASTY; PHYSICAL-DISABILITY; BYPASS-SURGERY; LATE-LIFE; AGE; CARE; SURVIVAL AB Objective.-To characterize hospital diagnoses, procedures and charges, and nursing home admissions in the year when older persons become severely disabled, comparing those in whom severe disability develops rapidly with those in whom disability develops gradually. Design.-A prospective, population-based cohort study with at least 6 annual interviews beginning in 1982. Setting.-A total of 3 communities: East Boston, Mass, New Haven, Conn, and Iowa and Washington counties in Iowa. Subjects.-A total of 6070 persons at least 70 years old with at least 1 interview after the fourth annual follow-up and without evidence of previous severe disability, defined as disability in 3 or more activities of daily living (ADLs). Main Outcome Measures.-Characteristics associated with development of severe disability after the fourth annual follow-up, in which the disability is classified as catastrophic disability if the individual did not report any ADL disability in the 2 interviews prior to severe disability onset or as progressive disability if the individual had previous disability in 1 or 2 ADLs. Results.-In the year during which severe disability developed, hospitalizations were documented for 72.1% of those developing catastrophic disability and for 48.6% of those developing progressive disability. In the corresponding year, only 14.7% of those who were stable with no disability and 22.3% of those with some disability were hospitalized, The 6 most frequent principal discharge diagnoses included stroke, hip fracture, congestive heart failure, and pneumonia in both severe disability subsets; coronary heart disease and cancer in catastrophic disability; and diabetes and dehydration in progressive disability. These diagnoses occurred in 49% of those with catastrophic disability and 25% of those with progressive disability. In both severe disability subsets, the oldest patients received less intensive hospital care as indicated by charges for surgery, diagnostics, and rehabilitation and by the percentage who received major diagnostic procedures; they were also more often admitted to nursing homes. Conclusions.-In the year when they become severely disabled, a large proportion of older persons are hospitalized for a small group of diseases. Hospital-based interventions aimed at reducing the severity and functional consequences of these diseases could have a large impact on reduction of severe disability. C1 NIA,EPIDEMIOL DEMOG & BIOMETRY PROGRAM,BETHESDA,MD 20892. NATL RES INST INRCA,DEPT GERIATR,FLORENCE,ITALY. UNIV TENNESSEE,DEPT PREVENT MED,MEMPHIS,TN. NR 36 TC 96 Z9 97 U1 4 U2 5 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 5 PY 1997 VL 277 IS 9 BP 728 EP 734 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA WK026 UT WOS:A1997WK02600032 PM 9042845 ER PT J AU Marini, JC Gerber, NL AF Marini, JC Gerber, NL TI Osteogenesis imperfecta rehabilitation and prospects for gene therapy SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID GROWTH-HORMONE; SHORT CHILDREN; MUTATION; STABILITY; AXIS C1 NIH,WARREN GRANT MAGNUSON CLIN CTR,DEPT REHABIL MED,BETHESDA,MD 20892. RP Marini, JC (reprint author), NICHHD,HERITABLE DISORDERS BRANCH,BLDG 10,RM 9S241,BETHESDA,MD 20892, USA. NR 21 TC 34 Z9 36 U1 0 U2 1 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD MAR 5 PY 1997 VL 277 IS 9 BP 746 EP 750 DI 10.1001/jama.277.9.746 PG 5 WC Medicine, General & Internal SC General & Internal Medicine GA WK026 UT WOS:A1997WK02600035 PM 9042848 ER PT J AU Hodosi, G Kovac, P AF Hodosi, G Kovac, P TI A fundamentally new, simple, stereospecific synthesis of oligosaccharides containing the beta-mannopyranosyl and beta-rhamnopyranosyl linkage SO JOURNAL OF THE AMERICAN CHEMICAL SOCIETY LA English DT Article ID GLYCOSIDE SYNTHESIS; DISACCHARIDES RP Hodosi, G (reprint author), NIDDK,SECT CARBOHYDRATES,LMC,NIH,BETHESDA,MD 20892, USA. NR 22 TC 107 Z9 107 U1 0 U2 6 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0002-7863 J9 J AM CHEM SOC JI J. Am. Chem. Soc. PD MAR 5 PY 1997 VL 119 IS 9 BP 2335 EP 2336 DI 10.1021/ja964021y PG 2 WC Chemistry, Multidisciplinary SC Chemistry GA WL646 UT WOS:A1997WL64600052 ER PT J AU Dixit, M Yang, JL Poirier, MC Price, JO Andrews, PA Arteaga, CL AF Dixit, M Yang, JL Poirier, MC Price, JO Andrews, PA Arteaga, CL TI Abrogation of cisplatin-induced programmed cell death in human breast cancer cells by epidermal growth factor antisense RNA SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID RECEPTOR MONOCLONAL-ANTIBODIES; OVARIAN-CARCINOMA CELLS; DNA-REPAIR; CIS-DIAMMINEDICHLOROPLATINUM; TYROSINE KINASE; STRAND BREAKS; TUMOR CELLS; C-FOS; APOPTOSIS; ACTIVATION AB Background: Epidermal growth factor receptor (EGF-R) perturbation by receptor ligand(s), e.g., epidermal growth factor (EGF) and transforming growth factor-alpha (TGF-alpha), or receptor-specific antibodies accentuates cisplatin-induced toxicity in tumor cells, This sensitization occurs only in tumor cells with high expression of EGF-R but not in those with low expression of EGF-R. Purpose: Therefore, we have studied the role of EGF-R expression on cisplatin-mediated cytotoxicity. Methods: MDA-468 human breast cancer cells were stably transfected with a p-chloramphenicol acetyl transferase (pact[p]-CAT) vector containing a 4.1-kilobase full-length antisense EGF-R complementary DNA. EGF-R content was assessed by I-125-EGF binding and EGF-R immunoblot assays, Cisplatin sensitivity was evaluated by (a) colony-forming assay in vitro, (b) xenograft growth in nude mice, (c) cell cycle distribution of propidium iodide-labeled DNA, (d) DNA fragmentation in agarose gels, and (e) terminal deoxynucleotidyl transferase (Tdt) fluorescence in situ, Cisplatin uptake was measured by atomic absorption spectroscopy, and the levels of drug-DNA intrastrand adducts were determined by a dissociation-enhanced fluoroimmunoassay that utilizes an antibody against cisplatin-modified DNA. Results: Selected clones (MDA-468/AS-EGFR) exhibited more than 90% loss of both I-125-EGF binding and receptor content determined by western blot analysis, whereas clones transfected with the vector alone (MDA-468/p-CAT) had EGF-R levels similar to those of the parent cells, By use of a colony-forming assay, the 1-hour IC50 (i.e., the concentration of drug required for 1 hour to achieve 50% cell kill) for cisplatin was 2 mu M or less for parental and vector-transfected clones (n = 4), whereas it was 25 mu M or more for all MDA-468/AS-EGFR clones (n = 3), MDA-468/p-CAT clones exhibited internucleosomal DNA fragmentation, enhanced Tdt-end labeling in situ, and G(2) arrest 48 hours after a 1-hour incubation with 3-30 mu M cisplatin. Under these conditions, apoptosis and G(2) arrest mere undetectable in all MDA-468/AS-EGFR clones. An MDA-468 subline selected after long-term treatment with a TGF-alpha-Pseudomonas exotoxin A fusion protein 40 lacked EGF binding and also exhibited cisplatin resistance (1-hour IC50: >30 mu M) compared with parental cells, This EGF-R-dependent difference in cisplatin response was confirmed in a nude mouse xenograft model by use of high- and low-EGF-R-expressing cell clones. Total intracellular drug accumulation after a 1-hour cisplatin exposure, as measured by atomic absorption spectroscopy, was identical in both groups of cells, Intrastrand drug-DNA adducts, however, were statistically higher in high EGF-R expressors than in low-EGF-R-expressing clones. Conclusions: These data indicate that a critical level of EGF-R signaling, which is amplified in some common human cancers, is necessary for cisplatin-mediated apoptosis in tumor cells and suggest an inhibitory effect of this pathway on the repair of cisplatin-damaged DNA. C1 VANDERBILT UNIV,SCH MED,DIV MED ONCOL,DEPT MED,NASHVILLE,TN 37232. NCI,CELLULAR CARCINOGENESIS & TUMOR PROMOT LAB,DIV BASIC SCI,BETHESDA,MD 20892. VANDERBILT CANC CTR,NASHVILLE,TN. VET AFFAIRS MED CTR,NASHVILLE,TN 37212. GEORGETOWN UNIV,DEPT PHARMACOL,WASHINGTON,DC. VANDERBILT UNIV,SCH MED,DEPT CELL BIOL,NASHVILLE,TN 37240. FU NCI NIH HHS [R01 CA62212] NR 55 TC 65 Z9 66 U1 0 U2 3 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 5 PY 1997 VL 89 IS 5 BP 365 EP 373 DI 10.1093/jnci/89.5.365 PG 9 WC Oncology SC Oncology GA WL645 UT WOS:A1997WL64500009 PM 9060958 ER PT J AU Irvine, KR Chamberlain, RS Shulman, EP Rosenberg, SA Restifo, NP AF Irvine, KR Chamberlain, RS Shulman, EP Rosenberg, SA Restifo, NP TI Route of immunization and the therapeutic impact of recombinant anticancer vaccines SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID ESTABLISHED PULMONARY METASTASES; IMMUNE-RESPONSES; VIRUS; ANTIGEN; CELLS C1 NCI,SURG BRANCH,DIV BASIC SCI,BETHESDA,MD 20892. RI Restifo, Nicholas/A-5713-2008; OI Restifo, Nicholas P./0000-0003-4229-4580 FU Intramural NIH HHS [Z99 CA999999, Z01 BC010763-01] NR 9 TC 13 Z9 14 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 5 PY 1997 VL 89 IS 5 BP 390 EP 392 DI 10.1093/jnci/89.5.390 PG 3 WC Oncology SC Oncology GA WL645 UT WOS:A1997WL64500013 PM 9060962 ER PT J AU Potischman, N Swanson, CA Siiteri, P Hoover, RN AF Potischman, N Swanson, CA Siiteri, P Hoover, RN TI Reversal of relation between body mass and endogenous estrogen concentrations with menopausal status - Response SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Letter C1 NCI,DIV CANC EPIDEMIOL & GENET,ENVIRONM EPIDEMIOL PROGRAM,BETHESDA,MD 20892. NR 4 TC 1 Z9 1 U1 0 U2 1 PU NATL CANCER INSTITUTE PI BETHESDA PA 9030 OLD GEORGETOWN RD, BETHESDA, MD 20814 SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD MAR 5 PY 1997 VL 89 IS 5 BP 397 EP 398 PG 2 WC Oncology SC Oncology GA WL645 UT WOS:A1997WL64500017 ER PT J AU Bose, S Hendler, RW Shrager, RI Chan, SI Smith, PD AF Bose, S Hendler, RW Shrager, RI Chan, SI Smith, PD TI Multichannel analysis of single-turnover kinetics of cytochrome aa(3) reduction of O-2 SO BIOCHEMISTRY LA English DT Article ID C-OXIDASE; ELECTRON-TRANSFER; IONIC-STRENGTH; DIOXYGEN REDUCTION; ROOM-TEMPERATURE; OXYGEN; INTERMEDIATE; PH; STATE; DEPENDENCE AB The single-turnover kinetics of the oxidation of cytochrome aa(3) by O-2 have been studied using a new approach. Up to 1000 whole spectra covering both the Soret and alpha regions were sequentially collected at room temperature from single samples with a time resolution of 10 mu s. All of the spectral and time information were used in analyses based on singular value decomposition. Four spectral transitions (i.e., intermediates) were distinguished with time constants near 0.01, 0.1, 1.1, and 30 ins. Two different kinds of sequential models were evaluated, one linear and the other branched. Although past kinetic analyses have emphasized the linear sequential model, the complexity of the intramolecular electron transfer in this enzyme suggests that a branched model be considered. This is especially true in a single-turnover experiment where earlier optical and EPR studies have pointed unequivocally to a branched model [Clore et al. (1980) Biochem. J. 185, 139-154; Blair et al. (1985) J. Am. Chem. Soc. 107, 7389-7399]. In the present study, analysis of spectral data in terms of the linear model did not reveal the formation and decay of the expected oxyferryl intermediate, whereas analysis of the branched model did. The results obtained using the branched model are consistent with all of the available evidence from a broad range of physical techniques that have been applied to examine the single-turnover kinetics of the oxidation of reduced cytochrome aa(3) by O-2. C1 NHLBI,CELL BIOL LAB,NIH,BETHESDA,MD 20892. NIH,NATL CTR RES RESOURCES,DIV COMP RES & TECHNOL,BETHESDA,MD 20892. NIH,NATL CTR RES RESOURCES,BIOMED ENGN & INSTRUMENTAT PROGRAM,BETHESDA,MD 20892. CALTECH,ARTHUR AMOS NOYES LAB CHEM PHYS,PASADENA,CA 91125. NR 44 TC 11 Z9 11 U1 0 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD MAR 4 PY 1997 VL 36 IS 9 BP 2439 EP 2449 DI 10.1021/bi9617419 PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA WL643 UT WOS:A1997WL64300011 PM 9054548 ER PT J AU Garrett, DS Seok, YJ Liao, DI Peterkofsky, A Gronenborn, AM Clore, GM AF Garrett, DS Seok, YJ Liao, DI Peterkofsky, A Gronenborn, AM Clore, GM TI Solution structure of the 30 kDa N-terminal domain of enzyme I of the Escherichia coli phosphoenolpyruvate:sugar phosphotransferase system by multidimensional NMR SO BIOCHEMISTRY LA English DT Article ID NUCLEAR-MAGNETIC-RESONANCE; PHOSPHOCARRIER PROTEIN-HPR; HISTIDINE-CONTAINING PROTEIN; RESTRAINED MOLECULAR-DYNAMICS; HIGH-RESOLUTION STRUCTURE; HETERONUCLEAR NMR; BACILLUS-SUBTILIS; ACTIVE-SITE; 3-DIMENSIONAL STRUCTURES; PERDEUTERATED PROTEINS AB The three-dimensional solution structure of the 259-residue 30 kDa N-terminal domain of enzyme I (EIN) of the phosphoenolpyruvate:sugar phosphotransferase system of Escherichia coli has been determined by multidimensional nuclear magnetic resonance spectroscopy. Enzyme I, which is autophosphorylated by phosphoenolpyruvate, reversibly phosphorylates the phosphocarrier protein HPr, which in turn phosphorylates a group of membrane-associated proteins, known as enzymes II. To facilitate and confirm NH, N-15, and C-13 assignments, extensive use was made of perdeuterated N-15- and N-15/C-13-labeled protein to narrow line widths. Ninety-eight percent of the H-1, N-15, and C-13 assignments for the backbone and first side chain. atoms of protonated EIN were obtained using a combination of double and triple resonance correlation experiments. The structure determination was based on a total of 4251 experimental NMR restraints, and the precision of the coordinates for the final 50 simulated annealing structures is 0.79 +/- 0.18 Angstrom for the backbone atoms and 1.06 +/- 0.15 Angstrom for all atoms. The structure is ellipsoidal in shape, approximately 78 Angstrom long and 32 Angstrom wide, and comprises two domains: an alpha/beta domain (residues 1-20 and 148-230) consisting of six strands and three helices and an alpha-domain (residues 33-143) consisting of four helices. The two domains are connected by two linkers (residues 21-32 and 144-147), and in addition, at the C-terminus there is another helix which serves as a linker between the N- and C-terminal domains of intact enzyme I. A comparison with the recently solved X-ray structure of EIN [Liao, D.-I., Silverton, E., Seek, Y.-J., Lee, B. R., Peterkofsky, A., & Davies, D. R. (1996) Structure 4, 861-872] indicates that there are no significant differences between the solution and crystal structures within the errors of the coordinates. The active site His189 is located in a cleft at the junction of the a and alpha/beta domains and has a pK(a) of similar to 6.3. His-189 has a trans conformation about chi(1), a g(+) conformation about chi(2), and its N epsilon 2 atom accepts a hydrogen bond from the hydroxyl proton of Thr168. Since His189 is thought to be phosphorylated at the N epsilon 2 position, its side chain conformation would have to change upon phosphorylation. C1 NIDDKD,PHYS CHEM LAB,NIH,BETHESDA,MD 20892. NIDDKD,MOL BIOL LAB,NIH,BETHESDA,MD 20892. NHLBI,LAB BIOCHEM GENET,NIH,BETHESDA,MD 20892. RI Clore, G. Marius/A-3511-2008 OI Clore, G. Marius/0000-0003-3809-1027 NR 69 TC 147 Z9 151 U1 1 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 4 PY 1997 VL 36 IS 9 BP 2517 EP 2530 DI 10.1021/bi962924y PG 14 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA WL643 UT WOS:A1997WL64300020 PM 9054557 ER PT J AU Wuyts, A VanOsselaer, N Haelens, A Samson, I Herdewijn, P BenBaruch, A Oppenheim, JJ Proost, P VanDamme, J AF Wuyts, A VanOsselaer, N Haelens, A Samson, I Herdewijn, P BenBaruch, A Oppenheim, JJ Proost, P VanDamme, J TI Characterization of synthetic human granulocyte chemotactic protein 2: Usage of chemokine receptors CXCR1 and CXCR2 and in vivo inflammatory properties SO BIOCHEMISTRY LA English DT Article ID GROWTH-STIMULATORY ACTIVITY; NEUTROPHIL-ACTIVATING PROTEIN; HUMAN INTERLEUKIN-8 RECEPTORS; AMINO-ACID-SEQUENCE; MOLECULAR CHARACTERIZATION; BETA-THROMBOGLOBULIN; RABBIT SKIN; T-CELLS; IDENTIFICATION; INVIVO AB Human granulocyte chemotactic protein 2 (GCP-2) has originally been isolated from cytokine-stimulated osteosarcoma cells as a chemokine coproduced in minute amounts together with interleukin 8. Human GCP-2 (75 residues) was synthesized on a 0.25-mmol scale using Fmoc chemistry. After disulfide bridge formation and purification, monomeric GCP-2 was recovered as a 6-kDa protein; the pure synthetic protein showed a molecular mass of 8076 Da as determined by matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS). The exact amino acid sequence of synthetic GCP-2 was confirmed by Edman degradation. Synthetic GCP-2 was an equally active (minimal effective concentration of 1-3 nM) chemoattractant for neutrophilic granulocytes as was natural 75-residue GCP-2. At concentrations up to 30 nM, synthetic GCP-2 did not stimulate eosinophil, monocyte, or lymphocyte chemotaxis. GCP-2 induced a dose-dependent increase in [Ca2+](i) in neutrophils, 1 nM being the minimal effective concentration. The GCP-2-induced [Ca2+](i) increase was completely prevented by pertussis toxin. Prestimulation of neutrophils with equimolar concentrations of purified natural IL-8, GRO alpha, GRO gamma and ENA-78 abolished the [Ca2+](i) increase in response to 1 nM GCP-2. Alternatively, the [Ca2+](i) rise induced by these CXC chemokines was inhibited by pretreatment of neutrophils with GCP-2. GCP-2 stimulated [Ca2+](i) increases in CXCR1- and CXCR2-transfected cells, demonstrating that GCP-2 binds to both IL-8 receptors. Intradermal injection of synthetic GCP-2 resulted in a dose-dependent neutrophil accumulation and plasma extravasation in rabbit skin. To provoke this skin reaction, GCP-2. (10 pmol/site) was nearly as effective as IL-8, indicating that it is an important complementary mediator of the inflammatory response. C1 CATHOLIC UNIV LEUVEN,REGA INST MED RES,LAB MOL IMMUNOL,B-3000 LOUVAIN,BELGIUM. CATHOLIC UNIV LEUVEN,REGA INST MED RES,MED CHEM LAB,B-3000 LOUVAIN,BELGIUM. UNIV INSTELLING ANTWERP,FAC MED,DIV PHARMACOL,B-2610 WILRIJK,BELGIUM. NCI,FREDERICK CANC RES & DEV CTR,MOL IMMUNOREGULAT LAB,FREDERICK,MD 21702. NR 43 TC 103 Z9 107 U1 0 U2 3 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD MAR 4 PY 1997 VL 36 IS 9 BP 2716 EP 2723 DI 10.1021/bi961999z PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA WL643 UT WOS:A1997WL64300043 PM 9054580 ER PT J AU Mimaki, Y Kuroda, M Kameyama, A Sashida, Y Hirano, T Oka, K Maekawa, R Wada, T Sugita, K Beutler, JA AF Mimaki, Y Kuroda, M Kameyama, A Sashida, Y Hirano, T Oka, K Maekawa, R Wada, T Sugita, K Beutler, JA TI Cholestane glycosides with potent cytostatic activities on various tumor cells from Ornithogalum saundersiae bulbs SO BIOORGANIC & MEDICINAL CHEMISTRY LETTERS LA English DT Article AB Five cholestane glycosides (1 - 5) including three new ones (3 - 5) with potent cytostatic activity on leukemia HL-60 cells were isolated from Ornithogalum saundersiae bulbs. Compound 1, a main constituent in the bulbs, was revealed to be exceptionally cytostatic against various malignant tumor cells and effective to mouse P388 leukemia in in vivo evaluation. (C) 1997 Elsevier Science Ltd. All rights reserved. C1 SHIONOGI & CO LTD, DISCOVERY RES LABS 2, DEPT CELL INFORMAT, FUKUSHIMA KU, OSAKA 553, JAPAN. NCI, FREDERICK CANC RES & DEV CTR, LAB DRUG DISCOVERY RES & DEV, DEV THERAPEUT PROGRAM, FREDERICK, MD 21702 USA. RP Mimaki, Y (reprint author), TOKYO UNIV PHARM & LIFE SCI, SCH PHARM, 1432-1 HORINOUCHI, HACHIOJI, TOKYO 19203, JAPAN. RI Beutler, John/B-1141-2009 OI Beutler, John/0000-0002-4646-1924 NR 6 TC 123 Z9 132 U1 0 U2 2 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0960-894X J9 BIOORG MED CHEM LETT JI Bioorg. Med. Chem. Lett. PD MAR 4 PY 1997 VL 7 IS 5 BP 633 EP 636 DI 10.1016/S0960-894X(97)00071-1 PG 4 WC Chemistry, Medicinal; Chemistry, Organic SC Pharmacology & Pharmacy; Chemistry GA WL641 UT WOS:A1997WL64100027 ER PT J AU Barondes, SH Alberts, BM Andreasen, NC Bargmann, C Benes, F GoldmanRakic, P Gottesman, I Heinemann, SF Jones, EG Kirschner, M Lewis, D Raff, M Roses, A Rubenstein, J Snyder, S Watson, SJ Weinberger, DR Yolken, RH AF Barondes, SH Alberts, BM Andreasen, NC Bargmann, C Benes, F GoldmanRakic, P Gottesman, I Heinemann, SF Jones, EG Kirschner, M Lewis, D Raff, M Roses, A Rubenstein, J Snyder, S Watson, SJ Weinberger, DR Yolken, RH TI Workshop on schizophrenia SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Editorial Material DE mental illness; neurobiology; neurodevelopment; neurogenetics ID CORTEX AB On November 29-30, 1995, the National Academy of Sciences and the Institute of Medicine brought together experts in schizophrenia and specialists in other areas of the biological sciences in a workshop aimed at promoting the application of the latest biological information to this clinical problem. The workshop paid particular attention to evidence of pathology in the brains of people with schizophrenia, and to the possibility that this reflects an abnormality in brain development that eventually leads to the appearance of symptoms. The participants were impressed with the complexity of the problem, and felt that multiple approaches would be required to understand this disease. They recommended that a major focus should be on the search for predisposing genes, but that there should be parallel research in many other areas. C1 NATL ACAD SCI,WASHINGTON,DC 20418. UNIV IOWA,MHCRC,IOWA CITY,IA 52242. UNIV CALIF SAN FRANCISCO,DEPT ANAT,SAN FRANCISCO,CA 94143. MCLEAN HOSP,MAILMAN RES CTR,BELMONT,MA 02178. YALE UNIV,SCH MED,NEUROBIOL SECT,NEW HAVEN,CT 06510. UNIV VIRGINIA,DEPT PSYCHOL,CHARLOTTESVILLE,VA 22903. SALK INST,SAN DIEGO,CA 92186. UNIV CALIF IRVINE,COLL MED,DEPT ANAT & NEUROBIOL,IRVINE,CA 92717. HARVARD UNIV,SCH MED,DEPT CELL BIOL,BOSTON,MA 02115. UNIV PITTSBURGH,MED CTR,CTR NEUROSCI MENTAL DISORDERS,PITTSBURGH,PA 15213. UNIV LONDON UNIV COLL,DEPT BIOL,MOL CELL BIOL LAB,LONDON WC1E 6BT,ENGLAND. DUKE UNIV,DEPT MED,DIV NEUROL,DURHAM,NC 27710. JOHNS HOPKINS UNIV,DEPT NEUROSCI,BALTIMORE,MD 21205. UNIV MICHIGAN,MENTAL HLTH RES INST,ANN ARBOR,MI 48109. NIMH,NEUROSCI CTR ST ELIZABETHS,WASHINGTON,DC 20032. JOHNS HOPKINS UNIV,SCH MED,DEPT PEDIAT & INFECT DIS,BALTIMORE,MD 21205. RP Barondes, SH (reprint author), UNIV CALIF SAN FRANCISCO,DEPT PSYCHIAT,CTR NEUROBIOL & PSYCHIAT,SAN FRANCISCO,CA 94143, USA. RI G, I/D-8042-2011; Lewis, David/G-4053-2014; OI Lewis, David/0000-0002-3225-6778; Bargmann, Cornelia/0000-0002-8484-0618 NR 17 TC 24 Z9 26 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 4 PY 1997 VL 94 IS 5 BP 1612 EP 1614 DI 10.1073/pnas.94.5.1612 PG 3 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA WM059 UT WOS:A1997WM05900005 PM 9050825 ER PT J AU Adler, V Pincus, MR Minamoto, T Fuchs, SY Bluth, MJ BrandtRauf, PW Friedman, FK Robinson, RC Chen, JM Wang, XW Harris, CC Ronai, Z AF Adler, V Pincus, MR Minamoto, T Fuchs, SY Bluth, MJ BrandtRauf, PW Friedman, FK Robinson, RC Chen, JM Wang, XW Harris, CC Ronai, Z TI Conformation-dependent phosphorylation of p53 SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID TUMOR-SUPPRESSOR PROTEIN; DNA-BINDING FUNCTION; DOMAIN; ACTIVATION; POLYPEPTIDES; IRRADIATION; MUTATIONS AB Phosphorylation of the p53 tumor suppressor protein is known to modulate its functions, Using bacterially produced glutathione S-transferase (GST)-p53 fusion protein and baculovirus-expressed histidine-tagged p53 (Hi,p53), we have determined human p53 phosphorylation by purified forms of jun-N-kinase (JNK), protein kinase A (PKA), and beta subunit of casein kinase II (CKII beta) as well as by kinases present in whole cell extracts (WCEs), We demonstrate that PKA is potent p53 kinase, albeit, in a conformation- and concentration-dependent manner, as concluded by comparing full-length with truncated forms of p53, We further demonstrate JNK interaction with GST;p53 and the ability of JNK to phosphorylate truncated forms of GST-p53 or full-length (His)p53. Dependence of phosphorylation on conformation of p53 is further supported by the finding that the wild-type form of p53 (p53(wt)) undergoes better phosphorylation by CKII beta and by WCE kinases than mutant forms of p53 at amino acid 249 (p53(249)) or 273 (p53(273)), Moreover, shifting the kinase reaction's temperature from 37 degrees C to 18 degrees C reduces the phosphorylation of mutant p53 to a greater extent than of p53(wt)., Comparing truncated forms of p53 revealed that the ability of CKII beta, PKA, or WCE kinases to phosphorylate p53 requires amino acids 97-155 within the DNA-binding domain region, Among three 20-aa peptides spanning this region we have identified residues 97-117 that increase p53 phosphorylation by CKII beta while inhibiting p53 phosphorylation by PKA or WCE kinases, The importance of this region is further supported by computer modeling studies, which demonstrated that mutant p53(249) exhibits significant changes to the conformation of p53 within amino acids 97-117, In summary, phosphorylation-related analysis of different p53 forms in vitro indicates that conformation of p53 is a key determinant in its availability as a substrate for different kinases, as for the phosphorylation pattern generated by the same kinase. C1 SUNY HLTH SCI CTR,DEPT PATHOL & LAB MED,BROOKLYN,NY 11209. AMER HLTH FDN,MOL CARCINOGENESIS PROGRAM,VALHALLA,NY 10595. COLUMBIA UNIV COLL PHYS & SURG,DIV ENVIRONM SCI,NEW YORK,NY 10032. NCI,MOL CARCINOGENESIS LAB,BETHESDA,MD 20892. NCI,HUMAN CARCINOGENESIS LAB,BETHESDA,MD 20892. DUPONT CO INC,STINE HASKELL RES CTR,NEWARK,DE 19714. RI Wang, Xin/B-6162-2009; Friedman, Fred/D-4208-2016; OI RONAI, ZEEV/0000-0002-3859-0400 NR 38 TC 103 Z9 106 U1 0 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 4 PY 1997 VL 94 IS 5 BP 1686 EP 1691 DI 10.1073/pnas.94.5.1686 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA WM059 UT WOS:A1997WM05900019 PM 9050839 ER PT J AU Meacci, E Tsai, SC Adamik, R Moss, J Vaughan, M AF Meacci, E Tsai, SC Adamik, R Moss, J Vaughan, M TI Cytohesin-1, a cytosolic guanine nucleotide-exchange protein for ADP-ribosylation factor SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID BREFELDIN-A; BOVINE BRAIN; GOLGI; ARF; IDENTIFICATION; SEQUENCE; CELL; SEC7 AB Cytohesin-1, a protein abundant in cells of the immune system, has been proposed to be a human homolog of the Saccharomyces cerevisiae Sec7 gene product, which is crucial in protein transport, More recently, the same protein has been reported to be a regulatory factor for the alpha L beta 2 integrin in lymphocytes. Overexpression of human or yeast ADP-ribosylation factor (ARF) genes rescues yeast with Sec7 defects, restoring secretory pathway function, ARFs, 20-kDa guanine nucleotide-binding proteins initially identified by their ability to stimulate cholera toxin ADP-ribosyltransferase activity and now recognized as critical components in intracellular vesicular transport, exist in an inactive cytosolic form with GDP bound (ARF-GDP), Interaction with a guanine nucleotide-exchange protein (GEP) accelerates exchange of GDP for GTP, producing the active ARF-GTP, Both soluble and particulate GEPs have been described. To define better the interaction between ARF and Sec7-related proteins, effects of cytohesin-1, synthesized in Escherichia coli, on ARF activity were evaluated, Cytohesin-1 enhanced binding of S-35-labeled guanosine 5'-[gamma-thio]triphosphate [S-35]GTP[gamma S] or [H-3] GDP to ARF purified from bovine brain (i.e., it appeared to function as an ARF-GEP), Addition of cytohesin-1 to ARF3 with [S-35]GTP[gamma S] bound, accelerated [S-35]GTP[gamma S] release to a similar degree in the presence of unlabeled GDP or GTP[gamma S] and to a lesser degree with GDP[beta S]; release was negligible without added nucleotide, Cytohesin-1 also increased ARF1 binding to a Golgi fraction, but its effect was not inhibited by brefeldin A (BFA), a drug that reversibly inhibits Golgi function, In this regard, it differs from a recently reported BFA-sensitive ARF-GEP that contains a Sec7 domain. RP Meacci, E (reprint author), NHLBI,PULM CRIT CARE MED BRANCH,NIH,ROOM 6D-03,BLDG 10,10 CTR DR,MSC 1590,BETHESDA,MD 20892, USA. NR 23 TC 128 Z9 128 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 4 PY 1997 VL 94 IS 5 BP 1745 EP 1748 DI 10.1073/pnas.94.5.1745 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA WM059 UT WOS:A1997WM05900029 PM 9050849 ER PT J AU Komissarova, N Kashlev, M AF Komissarova, N Kashlev, M TI Transcriptional arrest: Escherichia coli RNA polymerase translocates backward, leaving the 3' end of the RNA intact and extruded SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE DNA and RNA footprinting; elongation complex ID ELONGATION FACTOR-SII; TERNARY COMPLEXES; STRUCTURAL-ANALYSIS; NASCENT TRANSCRIPT; CLEAVAGE; TERMINATION; MECHANISM AB RNA polymerase (RNAP) may become arrested during transcript elongation when ternary complexes remain intact but further RNA synthesis is blocked, Using a combination of DNA and RNA footprinting techniques, we demonstrate that the loss of catalytic activity upon arrest of Escherichia coli RNAP is accompanied by an isomerization of the ternary complex in which the enzyme disengages from the 3' end of the transcript and moves backward along the DNA with concomitant reverse threading of the intact RNA through the enzyme. The reversal of RNAP brings the active center to the internal RNA position and thereby it represents a step in factor-facilitated transcript cleavage. Secondary structure elements or the 5' end of the transcript can prevent the isomerization by blocking the RNA threading. The described novel property of RNAP has far-reaching implications for the understanding of the elongation mechanism and gene regulation. C1 NCI,FREDERICK CANC RES & DEV CTR,ABL BASIC RES PROGRAM,FREDERICK,MD 21702. PUBL HLTH RES INST,NEW YORK,NY 10016. FU NIGMS NIH HHS [GM49242] NR 26 TC 231 Z9 237 U1 1 U2 4 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD MAR 4 PY 1997 VL 94 IS 5 BP 1755 EP 1760 DI 10.1073/pnas.94.5.1755 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA WM059 UT WOS:A1997WM05900031 PM 9050851 ER PT J AU Chan, CK Hu, Y Takahashi, S Rousseau, DL Eaton, WA Hofrichter, J AF Chan, CK Hu, Y Takahashi, S Rousseau, DL Eaton, WA Hofrichter, J TI Submillisecond protein folding kinetics studied by ultrarapid mixing SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE cytochrome c; fluorescence; Forster energy transfer; polymer dynamics ID CYTOCHROME-C; CHYMOTRYPSIN INHIBITOR-2; ASSOCIATION; PRINCIPLES; TRANSITION; MECHANISM; LIGANDS; PATHWAY; CHAINS; ACID AB An ultrarapid-mixing continuous-flow method has been developed to study submillisecond folding of chemically denatured proteins, Turbulent flow created by pumping solutions through a small gap dilutes the denaturant in tens of microseconds, We have used this method to study cytochrome c folding kinetics in the previously inaccessible time range 80 mu s to 3 ms, To eliminate the heme-ligand exchange chemistry that complicates and slows the folding kinetics by trapping misfolded structures, measurements were made with the imidazole complex. Fluorescence quenching due to excitation energy transfer from the tryptophan to the heme was used to monitor the distance between these groups, The fluorescence decrease is biphasic. There is an unresolved process with tau < 50 mu s, followed by a slower, exponential process with tau = 600 mu s at the lowest denaturant concentration (0.2 M guanidine hydrochloride). These kinetics are interpreted as a barrier-free, partial collapse to the new equilibrium unfolded state at the lower denaturant concentration, followed by stower crossing of a free energy barrier separating the unfolded and folded states, The results raise several fundamental issues concerning the dynamics of collapse and barrier crossings in protein folding. C1 NIH,CHEM PHYS LAB,BETHESDA,MD 20892. AT&T BELL LABS,MURRAY HILL,NJ 07974. FU NIGMS NIH HHS [GM-48714] NR 54 TC 242 Z9 242 U1 1 U2 20 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 4 PY 1997 VL 94 IS 5 BP 1779 EP 1784 DI 10.1073/pnas.94.5.1779 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA WM059 UT WOS:A1997WM05900035 PM 9050855 ER PT J AU Smith, KA Chernova, OB Groves, RP Stark, MB Martinez, JL Davidson, JN Trent, JM Patterson, TE Agarwal, A Duncan, P Agarwal, ML Stark, GR AF Smith, KA Chernova, OB Groves, RP Stark, MB Martinez, JL Davidson, JN Trent, JM Patterson, TE Agarwal, A Duncan, P Agarwal, ML Stark, GR TI Multiple mechanisms of N-phosphonacetyl-L-aspartate resistance in human cell lines: Carbamyl-P synthetase/aspartate transcarbamylase/dihydro-orotase gene amplification is frequent only when chromosome 2 is rearranged SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE chromosome rearrangements; genomic stability; fluorescence in situ hybridization; induced amplification; isochromosome 2 ID RADIATION-INDUCED APOPTOSIS; NORMAL HUMAN FIBROBLASTS; SYRIAN-HAMSTER CELLS; WILD-TYPE P53; PYRIMIDINE BIOSYNTHESIS; MAMMALIAN-CELLS; GROWTH ARREST; EARLY STEPS; CAD GENES; DNA AB Rodent cells resistant to N-phosphonacetyl-L-aspartate (PALA) invariably contain amplified carbamyl-P synthetase/aspartate transcarbamylase/dihydro-orotase (CAD) genes, usually in widely spaced tandem arrays present as extensions of the same chromosome arm that carries a single copy of CAD in normal cells. In contrast, amplification of CAD is very infrequent in several human tumor cell lines, Cell lines with minimal chromosomal rearrangement and with unrearranged copies of chromosome 2 rarely develop intrachromosomal amplifications of CAD, These cells frequently become resistant to PALA through a mechanism that increases the aspartate transcarbamylase activity with no increase in CAD copy number, or they obtain one extra copy of CAD by forming an isochromosome 2p or by retaining an extra copy of chromosome 2, In cells with multiple chromosomal aberrations and rearranged copies of chromosome 2, amplification of CAD as tandem arrays from rearranged chromosomes is the most frequent mechanism of PALA resistance, All of these different mechanisms of PALA resistance are blocked in normal human fibroblasts. C1 NATL CTR HUMAN GENOME RES,CANC GENET LAB,BETHESDA,MD 20892. IMPERIAL CANC RES FUND,LINCOLNS INN FIELDS,LONDON WC2A 3PX,ENGLAND. CLEVELAND CLIN FDN,DEPT MOL BIOL,CLEVELAND,OH 44195. UNIV OXFORD,DEPT PHARMACOL,OXFORD OX1 3QT,ENGLAND. UNIV AUTONOMA MADRID,CSIC,CTR NACL BIOTECNOL,E-28049 MADRID,SPAIN. UNIV KENTUCKY,MED CTR,DEPT MICROBIOL & IMMUNOL,LEXINGTON,KY 40536. RI Martinez, Jose/C-4100-2008; Martinez, Jose/A-4725-2013 OI Martinez, Jose/0000-0001-8813-7607 FU NIGMS NIH HHS [GM-47644, GM-49345, R01 GM049345] NR 42 TC 19 Z9 19 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 4 PY 1997 VL 94 IS 5 BP 1816 EP 1821 DI 10.1073/pnas.94.5.1816 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA WM059 UT WOS:A1997WM05900042 PM 9050862 ER PT J AU Brown, KD Ziv, Y Sadanandan, SN Chessa, L Collins, FS Shiloh, Y Tagle, DA AF Brown, KD Ziv, Y Sadanandan, SN Chessa, L Collins, FS Shiloh, Y Tagle, DA TI The ataxia-telangiectasia gene product, a constitutively expressed nuclear protein that is not up-regulated following genome damage SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID CYCLE CHECKPOINT PATHWAY; WILD-TYPE P53; DNA-DAMAGE; KINASE; ARREST; REPAIR; CELLS; RADIOSENSITIVITY; AMPLIFICATION; CONSEQUENCES AB The product of the ataxia-telangiectasia gene (ATM) was identified by using an antiserum developed to a peptide corresponding to the deduced amino acid sequence, The ATM protein is a single, high-molecular weight protein predominantly confined to the nucleus of human fibroblasts, but is present in both nuclear and microsomal fractions from human lymphoblast cells and peripheral blood lymphocytes, ATM protein levels and localization remain constant throughout all stages of the cell cycle, Truncated ATM protein was not detected in lymphoblasts from ataxia-telangiectasia patients homozygous for mutations leading to premature protein termination, Exposure of normal human cells to gamma-irradiation and the radiomimetic drug neocarzinostatin had no effect on ATR;I protein levels, in contrast to a noted rise in p53 levels over the same time interval, These findings are consistent with a role for the ATM protein in ensuring the fidelity of DNA repair and cell cycle regulation following genome damage. C1 NATL HUMAN GENOME RES INST, NIH, LAB GENE TRANSFER, BETHESDA, MD 20892 USA. TEL AVIV UNIV, SACKLER SCH MED, DEPT HUMAN GENET, IL-69978 RAMAT AVIV, ISRAEL. UNIV ROMA LA SAPIENZA, DIPARTIMENTO MED SPERIMENTALE, I-00161 ROME, ITALY. FU NINDS NIH HHS [NS31763, R01 NS031763]; Telethon [E.0337] NR 46 TC 129 Z9 134 U1 0 U2 0 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD MAR 4 PY 1997 VL 94 IS 5 BP 1840 EP 1845 DI 10.1073/pnas.94.5.1840 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA WM059 UT WOS:A1997WM05900046 PM 9050866 ER PT J AU Wiest, DL Bhandoola, A Punt, J Kreibich, G McKean, D Singer, A AF Wiest, DL Bhandoola, A Punt, J Kreibich, G McKean, D Singer, A TI Incomplete endoplasmic reticulum (ER) retention in immature thymocytes as revealed by surface expression of ''ER-resident'' molecular chaperones SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID RECEPTOR-BETA-CHAIN; T-CELL; MEMBRANE-PROTEINS; GOLGI-APPARATUS; ANTIGEN RECEPTORS; SECRETORY PATHWAY; BINDING-PROTEIN; QUALITY-CONTROL; CD3 COMPONENTS; CALNEXIN AB The folding and assembly of nascent proteins in the endoplasmic reticulum (ER) is assisted by molecular chaperones that are themselves retained within the ER. We now report that a number of different ER proteins, including molecular chaperones, are selectively expressed on the surface of immature thymocytes, but their surface expression is extinguished upon further differentiation. Escape from the ER is only possible for newly synthesized ER proteins before they become permanently retained. Thus, the cellular process of ER retention is incomplete in immature thymocytes and provides an explanation for surface expression of partial receptor complexes that transduce differentiative signals during thymic development. C1 NCI,EXPT IMMUNOL BRANCH,NIH,BETHESDA,MD 20892. NYU,SCH MED,DEPT CELL BIOL,NEW YORK,NY 10016. MAYO CLIN & MAYO FDN,DEPT IMMUNOL,ROCHESTER,MN 55905. OI Wiest, David/0000-0002-0792-3188 NR 51 TC 72 Z9 72 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 4 PY 1997 VL 94 IS 5 BP 1884 EP 1889 DI 10.1073/pnas.94.5.1884 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA WM059 UT WOS:A1997WM05900054 PM 9050874 ER PT J AU Cirino, NM Li, GY Xiao, W Torrence, PF Silverman, RH AF Cirino, NM Li, GY Xiao, W Torrence, PF Silverman, RH TI Targeting RNA decay with 2',5' oligoadenylate-antisense in respiratory syncytial virus-infected cells SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID HUMAN ALVEOLAR MACROPHAGES; CONSTITUTIVE EXPRESSION; 2-5A-DEPENDENT RNASE; PROTEIN-SYNTHESIS; EPITHELIAL-CELLS; VACCINIA VIRUS; 2-5A ANTISENSE; RIBOSOMAL-RNA; VIRAL-RNA; INTERFERON AB Treatment of human cells with 2',5' oligoadenylate covalently linked to antisense (2-5A-antisense) results in the selective cleavage of targeted RNA species by 2-5A-dependent RNase L. Here we show that 2,5A-antisense containing stabilizing modifications at both termini are effective in suppressing the replication of respiratory syncytial virus (RSV) in human tracheal epithelial cells, The affinity of 2-5A-antisense for different regions in the RSV M2 and L mRNAs was predicted from a computer-generated model of the RNA secondary structure, The most potent 2-5A-antisense molecule caused a highly effective, dose-dependent suppression of RSV yields when added to previously infected cells, In contrast, control oligonucleotides, including an inactive dimeric form of 2-5A linked to antisense, 2-5A linked to a randomized sequence of nucleotides, and antisense molecules lacking 2-5A, had minimal effects on virus replication, The specificity of this approach was shown by reverse transcriptase-coupled PCR analysis of RSV M2, P, and N mRNA and of cellular glyceraldehyde-3 phosphate dehydrogenase mRNA, The RSV M2 mRNA amounts were depleted after treating RSV-infected cells with 2-5A-antisense targeted to this mRNA, whereas the amounts of the other RNA species were unchanged, These studies demonstrate that 2',5' oligoadenylate covalently linked to antisense (2-5A-antisense) can effectively suppress RSV replication by directing the cellular RNase L to selectively degrade an essential viral mRNA. C1 CLEVELAND CLIN FDN,DEPT CANC BIOL,RES INST,CLEVELAND,OH 44195. NIDDKD,SECT BIOMED CHEM,NIH,BETHESDA,MD 20892. FU NCI NIH HHS [1 PO1 CA 62220, P01 CA062220] NR 40 TC 60 Z9 71 U1 0 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 4 PY 1997 VL 94 IS 5 BP 1937 EP 1942 DI 10.1073/pnas.94.5.1937 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA WM059 UT WOS:A1997WM05900063 PM 9050883 ER PT J AU Peng, YW Rhee, SG Yu, WP Ho, YK Schoen, T Chader, GJ Yau, KW AF Peng, YW Rhee, SG Yu, WP Ho, YK Schoen, T Chader, GJ Yau, KW TI Identification of components of a phosphoinositide signaling pathway in retinal rod outer segments SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE phospholipase C; G protein; visual transduction ID PROTEIN-KINASE-C; LIGHT-MEDIATED BREAKDOWN; BOVINE PHOSPHOLIPASE-C; VERTEBRATE RETINA; ALPHA-SUBUNIT; RAT-BRAIN; PHOSPHATIDYLINOSITOL 4,5-BISPHOSPHATE; IMMUNOHISTOCHEMICAL LOCALIZATION; CONE PHOTORECEPTORS; INHIBITORY SUBUNIT AB Phototransduction in retinal rods involves a G protein-coupled signaling cascade that leads to cGMP hydrolysis and the closure of cGMP-gated cation channels that are open in darkness, producing a membrane hyperpolarization as the light response, For many years there have also been reports of the presence of a phosphoinositide pathway in the rod outer segment, though its functions and the molecular identities of its components are still unclear, Using immunocytochemistry with anti bodies against various phosphoinositide-specific phospholipase C (PLC) isozymes (beta 1-4, gamma 1-2, and delta 1-2), we have found PLC beta-like immunoreactivity in rod outer segments, Similar experiments with antibodies against the alpha-subunits of the G(q) family of G proteins, which are known to activate PLC beta 4, have also demonstrated G(alpha 11)-like immunoreactivity in this location, Immunoblots of total proteins from whole retina or partially purified rod outer segments with anti-PLC beta 4 and anti-C-alpha 11 antibodies gave, respectively, a single protein band of the expected molecular mass, suggesting specific labelings. The retinal locations of the two proteins were also supported by in situ hybridization experiments on mouse retina with probes specific for the corresponding mouse genes. These two proteins, or immunologically identical isoforms, therefore likely mediate the phosphoinositide signaling pathway in the rod outer segment, At present, G(alpha 11) or a G(alpha 11)-like protein represents the only G protein besides transducin (which mediates phototransduction) identified so far in the rod outer segment. Although absent in the outer segment layer, other PLC isoforms as well as G(alpha q) (another G(q) family member), are present elsewhere in the retina. C1 JOHNS HOPKINS UNIV,SCH MED,HOWARD HUGHES MED INST,BALTIMORE,MD 21205. JOHNS HOPKINS UNIV,SCH MED,DEPT NEUROSCI,BALTIMORE,MD 21205. JOHNS HOPKINS UNIV,SCH MED,DEPT OPHTHALMOL,BALTIMORE,MD 21205. NHLBI,BIOCHEM LAB,NIH,BETHESDA,MD 20892. UNIV ILLINOIS,DEPT BIOCHEM,CHICAGO,IL 60612. NEI,RETINAL CELL & MOL BIOL LAB,NIH,BETHESDA,MD 20892. FU NEI NIH HHS [EY06837, F32 EY006837, R01 EY006837, R37 EY006837] NR 58 TC 56 Z9 57 U1 0 U2 3 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD MAR 4 PY 1997 VL 94 IS 5 BP 1995 EP 2000 DI 10.1073/pnas.94.5.1995 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA WM059 UT WOS:A1997WM05900073 PM 9050893 ER PT J AU Rouse, B Azen, C Koch, R Matalon, R Hanley, W delaCruz, F Trefz, F Friedman, E Shifrin, H AF Rouse, B Azen, C Koch, R Matalon, R Hanley, W delaCruz, F Trefz, F Friedman, E Shifrin, H TI Maternal phenylketonuria collaborative study (MPKUCS) offspring: Facial anomalies, malformations, and early neurological sequelae SO AMERICAN JOURNAL OF MEDICAL GENETICS LA English DT Article DE MPKU; maternal phenylketonuria; congenital heart disease; microcephaly; facial dysmorphology ID HYPERPHENYLALANINEMIA AB Maternal phenylketonuria (PKU) in untreated women has resulted in offspring with microcephaly, mental retardation, congenital heart disease (CHD), and intrauterine growth retardation. The Maternal Phenylketonuria Collaborative Study (MPKUCS) was designed to determine the effect of dietary control of blood phenylalanine (Phe) during pregnancy in preventing damage to the fetus associated with untreated Maternal PKU. A cohort of offspring hom MPKUS pregnancies was ascertained and examined to evaluate malformations, including CHD, craniofacial abnormalities, microcephaly, intrauterine and postnatal growth retardation, other major and minor defects, and early abnormal neurological signs. For analysis, the women were grouped according to their mean Phe levels in mu mol/liter, less than or equal to 360, 361-600, 601-900, or >900, during critical gestational weeks of 0-8 (N=203) and 8-12 (N=190), and average for Phe exposure throughout pregnancy (N=183). Frequencies of congenital abnormalities increased with increasing maternal Phe levels. Significant relationships included average Phe 0-8 weeks and CHD (P=0.001); average Phe 8-12 weeks and brain, fetal, and postnatal growth retardation (P <0.0005 for all), wide nasal bridge (P <0.0005), and anteverted nares (P=0.001); and average Phe exposure during the entire pregnancy and neurological signs (P <0.0005). Although 14% of infants had CHD, none of the CHD occurred at 120-360 mu mol/liter and only one (3%) at 361-600 mu mol/liter. At levels of 120-360 mu mol/liter, there were three infants (6%) with microcephaly, two (4%) with postnatal growth, and none with intrauterine growth retardation, in contrast to 85%, 51%, and 26%, respectively, with Phe above 900 mu mol/liter. These data support the concept that women with PKU should begin a low-phenylalanine diet to achieve Phe levels of <360 mu mol/liter prior to conception and should maintain this throughout pregnancy. (C) 1997 Wiley-Liss, Inc. C1 CHILDRENS HOSP LOS ANGELES,LOS ANGELES,CA 90027. UNIV ILLINOIS,CHICAGO,IL. MIAMI CHILDRENS HOSP,RES INST,MIAMI,FL. HOSP SICK CHILDREN,TORONTO,ON M5G 1X8,CANADA. NICHHD,NIH,BETHESDA,MD 20892. UNIV TUEBINGEN KINDERKLIN,REUTLINGEN,GERMANY. RP Rouse, B (reprint author), UNIV TEXAS,MED BRANCH,CHILDRENS HOSP,301 UNIV BLVD,GALVESTON,TX 77555, USA. FU NICHD NIH HHS [N0I-HD-2-3155, N0I-HD-2-3156, N0I-HD-2-3148] NR 27 TC 50 Z9 56 U1 1 U2 3 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0148-7299 J9 AM J MED GENET JI Am. J. Med. Genet. PD MAR 3 PY 1997 VL 69 IS 1 BP 89 EP 95 DI 10.1002/(SICI)1096-8628(19970303)69:1<89::AID-AJMG17>3.0.CO;2-K PG 7 WC Genetics & Heredity SC Genetics & Heredity GA WL518 UT WOS:A1997WL51800017 PM 9066890 ER PT J AU DellAngelica, EC Ohno, H Ooi, CE Rabinovich, E Roche, KW Bonifacino, JS AF DellAngelica, EC Ohno, H Ooi, CE Rabinovich, E Roche, KW Bonifacino, JS TI AP-3: An adaptor-like protein complex with ubiquitous expression SO EMBO JOURNAL LA English DT Article DE adaptors; coats; endosomes; sorting signals ID TRANS-GOLGI NETWORK; LYSOSOMAL ACID-PHOSPHATASE; CYTOPLASMIC DOMAIN; COATED PITS; PLASMA-MEMBRANE; BREFELDIN-A; TARGETING SIGNALS; CELL-SURFACE; VESICLE COAT; CLATHRIN AB We have identified two closely related human proteins (sigma(3A) and sigma(3B)) that are homologous to the small chains, sigma(1) and sigma(2), of clathrin-associated adaptor complexes, Northern and Western blot analyses demonstrate that the products of both the sigma(3A) and sigma(3B) genes are expressed in a wide variety of tissues and cell lines. sigma(3A) and sigma(3B) are components of a large complex, named AP-3, that also contains proteins of apparent molecular masses of 47, 140 and 160 kDa. In non-neuronal cells, the 47 kDa protein most likely corresponds to the medium chain homolog p47A, and the 140 kDa protein is a homolog of the neuron-specific protein beta-NAP. Like other members of the medium-chain family, the p47A chain is capable of interacting with the tyrosine-based sorting signal YQRL from TGN38. Immunofluorescence microscopy analyses show that the sigma(3)-containing complex is present both in the area of the TGN and in peripheral structures, some of which contain the transferrin receptor, These results suggest that the sigma(3) chains are components of a novel, ubiquitous adaptor-like complex involved in the recognition of tyrosine-based sorting signals. C1 NICHHD,CELL BIOL & METAB BRANCH,NIH,BETHESDA,MD 20892. RI Ohno, Hiroshi/L-7899-2014; OI Ohno, Hiroshi/0000-0001-8776-9661; Roche, Katherine/0000-0001-7282-6539; Bonifacino, Juan S./0000-0002-5673-6370 NR 56 TC 299 Z9 303 U1 3 U2 9 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD, ENGLAND OX2 6DP SN 0261-4189 J9 EMBO J JI Embo J. PD MAR 3 PY 1997 VL 16 IS 5 BP 917 EP 928 DI 10.1093/emboj/16.5.917 PG 12 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA WN628 UT WOS:A1997WN62800003 PM 9118953 ER PT J AU Kang, YK Yoo, SH AF Kang, YK Yoo, SH TI Identification of the secretory vesicle membrane binding region of chromogranin A SO FEBS LETTERS LA English DT Article DE cloning; sequence; chromogranin A; pH; secretory vesicle membrane ID B SECRETOGRANIN-I; MESSENGER-RNA; CDNA SEQUENCE; PROTEIN-I; CONFORMATIONAL CHANGE; PANCREASTATIN; PRECURSOR; GENE AB Since the conserved near N-terminal region (residues 18-37) of chromogranin A (CGA) has tentatively been identified as the vesicle membrane interacting region using synthetic peptides, it was necessary to confirm this finding with CGA deletion proteins. In order to address this need and to clarify the discrepancies of the published amino acid sequences of CGA, we cloned a CGA gene and produced CGA deletion proteins of various sizes. The recombinant CGA protein lacking the first 16 amino acid residues bound to the vesicle membrane as well as the full-length CGA at pH 5.5. However, the CGA protein lacking the first 39 amino acid residues, which include the conserved near N-terminal region (residues 17-38), failed to interact with the vesicle membrane at pH 5.5, clearly indicating the essential role of the conserved near N-terminal region in the pH-dependent interaction of CGA with the vesicle membrane. (C) 1997 Federation of European Biochemical Societies. C1 NIDCD, NEUROCHEM LAB, NIH, BETHESDA, MD 20892 USA. NR 24 TC 16 Z9 17 U1 0 U2 0 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 3 PY 1997 VL 404 IS 1 BP 87 EP 90 DI 10.1016/S0014-5793(97)00099-9 PG 4 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA WM006 UT WOS:A1997WM00600019 PM 9074643 ER PT J AU Shores, EW Tran, T Grinberg, A Sommers, CL Shen, H Love, PE AF Shores, EW Tran, T Grinberg, A Sommers, CL Shen, H Love, PE TI Role of the multiple T cell receptor (TCR)-zeta chain signaling motifs in selection of the T cell repertoire SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article ID ANTIGEN RECEPTOR; ZETA-CHAIN; TRANSGENIC MICE; POSITIVE SELECTION; TYROSINE KINASES; THYMOCYTES; TRANSDUCTION; DIFFERENTIATION; INTERMEDIATE; ACTIVATION AB Immature thymocytes undergo a selection process within the thymus based on their T cell antigen receptor (TCR) specificity that results either in their maturation into functionally competent, self-MHC-restricted T cells (positive selection) or their deletion (negative selection). The outcome of thymocyte selection is thought to be controlled by signals transduced by the TCR that vary in relation to the avidity of the TCR-ligand interaction. The TCR is composed of four distinct signal transducing subunits (CD3-gamma, -delta, -epsilon, and zeta) that contain either one (CD3-gamma, -delta, -epsilon) or three (-zeta) signaling motifs (ITAMs) within their intracytoplasmic domains. A possible function for multiple TCR ITAMs could be to amplify signals generated by the TCR during selection. To determine the importance of the multiple TCR-S chain ITAMs in thymocyte selection, transgenes encoding alpha/beta TCRs with known specificity were bred into mice in which zeta chains lacking one or more ITAMs had been genetically substituted for endogenous zeta. A direct relationship was observed between the number of zeta chain ITAMs within the TCR complex and the efficiency of both positive and negative selection. These results reveal a role for multiple TCR ITAMs in thymocyte selection and identify a function for TCR signal amplification in formation of the T cell repertoire. C1 NICHHD,LAB MAMMALIAN GENES & DEV,NIH,BETHESDA,MD 20892. RP Shores, EW (reprint author), US FDA,DIV HEMATOL PROD,CTR BIOL EVALUAT & RES,HFM 538,BLDG 29A,RM 2B23,29 LINCOLN DR,BETHESDA,MD 20892, USA. NR 32 TC 102 Z9 102 U1 0 U2 0 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 SN 0022-1007 J9 J EXP MED JI J. Exp. Med. PD MAR 3 PY 1997 VL 185 IS 5 BP 893 EP 900 DI 10.1084/jem.185.5.893 PG 8 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA WM240 UT WOS:A1997WM24000011 PM 9120395 ER PT J AU Rousse, I Beaulieu, S Rowe, W Meaney, MJ Barden, N Rochford, J AF Rousse, I Beaulieu, S Rowe, W Meaney, MJ Barden, N Rochford, J TI Spatial memory in transgenic mice with impaired glucocorticoid receptor function SO NEUROREPORT LA English DT Article DE glucocorticoid receptors; hypothalamic-pituitary-adrenal axis; mice; Morris water maze; radial arm maze ID MIDDLE-AGED RATS; ANTISENSE RNA; YOUNG; DEFICITS AB SPATIAL learning and memory function of transgenic mice with impaired glucocorticoid receptor function was assessed in the Morris water maze and the radial arm maze. Transgenic mice took longer to find a submerged and a visual platform in the water maze task than did mice from the parent strain (B6C/3F1), although performance was improved in the visible platform condition relative to the submerged platform task. In the radial arm maze, transgenic mice made significantly more errors than B6C/3F1 mice. In both tasks, the behavioural strategies adopted by transgenic mice were non-optimal for correct performance. It is suggested that the impaired performance displayed by transgenic mice in both tests is largely attributable to these altered behavioural strategies. C1 MCGILL UNIV,DEPT PSYCHIAT,DOUGLAS HOSP,RES CTR,VERDUN,PQ H4H 1RS,CANADA. NIMH,BIOL PSYCHIAT BRANCH,BETHESDA,MD 20892. UNIV LAVAL,DEPT PHYSIOL,QUEBEC CITY,PQ,CANADA. NR 12 TC 47 Z9 48 U1 0 U2 0 PU RAPID SCIENCE PUBLISHERS PI LONDON PA 2-6 BOUNDARY ROW, LONDON, ENGLAND SE1 8NH SN 0959-4965 J9 NEUROREPORT JI Neuroreport PD MAR 3 PY 1997 VL 8 IS 4 BP 841 EP 845 DI 10.1097/00001756-199703030-00007 PG 5 WC Neurosciences SC Neurosciences & Neurology GA WU313 UT WOS:A1997WU31300008 PM 9141049 ER PT J AU Tabaton, M Perry, G Smith, M Vitek, M Angelini, G Dapino, D Garibaldi, S Zaccheo, D Odetti, P AF Tabaton, M Perry, G Smith, M Vitek, M Angelini, G Dapino, D Garibaldi, S Zaccheo, D Odetti, P TI Is amyloid beta-protein glycated in Alzheimer's disease? SO NEUROREPORT LA English DT Article DE Alzheimer's disease; amyloid P-protein; apolipoprotein E; non-enzymatic glycation ID END-PRODUCTS; PATHOLOGY; INDUCTION AB RECENT data suggest that protein glycation is involved in the process of amyloid formation in Alzheimer's disease (AD). To further investigate this issue, we analyzed the presence of advanced glycation end products (AGE) in soluble and insoluble forms of amyloid B-protein (AP) as well as in apolipoprotein E (apoE), a protein bound to amyloid deposits. Both proteins were extracted from cerebral cortex obtained from patients with AD and probed by immunoblotting with two antibodies specific for different AGE, already known to immunocytochemically label amyloid plaques. All the AGE antibodies failed to recognize either AP or apoE, whereas they reacted with synthetic AP glycated in vitro. These findings indicate that other proteins associated with amyloid deposits are candidates to be modified with AGE in Alzheimer's cerebral tissue. C1 CASE WESTERN RESERVE UNIV,INST PATHOL,CLEVELAND,OH 44106. PICOWER INST MED RES,MANHASSET,NY 11030. UNIV GENOA,DEPT INTERNAL MED,DIMI,I-16132 GENOA,ITALY. NATL CANC INST,GENOA,ITALY. RP Tabaton, M (reprint author), UNIV GENOA,INST ANAT,VIA DE TONI 10,I-16132 GENOA,ITALY. RI Smith, Mark/A-9053-2009; Perry, George/A-8611-2009; Angelini, Giovanna/C-8476-2013; OI Perry, George/0000-0002-6547-0172; ANGELINI, giovanna/0000-0003-1474-5452 FU Telethon [E.0126] NR 14 TC 13 Z9 13 U1 0 U2 2 PU RAPID SCIENCE PUBLISHERS PI LONDON PA 2-6 BOUNDARY ROW, LONDON, ENGLAND SE1 8NH SN 0959-4965 J9 NEUROREPORT JI Neuroreport PD MAR 3 PY 1997 VL 8 IS 4 BP 907 EP 909 DI 10.1097/00001756-199703030-00018 PG 3 WC Neurosciences SC Neurosciences & Neurology GA WU313 UT WOS:A1997WU31300021 PM 9141062 ER PT J AU Faraco, CD Vugman, I Siraganian, RP Jamur, MC Oliver, C AF Faraco, CD Vugman, I Siraganian, RP Jamur, MC Oliver, C TI Immunocytochemical identification of immature rat peritoneal mast cells using a monoclonal antibody specific for rat mast cells SO ACTA HISTOCHEMICA LA English DT Article DE mast cells; peritoneal cavity; rat; repopulation; maturation; monoclonal antibodies; immunomicroscopy ID BASOPHILIC LEUKEMIA-CELLS; BINDING; IGE; INVIVO AB The lack of immunological or morphological markers makes identification of immature mast cells difficult. In the present study we have used a rat mast cell specific monoclonal antibody (mAb AA4) to immunolabel mast cells during repopulation of the peritoneal cavity. Peritoneal cells were collected six days after injection of distilled water and examined by light and electron microscopy. mAb AA4 stained immature mast cells in various stages of maturation including a population of very immature mast cells that could not be identified using conventional staining methods. These cells had virtually no cytoplasmic granules and peripherally located located nuclei. Thus, immunolabeling with mAb AA4 has revealed a population of very immature mast cells not previously reported during repopulation of the peritoneal cavity. C1 OFF NAVAL RES,ARLINGTON,VA 22217. UNIV FED PARANA,DEPT BIOL CELULAR,BR-80060000 CURITIBA,PARANA,BRAZIL. UNIV SAO PAULO,FAC MED RIBEIRAO PRETO,DEPT BIOQUIM,RIBEIRAO PRET,SP,BRAZIL. NIDR,IMMUNOL LAB,NIH,BETHESDA,MD 20892. RI Jamur, Maria Celia/L-5520-2016 OI Jamur, Maria Celia/0000-0001-7065-8543 NR 14 TC 2 Z9 2 U1 0 U2 0 PU GUSTAV FISCHER VERLAG PI JENA PA VILLENGANG 2, D-07745 JENA, GERMANY SN 0065-1281 J9 ACTA HISTOCHEM JI Acta Histochem. PD MAR PY 1997 VL 99 IS 1 BP 23 EP 27 PG 5 WC Cell Biology SC Cell Biology GA WR359 UT WOS:A1997WR35900003 PM 9150793 ER PT J AU Timpone, JG Wright, DJ Li, N Egorin, MJ Enama, ME Mayers, J Galetto, G Gagnon, S Vargo, J Chirgwin, K Marcel, A Cohn, D Hopkins, B Dudley, M Geletko, S Standiford, H Cervino, K Mushatt, DM Greenspan, D Powderly, W Meyers, M Sampson, JH McMillan, G Novak, R Moreira, L AF Timpone, JG Wright, DJ Li, N Egorin, MJ Enama, ME Mayers, J Galetto, G Gagnon, S Vargo, J Chirgwin, K Marcel, A Cohn, D Hopkins, B Dudley, M Geletko, S Standiford, H Cervino, K Mushatt, DM Greenspan, D Powderly, W Meyers, M Sampson, JH McMillan, G Novak, R Moreira, L TI The safety and pharmacokinetics of single-agent and combination therapy with megestrol acetate and dronabinol for the treatment of HIV wasting syndrome SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Article ID AIDS; INFECTION; CACHEXIA; BREAST; CANCER; WEIGHT; PLASMA AB This randomized, open-labeled, multicenter study was designed to assess safety and pharmacokinetics of dronabinol (Marinol) tablets and megestrol acetate (Megace) micronized tablets, alone and in combination, for treatment of HIV wasting syndrome, Weight and quality of life data were also collected, Fifty-two patients (mean CD4(+) count, 59 cells/mu l) were randomized to one of four treatment arms: dronabinol 2.5 mg twice/day (D); megestrol acetate 750 mg/day (M750); megestrol acetate 750 mg/day+dronabinol 2.5 mg twice/day (R4750+D); or megestrol acetate 250 mg/day+dronabinol 2.5 mg twice/day (M250+D), After therapy initiation, 47 patients returned for at least one visit, and 39 completed the planned 12 weeks of study visits, Occurrence of adverse events, drug discontinuation, new AIDS-defining conditions, or CD4(+) T lymphocyte changes were not statistically significantly different among arms, Serious adverse events assessed as related to dronabinol included CNS events (e.g., confusion, anxiety, emotional lability, euphoria, hallucinations) and those assessed as related to megestrol acetate included dyspnea, liver enzyme changes, and hyperglycemia. The mean weight change +/- SE over 12 weeks was as follows: D, -2.0 +/- 1.3 kg; M750, +6.5 +/- 1.1 kg; M750+D, +6.0 +/- 1.0 kg; and M250+D, -0.3 +/- 1.0 kg (difference among treatment arms, p = 0.0001), Pharmacokinetic parameters measured after 2 weeks of therapy for M750 were C-max = 985 ng/ml and AUC = 22,487 ng x hr/ml, and for dronabinol and its active metabolite (HO-THC), respectively, were C-max = 2.01; 4.61 ng/ml and AUC = 5.3; 23.7 ng x hr/ml, For megestrol acetate, but not dronabinol, there was a positive correlation at week 2 between both C-max and AUC with each of the following: (1) weight change, (2) breakfast visual analog scale for hunger (VASH) score, and (3) dinner VASH score. C1 NIAID,DIV AIDS,NIH,BETHESDA,MD 20892. WESTAT CORP,ROCKVILLE,MD 20850. SOCIAL & SCI SYST INC,ROCKVILLE,MD 20852. UNIV KANSAS,SCH MED,WICHITA,KS. SUNY HLTH SCI CTR,BROOKLYN,NY 11203. DENVER PUBL HLTH ADM & DIS CONTROL,DENVER,CO. UNIV RHODE ISL,COLL PHARM,PROVIDENCE,RI. UNIV MARYLAND,SCH MED,CTR CANC,BALTIMORE,MD 21201. TULANE UNIV,SCH MED,NEW ORLEANS,LA 70112. UNIV WASHINGTON,SCH MED,ST LOUIS,MO. RES & EDUC GRP,PORTLAND,OR. UNIV ILLINOIS,CHICAGO,IL. FU NIAID NIH HHS [N01-AI-15123] NR 29 TC 62 Z9 65 U1 2 U2 4 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 SN 0889-2229 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD MAR 1 PY 1997 VL 13 IS 4 BP 305 EP 315 DI 10.1089/aid.1997.13.305 PG 11 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA WN483 UT WOS:A1997WN48300005 PM 9071430 ER PT J AU Epstein, AE Domanski, M Friedman, PL Greene, HL Hallstrom, AP Schron, E Wyse, DG Zipes, DP AF Epstein, AE Domanski, M Friedman, PL Greene, HL Hallstrom, AP Schron, E Wyse, DG Zipes, DP TI Are implantable cardioverter-defibrillators or drugs more effective in prolonging life? SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Editorial Material C1 NHLBI,BETHESDA,MD 20892. BRIGHAM & WOMENS HOSP,BOSTON,MA 02115. AVID,CLIN TRIAL CTR,SEATTLE,WA. UNIV CALGARY,CALGARY,AB,CANADA. INDIANA UNIV,INDIANAPOLIS,IN 46204. RP Epstein, AE (reprint author), UNIV ALABAMA,DIV CARDIOVASC DIS,UNIV STN,THT 321L,BIRMINGHAM,AL 35294, USA. NR 20 TC 11 Z9 12 U1 0 U2 1 PU EXCERPTA MEDICA INC PI NEW YORK PA 245 WEST 17TH STREET, NEW YORK, NY 10011 SN 0002-9149 J9 AM J CARDIOL JI Am. J. Cardiol. PD MAR 1 PY 1997 VL 79 IS 5 BP 661 EP 663 PG 3 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA WL735 UT WOS:A1997WL73500023 ER PT J AU Chamberlin, ME Ubagai, T Mudd, SH Levy, HL Chou, JY AF Chamberlin, ME Ubagai, T Mudd, SH Levy, HL Chou, JY TI Dominant inheritance of isolated hypermethioninemia is associated with a mutation in the human methionine adenosyltransferase 1A gene SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Article ID S-ADENOSYLMETHIONINE SYNTHETASE; MOLECULAR-CLONING; DEFICIENCY; PURIFICATION; EXPRESSION; PATHWAY AB Methionine adenosyltransferase (MAT) I/III deficiency, characterized by isolated persistent hypermethioninemia, is caused by mutations in the MAT1A gene encoding MAT alpha 1, the subunit of major hepade enzymes MAT I ([alpha 1](4)) and III ([alpha 1](2)). We have characterized 10 MAT1A mutations in MAT I/III-deficient individuals and shown that the associated hypermethioninemic phenotype was inherited as an autosomal recessive trait. However, dominant inheritance of hypermethioninemia, also hypothesized to be caused by MAT I/III deficiency, has been reported in two families. Here we show that the only mutation uncovered in one of these families, G, is a G-->A transition at nt 791 in exon VII of one MAT1A allele that converts an arginine at position 264 to a histidine (R264H). This single allelic R264H mutation was subsequently identified in two hypermethioninemic individuals in an additional family, C. Family C members were also found to inherit hypermethioninemia in a dominant fashion, and the available affected members analyzed carried the single allelic R264H mutation. Substitution of R-264 with histidine (R264H, the naturally occurring mutant), leucine (R264L), aspartic acid (R264D), or glutamic acid (R264E) greatly reduced MAT activity and severely impaired the ability of the MAT alpha 1 subunits to form homodimers essential for optimal catalytic activity. On the other hand, when lysine was substituted far R-264 (R264K), the mutant alpha 1 subunit was able to form dimers that retain significant MAT activity, suggesting that amino acid 264 is involved in intersubunit salt-bridge formation. Cotransfection studies show that R264/R264H MAT alpha 1 heterodimers are enzymatically inactive, thus providing an explanation for the R264H-mediated dominant inheritance of hypermethioninemia. C1 NICHHD,HERITABLE DISORDERS BRANCH,NIH,BETHESDA,MD 20892. NIMH,LAB GEN & COMPARAT BIOCHEM,NIH,BETHESDA,MD 20892. CHILDRENS HOSP,BOSTON,MA 02115. HARVARD UNIV,SCH MED,BOSTON,MA. NR 23 TC 40 Z9 42 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 1997 VL 60 IS 3 BP 540 EP 546 PG 7 WC Genetics & Heredity SC Genetics & Heredity GA WK403 UT WOS:A1997WK40300009 PM 9042912 ER PT J AU Muenke, M Gripp, KW McDonaldMcGinn, DM Gaudenz, K Whitaker, LA Bartlett, SP Markowitz, RI Robin, NH Nwokoro, N Mulvihill, JJ Losken, HW Mulliken, JB Guttmacher, AE Wilroy, RS Clarke, LA Hollway, G Ades, LC Haan, EA Mulley, JC Cohen, MM Bellus, GA Francomano, CA Moloney, DM Wall, SA Wilkie, AOM Zackai, EH AF Muenke, M Gripp, KW McDonaldMcGinn, DM Gaudenz, K Whitaker, LA Bartlett, SP Markowitz, RI Robin, NH Nwokoro, N Mulvihill, JJ Losken, HW Mulliken, JB Guttmacher, AE Wilroy, RS Clarke, LA Hollway, G Ades, LC Haan, EA Mulley, JC Cohen, MM Bellus, GA Francomano, CA Moloney, DM Wall, SA Wilkie, AOM Zackai, EH TI A unique point mutation in the fibroblast growth factor receptor 3 gene (FGFR3) defines a new craniosynostosis syndrome SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Article ID SAETHRE-CHOTZEN-SYNDROME; JACKSON-WEISS-SYNDROME; CROUZON-SYNDROME; PFEIFFER-SYNDROME; SYNDROME LOCUS; APERT SYNDROME; HETEROGENEITY; ACHONDROPLASIA; EXCLUSION; DOMAIN AB The underlying basis of many forms of syndromic craniosynostosis has been defined on a molecular level. However, many patients with familial or sporadic craniosynostosis do not have the classical findings of those craniosynostosis syndromes. Here we present 61 individuals from 20 unrelated families where coronal synostosis is due to an amino acid substitution (Pro250Arg) that results from a single point mutation in the fibroblast growth factor receptor 3 gene on chromosome 4p. In this instance, a new clinical syndrome is being defined on the basis of the molecular finding. In addition to the skull findings, some patients had abnormalities on radiographs of hands and feet, including thimble-like middle phalanges, coned epiphyses, and carpal and tarsal fusions. Brachydactyly was seen in some cases; none had clinically significant syndactyly or deviation of the great toe. Sensorineural hearing loss was present in some, and developmental delay was seen in a minority. While the radiological findings of hands and feet can be very helpful in diagnosing this syndrome, it is not in all cases clearly distinguishable on a clinical basis from other craniosynostosis syndromes. Therefore, this mutation should be tested for in patients with coronal synostosis. C1 UNIV PENN,CHILDRENS HOSP PHILADELPHIA,DEPT GENET,PHILADELPHIA,PA 19104. CASE WESTERN RESERVE UNIV,SCH MED,CLEVELAND,OH. UNIV PITTSBURGH,PITTSBURGH,PA. HARVARD UNIV,CHILDRENS HOSP,SCH MED,BOSTON,MA 02115. UNIV VERMONT,COLL MED,BURLINGTON,VT. UNIV TENNESSEE,MEMPHIS,TN. UNIV BRITISH COLUMBIA,VANCOUVER,BC V5Z 1M9,CANADA. WOMENS & CHILDRENS HOSP,ADELAIDE,SA,AUSTRALIA. DALHOUSIE UNIV,HALIFAX,NS,CANADA. JOHNS HOPKINS UNIV,NATL CTR HUMAN GENOME RES,NIH,BETHESDA,MD. JOHN RADCLIFFE HOSP,INST MOL MED,OXFORD OX3 9DU,ENGLAND. RADCLIFFE INFIRM,CRANIOFACIAL UNIT,OXFORD OX2 6HE,ENGLAND. RP Muenke, M (reprint author), UNIV PENN,CHILDRENS HOSP PHILADELPHIA,DEPT PEDIAT,DIV HUMAN GENET & MOL BIOL,34TH & CIV CTR BLVD,PHILADELPHIA,PA 19104, USA. RI Hollway, Georgina/E-6764-2010; OI Clarke, Lorne/0000-0003-0512-7281 FU NICHD NIH HHS [R01HD29862, R29HD28732]; Wellcome Trust NR 54 TC 258 Z9 264 U1 0 U2 6 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 1997 VL 60 IS 3 BP 555 EP 564 PG 10 WC Genetics & Heredity SC Genetics & Heredity GA WK403 UT WOS:A1997WK40300011 PM 9042914 ER PT J AU Matsumine, H Saito, M ShimodaMatsubayashi, S Tanaka, H Ishikawa, A NakagawaHattori, Y Yokochi, M Kobayashi, T Igarashi, S Takano, H Sanpei, K Koike, R Mori, H Kondo, T Mizutani, Y Schaffer, AA Yamamura, Y Nakamura, S Kuzuhara, S Tsuji, S Mizuno, Y AF Matsumine, H Saito, M ShimodaMatsubayashi, S Tanaka, H Ishikawa, A NakagawaHattori, Y Yokochi, M Kobayashi, T Igarashi, S Takano, H Sanpei, K Koike, R Mori, H Kondo, T Mizutani, Y Schaffer, AA Yamamura, Y Nakamura, S Kuzuhara, S Tsuji, S Mizuno, Y TI Localization of a gene for an autosomal recessive form of juvenile Parkinsonism to chromosome 6q25.2-27 SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Article ID MANGANESE-SUPEROXIDE-DISMUTASE; LINKAGE ANALYSIS; COMPLEX-I; DISEASE; TRAITS; DNA; MAP AB An autosomal recessive form of juvenile Parkinsonism (AR-JP) (MIM 600116) is a levodopa-responsive Parkinsonism whose pathological finding is a highly selective degeneration of dopaminergic neurons in the zona compacta of the substantia nigra. By linkage analysis of diallelic polymorphism of the Mn-superoxide dismutase gene (SOD2), we found a family with AR-JP showing perfect segregation of the disease with the SOD2 locus. By extending the linkage analysis to 13 families with AR-JP, we discovered strong evidence for the localization of the AR-JP gene at chromosome 6q25.2-27, including the SOD2 locus, with the maximal cumulative pairwise LOD scores of 7.26 and 7.71 at DGS305 (theta=.03) and D6S253 (theta=.02), respectively. Observation of obligate recombination events, as well as multipoint linkage analysis, placed the AR-JP gene in a 17-cM interval between D6S437 and D6S264. Delineation of the AR-JP gene will be an important step toward our understanding of the molecular mechanism underlying selective degeneration of the nigral neurons. C1 JUNTENDO UNIV,SCH MED,DEPT NEUROL,TOKYO 113,JAPAN. TOKYO METROPOLITAN EBARA HOSP,DEPT NEUROL,TOKYO,JAPAN. TOKYO METROPOLITAN MATSUZAWA HOSP,DEPT CLIN PATHOL,TOKYO,JAPAN. NIIGATA UNIV,BRAIN RES INST,DEPT NEUROL,NIIGATA 951,JAPAN. NISHI OJIYA NATL HOSP,DEPT NEUROL,NIIGATA,JAPAN. RICE UNIV,DEPT COMP SCI,HOUSTON,TX 77251. NIH,NATL CTR HUMAN GENOME RES,BETHESDA,MD 20892. HIROSHIMA UNIV,SCH MED,DEPT HLTH SCI,HIROSHIMA,JAPAN. HIROSHIMA UNIV,SCH MED,DEPT INTERNAL MED 3,HIROSHIMA,JAPAN. MIE UNIV,SCH MED,DEPT NEUROL,TSU,MIE,JAPAN. RI Schaffer, Alejandro/F-2902-2012 NR 39 TC 249 Z9 265 U1 1 U2 4 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 S WOODLAWN AVE, CHICAGO, IL 60637 SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD MAR PY 1997 VL 60 IS 3 BP 588 EP 596 PG 9 WC Genetics & Heredity SC Genetics & Heredity GA WK403 UT WOS:A1997WK40300015 PM 9042918 ER PT J AU Wartenfeld, R Golomb, E Katz, G Bale, SJ Goldman, B Pras, M Kastner, DL Pras, E AF Wartenfeld, R Golomb, E Katz, G Bale, SJ Goldman, B Pras, M Kastner, DL Pras, E TI Molecular analysis of cystinuria in Libyan Jews: Exclusion of the SLC3A1 gene and mapping of a new locus on 19q SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Article ID AMINO-ACID TRANSPORTER; BRUSH-BORDER VESICLES; LINKAGE ANALYSIS; RAT-KIDNEY; MUTATIONS; LOCALIZATION; HETEROGENEITY; EXPRESSION; CLONING; CDNA AB Cystinuria is a hereditary disorder of amino acid transport and is manifested by the development of kidney stones. In some patients the disease is caused by mutations in the SLC3A1 gene, which is located on the short arm of chromosome 2 and encodes a renal/intestinal transporter for cystine and the dibasic amino acids. In Israel cystinuria is especially common among Jews of Libyan origin. After excluding SLC3A1 as the disease-causing gene in Libyan Jewish patients, we performed a genomewide search that shows that the Libyan Jewish cystinuria gene maps to the Long arm of chromosome 19. Significant linkage was obtained for seven chromosome 19 markers. A maximal LOD score of 9.22 was obtained with the marker D19S882. Multipoint data and recombination analysis placed the gene in an 8-cM interval between the markers D19S409 and D19S208. Significant Linkage disequilibrium was observed for alleles of four markers, and a specific haplotype comprising the markers D19S225, D19S208, D19S220, and D19S422 was found in 11 of 17 carrier chromosomes, versus 1 of 58 Libyan Jewish noncarrier chromosomes. C1 CHAIM SHEBA MED CTR,DEPT MED C,IL-52621 TEL HASHOMER,ISRAEL. CHAIM SHEBA MED CTR,DEPT MED F,IL-52621 TEL HASHOMER,ISRAEL. CHAIM SHEBA MED CTR,INST HUMAN GENET,IL-52621 TEL HASHOMER,ISRAEL. CHAIM SHEBA MED CTR,HELLER INST MED RES,IL-52621 TEL HASHOMER,ISRAEL. TEL AVIV UNIV,SACKLER SCH MED,DEPT PATHOL,IL-69978 TEL AVIV,ISRAEL. UNIV FLORIDA,DIV UROL,GAINESVILLE,FL. NIAMSD,SKIN BIOL LAB,BETHESDA,MD. NIAMSD,ARTHRIT & RHEUMATISM BRANCH,BETHESDA,MD. NR 40 TC 62 Z9 63 U1 0 U2 1 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 S WOODLAWN AVE, CHICAGO, IL 60637 SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD MAR PY 1997 VL 60 IS 3 BP 617 EP 624 PG 8 WC Genetics & Heredity SC Genetics & Heredity GA WK403 UT WOS:A1997WK40300019 PM 9042922 ER PT J AU Sakul, H Pratley, R Cardon, L Ravussin, E Mott, D Bogardus, C AF Sakul, H Pratley, R Cardon, L Ravussin, E Mott, D Bogardus, C TI Familiar ty of physical and metabolic characteristics that predict the development of non-insulin-dependent diabetes mellitus in pima Indians SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Article ID MAXIMUM-LIKELIHOOD; MALE TWINS; BODY-FAT; RESISTANCE; OBESITY; LINKAGE; CONCORDANCE; POPULATION AB Susceptibility to non-insulin-dependent diabetes mellitus (NIDDM) is largely genetically determined. In Pima Indians, obesity, insulin resistance, and a low acute insulin response (AIR) to an intravenous glucose infusion are each predictors of the disease. To ascertain whether these phenotypes are genetically determined, we estimated their familiality in nondiabetic Pima Indians with a maximum-likelihood method. Percentage body fat (PFAT) was highly familial (h(2) = .76), whereas waist/thigh circumference ratio (WIT ratio) was not significantly familial after controlling for PFAT (h(2) = .16). AIR was also highly familial (h(2) = .80 at 10 min), even after controlling for PFAT and insulin action (h(2) = .70). Insulin action at physiologic plasma insulin concentrations was familial(h(2) = .61) but less so after controlling for PFAT and W/T ratio (h(2) = .38). At maximally stimulating insulin concentrations, insulin action was familial (h(2) = .45) and was less influenced by controlling for PFAT and W/T ratio (h(2) = .49). We conclude that in Pima Indians (1) PFAT and ATR are highly familial traits, (2) central distribution of fat is not a familial trait when controlled for PFAT, (3) 38%-49% of the variance in insulin action, independent of the effect of obesity, is familial, and (4) PFAT, AIR, and insulin action are useful traits to study genetic susceptibility to NIDDM. Because genetic parameter estimates are applicable only to the populations from which they were estimated, it is important to determine whether these estimates of familialities in Pima Indians can be confirmed in other populations before the utility of these traits in searching for NIDDM susceptibility genes in those populations can be fully advocated. C1 NIDDKD,CLIN DIABET & NUTR SECT,NIH,PHOENIX,AZ 85016. SEQUANA THERAPEUT INC,LA JOLLA,CA. NR 31 TC 79 Z9 82 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 1997 VL 60 IS 3 BP 651 EP 656 PG 6 WC Genetics & Heredity SC Genetics & Heredity GA WK403 UT WOS:A1997WK40300023 PM 9042926 ER PT J AU Kaplan, NL Martin, ER Weir, BS AF Kaplan, NL Martin, ER Weir, BS TI Power studies for the transmission/disequilibrium tests with multiple alleles SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Article ID MONTE-CARLO TESTS; LINKAGE DISEQUILIBRIUM; MARKER LOCI; ASSOCIATION; SIMULATION; DISEASE AB Case-control studies compare marker-allele distributions in affected and unaffected individuals, and significant results suggest linkage but may simply reflect population structure. For markers with m alleles (m greater than or equal to 2), a McNemar-like statistic, I, estimates the level of population association between marker and disease loci. To test for linkage after significant case-control tests, within-family tests are performed. These operate on the contingency table, with i, jth element equal to the number of parents that transmit marker allele M(i) and do not transmit marker allele M(j) to an affected offspring. The dimension of the table is the number of alleles at the marker locus. Three test statistics have recently been proposed in the literature: T-c compares symmetric pairs of cells (i, j) and (j, i), T-m compares row and column totals for the same marker allele, and a likelihood ratio statistic T-l uses all the cells in the table. In addition, we consider a new statistic, T-mhet, that uses only the heterozygous parents and is approximately chi(2) With (m - 1) df. We use a Monte Carlo test to guarantee valid tests and to demonstrate the inferiority of T-c and the equality of T-m and T-l in terms of power. The power of the T-mhet test is close but not always equal to the power of the T-m test. We also show that under the alternative hypothesis of linkage, T-m is approximately noncentral chi(2) with (m - 1) df and noncentrality parameter 2N(T)(1 - 2 theta)I-2*, when data on single affecteds in N-T families are used. If the disease has a low population frequency, then I* is estimated using the case-control statistic I. This offers a basis for choosing sample size, or choosing a marker system. C1 N CAROLINA STATE UNIV,DEPT STAT,PROGRAM STAT GENET,RALEIGH,NC 27695. RP Kaplan, NL (reprint author), NIEHS,BIOSTAT BRANCH,POB 12233,RES TRIANGLE PK,NC 27709, USA. FU NIGMS NIH HHS [P01 GM45344, T32 GM08443]; NINDS NIH HHS [R01 NS23360] NR 25 TC 81 Z9 84 U1 0 U2 2 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 S WOODLAWN AVE, CHICAGO, IL 60637 SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD MAR PY 1997 VL 60 IS 3 BP 691 EP 702 PG 12 WC Genetics & Heredity SC Genetics & Heredity GA WK403 UT WOS:A1997WK40300027 PM 9042930 ER PT J AU Hayes, RB Klein, S Suruda, A Schulte, P Boeniger, M Stewart, P Livingston, GK Oesch, F AF Hayes, RB Klein, S Suruda, A Schulte, P Boeniger, M Stewart, P Livingston, GK Oesch, F TI O-6-alkylguanine DNA alkyltransferase activity in student embalmers SO AMERICAN JOURNAL OF INDUSTRIAL MEDICINE LA English DT Article DE formaldehyde; occupational exposure; DNA repair; embalming ID PERIPHERAL-BLOOD LYMPHOCYTES; O6-ALKYLGUANINE-DNA ALKYLTRANSFERASE; REPAIR CAPACITIES; FORMALDEHYDE; CELLS; METHYLTRANSFERASE; INHIBITION; EXPOSURE; DAMAGE AB O-6-Alkylguanine-DNA alkyltransferase (AGT) activity was assessed in peripheral blood lymphocytes among 23 mortuary science students before and after 9 weeks in a laboratory course in techniques of embalming. Formaldehyde exposure was established by environmental monitoring. The average air concentration of formaldehyde during embalming was about 1.5 ppm. At the pre-exposure sampling, baseline DNA repair capacity tended to be reduced in subjects who reported a prior history of embalming (p = 0.08). From pre- to post-exposure, 17 subjects decreased in DNA repair capacity, while only 6 increased (p < 0.05). Analysis of variance, including adjustment for age, sex, and smoking status, confirmed these findings. Among the eight subjects who had no embalming experience during the 90 days before study, seven had decreased and one had increased AGT activity during the period of study (p < 0.05). For those with prior embalming experience, 10 subjects decreased in AGT activity, while 5 increased (p < 0.05). Although the major chemical exposure in embalming practice was to formaldehyde, no clear link was established between amount of formaldehyde exposure and AGT activity. (C) 1997 Wiley-Liss, Inc. C1 UNIV MAINZ,INST TOXICOL,D-6500 MAINZ,GERMANY. NIOSH,DIV SURVEILLANCE HAZARD EVALUAT & FIELD STUDI,CINCINNATI,OH 45226. UNIV CINCINNATI,SCH MED,DEPT ENVIRONM HLTH SCI,CINCINNATI,OH. RP Hayes, RB (reprint author), NCI,ENVIRONM EPIDEMIOL BRANCH,BETHESDA,MD 20892, USA. NR 27 TC 8 Z9 10 U1 0 U2 1 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0271-3586 J9 AM J IND MED JI Am. J. Ind. Med. PD MAR PY 1997 VL 31 IS 3 BP 361 EP 365 DI 10.1002/(SICI)1097-0274(199703)31:3<361::AID-AJIM13>3.0.CO;2-Z PG 5 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA WK699 UT WOS:A1997WK69900013 PM 9055960 ER PT J AU Klebanoff, MA Schulsinger, C Mednick, BR Secher, NJ AF Klebanoff, MA Schulsinger, C Mednick, BR Secher, NJ TI Preterm and small-for-gestational-age birth across generations SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Article DE small for gestational age; preterm birth; generations; genetics ID WEIGHT; PREGNANCY AB OBJECTIVE: Our purpose was to determine whether women who were themselves small for gestational age at birth are at risk of giving birth to a small-for-gestational-age child and whether women who were themselves preterm at birth are at risk for preterm delivery. STUDY DESIGN: Women born in Copenhagen as subjects in the Danish Perinatal Study (1959 to 1961) were traced through the Danish Population Register. Information was obtained on their pregnancies during 1974 through 1989. RESULTS: A total of 25% of the children of small-for-gestational-age women were small for gestational age compared with 11% of the children of non-small-for-gestational-age women. Eleven percent of the children of preterm women were preterm compared with 7% of the children of women born at term. The adjusted odds ratios were 2.0 (95% confidence interval 1.4 to 3.0) for women who were small for gestational age to have small-for-gestational-age children and 1.5 (95% confidence interval 0.9 to 2.5) for women who were born preterm to have preterm children. Small-for-gestational-age women were not at significantly increased risk of preterm delivery (odds ratio 1.2), and preterm women were not at significantly increased risk of having small-for-gestational-age children (odds ratio 1.3). CONCLUSIONS: Reduced intrauterine growth of the mother is a risk factor for reduced intrauterine growth of her children. However, preterm birth of the mother is not strongly associated with preterm birth of her children. C1 UNIV COPENHAGEN,INST SYGDOMSFOREBYGGELSE,COPENHAGEN,DENMARK. UNIV SO CALIF,DEPT EDUC PSYCHOL,LOS ANGELES,CA 90089. AARHUS UNIV,DEPT GYNECOL & OBSTET,DK-8000 AARHUS C,DENMARK. RP Klebanoff, MA (reprint author), NICHHD,DIV EPIDEMIOL STAT & PREVENT RES,EPIDEMIOL BRANCH,NIH,6100 BLDG,7B04,BETHESDA,MD 20892, USA. FU NICHD NIH HHS [N01-HD-7-2902] NR 16 TC 68 Z9 68 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 1997 VL 176 IS 3 BP 521 EP 526 DI 10.1016/S0002-9378(97)70540-4 PG 6 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA WR886 UT WOS:A1997WR88600005 PM 9077599 ER PT J AU Booth, VJ Nelson, KB Dambrosia, JM Grether, JK AF Booth, VJ Nelson, KB Dambrosia, JM Grether, JK TI What factors influence whether placentas are submitted for pathologic examination? SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Article DE placental pathology; fetus; neonate ID CEREBRAL-PALSY; RISK AB OBJECTIVE: Our purpose was to investigate factors associated with submission of placentas for pathologic examination. STUDY DESIGN: In a population-based study of the etiology of cerebral palsy, data were abstracted for 627 singleton survivors to age 3 years. Children included as cases had moderate-to-severe cerebral palsy; controls were randomly selected infants born in the same counties and years. RESULTS: Placentas were submitted for pathologic examination for 150 children (24%) of those included in this study. Placentas were more often submitted for children born weighing <1500 gm than for other birth weight groups (p < 0.0001). Placentas from cesarean section deliveries were submitted more often than those from vaginal deliveries (p < 0.0001), elective repeat as often as indicated or emergency cesarean sections. Maternal and neonatal disorders suggested by the College of American Pathologists as indications for placental examination were present in 161 (43%) of controls born weighing greater than or equal to 2500 gm. These indications were not associated with pathologic submissions. CONCLUSIONS: Within birth weight groups the main determinant of placental submission for laboratory examination was surgical delivery, whether indicated or elective. Maternal and infant conditions had little influence on the likelihood of submission. C1 NINCDS,NEUROEPIDEMIOL BRANCH,NIH,BETHESDA,MD 20892. NINCDS,BIOMETRY & FIELD STUDIES BRANCH,NIH,BETHESDA,MD 20892. CALIF DEPT HLTH SERV,CALIF BIRTH DEFECTS MONITORING PROGRAM,SACRAMENTO,CA 95814. NR 14 TC 12 Z9 12 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 1997 VL 176 IS 3 BP 567 EP 571 DI 10.1016/S0002-9378(97)70549-0 PG 5 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA WR886 UT WOS:A1997WR88600014 PM 9077608 ER PT J AU Brinton, LA Gridley, G Persson, I Baron, J Bergqvist, A AF Brinton, LA Gridley, G Persson, I Baron, J Bergqvist, A TI Cancer risk after a hospital discharge diagnosis of endometriosis SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Article DE endometriosis; neoplasms ID BREAST-CANCER; WOMEN; CARCINOMA; EPIDEMIOLOGY; OVARY AB OBJECTIVES: Our goal was to determine the risk of cancer after hospitalization for endometriosis. STUDY DESIGN: Records of 20,686 women hospitalized with endometriosis during the period 1969 to 1983, as identified through the nationwide Swedish Inpatient Register, were linked against the National Swedish Cancer Registry through 1989 to identify all subsequent diagnoses of cancer. The study subjects were followed up for a mean of 11.4 years, with the cohort contributing 216,851 woman years of follow-up. Standardized incidence ratios were computed by the use of age- and period-specific incidence rates derived from the Swedish population. Because of the high proportion of subjects with gynecologic operations (55.6%), evaluation of the risk of gynecologic cancers involved truncation of person years at the time of any such operation. RESULTS: The overall cancer risk was 1.2 (95% confidence interval 1.1 to 1.3). Significant excesses were observed for breast cancer (standardized incidence ratio = 1.3, 95% confidence interval 1.1 to 1.4), ovarian cancer (1.9, 1.3 to 2.8), and hematopoietic malignancies (1.4, 1.0 to 1.8); this latter excess was largely driven by an excess risk of non-Hodgkin's lymphoma (1.8, 1.2 to 2.6). The risk of ovarian cancer was particularly elevated among subjects with a long-standing history of ovarian endometriosis (4.2, 2.0 to 7.7). Cervical cancer risk was slightly reduced (0.7, 0.4 to 1.3) whereas no association was observed for cancer of the endometrium (1.1, 0.6 to 1.9). CONCLUSIONS: These findings suggest that further attention be given to the risk of breast, ovarian and hematopoietic cancers among women with endometriosis and to exploring possible hormonal and immunologic reasons for the excess risks. C1 UNIV UPPSALA HOSP, DEPT OBSTET & GYNECOL, UPPSALA, SWEDEN. DARTMOUTH UNIV, BIOSTAT & EPIDEMIOL GRP, HANOVER, NH USA. HUDDINGE UNIV HOSP, DEPT OBSTET & GYNECOL, S-14186 HUDDINGE, SWEDEN. RP Brinton, LA (reprint author), NCI, DIV CANC EPIDEMIOL & GENET, EXECUT PLAZA N, ROOM 443, BETHESDA, MD 20892 USA. RI Brinton, Louise/G-7486-2015 OI Brinton, Louise/0000-0003-3853-8562 FU NCI NIH HHS [N01-CP-85636] NR 25 TC 298 Z9 312 U1 2 U2 9 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 1997 VL 176 IS 3 BP 572 EP 579 DI 10.1016/S0002-9378(97)70550-7 PG 8 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA WR886 UT WOS:A1997WR88600015 PM 9077609 ER PT J AU Sherer, DM Spong, CY Salafia, CM AF Sherer, DM Spong, CY Salafia, CM TI Residual amniotic fluid volume in preterm rupture of membranes: Association with fetal presentation and incidence of clinical and histologic evidence of infection SO AMERICAN JOURNAL OF PERINATOLOGY LA English DT Article DE premature rupture of membranes; prematurity; amniotic fluid volume; fetal presentation; chorioamnionitis; ultrasonography ID PREMATURE RUPTURE; RISK FACTOR; OLIGOHYDRAMNIOS; PREGNANCY AB The objective of this study was assess whether residual amniotic fluid volume (AFV) following premature rupture of the membranes (FROM) is associated with fetal presentation, or the prevalence of either clinical or histologic infection in patients delivering below 32 weeks' gestation. From an established database of 465 deliveries below 32 weeks' gestation, patients with singleton, nonanomalous fetuses with AFV assessment within 24 hours of delivery were studied (n=146). Fetal presentation was confirmed by ultrasound identifying 46 breech and 100 vertex-presenting fetuses. Premature rupture of the membranes was diagnosed by sterile speculum examination. Clinical chorioamnionitis was diagnosed by previously published criteria. Histopathology examination of the extraplacental amnion and the umbilical cord were performed by a single pathologist blinded to clinical data. Outcome variables evaluated: rupture-to-delivery interval, gestational age at delivery, neonatal morbidity parameters (1- and 5-min Apgar scores <5 and 7, respectively; incidence of respiratory distress syndrome; bronchopulmonary dysplasia; retinopathy of prematurity; neonatal sepsis; intraventricular hemorrhage; days of ventilation; and hospitalization), and placental histologic parameters of maternal and/or fetal acute inflammation. Statistical analysis included contingency tables and analysis of variance with p<.05 considered significant, after corrections for multiple comparisons when appropriate. Residual AF volume following FROM was significantly lower in breech compared with vertex presentation (AFV=0 in 20 vs. 34; AFV=1 in 19 vs. 27; AFV=2 in 7 vs. 39, respectively, p=.014). No significant difference was noted in the rupture-to-delivery interval, gestational age at delivery, neonatal morbidity parameters, or histologic evidence of maternal and/or fetal acute inflammation (50% vs. 42%, p>.2) between gestations with breech or vertex presentations. The incidence of clinical chorioamnionitis was significantly lower in breech compared with vertex presention (40% vs. 60%, p<.05). We conclude that following FROM below 32 weeks' gestation, in breech-presenting fetuses, the residual AFV and incidence of clinical chorioamnionitis are significantly decreased compared with vertex-presenting fetuses. C1 NICHHD,PERINATAL RES FACIL,INTRAMURAL DIV,NIH,WASHINGTON,DC. NR 14 TC 2 Z9 3 U1 0 U2 1 PU THIEME MEDICAL PUBL INC PI NEW YORK PA 333 SEVENTH AVE, NEW YORK, NY 10001 SN 0735-1631 J9 AM J PERINAT JI Am. J. Perinatol. PD MAR PY 1997 VL 14 IS 3 BP 125 EP 128 DI 10.1055/s-2007-994111 PG 4 WC Obstetrics & Gynecology; Pediatrics SC Obstetrics & Gynecology; Pediatrics GA WQ189 UT WOS:A1997WQ18900002 PM 9259912 ER PT J AU Karafet, T Zegura, SL VuturoBrady, J Posukh, O Osipova, L Wiebe, V Romero, F Long, JC Harihara, S Jin, F Dashnyam, B Gerelsaikhan, T Omoto, K Hammer, MF AF Karafet, T Zegura, SL VuturoBrady, J Posukh, O Osipova, L Wiebe, V Romero, F Long, JC Harihara, S Jin, F Dashnyam, B Gerelsaikhan, T Omoto, K Hammer, MF TI Y chromosome markers and trans-Bering Strait dispersals SO AMERICAN JOURNAL OF PHYSICAL ANTHROPOLOGY LA English DT Article DE Y chromosome combination haplotypes; native American origins; Asian source regions ID SOUTHERN AFRICAN POPULATIONS; MITOCHONDRIAL-DNA ANALYSIS; NATIVE-AMERICANS; MTDNA; POLYMORPHISMS; HAPLOTYPES; REGION; AMPLIFICATION; AFFINITIES; INSERTION AB Five polymorphisms involving two paternally inherited loci were surveyed in 38 world populations (n = 1,631) to investigate the origins of Native Americans. One of the six Y chromosome combination haplotypes (1T) was found at relatively high frequencies (17.8-75.0%) in nine Native American populations (n = 206) representing the three major linguistic divisions in the New World. Overall, these data do not support the Greenberg et al. (1986) tripartite model for the early peopling of the Americas. The 1T haplotype was also discovered at a low frequency in Siberian Eskimos (3/22), Chukchi (1/6), and Evens (1/65) but was absent from 17 other Asian populations (n = 987). The perplexing presence of the 1T haplotype in northeastern Siberia may be due to back-migration from the New World to Asia. (C) 1997 Wiley-Liss, Inc. C1 UNIV ARIZONA,LAB MOL SYSTEMAT & EVOLUT,TUCSON,AZ 85721. UNIV ARIZONA,DEPT ANTHROPOL,TUCSON,AZ 85721. RUSSIAN ACAD SCI,INST CYTOL & GENET,LAB HUMAN MOL & EVOLUTIONARY GENET,NOVOSIBIRSK 630090,RUSSIA. NIAAA,NEUROGENET LAB,NIH,ROCKVILLE,MD 20852. UNIV TOKYO,DEPT BIOL SCI,TOKYO,JAPAN. MONGOLIAN ACAD SCI,INST BIOTECHNOL,ULAANBAATAR,MONGOL PEO REP. INT RES CTR JAPANESE STUDIES,KYOTO,JAPAN. RI Osipova, Ludmila/O-6480-2014; Posukh, Olga/Q-6065-2016 OI Osipova, Ludmila/0000-0001-7602-1156; Posukh, Olga/0000-0003-1352-3591 FU NIGMS NIH HHS [GM53566] NR 69 TC 75 Z9 77 U1 1 U2 1 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0002-9483 J9 AM J PHYS ANTHROPOL JI Am. J. Phys. Anthropol. PD MAR PY 1997 VL 102 IS 3 BP 301 EP 314 DI 10.1002/(SICI)1096-8644(199703)102:3<301::AID-AJPA1>3.0.CO;2-Y PG 14 WC Anthropology; Evolutionary Biology SC Anthropology; Evolutionary Biology GA WR629 UT WOS:A1997WR62900001 PM 9098500 ER PT J AU Langlois, JA Keyl, PM Guralnik, JM Foley, DJ Marottoli, RA Wallace, RB AF Langlois, JA Keyl, PM Guralnik, JM Foley, DJ Marottoli, RA Wallace, RB TI Characteristics of older pedestrians who have difficulty crossing the street SO AMERICAN JOURNAL OF PUBLIC HEALTH LA English DT Article ID EXERCISE AB Objectives. This study examined the sociodemographic and health characteristics and problems of older pedestrians. Methods. Interviews and assessments were conducted with 1249 enrollees aged 72 or older from the New Haven, Conn, community of the Established Populations for Epidemiologic Studies of the Elderly who agreed to participate in a seventh follow-up. Results. Approximately 11% of the New Haven residents reported difficulty crossing the street. Older pedestrians needing help in one or more activities of dairy living were more than 10 times as likely as others, and those with the slowest walking speeds were nearly 3 times as likely as others, to report difficulty crossing the street. Fewer than 1% of these pedestrians aged 72 or older had a normal walking speed sufficient to cross the street in the time typically allotted at signalized intersections (1.22 m/sec). Conclusions. Crossing times at signalized intersections in areas with large populations of elders should be extended, and the recommended walking speed for timing signalized crossings should be modified to reflect the range of abilities among older pedestrians. C1 JOHNS HOPKINS UNIV,SCH MED,DEPT EMERGENCY MED,BALTIMORE,MD. JOHNS HOPKINS UNIV,SCH HYG & PUBL HLTH,DEPT EPIDEMIOL,BALTIMORE,MD. VET ADM MED CTR,DEPT MED,NEW HAVEN,CT. YALE UNIV,SCH MED,NEW HAVEN,CT. UNIV IOWA,DEPT PREVENT MED & ENVIRONM HLTH,COLL MED,IOWA CITY,IA 52242. RP Langlois, JA (reprint author), NIA,EPIDEMIOL DEMOG & BIOMETRY PROGRAM,GATEWAY BLDG,SUITE 3C-309,7201 WISCONSIN AVE,BETHESDA,MD 20892, USA. FU NIA NIH HHS [N01-AG-0-2105, N01-AG-0-2106] NR 20 TC 118 Z9 120 U1 0 U2 8 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 1997 VL 87 IS 3 BP 393 EP 397 DI 10.2105/AJPH.87.3.393 PG 5 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA WR017 UT WOS:A1997WR01700013 PM 9096539 ER PT J AU Collins, JW Herman, AA David, RJ AF Collins, JW Herman, AA David, RJ TI Very-low-birthweight infants and income incongruity among African American and white parents in Chicago SO AMERICAN JOURNAL OF PUBLIC HEALTH LA English DT Article ID LOW-BIRTH-WEIGHT; PRENATAL-CARE; PRETERM DELIVERY; RISK-FACTORS; BLACK-WOMEN; HEALTH AB Objectives. Illinois vital records for 1982/1983 and US census income data for 1980 were analyzed to ascertain the relationship of income incongruity, race, and very low birthweight. Methods. Positive income incongruity was considered present when study infants resided in wealthier neighborhoods than non-Latino Whites at the same level of parental education attainment and marital status. Results. The odds ratios of very low birthweight for African Americans (n = 44 266) and Whites (n = 27 139) who experienced positive income incongruity were 0.7 (95% confidence interval [CI] = 0.5, 0.9) and 0.6 (95% CI = 0.5, 0.9), respectively. Conclusions. Positive income incongruity is associated with lower race-specific rates of very low birthweight. C1 NICHHD,NIH,BETHESDA,MD 20892. UNIV ILLINOIS,COOK CTY HOSP,COLL MED,CHICAGO,IL 60612. RP Collins, JW (reprint author), NORTHWESTERN UNIV,CHILDRENS MEM HOSP,SCH MED,DIV NEONATOL 45,2300 CHILDRENS PLAZA,CHICAGO,IL 60614, USA. NR 21 TC 33 Z9 33 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 1997 VL 87 IS 3 BP 414 EP 417 DI 10.2105/AJPH.87.3.414 PG 4 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA WR017 UT WOS:A1997WR01700017 PM 9096543 ER PT J AU Spong, CY Scherer, DM Ghidini, A Pezzullo, JC Salafia, CM Eglinton, GS AF Spong, CY Scherer, DM Ghidini, A Pezzullo, JC Salafia, CM Eglinton, GS TI Midtrimester amniotic fluid tumor necrosis factor-alpha does not predict small-for-gestational-age infants SO AMERICAN JOURNAL OF REPRODUCTIVE IMMUNOLOGY LA English DT Article DE amniotic fluid; small-for-gestational-age; TNF-alpha ID INTRAUTERINE GROWTH-RETARDATION; FETAL GROWTH; BIRTH-WEIGHT AB PROBLEM: To evaluate the independent ability of midtrimester amniotic fluid tumor necrosis factor-alpha (TNF-alpha) in the prediction of small-for-gestational-age (SGA) infants. METHOD OF STUDY: In this case-control study, patients delivering a SGA infant were matched with controls based on GA at delivery, maternal age, race, and parity. Patients with immune disease, chronic hypertension, diabetes, asthma, congenital hearts disease, multiple gestation, and fetal anomalies were excluded. Amniotic fluid samples were immunoassayed for TNF-alpha. Potential confounding variables evaluated were maternal serum alpha-fetoprotein level, smoking history, pregnancy induced hypertension, and neonatal gender. Statistical analysis included Fisher's exact test and ANOVA after log transformation with P < 0.05 considered significant. RESULTS: Eighteen patients delivered SGA neonates and were matched with 41 controls. No significant differences were identified in the confounding variables between patients with SGA neonates and controls. Amniotic fluid TNF-alpha levels were not significantly different between patients subsequently delivering SGA neonates and controls [median 7.63 (range 0.25-16.1) pg/mL versus 9.39 (0.25-66.9) pg/mL, P = 0.8]. CONCLUSIONS: Midtrimester amniotic fluid TNF-alpha levels are not predictive of SGA neonates when compared with controls matched for gestational age at delivery. C1 GEORGETOWN UNIV,MED CTR,PERINATAL RES FACIL,WASHINGTON,DC 20007. GEORGETOWN UNIV,MED CTR,DEPT PATHOL,WASHINGTON,DC 20007. RP Spong, CY (reprint author), GEORGETOWN UNIV,MED CTR,PERINATAL RES BRANCH,NICHD,DIV MATERNAL FETAL MED,DEPT OBSTET & GYNECOL,WASHINGTON,DC 20007, USA. FU NICHD NIH HHS [N01-HD-3-3198] NR 12 TC 10 Z9 10 U1 0 U2 2 PU MUNKSGAARD INT PUBL LTD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 8755-8920 J9 AM J REPROD IMMUNOL JI Am. J. Reprod. Immunol. PD MAR PY 1997 VL 37 IS 3 BP 236 EP 239 PG 4 WC Immunology; Reproductive Biology SC Immunology; Reproductive Biology GA WR647 UT WOS:A1997WR64700004 PM 9127645 ER PT J AU Brantly, M Lee, JH Hildeshiem, J Uhm, CS Prakash, UBS Staats, BA Crystal, RG AF Brantly, M Lee, JH Hildeshiem, J Uhm, CS Prakash, UBS Staats, BA Crystal, RG TI alpha 1-antitrypsin gene mutation hot spot associated with the formation of a retained and degraded null variant SO AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY LA English DT Article ID ALPHA-1-PROTEINASE INHIBITOR; ENDOPLASMIC-RETICULUM; FRAMESHIFT MUTATION; DEFICIENCY ALLELE; GOLGI-APPARATUS; C1 INHIBITOR; SECRETION; SUBSTITUTION; MECHANISM; DELETION AB Null alpha 1-antitrypsin (alpha 1AT) alleles represent the end of a continuum of variants associated with profound alpha 1AT deficiency and an increased risk of emphysema. This study characterizes the molecular basis of QOclayton, a new example of an alpha 1AT null allele arising from a mutational hot spot in the alpha 1AT gene. The QOclayton allele is identical to the normal M1(V213) alpha 1AT allele except for an insertion of a cytosine. This insertion occurs in the alpha 1AT sequence which normally has seven cytosines corresponding to amino acid residues 360 to 362. The QOclayton mutation is located in the same reiterated DNA sequence as the alpha 1AT QObolton deletion mutation and the insertion mutation allele QOsaarbruecken. The QOclayton cytosine insertion causes a 3' frameshift and results in the formation of a termination codon at residue 376, the same consequence as the alpha 1AT QOmattawa mutation (L353 T-insertion with a 3' frameshift). To determine the molecular mechanisms responsible for the absence of alpha 1AT associated with the QOclayton gene, an in vitro model of QOclayton was established using Chinese hamster ovary cells (CHO) transfected with the QOclayton gene. These cells were evaluated for alpha 1AT mRNA expression, protein synthesis and secretion. Although the QOclayton gene expresses a similar amount of alpha 1AT mRNA as compared with the normal alpha 1AT gene, no QOclayton protein is secreted. Protein trafficking and double-label immunofluorescence demonstrate that the QOclayton protein is retained in the rough endoplasmic reticulum or pre-Golgi compartment and is degraded (t(1/2) = 6.5 h). Since QOmattawa, QObolton, and QOsaarbruecken have similar termination sites in the alpha 1AT mRNA, they may share a similar intracellular fate. C1 MAYO CLIN & MAYO FDN,SCH MED,DIV THORAC DIS & INTERNAL MED,ROCHESTER,MN 55905. CORNELL MED CTR,DIV PULM & CRIT CARE MED,NEW YORK,NY. RP Brantly, M (reprint author), NHLBI,PULM CRIT CARE MED BRANCH,NIH,10 CTR DR,MSC-1590,BLDG 10,RM 6D03,BETHESDA,MD 20892, USA. NR 35 TC 22 Z9 22 U1 0 U2 2 PU AMER LUNG ASSOC PI NEW YORK PA 1740 BROADWAY, NEW YORK, NY 10019 SN 1044-1549 J9 AM J RESP CELL MOL JI Am. J. Respir. Cell Mol. Biol. PD MAR PY 1997 VL 16 IS 3 BP 225 EP 231 PG 7 WC Biochemistry & Molecular Biology; Cell Biology; Respiratory System SC Biochemistry & Molecular Biology; Cell Biology; Respiratory System GA WP342 UT WOS:A1997WP34200004 PM 9070606 ER PT J AU Lindroos, PM Coin, PG Badgett, A Morgan, DL Bonner, JC AF Lindroos, PM Coin, PG Badgett, A Morgan, DL Bonner, JC TI Alveolar macrophages stimulated with titanium dioxide, chrysotile asbestos, and residual oil fly ash upregulate the PDGF receptor-alpha on lung fibroblasts through an IL-1 beta-dependent mechanism SO AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY LA English DT Article ID GROWTH-FACTOR-ALPHA; SMOOTH-MUSCLE CELLS; IDIOPATHIC PULMONARY FIBROSIS; TUMOR-NECROSIS-FACTOR; UNITED-STATES CITIES; GENE-EXPRESSION; FACTOR-BETA; UP-REGULATION; MESSENGER-RNA; AIR-POLLUTION AB Enhanced proliferation of fibroblasts is a primary characteristic of lung fibrosis. Macrophage-secreted platelet-derived growth factor (PDGF) is a potent mitogen and chemoattractant for lung fibroblasts. The magnitude of the fibroblast PDGF response is dependent on the number of PDGF receptor alpha (PDGF-R alpha) relative to PDGF-R beta at the cell surface. We recently reported that upregulation of the PDGF-R alpha subtype by interleukin (IL)-1 beta results in enhanced lung fibroblast proliferation in response to PDGF-AA, PDGF-AB, and PDGF-BE whereas transforming growth factor (TGF)-beta 1 has the opposite effect. Both IL-1 beta and TGF-beta 1 are produced by particle-activated macrophages in vivo and in vitro. We studied the net effect of macrophage conditioned medium (M0CM), which contains both IL-1 beta and TGF-beta 1, on the expression of the lung fibroblast PDGF receptor system. M0CM obtained from unstimulated, titanium dioxide (TiO2)-, chrysotile asbestos-, or residual oil fly ash (ROFA)-exposed macrophages in vitro increased [I-125]PDGF-AA binding 3-, 6-, 6-, and 20-fold, respectively. These increases correlated with increased PDGF-R alpha mRNA and protein expression as shown by northern and western assays. PDGF-AB and -BB-stimulated [H-3]thymidine incorporation by fibroblasts was enhanced 5-, 5-, 10-, and 20-fold by pretreatment with M0CM from unstimulated, TiO2-, asbestos-, and ROFA-exposed macrophages, respectively. [I-125]PDGF-AA binding experiments using the IL-1 receptor antagonist blocked the upregulatory effect of all M0CM samples. Latent TGF-beta 1 present in M0CM was activated by acid treatment, inhibiting upregulation by similar to 60%, a result similar to experiments with IL-1 beta and TGF-beta 1 mixtures. Treatment with a TGF-beta neutralizing antibody restored full upregulatory activity to acidified M0CM. Thus activated macrophages increase lung fibroblast PDGF-R alpha primarily due to the secretion of IL-1 beta. Intratracheal instillation of ROFA particles in rats induced a 2-fold increase in total lung PDGF-R alpha mRNA in vivo. These findings support the idea that macrophage-derived IL-1 beta plays a key role in the initiation of a fibrotic response by increasing fibroblast PDGF-R alpha expression, thereby dramatically potentiating the mitogenic response to PDGE. C1 NIEHS, PULM PATHOBIOL LAB, AIRWAY INFLAMMAT SECT, RES TRIANGLE PK, NC 27709 USA. NIEHS, TOXICOL LAB, RESP TOXICOL SECT, RES TRIANGLE PK, NC 27709 USA. NR 51 TC 51 Z9 52 U1 0 U2 1 PU AMER THORACIC SOC PI NEW YORK PA 61 BROADWAY, FL 4, NEW YORK, NY 10006 USA SN 1044-1549 J9 AM J RESP CELL MOL JI Am. J. Respir. Cell Mol. Biol. PD MAR PY 1997 VL 16 IS 3 BP 283 EP 292 PG 10 WC Biochemistry & Molecular Biology; Cell Biology; Respiratory System SC Biochemistry & Molecular Biology; Cell Biology; Respiratory System GA WP342 UT WOS:A1997WP34200011 PM 9070613 ER PT J AU Ahmed, F Clemens, JD Rao, MR Ansaruzzaman, M Haque, E AF Ahmed, F Clemens, JD Rao, MR Ansaruzzaman, M Haque, E TI Epidemiology of shigellosis among children exposed to cases Shigella dysentery: A multivariate assessment SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE LA English DT Article ID NUTRITIONAL-STATUS; RURAL BANGLADESH; RISK; DISEASES; OUTCOMES AB We followed 1,756 young, rural Bangladeshi children less than five years of age for one month after identification of sentinel Shigella patients in their neighborhoods. Two hundred nineteen (12%) children developed Shigella diarrhea (shigellosis) and 227 (13%) developed culture-negative dysentery. Shigella flexneri (60%) and S. dysenteriae, type 1 (15%) were the most common isolates among shigellosis cases. Within individual neighborhoods, there was poor agreement (Kappa = 0.21) between Shigella species isolated from sentinel patients and from additional cases detected during surveillance. The risk of shigellosis increased substantially after infancy and peaked in the second year of life. Severe stunting, as assessed by height-for-age, was associated with an increased risk of shigellosis (adjusted odds ratio [ORa] = 1.67, 95% confidence interval [CI] = 1.09-2.57, P < 0.05), while breast-feeding was protectively associated (ORa = 0.40, 95% CI = 0.24-0.69, P < 0.001). Only 43% of the shigellosis cases reported bloody stools; frank dysentery occurred more frequently in S. dysenteriae 1 infections than in S. flexneri infections (ORa = 5.04, 95% CI = 1.76-14.48, P < 0.01), and was also associated with severe stunting (ORa = 2.16, 95% CI = 1.01-4.58, P < 0.05). Our findings show that the high risk of shigellosis in residentially exposed Bangladeshi children results from multiple Shigella strains circulating concurrently within the same neighborhood; demonstrate that the risk is notably modified by host age, nutritional status, and dietary patterns: and illustrate that the classic picture of dysentery is relatively infrequent and is correlated with the infecting species and with host nutritional status. C1 NICHHD,DIV EPIDEMIOL STAT & PREVENT RES,BETHESDA,MD 20892. INT CTR DIARRHOEAL DIS RES,DHAKA 1000,BANGLADESH. RI Osborne, Nicholas/N-4915-2015 OI Osborne, Nicholas/0000-0002-6700-2284 NR 26 TC 24 Z9 25 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 1997 VL 56 IS 3 BP 258 EP 264 PG 7 WC Public, Environmental & Occupational Health; Tropical Medicine SC Public, Environmental & Occupational Health; Tropical Medicine GA WW087 UT WOS:A1997WW08700003 PM 9129527 ER PT J AU Fleisher, TA AF Fleisher, TA TI Apoptosis SO ANNALS OF ALLERGY ASTHMA & IMMUNOLOGY LA English DT Review ID LYMPHOPROLIFERATIVE SYNDROME; CELL-DEATH; DISEASE; MUTATIONS; PATHOGENESIS; MECHANISMS; THERAPY; GENE; P53 AB Learning objectives: Reading this article will introduce the reader to the basic concept of physiologic cell death referred to as apoptosis. In addition, the role of apoptosis in immune function as well as its contribution to various clinical disorders will be developed. Data Source: The author's experience with recently described patients who have a unique autoimmune syndrome associated with a defect in apoptosis. In addition, recent reviews on the subject of apoptosis in health and disease served as informational outlines. Study Selection: Data source included pertinent reviews and articles meeting the educational objectives and these were critically reviewed. Results: Apoptosis is a critical process in cellular homeostasis that only recently has been appreciated. Its role in both immune development and the control of immune responses as well as in T cell cytotoxic effector function has been established. Information is accumulating that diseases such as cancer can be linked to underlying defects in the apoptosis pathway allowing cells that normally would have been eliminated to live. The role of alterations in apoptosis in other chronic diseases, including autoimmune and neurodegenerative disorders, is beginning to emerge. Conclusions: Apoptosis plays a central part in normal tissue homeostasis as well as having a role in a variety of clinical diseases that are characterized by either increased or decreased cell survival. RP Fleisher, TA (reprint author), NIH,WARREN G MAGNUSON CLIN CTR,BETHESDA,MD 20892, USA. NR 28 TC 18 Z9 18 U1 2 U2 2 PU AMER COLL ALLERGY ASTHMA IMMUNOLOGY PI ARLINGTON HTS PA 85 WEST ALGONQUIN RD SUITE 550, ARLINGTON HTS, IL 60005 SN 1081-1206 J9 ANN ALLERG ASTHMA IM JI Ann. Allergy Asthma Immunol. PD MAR PY 1997 VL 78 IS 3 BP 245 EP 249 PG 5 WC Allergy; Immunology SC Allergy; Immunology GA WP184 UT WOS:A1997WP18400001 PM 9087147 ER PT J AU Nam, JM AF Nam, JM TI Testing a genetic equilibrium across strata SO ANNALS OF HUMAN GENETICS LA English DT Article ID HARDY-WEINBERG LAW AB A score statistic for testing the Hardy-Weinberg law for data sampled from several populations with different allele frequencies is derived assuming a common coefficient of disequilibrium (odds ratio-type) across strata. The assumption can be examined by a chi-square goodness-of-fit test. It is unlikely such a model would be rejected in typical studies involving human populations. Under this model, a Wald-type test has substantially less power than the score test. hn approximate formula for the sample size required for a specific power of the st ratified score test for detecting departure from equilibrium is given. RP Nam, JM (reprint author), NCI,BIOSTAT BRANCH,6130 EXECUT BLVD,EPN-403,ROCKVILLE,MD 20892, USA. NR 12 TC 10 Z9 10 U1 1 U2 1 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 40 WEST 20TH STREET, NEW YORK, NY 10011-4211 SN 0003-4800 J9 ANN HUM GENET JI Ann. Hum. Genet. PD MAR PY 1997 VL 61 BP 163 EP 170 DI 10.1046/j.1469-1809.1997.6120163.x PN 2 PG 8 WC Genetics & Heredity SC Genetics & Heredity GA XC754 UT WOS:A1997XC75400008 PM 9177123 ER PT J AU Zenilman, ME Magnuson, TH Perfetti, R Chen, J Shuldiner, AR AF Zenilman, ME Magnuson, TH Perfetti, R Chen, J Shuldiner, AR TI Pancreatic reg gene expression is inhibited during cellular differentiation SO ANNALS OF SURGERY LA English DT Article; Proceedings Paper CT Annual Meeting of the American-Gastroenterological-Association CY MAY 14-17, 1995 CL SAN DIEGO, CA SP Amer Gastroenterol Assoc ID STONE PROTEIN; MESSENGER-RNA; AR42J CELLS; LINE AR42J; GROWTH; GLUCOCORTICOIDS; RECEPTORS; SEQUENCE; DNA AB Background and Objective Factors that control pancreatic regenerating (reg I) gene expression are unknown, but it is believed that its expression may correspond with cellular differentiation. The authors recently demonstrated that reg I is expressed in AR42J,a rat acinar cell line whose state of differentiation can be modulated by dexamethasone. They used this line to study reg I expression during cellular proliferation and differentiation. Methods After treatment of cells with 10 nmol/L dexamethasone, proliferation was assayed by thymidine incorporation; differentiation by expression of elastase I mRNA. Reg I mRNA levels were measured using a rat reg I cDNA probe, and reg I protein levels assayed by enzyme-linked immunosorbent assay of cellular lysates with a polyclonal antibody. The effect of gastrin, cholecystokinin and glucagon on reg I expression was also studied. Results When compared with controls, treatment with dexamethasone caused thymidine incorporation to decrease and elastase mRNA levels to increase. Reg I mRNA decreased from controls of 100 +/- 16% to 40 +/- 18% (p < 0.05), and reg I protein levels decreased as well. Gastrointestinal hormones had no significant effect on either elastase or reg I gene expression. Conclusions Expression of reg I inversely correlates with the level of cellular differentiation, can be modulated via the glucocorticoid receptor, and is a potential marker of gastrointestinal epithelial differentiation. Despite its presence within a pancreatic acinar cell line, reg I gene expression is not modulated by gastrointestinal hormones. C1 JOHNS HOPKINS UNIV, SCH MED, DEPT SURG, BALTIMORE, MD USA. NIA, LAB CLIN PHYSIOL, NIH, BALTIMORE, MD 21224 USA. RP Zenilman, ME (reprint author), YESHIVA UNIV ALBERT EINSTEIN COLL MED, DEPT SURG, MONTEFIORE MED PK, SUITE 125, 1575 BLONDELL AVE, BRONX, NY 10461 USA. NR 24 TC 17 Z9 18 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0003-4932 J9 ANN SURG JI Ann. Surg. PD MAR PY 1997 VL 225 IS 3 BP 327 EP 332 DI 10.1097/00000658-199703000-00013 PG 6 WC Surgery SC Surgery GA WM781 UT WOS:A1997WM78100013 PM 9060590 ER PT J AU Buell, JF Reed, E Lee, KB Parker, RJ Venzon, DJ Amikura, K Arnold, WS Fraker, DL Alexander, HR AF Buell, JF Reed, E Lee, KB Parker, RJ Venzon, DJ Amikura, K Arnold, WS Fraker, DL Alexander, HR TI Synergistic effect and possible mechanisms of tumor necrosis factor and cisplatin cytotoxicity under moderate hyperthermia against gastric cancer cells SO ANNALS OF SURGICAL ONCOLOGY LA English DT Article; Proceedings Paper CT 48th Annual Cancer Symposium of the Society-of-Surgical-Oncology CY MAR 21-26, 1995 CL BOSTON, MA SP Soc Surg Oncol DE gastric adenocarcinoma; TNF; cisplatin; hyperthermia ID WHOLE-BODY HYPERTHERMIA; PERITONEAL RECURRENCE; OVARIAN-CANCER; FACTOR-ALPHA; MITOMYCIN-C; PERFUSION; PLATINUM; CIS-DIAMMINEDICHLOROPLATINUM(II); DNA; SURGERY AB Background: Peritoneal carcinomatosis is a difficult management problem, and intraperitoneal treatment approaches may provide an opportunity to intensify dose and minimize toxicity. The current experiments were conducted to characterize the cytotoxic effects of cisplatin (cDDP), tumor necrosis factor (TNF), and hyperthermia (HT) on a gastric cancer cell line in vitro under conditions achievable with intraperitoneal treatment. Methods: Seoul National University gastric cancer cell line (SNU-5), a poorly differentiated gastric cancer cell line, was tested for sensitivity to various doses of cDDP, TNF, or combinations of the two at normothermia (37 degrees C) or HT (42.5 degrees C). The effect of TNF on cellular rates of cDDP accumulation, efflux, and cDDP-DNA adduct formation were evaluated using atomic absorbance spectrometry with Zeemen background correction. Results: During a 2-h exposure to various doses of cDDP with HT, we observed a supraadditive cytotoxicity of SNU-5 with 1 to 50 mu g/ml of TNF (p(2) = 0.0001). In the presence of the three-agent combination (HT, TNF, and cDDP) we observed statistically significant increases in total cellular accumulation of cisplatin (p(2) = 0.016); a nonsignificant decrease in cellular efflux of drug (p(2) = 0.098); and a 40% increase in persistent cisplatin DNA damage as measured by atomic absorption spectrophotometry (p(2) = 0.06). These patterns were specifically not seen with the combinations of cDDP and HT, or cDDP and TNF. Conclusions: These data provide the experimental basis for the use of TNF and cDDP with HT in the treatment of gastric cancer and support the investigation of these agents in vivo in the regional treatment of peritoneal carcinomatosis. C1 NCI,SURG BRANCH,SURG METAB SECT,NIH,BETHESDA,MD 20892. RI Venzon, David/B-3078-2008 NR 44 TC 21 Z9 21 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 1068-9265 J9 ANN SURG ONCOL JI Ann. Surg. Oncol. PD MAR PY 1997 VL 4 IS 2 BP 141 EP 148 DI 10.1007/BF02303797 PG 8 WC Oncology; Surgery SC Oncology; Surgery GA WP340 UT WOS:A1997WP34000010 PM 9084851 ER PT J AU Driscoll, JS Mayers, DL Bader, JP Weislow, OS Johns, DG Buckheit, RW AF Driscoll, JS Mayers, DL Bader, JP Weislow, OS Johns, DG Buckheit, RW TI 2'-fluoro-2',3'-dideoxyarabinosyladenine (F-ddA): Activity against drug-resistant human immunodeficiency virus strains and clades A-E SO ANTIVIRAL CHEMISTRY & CHEMOTHERAPY LA English DT Article DE HIV; cross-resistance; F-ddA; clade ID REVERSE-TRANSCRIPTASE INHIBITORS; ANTIRETROVIRAL AGENTS; REDUCED SENSITIVITY; HIV; TYPE-1; SUSCEPTIBILITIES; PHOSPHORYLATION; INFECTION; THERAPY; CELLS AB 2'-Fluoro-2',3'-dideoxyarabinosyladenine (F-ddA), an anti-human immunodeficiency virus (HIV) drug currently in clinical trial, was compared with zidovudine (ATT), ddl and ddC for anti-HIV activity and potency in HIV-1 strains both sensitive and resistant to zidovudine, ddl and non-nucleoside reverse transcriptase inhibitors. A variety of host cell systems [MT-2, MT-4, phytohaemagglutinin (PHA)-stimulated peripheral blood mononuclear cells (PBMC)] was used. F-ddA was effective against each of the drug-resistant isolates, including the strain resistant to ddl, the other purine dideoxynucleoside evaluated in this study. The anti-HIV-1 activities of F-ddA and zidovudine were also determined against clades A-E in PHA-PBMCs. Although activities were similar, zidovudine was significantly more potent than F-ddA in the PHA-PBMC system. C1 WALTER REED ARMY INST RES,ROCKVILLE,MD 20850. NCI,ANTIVIRAL EVALUAT BRANCH,ROCKVILLE,MD 20852. SRA TECHNOL,ROCKVILLE,MD 20850. FREDERICK CANC RES & DEV CTR,SO RES INST,VIROL RES GRP,FREDERICK,MD 21701. RP Driscoll, JS (reprint author), NCI,MED CHEM LAB,DIV BASIC SCI,NIH,BLDG 37,ROOM 5C-02,BETHESDA,MD 20892, USA. NR 28 TC 16 Z9 17 U1 0 U2 0 PU INT MEDICAL PRESS PI LONDON PA 125 HIGH HOLBORN, LONDON, ENGLAND WC1V 6QA SN 0956-3202 J9 ANTIVIR CHEM CHEMOTH JI Antivir. Chem. Chemother. PD MAR PY 1997 VL 8 IS 2 BP 107 EP 111 PG 5 WC Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Virology SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Virology GA WN489 UT WOS:A1997WN48900004 ER PT J AU Plascjak, PS Kim, K Meyer, W Divel, J Der, M Eckelman, WC AF Plascjak, PS Kim, K Meyer, W Divel, J Der, M Eckelman, WC TI An automated radiopharmaceutical dispenser SO APPLIED RADIATION AND ISOTOPES LA English DT Article AB An automated radiopharmaceutical dispenser, that offers several advantages over manual procedures, has been developed. It employs a personal computer interfaced to a precision syringe drive module, a dose calibrator, and a printer. The operating program provides menu-selection operation and documentation of procedures and individual doses delivered. All materials in contact with the radiopharmaceutical are sterile and disposable. A novel transport safe is employed to further reduce radiation exposure. Published by Elsevier Science Ltd. RP Plascjak, PS (reprint author), NIH,PET DEPT,BLDG 10,BETHESDA,MD 20892, USA. NR 2 TC 3 Z9 3 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0969-8043 J9 APPL RADIAT ISOTOPES JI Appl. Radiat. Isot. PD MAR PY 1997 VL 48 IS 3 BP 345 EP 348 DI 10.1016/S0969-8043(96)00215-1 PG 4 WC Chemistry, Inorganic & Nuclear; Nuclear Science & Technology; Radiology, Nuclear Medicine & Medical Imaging SC Chemistry; Nuclear Science & Technology; Radiology, Nuclear Medicine & Medical Imaging GA WL882 UT WOS:A1997WL88200007 PM 9116653 ER PT J AU Woolf, SH Bell, HS Berman, B Brenner, ZD Hoffman, FA Hudgings, C Ignatius, H Peeke, PM Yacher, J AF Woolf, SH Bell, HS Berman, B Brenner, ZD Hoffman, FA Hudgings, C Ignatius, H Peeke, PM Yacher, J TI Clinical practice guidelines in complementary and alternative medicine - An analysis of opportunities and obstacles SO ARCHIVES OF FAMILY MEDICINE LA English DT Article ID CHIROPRACTIC MANIPULATION; UNCONVENTIONAL MEDICINE; ACUPUNCTURE TREATMENT; CHILDHOOD DIARRHEA; CONTROLLED TRIAL; HEPATITIS-B; HOMEOPATHT; PAIN; REALITY; NECK AB An estimated 1 of 3 Americans uses some form of complementary and alternative medicine (CAM), such as acupuncture, homeopathy, or herbal medicine. In 1995, the National Institutes of Health Office of Alternative Medicine convened an expert panel to examine the role of clinical practice guidelines in CAM. The panel concluded that CAM practices currently are unsuitable for the development of evidence-based practice guidelines, in part because of the lack of relevant outcomes data from well-designed clinical trials. Moreover, the notions of standardization and appropriateness, inherent in guideline development, face challenging methodologic problems when applied to CAM, which considers many different treatment practices appropriate and encourages highly individualized care. Due to different belief systems and divergent theories about the nature of health and illness, CAM disciplines have fundamental differences in how they define target conditions, causes of disease, interventions, and outcome measures of effectiveness. These differences are even more striking when compared with those used by Western medicine. The panel made a series of recommendations on strategies to strengthen the evidence base for future guideline development in CAM and to meet better the current information needs of clinicians, patients, and guideline developers who seek information about CAM treatments. RP Woolf, SH (reprint author), NIH, OFF ALTERNAT MED, PRACTICE & POLICY GUILDELINES PANEL, BETHESDA, MD USA. NR 73 TC 45 Z9 45 U1 2 U2 5 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA SN 1063-3987 J9 ARCH FAM MED JI Arch. Fam. Med. PD MAR-APR PY 1997 VL 6 IS 2 BP 149 EP 154 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA WN707 UT WOS:A1997WN70700015 ER PT J AU Marangell, LB George, MS Callahan, AM Ketter, TA Pazzaglia, PJ LHerrou, TA Leverich, GS Post, RM AF Marangell, LB George, MS Callahan, AM Ketter, TA Pazzaglia, PJ LHerrou, TA Leverich, GS Post, RM TI Effects of intrathecal thyrotropin-releasing hormone (protirelin) in refractory depressed patients SO ARCHIVES OF GENERAL PSYCHIATRY LA English DT Article; Proceedings Paper CT 19th Collegium-Internationale-Neuro-Psychopharmacologicum Congress CY JUN 27-JUL 01, 1994 CL WASHINGTON, DC SP Collegium Int Neuro Psychopharm ID AMYOTROPHIC LATERAL SCLEROSIS; ELECTROCONVULSIVE SHOCK; CEREBROSPINAL-FLUID; RAT-BRAIN; TRH; SYSTEM; SPASTICITY; BACLOFEN; THERAPY AB Background: Therapeutic effects of the tripeptide protirelin (thyrotropin-releasing hormone) have been postulated in the affective disorders, but direct assessment in humans has been hindered by poor blood-brain barrier permeability. Methods: Eight medication-free inpatients with refractory depression received 500 mu g of protirelin via a lumbar intrathecal injection and an identical sham lumbar puncture procedure, separated by 1 week, in a double-blind crossover design. Results: Five of eight patients responded to intrathecal protirelin, defined asa 50% or greater reduction in an abbreviated Hamilton Rating Scale for Depression score. Suicidality also was reduced significantly (P<.05). Responses were rapid and clinically robust, but short-lived. Conclusion: Administration of protirelin by an intrathecal route induced a rapid improvement in mood and suicidality in these refractory depressed patients, supporting the hypothesis that thyrotropin-releasing hormone could be a positive modulator of mood. C1 NIH,NIMH,BIOL PSYCHIAT BRANCH,BETHESDA,MD 20892. BAYLOR COLL MED,DEPT PSYCHIAT,HOUSTON,TX 77030. MED UNIV S CAROLINA,DEPT PSYCHIAT,CHARLESTON,SC 29425. MT SINAI MED CTR,DEPT PSYCHIAT,NEW YORK,NY 10029. ELECT VILLAGE SYST,CENTREVILLE,VA. STANFORD SCH MED,DEPT PSYCHIAT,STANFORD,CA. UNIV MISSISSIPPI,SCH MED,DEPT PSYCHIAT,JACKSON,MS 39216. NR 45 TC 76 Z9 79 U1 0 U2 1 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0003-990X J9 ARCH GEN PSYCHIAT JI Arch. Gen. Psychiatry PD MAR PY 1997 VL 54 IS 3 BP 214 EP 222 PG 9 WC Psychiatry SC Psychiatry GA WP355 UT WOS:A1997WP35500004 PM 9075462 ER PT J AU Pillemer, SR Fowler, SE Tilley, BC Alarcon, GS Heyse, SP Trentham, DE Neuner, R Clegg, DO Leisen, JCC Cooper, SM Duncan, H Tuttleman, M AF Pillemer, SR Fowler, SE Tilley, BC Alarcon, GS Heyse, SP Trentham, DE Neuner, R Clegg, DO Leisen, JCC Cooper, SM Duncan, H Tuttleman, M TI Meaningful improvement criteria sets in a rheumatoid arthritis clinical trial SO ARTHRITIS AND RHEUMATISM LA English DT Article ID OUTCOME MEASURES; PLACEBO; METHOTREXATE AB Objective. To compare 3 sets of criteria for meaningful improvement in a rheumatoid arthritis (RA) clinical trial, and to evaluate the implications of these criteria sets for RA trial design. Methods. Data were obtained from the Minocycline in Rheumatoid Arthritis (MIRA) trial (primary outcome measures: 50% improvement in joint tenderness and 50% improvement in joint swelling, based on joint scores), These MIRA data were evaluated against 1) the Paulus criteria (20% improvement in 4 of 6 measures: joint tenderness scores, joint swelling scores, physician's and patient's global assessments, erythrocyte sedimentation rate [ESR], and morning stiffness); and 2) the American College of Rheumatology (ACR) criteria (20% improvement in joint tenderness and joint swelling counts, and in 3 of 5 other measures: physician's and patient's global assessments, ESR, modified Health Assessment Questionnaire, and patient's pain assessment), The ACR criteria were modified using 3 of 4 remaining measures, since baseline pain assessment data were not available. Results. Percentages of minocycline-treated patients versus placebo-treated patients showing meaningful improvement were as follows: by MIRA criteria, for joint tenderness, 56% versus 41% (P = 0.021), and for joint swelling, 54% versus 39% (P = 0.023); by Paulus criteria, 41% versus 28% (P = 0.040); and by ACR criteria, 44% versus 26% (P = 0.004), Both the modified ACR criteria and the Paulus criteria demonstrated a reduced placebo response rate, Compared with the MIRA criteria, the ACR criteria increased, and the Paulus criteria decreased, absolute between-group differences in improvement; however, both criteria sets increased relative percentages of patients showing improvement in the minocycline group versus the placebo group, Study design considerations indicated that application of the ACR criteria would reduce the required sample size. Conclusion. Different placebo response rates and treatment group differences were found using the 3 RA improvement criteria sets, These findings support the use of the ACR criteria for defining improvement in RA clinical trials. C1 HENRY FORD HLTH SYST,DETROIT,MI. UNIV ALABAMA,BIRMINGHAM,AL. NIAID,BETHESDA,MD 20892. BETH ISRAEL HOSP,BOSTON,MA 02215. FED DRUG ADM,CTR DRUG EVALUAT & RES,ROCKVILLE,MD. UNIV UTAH,MED CTR,SALT LAKE CITY,UT. HENRY FORD HOSP,DETROIT,MI 48202. UNIV VERMONT,BURLINGTON,VT. RP Pillemer, SR (reprint author), NIAMSD,OFF DIRECTOR,NIH,BLDG 45,ROOM 5AS-37G,45 CTR DR,MSC 6500,BETHESDA,MD 20892, USA. FU NIAMS NIH HHS [N01-AR-1-2203, N01-AR-1-2202, N01-AR-1-2205] NR 16 TC 20 Z9 21 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD MAR PY 1997 VL 40 IS 3 BP 419 EP 425 DI 10.1002/art.1780400305 PG 7 WC Rheumatology SC Rheumatology GA WN158 UT WOS:A1997WN15800004 PM 9082927 ER PT J AU Raynal, P Pollard, HB Srivastava, M AF Raynal, P Pollard, HB Srivastava, M TI Cell cycle and post-transcriptional regulation of annexin expression in IMR-90 human fibroblasts SO BIOCHEMICAL JOURNAL LA English DT Article ID HUMAN-ENDOTHELIAL-CELLS; DEVELOPMENTAL REGULATION; PROTEIN-KINASE; CALPACTIN-I; GROWTH; PHOSPHORYLATION; SUBSTRATE; DIFFERENTIATION; PROLIFERATION; INHIBITION AB Based on the finding that the expression of some annexins varies dramatically as a function of cellular proliferation state [Schlaepfer and Haigler (1990) J. Cell Biol. 111, 229-238], it has been proposed that the cellular level of the annexins might be critical for the regulation of cell growth. To further test this hypothesis, we have studied the expression of various annexins in normal human IMR-90 fibroblasts synchronized by serum deprivation. Using immunoblotting, the cellular content of annexins (Anxs) II, V and VI was found to vary by less than 10% during the cell cycle. However, Anx IV expression increased by 50% during S-phase and the levels of Anxs I and VII were reduced by 40% in early G2/M. However, using RNase protection assays, the mRNAs of Anxs I and VII were found to be uniformly expressed throughout the cell cycle, suggesting that downregulation of both proteins in G2/M occurred through a post-transcriptional process. In addition, cells transfected with Anx VII cDNA were shown to contain an amount of Anx VII similar to wild-type cells, despite the elevation of Anx VII mRNA content in transfected cells by approx. 2 orders of magnitude. Vector misconstruction or possible secretion of the overexpressed protein were ruled out using appropriate controls. Therefore, as with cell-cycle regulation, Anx VII expression in transfected cells is also controlled by post-transcriptional mechanisms. Furthermore, using pulse-chase analysis, we have determined that annexin VII, and other Anxs, have a slow turnover rate, consistent with the limited changes of expression throughout the cell cycle. Taken together, these results question the hypothesis that cellular expression of Anxs plays a general role in cell growth and support the concept that post-transcriptional mechanisms may control levels of Anxs I and VII. C1 NIDDK,CELL BIOL & GENET LAB,NIH,BETHESDA,MD 20892. NR 24 TC 15 Z9 15 U1 0 U2 1 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 1997 VL 322 BP 365 EP 371 PN 2 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA WM107 UT WOS:A1997WM10700002 PM 9065751 ER PT J AU Lesiak, K Torrence, PF AF Lesiak, K Torrence, PF TI Efficient functionalization of 2',5'-oligoadenylates with sulfur SO BIOCONJUGATE CHEMISTRY LA English DT Article ID BIOLOGICAL-ACTIVITIES; 2-5A-DEPENDENT RNASE; ANTISENSE CHIMERAS; 2-5A ANTISENSE; OLIGONUCLEOTIDES; CLEAVAGE; TARGET AB To derivatize the 2'-terminus of 2',5'-oligoadenylates with a thiol group, the reaction of periodate-oxidized nucleotide and 2',5'-oligonucleotide with aminothiols was explored. Two separate synthetic approaches were employed, both of which relied upon the use of S-protected thiols. In one approach, 5'AMP was oxidized with sodium periodate to dialdehyde, which was reacted with cystamine hydrochloride. Sodium cyanoborohydride reduction of the unisolated intermediate aminal gave compound 4. The second approach involved reaction of S-(2-tetrahydropyranyl)cysteamine with the dialdehyde obtained by periodate oxidation of 5'AMP to yield, after reduction with Na(CN)BH3, the S-protected adduct 3. Intermediate 3 could be oxidized with aqueous iodine to give disulfide 4. Disulfide 4, obtained by either of the above routes, was reduced with dithiothreitol (DTT) to the thiol 5. This same reaction sequence was applied to 2-5A tetramer monophosphate, p5'A2'[p5'A2'](2)p5'A (6a), to give via 6b the 2'-terminal-modified derivative 6c. Aqueous iodine oxidation of 6c provided the disulfide 7, which reacted with DTT to give quantitative conversion to product, the free thiol 8. Both the disulfide 7 End the S-tetrahydropyranyl-protected derivative (6c) were bound effectively to the 2-5A-dependent RNase L of mouse L cells with IC50 values of 1 x 10-9 M for 7 and 8 x 10(-10) M for 6c, not significantly different from the corresponding value for the parent unmodified 2-5A (6a) itself. C1 NIDDKD,SECT BIOMED CHEM,MED CHEM LAB,NIH,BETHESDA,MD 20892. NR 29 TC 3 Z9 4 U1 0 U2 5 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 1043-1802 J9 BIOCONJUGATE CHEM JI Bioconjugate Chem. PD MAR-APR PY 1997 VL 8 IS 2 BP 199 EP 203 DI 10.1021/bc970012i PG 5 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Chemistry, Multidisciplinary; Chemistry, Organic SC Biochemistry & Molecular Biology; Chemistry GA WQ215 UT WOS:A1997WQ21500015 PM 9095361 ER PT J AU Reed, MW Panyutin, IG Hamlin, D Lucas, DD Wilbur, DS AF Reed, MW Panyutin, IG Hamlin, D Lucas, DD Wilbur, DS TI Synthesis of I-125-labeled oligonucleotides from tributylstannylbenzamide conjugates SO BIOCONJUGATE CHEMISTRY LA English DT Article ID I-125; DNA; RADIOHALOGENATION; RADIOTOXICITY; DAMAGE; PROBES; DECAY AB A rapid and efficient method for the synthesis of I-125-labeled oligodeoxynucleotides ([I-125]ODNs) is described. The key intermediates are tributylstannylbenzamide-modified ODNs (Sn-ODNs). Reaction conditions are described for the preparation of 5'-modified Sn-ODNs. Treatment with NaI and chloramine T gave conversion to the desired I-ODN, which was easily isolated by reversed phase chromatography. Thermal denaturation (T-m) studies showed that hybridization properties were not disturbed by the 4-iodobenzamide modification. An [I-125]ODN was prepared and characterized by hybridization to P-32-labeled DNA targets. Sequence specific cleavage of the target DNA strand by I-125 was measured. C1 NIH,DEPT NUCL MED,CTR CLIN,BETHESDA,MD 20892. UNIV WASHINGTON,DEPT RADIAT ONCOL,SEATTLE,WA 98195. RP Reed, MW (reprint author), EPOCH PHARMACEUT INC,1725 220TH ST SE,104,BOTHELL,WA 98021, USA. NR 19 TC 14 Z9 14 U1 0 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 1043-1802 J9 BIOCONJUGATE CHEM JI Bioconjugate Chem. PD MAR-APR PY 1997 VL 8 IS 2 BP 238 EP 243 DI 10.1021/bc970016n PG 6 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Chemistry, Multidisciplinary; Chemistry, Organic SC Biochemistry & Molecular Biology; Chemistry GA WQ215 UT WOS:A1997WQ21500020 PM 9095366 ER PT J AU Wolffe, AP Khochbin, S Dimitrov, S AF Wolffe, AP Khochbin, S Dimitrov, S TI What do linker histones do in chromatin? SO BIOESSAYS LA English DT Article ID RNA POLYMERASE-II; IN-VIVO; GENE-TRANSCRIPTION; CRYSTAL-STRUCTURE; GLOBULAR DOMAIN; NUCLEOSOME; H1; PROMOTER; H-1; SEQUENCE AB Knockout experiments in Tetrahymena show that linker histone H1 is not essential for nuclear assembly or cell viability. These results, together with a series of biochemical and cell biological observations, challenge the existing paradigm that requires linker histones to be a key organizing component of higher-order chromatin structure. The H1 knockouts also reveal a much more subtle role for H1. Instead of acting as a general transcriptional repressor, H1 is found to regulate a limited number of specific genes. Surprisingly, H1 can both activate and repress transcription. We discuss how this architectural protein might accomplish this important regulatory role. C1 FAC MED,INST ALBERT BONNIOT,INSERM,U309,F-38706 LA TRONCHE,FRANCE. CNRS,UMR 5538,F-75700 PARIS,FRANCE. RP Wolffe, AP (reprint author), NICHHD,MOL EMBRYOL LAB,NIH,BETHESDA,MD 20892, USA. RI dimitrov, stefan/M-7697-2013; Khochbin, Saadi/M-8090-2013 NR 70 TC 112 Z9 115 U1 0 U2 1 PU COMPANY OF BIOLOGISTS LTD PI CAMBRIDGE PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE, CAMBS, ENGLAND CB4 4DL SN 0265-9247 J9 BIOESSAYS JI Bioessays PD MAR PY 1997 VL 19 IS 3 BP 249 EP 255 DI 10.1002/bies.950190311 PG 7 WC Biochemistry & Molecular Biology; Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics GA WN546 UT WOS:A1997WN54600010 PM 9080775 ER PT J AU duManoir, S AF duManoir, S TI Diagnostic significance of the spectral karyotype SO BIOFUTUR LA French DT Article ID FLUORESCENCE INSITU HYBRIDIZATION; DNA PROBES RP duManoir, S (reprint author), NIH,NATL CTR HUMAN GENOME RES,BLDG 49,ROOM 4B24,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 11 TC 0 Z9 0 U1 0 U2 0 PU EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER PI PARIS PA 141 RUE JAVEL, 75747 PARIS, FRANCE SN 0294-3506 J9 BIOFUTUR JI Biofutur PD MAR PY 1997 IS 165 BP A5 EP A5 PG 1 WC Biotechnology & Applied Microbiology SC Biotechnology & Applied Microbiology GA WP763 UT WOS:A1997WP76300010 ER PT J AU Follmann, DA AF Follmann, DA TI An appropriate generalized linear model with random effects for informative missing data SO BIOMETRICS LA English DT Letter RP Follmann, DA (reprint author), NHLBI,ROCKLEDGE CTR 2,ROOM 8216,BETHESDA,MD 20892, USA. NR 3 TC 0 Z9 0 U1 0 U2 0 PU INTERNATIONAL BIOMETRIC SOC PI WASHINGTON PA 808 17TH ST NW SUITE 200, WASHINGTON, DC 20006-3910 SN 0006-341X J9 BIOMETRICS JI Biometrics PD MAR PY 1997 VL 53 IS 1 BP 384 EP 384 PG 1 WC Biology; Mathematical & Computational Biology; Statistics & Probability SC Life Sciences & Biomedicine - Other Topics; Mathematical & Computational Biology; Mathematics GA WN180 UT WOS:A1997WN18000035 ER PT J AU Proschan, MA AF Proschan, MA TI Conditional power with Fisher's least significant difference procedure SO BIOMETRIKA LA English DT Article DE monitoring; multi-armed trial; stochastic curtailment ID ISCHEMIA PILOT ACIP; CLINICAL-TRIALS; DESIGN AB Conditional power calculations are very useful for assessing-the likelihood of an ultimately statistically significant result given the current data. We show how to calculate conditional power in a multi-armed trial using the classic Fisher least significant difference, LSD, procedure. We obtain upper bounds on the probabilities of Type 1 and Type 2 errors analogous to those in two-armed trials, and show that these bounds are equalities under continuous monitoring. RP Proschan, MA (reprint author), NHLBI,ROCKLEDGE CTR 2,6701 ROCKLEDGE DR,MSC 7938,BETHESDA,MD 20892, USA. NR 19 TC 2 Z9 2 U1 1 U2 2 PU BIOMETRIKA TRUST PI LONDON PA UNIV COLLEGE LONDON GOWER ST-BIOMETRIKA OFFICE, LONDON, ENGLAND WC1E 6BT SN 0006-3444 J9 BIOMETRIKA JI Biometrika PD MAR PY 1997 VL 84 IS 1 BP 197 EP 208 DI 10.1093/biomet/84.1.197 PG 12 WC Biology; Mathematical & Computational Biology; Statistics & Probability SC Life Sciences & Biomedicine - Other Topics; Mathematical & Computational Biology; Mathematics GA WT082 UT WOS:A1997WT08200017 ER PT J AU Slud, EV Korn, EL AF Slud, EV Korn, EL TI Semiparametric two-sample tests in clinical trials with a post-randomisation response indicator SO BIOMETRIKA LA English DT Article DE auxiliary endpoints; delta method; maximum partial likelihood estimator; proportional hazards model; stratification; surrogate endpoints ID REGRESSION-MODELS; SURVIVAL-DATA; MISSING DATA; VALIDATION; VARIABLES; DISEASE AB In many clinical trials involving survival endpoints; one has additional data on some binary indicator of 'response', such as initial tumour shrinkage in cancer trials. This paper studies the case of randomised clinical trials where the response indicator is available shortly after randomisation, and where one can assume that, within each stratum defined by the response indicator, a two treatment-group proportional-hazards model holds. The same model may also describe some incompletely randomised or observational studies. Asymptotic relative efficiencies for Kaplan-Meier-based estimators versus maximum partial likelihood estimators are examined under this model for estimating either the difference in survival probabilities at a specified time or the parameter estimated by the logrank numerator. It is shown that the efficiency gains using the model are more promising when estimating the difference in survival probabilities. An example is given comparing the long-term survival experience of two groups of patients with advanced Hodgkin's disease. C1 UNIV MARYLAND,DEPT MATH,COLLEGE PK,MD 20742. NCI,BETHESDA,MD 20892. RP Slud, EV (reprint author), INFORMAT MANAGEMENT SERV INC,COLLEGE PK,MD 20742, USA. NR 27 TC 4 Z9 4 U1 0 U2 1 PU BIOMETRIKA TRUST PI LONDON PA UNIV COLLEGE LONDON GOWER ST-BIOMETRIKA OFFICE, LONDON, ENGLAND WC1E 6BT SN 0006-3444 J9 BIOMETRIKA JI Biometrika PD MAR PY 1997 VL 84 IS 1 BP 221 EP 230 DI 10.1093/biomet/84.1.221 PG 10 WC Biology; Mathematical & Computational Biology; Statistics & Probability SC Life Sciences & Biomedicine - Other Topics; Mathematical & Computational Biology; Mathematics GA WT082 UT WOS:A1997WT08200019 ER PT J AU Domagala, JM Bader, JP Gogliotti, RD Sanchez, JP Stier, MA Song, YT Prasad, JVNV Tummino, PJ Scholten, J Harvey, P Holler, T Gracheck, S Hupe, D Rice, WG Schultz, R AF Domagala, JM Bader, JP Gogliotti, RD Sanchez, JP Stier, MA Song, YT Prasad, JVNV Tummino, PJ Scholten, J Harvey, P Holler, T Gracheck, S Hupe, D Rice, WG Schultz, R TI A new class of anti-HIV-1 agents targeted toward the nucleocapsid protein NCp7: The 2,2'-dithiobisbenzamides SO BIOORGANIC & MEDICINAL CHEMISTRY LA English DT Article ID STRAND TRANSFER; ZINC FINGERS; HIV-1; AIDS; STRATEGIES; INHIBITION; BEHAVIOR; THERAPY; RNA AB As part of the National Cancer Institute's Drug Screening Program, a new class of antiretrovirals active against the human immunodeficiency virus HIV-1 has been identified, and the HIV-I nucleocapsid protein NCp7 was proposed as the target of antiviral action. The 2,2'-dithiobis-[4'-(sulfamoyl)benzanilide] (3x) and the 2,2'-dithiobis(5-acetylamino)benzamide (10) represented the prototypic lead structures. A wide variety of 2,2'-dithiobisbenzamides were prepared and tested for anti-HIV-l activity, cytotoxicity, and their ability to extrude zinc from the zinc fingers for NCp7. The structure-activity relationships demonstrated that the ability to extrude zinc from NCp7 resided in the 2,2'-dithiobisbenzamide core structure. The 3,3' and the 4,4' isomers were inactive. While many analogs based upon the core structure retained the zinc extrusion activity, the best overall anti-HIV-1 activity was only found in a narrow set of derivatives possessing carboxylic acid, carboxamide, or phenylsulfonamide functional groups. These functional groups were more important for reducing cytotoxicity than improving antiviral potency or activity vs NCp7. All of the compounds with antiviral activity also extruded zinc from NCp7. From this study several classes of low mu M anti-HIV agents with simple chemical structures were identified as possible chemotherapeutic agents for the treatment of AIDS. (C) 1997 Elsevier Science Ltd. C1 PARKE DAVIS PHARMACEUT RES,DEPT THERAPEUT,ANN ARBOR,MI 48105. ANTIVIRAL EVALUAT DEV THERAPEUT PROGRAM,BETHESDA,MD 20892. NCI,SAIC,FREDERICK,MD 21702. RP Domagala, JM (reprint author), PARKE DAVIS PHARMACEUT RES,DEPT CHEM,2800 PLYMOUTH RD,ANN ARBOR,MI 48105, USA. NR 34 TC 37 Z9 38 U1 0 U2 4 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0968-0896 J9 BIOORGAN MED CHEM JI Bioorg. Med. Chem. PD MAR PY 1997 VL 5 IS 3 BP 569 EP 579 DI 10.1016/S0968-0896(96)00269-6 PG 11 WC Biochemistry & Molecular Biology; Chemistry, Medicinal; Chemistry, Organic SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Chemistry GA WZ154 UT WOS:A1997WZ15400015 PM 9113335 ER PT J AU Li, YX Stojilkovic, SS Keizer, J Rinzel, J AF Li, YX Stojilkovic, SS Keizer, J Rinzel, J TI Sensing and refilling calcium stores in an excitable cell SO BIOPHYSICAL JOURNAL LA English DT Article ID INTRACELLULAR CA2+ STORES; SMOOTH-MUSCLE CELLS; PITUITARY GONADOTROPHS; OSCILLATIONS; MEMBRANE; ACTIVATION; RECEPTORS; ENTRY; MODEL; WAVES AB Inositol 1,4,5-trisphosphate (IP3)-induced Ca2+ mobilization leads to depletion of the endoplasmic reticulum (ER) and an increase in Ca2+ entry. We show here for the gonadotroph, an excitable endocrine cell, that sensing of ER Ca2+ content can occur without the Ca2+ release-activated Ca2+ current (I-crac), but rather through the coupling of IP3-induced Ca2+ oscillations to plasma membrane voltage spikes that gate Ca2+ entry. Thus we demonstrate that capacitative Ca2+ entry is accomplished through Ca2+-controlled Ca2+ entry. We develop a comprehensive model, with parameter values constrained by available experimental data, to simulate the spatiotemporal behavior of agonist-induced Ca2+ signals in both the cytosol and ER lumen of gonadotrophs. The model combines two previously developed models, one for ER-mediated Ca2+ oscillations and another for plasma membrane potential-driven Ca2+ oscillations. Simulations show agreement with existing experimental records of store content, cytosolic Ca2+ concentration ([Ca2+](i)), and electrical activity, and make a variety of new, experimentally testable predictions. In particular, computations with the model suggest that [Ca2+](i) in the vicinity of the plasma membrane acts as a messenger for ER content via Ca2+-activated K+ channels and Ca2+ pumps in the plasma membrane. We conclude that, in excitable cells that do not express I-crac, [Ca2+](i) profiles provide a sensitive mechanism for regulating net calcium flux through the plasma membrane during both store depletion and refilling. C1 NIADDKD,MATH RES BRANCH,NIH,BETHESDA,MD 20814. NICHHD,ENDOCRINOL & REPROD RES BRANCH,NIH,BETHESDA,MD 20814. UNIV CALIF DAVIS,INST THEORET DYNAM,SECT NEUROBIOL PHYSIOL & BEHAV,DAVIS,CA 95616. FU NCRR NIH HHS [R01 RR1081-01A1] NR 42 TC 52 Z9 52 U1 0 U2 0 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD MAR PY 1997 VL 72 IS 3 BP 1080 EP 1091 PG 12 WC Biophysics SC Biophysics GA WJ824 UT WOS:A1997WJ82400012 PM 9138557 ER PT J AU Haberkern, CM Neumayr, LD Orringer, EP Earles, AN Robertson, SM Black, D Abboud, MR Koshy, M Idowu, O Vichinsky, EP AF Haberkern, CM Neumayr, LD Orringer, EP Earles, AN Robertson, SM Black, D Abboud, MR Koshy, M Idowu, O Vichinsky, EP TI Cholecystectomy in sickle cell anemia patients: Perioperative outcome of 364 cases from the national preoperative transfusion study SO BLOOD LA English DT Article ID LAPAROSCOPIC CHOLECYSTECTOMY; ELECTIVE CHOLECYSTECTOMY; CHOLELITHIASIS; DISEASE; CHILDREN; HEMOGLOBINOPATHIES; MANAGEMENT; EXPERIENCE; COMPLICATIONS; HEMATOCRIT AB Cholecystectomy is the most common surgical procedure performed in sickle cell anemia (SCA) patients. We investigated the effects of transfusion and surgical method on perioperative outcome. A total of 364 patients underwent cholecystectomy: group 1 (randomized to aggressive transfusion) 110 patients; group 2 (randomized to conservative transfusion) 120 patients; group 3 (nonrandomized nontransfusion) 37 patients; and group 4 (nonrandomized transfusion) 97 patients. Patients were similar except group 3 patients were more likely to be female, over 20 years old, smokers, and more healthy by American Society of Anesthesiologists (ASA) physical status score. Total complication rate was 39%: sickle cell events 19%; intraoperative or recovery room events 11%; transfusion complications 10%; postoperative surgical events 4%; and death 1%. Group 3 patients had the highest incidence of sickle cell events (32%). Open cholecystectomies were performed in 58% and laparoscopic in 42%. Laparoscopic patients were younger and more healthy by ASA score. Laparoscopic patients had longer anesthesia time (3,2 v 2.9 hours), but shorter hospitalization time (6.4 days v 9.8). Complications were similar between these two groups, We conclude that SCA patients undergoing cholecystectomy have a high perioperative morbidity, and the incidence of sickle cell events may be higher in patients not preoperatively transfused. We recommend a conservative preoperative transfusion regimen, and we encourage the use of the laparoscopic technique for SCA patients undergoing elective cholecystectomy. (C) 1997 by The American Society of Hematology. C1 CHILDRENS HOSP OAKLAND,DEPT HEMATOL ONCOL,OAKLAND,CA 94609. UNIV WASHINGTON,DEPT ANESTHESIOL,SEATTLE,WA 98195. UNIV WASHINGTON,DEPT PEDIAT,SEATTLE,WA 98195. CHILDRENS HOSP,SEATTLE,WA. UNIV WASHINGTON,MED CTR,SEATTLE,WA 98195. UNIV N CAROLINA,SCH MED,DEPT HEMATOL,CHAPEL HILL,NC. UNIV CALIF SAN FRANCISCO,PREVENT SCI GRP,SAN FRANCISCO,CA 94143. MED UNIV S CAROLINA,DEPT PEDIAT,CHARLESTON,SC 29425. UNIV ILLINOIS,DEPT MED,CHICAGO,IL. CHILDRENS HOSP OAKLAND,DEPT SURG,OAKLAND,CA 94609. ALBERT EINSTEIN COLL MED,BRONX,NY 10467. ALTA BATES COMMUNITY HOSP,BERKELEY,CA. BAYLOR COLL MED,HOUSTON,TX 77030. BRONX LEBANON HOSP CTR,BRONX,NY. CAROLINAS MED CTR,CHARLOTTE,NC 28203. CHILDRENS HOSP,NATL MED CTR,WASHINGTON,DC. CHILDRENS HOSP OAKLAND,OAKLAND,CA. SUNY COLL BUFFALO,CHILDRENS HOSP BUFFALO,BUFFALO,NY 14222. CHILDRENS HOSP PHILADELPHIA,PHILADELPHIA,PA 19104. CHILDRENS MEM HOSP,CHICAGO,IL 60614. CHILDRENS MERCY HOSP,KANSAS CITY,MO 64108. COLUMBIA PRESBYTERIAN MED CTR,NEW YORK,NY 10032. DUKE UNIV,MED CTR,DURHAM,NC. E CAROLINA UNIV,GREENVILLE,NC. EMORY UNIV,ATLANTA,GA 30322. HIGHLAND HOSP,OAKLAND,CA. HOSP ST JUSTINE,MONTREAL,PQ,CANADA. HOSP SICK CHILDREN,TORONTO,ON M5G 1X8,CANADA. INTERFAITH MED CTR,BROOKLYN,NY. LEBONHEUR CHILDRENS HOSP & MED CTR,MEMPHIS,TN. MED COLL GEORGIA,AUGUSTA,GA 30912. MONTEFIORE HOSP,BRONX,NY. MONTREAL CHILDRENS HOSP,MONTREAL,PQ H3H 1P3,CANADA. NYU,MED CTR,NEW YORK,NY 10016. SAN FRANCISCO GEN HOSP,SAN FRANCISCO,CA 94110. SUNY DOWNSTATE MED CTR,BROOKLYN,NY. ST LUKES ROOSEVELT HOSP,NEW YORK,NY 10025. STANFORD UNIV,CHILDRENS HOSP,STANFORD,CA 94305. UNIV MISSOURI,TRUMAN MED CTR,KANSAS CITY,MO 64108. UNIV CINCINNATI,CINCINNATI,OH. UNIV COLORADO,DENVER,CO 80202. UNIV MIAMI,MIAMI,FL 33152. UNIV MISSISSIPPI,JACKSON,MS 39216. UNIV S ALABAMA,MOBILE,AL 36688. UNIV SO CALIF,MED CTR,LOS ANGELES,CA. COLUMBIA UNIV COLL PHYS & SURG,HARLEM HOSP CTR,NEW YORK,NY 10032. MAYO CLIN,MINNEAPOLIS,MN. CHILDRENS HOSP PHILADELPHIA,PHILADELPHIA,PA 19104. UNIV IOWA HOSP & CLIN,IOWA CITY,IA 52242. ST LOUIS CHILDRENS HOSP,ST LOUIS,MO 63178. NHLBI,NIH,ROCKVILLE,MD. NIH,SICKLE CELL DIS BRANCH,ROCKVILLE,MD. WASHINGTON UNIV,SCH MED,ST LOUIS,MO. FU NHLBI NIH HHS [HL-20985] NR 37 TC 81 Z9 84 U1 1 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD MAR 1 PY 1997 VL 89 IS 5 BP 1533 EP 1542 PG 10 WC Hematology SC Hematology GA WK477 UT WOS:A1997WK47700009 PM 9057634 ER PT J AU StetlerStevenson, M Mansoor, A Lim, M Fukushima, P Kehrl, J Marti, G Ptaszynski, K Wang, J StetlerStevenson, WG AF StetlerStevenson, M Mansoor, A Lim, M Fukushima, P Kehrl, J Marti, G Ptaszynski, K Wang, J StetlerStevenson, WG TI Expression of matrix metalloproteinases and tissue inhibitors of metalloproteinases in reactive and neoplastic lymphoid cells SO BLOOD LA English DT Article ID ERYTHROID-POTENTIATING ACTIVITY; GROWTH-PROMOTING ACTIVITY; IV COLLAGENASE; T-CELLS; EXTRACELLULAR-MATRIX; GELATINASE; LEUKEMIA; PROTEIN; TIMP-2; GENE AB We have studied the expression of gelatinase A, gelatinase B, interstitial collagenase, tissue inhibitor of metalloproteinase (TIMP)-1 and TIMP-2 in reactive lymphoid cells, as well as in a series of cell lines derived from neoplasms of B- and T-cell lineage. Using both Northern blot analysis and zymography, gelatinase B activity was detected by zymography in two Burkitt cell lines and in a tonsillar cell suspension, while gelatinase A and interstitial collagenase activities were not detected by either method. TMP-1 expression was demonstrated by Northern blot analysis in the multipotential neoplastic K-562 cell line, the high grade Burkitt's B-cell lymphoma lines, isolated tonsillar B cells and at low levels in peripheral blood T cells, but was not expressed in any of the neoplastic T-cell lines or isolated peripheral blood B cells. In contrast, TIMP-2 expression was restricted to tissues containing cells of T-cell lineage with high levels being observed in the neoplastic T-cell lines and lower levels in normal peripheral blood T cells and hyperplastic tonsil. Expression of TIMP-1 and TIMP-2 was confirmed at the protein level by reverse zymography and immunofluorescence assays using antihuman TIMP polyclonal antibodies. Expression of gelatinase B by the high grade B-cell Burkitt's lymphoma cell lines is consistent with previous findings in large cell immunoblastic lymphomas and indicates that this enzyme may play an important role in high grade non-Hodgkin's lymphomas. TIMP expression correlated with cell lineage in that TIMP-1 was primarily observed in B cells and TIMP-2 was restricted to T cells. C1 NCI,HEMATOPATHOL SECT,FLOW CYTOMETRY UNIT,BETHESDA,MD 20892. NIAID,IMMUNOREGULAT LAB,NIH,BETHESDA,MD 20892. US FDA,CTR BIOL EVALUAT & RES,FLOW & IMAGE CYTOMETRY SECT,LAB MED & MOL GENET,BETHESDA,MD. RP StetlerStevenson, M (reprint author), NCI,EXTRACELLULAR MATRIX PATHOL SECT,PATHOL LAB,DIV CLIN SCI,NIH,BLDG 10,ROOM 2A-33,BETHESDA,MD 20892, USA. RI Stetler-Stevenson, William/H-6956-2012; OI Stetler-Stevenson, William/0000-0002-5500-5808; Kehrl, John/0000-0002-6526-159X NR 45 TC 98 Z9 100 U1 0 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD MAR 1 PY 1997 VL 89 IS 5 BP 1708 EP 1715 PG 8 WC Hematology SC Hematology GA WK477 UT WOS:A1997WK47700029 PM 9057654 ER PT J AU Weil, WM Linton, GF WhitingTheobald, N Vowells, SJ Rafferty, SP Li, F Malech, HL AF Weil, WM Linton, GF WhitingTheobald, N Vowells, SJ Rafferty, SP Li, F Malech, HL TI Genetic correction of p67(phox) deficient chronic granulomatous disease using peripheral blood progenitor cells as a target for retrovirus mediated gene transfer SO BLOOD LA English DT Article ID COLONY-STIMULATING FACTOR; BONE-MARROW TRANSPLANTATION; RESPIRATORY BURST OXIDASE; NEUTROPHIL NADPH OXIDASE; HUMAN GM-CSF; AUTOLOGOUS TRANSPLANTATION; STEM-CELLS; HEMATOPOIETIC PROGENITORS; SUPEROXIDE GENERATION; CYTOSOLIC COMPONENT AB Chronic granulomatous disease (CGD) can result from any of four single gene defects involving the components of the superoxide (O-2(-)) generating phagocyte nicotinamide adenine dinucleotide phosphate (NADPH) oxidase. We show that transduction of peripheral blood CD34(+) hematopoietic progenitors from a p67(phox) deficient CGD patient with replication defective amphotropic retrovirus encoding p67(phox) (MFGS-p67(phox)) significantly corrected the CGD functional defect in phagocyte oxidase activity in vitro. Using a chemiluminescence assay of oxidase activity, we showed that transduced patient CD34(+) progenitors differentiating to myeloid cells in culture produced 25% of the total superoxide produced by normal CD34(+) progenitors differentiating in culture. A flow cytometric assay of oxidase activity used to assess the oxidase function of individual cells in the cultures indicated that up to 32% of maturing granulocytes derived from transduced CD34(+) progenitors from the p67(phox) CGD patient were oxidase positive with the average level of correction per granulocyte of 85% of that seen with granulocytes in similar cultures of CD34(+) progenitors from normal volunteers, Nitroblue tetrazolium dye reduction assays of colonies of transduced progenitors in soft agar indicated that in some studies restoration of oxidase activity occurred in myeloid cells within 44% of granulocyte-erythrocyte-monocyte colonies, and within 28% of the combined group of granulocyte colonies/monocyte colonies/granulocyte-monocyte colonies, These high correction rates were achieved without any selective regimen to enrich for transduced cells, This study provides a basis for development of gene therapy for the p67(phox) deficient form of CGD. C1 NIAID,HOST DEF LAB,NIH,BETHESDA,MD 20892. NR 61 TC 34 Z9 35 U1 0 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD MAR 1 PY 1997 VL 89 IS 5 BP 1754 EP 1761 PG 8 WC Hematology SC Hematology GA WK477 UT WOS:A1997WK47700035 PM 9057660 ER PT J AU Altman, F AF Altman, F TI Where is the ''neuro'' in psychoneuroimmunology? A commentary on increasing research on the ''neuro'' component of psychoneuroimmunology SO BRAIN BEHAVIOR AND IMMUNITY LA English DT Editorial Material AB The role of the central nervous system in generating the interrelationships among stress, endocrine and peripheral immune function, and disease receives relatively little experimental attention. This commentary encourages a greater emphasis on such research with a particular emphasis on the use of electrophysiological and neural imaging techniques. (C) 1997 Academic Press. RP Altman, F (reprint author), NIMH,5600 FISHERS LANE,ROOM 10-104,ROCKVILLE,MD 20857, USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0889-1591 J9 BRAIN BEHAV IMMUN JI Brain Behav. Immun. PD MAR PY 1997 VL 11 IS 1 BP 1 EP 8 DI 10.1006/brbi.1997.0476 PG 8 WC Immunology; Neurosciences SC Immunology; Neurosciences & Neurology GA XD773 UT WOS:A1997XD77300001 PM 9193763 ER PT J AU DoddO, JM Zheng, GM Silverman, HS Lakatta, EG Ziegelstein, RC AF DoddO, JM Zheng, GM Silverman, HS Lakatta, EG Ziegelstein, RC TI Endothelium-independent relaxation of aortic rings by the nitric oxide synthase inhibitor diphenyleneiodonium SO BRITISH JOURNAL OF PHARMACOLOGY LA English DT Article DE diphenyleneiodonium; vasodilatation; endothelium; nitric oxide synthase; guanylate cyclase ID SMOOTH-MUSCLE CELLS; PULMONARY-ARTERY; BLOOD-PRESSURE; RAT AORTA; MACROPHAGE; PATHWAY; BRAIN AB 1 The flavoprotein binder diphenyleneiodonium (DPI) is a potent, irreversible inhibitor of nitric oxide synthase (NOS), but produces only a transient presser response following systemic administration to animals, despite evidence of persistent NOS inhibition. To characterize further the effects of DPI on vascular tone, isometric tension was recorded from rat isolated aortic rings mounted between steel wires in an organ bath. 2 The NOS inhibitor N-G-nitro-L-arginine methyl ester (L-NAME, 1 mM) initiated an additional contraction of prostaglandin F-2 alpha-preconstricted rings with endothelium which was sustained throughout the period of L-NAME exposure (+234+/-39% at 15 min). In contrast, addition of DPI (5 mu M) to rings with endothelium produced a transient initial contraction (+111+/-27% at 2 min) followed by a more sustained relaxation (-27+/-19% at 15 min, P<0.001 vs L-NAME). 3 The contraction to DPI was also observed in rings without endothelium, was abolished by L-NAME pretreatment, and was unaffected by the alpha-adrenoreceptor inhibitor prazosin. Relaxation in response to DPI was not inhibited by endothelium removal or by pretreatment with either L-NAME or with the ATP-sensitive potassium channel blocker glibenclamide. 4 The endothelium-independent relaxation to DPI was inhibited at 23 degrees C and its time course was delayed by pretreatment with the guanylate cyclase inhibitor methylene blue. 5 Thus, in addition to a transient initial contraction due to NOS inhibition, DPI produces an endothelium-independent, temperature-dependent relaxation which appears in part due to activation of guanylate cyclase. This relaxant effect of DPI may explain the transient nature of its presser effect in vivo despite sustained NOS inhibition. C1 JOHNS HOPKINS BAYVIEW MED CTR,DIV CARDIOL,DEPT MED,BALTIMORE,MD 21224. JOHNS HOPKINS UNIV HOSP,DEPT MED,DIV CARDIOL,BALTIMORE,MD 21287. JOHNS HOPKINS UNIV HOSP,DEPT ANESTHESIOL & CRIT CARE MED,BALTIMORE,MD 21287. NIA,CARDIOVASC SCI LAB,CTR GERONTOL RES,NIH,BALTIMORE,MD 21224. NR 30 TC 12 Z9 12 U1 0 U2 1 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE, HAMPSHIRE, ENGLAND RG21 6XS SN 0007-1188 J9 BRIT J PHARMACOL JI Br. J. Pharmacol. PD MAR PY 1997 VL 120 IS 5 BP 857 EP 864 DI 10.1038/sj.bjp.0701014 PG 8 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA WL161 UT WOS:A1997WL16100019 PM 9138692 ER PT J AU AlDamluji, S Porter, D Krsmanovic, LZ Knutson, JR Kopin, IJ AF AlDamluji, S Porter, D Krsmanovic, LZ Knutson, JR Kopin, IJ TI Visual detection of transport-P in peptidergic neurones SO BRITISH JOURNAL OF PHARMACOLOGY LA English DT Article DE biological transport; uptake; hypothalamus; prazosin; desipramine ID ISOLATED RAT-HEART; NEUROTRANSMITTER TRANSPORTERS; NORADRENALINE; INHIBITION; SECRETION; STEROIDS; UPTAKE2 AB 1 Hypothalamic peptidergic neurones possess an uptake process for amines (transport-P), for which prazosin is a substrate. It is characterized by a paradoxical increase in the accumulation of [H-3]-prazosin when the concentration of unlabelled prazosin is increased above 10(-7) M. This increase is due to activation of a proton-dependent, vacuolar-type ATPase-linked pump that is blocked by tricyclic antidepressants. This study utilized a fluorescence method to detect amine uptake in individual cells. 2 Prazosin is fluorescent but most of its emission spectrum is in the ultraviolet range. We therefore used an analogue of prazosin in which the furan ring had been substituted with a fluorescent group, BODIPY FL. This compound's emission maximum is in the green part of the visible spectrum. 3 BODIPY FL prazosin accumulated in immortalised peptidergic neurones and the characteristic emission spectrum of the compound was evident in these cells. Accumulation of BODIPY FL prazosin was saturable and was inhibited by the tricyclic antidepressant desipramine and by unlabelled prazosin. As previously described for prazosin, uptake of BODIPY FL prazosin was blocked by cold temperature and by the organic base chloroquine. Thus, prazosin and BODIPY FL prazosin were accumulated by the same uptake process. 4 BODIPY FL prazosin accumulated in a granular distribution, which is compatible with storage in intracellular vesicles. 5 Hypothalamic cells from foetal rats in primary culture also accumulated BODIPY FL prazosin by a desipramine-sensitive process. Uptake was predominantly in neurones and glial cells did not accumulate the amine. 6 Fluorescent detection provides visual evidence for amine uptake in peptidergic neurones and should enable detailed study of the distribution of this process in the brain. C1 NINCDS,CHEM NEUROSCI BRANCH,NIH,BETHESDA,MD 20892. NHLBI,CELL BIOL LAB,NIH,BETHESDA,MD 20892. NICHHD,ENDOCRINOL & REPROD RES BRANCH,NIH,BETHESDA,MD 20892. NR 16 TC 8 Z9 8 U1 0 U2 1 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE, HAMPSHIRE, ENGLAND RG21 6XS SN 0007-1188 J9 BRIT J PHARMACOL JI Br. J. Pharmacol. PD MAR PY 1997 VL 120 IS 5 BP 876 EP 882 DI 10.1038/sj.bjp.0700970 PG 7 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA WL161 UT WOS:A1997WL16100021 PM 9138694 ER PT J AU Post, RM Denicoff, KD Frye, MA Leverich, GS AF Post, RM Denicoff, KD Frye, MA Leverich, GS TI Re-evaluating carbamazepine prophylaxis in bipolar disorder SO BRITISH JOURNAL OF PSYCHIATRY LA English DT Editorial Material ID MANIC-DEPRESSIVE ILLNESS; REFRACTORY AFFECTIVE-DISORDERS; SODIUM VALPROATE; LITHIUM; EFFICACY; DIVALPROEX; TRIAL RP Post, RM (reprint author), NIMH,BIOL PSYCHIAT BRANCH,BLDG 10,ROOM 3N212,10 CTR DR,MSC 1272,BETHESDA,MD 20892, USA. NR 34 TC 20 Z9 21 U1 0 U2 0 PU ROYAL COLLEGE OF PSYCHIATRISTS PI LONDON PA BRITISH JOURNAL OF PSYCHIATRY 17 BELGRAVE SQUARE, LONDON, ENGLAND SW1X 8PG SN 0007-1250 J9 BRIT J PSYCHIAT JI Br. J. Psychiatry PD MAR PY 1997 VL 170 BP 202 EP 204 PG 3 WC Psychiatry SC Psychiatry GA WP367 UT WOS:A1997WP36700002 ER PT J AU Kerr, JM Hiscock, DRR Grzesik, W Robey, PG Young, MF AF Kerr, JM Hiscock, DRR Grzesik, W Robey, PG Young, MF TI The human bone sialoprotein gene contains an NF-E1/YY1 cis-acting sequence with putative regulatory activity SO CALCIFIED TISSUE INTERNATIONAL LA English DT Article DE bone sialoprotein; UMR106-01 BSP; YY1 motif; CCAAT; TATA motif ID MESSENGER-RNA EXPRESSION; TRANSCRIPTION FACTOR YY1; BINDING-SITES; MATRIX PROTEIN; PROMOTER; BSP; DNA; IDENTIFICATION; LOCALIZATION; INITIATOR AB Bone sialoprotein (BSP) is a noncollagenous matrix glycoprotein localized predominantly in mineralized tissues but also detected in extraskeletal sites undergoing focal mineralization. We have previously characterized the human BSP gene and have shown that the upstream sequence contains inverted TATA and CCAAT motifs at the expected locations from the transcriptional start site (J. M. Kerr et al. [13]) and a potential YY1 binding motif located within the first 30 bp of intron 1 of the human gene. Deletion analyses of the human BSP promoter/exon 1 sequence fused to a CAT reporter gene indicate that CCAAT enhances basal transcription of BSP in transiently transfected rat UMR106-01 BSP osteosarcoma and rat skin fibroblasts. Though this enhancing activity was lost with inclusion of 68 bp of intron containing a YY1 motif in these constructs, reporter activity in the UMR106-01-BSP cells was elevated four- to seven-fold relative to that of rat fibroblasts. Gel electrophoretic mobility shift, UV-crosslinking, and southwestern experiments indicate that YY1 is present only in the extracts of nuclei isolated from the UMR cells and may contribute to the elevated transcriptional activity of the human BSP promoter construct in UMR105-01-BSP. C1 NIDR,BONE RES BRANCH,NIH,BETHESDA,MD 20892. RI Robey, Pamela/H-1429-2011 OI Robey, Pamela/0000-0002-5316-5576 NR 40 TC 8 Z9 8 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0171-967X J9 CALCIFIED TISSUE INT JI Calcif. Tissue Int. PD MAR PY 1997 VL 60 IS 3 BP 276 EP 282 DI 10.1007/s002239900229 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA WK903 UT WOS:A1997WK90300012 PM 9069166 ER PT J AU Troisi, R Schairer, C Chow, WH Schatzkin, A Brinton, LA Fraumeni, JF AF Troisi, R Schairer, C Chow, WH Schatzkin, A Brinton, LA Fraumeni, JF TI A prospective study of menopausal hormones and risk of colorectal cancer (United States) SO CANCER CAUSES & CONTROL LA English DT Article DE colorectal cancer; hormone replacement therapy; menopausal estrogens; United States; women ID LARGE-BOWEL-CANCER; EXOGENOUS FEMALE HORMONES; COLON-CANCER; REPRODUCTIVE FACTORS; REPLACEMENT THERAPY; WOMEN; ESTROGEN; ACCURACY; HISTORY; COHORT AB The relation of colorectal cancer and its subsites with use of menopausal hormones was evaluated in the United States among 40,464 postmenopausal women, 41 to 80 years of age, who initially volunteered for a nationwide breast-cancer screening program and were followed for an average of 7.7 years. Ever-use of menopausal hormones was not associated with risk of total colorectal cancers (relative risk [RR] = 0.99, 95 percent confidence interval [CI] = 0.79-1.2) or cancers of the colon (RR = 1.1, CI = 0.81-1.6) or rectum (RR = 1.1, CI = 0.59-1.9). Recent hormone users, however, had a small nonsignificant reduction in risk of colorectal cancer (RR = 0.78, CI = 0.55-1.1), which was most pronounced for distal colon (RR = 0.68, CI = 0.29-1.6) and rectal tumors (RR = 0.64, CI = 0.24-1.7). No effect was observed for former hormone users, and risk generally did not vary by time since last use, type of regimen, or duration of use. However, the reduced risk for recent users was stronger for users of five or more years' duration. These data show some lowering of colorectal cancer risk among recent menopausal hormone users of long duration. C1 NCI,ENVIRONM EPIDEMIOL BRANCH,DIV CANC PREVENT & CONTROL,BETHESDA,MD 20892. RP Troisi, R (reprint author), NCI,ENVIRONM EPIDEMIOL BRANCH,DIV CANC EPIDEMIOL & GENET,EXECUT PLAZA N ROOM 443,BETHESDA,MD 20892, USA. RI Brinton, Louise/G-7486-2015 OI Brinton, Louise/0000-0003-3853-8562 NR 28 TC 61 Z9 61 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 1997 VL 8 IS 2 BP 130 EP 138 DI 10.1023/A:1018455810238 PG 9 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA WU351 UT WOS:A1997WU35100003 PM 9134236 ER PT J AU Zahm, SH Weisenburger, DD Holmes, FF Cantor, KP Blair, A AF Zahm, SH Weisenburger, DD Holmes, FF Cantor, KP Blair, A TI Tobacco and non-Hodgkin's lymphoma: Combined analysis of three case-control studies (United States) SO CANCER CAUSES & CONTROL LA English DT Article DE case-control studies; non-Hodgkin's lymphoma; smoking; tobacco; United States ID SOFT-TISSUE SARCOMA; AGRICULTURAL RISK-FACTORS; HAIR COLORING PRODUCTS; MALE BRITISH DOCTORS; CIGARETTE-SMOKING; MULTIPLE-MYELOMA; FOLLOW-UP; LEUKEMIA; MORTALITY; VETERANS AB The role of tobacco in the etiology of non-Hodgkin's lymphoma (NHL) was evaluated in a combined analysis of data from three population-based case-control studies conducted in four midwestern states of the United States: Nebraska, Iowa, Minnesota, and Kansas. Interviews were obtained from 1,177 cases (993 men, 184 women) and 3,625 controls (2,918 men, 707 women) or, if deceased, from their next-of-kin. Overall, there was no association between NHL and tobacco use (odds ratio [OR] = 1.0, 95 percent confidence interval [CI] = 0.8-1.1) or cigarette smoking (OR = 1.0, CI = 0.8-1.1). A slight negative association evident in analyses by intensity and duration of smoking was not present when interviews from proxy respondents were eliminated. There was a suggestion of a positive association between smoking and NHL among women (OR = 1.3, CI = 0.9-1.9), although there was no clear exposure-response relationship. This large case-control analysis provides no evidence that smoking is linked to the development of NHL among men. The possible role of smoking in the etiology of NHL among women needs further evaluation. C1 UNIV NEBRASKA, MED CTR, DEPT PATHOL & MICROBIOL, OMAHA, NE USA. UNIV KANSAS, MED CTR, DEPT INTERNAL MED, KANSAS CITY, KS 66103 USA. RP Zahm, SH (reprint author), NCI, OCCUPAT EPIDEMIOL BRANCH, DIV CANC EPIDEMIOL & GENET,EXECUT PLAZA N, ROOM 418, 6130 EXECUT BLVD, ROCKVILLE, MD 20892 USA. NR 48 TC 49 Z9 50 U1 3 U2 4 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0957-5243 EI 1573-7225 J9 CANCER CAUSE CONTROL JI Cancer Causes Control PD MAR PY 1997 VL 8 IS 2 BP 159 EP 166 DI 10.1023/A:1018412027985 PG 8 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA WU351 UT WOS:A1997WU35100006 PM 9134239 ER PT J AU ProbstHensch, NM Sinha, R Longnecker, MP Witte, JS Ingles, SA Frankl, HD Lee, ER Haile, RW AF ProbstHensch, NM Sinha, R Longnecker, MP Witte, JS Ingles, SA Frankl, HD Lee, ER Haile, RW TI Meat preparation and colorectal adenomas in a large sigmoidoscopy-based case-control study in California (United States) SO CANCER CAUSES & CONTROL LA English DT Article DE adenoma; amines; colon; meat-products; mutagens; United States ID HETEROCYCLIC AMINE CARCINOGENS; COVALENT DNA-BINDING; COLON-CANCER; METABOLIC-ACTIVATION; FAMILY HISTORY; COOKED FOODS; FRIED FOODS; RISK; DIET; POLYPS AB The often observed association between red meat and colorectal cancer could be due in part to mutagens, such as heterocyclic amines (HCA), that are present in cooked meat. HCAs are highly mutagenic and cause intestinal tumors in animals. The hypothesis that HCAs are also carcinogenic to humans remains to be substantiated in epidemiologic studies. We determined the associations of meat preparation and frequency of intake (proxy variables for HCA exposure, since HCA concentration depends on the type of meat and the way it is cooked) with the prevalence of distal colorectal adenomas in a sigmoidoscopy-based case-control study of 488 matched pairs of subjects from two California (United States) Kaiser Permanente Medical Centers. A more than twofold difference in adenoma prevalence between subjects at extreme ends of estimated HCA intake was observed. For subjects who ate red meat more than once per week, fried it more than 10 percent of the time, and ate it with a darkly browned surface, compared with subjects who ate red meat one time or less per week, fried it 10 or less percent of the time, and ate it with a lightly browned surface, the odds ratio was 2.2 (95 percent confidence interval = 1.1-4.3). Adenoma prevalence also increased with frequency of frying red meat (P trend = 0.004). These results are consistent with a carcinogenic effect of HCA. C1 UNIV SO CALIF,KENNETH NORRIS JR COMPREHENS CANC CTR,DEPT PREVENT MED,LOS ANGELES,CA 90033. NCI,NUTR EPIDEMIOL SECT,EPIDEMIOL BIOSTAT PROGRAM,NIH,ROCKVILLE,MD. NIEHS,EPIDEMIOL BRANCH,RES TRIANGLE PK,NC 27709. CASE WESTERN RESERVE UNIV,SCH MED,DEPT BIOSTAT & EPIDEMIOL,CLEVELAND,OH 44106. KAISER PERMANENTE,DEPT GASTROENTEROL,LOS ANGELES,CA. RI Sinha, Rashmi/G-7446-2015; OI Sinha, Rashmi/0000-0002-2466-7462; Longnecker, Matthew/0000-0001-6073-5322 FU NCI NIH HHS [CA51923, CA63699] NR 54 TC 80 Z9 81 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 1997 VL 8 IS 2 BP 175 EP 183 DI 10.1023/A:1018416128894 PG 9 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA WU351 UT WOS:A1997WU35100008 PM 9134241 ER PT J AU Boice, JD Friis, S McLaughlin, JK Mellemkjaer, L Blot, WJ Fraumeni, JF Olsen, JH AF Boice, JD Friis, S McLaughlin, JK Mellemkjaer, L Blot, WJ Fraumeni, JF Olsen, JH TI Cancer following breast reduction surgery in Denmark SO CANCER CAUSES & CONTROL LA English DT Article DE breast cancer; breast reduction surgery; cohort study; Denmark ID MAMMOGRAPHIC PATTERNS; RISK-FACTORS; MAMMAPLASTY; LATERALITY; CARCINOMA; SIZE; MASS; AGE AB Intuitively, breast tissue mass should be directly related to a woman's risk of breast cancer, simply because having more cells at risk would seem to increase the potential for malignant transformation. However, studies attempting to link breast size with breast cancer risk have been inconsistent. Limitations include crude measures of breast size, the inability to distinguish glandular from adipose tissue, and the confounding influence of co-factors such as obesity. A nationwide study in Denmark was undertaken to investigate the effect of breast reduction surgery on the subsequent risk of breast cancer, including an evaluation of the patterns of risk by age and time since surgery. The Danish Hospital Discharge Registry was used to identify women who underwent reduction mammaplasty between 1977 and 1992. Linkage based on personal identification numbers with the Danish Cancer Registry provided information on cancer incidence. Expected numbers of cancers were calculated from rates in the general population. Among 7,720 women whose breasts were surgically reduced, 182 cancers were subsequently observed cf 209 expected (standardized incidence ratio [SIR] = 0.9;95 percent confidence interval[cr] = 0.7-1.0). Breast cancer was significantly reduced by nearly 50 percent (29 observed cf 53.9 expected, SIR = 0.5, CI = 0.4-0.8), and accounted for the overall deficit in cancer. The risk reductions were related inversely to age at surgery, with significant deficits apparent only among women 40 years of age and older at surgery and especially among those over age 50 (SIR = 0.3). No clear trend was apparent with increasing years post-surgery. The findings indicate that breast reduction surgery among women over age 40 is associated with a lower subsequent risk of breast cancer, but the surgery and presumably glandular mass appear less closely related to breast cancer risk among younger women. C1 DANISH CANC SOC,DIV CANC EPIDEMIOL,COPENHAGEN,DENMARK. NCI,DIV CANC EPIDEMIOL & GENET,BETHESDA,MD 20892. RP Boice, JD (reprint author), INT EPIDEMIOL INST,1550 RES BLVD,ROCKVILLE,MD 20850, USA. NR 37 TC 33 Z9 33 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 1997 VL 8 IS 2 BP 253 EP 258 DI 10.1023/A:1018484616598 PG 6 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA WU351 UT WOS:A1997WU35100017 PM 9134250 ER PT J AU EricksonMiller, CL May, RD Tomaszewski, J Osborn, B Murphy, MJ Page, JG Parchment, RE AF EricksonMiller, CL May, RD Tomaszewski, J Osborn, B Murphy, MJ Page, JG Parchment, RE TI Differential toxicity of camptothecin, topotecan and 9-aminocamptothecin to human, canine, and murine myeloid progenitors (CFU-GM) in vitro SO CANCER CHEMOTHERAPY AND PHARMACOLOGY LA English DT Article DE pharmacodynamics; topoisomerase I; hematopoiesis; neutropenia; myelosuppression ID TOPOISOMERASE-I INHIBITOR; PHASE-I; SOLID TUMORS; INVITRO MYELOTOXICITY; ANTITUMOR-ACTIVITY; CLINICAL-TRIAL; CELLS-INVITRO; XENOGRAFTS; ANALOGS; CANCER AB Purpose: 20(S)-Camptothecin (CAM), topotecan (TPT, active ingredient in Hycamtin) and 9-amino-20(S)camptothecin (9AC) are topoisomerase I inhibitors that cause similar dose-limiting toxicities to rapidly renewing tissues, such as hematopoietic tissues, in humans, mice, and dogs. However, dose-limiting toxicity occurs at tenfold lower doses in humans than in mice. The purpose of the current study was to determine whether hematopoietic progenitors of the myeloid lineage from humans, mice, and dogs exhibit the differential sensitivity to these compounds that is evident in vivo. Methods: Drug-induced inhibition of in vitro colony formation by a myeloid progenitor in human, murine, and canine marrow colony-forming unit-granulocyte/macrophage (CFU-GM) provided the basis for interspecies comparisons at concentrations which inhibited colony formation by 50% (IC50) and 90% (IC90). Results: Murine IC90 values were 2.6-, 2.3-, 10-, 21-, 5.9-, and 11-fold higher than human values for CAM lactone (NSC-94600) and sodium salt (NSC-100880), TPT (NSC-609699), and racemic (NSC-629971), semisynthetic and synthetic preparations (NSC-603071) of 9AC, respectively. In contrast, canine IC90 values were the same as, or lower than, the human IC90 values for all six compounds. Conclusions: The greater susceptibility of humans and dogs to the myelotoxicity of camptothecins, compared to mice, was evident in vitro at the cellular level. Differential sensitivity between murine and human myeloid progenitors explains why the curative doses of TPT and 9AC in mice with human tumor xenografts are not achievable in patients. Realizing the curative potential of these compounds in humans will require the development of therapies to increase drug tolerance of human CFU-GM at least to a level equal to that of murine CFU-GM. Because these interspecies differences are complicated by species-specific effects of plasma proteins on drug stability, not all in vitro assay conditions will yield results which can contribute to the development of such therapies. C1 WAYNE STATE UNIV,DIV HEMATOL ONCOL,DETROIT,MI 48201. HIPPLE CANC RES CTR,DAYTON,OH 45439. SO RES INST,CELL BIOL & IMMUNOL GRP,BIRMINGHAM,AL 35205. NCI,TOXICOL & PHARMACOL BRANCH,DTP,DCTDC,NIH,BETHESDA,MD 20892. SO RES INST,PRECLIN TOXICOL DIV,BIRMINGHAM,AL 35205. FU NCI NIH HHS [N01-CM-87259, CM-07361] NR 40 TC 80 Z9 82 U1 0 U2 1 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0344-5704 J9 CANCER CHEMOTH PHARM JI Cancer Chemother. Pharmacol. PD MAR PY 1997 VL 39 IS 5 BP 467 EP 472 DI 10.1007/s002800050600 PG 6 WC Oncology; Pharmacology & Pharmacy SC Oncology; Pharmacology & Pharmacy GA WJ509 UT WOS:A1997WJ50900013 PM 9054963 ER PT J AU Rugge, M Bovo, D Busatto, G Parenti, AR Fawzy, S Guido, M Ancona, E Ninfo, V Ruol, A Shiao, YH AF Rugge, M Bovo, D Busatto, G Parenti, AR Fawzy, S Guido, M Ancona, E Ninfo, V Ruol, A Shiao, YH TI p53 alterations but no human papillomavirus infection in preinvasive and advanced squamous esophageal cancer in Italy SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID POLYMERASE CHAIN-REACTION; TUMOR-SUPPRESSOR GENE; IN-SITU HYBRIDIZATION; CELL CARCINOMAS; PRECANCEROUS LESIONS; UTERINE CERVIX; HIGH-RISK; DNA; PROTEIN; MUTATIONS AB Geographic differences in exposure to suspected carcinogens have been identified in esophageal carcinogenesis, and both p53 alterations and human papillomavirus (HPV) infection have been reported in esophageal squamous carcinoma (ESC) from high-risk areas, including China and South Africa. The status of p53 alterations and HPV infection in ESC has not been determined in northern Italy, where the incidence of ESC is low. Formalin-fixed paraffin-embedded esophageal samples containing normal, dysplastic, and carcinomatous tissue from 18 patients were examined for p53 protein accumulation with immunohistochemistry, p53 mutation (exons 5-8) with PCR-single-strand conformation polymorphism analysis and DNA sequencing, and HPV infection with PCR using general primers to amplify the L1 gene. Accumulation of p53 protein was observed in both precancerous and carcinomatous lesions. p53 mutations were rare in dysplastic lesions but were detected in 9 of 18 carcinomas, a finding consistent with reports from other geographic areas. Examination of the p53 mutation spectrum revealed no hot spot mutation. In contrast, HPV was not found in any of these 18 cases. This is consistent with the findings from other low ESC risk areas in which HPV infection may not play a crucial role in esophageal oncogenesis, whereas the high risk of ESC in China and South Africa may be attributed to frequent HPV infection. C1 UNIV PADUA,CATTEDRA ANAT PATOL 3,I-35121 PADUA,ITALY. UNIV PADUA,CATTEDRA PATOL CHIRURG,I-35121 PADUA,ITALY. TANTA UNIV,DEPT GENET,KAFREL SHEIKA,EGYPT. NCI,FREDERICK CANC RES & DEV CTR,COMPARAT CARCINOGENESIS LAB,NIH,FREDERICK,MD 21702. RP Rugge, M (reprint author), UNIV PADUA,DEPT PATHOL,CATTEDRA ISTOCHIM & IMMUNOISTOCHIM PATOL,VIA A GABELLI 61,I-35121 PADUA,ITALY. RI Rugge, Massimo/K-7525-2016 NR 51 TC 27 Z9 27 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 1997 VL 6 IS 3 BP 171 EP 176 PG 6 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA WN244 UT WOS:A1997WN24400004 PM 9138659 ER PT J AU Dorgan, JF Stanczyk, FZ Longcope, C Stephenson, HE Chang, L Miller, R Franz, C Falk, RT Kahle, L AF Dorgan, JF Stanczyk, FZ Longcope, C Stephenson, HE Chang, L Miller, R Franz, C Falk, RT Kahle, L TI Relationship of serum dehydroepiandrosterone (DHEA), DHEA sulfate, and 5-androstene-3 beta,17 beta-diol to risk of breast cancer in postmenopausal women SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID ALCOHOL-CONSUMPTION; CELLS; METABOLISM; MCF-7; GROWTH; C-19-DELTA-5-STEROIDS; ESTRADIOL; SECRETION; FEMALES; GLAND AB Laboratory evidence suggests a role for dehydroepiandrosterone (DHEA) and its metabolite 5-androstene-3 beta,17 beta-diol (ADIOL) in mammary tumor growth. Serum DHEA also has been related to breast cancer in postmenopausal women, but the relationship of ADIOL to risk has not been evaluated previously. To assess the relationship of serum DHEA, its sulfate (DHEAS), and ADIOL with breast cancer risk in postmenopausal women, we conducted a prospective nested case-control study using serum from the Columbia, MO Breast Cancer Serum Bank. Cases included 71 healthy postmenopausal volunteers not taking replacement estrogens when they donated blood and who were diagnosed with breast cancer up to 10 years later (median, 2.9 years). Two randomly selected controls, who also were postmenopausal and not taking estrogens, were matched to each case on exact age, date (+/-1 year), and time (+/-2 h) of blood collection. Significant (trend P = 0.02) gradients of increasing risk of breast cancer were observed for increasing concentrations of DHEA and ADIOL, and women whose serum levels of these hormones were in the highest quartiles were at a significantly elevated risk compared to those in the lowest; their risk ratios were 4.0 (95% confidence interval (CI), 1.3-11.8) and 3.0 (95% CI, 1.0-8.6), respectively. The relationship of DHEAS to breast cancer was less consistent, but women whose serum DHEAS concentration was in the highest quartile also exhibited a significantly elevated risk ratio of 2.8 (95% CI, 1.1-7.4). Results of this prospective study support a role for the adrenal androgens, DHEA, DHEAS, and ADIOL, in the etiology of breast cancer. C1 UNIV SO CALIF,SCH MED,WOMENS HOSP,DEPT OBSTET & GYNECOL,LOS ANGELES,CA 90033. UNIV MASSACHUSETTS,SCH MED,DEPT OBSTET & GYNECOL,WORCESTER,MA 01655. UNIV MASSACHUSETTS,SCH MED,DEPT MED,WORCESTER,MA 01655. UNIV MISSOURI,HLTH SCI CTR,DEPT SURG,COLUMBIA,MO 65212. ELLIS FISCHEL CANC CTR,CANC SCREENING SERV,COLUMBIA,MO 65203. NCI,DIV CANC ETIOL & GENET,NIH,BETHESDA,MD 20892. INFORMAT MANAGEMENT SERV INC,SILVER SPRING,MD 20904. RP Dorgan, JF (reprint author), NCI,DIV CANC PREVENT & CONTROL,NIH,EXECUT PLAZA N,ROOM 211,6130 EEXCUT BLVD,BETHESDA,MD 20892, USA. NR 34 TC 93 Z9 94 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 1997 VL 6 IS 3 BP 177 EP 181 PG 5 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA WN244 UT WOS:A1997WN24400005 PM 9138660 ER PT J AU Strickler, HD Schiffman, MH Eklund, C Glass, AG Scott, DR Sherman, ME Wacholder, S Kurman, RJ Manos, MM Schiller, JT Dillner, J AF Strickler, HD Schiffman, MH Eklund, C Glass, AG Scott, DR Sherman, ME Wacholder, S Kurman, RJ Manos, MM Schiller, JT Dillner, J TI Evidence for at least two distinct groups of humoral immune reactions to papillomavirus antigens in women with squamous intraepithelial lesions SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID ANAL EPIDERMOID CARCINOMA; CERVICAL-CANCER; CONFORMATIONAL EPITOPES; ANTIBODIES; TYPE-16; INFECTION; NEOPLASIA; PROSPECTS; PROTEINS; SERA AB Serological markers of squamous intraepithelial lesions (SILs), the precursors of cervical cancer, have not been studied extensively. To screen for antibody responses that might be associated with SILs, we measured IgG and/or IgA to nine antigens based on papillomaviruses, the infectious cause of SIL and cervical cancer, using an ELISA format. Cases were 59 women with low grade SIL (LSIL) and 38 with high grade SIL (HSIL), Controls were 50 women chosen to minimize the possibility that they ever had SILs [individuals who had no history of SIL and repeatedly tested negative for cervical human papillomavirus (HPV) DNA], frequency age-matched to cases. The data showed that five antibodies had strong positive associations with SILs and that one was inversely related to SILs. By studying these antibodies in pairs, furthermore, we found that case-control differences were enhanced. In particular, the combination of IgG to an epitope in the E6 protein of HPV 16 (E6:10) and IgA to HPV 16 virus-like particles (VLPs) was detected in 53% of LSILs and 65% of HSILs but only 9% of controls, These same responses were both negative in just 6% of LSILs and zero HSILs, compared to 59% of controls. Notably, E6:10 IgG and HPV 16 VLP IgA were not correlated with each other, and the other antibody responses positively associated with SILs could be broken into two groups: those correlated with E610 IgG and those correlated with HPV 16 VLP IgA. Overall, the data suggest that several papillomavirus antibodies may be strongly related to SILs, and that they can be divided into at least two independent groups of humoral immune reactions. C1 KAROLINSKA INST,STOCKHOLM,SWEDEN. KAISER PERMANENTE,PORTLAND,OR 97227. GEORGE WASHINGTON UNIV,WASHINGTON,DC 20037. JOHNS HOPKINS UNIV,BALTIMORE,MD 21287. CETUS CORP,EMERYVILLE,CA 94608. RP Strickler, HD (reprint author), NCI,VIRAL EPIDEMIOL BRANCH,NIH,EPN 434,6130 EXECUT BLVD,BETHESDA,MD 20892, USA. NR 27 TC 13 Z9 13 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 1997 VL 6 IS 3 BP 183 EP 188 PG 6 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA WN244 UT WOS:A1997WN24400006 PM 9138661 ER PT J AU Li, ZW Shanmugam, N Katayose, D Huber, B Srivastava, S Cowan, K Seth, P AF Li, ZW Shanmugam, N Katayose, D Huber, B Srivastava, S Cowan, K Seth, P TI Enzyme/prodrug gene therapy approach for breast cancer using a recombinant adenovirus expressing Escherichia coli cytosine deaminase SO CANCER GENE THERAPY LA English DT Article DE gene transfer; 5-fluorocytosine; 5-fluorouracil; cancer; suicide gene; viral vectors; nonmammalian enzyme ID IN-VIVO; COLORECTAL-CARCINOMA; 5-FLUOROCYTOSINE; VECTORS AB A recombinant adenovirus expressing Escherichia coli cytosine deaminase (AdCD) was constructed with the purpose of exploring its utility for the treatment of breast cancer. Infection of the human breast cancer cell line, MDA-MB-231, with AdCD resulted in high levels of cytosine deaminase enzyme activity. MDA-MB-231 cells infected with AdCD were 1000-fold more sensitive to 5-fluorocytosine (5-FC) than cells infected with a control adenovirus. Cell mixing experiments indicated that only 10% of AdCD-infected cells in a population were needed to induce complete cytotoxicity of noninfectious cells exposed to 5-FC. This suggests that bystander effects play an important role in AdCD-mediated cytotoxicities. Direct injection of AdCD into human breast MDA-MB-231-derived tumors grown as xenografts in nude mice, followed by daily intraperitoneal injection of 5-FC was sufficient to inhibit tumor growth. These results suggest that in vivo gene therapy for breast cancer using AdCD is feasible. C1 NCI, MED BREAST CANC SECT, MED BRANCH, NIH, BETHESDA, MD 20892 USA. GLAXO WELLCOME INC, DIV PHARMACOL, RES TRIANGLE PK, NC 27709 USA. UNIFORMED SERV UNIV HLTH SCI, DEPT SURG, BETHESDA, MD 20814 USA. NR 17 TC 42 Z9 50 U1 1 U2 2 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0929-1903 EI 1476-5500 J9 CANCER GENE THER JI Cancer Gene Ther. PD MAR-APR PY 1997 VL 4 IS 2 BP 113 EP 117 PG 5 WC Biotechnology & Applied Microbiology; Oncology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Oncology; Genetics & Heredity; Research & Experimental Medicine GA WN569 UT WOS:A1997WN56900005 PM 9080120 ER PT J AU Turley, JM Fu, T Ruscetti, FW Mikovits, JA Bertolette, DC BirchenallRoberts, MC AF Turley, JM Fu, T Ruscetti, FW Mikovits, JA Bertolette, DC BirchenallRoberts, MC TI Vitamin E succinate induces Fas-mediated apoptosis in estrogen receptor-negative human breast cancer cells SO CANCER RESEARCH LA English DT Article ID ALPHA-TOCOPHERYL SUCCINATE; GROWTH-FACTOR-BETA; PROTEIN-KINASE-C; TUMOR-NECROSIS-FACTOR; B-16 MELANOMA-CELLS; ANTI-FAS; PROMYELOCYTIC LEUKEMIA; DOWN-REGULATION; RETINOIC ACID; H-RAS AB Vitamin E succinate (VES), a derivative of the fat-soluble vitamin D-alpha-tocopherol (vitamin E), inhibited growth and induced apoptotic cell death of estrogen receptor-negative human breast cancer cells, VES-induced apoptosis in MDA-MB-231 and SKBR-3 cells occurred through a Fas pathway, Total protein levels of the Fas receptor (Fas; APO-1/CD-95) and the Fas Ligand (Fas-L) were increased following VES treatment, In addition, VES increased cell surface Fas expression, Fas-neutralizing antibodies and Fas-L antisense oligonucleotides blocked VES-induced apoptosis, The presence of Fas-L antisense oligonucleotides also completely blocked the VES-mediated increase in Fas-L protein expression. These data indicate a role for Fas signaling in VES-mediated apoptotic cell death of human breast cancer cells. These findings also suggest that VES may be of clinical use in the treatment of aggressive human breast cancers, particularly those that are refractory to antiestrogen therapy. C1 NCI, LAB LEUKOCYTE BIOL, DIV BASIC SCI, FREDERICK, MD 21702 USA. NCI, FREDERICK CANC RES & DEV CTR, INTRAMURAL RES SUPPORT PROGRAM, APPLICAT INT CORP, FREDERICK, MD 21702 USA. NR 61 TC 105 Z9 117 U1 0 U2 3 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD MAR 1 PY 1997 VL 57 IS 5 BP 881 EP 890 PG 10 WC Oncology SC Oncology GA WK897 UT WOS:A1997WK89700020 PM 9041190 ER PT J AU Bright, RK Vocke, CD EmmertBuck, MR Duray, PH Solomon, D Fetsch, P Rhim, JS Linehan, WM Topalian, SL AF Bright, RK Vocke, CD EmmertBuck, MR Duray, PH Solomon, D Fetsch, P Rhim, JS Linehan, WM Topalian, SL TI Generation and genetic characterization of immortal human prostate epithelial cell lines derived from primary cancer specimens SO CANCER RESEARCH LA English DT Article ID TUMOR-INFILTRATING LYMPHOCYTES; ALLELIC LOSS; SUPPRESSOR GENE; LOCI; IMMUNOTHERAPY; CHROMOSOME-8; CARCINOMA; DELETION; DNA AB Difficulty in establishing long-term human prostate epithelial cell lines has impeded efforts to understand prostate tumorigenesis and to develop alternative therapies for prostate cancer, In the current study, we describe a method that was successful in generating 14 immortal benign or malignant prostate epithelial cell cultures from primary adenocarcinomas of the prostate resected from sir successive patients, Immortalization with the E6 and E7 transforming proteins of human papilloma virus serotype 16 was necessary to establish long-term cultures, Microscopic examination of fresh tumor specimens exhibited a variable mixture of benign and malignant epithelium. Thus, single-cell cloning of tumor-derived cell cultures was essential for defining tumor cell lines, Efforts to characterize these cultures using traditional criteria such as karyotype, growth in nude mice, and prostate-specific antigen expression were noninformative, However, allelic Loss of heterozygosity (LOH) represents a powerful alternative method for characterizing tumor cell lines originating from primary adenocarcinomas of the prostate, Microdissected fresh tumors from four of sis patients revealed LOH at multiple loci on chromosome 8p, as assessed by PCR, LOH on chromosome 8p matching the patterns found in microdissected tumors was also observed in a tumor-derived cell line and its clones, as well as in one clone from a tumor-derived cell line from a second patient, LOH was not observed in immortal lines generated from autologous benign prostatic epithelium, seminal vesicle epithelium, or fibroblasts, The multifocal nature of prostate cancer, as well as the presence of an entire spectrum of malignant transformation within individual prostate glands, necessitates this type of careful analysis of derivative cell cultures for their validation as in vitro models that accurately reflect the primary cancers from which they are derived. C1 NCI,SURG BRANCH,PATHOL LAB,LAB MOL ONCOL,NIH,BETHESDA,MD 20892. NR 32 TC 126 Z9 127 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 1997 VL 57 IS 5 BP 995 EP 1002 PG 8 WC Oncology SC Oncology GA WK897 UT WOS:A1997WK89700036 PM 9041206 ER PT J AU Mooney, LA Bell, DA Santella, RM VanBennekum, AM Ottman, R Paik, M Blaner, WS Lucier, GW Covey, L Young, TL Cooper, TB Glassman, AH Perera, FP AF Mooney, LA Bell, DA Santella, RM VanBennekum, AM Ottman, R Paik, M Blaner, WS Lucier, GW Covey, L Young, TL Cooper, TB Glassman, AH Perera, FP TI Contribution of genetic and nutritional factors to DNA damage in heavy smokers SO CARCINOGENESIS LA English DT Article ID S-TRANSFERASE M1; LUNG-CANCER; CYP1A1 GENE; FOUNDRY WORKERS; ADDUCT LEVELS; VITAMIN-C; SUSCEPTIBILITY; GLUTATHIONE; POLYMORPHISM; SMOKING AB Prior epidemiological evidence suggests that genes controlling the metabolism of carcinogens and antioxidant/nutritional status are associated with lung cancer risk, possibly through their ability to modulate DNA damage by carcinogens. We performed a cross-sectional analysis of 159 heavy smokers from a cohort of subjects enrolled in a smoking cessation program. A total of 159 blood samples were analyzed to determine the relative contributions of genetic polymorphisms [CYP1A1 MspI and exon 7 and glutathione S-transferase M1 (GSTM1)] and plasma micronutrients to polycyclic aromatic hydrocarbon-DNA (PAH-DNA) adduct levels. DNA damage in smokers was affected by genetic polymorphisms and nutritional status. Smokers with the CYP1A1 exon 7 valine polymorphism had significantly higher (2-fold, P less than or equal to 0.03) levels of DNA damage than those without. In parallel models, PAH-DNA adducts were inversely associated with plasma levels of retinol (beta = -0.93, P = 0.01), beta-carotene (P = -0.18, P = 0.09), and a-tocopherol (beta = -0.28, P = 0.21) in 159 subjects. The association between smoking-adjusted plasma beta-carotene levels and DNA damage was only significant in those subjects lacking the GSTM1 detoxification gene (beta = -0.30, P = 0.05, n = 75). There was a statistical interaction between beta-carotene and alpha-tocopherol; when beta-carotene was low, alpha-tocopherol had a significant protective effect (beta = -0.78, P = 0.04) on adducts, but not when beta-carotene was high (P = -0.16, P = 0.57). Plasma alpha-tocopherol was significantly correlated with beta-carotene (r = 0.36, P = 0.0005) and less strongly with retinol (r = 0.20, P = 0.0005). These results suggest that several micronutrients may act in concert to protect against DNA damage and highlight the importance of assessing overall antioxidant status. In conclusion, a subset of smokers may be at increased risk of DNA damage and possibly lung cancer due to the combined effect of low plasma micronutrients and genetic susceptibility factors. The use of biological markers to assess efficacy of interventions and to study mechanisms of micronutrients is timely given the current debate regarding the use of chemopreventive agents in high risk populations. C1 COLUMBIA UNIV,SCH PUBL HLTH,DIV ENVIRONM HLTH SCI,NEW YORK,NY 10032. NIEHS,RES TRIANGLE PK,NC 27709. COLUMBIA UNIV,INST HUMAN NUTR,NEW YORK,NY 10032. NEW YORK STATE PSYCHIAT INST & HOSP,NEW YORK,NY 10032. RI Ottman, Ruth/O-2371-2013; OI Mooney, LaVerne A./0000-0003-1120-356X FU NCI NIH HHS [CA13696]; NIDA NIH HHS [5-R-DA04732]; NIEHS NIH HHS [1-PO1-ESO5294] NR 54 TC 125 Z9 126 U1 0 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD, ENGLAND OX2 6DP SN 0143-3334 J9 CARCINOGENESIS JI Carcinogenesis PD MAR PY 1997 VL 18 IS 3 BP 503 EP 509 DI 10.1093/carcin/18.3.503 PG 7 WC Oncology SC Oncology GA WN637 UT WOS:A1997WN63700008 PM 9067549 ER PT J AU Witschi, H Espiritu, I Peake, JL Wu, K Maronpot, RR Pinkerton, KE AF Witschi, H Espiritu, I Peake, JL Wu, K Maronpot, RR Pinkerton, KE TI The carcinogenicity of environmental tobacco smoke SO CARCINOGENESIS LA English DT Article ID STRAIN-A MICE; PULMONARY TUMOR RESPONSE; DIETARY BUTYLATED HYDROXYTOLUENE; CIGARETTE SIDESTREAM SMOKE; CELL-KINETICS; MOUSE LUNG; RESPIRATORY-TRACT; HEPATIC CYTOCHROME-P450; SUBCHRONIC INHALATION; CALORIC RESTRICTION AB Male strain A/J mice were exposed for 6 h a day, 5 days a week to environmental tobacco smoke (ETS) generated from Kentucky 1R4F reference cigarettes, Chamber concentrations were 87 mg/m(3) of total suspended particulate matter (TSP), 246 p.p.m. of CO and 16 mg/m(3) of nicotine, After 5 months, 33% of the ETS exposed and 11% of the control animals had one or several lung tumors; the difference was statistically not significant, A second group of animals exposed for 5 months to ETS was allowed to recover for another 4 months in filtered air, When they were killed, 85% of the ETS animals had lung tumors (average number per lung: 1.4 +/- 0.2), whereas in the control group 38% had lung tumors (average number of lung tumors in all animals 0.5 +/- 0.2), The differences in tumor incidence and multiplicity were statistically significant. More than 80% of all tumors were adenomas, the rest adenocarcinomas. When animals were pretreated with a carcinogen, lung tumor multiplicity was lower in the ETS exposed animals after 5 months compared,vith controls injected with a carcinogen and kept in air. However, after an additional 4 month recovery period in air, lung tumor multiplicities were the same in ETS plus carcinogen exposed mice as in carcinogen-treated air-exposed controls, Histopathologic and morphometric analysis of the lung tissue failed to reveal any differences between ETS exposed and control animals, However, immediately after ETS exposure, immunohistochemistry revealed increased staining for CYP1A1 in airway epithelia and lung parenchyma; following recovery in air, the staining disappeared again, Analysis of cell kinetics showed an initial burst of increased DNA synthesis in the epithelial cells of the airways and a smaller early positive response in the parenchyma, Feeding of butylated hydroxytoluene during ETS exposure did not modulate lung tumor development, It was concluded that ETS is a pulmonary carcinogen in strain A/J mice. C1 NIEHS, RES TRIANGLE PK, NC 27709 USA. SCH VET MED, DEPT MOL BIOSCI, RES TRIANGLE PK, NC USA. SCH VET MED, DEPT ANAT PHYSIOL & CELL BIOL, RES TRIANGLE PK, NC USA. RP Witschi, H (reprint author), UNIV CALIF DAVIS, INST TOXICOL & ENVIRONM HLTH, DAVIS, CA 95616 USA. FU NIEHS NIH HHS [ES-05707] NR 78 TC 114 Z9 116 U1 0 U2 3 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0143-3334 J9 CARCINOGENESIS JI Carcinogenesis PD MAR PY 1997 VL 18 IS 3 BP 575 EP 586 DI 10.1093/carcin/18.3.575 PG 12 WC Oncology SC Oncology GA WN637 UT WOS:A1997WN63700018 PM 9067559 ER PT J AU Hasegawa, M Nagao, K Kinoshita, Y Rodbard, D Asahina, A AF Hasegawa, M Nagao, K Kinoshita, Y Rodbard, D Asahina, A TI Increased pulse wave velocity and shortened pulse wave transmission time in hypertension and aging SO CARDIOLOGY LA English DT Article DE pulse wave velocity; pulse transmission time; hypertension; aging; carotid phonoarteriography ID ARTERIAL AB We measured pulse wave velocity (PWV) and pulse transmission time (PTT) in 29 patients with hypertension, ranging in age from 37 to 73 years, in a series of 36 normal subjects with the same age range, and in an additional series of 44 normal subjects aged 18-35 years. PWV increases linearly with age for both normal subjects and patients with hypertension, with a corresponding significant decrease in PTT. There was a statistically highly significant (p < 0.001) increase in PWV in hypertension at all ages examined, The present simple noninvasive methods may be useful when evaluating risk factors for atherosclerosis and when evaluating response to therapeutic intervention. C1 NIH,DIV COMP RES & TECHNOL,BETHESDA,MD 20892. CHIBA UNIV,HLTH SCI CTR,CHIBA,JAPAN. NR 13 TC 17 Z9 17 U1 0 U2 3 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0008-6312 J9 CARDIOLOGY JI Cardiology PD MAR-APR PY 1997 VL 88 IS 2 BP 147 EP 151 DI 10.1159/000177321 PG 5 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA WP260 UT WOS:A1997WP26000004 PM 9096914 ER PT J AU Bird, GSJ Obie, JF Putney, JW AF Bird, GSJ Obie, JF Putney, JW TI Effect of cytoplasmic Ca2+ on (1,4,5)IP3 formation in vasopressin-activated hepatocytes SO CELL CALCIUM LA English DT Article ID INOSITOL TRISPHOSPHATE; CALCIUM OSCILLATIONS; CYCLIC-AMP; CELLS; SPIKING; STORES AB The role of cytoplasmic calcium as a regulator of phospholipase C in vasopressin-activated hepatocytes was examined. According to models in which calcium spiking arises because of a positive feedback by calcium on phospholipase C, Ca2+ is seen as a positive modulator of phospholipase C under conditions of submaximal receptor activation. However, in hepatocytes whose precursor lipids had been labeled by incubation in [H-3]-inositol, no increase in [H-3]-(1,4,5)IP3 was detected in response to thapsigargin, in either unstimulated cells, or in cells stimulated with 1 nM vasopressin. Addition of a maximal concentration of vasopressin (1 mu M) caused a rapid and substantial increase in [H-3]-(1,4,5)IP3. These results indicate that changes in cytoplasmic calcium do not influence phospholipase C activity in hepatocytes, even under conditions of submaximal agonist activation. These findings also support models that provide for calcium spiking at constant levels of (1,4,5)IP3 at least in the case of the rat hepatocyte. C1 NIEHS,CALCIUM REGULAT SECT,CELLULAR & MOL PHARMACOL LAB,NIH,RES TRIANGLE PK,NC 27709. NR 21 TC 11 Z9 11 U1 0 U2 0 PU CHURCHILL LIVINGSTONE PI EDINBURGH PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE, LEITH WALK, EDINBURGH EH1 3AF, MIDLOTHIAN, SCOTLAND SN 0143-4160 J9 CELL CALCIUM JI Cell Calcium PD MAR PY 1997 VL 21 IS 3 BP 253 EP 256 DI 10.1016/S0143-4160(97)90049-X PG 4 WC Cell Biology SC Cell Biology GA WQ728 UT WOS:A1997WQ72800008 PM 9105734 ER PT J AU Putney, JW AF Putney, JW TI Type 3 inositol 1,4,5-trisphosphate receptor and capacitative calcium entry SO CELL CALCIUM LA English DT Review ID PLASMA-MEMBRANE; MOLECULAR-CLONING; HUMAN HOMOLOG; ACINAR-CELLS; IP3 RECEPTOR; MAST-CELLS; T-CELLS; DEPLETION; LOCALIZATION; CHANNELS AB It is well established that depletion of intracellular stores of calcium can activate calcium influx across the plasma membrane, a process known as 'capacitative calcium entry'. Recent research and reviews have focussed on homologs of the Drosophila mutant, trp, as candidates for the channels underlying this phenomenon. However, there is recent evidence that the type 3 inositol 1,4,5-trisphosphate {(1,4,5)IP3} receptor can also function as a capacitative calcium entry channel, specifically: (i) in some cell types, the properties of Ca2+ store depletion-activated currents and channels resemble those of an (1,4,5)IP3 receptor; (ii) in these same cell types, (1,4,5)IP3 directly activates channels in the plasma membrane (including in one study, the same channels activated by depletion of Ca2+ stores); and (iii) expression of the type 3 receptor in Xenopus oocytes resulted in the association of this receptor with the plasma membrane, and facilitation of Ca2+ entry across the plasma membrane. The type 3 receptor may represent one type of capacitative calcium entry channel expressed in some cell types and, in other cell types, channels with markedly different properties (i.e. trp) may carry out this function. Furthermore, as there is little, if any, homology between the IP3 and trp protein families, this may represent an example of convergent evolution of function. RP Putney, JW (reprint author), NIEHS,CALCIUM REGULAT SECT,CELLULAR & MOL PHARMACOL LAB,NIH,POB 12233,RES TRIANGLE PK,NC 27709, USA. NR 41 TC 121 Z9 121 U1 0 U2 1 PU CHURCHILL LIVINGSTONE PI EDINBURGH PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE, LEITH WALK, EDINBURGH EH1 3AF, MIDLOTHIAN, SCOTLAND SN 0143-4160 J9 CELL CALCIUM JI Cell Calcium PD MAR PY 1997 VL 21 IS 3 BP 257 EP 261 DI 10.1016/S0143-4160(97)90050-6 PG 5 WC Cell Biology SC Cell Biology GA WQ728 UT WOS:A1997WQ72800009 PM 9105735 ER PT J AU Rinaudo, JS Thorgeirsson, SS AF Rinaudo, JS Thorgeirsson, SS TI Detection of a tyrosine-phosphorylated form of cyclin A during liver regeneration SO CELL GROWTH & DIFFERENTIATION LA English DT Article ID POLYMERASE CHAIN-REACTION; MESSENGER-RNA EXPRESSION; CELL NUCLEAR ANTIGEN; S-PHASE; PROTEIN-KINASE; RAT-LIVER; A-TYPE; ACTIVATION; P34CDC2; PROLIFERATION AB Cyclin A functions in both the S and G(2)-M phases of the cell cycle. The expression of cyclin A during liver regeneration was compared with that of cyclin B1 and p34cdc2 Liver regeneration was followed at 2-h intervals from 12 to 48 h after partial hepatectomy (PH). Immunohistochemical staining using proliferating cell nuclear antigen revealed DNA synthesis peaks at 18 h after PH. The most intense nuclear staining of hepatocytes with cyclins A and B1 and p34cdc2 antibodies occurred at 26 h post-PH, which corresponds with the onset of mitosis, Quantitative mRNA expression of cyclins A and B1 and p34cdc2 was determined by competitive reverse transcription-PCR. Construction of mRNA internal standards and coamplification during reverse transcription-PCR allowed quantitation of all three cell cycle genes. At 24 h post-PH, cyclin A mRNA levels were approximately 5 fg/100 ng total RNA. In contrast, cyclin B1 and p34cdc2 levels were 20-fold higher, 100 fg/100 ng total RNA, Cyclin B1 and p34cdc2 mRNA levels showed two peaks, at 26 and 38-44 h post-PH, whereas the levels of cyclin A were constant during this interval, Immunoblots revealed the presence of cyclin A in normal liver, and significant amounts were present as early as 12 h post-PH, At 26 h post-PH, tyrosine-phosphorylated forms of cyclin A were detected, Cyclin B1 and p34cdc2 protein were not present until 22-24 h post-PH, and two peaks were observed, at 26 and 38-44 h, coinciding with the mRNA pattern. Histone H1 kinase activity was associated with the two peaks of cyclin B1 and p34cdc2 expression. The unique pattern of cyclin A expression and detection of tyrosine-phosphorylated forms suggest a different mechanism for the regulation of cyclin A during liver regeneration. C1 NCI,EXPT CARCINOGENESIS LAB,NIH,BETHESDA,MD 20892. NR 50 TC 10 Z9 10 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA PUBLIC LEDGER BLDG, SUITE 816, 150 S. INDEPENDENCE MALL W., PHILADELPHIA, PA 19106 SN 1044-9523 J9 CELL GROWTH DIFFER JI Cell Growth Differ. PD MAR PY 1997 VL 8 IS 3 BP 301 EP 309 PG 9 WC Cell Biology SC Cell Biology GA WM401 UT WOS:A1997WM40100005 ER PT J AU Halleck, MM Holbrook, NJ Skinner, J Liu, H Stevens, JL AF Halleck, MM Holbrook, NJ Skinner, J Liu, H Stevens, JL TI The molecular response to reductive stress in LLC-PK1 renal epithelial cells: Coordinate transcriptional regulation of gadd153 and grp78 genes by thiols SO CELL STRESS & CHAPERONES LA English DT Article ID PROTEIN (C/EBP)-RELATED GENE; CYSTEINE CONJUGATE TOXICITY; QUIESCENT BALB/3T3 CELLS; GH3 PITUITARY-CELLS; ENDOPLASMIC-RETICULUM; HEAT-SHOCK; MESSENGER-RNA; OXIDATIVE STRESS; GROWTH ARREST; DNA DAMAGE AB Organic thiols are toxic to eukaryotic cells. Treatment of cells with thiols activates expression of grp78, but it is not known if, like other forms of stress, there is a battery of stress response genes that are induced by thiols. In LLC-PK1 renal epithelial cells, mRNAs for both grp78 and gadd153 were induced by thiols with similar time, concentration and structure-activity dependence. Dithiothreitol (DTT) was the most potent reductant and inducer of gene expression among the thiols tested. Nuclear run-on assays demonstrated that DTT activated both grp78 and gadd153 genes transcriptionally. A hamster gadd153 promoter construct which contains enhancer elements necessary for gadd153 activation was stably integrated into the LLC-PK1 cell genome and was activated by DTT. Although auto-oxidation,of thiols can generate active oxygen species, transcriptional activation of the gadd153 promoter was not due to formation of hydrogen peroxide or superoxide since neither catalase nor superoxide dismutase prevented activation of the gadd153 promoter by DTT. The concentration dependence for activation of the gadd153 promoter correlated with inhibition of dome formation and protein synthesis, two toxic effects of DTT in LLC-PK1 cells. Thus, both grp78 and gadd153 are members of a gene battery which is responsive to reductive stress. There appears to be considerable, but not complete, overlap between the upstream signaling pathways for activation of both genes. C1 W ALTON JONES CELL SCI CTR,LAKE PLACID,NY 12946. NIA,MOL GENET LAB,BALTIMORE,MD 21224. FU NIDDK NIH HHS [DK38965, DK46267]; NIEHS NIH HHS [ES05569] NR 74 TC 35 Z9 36 U1 0 U2 1 PU CHURCHILL LIVINGSTONE PI EDINBURGH PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE, LEITH WALK, EDINBURGH EH1 3AF, MIDLOTHIAN, SCOTLAND SN 1355-8145 J9 CELL STRESS CHAPERON JI Cell Stress Chaperones PD MAR PY 1997 VL 2 IS 1 BP 31 EP 40 DI 10.1379/1466-1268(1997)002<0031:TMRTRS>2.3.CO;2 PG 10 WC Cell Biology SC Cell Biology GA WU689 UT WOS:A1997WU68900004 PM 9250393 ER PT J AU Jorcyk, CL Garrett, LJ Maroulakou, IG Watson, DK Green, JE AF Jorcyk, CL Garrett, LJ Maroulakou, IG Watson, DK Green, JE TI Multiple regulatory regions control the expression of Ets-1 in the developing mouse: Vascular expression conferred by intron I SO CELLULAR AND MOLECULAR BIOLOGY LA English DT Article DE gene regulation; promoter; enhancer-trap; reporter gene; beta-galactosidase; angiogenesis ID ONCOGENE C-ETS; LONG TERMINAL REPEAT; DNA-BINDING; TRANSCRIPTION FACTOR; T-CELLS; V-ETS; GENE; PROTOONCOGENE; PROMOTER; LEUKEMIA AB Ets-1, a developmentally-regulated protooncogene, is expressed in multiple tissues during different stages of mouse development and cellular differentiation including high levels in lymphoid organs and endothelium. The putative roles of this DNA-binding protein in lymphoid development and maturation, as well as in angiogenesis and tumor vascularization, suggest that the regulation of Ets-1 may be critical to understanding these important developmental processes. We have cloned the mouse Ets-1 5' flanking region which shows significant homology to the human 5' flanking region, including potential transcription factor binding sites. Various amounts of mouse Ets-1 5' flanking, exon and intron sequences have been fused to the E. coli lacZ reporter gene and introduced into the mouse germline to identify genomic regions which regulate the developmental and tissue-specific expression of Ets-1. The 2.4 kb 5' flanking region of Ets-1 directs lacZ expression to the folding neural tube of embryos at gestational day 8.5 which is identical to the endogenous expression pattern of Ets-1. However, at later times in gestation, up to 5.3 kb of 5' flanking region results only in aberrant expression and is not able to confer lacZ expression in lymphoid or vascular tissues. When the first exon and 9 kb of the first intron are included with 5' flanking sequences, using an enhancer-trap-strategy, lacZ expression is observed in developing vessels, meninges and choroid plexus which correlates to endogenous Ets-1 expression. Further characterization of the vascular-specific element contained within intron I will provide important insights into the mechanisms controlling gene expression during angiogenesis. C1 NCI, FREDERICK CANC RES & DEV CTR, ONCOL MOL LAB, FREDERICK, MD 21702 USA. NIH, NATL CTR HUMAN GENOME RES, BETHESDA, MD 20892 USA. MED UNIV S CAROLINA, CTR MOL & STRUCT BIOL, HOLLINGS CANC CTR, CHARLESTON, SC 29425 USA. NR 42 TC 16 Z9 16 U1 0 U2 0 PU C M B ASSOC PI POITIERS PA 40 AVENUE RECTEUR PINEAU, BAT MECANIQUE, 86022 POITIERS, FRANCE SN 0145-5680 J9 CELL MOL BIOL JI Cell. Mol. Biol. PD MAR PY 1997 VL 43 IS 2 BP 211 EP 225 PG 15 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA WV117 UT WOS:A1997WV11700007 PM 9130605 ER PT J AU Gattass, R Sousa, APB Mishkin, M Ungerleider, LG AF Gattass, R Sousa, APB Mishkin, M Ungerleider, LG TI Cortical projections of area V2 in the Macaque SO CEREBRAL CORTEX LA English DT Article ID SUPERIOR TEMPORAL SULCUS; MONKEY VISUAL-CORTEX; POSTERIOR PARIETAL CORTEX; RHESUS-MONKEY; CEBUS MONKEY; TOPOGRAPHIC ORGANIZATION; VISUOTOPIC ORGANIZATION; SQUIRREL-MONKEY; OWL MONKEYS; EXTRASTRIATE CORTEX AB To determine the locus, extent and topographic organization of cortical projections of area V2, we injected tritiated amino acids under electrophysiological control into 15 V2 sites in 14 macaques. The injection sites included the foveal representation and representations ranging from central to far peripheral eccentricities in both the upper and lower visual fields. The results indicated that all V2 sites project topographically back to V1 and forward to V3, V4 and MT. There is also a topographically organized projection from V2 to V4t, but this projection is limited to the lower visual field representation. V2 thus appears to project to virtually all the visual cortex within the occipital lobe. In addition to these projections to occipital visual areas, V2 sites representing eccentricities of similar to 30 degrees and greater project to three visual areas in parietal cortex - the medial superior temporal (MST), parieto-occipital (PO) and ventral intraparietal (VIP) areas. This peripheral field representation of V2 also projects to area VTF, a visual area located in area TF on the posterior parahippocampal gyrus. Projections from the peripheral field representation of V2 to parietal areas could provide a direct route for rapid activation of circuits serving spatial vision and spatial attention. C1 NIMH,NEUROPSYCHOL LAB,BETHESDA,MD 20892. UNIV FED RIO DE JANEIRO,INST BIOFIS CARLOS CHAGAS FILHO,BR-21941 RIO JANEIRO,BRAZIL. NIMH,NEUROPSYCHOL LAB,BETHESDA,MD 20892. NR 95 TC 84 Z9 84 U1 1 U2 9 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 PY 1997 VL 7 IS 2 BP 110 EP 129 DI 10.1093/cercor/7.2.110 PG 20 WC Neurosciences SC Neurosciences & Neurology GA WJ361 UT WOS:A1997WJ36100003 PM 9087820 ER PT J AU Lamb, ME Sternberg, KJ Esplin, PW Hershkowitz, I Orbach, Y Hovav, M AF Lamb, ME Sternberg, KJ Esplin, PW Hershkowitz, I Orbach, Y Hovav, M TI Criterion-based content analysis: A field validation study SO CHILD ABUSE & NEGLECT LA English DT Article DE child witnesses; credibility; sexual abuse; CBCA ratings ID SEXUAL ABUSE; CHILDREN AB Transcript of forensic interviews with 98 alleged victims of child sexual abuse were scored for the presence or absence of certain criteria believed to be more characteristic of accounts concerning experienced than nonexperienced events. Other information regarding the events was independently evaluated by individuals unfamiliar with the children's accounts. As predicted, more of the CBCA criteria were present in accounts independently rated as Likely or Very Likely to have occurred (M = 6.74) than in accounts of events deemed Unlikely or Very Unlikely to have occurred (M = 4.85). In addition, several of the criteria were helpful in distinguishing between plausible and implausible accounts. The group differences were not as dramatic as those reported in earlier studies, however, and the results suggest caution regarding forensic application of the CBCA system. C1 MINIST LABOR & SOCIAL WELF, DIV CORRECT SERV & SERV YOUTH DISTRESS, JERUSALEM, ISRAEL. RP Lamb, ME (reprint author), NICHHD, SECT SOCIAL & EMOT DEV, NIH, 9190 ROCKVILLE PIKE, BETHESDA, MD 20814 USA. NR 21 TC 61 Z9 62 U1 1 U2 4 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0145-2134 J9 CHILD ABUSE NEGLECT JI Child Abuse Negl. PD MAR PY 1997 VL 21 IS 3 BP 255 EP 264 DI 10.1016/S0145-2134(96)00170-6 PG 10 WC Family Studies; Psychology, Social; Social Work SC Family Studies; Psychology; Social Work GA WL710 UT WOS:A1997WL71000006 PM 9134256 ER PT J AU Pietrini, P Guazzelli, M AF Pietrini, P Guazzelli, M TI Life events in the course of chronic diseases: A psychological myth or a psycho-neuro-biochemical loop? SO CLINICAL AND EXPERIMENTAL RHEUMATOLOGY LA English DT Editorial Material ID RHEUMATOID-ARTHRITIS; IMMUNE-SYSTEM; STRESS; DEPRESSION; ILLNESS C1 NINCDS,NIH,COGNIT NEUROSCI BRANCH,BETHESDA,MD 20892. UNIV PISA,DIPARTIMENTO SCI UOMO & AMBIENTE,PISA,ITALY. UNIV PISA,IST CLIN PSICHIAT,PISA,ITALY. NR 28 TC 13 Z9 13 U1 2 U2 2 PU CLINICAL & EXPER RHEUMATOLOGY PI PISA PA VIA SANTA MARIA 31, 56126 PISA, ITALY SN 0392-856X J9 CLIN EXP RHEUMATOL JI Clin. Exp. Rheumatol. PD MAR-APR PY 1997 VL 15 IS 2 BP 125 EP 128 PG 4 WC Rheumatology SC Rheumatology GA WX895 UT WOS:A1997WX89500001 PM 9196862 ER PT J AU Meeker, TC Lay, LT Wroblewski, JM Turturro, F Li, ZW Seth, P AF Meeker, TC Lay, LT Wroblewski, JM Turturro, F Li, ZW Seth, P TI Adenoviral vectors efficiently target cell lines derived from selected lymphocytic malignancies, including anaplastic large cell lymphoma and Hodgkin's disease SO CLINICAL CANCER RESEARCH LA English DT Article ID GENE-THERAPY; BURKITTS-LYMPHOMA; INFECTION; APOPTOSIS; CANCER; TUMORS; HEAD; NECK; LACZ; P53 AB We have hypothesized that adenoviral vectors might mediate gene transfer into cell lines derived from human lymphocytic malignancies, such as lymphoma, lymphocytic leukemia, and myeloma, A panel of 33 cell lines was studied for their ability to be transduced by an adenoviral (AD) vector encoding the Escherichia coli beta-galactosidase gene (AD-beta gal). A cytochemical assay and a flow cytometry assay both demonstrated that a subset of lymphocytic cell lines can be efficiently transduced by adenoviral vectors. In particular, three: of three anaplastic large cell lymphoma lines, two of two Hodgkin's disease cell lines, two of seven Burkitt's lymphoma cell lines, and three of five myeloma cell lines exhibited efficient gene transfer. The ability of an AD vector expressing the thymidine kinase (tk) gene from herpes simplex virus-1 (AD-tk) followed by ganciclovir (GCV) to kill 11 of these lymphocytic cell lines was studied, In eight of the cell lines tested, more than 68% of the cells were killed by AD-tk/GCV. Similar results were obtained using an adenoviral vector expressing the wildtype p53 tumor suppressor gene (AD-p53). Thus, AD-tk/GCV and AD-p53 both demonstrated efficient killing of these cell lines. These data document that adenoviral vectors are valuable reagents for the introduction of genes into selected lymphocytic cell lines. These data also suggest that adenoviral vectors might be useful for gene therapy of subsets of lymphocytic malignancy. C1 UNIV KENTUCKY,DEPT MED,LEXINGTON,KY 40536. UNIV KENTUCKY,DEPT BIOCHEM,LEXINGTON,KY 40536. NCI,MED BRANCH,MED BREAST SECT,NIH,BETHESDA,MD 20892. RP Meeker, TC (reprint author), UNIV KENTUCKY,MED CTR,MARKEY CANC CTR,DIV HEMATOL ONCOL,CC405,800 ROSE ST,LEXINGTON,KY 40536, USA. NR 38 TC 26 Z9 26 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA PUBLIC LEDGER BLDG, SUITE 816, 150 S. INDEPENDENCE MALL W., PHILADELPHIA, PA 19106 SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD MAR PY 1997 VL 3 IS 3 BP 357 EP 364 PG 8 WC Oncology SC Oncology GA WY368 UT WOS:A1997WY36800005 PM 9815692 ER PT J AU Georgiadis, MS Russell, EK Gazdar, AF Johnson, BE AF Georgiadis, MS Russell, EK Gazdar, AF Johnson, BE TI Paclitaxel cytotoxicity against human lung cancer cell lines increases with prolonged exposure durations SO CLINICAL CANCER RESEARCH LA English DT Article ID TAXOL; INFUSION; DRUG; EXPRESSION; TRIAL; ASSAY AB Paclitaxel blocks cells in G(2)-M, and this may result in a schedule-dependent effect on paclitaxel cytotoxicity, To test this hypothesis, we evaluated paclitaxel cytotoxicity in 28 human lung cancer cell lines, Fourteen of the cell lines were derived from patients with non-small cell lung cancer (NSCLC), and 14 were from patients with small cell lung cancer (SCLC), All cell lines were exposed to a range of paclitaxel concentrations for durations of 3, 24, and 120 h, and cytotoxicity was measured with a tetrazolium-based assay. The median IC50 values for all 28 cell lines at exposure durations of 3, 24, and 120 h were >32 mu M, 23 mu M, and 0.38 mu M, respectively. The median IC50 values for the NSCLC cell lines were >32 mu M, 9.4 mu M, and 0.027 mu M at exposure Durations of 3, 24, and 120 h, respectively, For the 14 SCLC cell lines, the median IC50 values were >32 mu M, 25 mu m, and 5.0 mu m, respectively, Five of the 14 SCLC cell lines had IC50 values at 120 h of paclitaxel exposure that were 1000-fold less than the remaining SCLC cell lines, The me dian IC50 values for these five sensitive SCLC cell lines at 3-, 24-, and 120-h exposures were >32 mu m, 23 mu M, and <0.0032 mu M, respectively. These in vitro cytotoxicity results were independent of the paclitaxel diluent, a 1:1 solution of ethanol and Cremophor EL. We conclude that longer durations of paclitaxel exposure result in an increase in the chemosensitivity of some human lung cancer cell lines and that this phenomenon is more consistent within NSCLC cell lines than in SCLC cell lines. C1 NCI, NAVY MED ONCOL BRANCH, BETHESDA, MD 20889 USA. RP Georgiadis, MS (reprint author), NATL NAVAL MED CTR, DEPT INTERNAL MED, DIV HEMATOL ONCOL, BETHESDA, MD 20889 USA. RI Ain, Kenneth/A-5179-2012 OI Ain, Kenneth/0000-0002-2668-934X NR 22 TC 51 Z9 54 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 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD MAR PY 1997 VL 3 IS 3 BP 449 EP 454 PG 6 WC Oncology SC Oncology GA WY368 UT WOS:A1997WY36800017 PM 9815704 ER PT J AU Burger, AM Kaur, G Hollingshead, M Fischer, RT Nagashima, K Malspeis, L Duncan, KLK Sausville, EA AF Burger, AM Kaur, G Hollingshead, M Fischer, RT Nagashima, K Malspeis, L Duncan, KLK Sausville, EA TI Antiproliferative activity in vitro and in vivo of the spicamycin analogue KRN5500 with altered glycoprotein expression in vitro SO CLINICAL CANCER RESEARCH LA English DT Article ID ANTITUMOR-ACTIVITY; CELL-GROWTH; INHIBITORS; 1-DEOXYNOJIRIMYCIN; BIOSYNTHESIS; CYTOTOXICITY; PROTEINS; ASSAY AB The spicamycin analogue KRN5500 (NSC 650426; SPA) is derived from Streptomyces alanosinicus. The unique structure contains a purine, an aminoheptose sugar, glycine, and a tetradecadiene fatty acid, SPA potently inhibits the growth of certain human tumor cell lines in vitro (IC50 for growth <100 nM) and displays marked activity in vivo in Cole 205 colon carcinoma xenografts, Selective inhibition of labeled precursor incorporation was not evident at 1 or 4 h of exposure to the drug, but at 8 h. [H-3]leucine incorporation was inhibited by approximately 40% at or below the IC50 for cell growth, Because of the structural similarity of SPA to inhibitors of glycoprotein processing, we examined the effect of SPA on indicators of glycoprotein synthesis and processing in HL60TB promyelocytic leukemia and Cole 205 colon carcinoma cells, Brief periods of exposure (similar to 30 min) to SPA at the IC50 for growth increased incorporation of [H-3]mannose. When examined by Western blotting after prolonged (40-48 h) incubation with lectins that target mannose-containing carbohydrates, Galanthus nivalis agglutinin and concanavalin A, a qualitative change in the pattern of mannose-containing glycoproteins was observed in HL60TB cells. Significant changes in the pattern of surface glycoprotein expression in intact cells were demonstrated by flow cytometry using fluorescence-labeled lectins. An increase in the number of cells binding G. nivalis agglutinin (indicating terminal mannose) was noted, but a decrease in the amount of lectin bound per cell was noted for wheat germ agglutinin (detecting sialic acid and terminal beta-N-acetyl glucosamine residues), Electron microscopy revealed loss of microvilli, and the Golgi apparatus appeared inflated, Our findings, therefore, raise the possibility that cells exposed to SPA have altered glycoprotein processing after exposure to low concentrations of drug, prior to the occurrence of overt cytotoxicity. These effects are consistent with a prominent early effect of SPA on the enzymatic machinery or organelles important for proper glycoprotein processing and emphasize the novelty of this agent's likely mechanism of action. C1 NCI,DEV THERAPEUT PROGRAM,DIV CANC TREATMENT DIAG & CTR,DIV BASIC SCI,NIH,BETHESDA,MD 20892. NCI,BIOL CHEM LAB,DIV BASIC SCI,NIH,BETHESDA,MD 20892. NCI,BIOL TESTING BRANCH,DIV BASIC SCI,NIH,BETHESDA,MD 20892. NCI,LAB PHARMACEUT CHEM,DIV BASIC SCI,NIH,BETHESDA,MD 20892. NCI,FREDERICK CANC RES & DEV CTR,SAIC FREDERICK,FREDERICK,MD 21702. NCI,FREDERICK CANC RES & DEV CTR,BIOL RESPONSE MODIFIERS PROGRAM,FREDERICK,MD 21702. RI Duncan, Kimberly /C-3655-2013 NR 28 TC 18 Z9 18 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA PUBLIC LEDGER BLDG, SUITE 816, 150 S. INDEPENDENCE MALL W., PHILADELPHIA, PA 19106 SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD MAR PY 1997 VL 3 IS 3 BP 455 EP 463 PG 9 WC Oncology SC Oncology GA WY368 UT WOS:A1997WY36800018 PM 9815705 ER PT J AU Scott, FM Modali, R Lehman, TA Seddon, M Kelly, K Dempsey, EC Wilson, V Tockman, MS Mulshine, JL AF Scott, FM Modali, R Lehman, TA Seddon, M Kelly, K Dempsey, EC Wilson, V Tockman, MS Mulshine, JL TI High frequency of K-ras codon 12 mutations in bronchoalveolar lavage fluid of patients at high risk for second primary lung cancer SO CLINICAL CANCER RESEARCH LA English DT Article ID ONCOGENE MUTATIONS; ADENOCARCINOMA; TRANSFORMATION; DIAGNOSIS; CARCINOMA; LIGASE AB A high frequency of K-ras mutations may indicate preneoplastic changes in the bronchial epithelium as a result of genotoxic injury. With the use of sensitive detection techniques, we report a higher prevalence of K-ras mutations in bronchoalveolar lavage than has been reported previously for lung cancer, A PCR/ligase chain reaction technique was used to determine K-ras codon 12 mutations in a group of 52 bronchoalveolar lavage specimens from patients at risk of a second lung cancer, Of the specimens examined, 84% contained at least one mutation in K-ras codon 12, corroborated by an allele-specific hybridization method, These results suggest that point mutations in K-ras codon 12 are widespread in the bronchial epithelium. Based on these preliminary findings, further evaluation of this efficient sensitive assay to monitor Kras status should be conducted in larger clinical cohorts where clinical outcomes will ultimately be available, Such a trial will define the utility of K-ras codon 12 mutation status as a marker of lung cancer. C1 NCI,BIOMARKERS & PREVENT RES BRANCH,ROCKVILLE,MD 20850. BIOSERVE BIOTECHNOL LTD,LAUREL,MD 20707. UNIV COLORADO,HLTH SCI CTR,DENVER,CO 80262. DEPT VET AFFAIRS MED CTR,DENVER,CO 80220. LOUISIANA STATE UNIV,DEPT ZOOL & PHYSIOL,BATON ROUGE,LA 70803. JOHNS HOPKINS UNIV,SCH HYG & PUBL HLTH,BALTIMORE,MD 21205. FU NCI NIH HHS [CA58187-01, CA58184-01] NR 27 TC 26 Z9 26 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 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD MAR PY 1997 VL 3 IS 3 BP 479 EP 482 PG 4 WC Oncology SC Oncology GA WY368 UT WOS:A1997WY36800021 PM 9815708 ER PT J AU Goodman, LA Liu, BCS Thiele, CJ Schmidt, ML Cohn, SL Yamashiro, JM Pai, DSM Ikegaki, N Wada, RK AF Goodman, LA Liu, BCS Thiele, CJ Schmidt, ML Cohn, SL Yamashiro, JM Pai, DSM Ikegaki, N Wada, RK TI Modulation of N-myc expression alters the invasiveness of neuroblastoma SO CLINICAL & EXPERIMENTAL METASTASIS LA English DT Article DE invasion; motility; neuroblastoma; N-myc ID RECONSTITUTED BASEMENT-MEMBRANE; NEURO-BLASTOMA CELLS; RETINOIC ACID; ADHESION MOLECULES; LUNG COLONIZATION; CARCINOMA CELLS; MELANOMA; AMPLIFICATION; INHIBITION; INVASION AB N-myc oncogene expression plays a pivotal role in the biology of neuroblastoma, a common childhood tumor. High N-myc expression is associated with advanced disease stage, and in animal models, increased expression results in increased metastatic potential, In normal embryologic development, N-myc expression is associated with neuroblast migration out from the neural crest, To further define the relationship between N-myc and metastasis, an in vitro assay was adapted to measure tumor cell attachment, motility, and proteolytic ability in neuroblastoma cell lines, These parameters were examined in a non-amplified, uniformly N-myc overexpressing cell line and its anti-sense N-myc expressing clones, These lines have been characterized previously, and have a decrease in N-myc expression, growth rate, and tumorigenicity relative to the parent line and vector-only control transfectant, Decrease in N-myc expression resulted in a non-proportional increase of tumor cell attachment, and a proportional decrease in both tumor cell motility and proteolytic ability, In further experiments, assay of a N-myc-amplified overexpressing cell line with an intrinsic heterogeneous pattern of expression demonstrated that motile cells expressed higher amounts of N-myc relative to the general population, Together these relationships indicate that N-myc plays a causative role in the invasive phenotype, and suggest that metastasis may, in part, result from the disruption of a developmentally important normal process. C1 UNIV CALIF LOS ANGELES,SCH MED,DEPT PEDIAT,DIV HEMATOL ONCOL,GWYNNE HAZEN CHERRY MEM LABS,LOS ANGELES,CA 90024. JONSSON COMPREHENS CANC CTR,LOS ANGELES,CA. MT SINAI SCH MED,DEPT UROL,NEW YORK,NY. NCI,PEDIAT BRANCH,BETHESDA,MD 20892. UNIV ILLINOIS,DEPT PEDIAT ONCOL,CHICAGO,IL. NORTHWESTERN UNIV,CHICAGO,IL 60611. CHILDRENS MEM HOSP,DEPT PEDIAT,CHICAGO,IL 60614. UNIV PENN,SCH MED,DEPT HUMAN GENET,PHILADELPHIA,PA 19104. OI Cohn, Susan/0000-0001-5749-7650 FU NINDS NIH HHS [NS34432] NR 42 TC 31 Z9 31 U1 0 U2 0 PU RAPID SCIENCE PUBLISHERS PI LONDON PA 2-6 BOUNDARY ROW, LONDON, ENGLAND SE1 8NH SN 0262-0898 J9 CLIN EXP METASTAS JI Clin. Exp. Metastasis PD MAR PY 1997 VL 15 IS 2 BP 130 EP 139 DI 10.1023/A:1018448710006 PG 10 WC Oncology SC Oncology GA WN568 UT WOS:A1997WN56800006 PM 9062389 ER PT J AU Rousseau, F Pueyo, S Morlat, P Hafner, R Chene, G Leport, C Luft, BJ Miro, J Aubertin, J Salamon, R Vilde, JL AF Rousseau, F Pueyo, S Morlat, P Hafner, R Chene, G Leport, C Luft, BJ Miro, J Aubertin, J Salamon, R Vilde, JL TI Increased risk of toxoplasmic encephalitis in human immunodeficiency virus-infected patients with pyrimethamine-related rash SO CLINICAL INFECTIOUS DISEASES LA English DT Article; Proceedings Paper CT 34th Interscience Conference on Antimicrobial Agents and Chemotherapy CY OCT 03-07, 1994 CL ORLANDO, FL ID PNEUMOCYSTIS-CARINII PNEUMONIA; HIV-INFECTION; PRIMARY PROPHYLAXIS; TRIMETHOPRIM-SULFAMETHOXAZOLE; HYPERSENSITIVITY REACTIONS; RANDOMIZED TRIAL; DISEASE; AIDS; MANIFESTATIONS; COMPLICATIONS AB Although drug-induced rash is frequent in human immunodeficiency virus (HIV)-infected patients, rash due to pyrimethamine has not been described previously, In a randomized, double-blind, placebo-controlled study of pyrimethamine as primary prophylaxis for toxoplasmic encephalitis, the incidence of rash (per hundred patient-years) was 8.1 in the pyrimethamine group versus 1.5 in the placebo group (P < .0002). The 1-year incidence of toxoplasmic encephalitis after occurrence of rash was 37%, as compared with 9.6% in the pyrimethamine group without rash, with a 3.7 times higher risk for patients with pyrimethamine-induced rash (P = .001); the incidence was 13% in the placebo group, At the time of toxoplasmic encephalitis, pyrimethamine was successfully readministered to 80% of patients who discontinued it because of rash, Thus, pyrimethamine, when used for prophylaxis, does induce rash in HIV-infected patients. These patients are at higher risk for toxoplasmic encephalitis and should be carefully monitored for it. C1 UNIV PARIS 07,SERV MALAD INFECT & TROP,HOP BICHAT CLAUDE BERNARD,F-75877 PARIS 18,FRANCE. UNIV BORDEAUX 2,HOP ST ANDRE,INSERM U330,F-33076 BORDEAUX,FRANCE. HOP PELLEGRIN,BORDEAUX,FRANCE. SUNY STONY BROOK,STONY BROOK,NY 11794. NIAID,DIV AIDS,BETHESDA,MD 20892. HOSP CLIN BARCELONA,BARCELONA,SPAIN. RI chene, genevieve/H-8665-2014; OI Luft, Benjamin/0000-0001-9008-7004 NR 31 TC 10 Z9 10 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 S WOODLAWN AVE, CHICAGO, IL 60637 SN 1058-4838 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD MAR PY 1997 VL 24 IS 3 BP 396 EP 402 PG 7 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA WK382 UT WOS:A1997WK38200017 PM 9114191 ER PT J AU Torres, RA Weinberg, W Stansell, J Leoung, G Kovacs, J Rogers, M Scott, J AF Torres, RA Weinberg, W Stansell, J Leoung, G Kovacs, J Rogers, M Scott, J TI Atovaquone for salvage treatment and suppression of toxoplasmic encephalitis in patients with AIDS SO CLINICAL INFECTIOUS DISEASES LA English DT Article; Proceedings Paper CT 10th International Conference on AIDS CY AUG 07-12, 1994 CL YOKOHAMA, JAPAN ID ACQUIRED-IMMUNODEFICIENCY-SYNDROME; PNEUMOCYSTIS-CARINII PNEUMONIA; CENTRAL-NERVOUS-SYSTEM; PYRIMETHAMINE; SULFADIAZINE; EFFICACY; THERAPY; COMBINATION; CLINDAMYCIN; 566C80 AB To examine the efficacy of atovaquone as salvage therapy in patients with AIDS-related toxoplasmic encephalitis, 93 patients with AIDS and toxoplasmic encephalitis who were intolerant of standard therapy (pyrimethamine plus sulfadiazine or clindamycin) or for whom such therapy was failing were treated with atovaquone tablets (750 mg four times daily) for 18 weeks, Plasma levels of atovaquone were measured with high-pressure liquid chromatography, and the clinical and radiological responses and survival were compared according to median plasma concentration groups. During the acute-therapy phase (the first 6 weeks), the conditions of 52% and 37% of the patients, respectively, were clinically or radiologically improved; the conditions of 26% and 15% remained clinically or radiologically improved by week 18. Median survival for all patients was 189 days (Kaplan-Meier estimate). A post-hoc analysis revealed a positive relationship between clinical and radiological responses and median atovaquone plasma concentrations. Survival time among patients with high or medium median steady-state plasma concentrations (319 and 289 days) was significantly better than that among those with low plasma concentrations (114 days; P=.003 and P=.006, respectively). C1 INFECT DIS RES CONSORTIUM GEORGIA,ATLANTA,GA. SAN FRANCISCO GEN HOSP,SAN FRANCISCO,CA 94110. ST FRANCIS MEM HOSP,SAN FRANCISCO,CA 94109. NIH,CTR CLIN,BETHESDA,MD 20892. BURROUGHS WELLCOME CO,RES TRIANGLE PK,NC 27709. RP Torres, RA (reprint author), ST VINCENTS HOSP & MED CTR,AIDS CTR,412 6TH AVE,SUITE 401,NEW YORK,NY 10011, USA. NR 18 TC 44 Z9 48 U1 1 U2 1 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 S WOODLAWN AVE, CHICAGO, IL 60637 SN 1058-4838 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD MAR PY 1997 VL 24 IS 3 BP 422 EP 429 PG 8 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA WK382 UT WOS:A1997WK38200020 PM 9114194 ER PT J AU Lowy, DR AF Lowy, DR TI HPV infection: Future prospects SO CLINICS IN DERMATOLOGY LA English DT Article ID HUMAN PAPILLOMAVIRUS TYPE-16; VIRUS-LIKE PARTICLES; L1 PROTEIN; IMMUNIZATION; CARCINOMA; E6; REGRESSION; COMPLEX; RABBITS; CELLS RP Lowy, DR (reprint author), NCI,CELLULAR ONCOL LAB,DIV BASIC SCI,BLDG 36,ROOM 1D-32,BETHESDA,MD 20892, USA. NR 33 TC 1 Z9 1 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0738-081X J9 CLIN DERMATOL JI Clin. Dermatol. PD MAR-APR PY 1997 VL 15 IS 2 BP 299 EP 302 DI 10.1016/S0738-081X(97)00070-9 PG 4 WC Dermatology SC Dermatology GA XA809 UT WOS:A1997XA80900012 PM 9167913 ER PT J AU Potkay, S Garnett, NL Miller, JG Pond, CL Doyle, DJ AF Potkay, S Garnett, NL Miller, JG Pond, CL Doyle, DJ TI Frequently asked questions about the public health service policy on humane care and use of laboratory animals SO CONTEMPORARY TOPICS IN LABORATORY ANIMAL SCIENCE LA English DT Article AB Adherence to the provisions of the Public Health Service (PHS) Policy on Humane Care and Use of Laboratory Animals and related U.S. Department of Agriculture Animal Welfare regulations is a prerequisite for receiving PHS support for conducting animal-related activities, As one of its duties specified in the PHS Policy, the Office for Protection from Research Risks (OPRR) here provides guidance regarding questions that have been raised by institutions seeking to comply with those requirements, These questions include institutional reporting requirements, collaborative activities, performance of multiple survival surgeries, care and use of cold-blooded vertebrates, tracking of animal use, animal study areas, and other Animal Care and Use Committee issues, In reviewing these questions and answers, readers are asked to keep in mind that many of these issues are highly context-specific and that over-generalization is to be avoided. RP Potkay, S (reprint author), NIH,DIV ANIM WELF,OFF PROTECT RES RISKS,6100 EXECUT BLVD,SUITE 3B01,MSC 7507,ROCKVILLE,MD 20892, USA. NR 17 TC 9 Z9 9 U1 0 U2 0 PU AMER ASSOC LABORATORY ANIMAL SCIENCE PI CORDOVA PA 70 TIMBERCREEK DR, SUITE 5, CORDOVA, TN 38018 SN 1060-0558 J9 CONTEMP TOP LAB ANIM JI Contemp. Top. Lab. Anim. Sci. PD MAR PY 1997 VL 36 IS 2 BP 47 EP 50 PG 4 WC Veterinary Sciences; Zoology SC Veterinary Sciences; Zoology GA WP271 UT WOS:A1997WP27100004 PM 16426019 ER PT J AU Kass, SU Landsberger, N Wolffe, AP AF Kass, SU Landsberger, N Wolffe, AP TI DNA methylation directs a time dependent repression of transcription initiation SO CURRENT BIOLOGY LA English DT Article ID RNA POLYMERASE-II; MOUSE H19 GENE; CHROMATIN STRUCTURE; CPG METHYLATION; PROMOTER; 5-METHYLCYTOSINE; EXPRESSION; HISTONE-H1; BINDING; INVITRO AB Background: The regulation of DNA methylation is required for differential expression of imprinted genes during vertebrate development, Earlier studies that monitored the activity of the Herpes simplex virus (HSV) thymidine kinase (tk) gene after injection into rodent cells have suggested that assembly of chromatin influences the methylation-dependent repression of gene activity, Here, we examine the mechanism of methylation-dependent HSV tk gene regulation by direct determination of nucleoprotein organization during the establishment of a transcriptionally silenced state after microinjection of templates with defined methylation states into Xenopus oocyte nuclei. Results: The transcriptional silencing conferred by a methylated DNA segment was not immediate, as methylated templates were initially assembled into active transcription complexes. The eventual loss of DNase I hypersensitive sites and inhibition of transcription at the HSV rk promoter only occurred after several hours. Flanking methylated vector DNA silenced the adjacent unmethylated HSV tk promoter, indicative of a dominant transmissible repression originating from a center of methylation. The resulting repressive nucleoprotein structure silenced transcription in the presence of activators that are able to overcome repression of transcription by nucleosomes. Conclusions: Silencing of transcription by DNA methylation is achieved at the level of transcription initiation and involves the removal of transcriptional machinery from active templates, This transcriptional repression can occur by indirect mechanisms involving the time-dependent assembly of repressive nucleoprotein complexes, which are able to inhibit transcription more effectively than nucleosomes alone. C1 NICHHD,MOL EMBRYOL LAB,NIH,BETHESDA,MD 20892. OI Landsberger, Nicoletta/0000-0003-0820-3155 NR 35 TC 237 Z9 247 U1 2 U2 5 PU CURRENT BIOLOGY LTD PI LONDON PA 34-42 CLEVELAND STREET, LONDON, ENGLAND W1P 6LB SN 0960-9822 J9 CURR BIOL JI Curr. Biol. PD MAR 1 PY 1997 VL 7 IS 3 BP 157 EP 165 DI 10.1016/S0960-9822(97)70086-1 PG 9 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA WN579 UT WOS:A1997WN57900024 PM 9395433 ER PT J AU Feinberg, MB McLean, AR AF Feinberg, MB McLean, AR TI AIDS: Decline and fall of immune surveillance? SO CURRENT BIOLOGY LA English DT Article AB Recent observations cast doubt on the view that cytotoxic T cells play a key role in keeping HIV-1 infection in check, and that it is the decline in this mechanism of immune surveillance that permits progression to AIDS. C1 INST PASTEUR,LAB DYNAM LYMPHOCYTAIRE,F-75724 PARIS 15,FRANCE. RP Feinberg, MB (reprint author), NIH,OFF AIDS RES,BLDG 31,ROOM 4C06,31 CTR DR,BETHESDA,MD 20892, USA. NR 10 TC 13 Z9 13 U1 0 U2 0 PU CURRENT BIOLOGY LTD PI LONDON PA 34-42 CLEVELAND STREET, LONDON, ENGLAND W1P 6LB SN 0960-9822 J9 CURR BIOL JI Curr. Biol. PD MAR 1 PY 1997 VL 7 IS 3 BP R136 EP R140 DI 10.1016/S0960-9822(97)70072-1 PG 5 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA WN579 UT WOS:A1997WN57900009 PM 9162473 ER PT J AU White, SN Li, ZC Yu, ZK Kipnis, V AF White, SN Li, ZC Yu, ZK Kipnis, V TI Relationship between static chemical and cyclic mechanical fatigue in a feldspathic porcelain SO DENTAL MATERIALS LA English DT Article ID CRACK-PROPAGATION; POLYCRYSTALLINE CERAMICS; FRACTURE-TOUGHNESS; STRESS-CORROSION; BEHAVIOR; MODEL AB Objectives. The goal of this study was to determine if static chemical and cyclic mechanical fatigue are independent, or if they interact to produce greater than additive strength loss in a feldspathic porcelain. Methods. A blunt indentation technique was used to investigate the response of a feldspathic dental porcelain to cyclic mechanical fatigue and static chemical fatigue. All specimens were fabricated in a dry inert environment and then mechanically fatigued by cyclic loading and strength-tested in dry inert nitrogenous, ambient or wet environments. A series of experiments were performed to evaluate the effects of chemical and mechanical fatigue, and their interaction on strength loss; to determine the effects of, and interaction between, the factors of cyclic fatigue environment and strength test environment on strength; to ascertain if the type of environment during strength testing influenced specimen strength; and to distinguish between chemical damage caused by exposure to moisture alone and stress corrosion damage resulting from the strength testing environment, using a pair of two-way analysis of variance, a single one-way analysis of variance and a t-test (p < 0.05). Results. These experiments indicated that both static chemical fatigue and cyclic mechanical fatigue significantly reduced specimen strength, but they did not interact to produce greater than summative effects. It was also learned that chemical fatigue was not detected on initial exposure to moisture and that it occurred to a small extent during mechanical fatigue cycling, and primarily occurred during strength testing through a stress-corrosion phenomenon. Micrographs visually evaluated the effects of mechanical and chemical fatigue on surface contact damage. Significance. As both static chemical and cyclic mechanical fatigue influenced porcelain strength, they should both be considered in future evaluations. However, because they largely acted independently, they can be studied separately. C1 NATL CANC INST,ROCKVILLE,MD. RP White, SN (reprint author), UNIV SO CALIF,SCH DENT 4112,PINCUS BIOMAT RES LAB,LOS ANGELES,CA 90089, USA. FU NIDCR NIH HHS [DE RO3 11333-02] NR 24 TC 25 Z9 26 U1 0 U2 1 PU ACAD DENTAL MATERIALS PI DALLAS PA BAYLOR COLLEGE DENTISTRY, 3302 GASTON AVE, DALLAS, TX 75266-0677 SN 0109-5641 J9 DENT MATER JI Dent. Mater. PD MAR PY 1997 VL 13 IS 2 BP 103 EP 110 PG 8 WC Dentistry, Oral Surgery & Medicine; Materials Science, Biomaterials SC Dentistry, Oral Surgery & Medicine; Materials Science GA XM605 UT WOS:A1997XM60500005 PM 9467312 ER PT J AU Witta, SE Sato, SM AF Witta, SE Sato, SM TI XlPOU 2 is a potential regulator of Spemann's organizer SO DEVELOPMENT LA English DT Article DE XlPOU 2; POU domain; Spemann's Organizer; Xenopus ID BONE MORPHOGENETIC PROTEIN-4; HOMEO-BOX GENE; XENOPUS-EMBRYOS; NEURAL INDUCTION; VENTRALIZING FACTOR; MESODERM INDUCTION; AXIAL MESODERM; MARGINAL ZONE; CELL IDENTITY; FROG EMBRYOS AB XlPOU 2 a member of the class III POU-domain family, is expressed initially at mid-blastula transition (MET) and during gastrulation in the entire marginal zone mesoderm, including Spemann's Organizer (the Organizer). To identify potential targets of XlPOU 2, the interaction of XlPOU 2 with other genes co-expressed in the Organizer was examined by microinjecting XlPOU 2's mRNA into the lineage of cells that contributes to the Organizer, head mesenchyme and prechordal plate. XlPOU 2 suppresses the expression of a number of dorsal mesoderm-specific genes, including gsc, Xlim-1, Xotx2, noggin and chordin, but not Xnot. As a consequence of the suppression of dorsal mesoderm gene expression, bone morphogenetic factor-4 (Bmp-4), a potent inducer of ventral mesoderm, is activated in the Organizer. Gsc is a potential target of XlPOU 2. XlPOU 2 is capable of binding a class III POU protein binding site (CATTAAT) that is located within the gsc promoter, in the activin-inducible (distal) element. Furthermore, XlPOU 2 suppresses the activation of the gsc promoter by activin signaling. At the neurula and tailbud stages, dorsoanterior structures are affected: embryos displayed micropthalmia and the loss of the first branchial arch, as detected by the expression of pax-6, Xotx2 and en-2. By examining events downstream from the Wnt and chordin pathways, we determined that XlPOU 2, when overexpressed, acts specifically in the Organizer, downstream from GSK-3 beta of the Wnt pathway and upstream from chordin. The interference in dorsalizing events caused by XlPOU 2 was rescued by chordin. Thus, in addition to its direct neuralizing ability, in a different context, XlPOU 2 has the potential to antagonize dorsalizing events in the Organizer. C1 NIDDK,GENET & BIOCHEM BRANCH,NIH,BETHESDA,MD 20892. NR 76 TC 16 Z9 18 U1 0 U2 0 PU COMPANY OF BIOLOGISTS LTD PI CAMBRIDGE PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE, CAMBS, ENGLAND CB4 4DL SN 0950-1991 J9 DEVELOPMENT JI Development PD MAR PY 1997 VL 124 IS 6 BP 1179 EP 1189 PG 11 WC Developmental Biology SC Developmental Biology GA WR186 UT WOS:A1997WR18600009 PM 9102305 ER PT J AU BalintKurti, P Ginsburg, G RiveroLezcano, O Kimmel, AR AF BalintKurti, P Ginsburg, G RiveroLezcano, O Kimmel, AR TI rZIP, a RING-leucine zipper protein that regulates cell fate determination during Dictyostelium development SO DEVELOPMENT LA English DT Article DE zinc fingers; cAMP SH3 domains; trinucleotide repeats; Dictyostelium ID C-CBL PROTOONCOGENE; PATTERN-FORMATION; DNA-SEQUENCES; SH3 DOMAINS; KINASE; DISCOIDEUM; DROSOPHILA; PRESPORE; GENE; DIFFERENTIATION AB rZIP is an approx, 32 kDa, multi-domain protein of Dictyostelium discoideum whose structural motifs include a RING (zinc-binding) domain, a leucine zipper, a glutamine repeat, an SH3-binding region and a consensus phosphorylation site for MAP kinase, In vitro, rZIP forms homodimers and interacts specifically with the SH3 domain(s) of the Nck adaptor protein, rZIP is expressed maximally during cell differentiation at approximately equivalent levels in all cells, Disruption of the rZIP gene rzpA results in altered cellular aggregation, impaired slug migration, and aberrant patterning of prespore and prestalk cells, the major progenitor classes. In rzpA(-) strains, prespore-specific genes are overexpressed and prestalk expression zones are reduced, Conversely, constitutive overexpression of rzpA markedly decreases prespore-specific gene expression and significantly increases the expression of prestalk-specific genes. Further, induced transdifferentiation of prespore cells into prestalk cells is inhibited in rzpa(-) slugs, In light of these patterning defects, we suggest that the RING/zipper protein rZIP plays an important role in early cell fate decisions in Dictyostelium, acting as a positive regulator of prestalk differentiation and an inhibitor of prespore differentiation. C1 NIDDK,MMDS,CELLULAR & DEV BIOL LAB,BETHESDA,MD 20892. NIDR,CELLULAR DEV & ONCOL LAB,NIH,BETHESDA,MD 20892. RI Rivero-Lezcano, Octavio Miguel/J-9089-2015; OI Rivero-Lezcano, Octavio Miguel/0000-0002-8793-0731; Balint-Kurti, Peter/0000-0002-3916-194X NR 57 TC 13 Z9 14 U1 0 U2 0 PU COMPANY OF BIOLOGISTS LTD PI CAMBRIDGE PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE, CAMBS, ENGLAND CB4 4DL SN 0950-1991 J9 DEVELOPMENT JI Development PD MAR PY 1997 VL 124 IS 6 BP 1203 EP 1213 PG 11 WC Developmental Biology SC Developmental Biology GA WR186 UT WOS:A1997WR18600011 PM 9102307 ER PT J AU Cicchetti, D Richters, JE AF Cicchetti, D Richters, JE TI Examining the conceptual and scientific underpinnings of research in developmental psychopathology SO DEVELOPMENT AND PSYCHOPATHOLOGY LA English DT Editorial Material ID CHILD MALTREATMENT C1 NIMH,RES BRANCH,BETHESDA,MD. RP Cicchetti, D (reprint author), UNIV ROCHESTER,MT HOPE FAMILY CTR,187 EDINBURGH ST,ROCHESTER,NY 14608, USA. OI Richters, John/0000-0002-6780-1828 NR 16 TC 18 Z9 19 U1 1 U2 3 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 1997 VL 9 IS 2 BP 189 EP 191 PG 3 WC Psychology, Developmental SC Psychology GA XE595 UT WOS:A1997XE59500001 PM 9201441 ER PT J AU Richters, JE AF Richters, JE TI The Hubble hypothesis and the developmentalist's dilemma SO DEVELOPMENT AND PSYCHOPATHOLOGY LA English DT Review ID CONDUCT DISORDER; PSYCHOLOGY; PSYCHOPATHOLOGY; DEDUCTIVISM; CONTEXT AB Development psychopathology stands poised at the close of the 20th century on the horns of a major scientific dilemma. The essence of this dilemma lies in the contrast between its heuristically rich open system concepts on the one hand, and the closed system paradigm it adopted from mainstream psychology for investigating those models on the other. Many of the research methods, assessment strategies, and data analytic models of psychology's paradigm are predicted on closed system assumptions and explanatory models. Thus, they are fundamentally inadequate for studying humans, who are unparalleled among open systems in their wide ranging capacities for equifinal and multifinal functioning. Development psychopathology faces two challenges in successfully negotiating the developmentalist's dilemma. The first lies in recognizing how the current paradigm encourages research practices that are antithetical to development principles, yet continue to flourish. I argue that the developmentalist's dilemma is sustained by long standing, mutually enabling weaknesses in the paradigm's discovery methods and scientific standards. These interdependent weaknesses function like a distorted lens on the research process by variously sustaining the illusion of theoretical progress, obscuring the need for fundamental reforms, and both constraining and misguiding reform efforts. An understanding of how these influences arise and take their toll provides a foundation and rationale for engaging the second challenge. The essence of this challenge will be finding ways to resolve the developmentalist's dilemma outside the constraints of the existing paradigm by developing indigenous research strategies, methods, and standards with fidelity to the complexity of development phenomena. RP Richters, JE (reprint author), NIMH,CHILD & ADOLESCENT DISORDER BRANCH,ROOM 18C-17,5600 FISHERS LANE,ROCKVILLE,MD 20857, USA. OI Richters, John/0000-0002-6780-1828 NR 114 TC 110 Z9 111 U1 0 U2 4 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 1997 VL 9 IS 2 BP 193 EP 229 PG 37 WC Psychology, Developmental SC Psychology GA XE595 UT WOS:A1997XE59500002 PM 9201442 ER PT J AU Jensen, PS Hoagwood, K AF Jensen, PS Hoagwood, K TI The book of names: DSM-IV in context SO DEVELOPMENT AND PSYCHOPATHOLOGY LA English DT Article ID DEFICIT HYPERACTIVITY DISORDER; DIAGNOSTIC INTERVIEW SCHEDULE; ATTENTION-DEFICIT; 1ST-EPISODE SCHIZOPHRENIA; PSYCHIATRIC-DIAGNOSIS; HARMFUL DYSFUNCTION; MENTAL DISORDER; RISK-FACTORS; CHILDREN; VALIDITY AB The authors review the constraints of current mental disorder classification systems that rely upon descriptive symptom-based approaches, and weigh the benefits and hazards of these classification and diagnostic strategies. By focusing principally on superficial descriptions of symptoms. current systems fail to address the complex nature of persons transactions within and adaptations to difficult environments, While attempting to be atheoretical, current systems exclude types of information that may elucidate individuals' functioning across various contests, often because it is difficult to obtain such data reliably. With current approaches, misdiagnosis is likely, particularly when diagnostic criteria are applied to persons in nonclinical settings. Alternative approaches that take fuller advantage of clinicians' expertise and other forms of clinical data are reviewed. and recommendations are made for the next generation of classification systems. Application of evolutionary theory to psychiatry and psychology, as well as development of a theory and nosology of context in terms if persons' adaptations. are needed to expand our knowledge of normal and abnormal human development and psychopathology. C1 NIMH,SERV RES BRANCH,BETHESDA,MD. RP Jensen, PS (reprint author), NIMH,CHILD & ADOLESCENT DISORDERS RES BRANCH,ROOM 18-C17,5600 FASHERS LANE,ROCKVILLE,MD 20857, USA. OI Jensen, Peter/0000-0003-2387-0650 NR 80 TC 66 Z9 66 U1 4 U2 7 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 1997 VL 9 IS 2 BP 231 EP 249 PG 19 WC Psychology, Developmental SC Psychology GA XE595 UT WOS:A1997XE59500003 PM 9201443 ER PT J AU Schmidt, LA Fox, NA Rubin, KH Sternberg, EM Gold, PW Smith, CC Schulkin, J AF Schmidt, LA Fox, NA Rubin, KH Sternberg, EM Gold, PW Smith, CC Schulkin, J TI Behavioral and neuroendocrine responses in shy children SO DEVELOPMENTAL PSYCHOBIOLOGY LA English DT Article; Proceedings Paper CT 21st Annual Meeting of the Society-for-Neuroscience CY NOV 13, 1995 CL SAN DIEGO, CA SP Soc Neurosci DE temperament; fear; behavioral inhibition; shyness; startle; salivary cortisol; amygdala ID CORTICOTROPIN-RELEASING FACTOR; AMYGDALA CENTRAL NUCLEUS; ACOUSTIC STARTLE REFLEX; PARAVENTRICULAR NUCLEUS; BIOCHEMICAL MANIFESTATIONS; CONDITIONED FEAR; MESSENGER-RNA; INHIBITION; CORTISOL; EMOTION AB Previous research has shown that infants who display a high frequency of motor activity and negative affect at 4 months of age are likely to be behaviorally inhibited toddlers. We examined social behaviors, maternal report of temperament, salivary cortisol, and baseline startle responses at age 4 in a sample of children, some of whom displayed a high frequency of motor activity and negative affect at 4 months of age. Infants who displayed this temperamental profile were reported by their mothers as more shy at age 4 compared with other children. We also found that I-year-olds who displayed a high frequency of wary behavior during peer play exhibited relatively high morning salivary cortisol, were reported as contemporaneously shy by their mothers, and were behaviorally inhibited at 14 months of age. There were no significant relations found between baseline startle and morning salivary cortisol and measures of shyness at age 4. We speculate that high levels of cortisol in shy children may induce changes in the amygdala, exacerbating their fearfulness. (C) 1997 John Wiley & Sons, Inc. C1 NIMH, NEUROENDOCRINE IMMUNOL & BEHAV UNIT, CLIN NEUROENDOCRINOL BRANCH, BETHESDA, MD 20892 USA. NIMH, BEHAV NEUROSCI UNIT, CLIN NEUROENDOCRINOL BRANCH, BETHESDA, MD 20892 USA. RP Schmidt, LA (reprint author), UNIV MARYLAND, INST CHILD STUDY, COLLEGE PK, MD 20742 USA. FU NICHD NIH HHS [HD 17899] NR 59 TC 175 Z9 176 U1 4 U2 7 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0012-1630 EI 1098-2302 J9 DEV PSYCHOBIOL JI Dev. Psychobiol. PD MAR PY 1997 VL 30 IS 2 BP 127 EP 140 DI 10.1002/(SICI)1098-2302(199703)30:2<127::AID-DEV4>3.0.CO;2-S PG 14 WC Developmental Biology; Psychology SC Developmental Biology; Psychology GA WM131 UT WOS:A1997WM13100004 PM 9068967 ER PT J AU McCance, DR Hanson, RL Pettitt, DJ Bennett, PH Hadden, DR Knowler, WC AF McCance, DR Hanson, RL Pettitt, DJ Bennett, PH Hadden, DR Knowler, WC TI Diagnosing diabetes mellitus - Do we need new criteria? SO DIABETOLOGIA LA English DT Review DE diabetes mellitus; diagnosis; oral glucose tolerance test; fasting plasma glucose; 2-h plasma glucose; haemoglobin A(1c); retinopathy; nephropathy; complications ID PLASMA-GLUCOSE CONCENTRATIONS; PIMA-INDIANS; GLYCATED HEMOGLOBIN; GLYCOSYLATED HEMOGLOBIN; INSULIN-RESPONSE; TOLERANCE TEST; INTRAVENOUS GLUCOSE; GLUCOKINASE GENE; SCREENING-TESTS; BIMODALITY AB The current classification and diagnostic criteria for diabetes mellitus were introduced by the United States National Data Group in 1979 and endorsed by the World Health Organization in 1980, with modifications in 1985 and 1994. The criteria, chosen to reflect the risk of complications, were the synthesis of considerable thought and expertise and represented a consensus which, it was hoped, would prove helpful to all those involved with diabetes practising clinician, research scientist and epidemiologist alike. The inconvenience, variability and non-physiological nature of the oral glucose tolerance test (OGTT) are well-recognised. In spite of these limitations the 2-h post-load plasma glucose has remained the standard against which all other tests have been evaluated. This article reviews the original justification for the OGTT, and in the light of more recent epidemiological research seeks to place the current diagnostic criteria for diabetes into a pathophysiological, diagnostic and prognostic perspective. C1 NIDDKD,DIABET & ARTHRIT EPIDEMIOL SECT,PHOENIX,AZ. RP McCance, DR (reprint author), ROYAL VICTORIA HOSP,SIR GEORGE E CLARK METAB UNIT,BELFAST BT12 6BA,ANTRIM,NORTH IRELAND. RI Hanson, Robert/O-3238-2015 OI Hanson, Robert/0000-0002-4252-7068 NR 92 TC 69 Z9 70 U1 0 U2 2 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0012-186X J9 DIABETOLOGIA JI Diabetologia PD MAR PY 1997 VL 40 IS 3 BP 247 EP 255 DI 10.1007/s001250050671 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA WL952 UT WOS:A1997WL95200001 PM 9084961 ER PT J AU DeSilva, MG Notkins, AL Lan, MS AF DeSilva, MG Notkins, AL Lan, MS TI Molecular characterization of a pancreas-specific protein disulfide isomerase, PDIp SO DNA AND CELL BIOLOGY LA English DT Article ID ENDOPLASMIC-RETICULUM PROTEIN; N-GLYCOSIDASE-F; DISULPHIDE-ISOMERASE; SECRETORY PROTEINS; PEPTIDE BINDING; SEQUENCE; THIOREDOXIN; EXPRESSION; CLONING; GENE AB A novel tissue-specific cDNA, PDIp, was previously isolated from human pancreas. It encodes a protein that is structurally and functionally related to protein disulfide isomerase (PDI). To compare the expression pattern of PDI and PDIp in human pancreas and liver tissues, we prepared rabbit polyclonal antiserum against a recombinant glutathione-S-transferase-coupled PDIp fusion protein, Western blot analysis revealed that pancreas expresses both PDI and PDIp, whereas liver only expresses PDI. Rabbit antiserum raised against recombinant PDIp immunostained specifically to the acinar cells of human pancreas, Treatment of PDIp with peptide:N-glycosidase F caused PDIp down shift in the NaDodSO(4)-PAGE gel, indicating that PDIp is a glycoprotein. A 2.0-kb message was detected from mouse pancreas using a human PDIp cDNA probe, Similarly, PDIp glycoprotein was detected in mouse pancreas extract by anti-human PDIp antiserum, suggesting that PDIp is highly conserved in human and mouse pancreas, From these studies, we conclude that the pancreas expresses two members of PDI and that PDIp is a glycoprotein specifically expressed in pancreatic acinar cells. C1 NIDR,ORAL MED LAB,NIH,BETHESDA,MD 20892. NR 30 TC 39 Z9 43 U1 0 U2 2 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 SN 1044-5498 J9 DNA CELL BIOL JI DNA Cell Biol. PD MAR PY 1997 VL 16 IS 3 BP 269 EP 274 DI 10.1089/dna.1997.16.269 PG 6 WC Biochemistry & Molecular Biology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Cell Biology; Genetics & Heredity GA WR538 UT WOS:A1997WR53800003 PM 9115635 ER PT J AU Sei, Y vonLubitz, DKJE Abbracchio, MP Ji, XD Jacobson, KA AF Sei, Y vonLubitz, DKJE Abbracchio, MP Ji, XD Jacobson, KA TI Adenosine A(2) receptor agonist-induced neurotoxicity in rat cerebellar granule neurons SO DRUG DEVELOPMENT RESEARCH LA English DT Article DE adenosine receptors; nucleosides; neurotoxicity; adenylate cyclase; glutamic acid; brain ID CEREBRAL-ISCHEMIA; ADENINE-NUCLEOTIDES; CELLS; RELEASE AB Acute stimulation of A(3) adenosine receptors has been shown to intensify damage in an in vivo model of global cerebral ischemia and to induce cell death in cell cultures. To investigate the mechanism for these cytotoxic phenomena, adenosine analogs of varied receptor subtype selectivities were applied directly to rat cerebellar granule neurons in culture. Agonists of A(1), A(2A), and/or A(2B) receptors (CPA, NECA and CCS 21680) had no effect on neuronal survival during a 16 h incubation period. The highly selective adenosine A(3) receptor agonist 2-chloro-N-6-(3-iodobenzyl)adenosine-5'-N-methyluronamide (Cl-lB-MECA) at greater than or equal to 10 mu M induced cell death in a concentration-dependent fashion. A structurally related nucleoside, cladribine, which has cytotoxic properties via a non-adenosine receptor related mechanism, had no effect on cell survival. Adding dbcAMP to the culture to activate cyclic AMP-dependent protein kinases attenuated Cl-lB-MECA-induced neurotoxicity, suggesting the Cl-lB-MECA-induced neuronal cell death is mediated by an inhibition of cyclic AMP production. Glutamate (50 mu M) induced cell death to a degree comparable to that induced by 10 mu M Cl-lB-MECA. Furthermore, a subcytotoxic concentration of Cl-lB-MECA (1 mu M) significantly augmented glutamate neurotoxicity. In contrast, the adenosine A(1)/A(2) agonists, the adenosine A(1)/A(2) antagonist XAC, and the A(2A) antagonist SCH 58261 at micromolar concentrations had no effect on neuronal viability or on glutamate neurotoxicity. These results suggest that activation of adenosine Ag receptors may play an important role in regulating neuronal survival and death in cerebellar neurons. Drug Dev. Res. 40:267-273, 1997. (C) 1997 Wiley-Liss, Inc. C1 NIDDK, MOL RECOGNIT SECT, LBC, NIH, BETHESDA, MD 20892 USA. NIDDK, NEUROSCI LAB, NIH, BETHESDA, MD 20892 USA. UNIV MILAN, SCH PHARM, INST PHARMACOL SCI, MILAN, ITALY. RI Jacobson, Kenneth/A-1530-2009; Abbracchio, Maria Pia/B-9342-2014 OI Jacobson, Kenneth/0000-0001-8104-1493; Abbracchio, Maria Pia/0000-0002-7833-3388 NR 33 TC 34 Z9 34 U1 1 U2 1 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 1997 VL 40 IS 3 BP 267 EP 273 DI 10.1002/(SICI)1098-2299(199703)40:3<267::AID-DDR7>3.0.CO;2-I PG 7 WC Chemistry, Medicinal; Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA XP496 UT WOS:A1997XP49600007 ER PT J AU Lipska, BK Weinberger, DR AF Lipska, BK Weinberger, DR TI Novel research strategies in the pharmacology of schizophrenia SO DRUGS OF TODAY LA English DT Review ID EXCITOTOXIC HIPPOCAMPAL DAMAGE; ATYPICAL ANTIPSYCHOTIC-DRUGS; LONG-TERM HALOPERIDOL; C-FOS EXPRESSION; NUCLEUS-ACCUMBENS; DOPAMINE NEURONS; GENE-EXPRESSION; CLOZAPINE TREATMENT; RAT FOREBRAIN; INDUCE FOS AB Currently available drugs to treat schizophrenia prove to be only partially effective and often produce disturbing side effects. Because pathophysiological mechanisms underlying schizophrenia are unclear, and animal models with construct validity virtually do not exist, pharmaceutical research faces considerable difficulties in its attempt to develop more effective drugs to treat this disorder. Recent findings reviewed in this article about differences in the mode of action between typical and atypical neuroleptic drugs may provide some clues about the disease itself and about potential new therapies. The discovery of novel dopamine receptor subtypes as potential targets for the antipsychotic action may offer new possibilities for pharmaceutical industry. Glutamatergic AMPA receptors seem to be another important potential site of action for novel antischizophrenic drugs, in particular those targeting negative symptoms. Findings from studies on the effects of chronic treatment with typical and atypical drugs on postreceptor intracellular processes, such as expression of genes encoding transcription factors or their target genes, may elucidate mechanisms by which these drugs exert their therapeutic action. Finally, novel animal models with construct and predictive validity, which address neurodevelopmental aspects of the disorder, may bring us better understanding of the human disease and offer a novel strategy to explore unconventional treatment. RP Lipska, BK (reprint author), NIMH,CLIN BRAIN DISORDERS BRANCH,INTRAMURAL RES PROGRAM,NIH,NEUROSCI CTR ST ELIZABETHS,WASHINGTON,DC 20032, USA. RI Lipska, Barbara/E-4569-2017 NR 109 TC 3 Z9 3 U1 1 U2 2 PU J R PROUS SA PI BARCELONA PA APARTADO DE CORREOS 540, PROVENZA 388, 08025 BARCELONA, SPAIN SN 0025-7656 J9 DRUGS TODAY JI Drugs Today PD MAR PY 1997 VL 33 IS 2 BP 103 EP 113 PG 11 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA WT743 UT WOS:A1997WT74300004 ER PT J AU Sonies, B AF Sonies, B TI Dysphagia Research Society 1996 SO DYSPHAGIA LA English DT Editorial Material RP Sonies, B (reprint author), NIH,BLDG 10,BETHESDA,MD 20892, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0179-051X J9 DYSPHAGIA JI Dysphagia PD SPR PY 1997 VL 12 IS 2 BP 120 EP 120 PG 1 WC Otorhinolaryngology SC Otorhinolaryngology GA WL632 UT WOS:A1997WL63200010 ER PT J AU Roth, BJ Ko, D vonAlbertiniCarletti, IR Scaffidi, D Sato, S AF Roth, BJ Ko, D vonAlbertiniCarletti, IR Scaffidi, D Sato, S TI Dipole localization in patients with epilepsy using the realistically shaped head model SO ELECTROENCEPHALOGRAPHY AND CLINICAL NEUROPHYSIOLOGY LA English DT Article DE epilepsy; EEG; dipole; localization; realistically shaped head model; three-sphere model AB Dipole sources were localized in 3 patients with epilepsy using both the realistically shaped head model and the 3-sphere model. Interictal spikes were recorded from 63 closely spaced scalp electrodes. The scalp, skull, and brain surfaces were digitized from a MRI of each patient's head, and each surface was tessellated by 1600 triangles. Single dipole fits to the EEG were performed using both the realistically shaped head model and the 3-sphere model. The 2 models localized dipoles to positions that differed from one another by 1-3 cm. For dipoles localized to the temporal lobe, the most important difference between models was that the realistically shaped head model localized the dipole lower in the brain than the 3-sphere model. The realistically shaped head model was more in accordance with the ECoG findings than the 3-sphere model. (C) 1997 Elsevier Science Ireland Ltd. C1 NINCDS,CLIN NEUROPHYSIOL UNIT,EPILEPSY RES BRANCH,NIH,BETHESDA,MD 20892. RP Roth, BJ (reprint author), VANDERBILT UNIV,DEPT PHYS & ASTRON,BOX 1807,NASHVILLE,TN 37235, USA. RI Roth, Bradley/A-4920-2008 NR 10 TC 66 Z9 67 U1 2 U2 2 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0013-4694 J9 ELECTROEN CLIN NEURO JI Electroencephalogr. Clin. Neurophysiol. PD MAR PY 1997 VL 102 IS 3 BP 159 EP 166 DI 10.1016/S0013-4694(96)95111-5 PG 8 WC Engineering, Biomedical; Clinical Neurology SC Engineering; Neurosciences & Neurology GA WR224 UT WOS:A1997WR22400001 PM 9129570 ER PT J AU Li, G Waltham, M Anderson, NL Unsworth, E Treston, A Weinstein, JN AF Li, G Waltham, M Anderson, NL Unsworth, E Treston, A Weinstein, JN TI Rapid mass spectrometric identification of proteins from two-dimensional polyacrylamide gels after in gel proteolytic digestion SO ELECTROPHORESIS LA English DT Article; Proceedings Paper CT 2nd Siena 2D Electrophoresis - From Genome to Proteome CY SEP 16-18, 1996 CL SIENA, ITALY DE matrix assisted laser desorption ionization - mass spectrometry; two-dimensional polyacrylamide gel electrophoresis; proteolytic digestion; peptides; protein identification ID SEPARATED PROTEINS; SEQUENCE DATABASES; GENE-REGULATION; ELECTROPHORESIS; IONIZATION; ACRYLAMIDE; FRAGMENTS AB We report a rapid method for identifying proteins resolved by two-dimensional polyacrylamide gel electrophoresis (2-D PAGE) using matrix-assisted laser desorption ionization-mass spectrometry (MALDI-MS). In-gel digestion was performed in a way such that the volume ratio of trypsin solution to gel plug was quantitatively controlled to promote reproducible digestion and to maximize the digestion yield. To make the digestion samples more compatible with MALDI-MS, the volatile salt ammonium bicarbonate in the digestion buffer was largely removed prior to peptide extraction. Samples of mixed tryptic peptides from in-gel digestion were used without purification to obtain molecular weights by MALDI-MS with a-cyano, 4-hydroxy-cinnamic acid as the matrix. Modifications of MALDI sample loading procedures improved the detection sensitivity by one half to one order of magnitude. The peptide mass peaks in MALDI-MS spectra were distinguished from those of impurities by using several types of controls, and masses were corrected by using trypsin autodigestion fragments as internal calibration standards. Two different peptide-matching computer programs were used to interrogate sequence databases and identify proteins. Identification was enhanced by generation of orthogonal data sets (by using different proteases) and by including experimental values of isoelectric point (pI) and molecular weight to exclude false entries in the candidate lists. Approximately 1% of the material from a spot was used in each sample loading, and nine protein spots from rat liver 2-D PAGE gels were identified correctly, as judged by comparison with identification results previously obtained from Edman sequencing. A previously identified low-abundance spot was not identified by MALDI-MS, presumably because there was insufficient material in a single gel. The sample handling procedure reported here should permit us to identify many 2-D PAGE protein spots of medium abundance. C1 NCI,MOL PHARMACOL LAB,DIV BASIC SCI,NIH,BETHESDA,MD 20892. LARGE SCALE BIOL CORP,ROCKVILLE,MD. US FDA,BETHESDA,MD 20014. NCI,BIOMARKERS & PREVENT RES BRANCH,DIV CANC PREVENT & CONTROL,ROCKVILLE,MD. RI Waltham, Mark/A-1728-2009; OI Li, Guang/0000-0002-9022-2883 NR 38 TC 72 Z9 72 U1 1 U2 3 PU VCH PUBLISHERS INC PI DEERFIELD BEACH PA 303 NW 12TH AVE, DEERFIELD BEACH, FL 33442-1788 SN 0173-0835 J9 ELECTROPHORESIS JI Electrophoresis PD MAR-APR PY 1997 VL 18 IS 3-4 BP 391 EP 402 DI 10.1002/elps.1150180313 PG 12 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA WW358 UT WOS:A1997WW35800012 PM 9150917 ER PT J AU Lemkin, PF AF Lemkin, PF TI Comparing two-dimensional electrophoretic gel images across the Internet SO ELECTROPHORESIS LA English DT Article; Proceedings Paper CT 2nd Siena 2D Electrophoresis - From Genome to Proteome CY SEP 16-18, 1996 CL SIENA, ITALY DE image comparison; World Wide Web; Java; Internet; two-dimensional polyacrylamide electrophoresis; databases ID PROTEIN DISEASE DATABASE; HUMAN-BODY FLUIDS; SWISS-2DPAGE DATABASE; COMPUTER AB Scientists around the world often work on similar data so the need to share results and compare data arises periodically. We describe a method of comparing two two-dimensional (2-D) protein gels of similar samples created in different laboratories to help identify or suggest protein spot identification. Now that 2-D gels and associated databases frequently appear on the Internet, this opens up the possibility of visually comparing one's own experimental 2-D gel image data with data from another gel in a remote Internet database. In general, there are a few ways to compare images: (i) slide one gel (autoradiograph or stained gel) over the other while back-illuminated, or (ii) build a 2-D gel computer database from both gels after scanning and analyzing these gels. These are impractical since in the first case the gel from the Internet database is not locally available. In the second, the costs of building a multi-gel database solely to answer the question of whether a spot is the same spot may be excessive if only a single visual comparison is needed, We describe a distributed gel comparison program (URL: http://www-1mmb.ncifcrf.gov/flicker) which runs on any World Wide Web (WWW) connected computer and is invoked from a Java-capable web browser. One gel image is read from any Internet 2-D gel database (e.g. SWISS-2DPAGE) and the other may reside on the investigator's computer. Images may be more easily compared by first applying spatial warping or other transforms interactively on the user's computer. First, regions of interest are ''landmarked'' with several corresponding points in each gel image, then one gel image is warped to the geometry of the other. As the two gels are rapidly alternated, or flickered, in the same window, the user can slide one gel past the other to visually align corresponding spots by matching local morphology, This flicker-comparison technique may be applied to analyzing other types of one-dimensional and 2-D biomedical images. RP Lemkin, PF (reprint author), NCI,IMAGE PROC SECT,LMMB,FCRDC,NIH,BLD 469 ROOM 150,FREDERICK,MD 21702, USA. NR 28 TC 51 Z9 51 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 1997 VL 18 IS 3-4 BP 461 EP 470 DI 10.1002/elps.1150180321 PG 10 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA WW358 UT WOS:A1997WW35800020 PM 9150925 ER PT J AU Sanchez, JC Wirth, P Jaccoud, S Appel, RD Sarto, C Wilkins, MR Hochstrasser, DF AF Sanchez, JC Wirth, P Jaccoud, S Appel, RD Sarto, C Wilkins, MR Hochstrasser, DF TI Simultaneous analysis of cyclin and oncogene expression using multiple monoclonal antibody immunoblots SO ELECTROPHORESIS LA English DT Article; Proceedings Paper CT 2nd Siena 2D Electrophoresis - From Genome to Proteome CY SEP 16-18, 1996 CL SIENA, ITALY DE immunoblotting; two-dimensional polyacrylamide gel electrophoresis; immobilized pH gradient; protein identification ID 2-DIMENSIONAL ELECTROPHORESIS; GEL-ELECTROPHORESIS; PROTEIN EXPRESSION; CELLS; CANCER; GENES AB Cell dysfunction or dysregulation in cancer generally results from complex gene interactions, numerous cellular events and environmental influences which modify gene expression or post-translational protein modifications. Genetic analysis in itself cannot always predict: or diagnose multigenic diseases. The major technical difficulty is thus to defect, identify and measure simultaneously the expression of several genes and the post-translational modifications of their products. In order to progress io this direction, this paper describes a simple immunoblot method using several monoclonal antibodies to simultaneously analyze oncogene expression and cell cycle specific checkpoints in patient solid biopsies and transformed cell lines. One mg of normal human liver biopsy and HEPG2 (hepatoblastoma-derived cell line) protein samples have been separated by two-dimensional polyacrylamide gel electrophoresis (2-D PAGE) and transferred onto polyvinylidene difluoride (PVDF) membranes. The membranes were stained with amido black, scanned and tested separately with the nine monoclonal antibodies p53, c-myc, PCNA, MEK1, pan-ras, Cip1, Cdc2, Kip1, and TCTP. The nine antibodies of interest were then combined to form a mixture, and simultaneously used as the primary antibobies. This antibody mixture simultaneously detected the nine proteins of interest on both samples and it demonstrated the extensive expression changes and the presence of various isoforms most likely due to post-translational modifications of gene products. C1 UNIV HOSP GENEVA,CLIN CHEM LAB,GENEVA,SWITZERLAND. NCI,EXPT CARCINOGENESIS LAB,BETHESDA,MD 20892. UNIV HOSP GENEVA,CTR HOSP INFORMAT,GENEVA,SWITZERLAND. DESIO HOSP,CLIN CHEM LAB,MILAN,ITALY. UNIV GENEVA,DEPT BIOCHEM MED,GENEVA,SWITZERLAND. NR 27 TC 20 Z9 20 U1 0 U2 3 PU VCH PUBLISHERS INC PI DEERFIELD BEACH PA 303 NW 12TH AVE, DEERFIELD BEACH, FL 33442-1788 SN 0173-0835 J9 ELECTROPHORESIS JI Electrophoresis PD MAR-APR PY 1997 VL 18 IS 3-4 BP 638 EP 641 DI 10.1002/elps.1150180349 PG 4 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA WW358 UT WOS:A1997WW35800048 PM 9150953 ER PT J AU Myers, TG Anderson, NL Waltham, M Li, G Buolamwini, JK Scudiero, DA Paull, KD Sausville, EA Weinstein, JN AF Myers, TG Anderson, NL Waltham, M Li, G Buolamwini, JK Scudiero, DA Paull, KD Sausville, EA Weinstein, JN TI A protein expression database for the molecular pharmacology of cancer SO ELECTROPHORESIS LA English DT Article; Proceedings Paper CT 2nd Siena 2D Electrophoresis - From Genome to Proteome CY SEP 16-18, 1996 CL SIENA, ITALY DE two-dimensional polyacrylamide gel electrophoresis; protein database; cancer; pharmacology; chemosensitivity; cell culture; cell line; drug ID TUMOR-CELL-LINES; ANTICANCER DRUG SCREEN; INSTITUTE; DISCOVERY; FEASIBILITY; PROGRAM; ASSAY AB In the last six years, the Developmental Therapeutics Program (DTP) of the US National Cancer Institute (NCI) has screened over 60 000 chemical compounds and a larger number of natural product extracts for their ability to inhibit growth of 60 different cancer cell lines representing different organs of origin. Whereas inhibition of the growth of one cancer cell type gives no information on drug specificity, the relative growth inhibitory activities against 60 different cells constitute patterns that encode detailed information on mechanisms of action and resistance (as reviewed in Boyd and Paull, Drug Devel. Res. 1995, 34, 19-109 and Weinstein et al., Science 1997, 275, 343-349). In order to correlate the patterns of activity with properties of the cells, we and other laboratories are characterizing the cells with respect to a large number of factors at the DNA, mRNA, and protein levels. As part of that effort, we have developed a two-dimensional gel electrophoresis (2-DE) protein expression database covering all 60 cell types (Buolamwini ct al., submitted). Here we present analyses of the correlations among protein spots (i) in terms of their patterns of expression and (ii) in terms of their apparent relationships to the pharmacology of a set of 3989 screened compounds. The correlations tend to be stronger for the latter than for the former, suggesting that the spots have more robust signatures in terms of the pharmacology than in terms of expression levels. Links to pertinent databases and tools of analysis will be updated progressively at http ://www.nci.nih.gov/intra/lmp/jnwbio.htm and http ://epnwsl.ncifcrf.gov:2345/dis3d/dtp.html. C1 LARGE SCALE BIOL INC, ROCKVILLE, MD USA. NCI, FREDERICK CANC RES & DEV CTR, SAIC, FREDERICK, MD USA. NCI, INFORMAT TECHNOL BRANCH, DEV THERAPEUT PROGRAM, DIV CANC TREATMENT DIAGNOSIS, BETHESDA, MD 20892 USA. NCI, DCTDC, DTP, BETHESDA, MD 20892 USA. NCI, DIV BASIC SCI, MOL PHARMACOL LAB, BETHESDA, MD 20892 USA. RI Waltham, Mark/A-1728-2009; OI Li, Guang/0000-0002-9022-2883 NR 22 TC 70 Z9 73 U1 0 U2 1 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0173-0835 J9 ELECTROPHORESIS JI Electrophoresis PD MAR-APR PY 1997 VL 18 IS 3-4 BP 647 EP 653 DI 10.1002/elps.1150180351 PG 7 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA WW358 UT WOS:A1997WW35800050 PM 9150955 ER PT J AU Katzenellenbogen, BS Korach, KS AF Katzenellenbogen, BS Korach, KS TI A new actor in the estrogen receptor drama - Enter ER-beta SO ENDOCRINOLOGY LA English DT Editorial Material ID PROMOTER-CONTEXT; ANTIESTROGEN; EXPRESSION; SEQUENCE; TURNOVER; DYNAMICS C1 NIEHS, REPROD & DEV TOXICOL LAB, NIH, RES TRIANGLE PK, NC 27709 USA. RP Katzenellenbogen, BS (reprint author), UNIV ILLINOIS, DEPT MOL & INTEGRAT PHYSIOL, 524 BURRILL HALL, 407 S GOODWIN AVE, URBANA, IL 61801 USA. NR 22 TC 130 Z9 134 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 1997 VL 138 IS 3 BP 861 EP 862 DI 10.1210/en.138.3.861 PG 2 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA WJ739 UT WOS:A1997WJ73900001 PM 9048583 ER PT J AU Tonshoff, B Powell, DR Zhao, DL Durham, SK Coleman, ME Domene, HM Blum, WF Baxter, RC Moore, LC Kaskel, FJ AF Tonshoff, B Powell, DR Zhao, DL Durham, SK Coleman, ME Domene, HM Blum, WF Baxter, RC Moore, LC Kaskel, FJ TI Decreased hepatic insulin-like growth factor (IGF)-I and increased IGF binding protein-1 and -2 gene expression in experimental uremia SO ENDOCRINOLOGY LA English DT Article ID CHRONIC-RENAL-FAILURE; MESSENGER RIBONUCLEIC-ACIDS; ADULT-RAT LIVER; FACTOR-I; TISSUE DISTRIBUTION; HORMONE RECEPTOR; MOLECULAR-CLONING; SERUM; CHILDREN; RNA AB The imbalance between normal insulin-like growth factor-I (IGF-I) and markedly increased IGF binding protein (IGFBP) plasma levels plays a pathogenic role for growth retardation and catabolism in children with chronic renal failure. To investigate the mechanism of these alterations, experiments were performed in an experimental model of uremia in rats (5/6 nephrectomy) and in pair-fed and ad libitum-fed sham-operated controls. Using a specific solution hybridization/RNase protection assay, we observed a marked reduction of hepatic IGF-I messenger RNA (mRNA) abundance at steady state in uremic animals (37+/-5% of control) compared both with pair-fed (65+/-10%) and ad libitum-fed controls (100=11%) (P <0.001). Reduced IGF-I gene expression was clearly organ-specific; it was most pronounced in liver (significant vs.. pair-fed controls) and lung and muscle tissue (significant vs.. ad libitum-fed controls); no change was observed in kidney and heart tissue. To determine a potential mechanism of reduced hepatic IGF-I gene expression in uremia, the hepatic GH receptor gene expression in the same experimental animals was analyzed by specific solution hybridization/RNase protection assay. Uremic animals had a 20-30% reduction of hepatic GH receptor mRNA abundance compared with controls. Hepatic GHBP expression in uremia was decreased in parallel. Despite the reduction of hepatic IGF-I mRNA abundance, plasma IGF-I levels in uremia were not different from ad libitum-fed controls. This discrepancy is explained by an increased concentration of IGFBPs in uremic plasma. By RIA, plasma IGFBP-1 levels in uremia were increased 4-fold; by Western immunoblot, plasma IGFBF-2 levels were increased 7-fold and plasma IGFBP-4 levels were increased 2-fold compared with both control groups. Intact IGFBP-3 (M(r), similar to 48 kDa) and low molecular IGFBP-3 fragments mere not significantly different among the three groups. By Northern blot analysis, hepatic IGFBP-1 mRNA levels in uremia were 2-fold higher than in controls. IGFBP-2 mRNA abundance in Liver tissue was increased 4-fold, whereas in kidney there was a significant reduction of IGFBP-2 mRNA (30% of control). IGFBP-4 mRNA was increased by 50% in kidney but not in liver. Plasma insulin and corticosterone levels were not different among the groups. Our study shows that hepatic IGF-I gene expression was specifically reduced in uremia, partially as the consequence of a reduced hepatic GH receptor gene expression. One of the mechanisms contributing to increased IGFBP levels in uremia is increased hepatic gene expression of IGFBP-1 and IGFBP-5. The imbalance between reduced hepatic TGF-I production and increased hepatic IGFBP-1 and -2 production is likely to play a pathogenic role for catabolism and growth failure in CRF. C1 SUNY STONY BROOK, DEPT PEDIAT & PHYSIOL, STONY BROOK, NY 11794 USA. BAYLOR COLL MED, DEPT PEDIAT, HOUSTON, TX 77030 USA. NIDDKD, NIH, BETHESDA, MD 20892 USA. UNIV GIESSEN, CHILDRENS HOSP, D-35385 GIESSEN, GERMANY. KOLLING INST MED RES, ST LEONARDS, NSW 2065, AUSTRALIA. RI Baxter, Robert/F-3927-2012 OI Baxter, Robert/0000-0001-5061-2142 NR 51 TC 51 Z9 51 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 1997 VL 138 IS 3 BP 938 EP 946 DI 10.1210/en.138.3.938 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA WJ739 UT WOS:A1997WJ73900011 PM 9048593 ER PT J AU Chin, E Zamah, AM Landau, D Gronboek, H Flyvbjerg, A Leroith, D Bondy, CA AF Chin, E Zamah, AM Landau, D Gronboek, H Flyvbjerg, A Leroith, D Bondy, CA TI Changes in facilitative glucose transporter messenger ribonucleic acid levels in the diabetic rat kidney SO ENDOCRINOLOGY LA English DT Article ID RENAL HYPERTROPHY; TUBULAR FUNCTION; GENE-EXPRESSION; MELLITUS; METABOLISM; INTESTINE; MECHANISM; PROTEIN; FAMILY; SODIUM AB Facilitative glucose transporter (GLUTs 1, 2, 4, and 5) messenger RNAs (mRNAs) are differentially distributed in the rat nephron: GLUT1 is widely expressed, GLUT4 is selectively concentrated in thick ascending limbs, and GLUT2 and 5 are exclusively localized in proximal tubules, consistent with differential roles for these transporters in renal glucose handling. In the present study, quantitative in situ hybridization was used to evaluate changes in these mRNA levels during acute (2 and 7 days) and chronic (30, 90, and 180 days) streptozotocin-induced diabetes mellitus (STZ-DM). Medullary GLUT1 and GLUT4 mRNA levels were significantly increased during the acute phase but returned to normal after 1 week. Cortical GLUT1 mRNA levels, however, were decreased significantly from 7 days through 6 months of STZ-DM. Cortical GLUT2 mRNA was slightly increased acutely and increased 5-fold in chronic STZ-DM, with the largest increase focally concentrated in the convoluted portion of the proximal tubule. Proximal tubule GLUT5 mRNA levels also were increased significantly during chronic STZ-DM. In summary, medullary GLUT1 and GLUT4 mRNA levels are acutely increased in STZ-DM, paralleling the increased renal epithelial metabolic activity accompanying early diabetes. Proximal tubular GLUT2 and 5 mRNA levels were increased in chronic STZ-DM, possibly adapting to the increased need for glucose transport out of these epithelial cells, whereas the concomitant decrease in cortical GLUT1 expression may reflect the decreased requirement for basolateral import of glucose into these same cells. Thus, renal GLUTs demonstrate complex, nephron segment-specific and duration-dependent responses to the effects of STZ-DM. C1 NICHHD, DEV ENDOCRINOL BRANCH, NIH, BETHESDA, MD 20892 USA. UNIV ALABAMA, DIV ENDOCRINOL, BIRMINGHAM, AL USA. VET ADM MED CTR, BIRMINGHAM, AL USA. NIDDKD, DIABET BRANCH, NIH, BETHESDA, MD 20892 USA. CHILDRENS HOSP, NATL MED CTR, DEPT NEPHROL, WASHINGTON, DC 20010 USA. AARHUS KOMMUNE HOSP, INST EXPT CLIN RES, DK-8000 AARHUS C, DENMARK. NR 29 TC 52 Z9 53 U1 0 U2 2 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 1997 VL 138 IS 3 BP 1267 EP 1275 DI 10.1210/en.138.3.1267 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA WJ739 UT WOS:A1997WJ73900053 PM 9048635 ER PT J AU Zeldin, DC Foley, J Boyle, JE Moomaw, CR Tomer, KB Parker, C Steenbergen, C Wu, S AF Zeldin, DC Foley, J Boyle, JE Moomaw, CR Tomer, KB Parker, C Steenbergen, C Wu, S TI Predominant expression of an arachidonate epoxygenase in islets of Langerhans cells in human and rat pancreas SO ENDOCRINOLOGY LA English DT Article ID ENDOGENOUS EPOXYEICOSATRIENOIC ACIDS; INSULIN-SECRETION; IMMUNOHISTOCHEMICAL LOCALIZATION; LIPOXYGENASE PRODUCTS; ANTERIOR-PITUITARY; METABOLISM; RELEASE; CYTOCHROME-P-450; QUANTITATION; INHIBITORS AB Ou laboratory recently described a new human cytochrome P450 arachidonic acid epoxygenase (CYP2J2) and the corresponding rat homolog (CYP2J3). Immunoblotting studies using a polyclonal antibody raised against recombinant human CYP2J2 confirmed CYP2J protein expression in human and rat pancreatic tissues. Immunohistochemical staining of formalin-fixed paraffin-embedded rat and human pancreas using the anti-CYP2J2 IgG and avidin-biotin-peroxidase detection revealed that CYP2J protein expression was highly localized to cells in the islets of Langerhans, with minimal staining in pancreatic exocrine cells. Colocalization studies using antibodies to the glucagon, insulin, somatostatin, and pancreatic polypeptide as markers for alpha-, beta-, delta-, and PP cells, respectively, showed that CYP2J protein expression was abundantly present in all four cell types, but was highest in the glucagon-producing alpha-cells. Direct evidence for the epoxidation of arachidonic acid by pancreatic cytochrome P450 was provided by documenting, for the first time, the presence of epoxyeicosatrienoic acids in vivo in human and rat pancreas by gas chromatography/mass spectrometry. Importantly, the levels of immunoreactive CYP2J2 in different human pancreatic tissues were highly correlated with endogenous epoxyeicosatrienoic acid concentrations. We conclude that human and rat pancreas contain an arachidonic acid epoxygenase belonging to the CYP2J subfamily that is highly localized to islet cells. These data together with previous work showing effects of epoxyeicosatrienoic acids in stimulating insulin and glucagon secretion from isolated rat pancreatic islets support the hypothesis that epoxygenase products may be involved in stimulus-secretion coupling in the pancreas. C1 NIEHS, LAB EXPT PATHOL, NIH, RES TRIANGLE PK, NC 27709 USA. NIEHS, MOL BIOPHYS LAB, NIH, RES TRIANGLE PK, NC 27709 USA. UNIV N CAROLINA, DEPT MED, CHAPEL HILL, NC 27599 USA. DUKE UNIV, MED CTR, DEPT PATHOL, DURHAM, NC 27710 USA. RP NIEHS, PULM PATHOBIOL LAB, NIH, POB 12233, RES TRIANGLE PK, NC 27709 USA. RI Tomer, Kenneth/E-8018-2013 FU NHLBI NIH HHS [R01 HL039752] NR 49 TC 58 Z9 63 U1 1 U2 3 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 1997 VL 138 IS 3 BP 1338 EP 1346 DI 10.1210/en.138.3.1338 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA WJ739 UT WOS:A1997WJ73900062 PM 9048644 ER PT J AU Parrizas, M LeRoith, D AF Parrizas, M LeRoith, D TI Insulin-like growth factor-1 inhibition of apoptosis is associated with increased expression of the bcl-x(L) gene product. SO ENDOCRINOLOGY LA English DT Article ID FACTOR-I; CELL APOPTOSIS; BCL-2; MEMBERS; FAMILY; DEATH; BAX AB Differentiated PC12 cells, which become dependent on the presence of growth factors in the media and die by apoptosis after several hours of serum deprivation, were used to test the ability of IGF-1 to regulate the endogenous levels of the death-suppressing protein Bcl-x(L) IGF-1 was capable of preventing apoptosis of serum-deprived differentiated PC12 cells at physiological concentrations, with optimal results seen at 10(-8) M. Incubation with the hormone resulted in a significant increase of Bcl-x mRNA after 3-6 h incubation and a doubling of Bcl-x(L) protein levels by 24 h incubation. Our results show that the protective effect of IGF-1 in PC12 cells is associated with an up-regulation of Bcl-x(L) mRNA and protein levels. RP Parrizas, M (reprint author), NIDDKD, DIABET BRANCH, NIH, 10 CTR DR, MSC-1770, BETHESDA, MD 20892 USA. NR 22 TC 182 Z9 185 U1 0 U2 2 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 1997 VL 138 IS 3 BP 1355 EP 1358 DI 10.1210/en.138.3.1355 PG 4 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA WJ739 UT WOS:A1997WJ73900065 PM 9048647 ER PT J AU Newlin, DB AF Newlin, DB TI A behavior-genetic approach to multiple chemical sensitivity SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Article; Proceedings Paper CT Conference on Experimental Approaches to Chemical Sensitivity CY SEP 20-22, 1995 CL PRINCETON, NJ DE behavior genetics; multiple chemical sensitivity; twins; adoptees; animal models; drug abuse; alcoholism ID ALCOHOL DEPENDENCE; NALTREXONE; LOCUS AB This report emphasizes the application of behavior-genetic designs to the study of sensitivity to toxic chemicals, and features of multiple chemical sensitivity and substance abuse that are polar opposites. The implications of these issues for future research are discussed in relation to twin, adoption, and sibling pair studies, as well as in relation to the degree to which genetically selected lines of rodents that have been developed in the alcoholism field are applicable to multiple chemical sensitivity. RP Newlin, DB (reprint author), NIDA,INTRAMURAL RES PROGRAM,5500 NATHAN SHOCK DR,BALTIMORE,MD 21224, USA. NR 26 TC 10 Z9 10 U1 1 U2 1 PU US DEPT HEALTH HUMAN SERVICES PUBLIC HEALTH SERVICE PI RES TRIANGLE PK PA NATL INST HEALTH, NATL INST ENVIRONMENTAL HEALTH SERVICES, PO BOX 12233, RES TRIANGLE PK, NC 27709-2233 SN 0091-6765 J9 ENVIRON HEALTH PERSP JI Environ. Health Perspect. PD MAR PY 1997 VL 105 SU 2 BP 505 EP 508 DI 10.2307/3433360 PG 4 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA XB827 UT WOS:A1997XB82700015 PM 9167987 ER PT J AU Bell, IR Rossi, J Gilbert, ME Kobal, G Morrow, LA Newlin, DB Sorg, BA Wood, RW AF Bell, IR Rossi, J Gilbert, ME Kobal, G Morrow, LA Newlin, DB Sorg, BA Wood, RW TI Testing the neural sensitization and kindling hypothesis for illness from low levels of environmental chemicals SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Article; Proceedings Paper CT Conference on Experimental Approaches to Chemical Sensitivity CY SEP 20-22, 1995 CL PRINCETON, NJ DE sensitization; kindling; mesolimbic; human; animal; time factors; low-level exposures; psychophysiology ID TIME-DEPENDENT SENSITIZATION; ORGANIC-SOLVENT EXPOSURE; SELF-REPORTED ILLNESS; POSTTRAUMATIC-STRESS-DISORDER; BEHAVIORAL SENSITIZATION; DRUG VARIABILITY; DOPAMINE RELEASE; CHILDHOOD ABUSE; SEX-DIFFERENCES; WHITE PAPER AB Sensitization in the neuroscience and pharmacology literatures is defined as progressive increase in the size of a response over repeated presentations of a stimulus. Types of sensitization include stimulant drug-induced time-dependent sensitization (TDS), an animal model related to substance abuse, and limbic kindling, an animal model for temporal lobe epilepsy, Neural sensitization (primarily nonconvulsive or subconvulsive) to the adverse properties of substances has been hypothesized to underlie the initiation and subsequent elicitation of heightened sensitivity to low levels of environmental chemicals. A corollary of the sensitization model is that individuals with illness from low-level chemicals are among the more sensitizable members of the population. The Working Group on Sensitization and Kindling identified two primary goals for a research approach to this problem: to perform controlled experiments to determine whether or not sensitization to low-level chemical exposures occurs in multiple chemical sensitivity (MCS) patients; and to use animal preparations for kindling and TDS as nonhomologous models for the initiation and elicitation of MCS. C1 UNIV ARIZONA,DEPT PSYCHOL,TUCSON,AZ 85721. UNIV ARIZONA,DEPT PSYCHIAT,TUCSON,AZ 85721. UNIV ARIZONA,DEPT FAMILY & COMMUNITY MED,TUCSON,AZ 85721. USN,MED RES INST DETACHMENT TOXICOL,TRISERV TOXICOL CONSORTIUM,WRIGHT PATTERSON AFB,OH. US EPA,RES TRIANGLE PK,NC 27711. UNIV ERLANGEN NURNBERG,DEPT PHARMACOL & TOXICOL,D-8520 ERLANGEN,GERMANY. UNIV PITTSBURGH,DEPT PSYCHIAT,PITTSBURGH,PA. NIDA,BALTIMORE,MD 21224. WASHINGTON STATE UNIV,DEPT VET & COMPARAT ANAT PHARMACOL & PHYSIOL,PULLMAN,WA 99164. NYU,DEPT ENVIRONM MED,NEW YORK,NY 10016. RP Bell, IR (reprint author), VET AFFAIRS MED CTR,DEPT PSYCHIAT,3601 S 6TH AVE,MAIL STOP 116A,TUCSON,AZ 85723, USA. NR 102 TC 23 Z9 23 U1 1 U2 3 PU US DEPT HEALTH HUMAN SERVICES PUBLIC HEALTH SERVICE PI RES TRIANGLE PK PA NATL INST HEALTH, NATL INST ENVIRONMENTAL HEALTH SERVICES, PO BOX 12233, RES TRIANGLE PK, NC 27709-2233 SN 0091-6765 J9 ENVIRON HEALTH PERSP JI Environ. Health Perspect. PD MAR PY 1997 VL 105 SU 2 BP 539 EP 547 DI 10.2307/3433366 PG 9 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA XB827 UT WOS:A1997XB82700021 PM 9167993 ER PT J AU Longnecker, MP AF Longnecker, MP TI Food labels, trans fatty acids, and coronary heart disease SO EPIDEMIOLOGY LA English DT Editorial Material ID MYOCARDIAL-INFARCTION; RISK RP Longnecker, MP (reprint author), NIEHS,EPIDEMIOL BRANCH,POB 12233,MD A3-05,RES TRIANGLE PK,NC 27709, USA. OI Longnecker, Matthew/0000-0001-6073-5322 NR 14 TC 0 Z9 0 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 1044-3983 J9 EPIDEMIOLOGY JI Epidemiology PD MAR PY 1997 VL 8 IS 2 BP 122 EP 123 PG 2 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA WK432 UT WOS:A1997WK43200003 PM 9229200 ER PT J AU Merrill, RM Brawley, OW AF Merrill, RM Brawley, OW TI Prostate cancer incidence and mortality rates among white and black men SO EPIDEMIOLOGY LA English DT Article DE prostate cancer; incidence; mortality; stage at diagnosis; age at diagnosis; race; time trends ID RADICAL PROSTATECTOMY; UNITED-STATES; BREAST-CANCER; TRENDS; ANTIGEN; DIAGNOSIS; RISE AB This paper presents prostate cancer incidence and mortality rates in the United States by factors associated with the disease at diagnosis and explores racial differences in these rates. The analysis is based on population-based cancer data from the Surveillance, Epidemiology, and End Results (SEER) Program of the National Cancer Institute. Incidence rates increased sharply from 1973 to 1992 (more so among whites), with the increase attributed to screening and preferential finding of low-risk, slow-growing tumors (chat is, length bias). Mortality rates increased slightly (more so among blacks). The 1988-1992 white and black prostate cancer mortality rates comprise cases diagnosed as early as 1973. These rates remained fairly constant for each stage category at diagnosis, except for black men diagnosed with localized or unstaged disease, in whom the rates increased. Of the white prostate cancer cases, 33% are diagnosed with localized disease, 16% are diagnosed with regional disease, and 38% are diagnosed with distant disease. The corresponding percentages for black patients are 31, 12, and 45%. Prostate cancer mortality rates for blacks diagnosed with localized, regional, distant, and unstaged disease are 1.9, 1.5, 2.4, and 2.0 times those of whites. The time from diagnosis to death depends on the stage and age at diagnosis, with the time somewhat longer for whites than blacks. This longer time period is due, in part, to better staging and length bias. The effect of therapy on prostate cancer mortality rates is unclear. RP Merrill, RM (reprint author), NCI,CANC CONTROL RES PROGRAM,APPL RES BRANCH,9000 ROCKVILLE PIKE,EPN 313,BETHESDA,MD 20892, USA. NR 36 TC 90 Z9 91 U1 0 U2 3 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 1044-3983 J9 EPIDEMIOLOGY JI Epidemiology PD MAR PY 1997 VL 8 IS 2 BP 126 EP 131 DI 10.1097/00001648-199703000-00001 PG 6 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA WK432 UT WOS:A1997WK43200006 PM 9229202 ER PT J AU Weiss, HA Potischman, NA Brinton, LA Brogan, D Coates, RJ Gammon, MD Malone, KE Schoenberg, JB AF Weiss, HA Potischman, NA Brinton, LA Brogan, D Coates, RJ Gammon, MD Malone, KE Schoenberg, JB TI Prenatal and perinatal risk factors for breast cancer in young women SO EPIDEMIOLOGY LA English DT Article DE breast cancer; prenatal; estrogen; breastfeeding; twins ID MATERNAL AGE; CIGARETTE-SMOKING; UNITED-STATES; PREGNANCY; EXPOSURE; BIRTH; MILK; ESTROGENS; DAUGHTERS; ESTRADIOL AB There is increasing interest in the role of early life exposures in breast carcinogenesis, especially estrogen exposure in utero. Estrogen levels during pregnancy may be higher in twin pregnancies and among older women and slightly lower among smokers. We analyzed early life risk factors in a population-based case-control study in the United States of 2,202 breast cancer cases and 2,009 controls under age 55 years. Twins were at an increased risk of breast cancer compared with singletons (relative risk = 1.62; 95% confidence interval = 1.0-2.7), particularly women with a twin brother (relative risk = 2.06), a finding consistent with the observation of high estrogen levels in dizygotic twin pregnancies. Little association was seen between maternal age at birth and breast cancer risk. We carried out further analyses for 534 cases and 497 controls under age 45 years, using data from a questionnaire completed by their mothers relating to the daughters' early life exposures. There was no evidence of an effect of smoking or diethylstilbestrol exposure during pregnancy on daughters' breast cancer risk. A reduced breast cancer risk was seen among women who had been breastfed (relative risk = 0.74; 95% confidence interval = 0.6-1.0). These findings indicate some effect of early life exposures on breast cancer risk, although the role of estrogen exposure may be less central than previously suggested. C1 NCI,DIV CANC EPIDEMIOL & GENET,BETHESDA,MD 20892. RI Brinton, Louise/G-7486-2015 OI Brinton, Louise/0000-0003-3853-8562 NR 52 TC 100 Z9 102 U1 0 U2 4 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 1044-3983 J9 EPIDEMIOLOGY JI Epidemiology PD MAR PY 1997 VL 8 IS 2 BP 181 EP 187 DI 10.1097/00001648-199703000-00010 PG 7 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA WK432 UT WOS:A1997WK43200015 PM 9229211 ER PT J AU Kramer, BS Gohagan, JK Prorok, PC AF Kramer, BS Gohagan, JK Prorok, PC TI Is screening for prostate cancer the current gold standard? ''No'' SO EUROPEAN JOURNAL OF CANCER LA English DT Article ID MEDICARE PROVIDE REIMBURSEMENT; RADICAL PROSTATECTOMY; DECISION-ANALYSIS; FOLLOW-UP; ANTIGEN; SERUM; MEN; STRATEGIES; CARCINOMA; OUTCOMES C1 NCI,BIOMETRY BRANCH,DIV CANC PREVENT & CONTROL,BETHESDA,MD 20892. RP Kramer, BS (reprint author), NCI,EARLY DETECT & COMMUNITY ONCOL PROGRAM,9000 ROCKVILLE PIKE,BLDG 31,ROOM 10A49,BETHESDA,MD 20892, USA. NR 50 TC 12 Z9 13 U1 1 U2 2 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0959-8049 J9 EUR J CANCER JI Eur. J. Cancer PD MAR PY 1997 VL 33 IS 3 BP 348 EP 353 PG 6 WC Oncology SC Oncology GA WR551 UT WOS:A1997WR55100013 PM 9155515 ER PT J AU Marth, T Strober, W Seder, RA Kelsall, BL AF Marth, T Strober, W Seder, RA Kelsall, BL TI Regulation of transforming growth factor-beta production by interleukin-12 SO EUROPEAN JOURNAL OF IMMUNOLOGY LA English DT Article DE oral tolerance; cellular differentiation; T lymphocyte; transgenic mouse; autoimmunity ID EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS; MYELIN BASIC-PROTEIN; ORAL TOLERANCE; T-CELLS; INFLAMMATORY CYTOKINES; INTERFERON-GAMMA; TGF-BETA; INDUCTION; ANTIGEN; MICE AB The induction of peripheral tolerance following oral antigen administration in several autoimmune disease and conventional animal models correlates with the production of transforming growth factor-beta (TGF-beta) and T helper type 2 (Th2) cytokines. The factors regulating TGF-beta production and its relation to the Th2 response, however, have not been defined. We demonstrate that the systemic administration of antibodies to interleukin (IL)-12 to ovalbumin (OVA)-T cell receptor (TCR) transgenic mice fed high doses of OVA, followed by systemic OVA challenge, substantially enhances TGF-beta, but not IL-4 production by peripheral T cells. Furthermore, we demonstrate in an in vitro T cell differentiation model that naive (CD4(+)/Mel-14(hi)) OVA-TCR-T cells stimulated with OVA-pulsed dendritic cells (DC) produce four- to fivefold higher amounts of TGF-beta when cultured with anti-IL-12 or anti-interferon-gamma (IFN-gamma). In this in vitro system, IL-4 was not required for TGF-beta production by T cells; however, it appeared to enhance levels of TGF-beta by promoting the growth of TGF-beta producing cells. Our findings demonstrate that IL-12 and IFN-gamma are important negative regulators of TGF-beta production both in vivo and in vitro, and that their modulation may be of benefit for the treatment of autoimmune disorders. C1 NIAID,MUCOSAL IMMUN SECT,LCI,NIH,BETHESDA,MD 20892. NIAID,CLIN INVEST LAB,LYMPHOKINE REGULAT UNIT,NIH,BETHESDA,MD 20892. NR 35 TC 68 Z9 72 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 1997 VL 27 IS 5 BP 1213 EP 1220 DI 10.1002/eji.1830270524 PG 8 WC Immunology SC Immunology GA WZ369 UT WOS:A1997WZ36900023 PM 9174613 ER PT J AU Maric, D Maric, I Ma, W Lahojuji, F Somogyi, R Wen, XL Sieghart, W Fritschy, JM Barker, JL AF Maric, D Maric, I Ma, W Lahojuji, F Somogyi, R Wen, XL Sieghart, W Fritschy, JM Barker, JL TI Anatomical gradients in proliferation and differentiation of embryonic rat CNS accessed by buoyant density fractionation: alpha 3, beta 3 and gamma 2 GABA(A) receptor subunit co-expression by post-mitotic neocortical neurons correlates directly with cell buoyancy SO EUROPEAN JOURNAL OF NEUROSCIENCE LA English DT Article DE central nervous system; development; flow cytometry; Percoll ID CENTRAL-NERVOUS-SYSTEM; MESSENGER-RNAS; A-RECEPTOR; SPINAL-CORD; RAPID ISOLATION; FLOW-CYTOMETRY; BRAIN; PERCOLL; CYCLE; NEUROGENESIS AB Development of the CNS occurs as a complex cascade of pre-programmed events involving distinct phases of cell proliferation and differentiation. Here we show these phases correlate with cells of specific buoyant densities which can be readily accessed by density gradient fractionation. Sprague-Dawley dams were pulse-labelled with bromodeoxyuridine (BrdU) and selected regions of embryonic (E) CNS tissues at E11-22 dissociated with papain into single-cell suspensions, Proliferative cell populations were assessed by anti-BrdU and propidium iodide staining using flow cytometry. Cell differentiation was evaluated using molecular and immunocytochemical probes against mRNAs and antigens differentiating the neuroepithelial, neuronal and glial cell lineages. The results show the emergence of distinctive spatiotemporal changes in BrdU(+) populations throughout the CNS during embryonic development, which were followed by corresponding changes in the cellular distributions of antigens distinguishing specific cell types, Fractionation of neocortical cells using discontinuous Percoll gradients revealed that an increasing number of cells increase their buoyancy during corticogenesis. Immunocytochemical and molecular characterization showed that the proliferative and progenitor cell populations are for the most part associated with lower buoyancy or higher specific buoyant densities (>1.056 g/ml) whereas the post-mitotic, differentiated neurons generally separated into fractions of higher buoyancy or lower specific buoyant densities (<1.043 g/ml). Immunostaining with antibodies against several GABA(A) receptor subunits (alpha 3, beta 3, gamma 2) revealed that the highest percent (70-90%) of immunopositive cells could be identified in the most buoyant, differentiating neurons found in the cortical plate/subplate regions, with the lowest percent of the immunopositive cells found in the least buoyant, proliferative and progenitor cell populations originating from the ventricular/subventricular zones. Taken together, these results indicate that buoyant density is a distinguishing characteristic of embryonic CNS cells transforming from primarily proliferative to mainly differentiating, and that fractionation of these cells according to their buoyant densities provides rapid access to the properties of specific cell lineages during the prenatal period of CNS development. C1 UNIV VIENNA,PSYCHIAT CLIN,DEPT BIOCHEM PSYCHIAT,A-1090 VIENNA,AUSTRIA. UNIV ZURICH,INST PHARMACOL,CH-8006 ZURICH,SWITZERLAND. RP Maric, D (reprint author), NINCDS,NEUROPHYSIOL LAB,NIH,BLDG 36,RM 2C02,BETHESDA,MD 20892, USA. RI Sieghart, Werner/A-4877-2013 OI Sieghart, Werner/0000-0002-0443-0302 NR 71 TC 33 Z9 33 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD, ENGLAND OX2 6DP SN 0953-816X J9 EUR J NEUROSCI JI Eur. J. Neurosci. PD MAR PY 1997 VL 9 IS 3 BP 507 EP 522 DI 10.1111/j.1460-9568.1997.tb01628.x PG 16 WC Neurosciences SC Neurosciences & Neurology GA WW352 UT WOS:A1997WW35200010 PM 9104593 ER PT J AU Kertzman, C Schwarz, U Zeffiro, TA Hallett, M AF Kertzman, C Schwarz, U Zeffiro, TA Hallett, M TI The role of posterior parietal cortex in visually guided reaching movements in humans SO EXPERIMENTAL BRAIN RESEARCH LA English DT Article DE visually guided reaching; PET; MRI; posterior parietal cortex; human ID POSITRON EMISSION TOMOGRAPHY; BEHAVING RHESUS-MONKEY; CORTICAL MOTOR AREAS; CEREBRAL BLOOD-FLOW; NEURONAL-ACTIVITY; ARM MOVEMENTS; VOLUNTARY MOVEMENTS; CINGULATE CORTEX; NEURAL REPRESENTATIONS; EXTRAPERSONAL SPACE AB Positron emission tomography (PET) was used to identify the brain areas involved in visually guided reaching by measuring regional cerebral bloodflow (rCBF) in six normal volunteers while they were fixating centrally and reaching with the left or right arm to targets presented in either the right or the left visual field. The PET images were registered with magnetic resonance images from each subject so that increases in rCBF could be localized with anatomical precision in individual subjects. Increased neural activity was examined in relation to the hand used to reach, irrespective of field of reach (hand effect), and the effects of target field of reach, irrespective of hand used (field effect). A separate analysis on intersubject, averaged PET data was also performed. A comparison of the results of tile two analyses showed close correspondence in the areas of activation that were identified. We did not find a strict segregation of regions associated exclusively with either hand or field. Overall, significant rCBF increases in the hand sind field conditions occurred bilaterally in the supplementary motor area, premotor cortex, cuneus, lingual gyrus, superior temporal cortex, insular cortex, thalamus, and putamen. Primary motor cortex, postcentral gyrus, and the superior parietal lobule (intraparietal sulcus) showed predominantly a contralateral hand effect, whereas the inferior parietal lobule showed this effect for the left hand only. Greater contralateral responses for the right hand were observed in the secondary motor areas. Only the anterior and posterior cingulate cortices exhibited strong ipsilateral hand effects, Field of reach was more com monly associated with bilateral patterns of activation in the areas with contralateral or ipsilateral hand effects, These results suggest that the Visual and motor components of reaching may have a different functional organization and that many brain regions represent both limb of reach and field of reach. However, since posterior parietal cortex is connected with all of these regions, we suggest that it plays a crucial role in the integration of limb and field coordinates. C1 NINCDS,HUMAN MOTOR CONTROL SECT,MED NEUROL BRANCH,NIH,BETHESDA,MD 20891. NR 90 TC 112 Z9 112 U1 0 U2 3 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0014-4819 J9 EXP BRAIN RES JI Exp. Brain Res. PD MAR PY 1997 VL 114 IS 1 BP 170 EP 183 DI 10.1007/PL00005617 PG 14 WC Neurosciences SC Neurosciences & Neurology GA WT799 UT WOS:A1997WT79900018 PM 9125463 ER PT J AU Lackner, PA Rodriguez, L Sato, S Lizak, MJ Wyman, M Kador, PF AF Lackner, PA Rodriguez, L Sato, S Lizak, MJ Wyman, M Kador, PF TI Age-dependent lens changes in galactose-fed dogs SO EXPERIMENTAL EYE RESEARCH LA English DT Article DE sugar cataract formation; galactosemia; NADPH-dependent reductase activity; aldose reductase; aldehyde reductase ID ALDOSE REDUCTASE; CATARACT FORMATION; SUGAR CATARACT AB Aldose reductase initiated sugar cataract formation in 9-month old galactose-fed dogs has been documented to progress from an accentuation of lens sutures (1 month after initial feeding) to the appearance of cortical vacuoles (3 months), cortical opacities (4-6 months) and eventually the progressive formation of a clear zone at the cortical equatorial regions of the cataractous lenses (> 12 months). Here, the effect of age on the onset and degree of sugar cataract formation has been investigated in beagles fed a 30% galactose diet starting at 2, 6, and 24 months of age. Cataract formation was monitored by slit lamp and retroillumination microscopy. Compared to 9-month old dogs, cataract formation in the younger dogs was more rapid and the lens changes were more severe. In the 2-month old group of dogs, galactose-feeding resulted in a rapid formation of dense cataracts which began to resorb after 106 days of galactose feeding with only opaque nuclear remnants remaining after eight months. These changes were mirrored by age-dependent reductions of lenticular NADPH-dependent reductase activity. (C) 1997 Academic Press Limited. C1 NEI,LAB OCULAR THERAPEUT,NIH,BETHESDA,MD 20892. NR 18 TC 20 Z9 21 U1 0 U2 1 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 1997 VL 64 IS 3 BP 431 EP 436 DI 10.1006/exer.1996.0221 PG 6 WC Ophthalmology SC Ophthalmology GA WT310 UT WOS:A1997WT31000017 PM 9196395 ER PT J AU Egwuagu, CE Chepelinsky, AB AF Egwuagu, CE Chepelinsky, AB TI Extralenticular expression of the alpha A-crystallin promoter gamma interferon transgene SO EXPERIMENTAL EYE RESEARCH LA English DT Letter ID LENS-SPECIFIC EXPRESSION; BINDING-PROTEIN-I; ECTOPIC EXPRESSION; MICE; GENE; DIFFERENTIATION; EYES; ACTIVATION; ONCOGENE; ABLATION C1 NEI, IMMUNOL LAB, NIH, BETHESDA, MD 20892 USA. NEI, MOL & DEV BIOL LAB, NIH, BETHESDA, MD 20892 USA. NR 33 TC 7 Z9 7 U1 0 U2 0 PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0014-4835 J9 EXP EYE RES JI Exp. Eye Res. PD MAR PY 1997 VL 64 IS 3 BP 491 EP 495 DI 10.1006/exer.1996.0202 PG 5 WC Ophthalmology SC Ophthalmology GA WT310 UT WOS:A1997WT31000024 PM 9196402 ER PT J AU Orlic, D Girard, LJ Lee, D Anderson, SM Puck, JM Bodine, DM AF Orlic, D Girard, LJ Lee, D Anderson, SM Puck, JM Bodine, DM TI Interleukin-7R alpha mRNA expression increases as stem cells differentiate into T and B lymphocyte progenitors SO EXPERIMENTAL HEMATOLOGY LA English DT Article DE interleukin receptors; lymphopoiesis; hematopoietic stem cells; flow cytometry ID RECEPTOR-GAMMA-CHAIN; MOUSE BONE-MARROW; MICE LACKING JAK3; C-KIT; IL-2 RECEPTOR; FUNCTIONAL COMPONENT; LINEAGE COMMITMENT; DEFICIENT MICE; GENE AB The gamma(common) (gamma(c)) chain is a partner in several interleukin receptor complexes, including the interleukin-2 receptor (IL-2R), IL-4R, and IL-7R. Mutations in the gamma(c) gene are associated with X-linked severe combined immunodeficiency (SCID). Using reverse transcriptase-PCR, we examined the level of mRNA-encoding gamma(c) and its partners in mouse pluripotent hematopoietic stem cells (PHSCs), which repopulate both bone marrow and thymus. We also assayed developing lymphocytes to define which, if any, IL-R complexes are expressed at the earliest stage of T and B lymphocyte maturation. RNA extracted from bone marrow-derived PHSCs did not contain detectable levels of mRNA-encoding IL-7R alpha. However, the most primitive (CD4(-) CD8(-)) T cells from the thymus and the most primitive (c-kit(+) B220(+)) B cells from bone marrow contained high levels of IL-7R alpha mRNA. There were no detectable differences between PHSCs and primitive or more mature T and B cells for expression of gamma(c) mRNA. We conclude that the onset of IL-7R formation occurs at the earliest stage of differentiation of T and B lymphocytes. Our findings are consistent with the hypothesis that the absence of an intact IL-7R (IL-7R alpha and gamma(c)) may be a critical loss that interrupts lymphopoiesis. C1 NHGRI,IMMUNOL GENET SECT,LAB GENE TRANSFER,NIH,BETHESDA,MD 20892. NHLBI,HEMATOL BRANCH,NIH,BETHESDA,MD 20892. RP Orlic, D (reprint author), NHGRI,HEMATOPOIESIS SECT,LAB GENE TRANSFER,NIH,49 CONVENT DR,BLDG 49,ROOM 3A11,BETHESDA,MD 20892, USA. NR 36 TC 22 Z9 22 U1 0 U2 1 PU CARDEN JENNINGS PUBL CO LTD PI CHARLOTTESVILLE PA BLAKE CTR, STE 200, 1224 W MAIN ST, CHARLOTTESVILLE, VA 22903 SN 0301-472X J9 EXP HEMATOL JI Exp. Hematol. PD MAR PY 1997 VL 25 IS 3 BP 217 EP 222 PG 6 WC Hematology; Medicine, Research & Experimental SC Hematology; Research & Experimental Medicine GA WP336 UT WOS:A1997WP33600007 PM 9091297 ER PT J AU Kopp, JB AF Kopp, JB TI Gene expression in kidney using transgenic approaches SO EXPERIMENTAL NEPHROLOGY LA English DT Article DE transgenic animals; kidney disease; HIV-associated nephropathy; focal segmental glomerulosclerosis ID HIV-ASSOCIATED NEPHROPATHY; CELL-SPECIFIC EXPRESSION; MAMMALIAN-CELLS; FUSION GENES; ANIMAL-MODELS; MICE; PROMOTER; TISSUE; GROWTH; GLOMERULOSCLEROSIS RP Kopp, JB (reprint author), NIDDKD,KIDNEY DIS SECT,NIH,BLDG 10,ROOM 3N116,BETHESDA,MD 20892, USA. OI Kopp, Jeffrey/0000-0001-9052-186X NR 50 TC 6 Z9 6 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 1997 VL 5 IS 2 BP 157 EP 167 PG 11 WC Urology & Nephrology SC Urology & Nephrology GA WT522 UT WOS:A1997WT52200009 PM 9108999 ER PT J AU Mouradian, MM Chase, TN AF Mouradian, MM Chase, TN TI Gene therapy for Parkinson's disease: An approach to the prevention or palliation of levodopa-associated motor complications SO EXPERIMENTAL NEUROLOGY LA English DT Article; Proceedings Paper CT Conference on Gene Therapy for Parkinsons Diseases - Rationale, Prospects, and Limitations CY APR 11-13, 1996 CL WASHINGTON, D.C. SP Natl Parkinson Fdn, Natl Fdn Brain Res ID CENTRAL PATHOPHYSIOLOGICAL MECHANISMS; CENTRAL DOPAMINERGIC MECHANISMS; ENCAPSULATED PC12 CELLS; NMDA RECEPTOR BLOCKADE; BEHAVIORAL RECOVERY; ENGINEERED CELLS; BASAL GANGLIA; L-DOPA; FLUCTUATIONS; RATS AB Gene therapy holds considerable potential for the treatment of central nervous system disease. The introduction of functional genes into the brain of patients with Parkinson's disease may, for example, prove useful as a means to replace a defective gene, introduce a potentially neuroprotective or neurorestorative protein, or permit the physiological delivery of a deficient neurotransmitter. Recent observations suggest that the oral administration of currently available dopaminomimetics to relatively advanced parkinsonian patients leads to nonphysiologic intermittent stimulation of striatal neurons that express dopamine receptors. Resultant activation of signal transduction pathways from these dopaminergic receptors on medium-sized GABAergic neurons apparently induces long-term potentiation of adjacent glutamatergic receptors of the N-methyl-D-aspartate subtype. The effects of dopaminergic drugs thus become modified in ways that favor the clinical appearance of response fluctuations and peak-dose dyskinesias. In parkinsonian models as well as in patients with Parkinson's disease, continuous dopaminergic replacement tends to prevent or alleviate these adverse effects. By continuously maintaining appropriate cerebral dopamine concentrations, molecular techniques which stimulate an increase in the intrastriatal activity of tyrosine hydroxylase, the rate-limiting enzyme for dopamine synthesis, might be expected to palliate parkinsonian symptoms with less risk of the disabling consequences of current therapy. Clinical study of these approaches could also serve as initial, relatively simple, proof-of-principle evaluations of the safety and efficacy of genetic approaches to the treatment of basic disease processes in Parkinson's disease and related neurodegenerative disorders. (C) 1997 Academic Press. RP NINCDS, EXPT THERAPEUT BRANCH, NIH, BLDG 36, RM 4D04, BETHESDA, MD 20892 USA. OI Mouradian, M. Maral/0000-0002-9937-412X NR 65 TC 9 Z9 10 U1 0 U2 2 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0014-4886 EI 1090-2430 J9 EXP NEUROL JI Exp. Neurol. PD MAR PY 1997 VL 144 IS 1 BP 51 EP 57 DI 10.1006/exnr.1996.6388 PG 7 WC Neurosciences SC Neurosciences & Neurology GA WR752 UT WOS:A1997WR75200012 PM 9126152 ER PT J AU Liberski, PP Brown, P Cervenakova, L Gajdusek, DC AF Liberski, PP Brown, P Cervenakova, L Gajdusek, DC TI Interactions between astrocytes and oligodendroglia in human and experimental Creutzfeldt-Jakob disease and scrapie SO EXPERIMENTAL NEUROLOGY LA English DT Article ID STRAUSSLER-SCHEINKER SYNDROME; BRAIN; MICROGLIA; LESIONS; ALPHA; KURU; MICE AB We report here a rare interaction between reactive astrocytes and oligodendrocytes, first detected ill a brain biopsy of human Creutzfeldt-Jakob disease (CJD) and then in experimental CJD in mice and in two models (263K and 22CH) of scrapie in hamsters, In human CJD brain biopsy, low-power electron microscopy revealed numerous examples of astrocytes and oligodendroglial cells in close apposition. At higher magnification, both types of cells were occasionally connected by adhesive plaque junctions (attenuated desmosomes), More complex structures were also seen. Astrocytic cytoplasm was penetrated by oligodendroglial processes or oligodendroglial cells were completely surrounded by astrocytic processes. An analogous phenomenon was identified in the brains of CJD-infected mice and in two models of scrapie-infected hamsters, In the CJD brain biopsy and in brain specimens from CJD-infected mice and scrapie-infected hamsters, GFAP-immunoreactive hypertrophic astrocytes were readily identified, particularly in those areas where the tissue damage was the most extensive. Oligodendrocytes frequently surrounded hypertrophic astrocytic processes or cell bodies and remained unstained in GFAP preparation. The significance of the interactions between astrocytes and oligodendrocytes is unclear at the present time, As in MS and other brain pathologies in which it has been studied, this interaction is not associated with a reaction toward any infectious pathogen but it may be an early cellular event that triggers further brain tissue destruction. (C) 1997 Academic Press. C1 MED ACAD LODZ,LAB TUMOR BIOL,PL-93509 LODZ,POLAND. MED ACAD LODZ,LAB ELECTRON MICROSCOPY & NEUROPATHOL,PL-93509 LODZ,POLAND. POLISH MOTHER MEM HOSP,ELECTRON MICROSCOPY LAB,DEPT PATHOL,LODZ,POLAND. RP Liberski, PP (reprint author), NINCDS,CENT NERVOUS SYST STUDIES LAB,NIH,BLDG 36,RM 4D04,BETHESDA,MD 20892, USA. NR 32 TC 8 Z9 8 U1 1 U2 1 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0014-4886 J9 EXP NEUROL JI Exp. Neurol. PD MAR PY 1997 VL 144 IS 1 BP 227 EP 234 DI 10.1006/exnr.1997.6422 PG 8 WC Neurosciences SC Neurosciences & Neurology GA WR752 UT WOS:A1997WR75200035 PM 9126175 ER PT J AU Thierry, AR Rabinovich, P Peng, B Mahan, LC Bryant, JL Gallo, RC AF Thierry, AR Rabinovich, P Peng, B Mahan, LC Bryant, JL Gallo, RC TI Characterization of liposome-mediated gene delivery: Expression, stability and pharmacokinetics of plasmid DNA SO GENE THERAPY LA English DT Article DE gene transfer; liposomes; plasmid DNA; biodistribution; pharmacokinetics ID CYSTIC-FIBROSIS; LIVER-CELLS; COATED DNA; TRANSFECTION; THERAPY; MICE; MOUSE; EFFICIENT; COMPLEXES; HUMANS AB We have characterized a new synthetic gene delivery system, termed DLS, which may be suitable for systemic gene therapy. DLS constitutes a lipopolyamine and a neutral lipid and associated plasmic DNA in the formation of lamellar vesicles (DSL-DNA). The ratio of and lipid to DNA as well as the method of preparation were optimized to a high in vitro transfection efficiency compared with reported for cationic lipid systems. DLS-DNA showed a rapid cellular uptake and distribution in the cytoplasmic and nuclear (especially the nucleoli) compartment as determined by laser-assisted confocal microscopy. There was little or no plasmid DNA degradation over a period of 20 min, relatively slow plasma clearance, and effective and rapid cellular uptake of DLS-DNA following intravenous administration in mice. Supercoiled plasmid DNA could be defected in blood cells up to 1 h after injection. Systemic administration of DLS-DNA yielded transgene expression in mouse tissues, such as in lung or liver. The ratio of DLS:DNA and the procedure used to form DLS-DNA affected both the level cellular specificity of expression of a luciferase reporter gene showing that in vitro transfection efficiency of DLS-DNA formulations cannot be easily extrapolated to an in vivo setting. Optimization of the formulation of a PNA delivery system was critical to obtain a defined structure resulting in a preparation with high reproducibility and stability, greater homogeneity of particle size and high efficacy following systemic gene transfer. In addition, the DLS system may be formulated for specific target tissues and may have a wide range of applications for gene therapy. C1 NCI,TUMOR CELL BIOL LAB,BETHESDA,MD 20892. NINCDS,NEUROCHEM LAB,BETHESDA,MD 20892. NIDR,ANIM CARE UNIT,NIH,BETHESDA,MD 20892. RI thierry, alain/F-9492-2014 NR 35 TC 127 Z9 128 U1 2 U2 9 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE, HAMPSHIRE, ENGLAND RG21 6XS SN 0969-7128 J9 GENE THER JI Gene Ther. PD MAR PY 1997 VL 4 IS 3 BP 226 EP 237 DI 10.1038/sj.gt.3300350 PG 12 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA WM745 UT WOS:A1997WM74500007 PM 9135736 ER PT J AU IshiiMorita, H Agbaria, R Mullen, CA Hirano, H Koeplin, DA Ram, Z Oldfield, EH Johns, DG Blaese, RM AF IshiiMorita, H Agbaria, R Mullen, CA Hirano, H Koeplin, DA Ram, Z Oldfield, EH Johns, DG Blaese, RM TI Mechanism of 'bystander effect' killing in the herpes simplex thymidine kinase gene therapy model of cancer treatment SO GENE THERAPY LA English DT Article DE thymidine kinase; suicide gene; bystander effect; ganciclovir; cancer; gene therapy ID EXPERIMENTAL BRAIN-TUMORS; INDUCED DNA-POLYMERASE; IN-VITRO; PRODUCER CELLS; GLIOMA-CELLS; INVIVO; 9-(1,3-DIHYDROXY-2-PROPOXYMETHYL)GUANINE; PHOSPHORYLATION; TRANSDUCTION; GANCICLOVIR AB 'Bystander' killing of adjacent wild-type tumor cells was seen when tumors transduced with the herpes thymidine kinase gene were treated with the antiviral agent ganciclovir (GCV). Some tumors were 'bystander-resistant'. Mixtures of different 'sensitive' tumor lines showed cross-transfer of bystander killing, while in mixtures of 'resistant' with 'sensitive' tumors, the resistant phenotype was predominant. Using H-GCV with 'sensitive' mixtures, phosphorylated H-3-GCV was found in both herpes thymidine kinase transduced and unmodified cells, while 'resistant' cell combinations showed little or no transfer of phosphorylated GCV between cells. The capacity of intracellularly produced nucleotide toxin to spread from cell to cell within a tumor mass effectively amplifies the apparent efficiency of gene transfer in the tumor and makes feasible the use of this system for therapy of localized cancer. C1 NIH,CLIN GENE THERAPY BRANCH,NATL CTR HUMAN GENOME RES,BETHESDA,MD 20892. NCI,MED CHEM LAB,BETHESDA,MD 20892. NCI,EXPT IMMUNOL BRANCH,BETHESDA,MD 20892. HOWARD HUGHES MED RES INST,SCHOLARS PROGRAM,BETHESDA,MD. NINCDS,SURG NEUROL BRANCH,NIH,BETHESDA,MD 20892. NR 33 TC 126 Z9 128 U1 0 U2 0 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE, HAMPSHIRE, ENGLAND RG21 6XS SN 0969-7128 J9 GENE THER JI Gene Ther. PD MAR PY 1997 VL 4 IS 3 BP 244 EP 251 DI 10.1038/sj.gt.3300379 PG 8 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA WM745 UT WOS:A1997WM74500009 PM 9135738 ER PT J AU Chidambaram, A Gailani, M Gerrard, B Stewart, C Goldstein, A Chumakov, I Bale, AE Dean, M AF Chidambaram, A Gailani, M Gerrard, B Stewart, C Goldstein, A Chumakov, I Bale, AE Dean, M TI Characterization of a YAC contig containing the NBCCS locus and a novel Kruppel-type zinc finger sequence on chromosome segment 9q22.3 SO GENES CHROMOSOMES & CANCER LA English DT Article ID CELL-CARCINOMA-SYNDROME; ANEMIA GROUP-C; CANDIDATE GENES; NEVUS SYNDROME; HUMAN GENOME; CPG ISLANDS; LOCALIZATION; PROTEINS; FAMILIES AB Gorlin's syndrome or nevoid basal cell carcinoma syndrome (NBCCS) is an autosomal dominant disorder characterized by a familial or hereditary predisposition to basal cell carcinomas (generally multiple and of early onset), odontogenic keratocysts (jaw cysts), palmar and plantar pits, a wide variety of developmental defects, as well as cancers such as medulloblastomas and ovarian fibromas. The gene for NBCCS has been mapped to human chromosome region 9q22.1-q31 by linkage analysis and by cytogenetic evidence of deletions in this region in patients with the syndrome. This is supported by loss of heterozygosity in tumors of polymorphic marker loci flanked by D9S197 and D9S180. We have utilized sequence tagged site (STS) mapping and somatic cell hybrid panel analysis to construct two overlapping yeast artificial chromosome (YAC) contigs spanning this region of the genome. We used the YAC contigs to identify a new zinc finger gene containing a highly informative microsatellite locus. (C) 1997 Wiley-Liss, Inc. C1 NCI,VIRAL CARCINOGENESIS LAB,FREDERICK CANC RES & DEV CTR,FREDERICK,MD 21702. NCI,INTRAMURAL RES SUPPORT PROGRAM,SAIC FREDERICK,FREDERICK CANC RES & DEV CTR,FREDERICK,MD 21702. YALE UNIV,SCH MED,DEPT GENET,NEW HAVEN,CT 06510. NCI,GENET EPIDEMIOL BRANCH,BETHESDA,MD 20892. GENETHON,EVRY,FRANCE. RI Dean, Michael/G-8172-2012 OI Dean, Michael/0000-0003-2234-0631 NR 25 TC 6 Z9 7 U1 0 U2 1 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 1045-2257 J9 GENE CHROMOSOME CANC JI Gene Chromosomes Cancer PD MAR PY 1997 VL 18 IS 3 BP 212 EP 218 DI 10.1002/(SICI)1098-2264(199703)18:3<212::AID-GCC7>3.0.CO;2-4 PG 7 WC Oncology; Genetics & Heredity SC Oncology; Genetics & Heredity GA WM741 UT WOS:A1997WM74100008 PM 9071574 ER PT J AU Liu, J Nau, MM Zucman-Rossi, J Powell, JI Allegra, CJ Wright, JJ AF Liu, J Nau, MM Zucman-Rossi, J Powell, JI Allegra, CJ Wright, JJ TI LINE-I element insertion at the t(11;22) translocation breakpoint of a desmoplastic small round cell tumor SO GENES CHROMOSOMES & CANCER LA English DT Article ID HUMAN TRANSPOSABLE ELEMENT; CHROMOSOME-TRANSLOCATION; CHIMERIC TRANSCRIPTS; EWING FAMILY; GENE FUSION; L1 ELEMENT; EWS GENE; SEQUENCE; RETROTRANSPOSONS; MUTATION AB A t(11;22)(p13;p12) chromosomal translocation, juxtaposing the Wilms' tumor (WT1) and Ewing's sarcoma (EWS) genes, is the cytogenetic hallmark of desmoplastic small round cell tumor (DSRCT), a primitive multiphenotypic sarcoma arising in serosal tissues. Chimeric transcripts generated by this rearrangement encode an aberrant transcription factor that fuses the 5' region of EWS with a 3' WT1 segment. We describe the insertion of a LINE-1 DNA mobile genetic element at the genomic breakpoint of a DSRCT chromosomal translocation. A 480 bp heterologous DNA segment with homology to the LINE-1 DNA consensus sequence was located between EWS intron 8 and WT1 exon 8 in the productively rearranged allele. Sequence homology corresponded to the LINE-1 ORF-2, which encodes a protein with reverse-transcriptase activity. The heterologous inserted fragment was not evident in the germline of normal tissue from the patient, suggesting that transposition occurred in somatic cells, possibly during the process of chromosomal rearrangement. This case represents the first example of LINE-1 DNA transposition at the fusion site of a tumor-associated chromosomal rearrangement. (C) 1997 Wiley-Liss, Inc. C1 NATL NAVAL MED CTR, NCI, NAVY MED ONCOL BRANCH, BETHESDA, MD 20889 USA. NIH, COMPUTAT BIOSCI & ENGN LAB, DIV COMP RES & TECHNOL, BETHESDA, MD 20892 USA. INST CURIE, LAB GENET TUMEURS, PARIS, FRANCE. NR 44 TC 36 Z9 38 U1 0 U2 1 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1045-2257 J9 GENE CHROMOSOME CANC JI Gene Chromosomes Cancer PD MAR PY 1997 VL 18 IS 3 BP 232 EP 239 DI 10.1002/(SICI)1098-2264(199703)18:3<232::AID-GCC10>3.0.CO;2-K PG 8 WC Oncology; Genetics & Heredity SC Oncology; Genetics & Heredity GA WM741 UT WOS:A1997WM74100011 PM 9071577 ER PT J AU Touchman, JW Bouffard, GG Weintraub, LA Idol, JR Wang, LP Robbins, CM Nussbaum, JC Lovett, M Creen, ED AF Touchman, JW Bouffard, GG Weintraub, LA Idol, JR Wang, LP Robbins, CM Nussbaum, JC Lovett, M Creen, ED TI 2006 expressed-sequence tags derived from human chromosome 7-enriched cDNA libraries SO GENOME RESEARCH LA English DT Article ID DOMINANT RETINITIS-PIGMENTOSA; CEREBRAL CAVERNOUS MALFORMATION; SAETHRE-CHOTZEN-SYNDROME; HUMAN GENOME; HUMAN BRAIN; CAENORHABDITIS-ELEGANS; POSITIONAL CLONING; TAGGED-SITES; LINKAGE MAP; GENE AB The establishment and mapping of gene-specific DNA sequences greatly complement the ongoing efforts to map and sequence all human chromosomes. To facilitate our studies of human chromosome 7, we have generated and analyzed 2006 expressed-sequence tags (ESTs) derived from a collection of direct selection cDNA libraries that are highly enriched for human chromosome 7 gene sequences. Similarity searches indicate that approximately two-thirds of the ESTs are not represented by sequences in the public databases, including those in dbEST. In addition, a large fraction (68%) of the ESTs do not have redundant or overlapping sequences within our collection. Human DNA-specific sequence-tagged sites (STSs) have been developed from 190 of the ESTs. Remarkably, 180 (96%) of these STSs map to chromosome 7, demonstrating the robustness of chromosome enrichment in constructing the direct selection cDNA libraries. Thus far, 140 of these EST-specific STSs have been assigned unequivocally to YAC contigs that are distributed across the chromosome. Together, these studies provide >2000 ESTs highly enriched for chromosome 7 gene sequences, 180 new chromosome 7 STSs corresponding to ESTs, and a definitive demonstration of the ability to enrich for chromosome-specific cDNAs by direct selection. Furthermore, the libraries, sequence data, and mapping information will contribute to the construction of a chromosome 7 transcript map. C1 NIH,GENOME TECHNOL BRANCH,NATL HUMAN GENOME RES INST,BETHESDA,MD 20892. UNIV TEXAS,SW MED CTR,DEPT OTORHINOLARYNGOL,DALLAS,TX 75235. UNIV TEXAS,SW MED CTR,MCDERMOTT CTR HUMAN GROWTH & DEV,DALLAS,TX 75235. FU NHGRI NIH HHS [HG00368] NR 73 TC 17 Z9 22 U1 0 U2 0 PU COLD SPRING HARBOR LAB PRESS PI PLAINVIEW PA 1 BUNGTOWN RD, PLAINVIEW, NY 11724 SN 1054-9803 J9 GENOME RES JI Genome Res. PD MAR PY 1997 VL 7 IS 3 BP 281 EP 292 DI 10.1101/gr.7.3.281 PG 12 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity GA WN594 UT WOS:A1997WN59400009 PM 9074931 ER PT J AU Dyer, KD Handen, JS Rosenberg, HF AF Dyer, KD Handen, JS Rosenberg, HF TI The genomic structure of the human Charcot-Leyden crystal protein gene is analogous to those of the galectin genes SO GENOMICS LA English DT Article ID LACTOSE-BINDING LECTIN; SELECTIVE EXPRESSION; MOLECULAR-CLONING; ANIMAL LECTIN; MAC-2 ANTIGEN; MUSCLE LECTIN; LYSOPHOSPHOLIPASE; FAMILY; CELLS; LAMININ AB The Charcot-Leyden crystal (CLC) protein, or eosinophil lysophospholipase, is a characteristic protein of human eosinophils and basophils; recent work has demonstrated that the CLC protein is both structurally and functionally related to the galectin family of beta-galactoside binding proteins. The galectins as a group share a number of features in common, including a linear ligand binding site encoded on a single exon, In this work, we demonstrate that the intron-exon structure of the gene encoding CLC is analogous to those encoding the galectins. The coding sequence of the CLC gene is divided into four exons, with the entire beta-galactoside binding site encoded by exon III. We have isolated CLC beta-galactoside binding sites from both orangutan (Pongo pygmaeus) and murine (Mus musculus) genomic DNAs, both encoded on single exons, and noted conservation of the amino acids shown to interact directly with the beta-galactoside ligand. The most likely interpretation of these results suggests the occurrence of one or more exon duplication and insertion events, resulting in the distribution of this lectin domain to CLC as well as to the multiple galectin genes. C1 NIAID,LHD,NIH,BETHESDA,MD 20892. GEORGETOWN UNIV,MED CTR,DEPT PHYSIOL & BIOPHYS,WASHINGTON,DC 20057. NR 34 TC 24 Z9 27 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 0888-7543 J9 GENOMICS JI Genomics PD MAR 1 PY 1997 VL 40 IS 2 BP 217 EP 221 DI 10.1006/geno.1996.4590 PG 5 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA WN317 UT WOS:A1997WN31700001 PM 9119387 ER PT J AU Tamimi, RM Steingrimsson, E MontgomeryDyer, K Copeland, NG Jenkins, NA Tapscott, SJ AF Tamimi, RM Steingrimsson, E MontgomeryDyer, K Copeland, NG Jenkins, NA Tapscott, SJ TI NEUROD2 and NEUROD3 genes map to human chromosomes 17q12 and 5q23-q31 and mouse chromosomes 11 and 13, respectively SO GENOMICS LA English DT Article ID LOOP-HELIX PROTEIN AB NEUROD2 and NEUROD3 are transcription factors involved in neurogenesis that are related to the basic helix-loop-helix protein NEUROD, NEUROD2 maps to human chromosome 17q12 and mouse chromosome 11. NEUROD3 maps to human chromosome 5q23-q31 and mouse chromosome 13. (C) 1997 Academic Press. C1 FRED HUTCHINSON CANC RES CTR,SEATTLE,WA 98104. NCI,FREDERICK CANC RES & DEV CTR,ABL BASIC RES PROGRAM,MAMMALIAN GENET LAB,FREDERICK,MD 21702. UNIV WASHINGTON,SCH MED,DEPT NEUROL,SEATTLE,WA 98195. NR 16 TC 5 Z9 5 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0888-7543 J9 GENOMICS JI Genomics PD MAR 1 PY 1997 VL 40 IS 2 BP 355 EP 357 DI 10.1006/geno.1996.4578 PG 3 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA WN317 UT WOS:A1997WN31700019 PM 9119405 ER PT J AU Walker, RL Anziano, P Meltzer, PS AF Walker, RL Anziano, P Meltzer, PS TI A PAC containing the human mitochondrial DNA polymerase gamma gene (POLG) maps to chromosome 15q25 SO GENOMICS LA English DT Article C1 NIH,NATL CTR HUMAN GENOME RES,CANC GENET LAB,BETHESDA,MD 20892. UNIV NEVADA,DEPT PEDIAT,RENO,NV 89557. NR 5 TC 19 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 0888-7543 J9 GENOMICS JI Genomics PD MAR 1 PY 1997 VL 40 IS 2 BP 376 EP 378 DI 10.1006/geno.1996.4580 PG 3 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA WN317 UT WOS:A1997WN31700025 PM 9119411 ER PT J AU Butler, RN Cohen, G Lewis, MI SimmonsClemmons, W Sunderland, T AF Butler, RN Cohen, G Lewis, MI SimmonsClemmons, W Sunderland, T TI Late-life depression: How to make a difficult diagnosis - A roundtable discussion .1. SO GERIATRICS LA English DT Editorial Material AB Approximately 15% of persons age 65 and older have major depression. Risk factors include a recent loss (eg, widowhood or mastectomy), living alone, co-morbidities (eg, hypertension, stroke, cognitive deficits), and drug interactions. Warning signs of depression may include weight loss, sleep problems, feelings of guilt or worthlessness, loss of interest in sexual relations, or changes in activities of daily living. The diagnosis of depression is easy to miss if the physician doesn't look for it, because older persons often don't mention feeling depressed. Yet undetected depression can be deadly for older patients, who have the highest rate of suicide among all Americans. Plans for suicide may be direct or covert, as in not eating or not taking heart medication. C1 MT SINAI MED CTR,DEPT GERIATR & ADULT DEV,NEW YORK,NY 10029. GEORGE WASHINGTON UNIV,WASHINGTON,DC. CTR AGING,WASHINGTON,DC. MT SINAI MED CTR,DEPT COMMUNITY MED,DIV SOCIAL WORK,NEW YORK,NY 10029. NIMH,GERIATR PSYCHIAT BRANCH,BETHESDA,MD 20892. RP Butler, RN (reprint author), MT SINAI MED CTR,INT LONGEV CTR US,NEW YORK,NY 10029, USA. NR 2 TC 9 Z9 9 U1 0 U2 0 PU ADVANSTAR COMMUNICATIONS PI DULUTH PA 131 W FIRST ST, DULUTH, MN 55802 SN 0016-867X J9 GERIATRICS JI Geriatrics PD MAR PY 1997 VL 52 IS 3 BP 37 EP & PG 6 WC Geriatrics & Gerontology SC Geriatrics & Gerontology GA WM214 UT WOS:A1997WM21400005 PM 9068622 ER PT J AU Frank, RG McGuire, TG Bae, JP Rupp, A AF Frank, RG McGuire, TG Bae, JP Rupp, A TI Solutions for adverse selection in behavioral health care SO HEALTH CARE FINANCING REVIEW LA English DT Article ID SERVICES; INSURANCE; DEMAND AB Health plans have incentives to discourage high-cost enrollees (such as persons with mental illness) from joining. Public policy to counter incentives created by adverse selection is difficult when managed care controls cost through methods that are largely beyond the grasp of direct regulation. In this article, the authors evaluate three approaches to dealing with selection incentives: risk adjustment, the carving out of benefits, and cost-or risk-sharing between the payer and the plan. Adverse selection is a serious problem in the context of managed care. Risk adjustment is not likely to help much, but carving out the benefit and cost-sharing are promising directions for policy. C1 BOSTON UNIV,BOSTON,MA 02215. US HLTH CARE FINANCING ADM,BALTIMORE,MD 21207. NIMH,BETHESDA,MD. RP Frank, RG (reprint author), HARVARD UNIV,SCH MED,DEPT HLTH CARE POLICY,180 LONGWOOD AVE,BOSTON,MA 02115, USA. FU PHS HHS [18-C-90314/1] NR 37 TC 24 Z9 24 U1 0 U2 1 PU HEALTH CARE FINANCING REVIEW PI BALTIMORE PA 7500 SECURITY BLVD, C-3-11-07, BALTIMORE, MD 21224-1850 SN 0195-8631 J9 HEALTH CARE FINANC R JI Health Care Finan. Rev. PD SPR PY 1997 VL 18 IS 3 BP 109 EP 122 PG 14 WC Health Care Sciences & Services; Health Policy & Services SC Health Care Sciences & Services GA XQ607 UT WOS:A1997XQ60700008 PM 10170344 ER PT J AU Herion, D Hoofnagle, JH AF Herion, D Hoofnagle, JH TI The interferon sensitivity determining region: All hepatitis C virus isolates are not the same SO HEPATOLOGY LA English DT Editorial Material ID INFECTION RP Herion, D (reprint author), NIDDKD,LIVER DIS SECT,DIGEST DIS BRANCH,NIH,BLDG 10,ROOM 9B06,BETHESDA,MD 20892, USA. NR 21 TC 73 Z9 74 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD MAR PY 1997 VL 25 IS 3 BP 769 EP 771 DI 10.1002/hep.510250346 PG 3 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA WL830 UT WOS:A1997WL83000046 PM 9049233 ER PT J AU Spiegel, AM AF Spiegel, AM TI The molecular basis of disorders caused by defects in G proteins SO HORMONE RESEARCH LA English DT Review DE GTPase; signal transduction; G protein-coupled receptors; mutations ID MCCUNE-ALBRIGHT SYNDROME; STIMULATORY G-PROTEIN; HEREDITARY OSTEODYSTROPHY; ACTIVATING MUTATIONS; ADENYLYL-CYCLASE; PITUITARY-TUMORS; ENDOCRINE; ONCOGENES; GROWTH AB G proteins couple receptors for many hormones to effecters that regulate second messenger metabolism. G protein dysfunction could involve gain or loss of function. For G(s), the G protein that couples receptors to stimulation of cAMP formation, examples of both types have already been defined. Germline loss of function mutations in the G(s alpha) gene are responsible for a form of inherited hormone resistance termed pseudohypoparathyroidism (Albright hereditary osteodystrophy). Conversely, somatic gain of function mutations cause constitutive stimulation of cAMP, independent of receptor activation, in acromegaly, in hyperfunctional thyroid nodules, and in the McCune-Albright syndrome. Future work is likely to uncover additional disorders caused by defective G proteins with implications for diagnosis and treatment. RP Spiegel, AM (reprint author), NIDDKD,METAB DIS BRANCH,NIH,BLDG 10,RM 9N-222,BETHESDA,MD 20892, USA. NR 28 TC 53 Z9 54 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0301-0163 J9 HORM RES JI Horm. Res. PD MAR PY 1997 VL 47 IS 3 BP 89 EP 96 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA WJ969 UT WOS:A1997WJ96900001 PM 9050946 ER PT J AU Meslin, EM LemieuxCharles, L Wortley, JT AF Meslin, EM LemieuxCharles, L Wortley, JT TI An ethics framework for assisting clinician-managers in resource allocation decision making SO HOSPITAL & HEALTH SERVICES ADMINISTRATION LA English DT Article ID HEALTH-CARE; UNITED-STATES; MEDICINE; VALUES AB In response to continued pressure on the Canadian healthcare system, hospitals are implementing structural changes to address issues of cost containment, utilization, and resource allocation. One strategy has been to decentralize managerial decision making to clinicians, creating ''clinician-managers'' (CMs). We surveyed 3,000 hospital-based CMs in Ontario, Canada (including physicians, nurses, and other health professionals), in order to understand the nature and frequency of the ethical issues they face as a consequence of their involvement in resource allocation decisions, and to identify mechanisms for dealing with these problems in their hospitals. Based on the survey results, we developed a Management Ethics Framework to assist CMs to reach an ethically justifiable resolution of these types of problems, both individually, and in the context of their membership in the healthcare team. The results, and particularly the discussion that follows, represent a confluence of philosophical, clinical, and organizational perspectives on ethics and resource allocation by clinicians. C1 UNIV TORONTO,DEPT HLTH ADM,HOSP MANAGEMENT RES UNIT,TORONTO,ON M5S 1A8,CANADA. NIH,ELSI RES PROGRAM,NATL CTR HUMAN GENOME RES,BETHESDA,MD. UNIV TORONTO,DEPT SOCIOL,TORONTO,ON M5S 1A1,CANADA. NR 50 TC 5 Z9 5 U1 0 U2 3 PU AMER COLL HEALTHCARE EXEC HEALTH ADMINISTRATION PRESS PI CHICAGO PA ONE NORTH FRANKLIN ST SUITE 1700, CHICAGO, IL 60606 SN 8750-3735 J9 HOSP HEALTH SERV ADM JI Hosp. Health Serv. Adm. PD SPR PY 1997 VL 42 IS 1 BP 33 EP 48 PG 16 WC Health Policy & Services SC Health Care Sciences & Services GA WF348 UT WOS:A1997WF34800004 PM 10164897 ER PT J AU Latif, F Duh, FM Bader, S Sekido, Y Li, H Geil, L Zbar, B Minna, JD Lerman, MI AF Latif, F Duh, FM Bader, S Sekido, Y Li, H Geil, L Zbar, B Minna, JD Lerman, MI TI The human homolog of the rodent immediate early response genes, PC4 and TIS7, resides in the lung cancer tumor suppressor gene region on chromosome 3p21 SO HUMAN GENETICS LA English DT Article ID RENAL-CELL CARCINOMA; SWISS 3T3 CELLS; SHORT ARM; HOMOZYGOUS DELETION; HETEROZYGOSITY; ALLELES; SEQUENCES; CLONING AB Recently, human chromosome band 3p21.3 was shown to undergo overlapping homozygous deletions in several small cell lung cancer lines further defining a putative tumor suppressor gene(s) region. We report the cloning and mutational analysis of a novel human gene, SKMc15, from the commonly homozygously deleted region in three small cell lung cancer lines (NCI-H1450, NCI-H740, GLC20). It has 11 exons ranging in size from 50 to 541 bp with an open reading frame of 442 amino acids. The gene covers 7 to 10 kb of genomic DNA; the message of 1.8 to 2 kb is expressed in all analyzed fetal and adult human and mouse tissues including heart, brain, placenta, lung liver, skeletal muscle, kidney, testis and pancreas and in small cell and non-small cell cancer lines. The intron/exon boundaries were used to analyze the gene for mutations by exon PCR-SSCP sequencing in 60 small cell lung cancer cell lines. No loss-of-function mutations were detected. The cDNA sequence has high homology, 75% at the protein level, to the rat early response gene PC4 and its murine homolog TIS7. In addition, the known partial sequence of the putative mouse interferon beta 2 (64 amino acids) gene is highly conserved in PC4/TIS7 (94%) and in SKMc15 (83%) at the amino acid level. The sequence TAAAT, which is thought to be involved in mRNA degradation, is present in the 3' UTR of SKMc15 and in the 3' UTR of PC4 and TIS7 genes. C1 NCI,FREDERICK CANC RES & DEV CTR,INTRAMURAL RES SUPPORT PROGRAM,SAIC FREDERICK,FREDERICK,MD 21702. UNIV TEXAS,SW MED CTR,HAMON CTR THERAPEUT ONCOL RES,DALLAS,TX 75235. RP Latif, F (reprint author), NCI,FREDERICK CANC RES & DEV CTR,IMMUNOBIOL LAB,SAIC FREDERICK,FREDERICK,MD 21702, USA. RI Sekido, Yoshitaka/P-9756-2015 FU NCI NIH HHS [P20CA58220] NR 30 TC 24 Z9 25 U1 0 U2 8 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0340-6717 J9 HUM GENET JI Hum. Genet. PD MAR PY 1997 VL 99 IS 3 BP 334 EP 341 DI 10.1007/s004390050368 PG 8 WC Genetics & Heredity SC Genetics & Heredity GA WM468 UT WOS:A1997WM46800010 PM 9050919 ER PT J AU Biesecker, LG Schaffer, AA AF Biesecker, LG Schaffer, AA TI Automated selection of short tandem repeat polymorphism markers for whole genome screening for segmental aneusomy SO HUMAN HEREDITY LA English DT Article DE monosomy; trisomy; genotyping; computer algorithm; chromosome aberrations ID POLYMERASE CHAIN-REACTION; MENTAL-RETARDATION; HYBRIDIZATION; FLUORESCENCE; SETS AB Current clinical diagnostic techniques for the detection of small duplications and deletions include microscopic cytogenetics with Giemsa banding and FISH, An alternative approach is to use genetic markers, to detect duplications and deletions. The application of this technique to the entire genome as a test for segmental aneusomy requires a method for selecting a panel of markers that could be used and an estimate of the statistical power. We have developed a computer program, DECIDE, that performs these tasks. Given an input map of markers, DECIDE generates a near optimal list of markers and estimates the probability of detecting monosomy or trisomy of varying physical size. We demonstrate the program on a large map of markers obtained from the Southampton and CEPH databases. We conclude that this approach to screening for duplications and deletions is theoretically possible and would have a power comparable to routine Giemsa-banded chromosome analysis. C1 RICE UNIV,DEPT COMP SCI,HOUSTON,TX 77251. RP Biesecker, LG (reprint author), NATL HUMAN GENOME RES INST,NIH,BLDG 49,ROOM 4A80,BETHESDA,MD 20892, USA. RI Schaffer, Alejandro/F-2902-2012 NR 17 TC 3 Z9 3 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0001-5652 J9 HUM HERED JI Hum. Hered. PD MAR-APR PY 1997 VL 47 IS 2 BP 76 EP 85 DI 10.1159/000154395 PG 10 WC Genetics & Heredity SC Genetics & Heredity GA WN819 UT WOS:A1997WN81900003 PM 9097089 ER PT J AU Wyszynski, DF Maestri, N Lewanda, AF McIntosh, I Smith, EA GarciaDelgado, C VinagerasGuarneros, E Wulfsberg, E Beaty, TH AF Wyszynski, DF Maestri, N Lewanda, AF McIntosh, I Smith, EA GarciaDelgado, C VinagerasGuarneros, E Wulfsberg, E Beaty, TH TI No evidence of linkage for cleft lip with or without cleft palate to a marker near the transforming growth factor alpha locus in two populations SO HUMAN HEREDITY LA English DT Article DE linkage; birth defects; polymerase chain reaction; malformations ID AUTOSOMAL MAJOR LOCUS; GENETIC-VARIATION; POSSIBLE ASSOCIATION; BAMHI POLYMORPHISM; RFLPS; TGFA; DISEQUILIBRIUM; MALFORMATIONS; CHROMOSOME-2; INHERITANCE AB Nonsyndromic cleft lip with or without cleft palate is a common birth defect, affecting approximately 1 in 1,000 Caucasian newborns. Thirty-five multiplex families from the mid-Atlantic region of the United States and 22 families from central Mexico with a nonsyndromic form of cleft lip with or without cleft palate were selected for a linkage analysis. A tetranucleotide repeat marker (D2S443) located on the same yeast artificial chromosome as the transforming growth factor alpha locus was tested for linkage to a putative susceptibility Mendelian locus under varying levels of pentrance. No evidence for linkage between D2S443 and a susceptibility locus for cleft lip with or without cleft palate was found. Insight is given to explain this outcome in spite of the statistically significant associations found by other investigators. C1 NIH,NATL CTR HUMAN GENOME RES,MED GENET BRANCH,BETHESDA,MD 20892. JOHNS HOPKINS UNIV,SCH MED,DEPT PEDIAT,BALTIMORE,MD 21205. GEORGE WASHINGTON UNIV,DEPT MED GENET,WASHINGTON,DC. JOHNS HOPKINS UNIV,SCH MED,DEPT MED,BALTIMORE,MD 21205. UNIV MARYLAND,SCH MED,DIV HUMAN GENET,BALTIMORE,MD 21201. HOSP INFANTIL MEXICO DR FEDERICO GOMEZ,DEPT HUMAN GENET,MEXICO CITY,DF,MEXICO. HOSP INFANTIL MEXICO DR FEDERICO GOMEZ,DEPT PLAST & RECONSTRUCT SURG,MEXICO CITY,DF,MEXICO. RP Wyszynski, DF (reprint author), JOHNS HOPKINS UNIV,SCH HYG & PUBL HLTH,DEPT EPIDEMIOL,615 N WOLFE ST,BALTIMORE,MD 21205, USA. FU NCRR NIH HHS [RR03655]; NIDCR NIH HHS [R01-DE10293] NR 62 TC 25 Z9 28 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0001-5652 J9 HUM HERED JI Hum. Hered. PD MAR-APR PY 1997 VL 47 IS 2 BP 101 EP 109 DI 10.1159/000154397 PG 9 WC Genetics & Heredity SC Genetics & Heredity GA WN819 UT WOS:A1997WN81900005 PM 9097091 ER PT J AU Martayan, A Fiscella, M Setini, A Ciccarelli, G Gambari, R Feriotto, G Beretta, A Siccardi, AG Appella, E Giacomini, P AF Martayan, A Fiscella, M Setini, A Ciccarelli, G Gambari, R Feriotto, G Beretta, A Siccardi, AG Appella, E Giacomini, P TI Conformation and surface expression of free HLA-CW1 heavy chains in the absence of beta(2)-microglobulin SO HUMAN IMMUNOLOGY LA English DT Article ID MAJOR HISTOCOMPATIBILITY COMPLEX; CLASS-I MOLECULES; CELL-SURFACE; MONOCLONAL-ANTIBODIES; MEMBRANE-PROTEINS; PEPTIDE LIGAND; HLA-C; BETA-2-MICROGLOBULIN; ASSOCIATION; H-2DB AB A beta(2)-microglobulin (beta(2)m)-deficient kidney carcinoma cell line and three monoclonal antibodies to the alpha 1 (L31), alpha 2 (W6/32), and alpha 3 (Q1/28) domain of class I HLA molecules were selected to assess the role of beta(2)m in regulating the conformation and surface expression of HLA-C molecules. HLA-A2, -B27, and -CW1 molecules synthesized by beta(2)m-deficient cells were compared to heavy chains synthesized in transfectants expressing a large excess of beta(2)m. As assessed by differential binding with monoclonal antibodies and partitioning studies in the detergent TX-114, no HLA-A2, -B27, or -CW1 molecules can be expressed, in a correct conformation, by beta(2)m-deficient cells. These cells, however, do express low bur significant amounts of free HLA-CW1 heavy chains at the cell surface. Transfection with beta(2)m causes a coordinate change in the antibody reactivity of the three domains of HLA-CW1 molecules, thereby providing the first experimental demonstration that assembly with beta(2)m affects the folding of nor only the alpha 1 and alpha 2, but also of the alpha 3 domain. HLA-CW1 heavy chains, when free of beta(2)m, are less soluble in the detergent TX-114 than free HLA-B27 heavy chains, and when associated with beta(2)m share an alpha 3 domain epitope with free HLA-A2 and -B27 heavy chains. Moreover, their assembly with beta(2)m is largely incomplete. These data additionally demonstrate an impaired ability of HLA-CW1 ro properly fold and establish a dose similarity of HLA-CW1 to murine D-b and L-d molecules. Although the functional role, if any, of free HLA-CW1 heavy chains remains to be determined, the present study demonstrates that the absence of beta(2)m does not completely ablate class I expression in neoplastic cells of human origin. (C) American Society for Histocompatibility and Immunogenetics, 1997. C1 CRS,REGINA ELENA INST,IMMUNOL LAB,I-00158 ROME,ITALY. NCI,CELL BIOL LAB,NIH,BETHESDA,MD 20892. UNIV FERRARA,BIOCHEM LAB,I-44100 FERRARA,ITALY. DIBIT S RAFFAELE,MILAN,ITALY. RI Gambari, Roberto/F-9555-2015; Giacomini, Patrizio/K-5217-2016 OI Gambari, Roberto/0000-0001-9205-6033; Giacomini, Patrizio/0000-0001-6109-1709 NR 39 TC 16 Z9 16 U1 1 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0198-8859 J9 HUM IMMUNOL JI Hum. Immunol. PD MAR PY 1997 VL 53 IS 1 BP 23 EP 33 DI 10.1016/S0198-8859(96)00256-X PG 11 WC Immunology SC Immunology GA WU797 UT WOS:A1997WU79700004 PM 9127144 ER PT J AU Nayar, R Zhuang, ZP Merino, MJ Silverberg, SG AF Nayar, R Zhuang, ZP Merino, MJ Silverberg, SG TI Loss of heterozygosity on chromosome 11q13 in lobular lesions of the breast using tissue microdissection and polymerase chain reaction SO HUMAN PATHOLOGY LA English DT Article; Proceedings Paper CT USCAP Meeting CY MAR 26, 1996 CL WASHINGTON, DC SP USCAP DE breast cancer; lobular carcinoma; LCIS; ALH; microdissection; polymerase chain reaction; chromosome 11q13; loss of heterozygosity ID CARCINOMA INSITU; FOLLOW-UP; CANCER; EXPRESSION; GENE AB Demonstration of identical allelic loss on chromosome 11q13 in synchronous in situ (DCIS) and invasive ductal (LDC) breast carcinoma has provided molecular evidence of the progression of DCIS to IDC, We investigated loss of heterozygosity (LOH) at chromosome 11q13 in the spectrum of ''marker/premalignant'' and ''malignant'' lobular lesions of the breast, including atypical lobular hyperplasia (ALH), lobular carcinoma in situ (LCIS), and infiltrating lobular carcinoma (ILC), Thirty-eight cases with various combinations of ALH, LCIS, and ILC were studied, Synchronous ductal lesions were present in 9 of 38 cases. Areas of interest were specifically isolated by tissue microdissection. The extracted DNA was amplified by polymerase chain reaction (PCR) and analyzed with two polymorphic markers for chromosome 11q13 (INT2 and PYGM). LOH at 11q13 was identified in ILC and LCIS in approximately one third of informative cases. LCIS in association with ILC showed a loss in 50% of cases, whereas pure LCIS in the absence of ILC had a much lower frequency of LOH, which was comparable to that of pure ALH. These results suggest that LOH on chromosome 11q13 may play an important role in development of ILC, similar to that of IDC from DCIS/ADH. Additionally, frequent LOH in ILC and LCIS associated with ILC and a significantly lower and comparable frequency of LOH in LCIS without ILC and ALH implies that genetic alteration(s) on chromosome 11q13 may be important in the transition of LCIS to ILC, LOH was detected in three of nine synchronous ductal lesions (one IDC and two DCIS), confirming our earlier findings and indicating that lobular and ductal neoplasia in the breast show some similar genetic changes. We hypothesize that LOH may help in separating morphologically similar yet genetically different subgroups of ALH and LCIS into one group with genetic changes and an increased potential to progress to invasive cancer and another group, the ''marker'' lesions of LCIS/ALH, that remain stable or possibly regress. C1 NCI,DEPT PATHOL,PATHOL LAB,BETHESDA,MD 20892. GEORGE WASHINGTON UNIV,MED CTR,DEPT PATHOL,WASHINGTON,DC 20037. NR 22 TC 51 Z9 51 U1 0 U2 0 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 1997 VL 28 IS 3 BP 277 EP 282 DI 10.1016/S0046-8177(97)90124-6 PG 6 WC Pathology SC Pathology GA WK507 UT WOS:A1997WK50700004 PM 9042790 ER PT J AU Mansoor, A Stevenson, MS Li, RZ Frekko, K Weiss, W Ahmad, M Khan, AH Mushtaq, S Saleem, M Raffeld, M Kingma, DW Jaffe, ES AF Mansoor, A Stevenson, MS Li, RZ Frekko, K Weiss, W Ahmad, M Khan, AH Mushtaq, S Saleem, M Raffeld, M Kingma, DW Jaffe, ES TI Prevalence of Epstein-Barr viral sequences and EBV LMP1 oncogene deletions in Burkitt's lymphoma from Pakistan: Epidemiological correlations SO HUMAN PATHOLOGY LA English DT Article DE Epstein-Barr virus; LMP1; Burkitt's lymphoma; epidemiology; oncogene ID POLYMERASE CHAIN-REACTION; LATENT GENE-EXPRESSION; NON-HODGKINS-LYMPHOMA; LYMPHOPROLIFERATIVE DISORDERS; NASOPHARYNGEAL CARCINOMA; INSITU HYBRIDIZATION; T-CELL; VIRUS ASSOCIATION; TURKISH CHILDREN; UNITED-STATES AB To investigate the potential relationship of socioeconomic status with the prevalence of Epstein-Barr virus (EBV) and to understand the significance of del-LMP-1 within EBV+ cases of Burkitt's lymphoma (BL), we studied 10 cases of BL, 30 cases of diffuse large cell lymphoma (DLCL) arising in nonimmunocompromised patients, and 30 reactive tonsillar biopsy specimens from Pakistan. Each lymphoma was analyzed for EBV by EBER1 RNA in situ hybridization (EBV-RISH). Cases showing hybridization signal within neoplastic cells and all reactive tonsillar tissues were analyzed for EBV strain type by EBNA-2 polymerase chain reaction (PCR) and for the presence of a del-LMP-1 by PCR. Eight of 10 (80%) of BL were EBV+, each containing EBV strain A and a wild-type LMP-1 gene. In contrast, only 4 of 30 DLCL (13%) cases were EBV positive (three strain A, one strain B), each containing a wild-type LMP-1 gene. Fifteen of 30 tonsillar biopsy specimens contained EBV, all of which were strain A. and wild-type for LMP1. The prevalence of EBV in BL from Pakistan is slightly lower than in BL in endemic regions, but significantly higher than in BL in North America. EBV positivity probably reflects the socioeconomic status of the patient population and age at seroconversion. The absence of del-LMP-1 within all EBV+ BL cases is consistent with the view that del-LMP-1 is not involved in the pathogenesis of BL, and the presence of del-LMP-1 in EBV+ cases of BL reported in other studies may likely reflect the prevalence of a viral strain containing the 30-bp deletion within the respective population studied. C1 NCI,PATHOL LAB,HEMATOPATHOL SECT,BETHESDA,MD 20892. ARMED FORCES INST PATHOL,RAWALPINDI,PAKISTAN. NR 51 TC 18 Z9 20 U1 0 U2 2 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 1997 VL 28 IS 3 BP 283 EP 288 DI 10.1016/S0046-8177(97)90125-8 PG 6 WC Pathology SC Pathology GA WK507 UT WOS:A1997WK50700005 PM 9042791 ER PT J AU Lindsay, CK Thorgeirsson, UP Tsuda, H Hirohashi, S AF Lindsay, CK Thorgeirsson, UP Tsuda, H Hirohashi, S TI Expression of tissue inhibitor of metalloproteinase-1 and type IV collagenase/gelatinase messenger RNAs in human breast cancer SO HUMAN PATHOLOGY LA English DT Article DE tissue inhibitor of metalloproteinases-1; matrix metalloproteinases; breast cancer ID ENDOTHELIAL-CELL PROLIFERATION; MATRIX METALLOPROTEINASES; METALLO-PROTEINASES; GROWTH-FACTOR; LOCALIZATION; ANGIOGENESIS; CARCINOMAS; INVASION; TIMP-2; METASTASIS AB The relationship between malignant epithelial cell growth and the formation of tumor stroma is poorly understood. To investigate the roles of type TV collagenases/gelatinases and tissue inhibitor of metalloproteinase-l (TIMP-1) in human breast cancer, ive localized their messenger RNAs (mRNAs) in normal and malignant breast tissue. Type IV collagenase/gelatinase mRNAs were expressed at low levels by some tumor cells. High levels of TIMP-1 mRNA were found in all areas where tissue remodeling was evident, particularly in cells at the tumor-stromal interface. Small blood vessels in both the tumor and stroma were often outlined by high levels of TIMP-1 mRNA. These results indicate that TIMP-1 and type TV collagenases/gelatinases are expressed independently in breast cancer. C1 NCI,TUMOR BIOL & CARCINOGENESIS SECT,CELLULAR CARCINOGENESIS & TUMOR PROMOT LAB,DIV BASIC SCI,BETHESDA,MD 20892. NATL CANC CTR,RES INST,DIV PATHOL,TOKYO 104,JAPAN. NR 43 TC 16 Z9 16 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0046-8177 J9 HUM PATHOL JI Hum. Pathol. PD MAR PY 1997 VL 28 IS 3 BP 359 EP 366 DI 10.1016/S0046-8177(97)90136-2 PG 8 WC Pathology SC Pathology GA WK507 UT WOS:A1997WK50700016 PM 9042802 ER PT J AU Klett, CPR Bonner, T Printz, MP AF Klett, CPR Bonner, T Printz, MP TI Muscarinic M1 receptors - A candidate gene for hypertension in the SHR SO HYPERTENSION LA English DT Meeting Abstract C1 UNIV CALIF SAN DIEGO,DEPT PHARMACOL,LA JOLLA,CA 92093. NIMH,CELL BIOL LAB,BETHESDA,MD 20892. 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 0194-911X J9 HYPERTENSION JI Hypertension PD MAR PY 1997 VL 29 IS 3 BP 196 EP 196 PG 1 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA WL828 UT WOS:A1997WL82800219 ER PT J AU Cibotti, R Punt, JA Dash, KS Sharrow, SO Singer, A AF Cibotti, R Punt, JA Dash, KS Sharrow, SO Singer, A TI Surface molecules that drive T cell development in vitro in the absence of thymic epithelium and in the absence of lineage-specific signals SO IMMUNITY LA English DT Article ID POSITIVE SELECTION; CD4(+)CD8(+) THYMOCYTES; MONOCLONAL-ANTIBODY; RECEPTOR EXPRESSION; NEGATIVE SELECTION; MURINE; MICE; MATURATION; PROTEIN; MHC AB Differentiation of immature double positive (DP) CD4(+) CD8(+). thymocytes into single positive (SP) CD4(+) and CD8(+) T cells is referred to as positive selection and requires physical contact with thymic cortical epithelium. We now have identified ''coinducer'' molecules on DP thymocytes that, together with TCR, signal DP thymocytes to differentiate into SP T cells in vitro in the absence of thymic epithelium. A remarkable number of different molecules on DP thymocytes possessed ''coinducing'' activity, including CD2, CD5, CD24, CD28, CD49d, CD81, and TSA-1. Interestingly, in vitro differentiation occurred in the absence of lineage-specific signals, yet resulted in the selective generation of CD4(+)CD8(-) T cells. Thus, the present study has identified surface molecules that can signal DP thymocytes to differentiate into SP T cells in the absence of thymic epithelium and has characterized a default pathway for CD4(+) T cell differentiation. C1 NCI,EXPT IMMUNOL BRANCH,NIH,BETHESDA,MD 20892. NR 46 TC 87 Z9 88 U1 0 U2 1 PU CELL PRESS PI CAMBRIDGE PA 1050 MASSACHUSETTES AVE, CIRCULATION DEPT, CAMBRIDGE, MA 02138 SN 1074-7613 J9 IMMUNITY JI Immunity PD MAR PY 1997 VL 6 IS 3 BP 245 EP 255 DI 10.1016/S1074-7613(00)80327-1 PG 11 WC Immunology SC Immunology GA XC618 UT WOS:A1997XC61800004 PM 9075925 ER PT J AU Muller, KM Luedecker, CJ Udey, MC Farr, AG AF Muller, KM Luedecker, CJ Udey, MC Farr, AG TI Involvement of E-cadherin in thymus organogenesis and thymocyte maturation SO IMMUNITY LA English DT Article ID EPITHELIAL-CELLS; MONOCLONAL-ANTIBODY; ADHESION MOLECULES; EMBRYONIC HISTOGENESIS; IMMATURE THYMOCYTES; STROMAL CELLS; EXPRESSION; INTEGRIN; MORPHOGENESIS; RECEPTOR AB We examined the role of E-cadherin expressed by thymic epithelial cells and immature thymocytes in thymus organogenesis and thymocyte development. ECCD-1 MAb, which blocks homotypic E-cadherin interactions, inhibited epithelial organization and thymocyte development in reaggregate fetal thymic organ cultures. It also interfered with the differentiation of fetal liver cells or fetal thymocytes within deoxyguanosine-treated thymic lobes, but did not affect thymocyte development in intact cultured fetal thymic lobes. In contrast, antibodies that selectively inhibit interactions between E-cadherin and alpha(E) beta(7) integrins did not perturb thymic epithelial organization or thymocyte development, suggesting that homotypic E-cadherin interactions play an important role in thymus development and function. C1 UNIV WASHINGTON,SCH MED,DEPT BIOL STRUCT,SEATTLE,WA 98195. UNIV WASHINGTON,SCH MED,DEPT IMMUNOL,SEATTLE,WA 98195. NCI,DERMATOL BRANCH,BETHESDA,MD 20892. FU NIA NIH HHS [AG 04360]; NIAID NIH HHS [AI 24137] NR 51 TC 42 Z9 42 U1 0 U2 4 PU CELL PRESS PI CAMBRIDGE PA 1050 MASSACHUSETTES AVE, CIRCULATION DEPT, CAMBRIDGE, MA 02138 SN 1074-7613 J9 IMMUNITY JI Immunity PD MAR PY 1997 VL 6 IS 3 BP 257 EP 264 DI 10.1016/S1074-7613(00)80328-3 PG 8 WC Immunology SC Immunology GA XC618 UT WOS:A1997XC61800005 PM 9075926 ER PT J AU Kumar, A Kang, YH Gowda, K Mullen, CA Gordon, DM Kumar, S Hoffman, SL AF Kumar, A Kang, YH Gowda, K Mullen, CA Gordon, DM Kumar, S Hoffman, SL TI Autologous lymphoblastoid cell lines stably transfected with Plasmodium falciparum circumsporozoite protein as targets in cytotoxic T-lymphocyte assays SO IMMUNOLOGY LETTERS LA English DT Article DE malaria; Plasmodium falciparum; circumsporozoite protein; transfection; cytotoxic T-lymphocyte ID SPOROZOITE SURFACE PROTEIN-2; MALARIA; RESPONSES; EPITOPES; VOLUNTEERS; VACCINE AB To produce cell lines that can be used as a continuous source of antigen presenting cells for stimulating T-celI lines and clones and as targets in cytotoxic T-lymphocyte (CTL) assays, we used a retroviral vector with a simian virus (SV40) early promotor to transfer a Plasmodiumm falciparum circumsporozoite (PfCSP) gene into human EBV transformed B-lymphoblastoid cell lines (B-LCL). We herein report successful, stable transfection and cell surface expression of this gene, as confirmed by PCR, Western blot analysis and immunoelectron microscopy. One of three successfully transfected autologous cell lines expressed PfCSP on the cell surface and was lysed by CD8(+) T-cell dependent CTL from a donor volunteer who had been immunized with irradiated P. falciparum sporozoites. Such cell lines should provide excellent tools for characterizing human CD8(+) T-cell responses against Plasmadium sp. proteins. (C) 1997 Elsevier Science B.V. C1 NATL NAVAL MED CTR, DIV PATHOBIOL, BETHESDA, MD 20814 USA. UNIV TEXAS, DIV PEDIAT, HOUSTON, TX 77030 USA. WALTER REED ARMY INST RES, DIV COMMUNICABLE DIS & IMMUNOL, WASHINGTON, DC USA. NIAID, PARASIT DIS LAB, NIH, BETHESDA, MD 20892 USA. RP Kumar, A (reprint author), NATL NAVAL MED CTR, MALARIA PROGRAM, BETHESDA, MD 20814 USA. NR 19 TC 1 Z9 1 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-2478 J9 IMMUNOL LETT JI Immunol. Lett. PD MAR PY 1997 VL 55 IS 3 BP 183 EP 187 DI 10.1016/S0165-2478(97)02702-8 PG 5 WC Immunology SC Immunology GA WY161 UT WOS:A1997WY16100010 PM 9161886 ER PT J AU Gershoni, JM Stern, B Denisova, G AF Gershoni, JM Stern, B Denisova, G TI Combinatorial libraries, epitope structure and the prediction of protein conformations SO IMMUNOLOGY TODAY LA English DT Article ID SECONDARY-STRUCTURE; GLOBULAR-PROTEINS; IDENTIFICATION; PEPTIDES; GP120 AB The construction of combinatorial phage-display epitope libraries is a relatively recent innovation. This article describes how such libraries can be used to elucidate protein secondary structures. C1 NCI,TUMOR IMMUNOL & BIOL LAB,NATL INST HLTH,BETHESDA,MD 20892. RP Gershoni, JM (reprint author), TEL AVIV UNIV,DEPT CELL RES & IMMUNOL,IL-69978 TEL AVIV,ISRAEL. NR 15 TC 17 Z9 24 U1 0 U2 0 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, OXON, ENGLAND OX5 1GB SN 0167-5699 J9 IMMUNOL TODAY JI Immunol. Today PD MAR PY 1997 VL 18 IS 3 BP 108 EP 110 DI 10.1016/S0167-5699(97)01024-4 PG 3 WC Immunology SC Immunology GA WK575 UT WOS:A1997WK57500004 PM 9078681 ER PT J AU Medin, JA Karlsson, S AF Medin, JA Karlsson, S TI Viral vectors for gene therapy of hematopoietic cells SO IMMUNOTECHNOLOGY LA English DT Review DE gene transfer; gene therapy; hematopoiesis; viruses; stem cells ID HUMAN-IMMUNODEFICIENCY-VIRUS; RECOMBINANT ADENOASSOCIATED VIRUS; ADENO-ASSOCIATED VIRUS; PERIPHERAL-BLOOD LYMPHOCYTES; DIHYDROFOLATE-REDUCTASE CDNA; HIGH-LEVEL EXPRESSION; HERPES-SIMPLEX VIRUS; GAMMA-GLOBIN GENE; HUMAN FOAMY VIRUS; IN-VIVO AB Hematopoietic cells, in particular hematopoietic stem cells, are important targets for the development of gene therapy for hematological and other disorders. So far, simple retroviral vectors based on Murine Leukemia Virus (MLV) have been the main delivery vehicles for the transfer of corrective genes into primary hematopoietic cells. While the gene transfer efficiency of progenitor cells has been very efficient using these vectors, it has been much more problematic to obtain efficient gene transfer into repopulating human hematopoietic stem cells. The main reason for this is due to the quiescent nature of these cells and the fact that MLV-based vectors require dividing target cells. It may be that efficient gene transfer into hematopoietic stem cells can be accomplished by stimulating the cells to divide in vitro or by developing new vector systems that can isolate transduced cells or that can deliver genes permanently into nondividing target cells. This review will discuss the progress and problems of these approaches in developing effective gene therapy for hematopoietic cells. (C) 1997 Elsevier Science B.V. C1 NINCDS,NIH,DEV & METAB NEUROL BRANCH,BETHESDA,MD 20892. LUND UNIV,GENE THERAPY CTR,S-22362 LUND,SWEDEN. NR 102 TC 25 Z9 26 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1380-2933 J9 IMMUNOTECHNOLOGY JI Immunotechnology PD MAR PY 1997 VL 3 IS 1 BP 3 EP 19 DI 10.1016/S1380-2933(96)00059-0 PG 17 WC Biotechnology & Applied Microbiology; Immunology SC Biotechnology & Applied Microbiology; Immunology GA WW616 UT WOS:A1997WW61600001 PM 9154464 ER PT J AU Fiorentini, S Matczak, E Gallo, RC Reitz, MS Keydar, I Watkins, BA AF Fiorentini, S Matczak, E Gallo, RC Reitz, MS Keydar, I Watkins, BA TI Humanization of an antibody recognizing a breast cancer specific epitope by CDR-grafting SO IMMUNOTECHNOLOGY LA English DT Article DE CDR-grafting; Muc-1; monoclonal antibodies; human antibodies; breast cancer; tumor antigens ID POLYMORPHIC EPITHELIAL MUCIN; MURINE MONOCLONAL-ANTIBODY; RESHAPING HUMAN-ANTIBODIES; TUMOR-ASSOCIATED ANTIGENS; POLYMERASE CHAIN-REACTION; MOLECULAR-CLONING; CELL-LINE; IMMUNOGLOBULIN HEAVY; HYPERVARIABLE LOOPS; FRAMEWORK RESIDUES AB Background: Muc1-H23 is a cell surface mucin that is expressed on normal breast luminal epithelial cells and over-expressed in most breast tumors. In addition, Muc-1 expressed by malignant cells is glycosylated differently than Muc-1 expressed by normal cells. This difference in glycosylation exposes a peptide epitope on malignant cells which is not exposed on normal cells. Murine monoclonal antibody H23 recognizes this epitope and stains 91%, of breast cancers, but only 1/56 non-malignant breast tissue samples. Objective: To create a human antibody that was equivalent to H23 for potential uses in imaging and/or the therapy of breast cancer, Study design: We decided to humanize H23 by CDR-grafting using overlap PCR, and to this end, designed and constructed a bacterial expression vector that would allow V-regions, cloned via unique restriction sites, to be expressed as Fab fragments. In this way, le hoped to be able to rapidly evaluate Fab constructs for binding to Muc-1 and to cells and tissue sections that expressed the antigen. Results: A fully humanized Fab fragment was able to bind Muc-1 peptide, as well as breast cancer cells known to express the epitope and tissue sections, generally showing the same reactivity as the native antibody. In addition, an analysis of sFab expressed with a [His](6) tag preceded by a factor Xa proteolytic cleavage site suggested that E. coli periplasmic signal peptidase was able to cleave the factor Xa site, thereby removing the [His](6) tag. Conclusion: We have generated a human antibody that is capable of recognizing a tumor specific epitope expressed by 91% of breast cancers. (C) 1997 Elsevier Science B.V. C1 UNIV BRESCIA,INST MICROBIOL,I-25123 BRESCIA,ITALY. COLUMBIA PRESBYTERIAN MED CTR,DIV HEMATOL ONCOL,NEW YORK,NY 10032. UNIV MARYLAND,INST HUMAN VIROL,BALTIMORE,MD 21201. TEL AVIV UNIV,GEORGE S WISE DEPT BIOL SCI,IL-69978 TEL AVIV,ISRAEL. NCI,TUMOR CELL BIOL LAB,BETHESDA,MD 20892. NR 55 TC 3 Z9 3 U1 1 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1380-2933 J9 IMMUNOTECHNOLOGY JI Immunotechnology PD MAR PY 1997 VL 3 IS 1 BP 45 EP 59 DI 10.1016/S1380-2933(96)00063-2 PG 15 WC Biotechnology & Applied Microbiology; Immunology SC Biotechnology & Applied Microbiology; Immunology GA WW616 UT WOS:A1997WW61600004 PM 9154467 ER PT J AU Zhou, P Sieve, MC Tewari, RP Seder, RA AF Zhou, P Sieve, MC Tewari, RP Seder, RA TI Interleukin-12 modulates the protective immune response in SCID mice infected with Histoplasma capsulatum SO INFECTION AND IMMUNITY LA English DT Article ID GROWTH-FACTOR-BETA; INTERFERON-GAMMA PRODUCTION; NECROSIS-FACTOR-ALPHA; NATURAL-KILLER-CELLS; ACQUIRED-IMMUNODEFICIENCY-SYNDROME; CD4(+) T-CELLS; AMPHOTERICIN-B; MONOCLONAL-ANTIBODIES; HUMAN MACROPHAGES; RESISTANCE AB Infection with Histoplasma capsulatum results in a subclinical infection in immunocompetent hosts due to an effective cellular immune response, By contrast, immunodeficient individuals can have a severe disseminated and potentially fatal disease, In a previous study, it was demonstrated that normal mice infected intravenously with H. capsalatum and treated with interleukin-12 (IL-12) at the time of infection were protected from a fatal outcome, In this study, we examined the immunomodulatory effects of IL-12 on disseminated histoplasmosis in immunodeficient SCID mice. SCID mice infected with H. capsulatum and treated,vith IL-12 showed an increase in survival and a reduction in the colony counts of H. capsulatum in internal organs at 14 days after infection, The protective effect of IL-12 was abrogated if animals were also treated with a neutralizing antibody to gamma interferon (IFN-gamma). IL-12 treatment also resulted in an increase in mRNA expression and protein production for IFN-gamma, tumor necrosis factor alpha (TNF-alpha), and nitric oxide from spleen cells, When IL-12 was combined with amphotericin B (AmB) treatment, there was a significant increase in survival compared with either modality alone, Moreover, combined treatment resulted in an increase in both IFN-gamma and TNF-alpha production, as well as in a substantial reduction in H, capsulatum burden at 35 and 90 days postinfection. This study demonstrates that IL-12 modulates the protective immune response to histoplasmosis in SCID mice and also suggests that IL-12 in combination with AmB may be useful as a treatment for H. capsulatum in immunodeficient hosts. C1 NIAID,LYMPHOKINE REGULAT UNIT,CLIN INVEST LAB,NIH,BETHESDA,MD 20892. SO ILLINOIS UNIV,SCH MED,DEPT MED MICROBIOL & IMMUNOL,SPRINGFIELD,IL. FU NIAID NIH HHS [R01-AI22283] NR 40 TC 41 Z9 42 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0019-9567 J9 INFECT IMMUN JI Infect. Immun. PD MAR PY 1997 VL 65 IS 3 BP 936 EP 942 PG 7 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA WK953 UT WOS:A1997WK95300014 PM 9038300 ER PT J AU Duensing, TD vanPutten, JPM AF Duensing, TD vanPutten, JPM TI Vitronectin mediates internalization of Neisseria gonorrhoeae by Chinese hamster ovary cells SO INFECTION AND IMMUNITY LA English DT Article ID THROMBIN-ANTITHROMBIN-III; HUMAN ENDOTHELIAL-CELLS; EPITHELIAL-CELLS; STAPHYLOCOCCUS-AUREUS; MUCOSAL CELLS; BINDING-SITE; S-PROTEIN; INVASION; ATTACHMENT; GONOCOCCI AB Gonococci producing a distinct opacity protein (OpaA in strain MS11) adhere to and are efficiently internalized by cultured epithelial cells such as the Chang conjunctiva cell line, Both adherence and uptake require interactions between OpaA and heparan sulfate proteoglycans on the mammalian cell surface. Chinese hamster ovary (CHO) cells also support adherence of gonococci through interactions of OpaA with cell surface heparan sulfate proteoglycans. However, despite this similarity in the requirements for adherence, CHO cells are not capable of internalizing gonococci, In this report, we characterized this apparent deficiency and identified a factor in fetal calf serum (FCS) which is capable of mediating uptake of gonococci by CHO cells, In the absence of FCS, OpaA(+) gonococci adhered to but were not internalized by CHO cells, whereas in the presence of up to 15% FCS, the bacteria were efficiently internalized by the cells, Preincubation of bacteria, but not cells, with FCS also stimulated internalization, suggesting that a factor present in FCS was binding to the surface of gonococci and subsequently stimulating entry, Using a combination of chromatographic purification procedures, we identified the adhesive glycoprotein vitronectin as the serum factor which mediates the internalization of gonococci by CHO cells, Vitronectin-depleted serum did not support gonococcal entry, and this deficiency was restored by the addition of purified vitronectin. Further experiments using a set of gonococcal recombinants, each expressing a single member of the family of Opa outer membrane proteins, demonstrated that vitronectin bound to the surface of OpaA-producing gonococci only and that the vitronectin-mediated uptake by the CHO cells was limited to this bacterial phenotype, To our knowledge, our data are the first example that vitronectin can serve as a molecule that drives bacterial entry into epithelial cells. RP Duensing, TD (reprint author), NIAID,ROCKY MT LABS,LMSF,NIH,903 S 4TH ST,HAMILTON,MT 59840, USA. OI van Putten, Jos/0000-0002-4126-8172 NR 37 TC 68 Z9 69 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0019-9567 J9 INFECT IMMUN JI Infect. Immun. PD MAR PY 1997 VL 65 IS 3 BP 964 EP 970 PG 7 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA WK953 UT WOS:A1997WK95300018 PM 9038304 ER PT J AU Heinzen, RA Hackstadt, T AF Heinzen, RA Hackstadt, T TI The Chlamydia trachomatis parasitophorous vacuolar membrane is not passively permeable to low-molecular-weight compounds SO INFECTION AND IMMUNITY LA English DT Article ID TOXOPLASMA-GONDII; INTRACELLULAR PARASITISM; INFECTED-CELLS; HOST-CELLS; PROTEIN; PSITTACI; TRIPHOSPHATES; METABOLISM; INCLUSION; GENE AB Chlamydia trachomatis is an obligately intracellular bacterial parasite of eucaryotic cells that undergoes a biphasic life cycle within a parasitophorous vacuole (PV) called an inclusion, The parasitophorous vacuolar membrane (PVM) constitutes a barrier between the replicating bacteria and the nutrient-rich environment of the host cytoplasm, To determine whether the chlamydial PVM contains pores that allow passive diffusion of metabolites between the host cytoplasm and the PV, fluorescent tracer molecules were introduced directly into the cytoplasm of infected cells by transfection or microinjection, Fluorescence microscopy and laser scanning confocal microscopy were subsequently employed to determine whether equilibration of the fluorescent tracers between the cytoplasm and the PV occurred, No movement of tracer molecules as small as 520 Da from the cytoplasm to the PV was observed, These data suggest that the chlamydial PV is not passively permeable to small molecules through open channels in the PVM. C1 NIAID,ROCKY MT LABS,INTRACELLULAR PARASITES LAB,HOST PARASITE SECT,NIH,HAMILTON,MT 59840. NR 38 TC 74 Z9 77 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0019-9567 J9 INFECT IMMUN JI Infect. Immun. PD MAR PY 1997 VL 65 IS 3 BP 1088 EP 1094 PG 7 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA WK953 UT WOS:A1997WK95300034 PM 9038320 ER PT J AU Duffy, PE Kaslow, DC AF Duffy, PE Kaslow, DC TI A novel malaria protein, Pfs28, and Pfs25 are genetically linked and synergistic as falciparum malaria transmission-blocking vaccines SO INFECTION AND IMMUNITY LA English DT Article ID PLASMODIUM-FALCIPARUM; SEXUAL STAGES; ANTIBODIES; EXPRESSION; ANTIGENS; PURIFICATION; CANDIDATE; IMMUNITY; YEAST AB Antibodies to Pfs28 block Plasmodium falciparum transmission and when combined with antibodies to Pfs25 provide synergy in blocking transmission. Pfs28 and Pfs25 are immunogenic, have limited antigenic diversity, and are structurally similar and genetically linked on chromosome 10. Pfs28 may prove a useful addition to Pfs25 in an effective transmission-blocking vaccine. C1 NIAID,PARASIT DIS LAB,MALARIA VACCINES SECT,NIH,BETHESDA,MD 20892. WALTER REED ARMY INST RES,DEPT IMMUNOL,WASHINGTON,DC 20307. NR 14 TC 110 Z9 116 U1 0 U2 5 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0019-9567 J9 INFECT IMMUN JI Infect. Immun. PD MAR PY 1997 VL 65 IS 3 BP 1109 EP 1113 PG 5 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA WK953 UT WOS:A1997WK95300039 PM 9038325 ER PT J AU Gomez, R Romero, R Edwin, SS David, C AF Gomez, R Romero, R Edwin, SS David, C TI Pathogenesis of preterm labor and preterm premature rupture of membranes associated with intraamniotic infection SO INFECTIOUS DISEASE CLINICS OF NORTH AMERICA LA English DT Review ID INTERLEUKIN-1 RECEPTOR ANTAGONIST; TUMOR-NECROSIS-FACTOR; INTRA-AMNIOTIC INFECTION; C-REACTIVE PROTEIN; FLUID GLUCOSE-CONCENTRATION; PLATELET-ACTIVATING-FACTOR; BLOOD-CELL COUNT; ENDOPEROXIDE-H SYNTHASE; INTACT FETAL MEMBRANES; GROWTH-FACTOR-BETA AB This article reviews the definition, frequency, microbiology, pathogenesis, and clinical significance of intrauterine infections occurring in the context of preterm labor with intact membranes and preterm premature rupture of membranes and then focuses on the role of the products of arachidonic acid metabolism and proinflammatory cytokines in the mechanisms of preterm parturition associated with intrauterine infection. C1 WAYNE STATE UNIV,DEPT OBSTET & GYNECOL,DETROIT,MI. NICHHD,PERINATOL RES BRANCH,BETHESDA,MD 20892. NR 218 TC 205 Z9 212 U1 2 U2 7 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0891-5520 J9 INFECT DIS CLIN N AM JI Infect. Dis. Clin. North Am. PD MAR PY 1997 VL 11 IS 1 BP 135 EP & DI 10.1016/S0891-5520(05)70347-0 PG 43 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA WM569 UT WOS:A1997WM56900011 PM 9067790 ER PT J AU Leyendecker, B Lamb, ME Scholmerich, A Fricke, DM AF Leyendecker, B Lamb, ME Scholmerich, A Fricke, DM TI Contexts as moderators of observed interactions: A study of Costa Rican mothers and infants from differing socioeconomic backgrounds SO INTERNATIONAL JOURNAL OF BEHAVIORAL DEVELOPMENT LA English DT Article ID FAMILY DEVELOPMENT PROJECT; PENNSYLVANIA INFANT; CHILD-DEVELOPMENT; SOCIAL-CLASSES; ATTACHMENT; BEHAVIOR; SECURITY; FATHER; SPEECH; TEMPERAMENT AB Twenty first-born infants from low SES families and 20 first-born infants from middle SES families in Costa Rica were observed for 12 hours when they were 14 weeks old. The goals of this study were to: (1) study the impact of length of observation and context on our measures of interactional engagement; and (2) compare the interactional experiences of the infants in the two groups in various functional (e.g. feeding, object play) and social (e.g. with mother, with mother and others) contexts. Attuned and disharmonious interactions, as well as the frequency of positive affect, soothing, and vocalisation, varied considerably across the functional contexts. In addition, disharmonious interactions increased and interactional engagement decreased when mothers and infants were joined by others. Highly unstable measures of individual differences were obtained when observations were limited to 45-minute blocks, but stability increased considerably as the duration of the observations expanded. The groups did not differ with respect to amounts of time spent in various functional and social contexts, in attuned or disharmonious states, or in high levels of interactional engagement. Within some of the functional contexts, however, significant group differences in levels of attuned interactions, infant vocalisation, and maternal response vocalisation were found. Overall, functional and social contexts clearly moderated interactional experiences. SES effects on verbal and other interactional measures were limited to some contexts and may thus represent the infants' overall experiences quite poorly. Consequently, comparisons based on a single context may be inadequate for studies of subjects from differing socioeconomic backgrounds. C1 NICHHD,SECT SOCIAL & EMOT DEV,BETHESDA,MD 20814. UNIV COSTA RICA,INST PSYCHOL RES,SAN JOSE,COSTA RICA. RI Schoelmerich, Axel/C-9039-2009 OI Schoelmerich, Axel/0000-0002-9844-3920 NR 70 TC 20 Z9 21 U1 2 U2 4 PU PSYCHOLOGY PRESS PI HOVE PA 27 CHURCH RD, HOVE, EAST SUSSEX, ENGLAND BN3 2FA SN 0165-0254 J9 INT J BEHAV DEV JI Int. J. Behav. Dev. PD MAR PY 1997 VL 21 IS 1 BP 15 EP 34 PG 20 WC Psychology, Developmental SC Psychology GA WV052 UT WOS:A1997WV05200002 PM 12296019 ER PT J AU Powell, SK Kleinman, HK AF Powell, SK Kleinman, HK TI Neuronal laminins and their cellular receptors SO INTERNATIONAL JOURNAL OF BIOCHEMISTRY & CELL BIOLOGY LA English DT Review DE laminin; laminin-binding proteins; integrins; neurite outgrowth; neuronal development ID JUNCTIONAL EPIDERMOLYSIS-BULLOSA; CENTRAL-NERVOUS-SYSTEM; HUMAN NEUROBLASTOMA-CELLS; RAT SYMPATHETIC NEURONS; HEPARIN-BINDING DOMAIN; DORSAL-ROOT GANGLION; CREST-DERIVED CELLS; N-MYC ONCOGENE; NEURITE OUTGROWTH; EXTRACELLULAR-MATRIX AB The laminins are a family of extracellular matrix glycoproteins expressed throughout developing neural tissues. The laminins are potent stimulators of neurite outgrowth irt vitro for a variety of cell types, presumably reflecting an in vivo role in stimulating axon outgrowth. In recent years, the laminins have been shown to occur in several distinct isoforms; currently, the precise functional differences between the laminin variants are not web understood. A variety of neuronal surface receptors have been identified for one laminin isoform, laminin-l. These receptors include several members of the integrin family, as well as non-integrin laminin-binding proteins such as LBP-110, the 67 kDa laminin-receptor, alpha-dystroglycan, and beta 1,4 galactosyltransferase. Little is currently knows about receptors for other laminin isoforms. RP Powell, SK (reprint author), NIDR, DEV BIOL LAB, NIH, 9000 ROCKVILLE PIKE, BETHESDA, MD 20892 USA. NR 133 TC 132 Z9 134 U1 2 U2 10 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 1357-2725 J9 INT J BIOCHEM CELL B JI Int J. Biochem. Cell Biol. PD MAR PY 1997 VL 29 IS 3 BP 401 EP 414 DI 10.1016/S1357-2725(96)00110-0 PG 14 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA XE095 UT WOS:A1997XE09500003 PM 9202420 ER PT J AU Singh, J Kelloff, GF Reddy, BS AF Singh, J Kelloff, GF Reddy, BS TI Modulation of alterations in p53 tumor suppressor gene and its association with activation of ras proto-oncogenes during chemoprevention of colon cancer SO INTERNATIONAL JOURNAL OF ONCOLOGY LA English DT Article DE colon cancer; chemoprevention; p53; ras genes; molecular markers ID COLORECTAL-CANCER; MUTATIONS; CARCINOGENESIS; DNA; AGENTS; TUMORIGENESIS; AZOXYMETHANE; METABOLISM; CARCINOMA; NEOPLASIA AB Previously, we reported (Carcinogenesis 15: 1317-1323, 1994) a high rate of activating point mutations in I ns proto-oncogenes in azoxymethane (AOM)-induced colon tumors, and a significant suppression of these mutations by dietary administration of chemopreventive agents, D,L-alpha-difluoromethylornithine (DFMO) and piroxicam. To understand the role of p53 tumor suppressor gene in chemoprevention of colon cancer and to study the association of p53 gene alterations with activation of ras genes, we determined point mutations in conserved regions (exons 5-9) of p53 gene and analyzed the occurrence of double event of ms activation acid p53 mutation. Groups of male F344 rats were fed the modified AIN-76A diet containing 0, 4000 ppm DFMO, or 150 ppm piroxicam and administered s.c. AOM at a dose rate of 15 mg/kg body wt, once weekly, for 4 weeks. Vehicle controls received s.c. equal volume of normal saline. Animals were sacrificed 32 weeks after the last AOM or saline injection and their grossly visible colon tumors were analyzed to determine p53 mutations by PCR amplification based single strand conformation polymorphism (SSCP) and direct DNA sequencing. Our results demonstrate that about 57% tumors from animals fed the control diet contained predominantly missense but also nonsense mutations, whereas only 30% tumors from animals on piroxicam diet, and none (0%) from animals fed the DFMO diet had similar mutations. Analysis of data revealed that about half of the tumors from animals on control diet possessed both ms and p53 mutations together, only 27% of colon tumors from animals on piroxicam diet and none of the tumors from animals on DFMO diet exhibited both ms and p53 mutations. These results indicate that the administration of piroxicam, a non-steroidal anti-inflammatory drug, and DFMO, a irreversible inhibitor of ornithine decarboxylase, may inhibit selective proliferation of initiated cells containing activated las and/or mutant p53. Dietary DFMO exerted more pronounced inhibition of selective amplification of initiated cells containing mutated ras and/or p53. C1 AMER HLTH FDN,DIV NUTR CARCINOGENESIS,VALHALLA,NY 10595. NCI,CHEMOPREVENT LAB,DIV CANC PREVENT & CONTROL,BETHESDA,MD 20892. NR 48 TC 5 Z9 5 U1 0 U2 1 PU INT JOURNAL ONCOLOGY PI ATHENS PA C/O PROFESSOR D A SPANDIDOS, EDITORIAL OFFICE, 1, S MERKOURI ST, ATHENS 116 35, GREECE SN 1019-6439 J9 INT J ONCOL JI Int. J. Oncol. PD MAR PY 1997 VL 10 IS 3 BP 449 EP 456 PG 8 WC Oncology SC Oncology GA WK746 UT WOS:A1997WK74600003 PM 21533396 ER PT J AU Petropoulos, VC Smith, W Kousvelari, E AF Petropoulos, VC Smith, W Kousvelari, E TI Comparison of retention and release periods for implant overdenture attachments SO INTERNATIONAL JOURNAL OF ORAL & MAXILLOFACIAL IMPLANTS LA English DT Article; Proceedings Paper CT 1995 Annual Meeting of the Academy-of-Osseointegration CY 1995 CL CHICAGO, IL SP Acad Osseointegrat DE break load; dislodgment; displacement; implant attachment; oblique force; overdenture; peak load; release period; retention; tensile forces AB The aim of this study mas to compare the retention and release periods of the Nobel Biocare bar and clip (NBC), Nobel Biocare ball (NB), Zest anchor (ZA), Zest magnet (ZM), and Sterngold ERA (SE) attachments on art implant-retained overdenture model. The attachments were tested using two permanently placed Branemark implants on a test model that was attached to an Instron machine (cross-head speed 50.8 mm/minute). Each attachment had one part embedded in a denturelike housing, and the other part screwed into the implants, Dislodging tensile forces were applied to the housings in two directions simulating function vertical and oblique, Eight tests were done in two directions with three samples of each attachment. The dislodging forces generated measurements of the peak load, break load, and displacement at peak load and break load. Release periods were calculated using displacements between the peak load and break load and the cross-head speed. Results showed the NBC to be significantly most retentive for the break load when subjected to vertical and oblique forces with mean values and standard deviations of 2104.5 +/- 506.7 g and 1958.1 +/- 165.4 g, respectively. Next most retentive was the SE, followed by the ZA and NE. The ZM was significantly least retentive (127.8 +/- 7.0 g and 143.5 +/- 19.7 g). For the release period, results showed the NBC to have significantly the fastest release period for vertical and oblique forces (1.86 x 10(-3) and 1.35 x 10(-4) minutes). The ZM significantly had the slowest release period for those forces (3.02 x 10(-2) and 2.35 x 10(-2) minutes). The data suggested that the NBC could be selected when a high degree of retention and fast release period are desired. The next most retentive was the SE;ZM was the least retentive and had the slowest release period. C1 TEMPLE UNIV, SCH BUSINESS ADM, PHILADELPHIA, PA 19122 USA. NIDR, DIV EXTRAMURAL RES, BIOMAT BIOMIMET & TISSUE ENGN PROGRAM, NIH, BETHESDA, MD 20892 USA. RP Petropoulos, VC (reprint author), UNIV PENN, SCH DENT MED, DEPT RESTORAT DENT, 4001 SPRUCE ST, PHILADELPHIA, PA 19104 USA. NR 20 TC 52 Z9 53 U1 1 U2 5 PU QUINTESSENCE PUBL CO INC PI CAROL STREAM PA 551 KIMBERLY DR, CAROL STREAM, IL 60188-1881 SN 0882-2786 J9 INT J ORAL MAX IMPL JI Int. J. Oral Maxillofac. Implants PD MAR-APR PY 1997 VL 12 IS 2 BP 176 EP 185 PG 10 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA XT373 UT WOS:A1997XT37300004 PM 9109267 ER PT J AU HoehnSaric, R Greenberg, BD AF HoehnSaric, R Greenberg, BD TI Psychobiology of obsessive-compulsive disorder: Anatomical and physiological considerations SO INTERNATIONAL REVIEW OF PSYCHIATRY LA English DT Review ID CEREBRAL BLOOD-FLOW; POSITRON EMISSION TOMOGRAPHY; GLUCOSE METABOLIC RATES; COMPUTED-TOMOGRAPHY; MAGNETIC-RESONANCE; SYMPTOM PROVOCATION; TOURETTES-SYNDROME; FLUOXETINE; BEHAVIOR; EEG AB Several models seek to explain the psychobiology of obsessive-compulsive disorder (OCD). While none fully explains brain mechanisms responsible for the psychopathology of OCD, such models, based on clinical and experimental studies, elucidate further direction. This article reviews evidence from clinical observations and from electrophysiological and imaging studies on which the models were based A variety of neurological diseases that involve the fronto-striatal and limbic/paralimbic systems are associated with obsessive and compulsive symptoms. Electrophysiological and imaging studies in OCD patients free from demonstrable neurological lesions, strongly suggest that these regions are involved in the pathobiology of obsessive-compulsive disorder. The most consistent findings in imaging studies were increased metabolism and blood flow in orbito-frontal regions at rest and, in addition, regional changes in the striatum and in limbic/paralimbic regions during symptom provocation. Imaging studies indicate predominant prefrontal hyperactivity, particularly on the right. Neuroimaging, electrophysiological and neuropsychological studies suggest that both hemispheres may contribute, perhaps to different degrees, to the pathophysiology of OCD. Since OCD ir a heterogeneous disorder, it if likely that regionally specific pathology in the disorder will be variable. C1 NIH,DEPT HLTH & HUMAN SERV,BETHESDA,MD 20892. RP HoehnSaric, R (reprint author), JOHNS HOPKINS UNIV,SCH MED,DEPT PSYCHIAT & BEHAV SCI,HENRY PHIPPS PSYCHIAT SERV,600 N WOLFE ST,BALTIMORE,MD 21287, USA. NR 107 TC 16 Z9 16 U1 5 U2 6 PU CARFAX PUBL CO PI ABINGDON PA PO BOX 25, ABINGDON, OXFORDSHIRE, ENGLAND OX14 3UE SN 0954-0261 J9 INT REV PSYCHIATR JI Int. Rev. Psych. PD MAR PY 1997 VL 9 IS 1 BP 15 EP 29 DI 10.1080/09540269775565 PG 15 WC Psychiatry SC Psychiatry GA WP578 UT WOS:A1997WP57800003 ER PT J AU Greenberg, BD Altemus, M Murphy, DL AF Greenberg, BD Altemus, M Murphy, DL TI The role of neurotransmitters and neurohormones in obsessive-compulsive disorder SO INTERNATIONAL REVIEW OF PSYCHIATRY LA English DT Review ID SEROTONIN REUPTAKE INHIBITORS; CEREBROSPINAL-FLUID NEUROCHEMISTRY; FLUOXETINE-TREATED PATIENTS; TRANSPORTER MESSENGER-RNA; DOUBLE-BLIND; META-CHLOROPHENYLPIPERAZINE; HEALTHY-VOLUNTEERS; TOURETTES-SYNDROME; NEUROENDOCRINE RESPONSES; BUSPIRONE AUGMENTATION AB There is considerable evidence that serotonergic systems modulate obsessive-compulsive disorder (OCD) symptomatology. The strongest such data are the antiobsessional effects of serotonin reuptake inhibitors (SRIs), unique among antidepressants. Although the mechanisms underlying the effectiveness of SRI treatment remain largely unknown, the available data support the position that enhanced 5-HT synaptic availability, resulting from a combination of effects on serotonin release and transport, is necessary for the therapeutic efficacy of SRI treatment. The ability of the serotonergic probe mCPP to exacerbate OCD symptoms in untreated patients, and findings that potent 5-HT receptor antagonists may reverse SRI-induced therapeutic benefits, also support serotonergic modulation of OCD symptomatology. There is as yet little evidence that dysregulation in serotonergic systems might be etiologically important in OCD. Although evidence that other neurotransmitter or neuropeptide systems are involved in OCD is considerably more preliminary than that implicating serotonergic mechanisms, there are some indications that such systems may be involved. Studies of the role of these systems, and how they may interact with serotonergic mechanisms, may be particularly helpful in further elucidating the neuropharmacology of OCD and in identifying potential new treatments. RP Greenberg, BD (reprint author), NIMH, CLIN SCI LAB, BLDG 10, RM 3D41, 10 CTR DR MSC 1264, BETHESDA, MD 20892 USA. NR 137 TC 10 Z9 10 U1 1 U2 2 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 0954-0261 J9 INT REV PSYCHIATR JI Int. Rev. Psych. PD MAR PY 1997 VL 9 IS 1 BP 31 EP 44 PG 14 WC Psychiatry SC Psychiatry GA WP578 UT WOS:A1997WP57800004 ER PT J AU Weber, T Major, EO AF Weber, T Major, EO TI Progressive multifocal leukoencephalopathy: Molecular biology, pathogenesis and clinical impact SO INTERVIROLOGY LA English DT Review DE polyomaviruses; tumor biology; progressive multifocal leukoencephalopathy ID JC VIRUS-DNA; POLYMERASE CHAIN-REACTION; HUMAN-IMMUNODEFICIENCY-VIRUS; HUMAN POLYOMAVIRUS JC; CENTRAL-NERVOUS-SYSTEM; LARGE T-ANTIGEN; HUMAN-BRAIN-TUMORS; DEFICIENCY SYNDROME AIDS; MYELIN BASIC-PROTEIN; HUMAN PAPOVAVIRUS JC AB The human polyomaviruses JC virus (JCV) and BK virus (BKV) have long been known as once-and neurooncogenic. Interest in their oncogenic potential has reemerged with the discovery of simian virus 40 DNA in human brain tumors including the pituitary as well as in bone tumors and mesotheliomas. The only human disease caused by an infection with the human polyomavirus JCV is progressive multifocal leukoencephalopathy (PML) characterized by a lytic infection of oligodendrocytes with consecutive demyelination. Malignant transformation of cell lines appears to be caused by a complex interaction of the viral large T (tumor) antigen with several transcription factors and tumor suppressor proteins such as p53 and the retinoblastoma protein. PML, once an extremely rare disease, has become much more frequent in the western world owing to the AIDS pandemic. An exceedingly complicated, cell-, tissue- and species-specific pattern of protein-DNA interaction and negative as well as positive feedback regulation by at least a dozen proteins and possibly mutations in the JC viral promoter-enhancer region govern host range and development of PML. The intricate molecular and immunological prerequisites ultimately leading to PML in humans have not yet been completely elucidated. C1 Marienkrankenhaus Hamburg, Neurol Klin, Dept Neurol, D-22087 Hamburg, Germany. NINDS, Lab Mol Med & Neurosci, NIH, Bethesda, MD 20892 USA. RP Weber, T (reprint author), Marienkrankenhaus Hamburg, Neurol Klin, Dept Neurol, Alfredstr 9, D-22087 Hamburg, Germany. NR 198 TC 83 Z9 84 U1 0 U2 1 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0300-5526 J9 INTERVIROLOGY JI Intervirology PD MAR-JUN PY 1997 VL 40 IS 2-3 BP 98 EP 111 DI 10.1159/000150537 PG 14 WC Virology SC Virology GA YR310 UT WOS:000071482400005 PM 9450227 ER PT J AU Kitze, B Brady, JN AF Kitze, B Brady, JN TI Human T cell lymphotropic retroviruses: Association with diseases of the nervous system SO INTERVIROLOGY LA English DT Review DE human T cell lymphotropic virus type I; HTLV-I-associated myelopathy tropical spastic paraparesis; viral persistence; transactivation; antiviral immune response ID VIRUS-TYPE-I; TROPICAL SPASTIC PARAPARESIS; CYTOTOXIC LYMPHOCYTES-T; HTLV TYPE-I; MAJOR HISTOCOMPATIBILITY COMPLEX; BLOOD MONONUCLEAR-CELLS; SPINAL-CORD LESIONS; OPEN READING FRAME; PX MESSENGER-RNA; MHC CLASS-II AB In less than 1% of persistently infected individuals, human T cell lymphotropic virus type I (HTLV-I) causes a chronic inflammatory disease of the central nervous system (CNS), called HTLV-I-associated myeiopathy/tropical spastic paraparesis. Important prerequisites for disease induction are oligoclonal expansion of HTLV-I-infected CD4+ T lymphocytes, their trafficking across the blood-brain barrier, expression of viral proteins in the CNS, and an increased immune response within the CNS. The HTLV-I Taxi protein has unique abilities to transactivate viral and cellular genes in T lymphocytes, but possibly also in cells of the CNS. Thus Taxi supports the persistence of HTLV-I, the ongoing immune responses within the CNS and the destruction of myelin and axons, most pronounced in the thoracic spinal cord. C1 Univ Gottingen, Dept Neurol, D-37075 Gottingen, Germany. NCI, Div Basic Sci, NIH, Bethesda, MD 20892 USA. RP Kitze, B (reprint author), Univ Gottingen, Dept Neurol, Robert Koch Str 40, D-37075 Gottingen, Germany. EM bkitze@compuserve.com NR 116 TC 3 Z9 3 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0300-5526 J9 INTERVIROLOGY JI Intervirology PD MAR-JUN PY 1997 VL 40 IS 2-3 BP 132 EP 142 DI 10.1159/000150540 PG 11 WC Virology SC Virology GA YR310 UT WOS:000071482400008 PM 9450230 ER PT J AU Hannaway, C AF Hannaway, C TI The medical mandarins: The French Academy of Medicine in the nineteenth and early twentieth centuries - Weisz,G SO ISIS LA English DT Book Review RP Hannaway, C (reprint author), NIH,AIDS ORAL HIST PROJECT,BETHESDA,MD 20892, USA. NR 1 TC 0 Z9 0 U1 1 U2 1 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 S WOODLAWN AVE, CHICAGO, IL 60637 SN 0021-1753 J9 ISIS JI Isis PD MAR PY 1997 VL 88 IS 1 BP 153 EP 154 DI 10.1086/383664 PG 2 WC History & Philosophy Of Science SC History & Philosophy of Science GA WY215 UT WOS:A1997WY21500042 ER PT J AU Yang, YH Mattay, VS Weinberger, DR Frank, JA Duyn, JH AF Yang, YH Mattay, VS Weinberger, DR Frank, JA Duyn, JH TI Localized echo-volume imaging methods for functional MRI SO JMRI-JOURNAL OF MAGNETIC RESONANCE IMAGING LA English DT Article; Proceedings Paper CT International-Society-for-Magnetic-Resonance-in-Medicine CY 1996 CL NEW YORK, NY SP Int Soc Magnet Resonance Med DE fMRI; echo volume imaging; motor cortex; BOLD; EPI ID NMR SPIN ECHOES; HUMAN BRAIN; BLOOD OXYGENATION; 1.5 T; CONTRAST; ACTIVATION; EPI AB To perform true three-dimensional activation experiments in the human brain, dedicated localized echo-volume imaging (L-EVI) methods were developed. Three-dimensional acquisition allows generation of activation maps with minimal vascular enhancement related to inflow effects. The rapid acquisition of the L-EVI (similar to 100 msec) reduces signal instabilities caused by motion, facilitating the detection of the small intensity changes expected with brain activation. Single-shot L-EVI was performed on normal volunteers at 1.5 T, imaging a three-dimensional predefined volume (240 x 45 x 45 mm(3)) in the superior portion of the brain with a spatial resolution of 3.75 x 5 x 5 mm(3). Increased brain coverage was achieved with a multi-volume imaging (three-shot) version, which simultaneously achieved effective suppression of signals from cerebrospinal fluid. In addition, both asymmetric spin-echo (ASE) and spin-echo (SE) versions of the technique were used to detect blood oxygenation level dependent (BOLD) signal changes in the motor cortex with a finger-tapping paradigm. Images obtained by the L-EVI sequence were qualitatively comparable to standard multislice two-dimensional echo-planar images. Both ASE and SE functional MRI (fMRI) experiments showed consistent activation in the contralateral primary sensorimotor cortex. Furthermore, significant differences in location and magnitude of activation was observed between the two methods, confirming theoretical predictions. C1 OIR,LAB DIAGNOST RADIOL RES,NIH,BETHESDA,MD 20892. RI Duyn, Jozef/F-2483-2010 NR 22 TC 27 Z9 27 U1 0 U2 1 PU SOC MAGNETIC RESONANCE IMAGING PI EASTON PA 1991 NORTHAMPTON ST, EASTON, PA 18042-3189 SN 1053-1807 J9 JMRI-J MAGN RESON IM JI JMRI-J. Magn. Reson. Imaging PD MAR-APR PY 1997 VL 7 IS 2 BP 371 EP 375 DI 10.1002/jmri.1880070220 PG 5 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA WP118 UT WOS:A1997WP11800019 PM 9090593 ER PT J AU Ostuni, JL Levin, RL Frank, JA DeCarli, C AF Ostuni, JL Levin, RL Frank, JA DeCarli, C TI Correspondence of closest gradient voxels - A robust registration algorithm SO JMRI-JOURNAL OF MAGNETIC RESONANCE IMAGING LA English DT Article; Proceedings Paper CT International-Society-for-Magnetic-Resonance-in-Medicine CY 1996 CL NEW YORK, NY SP Int Soc Magnet Resonance Med DE registration; sequence independent; robust; automatic; gradient matching; closest gradients ID AUTOMATED ALGORITHM; IMAGES AB A robust, automatic volume registration algorithm based on intensity gradients is presented, This algorithm can successfully perform registrations under conditions of unrelated intervolume voxel intensities, significant object displacements, and/or significant amounts of missing data, It also allows the user to visualize the registration convergence, clearly illustrating any source of registration errors. This algorithm consists of a matching algorithm based on iteratively finding the correspondence of the closest voxels containing a high three-dimensional intensity gradient magnitude, This algorithm was tested by registering T2-weighted MR volumes that had undergone varying displacement transformations to simultaneously acquired proton-density volumes, These transformations involved rotations of up to 25 degrees followed by translations of up to 25 mm along the axis of rotation, For all registrations, the mean registration error was less than one-fifth of a voxel and the mean registration time was less than 30 minutes, In conclusion, this algorithm is shown to be a powerful method of sequence-independent MR volume registration that is simple to both use and understand. RP Ostuni, JL (reprint author), NIH,LAB DIAGNOST RADIOL RES,BLDG 10,ROOM B1N256,10 CTR DR MSC 1074,BETHESDA,MD 20892, USA. RI DeCarli, Charles/B-5541-2009 NR 11 TC 57 Z9 57 U1 0 U2 0 PU SOC MAGNETIC RESONANCE IMAGING PI EASTON PA 1991 NORTHAMPTON ST, EASTON, PA 18042-3189 SN 1053-1807 J9 JMRI-J MAGN RESON IM JI JMRI-J. Magn. Reson. Imaging PD MAR-APR PY 1997 VL 7 IS 2 BP 410 EP 415 DI 10.1002/jmri.1880070227 PG 6 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA WP118 UT WOS:A1997WP11800026 PM 9090600 ER PT J AU Saggioro, D Rosato, A Esposito, G Rosenberg, MP Harrison, J Felber, BK Pavlakis, GN ChiecoBianchi, L AF Saggioro, D Rosato, A Esposito, G Rosenberg, MP Harrison, J Felber, BK Pavlakis, GN ChiecoBianchi, L TI Inflammatory polyarthropathy and bone remodeling in HTLV-I tax-transgenic mice SO JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES AND HUMAN RETROVIROLOGY LA English DT Article DE tax protein; arthropathy; bone remodeling ID T-CELL LEUKEMIA; VIRUS TYPE-I; RESEMBLING RHEUMATOID-ARTHRITIS; CONSTITUTIVE EXPRESSION; CYTOKINE PRODUCTION; INFECTION; LINES; GENE; HYPERCALCEMIA; POLYMYOSITIS AB Transgenic mice carrying the tax gene of human T-cell lymphotropic virus type I displayed a high prevalence of arthropathy. The percentage of affected animals increased with age, reaching a peak of 43% at 20 months. Southern analysis of deoxyribonucleic acid (DNA) from tissue samples indicated that disease development was related to tax copy number. Histopathologic evaluation of the ankle joints disclosed deep erosion of the synovial lining, fibrous tissue proliferation together with angiogenesis, mononuclear cell infiltration, and activation of osteoclasts. Radiologic examination confirmed joint involvement and revealed bone architecture modifications. The phenotype exhibited by the affected animals closely resembles that of seronegative arthritis in humans, and may indicate tax protein as a causal agent of arthropathy observed in HTLV-I infected individuals. C1 UNIV PADUA,IST,BIOTECHNOL SECT,I-35128 PADUA,ITALY. GLAXO WELLCOME RES & DEV INST,DEPT PHARMACOL,RES TRIANGLE PK,NC. NCI,FREDERICK CANC RES & DEV CTR,ABL BASIC RES PROGRAM,FREDERICK,MD. RP Saggioro, D (reprint author), UNIV PADUA,IST ONCOL,INTERUNIV CTR CANC RES,VIA GATTAMELATA 64,I-35128 PADUA,ITALY. RI Rosato, Antonio/E-8626-2010; OI Rosato, Antonio/0000-0002-5263-8386; Saggioro, Daniela/0000-0002-7136-2821 NR 36 TC 12 Z9 12 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 1 PY 1997 VL 14 IS 3 BP 272 EP 280 PG 9 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA WP137 UT WOS:A1997WP13700012 PM 9117461 ER PT J AU Philibert, RA Egeland, JA Paul, SM Ginns, EI AF Philibert, RA Egeland, JA Paul, SM Ginns, EI TI The inheritance of bipolar affective disorder: Abundant genes coming together SO JOURNAL OF AFFECTIVE DISORDERS LA English DT Editorial Material ID COMPLEX TRAITS; DISSECTION; GENETICS C1 UNIV MIAMI,SCH MED,DEPT PSYCHIAT,MIAMI,FL 33136. ELI LILLY & CO,LILLY RES LABS,INDIANAPOLIS,IN 46285. RP Philibert, RA (reprint author), NIMH,CLIN NEUROSCI BRANCH,NIH,BLDG 49,B1EE16,49 CONVENT DR,MSC4405,BETHESDA,MD 20892, USA. NR 17 TC 7 Z9 7 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-0327 J9 J AFFECT DISORDERS JI J. Affect. Disord. PD MAR PY 1997 VL 43 IS 1 BP 1 EP 3 DI 10.1016/S0165-0327(96)01417-6 PG 3 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA WT438 UT WOS:A1997WT43800001 PM 9127824 ER PT J AU Skopp, G Ganssmann, B Cone, EJ Aderjan, R AF Skopp, G Ganssmann, B Cone, EJ Aderjan, R TI Plasma concentrations of heroin and morphine-related metabolites after intranasal and intramuscular administration SO JOURNAL OF ANALYTICAL TOXICOLOGY LA English DT Article ID DIACETYLMORPHINE HEROIN; HUMAN-SERUM; PHARMACOKINETICS; BLOOD; DRUGS; MORPHINE-3-GLUCURONIDE; MORPHINE-6-GLUCURONIDE; PHARMACODYNAMICS C1 NIDA,ADDICT RES CTR,NIH,BALTIMORE,MD 21224. RP Skopp, G (reprint author), UNIV HEIDELBERG,INST LEGAL MED,VOSSSTR 2,D-69115 HEIDELBERG,GERMANY. NR 34 TC 25 Z9 28 U1 0 U2 2 PU PRESTON PUBLICATIONS INC PI NILES PA 7800 MERRIMAC AVE PO BOX 48312, NILES, IL 60648 SN 0146-4760 J9 J ANAL TOXICOL JI J. Anal. Toxicol. PD MAR-APR PY 1997 VL 21 IS 2 BP 105 EP 111 PG 7 WC Chemistry, Analytical; Toxicology SC Chemistry; Toxicology GA WP409 UT WOS:A1997WP40900002 PM 9083827 ER PT J AU Ryschon, TW Jarvis, JC Salmons, S Balaban, RS AF Ryschon, TW Jarvis, JC Salmons, S Balaban, RS TI High-energy phosphates and tension production in rabbit tibialis anterior/extensor digitorum longus muscles SO JOURNAL OF APPLIED PHYSIOLOGY LA English DT Article DE fatigue; chronic stimulation; P-31-magnetic resonance spectroscopy ID MITOCHONDRIAL GENE-EXPRESSION; STIMULATION-INDUCED DAMAGE; TWITCH SKELETAL-MUSCLES; CONTRACTILE ACTIVITY; MAGNETIC-RESONANCE; SLOW; TRANSFORMATION; NUCLEAR; SPECTROSCOPY; SENSITIVITY AB The effects of repetitive muscle contraction on energy state and tension production were studied in rabbit tibialis anterior/extensor digitorum longus muscles that had been subjected to 90 days of continuous indirect electrical stimulation at 10 Hz. Anesthetized chronically stimulated and control rabbits were challenged with 15 min of stimulation at 4 and 15 tetani/min. P-i-to-phasphacreatine (PCr) ratio (P-i/PCr) was measured in vivo before, during, and after acute stimulation by P-31- magnetic resonance spectroscopy, and tension was recorded at the same time. Although P-i/PCr was low at rest, it was significantly higher in chronically stimulated muscle than in control muscle (0.20 +/- 0.02 vs. 0.05 +/- 0.01, P < 0.05). Stimulation of control muscle for 15 min at both 4 and 15 tetani/min induced a significant rise in P-i/PCr, whereas the same conditions in chronically stimulated muscle did not produce any significant departure from initial levels. The tension produced by control muscle fell to 93 +/- 3% of its initial value during stimulation at 4 tetani/min and to 61 +/- 7% at 15 tetani/min, respectively. In chronically stimulated muscle, on the other hand, tension was potentiated above its initial level at both stimulation rates (135 +/- 15 and 138 +/- 11%, respectively) and remained significantly elevated throughout each trial. The ability of chronically stimulated muscle to sustain high revels of activity with minimal perturbations in P-i/PCr or decrement in tension is attributable to cellular adaptations that include a well-documented increase in oxidative capacity. C1 NHLBI,CARDIAC ENERGET LAB,BETHESDA,MD 20892. UNIV LIVERPOOL,DEPT HUMAN ANAT & CELL BIOL,LIVERPOOL L69 3BX,MERSEYSIDE,ENGLAND. RI Balaban, Robert/A-7459-2009 OI Balaban, Robert/0000-0003-4086-0948 NR 30 TC 1 Z9 1 U1 0 U2 0 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 8750-7587 J9 J APPL PHYSIOL JI J. Appl. Physiol. PD MAR PY 1997 VL 82 IS 3 BP 1024 EP 1029 PG 6 WC Physiology; Sport Sciences SC Physiology; Sport Sciences GA WM775 UT WOS:A1997WM77500044 PM 9074997 ER PT J AU Thompson, J Robrish, SA Bouma, CL Freedberg, DI Folk, JE AF Thompson, J Robrish, SA Bouma, CL Freedberg, DI Folk, JE TI Phospho-beta-glucosidase from Fusobacterium mortiferum: Purification, cloning, and inactivation by 6-phosphoglucono-delta-lactone SO JOURNAL OF BACTERIOLOGY LA English DT Article ID SUGAR PHOSPHOTRANSFERASE SYSTEM; GRAM-POSITIVE BACTERIA; ESCHERICHIA-COLI K12; NUCLEOTIDE-SEQUENCE; GLYCOSYL HYDROLASES; BGL OPERON; PHOSPHOENOLPYRUVATE; ATCC-25557; GLYCOSIDASES; SPECIFICITY AB 6-Phosphoryl-beta-D-glucopyranosyl:6-phosphoglucohydrolase (P-beta-glucosidase, EC 3.2.1.86) has been purified from Fusobacterium mortiferum. Assays for enzyme activity and results from Western immunoblots showed that P-beta-glucosidase (M(r), 53,000; pI, 4.5) was induced by growth of F. mortiferum on beta-glucosides. The novel chromogenic and fluorogenic substrates, p-nitrophenyl-beta-D-glucopyranoside-6-phosphate (pNP beta Glc6P) and 4-methylumbelliferyl-beta-D-glucopyranoside-6-phosphate (4MU beta Glc6P), respectively, were used for the assay of P-beta-glucosidase activity. The enzyme hydrolyzed several P-beta-glucosides, including the isomeric disaccharide phosphates cellobiose-6-phosphate, gentiobiose-6-phosphate, sophorose-6-phosphate, and laminaribiose-6-phosphate, to yield glucose-6-phosphate and appropriate aglycons. The kinetic parameters for each substrate are reported. P-beta-glucosidase from F. mortiferum was inactivated by 6-phosphoglucono-delta-lactone (P-glucono-delta-lactone) derived via oxidation of glucose 6-phosphate. The pbgA gene that encodes P-beta-glucosidase from F. mortiferum has been cloned and sequenced. The first 42 residues deduced from the nucleotide sequence matched those determined for the N terminus by automated Edman degradation of the purified enzyme. From the predicted sequence of 466 amino acids, two catalytically important glutamyl residues have been identified, Comparative alignment of the amino acid sequences of P-beta-glucosidase from Escherichia coli and F. mortiferum indicates potential binding sites for the inhibitory P-glucono-delta-lactone to the enzyme from F. mortiferum. C1 NIDR, STRUCT MOL BIOL UNIT, NIH, BETHESDA, MD 20892 USA. NIDR, LAB CELLULAR DEV & ONCOL, NIH, BETHESDA, MD 20892 USA. RP Thompson, J (reprint author), NIDR, MICROBIAL ECOL LAB,NIH,BLDG 30,ROOM 528, CONVENT DR MSC 4350, BETHESDA, MD 20892 USA. NR 53 TC 17 Z9 20 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0021-9193 J9 J BACTERIOL JI J. Bacteriol. PD MAR PY 1997 VL 179 IS 5 BP 1636 EP 1645 PG 10 WC Microbiology SC Microbiology GA WP415 UT WOS:A1997WP41500028 PM 9045824 ER PT J AU Winterling, KW Levine, AS Yasbin, RE Woodgate, R AF Winterling, KW Levine, AS Yasbin, RE Woodgate, R TI Characterization of DinR, the Bacillus subtilis SOS repressor SO JOURNAL OF BACTERIOLOGY LA English DT Article ID RECA PROTEIN ANALOG; LEXA REPRESSOR; DNA-DAMAGE; ESCHERICHIA-COLI; MOLECULAR CHARACTERIZATION; REGULATORY ELEMENTS; GENE; EXPRESSION; SEQUENCE; CLONING AB In Bacillus subtilis, exposure to DNA damage and the development of natural competence lead to the induction of the SOS regulon. It has been hypothesized that the DinR protein is the cellular repressor of the B. subtilis SOS system due to its homology to the Escherichia coli LexA transcriptional repressor. Indeed, comparison of DinR and its homologs from gram-negative and -positive bacteria revealed conserved structural motifs within the carboxyl-terminal domain that are believed to be important for autocatalysis of the protein. In contrast, regions within the DNA binding domain were conserved only within gram-negative or -positive genera, which possibly explains the differences in the sequence specificities between gram-negative and gram-positive SOS boxes. The hypothesis that DinR is the repressor of the SOS regulon in B. subtilis has been tested through overexpression, purification, and characterization of the DinR protein. Like E. coli LexA, B. subtilis DinR undergoes an autocatalytic reaction at alkaline pH at a siscile Ala(91)-Gly(92) bond. The cleavage reaction can also be mediated in vitro under more physiological conditions by the E. coli RecA protein, Bg using electrophoretic mobility shift assays, we demonstrated that DinR interacts with the previously characterized SOS box of the B. subtilis recA gene, but not with sequences containing single base pair mutations within the SOS box. Together, these observations strongly suggest that DinR is the repressor of the SOS regulon in B. subtilis. C1 NICHHD,SECT DNA REPLICAT REPAIR & MUTAGENESIS,NIH,BETHESDA,MD 20892. UNIV MARYLAND,DEPT BIOL SCI,CATONSVILLE,MD 21228. UNIV TEXAS,PROGRAM MOL & CELL BIOL,RICHARDSON,TX 75083. NR 37 TC 38 Z9 38 U1 0 U2 2 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 1997 VL 179 IS 5 BP 1698 EP 1703 PG 6 WC Microbiology SC Microbiology GA WP415 UT WOS:A1997WP41500035 PM 9045831 ER PT J AU Kaushal, S LaRussa, VF Hall, ER Gartner, S Kim, JH Perera, LP Yu, Z Kessler, SW Mosca, JD AF Kaushal, S LaRussa, VF Hall, ER Gartner, S Kim, JH Perera, LP Yu, Z Kessler, SW Mosca, JD TI Providing a microenvironment for the development of human CD34+ hematopoietic cells in SCID mice SO JOURNAL OF BIOMEDICAL SCIENCE LA English DT Article DE SCID mice; hematopoiesis; stromal cells; CD34+ cells; microenvironment ID TUMOR-NECROSIS-FACTOR; BONE-MARROW; HU MICE; STEM-CELLS; ANTIGENIC ANALYSIS; PROGENITOR CELLS; IN-VITRO; MOUSE; DIFFERENTIATION; GROWTH AB In order to develop a convenient small-animal model that can support the differentiation of human bone-marrow-derived CD34+ cells, we transplanted SCID mice with an immortalized human stromal cell line, Lof(11-10). The Lof(11-10) cell line has been characterized to produce human cytokines capable of supporting primitive human hematopoietic cell proliferation in vitro. Intraperitoneal injection of Lof(11-10) cells into irradiated SCID mice by itself resulted in a dose-dependent survival of the mice from lethal irradiation. The radioprotective survival was reflected by an increase in the growth and number of mouse bone-marrow-derived committed hematopoietic progenitors. The Lof(11-10) cells localized to the spleen, but not to the bone marrow of these animals and resulted in detectable levels of circulating human IL-6 in their plasma. Secondary intravenous injections of either human or simian CD34+ cells into the Lof(11-10)-transplanted SCID mice resulted in engraftment of injected cells within the bone marrow of these mice. The utility of this small-animal model that allows the growth and differentiation of human CD34+ cells and its potential use in clinical gene therapy protocols are discussed. C1 OSIRIS THERAPEUT INC,BALTIMORE,MD 21231. HENRY M JACKSON FDN ADVANCEMENT MIL MED,ROCKVILLE,MD. WALTER REED ARMY INST RES,ROCKVILLE,MD. TULANE CANC CTR,BONE MARROW TRANSPLANTAT PROGRAM,NEW ORLEANS,LA. UNIV MARYLAND,INST HUMAN VIROL,BALTIMORE,MD 21201. JOHNS HOPKINS UNIV HOSP,DEPT NEUROL,BALTIMORE,MD 21287. NIAID,NIH,BETHESDA,MD 20892. SYSTEMIX,PALO ALTO,CA. USN,MED RES UNIT 3,CAIRO,EGYPT. NR 32 TC 1 Z9 1 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1021-7770 J9 J BIOMED SCI JI J. Biomed. Sci. PD MAR-JUN PY 1997 VL 4 IS 2-3 BP 61 EP 68 DI 10.1007/BF02255595 PG 8 WC Cell Biology; Medicine, Research & Experimental SC Cell Biology; Research & Experimental Medicine GA YD087 UT WOS:A1997YD08700001 ER PT J AU Kim, IK Li, CCH Young, HA Lee, JH Kim, HS Pardhasaradhi, K Garcia, GE Chiang, PK AF Kim, IK Li, CCH Young, HA Lee, JH Kim, HS Pardhasaradhi, K Garcia, GE Chiang, PK TI Apoptosis of L1210 leukemia cells induced by 3-deazaadenosine analogs: Differential expression of c-myc, NF-Kappa B and molecular events SO JOURNAL OF BIOMEDICAL SCIENCE LA English DT Article DE apoptosis; cell cycle; 3-deazaadenosine analogs; L1210 lymphocytic leukemia cells; c-myc; NF-kappa B ID S-ADENOSYLHOMOCYSTEINE HYDROLASE; LEUKOCYTE ADHESION; ENDOTHELIAL-CELLS; MOUSE THYMOCYTES; GENE-EXPRESSION; HL-60 CELLS; ACTIVATION; DEATH; INDUCTION; P53 AB A new class of potent apogens (apoptosis-inducing agents) has been identified, consisting of 3-deazaadenosine (DZA), 3-deaza-(+/-)aristeromycin (DZAri) and 1-beta-D-arabinofuranosyl-1H-imidazo[4,5-(c) under bax-pyridine (ara-3-deazaadenine; DZAra-A). They are inhibitors of S-adenosylhomocysteine hydrolase and indirect inhibitors of methylation. Furthermore, they have also been found to form 3-deaza-nucleotide analogs. The DZA analogs, DZA, DZAri, and DZAra-A, induced DNA fragmentation in a dose-and time-dependent manner, reaching a maximum at 250 mu M after 72 h. Cycloheximide at 0.5 mu g/ml completely blocked the DNA fragmentation induced by 250 mu M of each of the analogs. Interestingly, exogenous 100 mu M L-homocysteine thiolactone abrogated the DNA fragmentation caused by DZAri and DZAra-A? but not by DZA. Flow cytometric analysis showed that DZA arrested the cells in the G(2)/M phase, whereas the S phase was arrested by DZAri. Correlated with the effect of DZA was a rapid decrease in the expression of c-myc, whereas nur77 and GAPDH were unaffected. In comparison, there was an elevated expression of IFN-gamma mRNA without apparent change in bax, p53 or GAPDH mRNA after 24 h. After treatment with DZA, there was an elevated expression of NF-kappa B DNA binding activity, which became more pronounced at 24 h. Simultaneously, there was an apparent disappearance of AP-1 activity. Thus, DZA most likely inhibited the RNA synthesis of c-myc, a reduction of which could trigger a cascade of gene transcription leading to apoptosis in L1210 cells. C1 WALTER REED ARMY MED CTR, WALTER REED ARMY INST RES, WASHINGTON, DC 20307 USA. CATHOLIC UNIV, COLL MED, DEPT BIOCHEM, SEOUL, SOUTH KOREA. NCI, FREDERICK CANC RES & DEV CTR, INTRAMURAL RES SUPPORT PROGRAM, FREDERICK, MD 21702 USA. NCI, FREDERICK CANC RES & DEV CTR, EXPT IMMUNOL LAB, FREDERICK, MD 21702 USA. NR 42 TC 10 Z9 10 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1021-7770 J9 J BIOMED SCI JI J. Biomed. Sci. PD MAR-JUN PY 1997 VL 4 IS 2-3 BP 83 EP 90 DI 10.1007/BF02255598 PG 8 WC Cell Biology; Medicine, Research & Experimental SC Cell Biology; Research & Experimental Medicine GA YD087 UT WOS:A1997YD08700004 ER PT J AU MontroseRafizadeh, C Kole, J Bartkowski, LM Lee, LH Blackmon, DL Behnken, SE Gearhart, JD Cohn, JA Montrose, MH AF MontroseRafizadeh, C Kole, J Bartkowski, LM Lee, LH Blackmon, DL Behnken, SE Gearhart, JD Cohn, JA Montrose, MH TI Gene targeting of a CFTR allele in HT29 human epithelial cells SO JOURNAL OF CELLULAR PHYSIOLOGY LA English DT Article ID TRANSMEMBRANE CONDUCTANCE REGULATOR; CYSTIC-FIBROSIS HETEROZYGOTES; ACTIVATED CHLORIDE CURRENTS; EMBRYONIC STEM-CELLS; MESSENGER-RNA; ANTISENSE OLIGODEOXYNUCLEOTIDE; MOUSE MODEL; DUCT CELLS; EXPRESSION; CHANNELS AB HT29 cells endogenously express the cystic fibrosis transmembrane conductance regulator (CFTR) and have been used previously as a model to examine cellular regulation of CFTR expression and chloride secretory function. Homologous recombination has been used to specifically disrupt CFTR transcription in the HT29-18-C-1 subclone. Experiments demonstrate successful disruption of a CFTR allele by DNA constructs, which target insertion of the neomycin phosphotransferase gene into CFTR exon 1 via homologous recombination. The mutation of one allele is a partial knockout because this cell line has multiple CFTR alleles. The mutation is confirmed by polymerase chain reaction (PCR) and genomic Southern blot analysis. A 52-68% reduction in CFTR mRNA levels is observed in the mutant cell line by both Northern and PCR analysis. However, Western blots show no decrease in total CFTR protein levels. Consistent with the lack of reduction in CFTR protein, the partial knockout mutant does not demonstrate alterations in cyclic AMP or calcium stimulation of chloride efflux or net osmolyte loss. Results suggest that posttranscriptional regulation of CFTR levels may contribute to maintenance of cellular chloride transport function. (C) 1997 Wiley-Liss, Inc. C1 JOHNS HOPKINS UNIV,DEPT MED,SCH MED,BALTIMORE,MD 21205. JOHNS HOPKINS UNIV,SCH MED,DEPT OBSTET & GYNECOL,BALTIMORE,MD 21205. NIA,GERONTOL RES CTR,NIH,BALTIMORE,MD 21224. DUKE UNIV,DEPT MED,DURHAM,NC 27710. VET ADM MED CTR,DURHAM,NC 27710. FU NIDDK NIH HHS [DK40701, DK44247] NR 45 TC 2 Z9 2 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0021-9541 J9 J CELL PHYSIOL JI J. Cell. Physiol. PD MAR PY 1997 VL 170 IS 3 BP 299 EP 308 PG 10 WC Cell Biology; Physiology SC Cell Biology; Physiology GA XK181 UT WOS:A1997XK18100011 PM 9066787 ER PT J AU Wong, DF Pearlson, GD Tune, LE Young, LT Meltzer, CC Dannals, RF Ravert, HT Reith, J Kuhar, MJ Gjedde, A AF Wong, DF Pearlson, GD Tune, LE Young, LT Meltzer, CC Dannals, RF Ravert, HT Reith, J Kuhar, MJ Gjedde, A TI Quantification of neuroreceptors in the living human brain .4. Effect of aging and elevations of D-2-like receptors in schizophrenia and bipolar illness SO JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM LA English DT Article DE positron emission tomography; dopamine receptors; schizophrenia; bipolar illness; psychosis; receptor quantification; dopamine; D-4 dopamine receptors ID POSITRON EMISSION TOMOGRAPHY; D2 DOPAMINE-RECEPTORS; C-11 N-METHYLSPIPERONE; BINDING; D-2; DENSITY; DISORDER; SITES; PET AB In a previous study of 10 drug-naive schizophrenic patients, the density of D-2 dopamine receptors was found to be elevated in the caudate nucleus. The study raised questions about the influence of the age of the patients, the relationship of receptor density to psychosis, and the accuracy of the method used to obtain this evidence. Using positron emission tomography and constrained analysis of the brain uptake of the radioligand N-[C-11]methylspiperone ([C-11]NMSP), we tested four questions: Were the assumptions underlying the quantitation valid? Is there an age decline of the density of D-2-like dopamine receptors in drug-naive schizophrenia and bipolar illness? If so, is it different from that observed in normal aging? Are D-2-like dopamine receptors elevated at any age in either drug-naive schizophrenic or psychotic bipolar illness patients? NMSP and haloperidol partition volumes and plasma protein fractions were not significantly different among patient groups and normal volunteers. The model-derived assay of radioligand metabolites in plasma was confirmed by high-performance liquid chromatography in the patient groups. Dp-like dopamine receptors declined with age, and the slope did not differ significantly between the schizophrenic patients, bipolar affective illness patients, and normal controls. Taking the effect of age into account, increases in D-2 dopamine receptor density were found in seven psychotic patients with bipolar affective illness compared with seven nonpsychotic patients and 24 control subjects as well as in 22 drug-naive schizophrenic patients compared with the 24 control subjects. C1 AARHUS UNIV HOSP,PET CTR,DK-8000 AARHUS,DENMARK. BISPEBJERG HOSP,DEPT NEUROL,DK-2400 COPENHAGEN,DENMARK. MCGILL UNIV,DEPT NEUROL & NEUROSURG,MONTREAL,PQ,CANADA. NIDA,ADDICT RES CTR,NEUROSCI BRANCH,DEPT RADIOL & RADIOL SCI,DIV NUCL MED,BALTIMORE,MD 21224. NIDA,ADDICT RES CTR,NEUROSCI BRANCH,DEPT ENVIRONM HLTH SCI,DIV RADIAT HLTH SCI,BALTIMORE,MD 21224. NIDA,ADDICT RES CTR,NEUROSCI BRANCH,DEPT PSYCHIAT,BALTIMORE,MD 21224. NIDA,ADDICT RES CTR,NEUROSCI BRANCH,DEPT NEUROSCI,BALTIMORE,MD 21224. FU NIMH NIH HHS [R01 MH40362, R01 MH42821]; OMHHE CDC HHS [KO1 MN00723] NR 44 TC 81 Z9 81 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 1997 VL 17 IS 3 BP 331 EP 342 PG 12 WC Endocrinology & Metabolism; Hematology; Neurosciences SC Endocrinology & Metabolism; Hematology; Neurosciences & Neurology GA WQ178 UT WOS:A1997WQ17800010 PM 9119906 ER PT J AU Vitiello, B AF Vitiello, B TI Treatment algorithms in child psychopharmacology research SO JOURNAL OF CHILD AND ADOLESCENT PSYCHOPHARMACOLOGY LA English DT Article AB Clinical trials in child psychiatry research have increased in complexity. Several factors have contributed to this change, including the need to compare multiple therapies, to re-create clinically relevant situations in research, to standardize treatment approaches, to account for the impact of comorbidity, to respond to the needs of individual patients, and to optimize treatment accordingly. To preserve the clinical and internal validity of the experimental interventions vis-g-vis their increasing complexity, researchers have started developing treatment algorithms. These deductive systems for handling data allow us to standardize and incorporate clinical judgment into study designs through the adoption of a stepwise decision making process. Treatment algorithms are different from treatment guidelines. Guidelines are general recommendations that apply to groups of patients with certain characteristics; they are not fully detailed and are created with the expectation that clinical judgment will be applied in individual cases. Algorithms are patient specific, are intended to capture all the relevant details of the clinical situation, and require minimal clinical judgment for their clinical application; they are designed to minimize the role of clinical judgment in research protocols. The entire multistep algorithm is tested in a clinical trial, not the single steps that constitute the algorithm, so proving the efficacy of an algorithm cannot replace a controlled assessment of the individual treatments embedded in the algorithm. Some characteristics, properties, and limitations of algorithms in child psychiatry and psychopharmacology research are presented along with two examples of algorithms currently used in child and adolescent psychopharmacology. Although treatment algorithms seldom have been used in pediatric psychiatry and psychopharmacology, there are indications that their use will increase in the near future and will allow the standardized introduction of clinical judgment into research design. RP Vitiello, B (reprint author), NIMH,CHILD & ADOLESCENT DISORDERS RES BRANCH,ROOM 18C-17,5600 FISHERS LANE,ROCKVILLE,MD 20857, USA. NR 7 TC 6 Z9 6 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 1997 VL 7 IS 1 BP 3 EP 8 DI 10.1089/cap.1997.7.3 PG 6 WC Pediatrics; Pharmacology & Pharmacy; Psychiatry SC Pediatrics; Pharmacology & Pharmacy; Psychiatry GA XE499 UT WOS:A1997XE49900002 PM 9192537 ER PT J AU Sarlis, NJ BruckerDavis, F Doppman, JL Skarulis, MC AF Sarlis, NJ BruckerDavis, F Doppman, JL Skarulis, MC TI MRI-demonstrable regression of a pituitary mass in a case of primary hypothyroidism after a week of acute thyroid hormone therapy SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID PRIMARY HYPO-THYROIDISM; REPLACEMENT THERAPY; FOLLOW-UP; ENLARGEMENT; GLAND; HYPERPLASIA; ADENOMAS; SELLA AB Although magnetic resonance imaging (MRI) characteristics of pituitary gland hyperplasia in primary hypothyroidism have been previously described, the time span necessary for the regression of the hyperplasia in response to acute thyroid hormone (TK) therapy has not been defined. A 26-yr-old woman underwent I-131 ablation 11 yr before admission. Intermittent poor compliance to levothyroxine (LT4) therapy led to inappropriately high serum thyroid-stimulating hormone (TSH) for her triiodothyronine (T3) and thyroxine (T4) levels. The patient was investigated to rule out TSH-secreting pituitary adenoma or resistance to TH. On admission, the patient's clinical features and thyroid function tests, as well. as thyrotropin-releasing hormone (TRH) and acute T3 suppression tests, were in favor of profound primary hypothyroidism. MRI revealed symmetrical enlargement of the pituitary gland with distinct morphological characteristics of a macroadenoma. The patient began high-dose TH therapy and was rescannned six days later. The follow-up scan revealed a dramatic shrinkage of the pituitary gland. Four weeks later, serum T4 and TSH were within the normal range, and repeat MRI scan of the pituitary at that time showed a normal gland. This case is the first to document dramatic shrinkage of pituitary hyperplasia in long-standing primary hypothyroidism within one week of acute TH therapy. MRI alone is unable to reliably differentiate between a TSH-secreting pituitary adenoma and hypothyroidism-induced pituitary hyperplasia. Dynamic endocrine testing as well as repeat pituitary MRI after a brief TH trial may provide a firm diagnosis in similar cases. C1 NIDDKD, MOL & CELLULAR ENDOCRINOL BRANCH, NIH, BETHESDA, MD 20892 USA. NIH, WARREN G MAGNUSON CLIN CTR, DEPT RADIOL, BETHESDA, MD 20892 USA. RP Sarlis, NJ (reprint author), NIDDKD, STEROID HORMONES SECT,CELLULAR & MOL BIOL LAB,NIH, BLDG 8,RM B2 A11, 8 CTR DR, BETHESDA, MD 20892 USA. NR 28 TC 41 Z9 52 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 1997 VL 82 IS 3 BP 808 EP 811 DI 10.1210/jc.82.3.808 PG 4 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA WM245 UT WOS:A1997WM24500019 PM 9062487 ER PT J AU Dorn, LD Burgess, ES Friedman, TC Dubbert, B Gold, PW Chrousos, GP AF Dorn, LD Burgess, ES Friedman, TC Dubbert, B Gold, PW Chrousos, GP TI The longitudinal course of psychopathology in Cushing's syndrome after correction of hypercortisolism SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID CORTICOTROPIN-RELEASING HORMONE; PITUITARY-ADRENAL AXIS; ATYPICAL DEPRESSION; PLASMA-CORTISOL; DISEASE; DISORDERS; STRESS AB Endogenous Cushing's syndrome (CS) is associated with significant psychopathology during the course of the disease. The purpose of this study was to evaluate the psychological and endocrine status of patients with CS after correction of their hypercortisolism. Thirty-three patients with active CS were examined before and at 3 months (28 patients), 6 months (25 patients), and 12 months (29 patients) after correction of hypercortisolism. Before cure, 66.7% of the patients had significant psychopathology, with the predominant diagnosis of atypical depressive disorder (AD) in 51.5% and/or major affective disorder in 12%. After cure, overall psychopathology decreased significantly to 53.6% at 3 months, 36% at 6 months, and 24.1% at 12 months, when there was a parallel recovery of the hypothalamic-pituitary-adrenal axis assessed by serial morning ACTH stimulation tests. There was an inverse correlation between psychological recovery and baseline morning cortisol, but no correlation with ACTH-stimulated cortisol values at 60 min. AD continued to be the prevailing diagnosis after correction of hypercortisolism, whereas the frequency of suicidal ideation and panic increased. The presence of AD before and after correction of hypercortisolism might be due to glucocorticoid-induced suppression of hypothalamic CRH secretion. The slight increase in the incidence of panic after correction of hypercortisolism might be due to a decreased glucocorticoid restraint at the central arousal/sympathetic catecholaminergic system. We conclude that GS is associated with AD symptomatology, which gradually improves with time after correction of hypercortisolism. Health care providers should be aware of changes in symptomatology, including suicidal ideation and panic attacks, that occur in a subgroup of patients. C1 NICHHD, DEV ENDOCRINOL BRANCH, BETHESDA, MD 20892 USA. NIMH, DEPT BEHAV PEDIAT, BETHESDA, MD 20892 USA. NIMH, DEPT CLIN NEUROENDOCRINOL, BETHESDA, MD 20892 USA. BROWN UNIV, BUTLER HOSP, PROVIDENCE, RI 02912 USA. CEDARS SINAI MED CTR, LOS ANGELES, CA 90048 USA. RP Dorn, LD (reprint author), UNIV PITTSBURGH, SCH NURSING, PITTSBURGH, PA 15261 USA. NR 35 TC 126 Z9 128 U1 2 U2 5 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 1997 VL 82 IS 3 BP 912 EP 919 DI 10.1210/jc.82.3.912 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA WM245 UT WOS:A1997WM24500038 PM 9062506 ER PT J AU Torpy, DJ Papanicolaou, DA Chrousos, GP AF Torpy, DJ Papanicolaou, DA Chrousos, GP TI Sexual dimorphism of the human stress response may be due to estradiol-mediated stimulation of hypothalamic corticotropin-releasing hormone synthesis SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Letter RP Torpy, DJ (reprint author), NICHHD, DEV ENDOCRINOL BRANCH,NIH,BLDG 10,ROOM 10N262, 9000 ROCKVILLE PIKE, BETHESDA, MD 20892 USA. NR 9 TC 15 Z9 16 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 1997 VL 82 IS 3 BP 982 EP 982 DI 10.1210/jc.82.3.982 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA WM245 UT WOS:A1997WM24500049 PM 9062517 ER PT J AU Zhang, YH DeWitt, DL McNeely, TB Wahl, SM Wahl, LM AF Zhang, YH DeWitt, DL McNeely, TB Wahl, SM Wahl, LM TI Secretory leukocyte protease inhibitor suppresses the production of monocyte prostaglandin H synthase-2, prostaglandin E(2), and matrix metalloproteinases SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article DE inflammation; connective tissue; collagenase; cyclooxygenase; signal transduction ID MACROPHAGE COLLAGENASE PRODUCTION; GROWTH-PROMOTING ACTIVITY; AMINO-ACID SEQUENCE; TISSUE INHIBITOR; PROTEINASE-INHIBITOR; POTENT INHIBITOR; EXPRESSION; CELLS; LIPOPOLYSACCHARIDE; CYCLOOXYGENASE AB Secretory leukocyte protease inhibitor (SLPI) is a serine protease inhibitor found in fluids lining mucosal surfaces. In addition to its primary function as an antiprotease, SLPI may also influence cellular functions associated with enzyme synthesis and retroviral infection. In this study, SLPI was examined for its effect on signaling events involved in the production of matrix metalloproteinases (MMPs) by monocytes, Addition of SLPI before stimulation with concanavalin A or LPS resulted in a significant inhibition of monocyte prostaglandin H synthase-2 (PGHS-2), a pivotal enzyme in the PGE(2)-cAMP dependent pathway of monocyte MMP synthesis. Suppression of PGHS-2 was detected with 0.1 mu g/ml of SLPI with a substantial inhibition at 1 and 10 mu g/ml. Attenuation of PGHS-2 by SLPI was accompanied by decreased production of PGE(2) resulting in the suppression of interstitial collagenase (MMP-1) and gelatinase B (MMP-9) that was reversed by PGE(2) or Bt(2)cAMP. The inhibitory effect of SLPI was largely independent of its antiprotease activity because SLPI muteins, with significantly lower antiprotease activity, also suppressed the induction of PGHS-2 and MMPs. The inhibitory effects of SLPI did not involve the modulation of monokine production since TNF-alpha and IL-10 were unaffected. These findings demonstrate that SLPI also functions as a potent antiinflammatory agent by interfering with the signal transduction pathway leading to monocyte MMP production. C1 NIDR,CELLULAR IMMUNOL SECT,IMMUNOL LAB,NIH,BETHESDA,MD 20892. MICHIGAN STATE UNIV,DEPT BIOCHEM,E LANSING,MI 48824. NR 33 TC 140 Z9 146 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 1 PY 1997 VL 99 IS 5 BP 894 EP 900 DI 10.1172/JCI119254 PG 7 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA WN152 UT WOS:A1997WN15200013 PM 9062347 ER PT J AU Miyajima, I Dombrowicz, D Martin, TR Ravetch, JV Kinet, JP Galli, SJ AF Miyajima, I Dombrowicz, D Martin, TR Ravetch, JV Kinet, JP Galli, SJ TI Systemic anaphylaxis in the mouse can be mediated largely through IgG, and Fc gamma RIII - Assessment of the cardiopulmonary changes, mast cell degranulation, and death associated with active or IgE- or IgG(1)-dependent passive anaphylaxis SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article DE allergy; asthma; Fc gamma RI; IgE; passive cutaneous anaphylaxis ID IMMUNOGLOBULIN-E; DEFICIENT MICE; KIT-LIGAND; ANTIBODY; RESPONSES; RECEPTORS; EXPRESSION; ACTIVATION; GENERATION; INHIBITION AB We attempted to elicit active anaphylaxis to ovalbumin, or passive IgE- or IgG(1)-dependent anaphylaxis, in mice lacking either the Fc(epsilon)RI alpha chain or the FcR gamma chain common to Fc(epsilon)RI and Fc gamma RI/III, or in mice lacking mast cells (Kit(W)/Kit(W-v) mice), and compared the responses to those in the corresponding wild-type mice. We found that the FcR gamma chain is required for the death, as well as for most of the pathophysiological changes, associated with active anaphylaxis or IgE- or IgG(1)-dependent passive anaphylaxis. Moreover, some of the physiological changes associated with either active, or IgG(1)-dependent passive, anaphylactic responses were significantly greater in Fc(epsilon)RI alpha chain -/- mice than in the corresponding normal mice. Finally, while both Kit(W)/Kit(W-v) and congenic +/+ mice exhibited fatal active anaphylaxis, mast cell-deficient mice exhibited weaker physiological responses than the corresponding wild-type mice in both active and IgG(1)-dependent passive systemic anaphylaxis. Our findings strongly suggest that while IgE antibodies and Fc(epsilon)RI may influence the intensity and/or kinetics of some of the pathophysiological changes associated with active anaphylaxis in the mouse, the mortality associated with this response can be mediated largely by IgG(1) antibodies and Fc gamma-RIII. C1 BETH ISRAEL DEACONESS MED CTR E,DEPT PATHOL,DIV EXPT PATHOL,BOSTON,MA 02215. HARVARD UNIV,SCH MED,BOSTON,MA 02215. NIAID,MOL ALLERGY & IMMUNOL SECT,NIH,ROCKVILLE,MD 20852. CHILDRENS HOSP,DEPT PEDIAT & PULM MED,BOSTON,MA 02115. ROCKEFELLER UNIV,LAB MOL GENET & IMMUNOL,NEW YORK,NY 10021. RI Dombrowicz, David/F-7044-2013 OI Dombrowicz, David/0000-0002-0485-8923 FU NCI NIH HHS [CA/AI-724074]; NHLBI NIH HHS [K11HL-02240]; NIAID NIH HHS [AI/CA-23990] NR 41 TC 253 Z9 261 U1 1 U2 7 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD MAR 1 PY 1997 VL 99 IS 5 BP 901 EP 914 DI 10.1172/JCI119255 PG 14 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA WN152 UT WOS:A1997WN15200014 PM 9062348 ER PT J AU Dombrowicz, D Flamand, V Miyajima, I Ravetch, JV Galli, SJ Kinet, JP AF Dombrowicz, D Flamand, V Miyajima, I Ravetch, JV Galli, SJ Kinet, JP TI Absence of Fc(epsilon)RI alpha chain results in upregulation of Fc gamma RIII-dependent mast cell degranulation and anaphylaxis - Evidence of competition between Fc(epsilon)RI and Fc gamma RIII for limiting amounts of FcR beta and gamma chains SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article DE allergy; asthma; Fc gamma RI; IgE; passive cutaneous anaphylaxis ID IMMUNOGLOBULIN-E; DEFICIENT MICE; CARDIOPULMONARY ALTERATIONS; MONOCLONAL-ANTIBODY; ACTIVE ANAPHYLAXIS; HIGH-AFFINITY; RECEPTOR; MOUSE; IGE; EXPRESSION AB In mouse mast cells, both Fc(epsilon)RI and Fc gamma RIII are alpha beta gamma 2 tetrameric complexes in which different alpha chains confer IgE or IgG ligand recognition while the signaling FcR beta and gamma chains are identical. We used primarily noninvasive techniques (changes in body temperature, dye extravasation) to assess systemic anaphylactic responses in nonanesthetized wild-type, Fc(epsilon)RI alpha chain -/- and FcR gamma chain -/- mice. We confirm that systemic anaphylaxis in mice can be mediated largely through IgG(1) and Fc gamma RIII and we provide direct evidence that these responses reflect activation of Fc gamma RIII rather than Fc gamma RI. Furthermore, we show that Fc gamma RIII-dependent responses are more intense in normal than in congenic mast cell-deficient Kit(W)/Kit(W-v) mice, indicating that Fc gamma RIII responses have mast cell-dependent and -independent components. Finally, we demonstrate that the upregulation of cell surface expression of Fc gamma RIII seen in Fc(epsilon)RI alpha chain -/- mice corresponds to an increased association of Fc gamma RIII alpha chains with FcR beta and gamma chains and is associated with enhanced Fc gamma RIII-dependent mast cell degranulation and systemic anaphylactic responses. Therefore, the phenotype of the Fc(epsilon)RI alpha chain -/- mice suggests that expression of Fc(epsilon)RI and Fc gamma RIII is limited by availability of the FcR beta and gamma chains and that, in normal mice, changes in the expression of one receptor (Fc(epsilon)RI) may influence the expression of functional responses dependent on the other (Fc gamma RIII). C1 BETH ISRAEL DEACONESS MED CTR E,DEPT PATHOL,DIV EXPT PATHOL,BOSTON,MA 02215. NIAID,MOL ALLERGY & IMMUNOL SECT,NIH,ROCKVILLE,MD 20852. ROCKEFELLER UNIV,LAB MOL GENET & IMMUNOL,NEW YORK,NY 10021. HARVARD UNIV,SCH MED,DEPT PATHOL,BOSTON,MA 02215. RI Dombrowicz, David/F-7044-2013 OI Dombrowicz, David/0000-0002-0485-8923 FU NCI NIH HHS [CA/AI-72074]; NIAID NIH HHS [AI/CA-23990]; NIGMS NIH HHS [GM-53950] NR 29 TC 147 Z9 150 U1 0 U2 2 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD MAR 1 PY 1997 VL 99 IS 5 BP 915 EP 925 DI 10.1172/JCI119256 PG 11 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA WN152 UT WOS:A1997WN15200015 PM 9062349 ER PT J AU Marschner, IC Mayers, DL Erice, A Smeaton, L Johnson, VA Richman, DD Reichelderfer, P Japour, AJ AF Marschner, IC Mayers, DL Erice, A Smeaton, L Johnson, VA Richman, DD Reichelderfer, P Japour, AJ TI Standardized peripheral blood mononuclear cell culture assay for zidovudine susceptibility testing of clinical human immunodeficiency virus type 1 isolates: Effect of reducing the numbers of replicates and concentrations SO JOURNAL OF CLINICAL MICROBIOLOGY LA English DT Article AB Zidovudine susceptibility was assessed for 525 clinical human immunodeficiency virus type 1 isolates, before and after reducing the number of replicates and zidovudine concentrations in the standardized consensus peripheral blood mononuclear cell culture assay. We conclude that omitting the 0.001 mu M concentration and using duplicate rather than triplicate wells are valid and cost-effective modifications of this expensive assay. C1 WALTER REED ARMY INST RES,DIV RETROVIROL,ROCKVILLE,MD 20850. UNIV MINNESOTA,DEPT LAB MED & PATHOL,MINNEAPOLIS,MN 55455. UNIV ALABAMA,SCH MED,DEPT MED,DIV INFECT DIS,BIRMINGHAM,AL 35294. VET AFFAIRS MED CTR,BIRMINGHAM,AL 35294. VET AFFAIRS MED CTR,SAN DIEGO,CA 92093. UNIV CALIF SAN DIEGO,DEPT PATHOL,SAN DIEGO,CA 92093. UNIV CALIF SAN DIEGO,DEPT MED,SAN DIEGO,CA 92093. NIAID,DIV AIDS,BETHESDA,MD 20892. BETH ISRAEL HOSP,DIV INFECT DIS,BOSTON,MA 02115. RP Marschner, IC (reprint author), HARVARD UNIV,SCH PUBL HLTH,CTR BIOSTAT AIDS RES,KRESGE 7,677 HUNTINGTON AVE,BOSTON,MA 02115, USA. FU NIAID NIH HHS [AI32777, AI27670, AI32794] NR 5 TC 1 Z9 1 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0095-1137 J9 J CLIN MICROBIOL JI J. Clin. Microbiol. PD MAR PY 1997 VL 35 IS 3 BP 756 EP 758 PG 3 WC Microbiology SC Microbiology GA WJ848 UT WOS:A1997WJ84800045 PM 9041428 ER PT J AU Young, L Topol, IA Rashin, AA Burt, SK AF Young, L Topol, IA Rashin, AA Burt, SK TI Building molecular charge distributions from fragments: Application to HIV-1 protease inhibitors SO JOURNAL OF COMPUTATIONAL CHEMISTRY LA English DT Article ID ATOMIC CHARGES AB Interaction energies are a function of the molecular charge distribution. In previous work, we found that the set of atomic partial charges giving the best agreement with experimental vacuum dipole moments were from density functional theory calculations using an extended basis set. Extension of such computations to larger molecules requires an atomic partial charge calculation beyond present computational resources. A solution to this problem is the calculation of atomic partial charges for segments of the molecule and reassociation of such fragments to yield partial charges for the entire molecule. Various partitions and reassociation methods for five molecules relevant to HIV-1 protease inhibitors are examined. A useful method of reassociation is introduced in which atomic partial charges for a large molecule are computed by fitting to the combined electrostatic potential calculated from the fragment partial charges. As expected, the best sites for partitions are shown to be carbon-carbon rather than carbon-nitrogen bonds. (C) 1997 by John Wiley & Sons, Inc. C1 BIOCHEMCOMP INC,TEANECK,NJ 07666. RP Young, L (reprint author), NCI,STRUCT BIOCHEM PROGRAM,FREDERICK BIOMED SUPERCOMP CTR,SAIC FREDERICK,FCRDC,FREDERICK,MD 21702, USA. NR 18 TC 7 Z9 7 U1 0 U2 1 PU JOHN WILEY & SONS INC PI NEW YORK PA 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0192-8651 J9 J COMPUT CHEM JI J. Comput. Chem. PD MAR PY 1997 VL 18 IS 4 BP 522 EP 532 DI 10.1002/(SICI)1096-987X(199703)18:4<522::AID-JCC6>3.0.CO;2-V PG 11 WC Chemistry, Multidisciplinary SC Chemistry GA WH731 UT WOS:A1997WH73100006 ER PT J AU Hirst, KL IbarakiOConnor, K Young, MF Dixon, MJ AF Hirst, KL IbarakiOConnor, K Young, MF Dixon, MJ TI Cloning and expression analysis of the bovine dentin matrix acidic phosphoprotein gene SO JOURNAL OF DENTAL RESEARCH LA English DT Article DE dentinogenesis; dentin; phosphoprotein; mineralization ID DENTINOGENESIS-IMPERFECTA; MESSENGER-RNA; BONE-MATRIX; BIOMINERALIZATION; DMP1 AB The dentin matrix acidic phosphoprotein gene has been mapped to human chromosome 4q21 and mouse chromosome 5q21. Expression studies have implicated a role for this gene in the mineralization of dentin. In the current investigation, a cDNA encoding bovine dentin matrix acidic phosphoprotein has been cloned and sequenced. A comparison of the bovine gene with its rat counterpart has indicated that the genes are conserved (67.4% identity; 79.5% similarity), particularly in the region of presumed functional elements such as the hydrophobic signal peptide sequence, the cell attachment Arg-Gly-Asp tripeptide, and numerous serine residues which are likely candidates for phosphorylation. Zoo blot analysis further indicated that a similar gene is found in all mammalian species tested, but not in chicks. However, Northern analysis has indicated that in the cow the message is detectable at high levels in fetal bovine brain and cultured long bone as well as in odontoblasts. These results support a potential role for dentin matrix acidic phosphoprotein in dentinogenesis. C1 UNIV MANCHESTER, SCH BIOL SCI, MANCHESTER M13 9PT, LANCS, ENGLAND. UNIV MANCHESTER, DEPT DENT MED, MANCHESTER M13 9PT, LANCS, ENGLAND. UNIV MANCHESTER, DEPT SURG, MANCHESTER M13 9PT, LANCS, ENGLAND. NIDR, BONE RES BRANCH, NIH, BETHESDA, MD 20892 USA. FU Wellcome Trust NR 18 TC 55 Z9 58 U1 1 U2 1 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0022-0345 EI 1544-0591 J9 J DENT RES JI J. Dent. Res. PD MAR PY 1997 VL 76 IS 3 BP 754 EP 760 PG 7 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA WU193 UT WOS:A1997WU19300007 PM 9109824 ER PT J AU Blakesley, VA Stannard, BS Kalebic, T Helman, LJ LeRoith, D AF Blakesley, VA Stannard, BS Kalebic, T Helman, LJ LeRoith, D TI Role of the IGF-I receptor in mutagenesis and tumor promotion SO JOURNAL OF ENDOCRINOLOGY LA English DT Review ID GROWTH-FACTOR-I; PHOSPHATIDYLINOSITOL KINASE-ACTIVITY; BREAST CANCER-CELLS; RAT GLIOBLASTOMA; SOMATOMEDIN RECEPTOR; EMBRYO FIBROBLASTS; TRANSFORMED CELLS; INHIBITS GROWTH; ATHYMIC MICE; WILMS-TUMOR C1 NIDDKD,DIABET BRANCH,SECT MOL & CELLULAR PHYSIOL,BETHESDA,MD 20892. NCI,MOL ONCOL SECT,PEDIAT BRANCH,NIH,BETHESDA,MD 20892. NR 51 TC 61 Z9 68 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 1997 VL 152 IS 3 BP 339 EP 344 DI 10.1677/joe.0.1520339 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA WM291 UT WOS:A1997WM29100001 PM 9071953 ER PT J AU Ehrich, DG Lundgren, JP Dionne, RA Nicoll, BK Nutter, JW AF Ehrich, DG Lundgren, JP Dionne, RA Nicoll, BK Nutter, JW TI Comparison of triazolam, diazepam, and placebo as outpatient oral premedication for endodontic patients SO JOURNAL OF ENDODONTICS LA English DT Article ID EFFICACY; ANXIETY AB Triazolam and diazepam were compared as oral antianxiety agents in a randomized double-blind, placebo-controlled clinical study of 79 endodontic patients with elevated anxiety regarding endodontic treatment. Patients who scored greater than or equal to 10 on the Corah Dental Anxiety Survey received oral formulations of triazolam (0.25 mg), diazepam (5 mg), or placebo. Before, during, and after the endodontic procedure, patients completed psychomotor tests and anxiety scales, and were evaluated for 24-h postoperative recall. In comparison with diazepam and placebo, triazolam was significantly better for decreased anxiety (p < 0.05), impaired cognitive function (p < 0.05), patients' rating of drug effectiveness (p < 0.05), and amnesia to clinical events (p < 0.02) and pictures (p < 0.03). Diazepam showed similar trends compared with placebo, but to a lesser degree. Diazepam also had a much longer recovery period. No adverse effects were noted with either drug. These findings suggest that orally administered triazolam (0.25 mg) is a safe and more effective anxiolytic agent than diazepam (5.0 mg) for endodontic patients. C1 UNIV MARYLAND,BALTIMORE COLL DENT SURG,DEPT ENDODONT,SCH DENT,BALTIMORE,MD 21201. NIDR,CLIN PHARMACOL UNIT,NIH,BETHESDA,MD 20892. USN,SCH DENT,ADV SPECIALTY EDUC PROGRAM ENDODONT,BETHESDA,MD 20814. NR 20 TC 13 Z9 13 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0099-2399 J9 J ENDODONT JI J. Endod. PD MAR PY 1997 VL 23 IS 3 BP 181 EP 184 DI 10.1016/S0099-2399(97)80272-5 PG 4 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA WL961 UT WOS:A1997WL96100011 PM 9594761 ER PT J AU Morris, GL Collins, S Bell, W Sahlroot, JT Matula, M Cereghino, JJ AF Morris, GL Collins, S Bell, W Sahlroot, JT Matula, M Cereghino, JJ TI Losigamone: A putative antiepileptic drug SO JOURNAL OF EPILEPSY LA English DT Article DE antiepileptic drugs; controlled clinical trial; losigamone; partial seizures; drug toxicity AB Losigamone (LSG) has shown anticonvulsant efficacy and low neurotoxicity in preclinical testing and has been tolerated in Phase I clinical trials. We report an open-label, add-on tolerability study of sb ascending LSG dosage levels from 600 to 2,100 mg daily in patients receiving phenytoin (PHT), carbamazepine (CBZ), or combination PHT/CBZ. Dosage was escalated weekly, with assessment including reports of adverse events (AE), seizure diary, neurologic and physical examination, electrocardiogram (EGG), and laboratory tests. No serious AE were reported, and those most common AE were headache and dizziness. No significant alteration in PHT, CDZ, or CBZ-epoxide(CBZ-E) levels was noted. No clinically significant change in laboratory tests was noted. A median seizure reduction during LSG treatment as compared with baseline of 39% was achieved during the study. All 9 patients continued into an extension study, and 3 have remained seizure-free for as long as 2 years. Some brief increases in seizure frequency were evident at the 1,800- and 2,100-mg daily dosage levels. We conclude that continued evaluation of LSG for the treatment of partial seizures is indicated. (C) 1997 by G. L. Morris III et al. C1 MED COLL WISCONSIN,DEPT NEUROL,MILWAUKEE,WI. NINCDS,EPIDEMIOL BRANCH,BETHESDA,MD 20892. NIAID,DIV BIOMETR,FOOD DRUG ADMIN,PORTLAND,OR. DIV AIDS,PORTLAND,OR. OREGON HLTH SCI UNIV,PORTLAND,OR 97201. NR 8 TC 9 Z9 9 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0896-6974 J9 J EPILEPSY JI J. Epilepsy PD MAR-APR PY 1997 VL 10 IS 2 BP 62 EP 66 DI 10.1016/S0896-6974(96)00085-0 PG 5 WC Clinical Neurology SC Neurosciences & Neurology GA WU517 UT WOS:A1997WU51700004 ER PT J AU Clark, CG Diamond, LS AF Clark, CG Diamond, LS TI Intraspecific variation and phylogenetic relationships in the genus Entamoeba as revealed by riboprinting SO JOURNAL OF EUKARYOTIC MICROBIOLOGY LA English DT Article DE cultivation; PCR; ribosomal RNA genes ID AXENIC CULTIVATION; HUMAN INFECTIONS; HISTOLYTICA-LIKE; DISPAR BRUMPT; SMALL-SUBUNIT; AMEBAS; ELECTROPHORESIS; IDENTIFICATION; GINGIVALIS; AMEBIASIS AB Eighty-seven isolates of amebae assigned to the genus Entamoeba have been studied by riboprinting (restriction enzyme polymorphism analysis of polymerase chain reaction amplified small subunit ribosomal RNA genes). Twenty-four distinct patterns were obtained, roost of which corresponded to previously described species. In three species (Entamoeba coli, Entamoeba gingivalis and Entamoeba moshkovskii) intraspecific variation was detected that led to the grouping of isolates into `ribodemes' (populations of amebae that share the same riboprint pattern). The riboprint data were used to estimate genetic distances among and within species for the construction of phylogenetic trees based on parsimony and distance analysts. The trees obtained with the two methods are largely congruent. In some cases the estimated distances between species were greater than the upper limit recommended for the fragment comigration method of analysis indicating unusually deep branches within this genus. However, it appears that those species producing cysts with eight nuclei, those producing cysts with one nucleus, and those producing cysts with four nuclei form morphologically based groups that are supported by the riboprint data. The oral parasite Entamoeba gingivalis, which does not encyst, clusters with the third group indicating secondary loss of this ability. C1 UNIV LONDON LONDON SCH HYG & TROP MED,DEPT MED PARASITOL,LONDON WC1E 7HT,ENGLAND. RP Clark, CG (reprint author), NIH,PARASIT DIS LAB,BETHESDA,MD 20892, USA. RI Clark, C Graham/H-3683-2011 OI Clark, C Graham/0000-0002-0521-0977 NR 72 TC 86 Z9 86 U1 0 U2 5 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 1997 VL 44 IS 2 BP 142 EP 154 DI 10.1111/j.1550-7408.1997.tb05951.x PG 13 WC Microbiology SC Microbiology GA WT515 UT WOS:A1997WT51500010 PM 9109261 ER PT J AU Schooler, C Neumann, E Caplan, LJ Roberts, BR AF Schooler, C Neumann, E Caplan, LJ Roberts, BR TI A time course analysis of stroop interference and facilitation: Comparing normal individuals and individuals with schizophrenia SO JOURNAL OF EXPERIMENTAL PSYCHOLOGY-GENERAL LA English DT Article; Proceedings Paper CT 36th Annual Meeting of the Psychonomic-Society CY NOV 10-12, 1995 CL LOS ANGELES, CA SP Psychon Soc ID DEFICIENT MOTOR SYNCHRONY; SELECTIVE ATTENTION; PREFRONTAL CORTEX; WORKING-MEMORY; IRRELEVANT INFORMATION; INHIBITION; DOPAMINE; MECHANISM; TARGET; COLOR AB Using randomized stimulus onset asynchrony (SOAs), the authors traced the time course of Stroop interference and facilitation in normal participants and participants with schizophrenia. Unlike earlier findings using blocked SOAs, singular peaks in interference, facilitation, or both occurred at particular SOAs. The peaks of normal participants and participants with schizophrenia differed. Findings are congruent with a model of Stroop performance that posits individual differences in processing speeds of target and nontarget stimulus dimensions, coupled with critical points in response selection. Participants with schizophrenia also showed more overall interference than normal control participants. A second experiment that added a temporal gap between the distracter word and target color obliterated Stroop effects only for individuals with schizophrenia. These findings provide a new empirical basis for models of Stroop effects. They are also consistent with hypotheses about the importance of the prefrontal cortex for working memory and prefrontal dysfunction in schizophrenia. RP Schooler, C (reprint author), NIMH, LAB SOCIOENVIRONM STUDIES, NIH, ROOM B1A-14, BETHESDA, MD 20892 USA. NR 56 TC 43 Z9 45 U1 1 U2 4 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 0096-3445 J9 J EXP PSYCHOL GEN JI J. Exp. Psychol.-Gen. PD MAR PY 1997 VL 126 IS 1 BP 19 EP 36 PG 18 WC Psychology, Experimental SC Psychology GA WK576 UT WOS:A1997WK57600004 PM 9090142 ER PT J AU Schooler, C Neumann, E Caplan, LJ Roberts, BR AF Schooler, C Neumann, E Caplan, LJ Roberts, BR TI Stroop theory, memory, and prefrontal cortical functioning: Reply to Cohen et al (1997) SO JOURNAL OF EXPERIMENTAL PSYCHOLOGY-GENERAL LA English DT Article ID SELECTIVE ATTENTION; TIME-COURSE; INHIBITION; WORD; ACTIVATION; DOPAMINE; CONTEXT; CORTEX AB In this article, the authors respond to J. D. Cohen, K. O. Dunbar, D. hi. Batch and T. S. Braver's (1997) comment on their target article. The present article (a) takes issue with the characterization given by Cohen et al. of the authors' approach as a classical speed-of-processing account of Stroop effects, (b) discusses the value and relevance of other theoretical concepts, such as traditional accounts of working memory and parallel distributed processing (PDP) approaches to Stroop effects, (c) further examines the possibility that the differences the authors observed in Experiment 2 between normal participants' performance and that of participants with schizophrenia may have been due to distracter stimulus degradation, particularly for participants with schizophrenia, and (d) argues for the relevance of the prefrontal cortex, as well as other brain areas, in accounting for their results. The authors conclude with a final theoretical question. RP Schooler, C (reprint author), NIMH,LAB SOCIOENVIRONM STUDIES,NIH,FED BLDG,ROOM B1A-14,BETHESDA,MD 20892, USA. NR 18 TC 5 Z9 5 U1 0 U2 1 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 SN 0096-3445 J9 J EXP PSYCHOL GEN JI J. Exp. Psychol.-Gen. PD MAR PY 1997 VL 126 IS 1 BP 42 EP 44 PG 3 WC Psychology, Experimental SC Psychology GA WK576 UT WOS:A1997WK57600006 PM 9090144 ER PT J AU Pequegnat, W Bray, JH AF Pequegnat, W Bray, JH TI Families and HIV/AIDS: Introduction to the special section SO JOURNAL OF FAMILY PSYCHOLOGY LA English DT Editorial Material ID HIV-INFECTION; GAY MEN; SEXUAL-BEHAVIOR; SOCIAL SUPPORT; AIDS; PREVENTION; IMPACT; RISK; TRANSMISSION; ADOLESCENTS AB This article provides an introduction and overview of the role of families in preventing and adapting to HIV/AIDS. The unique definition of family in the context of HIV/AIDS is discussed as well as the importance of considering the family as a context for research in this area. Families can be important in deterring the spread of the disease because of their pivotal role in education and training about sexual behavior and health promotion. Families also serve a critical role in helping their HIV-infected members cope with disease. A taxonomy of the problems faced by families is presented. The role of the National Institute of Mental Health's Initiative on Family and HIV/AIDS in supporting and stimulating current and future research is discussed. C1 BAYLOR COLL MED,DEPT FAMILY MED,HOUSTON,TX 77030. RP Pequegnat, W (reprint author), NIMH,OFF AIDS,PARKLAWN BLDG,ROOM 10-75,5600 FISHERS LANE,ROCKVILLE,MD 20857, USA. NR 44 TC 25 Z9 25 U1 1 U2 2 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 SN 0893-3200 J9 J FAM PSYCHOL JI J. Fam. Psychol. PD MAR PY 1997 VL 11 IS 1 BP 3 EP 10 DI 10.1037//0893-3200.11.1.3 PG 8 WC Psychology, Clinical; Family Studies SC Psychology; Family Studies GA WM847 UT WOS:A1997WM84700001 ER PT J AU Fujita, K Omura, S Silver, J AF Fujita, K Omura, S Silver, J TI Rapid degradation of CD4 in cells expressing human immunodeficiency virus type 1 Env and Vpu is blocked by proteasome inhibitors SO JOURNAL OF GENERAL VIROLOGY LA English DT Article ID KAPPA-B-ALPHA; CYTOPLASMIC DOMAIN; PROTEIN; UBIQUITINATION; PHOSPHORYLATION; LACTACYSTIN; INFECTION; RECEPTOR; ENCODES AB Human immunodeficiency virus (HIV) type 1 encodes three genes, Vpu, Env and Nef, that decrease cellular CD4. Vpu and Env act cooperatively to accelerate degradation of CD4 in the endoplasmic reticulum. Here we report that Vpu/Env-induced CD4 degradation is inhibited by lactacystin, a specific inhibitor of the proteasome, and by other proteasome inhibitors, but not by non-proteasome protease inhibitors, We also note that Vpu has amino acid sequence homology with a segment of I kappa B known to be involved in proteasome-mediated degradation, suggesting that HIV-1 could have transduced cellular sequences to enhance downregulation of CD4. C1 KITASATO INST,MINATO KU,TOKYO 108,JAPAN. RP Fujita, K (reprint author), NIAID,MOL MICROBIOL LAB,NIH,9000 ROCKVILLE PIKE,BLDG 4,ROOM 338,BETHESDA,MD 20892, USA. NR 23 TC 72 Z9 73 U1 0 U2 0 PU SOC GENERAL MICROBIOLOGY PI READING PA MARLBOROUGH HOUSE, BASINGSTOKE RD, SPENCERS WOODS, READING, BERKS, ENGLAND RG7 1AE SN 0022-1317 J9 J GEN VIROL JI J. Gen. Virol. PD MAR PY 1997 VL 78 BP 619 EP 625 PN 3 PG 7 WC Biotechnology & Applied Microbiology; Virology SC Biotechnology & Applied Microbiology; Virology GA WL178 UT WOS:A1997WL17800017 PM 9049413 ER PT J AU Agostini, HT Ryschkewitsch, CF Singer, EJ Stoner, GL AF Agostini, HT Ryschkewitsch, CF Singer, EJ Stoner, GL TI JC virus regulatory region rearrangements and genotypes in progressive multifocal leukoencephalopathy: Two independent aspects of virus variation SO JOURNAL OF GENERAL VIROLOGY LA English DT Article ID POLYOMAVIRUS; BRAIN; PROMOTER; GENOME AB JC virus (JCV) causes the central demyelinating disease progressive multifocal leukoencephalopathy (PML), JCV strains excreted in the urine are distinguishable from those in PML tissue by the configuration of their regulatory region to the right of ori: the archetypal regulatory region, 267 nucleotides long, is rearranged in PML tissue by deletion and duplication, Within the coding region JCV shows variations as a result of virus evolution. Four major genotypes are distinguishable of which Type 1 is based in Europe and Type 2 in Asia. Here, the regulatory region rearrangements and the viral genotypes of 29 JCV strains from PML brain were determined. Rearrangement patterns and genotypes were not associated, In general, deletions occurred before duplications, but exceptions to this rule exist. Each configuration of the 29 rearranged regulatory regions was unique and could be derived directly from the non-rearranged, archetypal form. C1 NINCDS,EXPT NEUROPATHOL LAB,NATL INST HLTH,BETHESDA,MD 20892. W LOS ANGELES VET AFFAIRS MED CTR,NEUROL SERV,LOS ANGELES,CA 90073. NR 16 TC 64 Z9 65 U1 0 U2 0 PU SOC GENERAL MICROBIOLOGY PI READING PA MARLBOROUGH HOUSE, BASINGSTOKE RD, SPENCERS WOODS, READING, BERKS, ENGLAND RG7 1AE SN 0022-1317 J9 J GEN VIROL JI J. Gen. Virol. PD MAR PY 1997 VL 78 BP 659 EP 664 PN 3 PG 6 WC Biotechnology & Applied Microbiology; Virology SC Biotechnology & Applied Microbiology; Virology GA WL178 UT WOS:A1997WL17800023 PM 9049419 ER PT J AU Spanik, S Lacka, J Koren, P Kukuckova, E Krupova, I Grausova, S Krcmery, V Trupl, J Kunova, A AF Spanik, S Lacka, J Koren, P Kukuckova, E Krupova, I Grausova, S Krcmery, V Trupl, J Kunova, A TI Increasing incidence of carbapenem-resistant Pseudomonas aeruginosa bacteraemia in a cancer centre over a seven-year period SO JOURNAL OF HOSPITAL INFECTION LA English DT Letter C1 UNIV TRNAVA,DEPT MED,BRATISLAVA 81250,SLOVAKIA. NCI,DEPT MED HEMATOL MICROBIOL,BETHESDA,MD 20892. NCI,ST ELIZABETH CANC INST,BETHESDA,MD 20892. NR 2 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO LTD PI LONDON PA 24-28 OVAL RD, LONDON, ENGLAND NW1 7DX SN 0195-6701 J9 J HOSP INFECT JI J. Hosp. Infect. PD MAR PY 1997 VL 35 IS 3 BP 250 EP 251 DI 10.1016/S0195-6701(97)90216-4 PG 2 WC Infectious Diseases SC Infectious Diseases GA WP424 UT WOS:A1997WP42400013 PM 9093926 ER PT J AU McMahan, CJ Sadofsky, MJ Schatz, DG AF McMahan, CJ Sadofsky, MJ Schatz, DG TI Definition of a large region of RAG1 that is important for coimmunoprecipitation of RAG2 SO JOURNAL OF IMMUNOLOGY LA English DT Article ID RECOMBINATION-ACTIVATING PROTEIN; V(D)J RECOMBINATION; GENES; INTERACTS; CLONING; SIGNAL; MICE AB Interaction between the RAG1 and RAG2 proteins is probably critical for V(D)J recombination. Using a coimmunoprecipitation assay, we define a large region of RAG1 (amino acids 504-1008) that is sufficient for interaction with RAG2. This region comprises the C-terminal half of the RAG1 protein, and is within the region defined as the recombinationally active core. Deletion of either of two regions of RAG1 (amino acids 504-570 or 850-1008) causes a loss of interaction with RAG2. Loss of coimmunoprecipitation is also seen with RAG1 core proteins containing deletions of smaller stretches of amino acids (amino acids 506-511 or 545-550), emphasizing the importance of this region of RAG1 in forming a complex with RAG2. A variety of other small deletion mutations within the amino acid region 504-1008 also decrease coimmunoprecipitation of RAG2 with RAG1, indicating that much or all of this region is important for complex formation. C1 YALE UNIV,SCH MED,HHMI SECT IMMUNOL,NEW HAVEN,CT 06520. YALE UNIV,HOWARD HUGHES MED INST,NEW HAVEN,CT 06520. NIDDKD,MOL BIOL LAB,NIH,BETHESDA,MD 20892. RI Schatz, David/A-6748-2013 OI Schatz, David/0000-0002-5669-1176 FU NIAID NIH HHS [AI32524] NR 31 TC 36 Z9 36 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 1997 VL 158 IS 5 BP 2202 EP 2210 PG 9 WC Immunology SC Immunology GA WJ660 UT WOS:A1997WJ66000027 PM 9036966 ER PT J AU Plaksin, D Polakova, K McPhie, P Margulies, DH AF Plaksin, D Polakova, K McPhie, P Margulies, DH TI A three-domain T cell receptor is biologically active and specifically stains cell surface MHC/peptide complexes SO JOURNAL OF IMMUNOLOGY LA English DT Article ID CLASS-I MOLECULES; ANTIBODY FAB-FRAGMENT; PEPTIDE-MHC COMPLEXES; V-ALPHA DOMAIN; ANTIGEN RECEPTOR; PLASMON RESONANCE; ESCHERICHIA-COLI; MONOCLONAL-ANTIBODY; CIRCULAR-DICHROISM; CRYSTAL-STRUCTURE AB We have expressed in bacteria a single-chain T cell receptor (scTCR) with specificity for an HIV gp120-derived peptide bound to the murine MHC-I molecule, H-2D(d). This scTCR consists of V alpha covalently linked to the V beta C beta domains that was solubilized, refolded, and purified in high yield. Specific binding of the scTCR to MHC/peptide complexes was demonstrated by surface plasmon resonance, with a K-d of 2 to 8 x 10(-6) M. This scTCR specifically inhibited T cell activation, and stained cell surface MHC/peptide complexes as measured by cytofluorimetry. The preservation of binding specificity by such a three-domain scTCR suggests that this structure is sufficient for specific MHC/peptide recognition and that this strategy will be of general use as applied to other TCR. C1 NIAID,MOL BIOL SECT,IMMUNOL LAB,NIH,BETHESDA,MD 20892. NIDDKD,LAB BIOMOL PHARMACOL,NIH,BETHESDA,MD 20892. RI Margulies, David/H-7089-2013; OI Margulies, David/0000-0001-8530-7375 NR 73 TC 41 Z9 41 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 1997 VL 158 IS 5 BP 2218 EP 2227 PG 10 WC Immunology SC Immunology GA WJ660 UT WOS:A1997WJ66000029 PM 9036968 ER PT J AU Johnatty, RN Taub, DD Reeder, SP TurcovskiCorrales, SM Cottam, DW Stephenson, TJ Rees, RC AF Johnatty, RN Taub, DD Reeder, SP TurcovskiCorrales, SM Cottam, DW Stephenson, TJ Rees, RC TI Cytokine and chemokine regulation of proMMP-9 and TIMP-1 production by human peripheral blood lymphocytes SO JOURNAL OF IMMUNOLOGY LA English DT Article ID TUMOR-NECROSIS-FACTOR; IV COLLAGENASE; MATRIX METALLOPROTEINASES; TISSUE INHIBITOR; EXTRACELLULAR-MATRIX; ENDOTHELIAL-CELLS; 92-KDA GELATINASE; HUMAN NEUTROPHIL; CANCER INVASION; T-LYMPHOCYTES AB The production and activation-of matrix-degrading proteinases such as the matrix metalloproteinases (MMP) by lymphocytes is likely to be an important factor in facilitating lymphocyte trafficking through the endothelial barrier and the extracellular matrix. Leukocyte infiltration into inflammatory sites occurs as a response to members of the chemokine superfamily and other inflammatory mediators. In the present study, highly purified leukocyte subpopulations were cultured with or without chemokines or cytokines, and their ability to express gelatinolytic MMPs and their inhibitors, the tissue inhibitors of metalloproteinase (TIMPs), was analyzed. In the absence of exogenous stimuli, purified CD4(+) T lymphocytes produced similar quantities of proMMP-9 and elevated levels of TIMP-1 compared with PBMC, while purified CD8(+) and CD3(+) populations exhibited less MMP-9 and TIMP-1 activity. In comparison, CD56(+) (NK) cells secreted barely detectable levels of proMMP-9 and TIMP-1. The secretion of proMMP-9 by PBMC and purified CD3(+), CD4(+), and CD8(+) lymphocytes was selectively modulated by beta chemokines and proinflammatory cytokines. ProMMP-9 secretion by CD3(+) and CD4(+), but not by CD8(+) T cells was augmented in response to TNF-alpha and IL-1, and down-regulated by IFN-gamma, while macrophage inflammatory protein (MIP)-1 alpha; MIP-1 beta, and RANTES (regulated upon activation and normally T cell expressed and secreted) (beta chemokines) up-regulated the secretion of proMMP-9 by all of the lymphocyte subsets tested. These results demonstrate that a number of proinflammatory cytokines and chemokines differentially regulate proMMP-9 secretion from purified CD4(+) and CD8(+) lymphocytes, while for purified CD3(+) T cells (consisting of CD4(+) and CD8(+) cells in approximately a 2:1 ratio), a predominantly CD4(+) lymphocyte response profile was demonstrated. C1 NOTTINGHAM TRENT UNIV,DEPT LIFE SCI,NOTTINGHAM NG11 8NS,ENGLAND. UNIV SHEFFIELD,SCH MED,INST CANC STUDIES,SHEFFIELD,S YORKSHIRE,ENGLAND. ROYAL HALLAMSHIRE HOSP,DEPT HISTOPATHOL,SHEFFIELD S10 2JF,S YORKSHIRE,ENGLAND. NCI,FREDERICK CANC RES & DEV CTR,CLIN SERV PROGRAM,FREDERICK,MD 21702. NR 83 TC 158 Z9 163 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 1997 VL 158 IS 5 BP 2327 EP 2333 PG 7 WC Immunology SC Immunology GA WJ660 UT WOS:A1997WJ66000042 PM 9036981 ER PT J AU Smith, M AF Smith, M TI Considerations on a possible viral etiology for B-precursor acute lymphoblastic leukemia of childhood SO JOURNAL OF IMMUNOTHERAPY LA English DT Review DE acute lymphoblastic leukemia; JC virus; etiology; B precursor; children ID PROGRESSIVE MULTIFOCAL LEUKOENCEPHALOPATHY; EPSTEIN-BARR-VIRUS; POLYOMAVIRUS JC-VIRUS; HUMAN PAPILLOMAVIRUS TYPE-16; ACUTE LYMPHOCYTIC-LEUKEMIA; LATENT MEMBRANE-PROTEIN; REED-STERNBERG CELLS; HODGKINS-DISEASE; SIMIAN VIRUS-40; BRAIN-TUMORS AB A large body of evidence supports the hypothesis that an infectious agent is involved in the etiology of acute lymphoblastic leukemia (ALL) in children in the 2-5-year age range. To explain these data, it has been proposed that some cases of pediatric ALL arise as a rare response to a common childhood infection, and that the leukemia-inducing potential of the agent is related to the timing of infection, with a greater leukemogenic effect for later infections compared with those occurring during infancy. An alternative model for the etiology of a subset of childhood ALL is proposed that places the critical infectious event during pregnancy rather than early childhood. In this model, the etiologic agent causes a primary infection in the mother that is transmitted to the fetus, and as a consequence of this in utero infection, the child is at increased risk of developing ALL before the age of 5 years. The characteristics that the causative infectious agent of childhood ALL occurring in the 2-5-year age range should possess include (a) ability to induce genomic instability; (b) specific effects on B lymphocytes and not on T lymphocytes; (c) higher rates of infection in regions with lower socioeconomic status; (d) limited general oncogenic potential; (e) minimal symptoms associated with the primary infection, and (f) ability to cross the placenta and infect the fetus, but not cause severe fetal abnormalities. A candidate virus meeting many of these criteria is the JC virus, a member of the polyomavirus family. Implications of the possible etiologic role of JC virus for some cases of childhood ALL (especially those with hyperdiploid leukemia cells) are discussed. RP Smith, M (reprint author), NCI,PEDIAT SECT,CIB,CTEP,RM 741,BETHESDA,MD 20892, USA. NR 122 TC 68 Z9 69 U1 0 U2 4 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 1053-8550 J9 J IMMUNOTHER JI J. Immunother. PD MAR PY 1997 VL 20 IS 2 BP 89 EP 100 DI 10.1097/00002371-199703000-00001 PG 12 WC Oncology; Immunology; Medicine, Research & Experimental SC Oncology; Immunology; Research & Experimental Medicine GA WR028 UT WOS:A1997WR02800001 PM 9087381 ER PT J AU Ogata, N Zanetti, AR Yu, MS Miller, RH Purcell, RH AF Ogata, N Zanetti, AR Yu, MS Miller, RH Purcell, RH TI Infectivity and pathogenicity in chimpanzees of a surface gene mutant of hepatitis B virus that emerged in a vaccinated infant SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article ID POLYMERASE CHAIN-REACTION; INDUCED ESCAPE MUTANT; RAS POINT MUTATIONS; NUCLEOTIDE-SEQUENCE; IMMUNE GLOBULIN; S-GENE; HEPATOCELLULAR-CARCINOMA; ENZYMATIC AMPLIFICATION; MONOCLONAL-ANTIBODY; AUSTRALIA-ANTIGEN AB Hepatitis B virus (HBV) variants with amino acid mutations in the a epitope of the major surface protein have been identified, and questions have been raised regarding their biologic properties. Dilutions of serum that contained the first such described HBV mutant, with an Arg-for-Gly substitution at codon 145 of the S gene, were inoculated into 6 seronegative chimpanzees. Five of the animals developed serologic and/or biochemical evidence of hepatitis B. A polymerase chain reaction-based assay that discriminated between the wild type and mutant viral genomes revealed that a pure population of the mutant genome was present in the 10(-6) and 10(-7) dilutions of the index serum, resulting in infection of the chimpanzees receiving these dilutions only with the mutant virus. A clone of the mutant virus replicated normally following transfection in vitro. Thus, this HBV surface gene mutant is viable, infectious, and pathogenic in chimpanzees. C1 NIAID,INFECT DIS LAB,HEPATITIS VIRUSES SECT,NIH,BETHESDA,MD 20892. UNIV MILAN,INST VIROL,MILAN,ITALY. NIIGATA UNIV,SCH MED,DEPT INTERNAL MED 3,NIIGATA 951,JAPAN. FU NIAID NIH HHS [AI-72623, AI-05069] NR 60 TC 61 Z9 64 U1 1 U2 2 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 S WOODLAWN AVE, CHICAGO, IL 60637 SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD MAR PY 1997 VL 175 IS 3 BP 511 EP 523 PG 13 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA WK411 UT WOS:A1997WK41100003 PM 9041321 ER PT J AU Pitt, J Brambilla, D Reichelderfer, P Landay, A McIntosh, K Burns, D Hillyer, GV Mendez, H Fowler, MG AF Pitt, J Brambilla, D Reichelderfer, P Landay, A McIntosh, K Burns, D Hillyer, GV Mendez, H Fowler, MG TI Maternal immunologic and virologic risk factors for infant human immunodeficiency virus type 1 infection: Findings from the Women and Infants Transmission Study SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article; Proceedings Paper CT 1st National Conference on Human Retroviruses and Related Infectious CY DEC 15, 1993 CL WASHINGTON, DC ID PROGNOSTIC VALUE; CLINICAL-TRIALS; HIV-1 INFECTION; CELL LEVELS; VIRAL LOAD; AIDS; SEROCONVERSION; QUANTITATION; ACTIVATION; CULTURE AB Maternal virus load of human immunodeficiency virus 1 (HIV-1) and maternal immunity are both associated with risk of an infected infant. The interrelationship of these two variables in describing that risk was assessed in a multisite study of 475 mother-infant pairs. Infant infection was associated with low CD4 cell percentage, high CD8, CD8/CD38, and CD8/DR cell percentages, persistently positive HIV-1 cultures, and high HIV-1 titer (P <. 001, .001, .005, .006, .001, and .013, respectively). The association of CD4 cell percentage and increased CD8, CD8/CD38, and CD8/DR cell percentages with transmission was restricted to the 42% of women whose HIV-1 cultures were not persistently positive (all P < .001). Women with at least 1 negative culture and high CD4 cell percentage or low CD8 cell percentage were at very low risk (0-4%) of transmitting HIV-1, while those with always positive cultures transmitted at a high rate (18%-27%), regardless of immune status. C1 SUNY HLTH SCI CTR,DEPT PEDIAT,BROOKLYN,NY 11203. NEW ENGLAND RES INST,WATERTOWN,MA 02172. RUSH PRESBYTERIAN ST LUKES MED CTR,CHILDRENS HOSP,DEPT IMMUNOL & MICROBIOL,DIV INFECT DIS,BOSTON,MA. HARVARD UNIV,SCH MED,DEPT PEDIAT,BOSTON,MA 02115. NICHHD,PEDIAT ADOLESCENT & MATERNAL AIDS BRANCH,NIH,BETHESDA,MD 20892. NIAID,DIV AIDS,BETHESDA,MD 20892. UNIV PUERTO RICO,DEPT MICROBIOL,SAN JUAN,PR 00936. RP Pitt, J (reprint author), COLUMBIA UNIV,COLL PHYS & SURG,DEPT PEDIAT,DIV INFECT DIS,650 W 168TH ST,BB-419,NEW YORK,NY 10032, USA. FU NIAID NIH HHS [AI-82506]; NICHD NIH HHS [HD-25714, HD-82913] NR 41 TC 60 Z9 65 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 1997 VL 175 IS 3 BP 567 EP 575 PG 9 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA WK411 UT WOS:A1997WK41100009 PM 9041327 ER PT J AU Kalish, LA Pitt, J Lew, J Landesman, S Diaz, C Hershow, R Hollinger, FB Pagano, M Smeriglio, V Moye, J AF Kalish, LA Pitt, J Lew, J Landesman, S Diaz, C Hershow, R Hollinger, FB Pagano, M Smeriglio, V Moye, J TI Defining the time of fetal or perinatal acquisition of human immunodeficiency virus type 1 infection on the basis of age at first positive culture SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article; Proceedings Paper CT XIth International Conference on AIDS CY JUL 07-13, 1996 CL VANCOUVER, CANADA ID TRANSMISSION; HIV-1 AB It has been suggested that a positive diagnostic test for human immunodeficiency virus type 1 (HIV-1) during the first 48 h of life is indicative of intrauterine transmission, whereas negative tests during the first week with positive tests later indicate intrapartum transmission. On the basis of data from all 140 infected infants in the Women and Infants Transmission Study (WITS), the probability was estimated that an HIV-1 culture would be positive for the first time at each day of life if cultures were performed daily. The estimated probabilities (+/-SE) by days 0, 2, 4, 7, 9, 16, and 30 of life are 27.4% (+/-6.4%), 27.4% (+/-13.0%), 45.3% (+/-20.5%), 45.3% (+/-22.5%), 65.3% (+/-20.0%), 88.4% (+/-7.8%), and 89.3% (+/-7.0%), respectively. The initial 27% probability is consistent with the hypothesis that transmission usually occurs during the intrapartum period. However, the distribution of age at first positive culture does not separate clearly into two distinct intervals. More definitive methods for determining the timing of transmission are needed. C1 HARVARD UNIV,SCH PUBL HLTH,BOSTON,MA 02115. COLUMBIA UNIV COLL PHYS & SURG,NEW YORK,NY 10032. SUNY HLTH SCI CTR,BROOKLYN,NY 11203. NIAID,NIDA,NIH,BETHESDA,MD 20892. NICHHD,NIH,BETHESDA,MD 20892. UNIV PUERTO RICO,SAN JUAN,PR 00936. UNIV ILLINOIS,CHICAGO,IL. BAYLOR COLL MED,HOUSTON,TX 77030. RP Kalish, LA (reprint author), NEW ENGLAND RES INST,9 GALEN ST,WATERTOWN,MA 02172, USA. OI moye, john/0000-0001-9976-8586 FU NIAID NIH HHS [AI-34856, AI-34842, AI-34858] NR 14 TC 54 Z9 54 U1 0 U2 2 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 S WOODLAWN AVE, CHICAGO, IL 60637 SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD MAR PY 1997 VL 175 IS 3 BP 712 EP 715 PG 4 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA WK411 UT WOS:A1997WK41100033 PM 9041351 ER PT J AU Racusen, LC Monteil, C Sgrignoli, A Lucskay, M Marouillat, S Rhim, JGS Morin, JP AF Racusen, LC Monteil, C Sgrignoli, A Lucskay, M Marouillat, S Rhim, JGS Morin, JP TI Cell lines with extended in vitro growth potential from human renal proximal tubule: Characterization, response to inducers, and comparison with established cell lines SO JOURNAL OF LABORATORY AND CLINICAL MEDICINE LA English DT Article ID EPITHELIAL-CELLS; PRIMARY CULTURE; NEOPLASTIC TRANSFORMATION; HUMAN-KIDNEY; DIFFERENTIATION; TRANSFECTION; EXPRESSION; INVITRO; LLC-PK1 AB Few model systems exist for the study of injury to human renal proximal tubule epithelium. Optimized differentiated human renal epithelial cell lines with extended in vitro growth potential would provide an alternative model system to primary culture or other available non-human mammalian kidney cell lines. For this purpose, human renal tubule epithelial cells were isolated from normal kidney cortex and exposed in culture to a hybrid immortalizing virus, adenovirus 12-SV40. Cell lines were developed by limiting dilution, and three selected cell lines were screened for growth pattern, production of immortalizing virus, tumorigenicity, and ploidy. Cell lines were also monitored for response to inducer agents and matrix factors and were screened for expression of biochemical properties and differentiation markers of renal epithelium. All three are nonproducers of the immortalizing virus and are nontumorigenic. They grow in monolayer, have intermediate growth kinetics, and express markers of renal proximal tubular epithelium by immunohistochemistry. They also express biochemical properties comparable to other widely used proximal tubular cell lines including LLC-RK1, OK, and HK-2 and comparable to human tubular cells in stable culture. Growth medium containing low levels of fetal calf serum, or epidermal growth factor combined with parathyroid hormone, produced optimal growth characteristics, brush border enzyme expression, biochemical properties, and glucose transport in a selected cell line. The addition of dimethyl sulfoxide allows maintenance in morphologically intact monolayers for prolonged periods. These cell lines should be useful model systems for the study of human renal proximal tubular injury or disease. C1 NATL CANC INST,BETHESDA,MD. UNIV ROUEN,INSERM,U295,ST ETIENNE,FRANCE. RP Racusen, LC (reprint author), JOHNS HOPKINS UNIV,SCH MED,DEPT PATHOL,624 ROSS BLDG,720 RUTLAND AVE,BALTIMORE,MD 21205, USA. FU NIDDK NIH HHS [R01-DK43811] NR 39 TC 160 Z9 162 U1 6 U2 13 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 SN 0022-2143 J9 J LAB CLIN MED JI J. Lab. Clin. Med. PD MAR PY 1997 VL 129 IS 3 BP 318 EP 329 DI 10.1016/S0022-2143(97)90180-3 PG 12 WC Medical Laboratory Technology; Medicine, General & Internal; Medicine, Research & Experimental SC Medical Laboratory Technology; General & Internal Medicine; Research & Experimental Medicine GA WK940 UT WOS:A1997WK94000009 PM 9042817 ER PT J AU Green, RM AF Green, RM TI Parental autonomy and the obligation not to harm one's child genetically SO JOURNAL OF LAW MEDICINE & ETHICS LA English DT Article ID RIGHTS; ISSUES C1 NIH,OFF GENOME ETH,NATL CTR HUMAN GENOME RES,BETHESDA,MD 20892. RP Green, RM (reprint author), DARTMOUTH COLL,ETH INST,HANOVER,NH 03755, USA. NR 58 TC 30 Z9 31 U1 0 U2 1 PU AMER SOC LAW MEDICINE ETHICS PI BOSTON PA 765 COMMONWEALTH AVE, 16TH FL, BOSTON, MA 02215 SN 0277-8459 J9 J LAW MED ETHICS JI J. Law Med. Ethics PD SPR PY 1997 VL 25 IS 1 BP 5 EP 15 DI 10.1111/j.1748-720X.1997.tb01389.x PG 11 WC Ethics; Law; Medical Ethics; Medicine, Legal SC Social Sciences - Other Topics; Government & Law; Medical Ethics; Legal Medicine GA XN897 UT WOS:A1997XN89700001 PM 11066476 ER PT J AU Biesecker, LG AF Biesecker, LG TI Clinical commentary: The law of unintended ethics SO JOURNAL OF LAW MEDICINE & ETHICS LA English DT Editorial Material RP Biesecker, LG (reprint author), NIH,BLDG 10,BETHESDA,MD 20892, USA. NR 1 TC 0 Z9 1 U1 0 U2 0 PU AMER SOC LAW MEDICINE ETHICS PI BOSTON PA 765 COMMONWEALTH AVE, 16TH FL, BOSTON, MA 02215 SN 0277-8459 J9 J LAW MED ETHICS JI J. Law Med. Ethics PD SPR PY 1997 VL 25 IS 1 BP 16 EP 18 DI 10.1111/j.1748-720X.1997.tb01390.x PG 3 WC Ethics; Law; Medical Ethics; Medicine, Legal SC Social Sciences - Other Topics; Government & Law; Medical Ethics; Legal Medicine GA XN897 UT WOS:A1997XN89700002 PM 11066469 ER PT J AU Farber, JM AF Farber, JM TI Mig and IP-10: CXC chemokines that target lymphocytes SO JOURNAL OF LEUKOCYTE BIOLOGY LA English DT Article DE cytokines; interferon; T cells; infection; angiogenesis; cancer ID INTERFERON-INDUCIBLE PROTEIN-10; HUMAN-PLATELET FACTOR-4; X-C CHEMOKINE; GAMMA-INTERFERON; FACTOR-IV; EXPRESSION; GENE; CELLS; ACTIVATION; CYTOKINES AB Mg and IP-10 are related members of the CXC subfamily of the chemokine family of cytokines. The murine Mig (MuMig), human IP-10, and the mouse homologue of IP-10, Crg-2, were all identified due to the dramatic inductions of their genes in monocytic cells treated with interferon-gamma (IFN-gamma), Studies using recombinant (r) human proteins show that, unlike most other CXC chemokines, rHuMig and rIP-10 have no activity on neutrophils but appear to target lymphocytes specifically, rHuMig and rIP-10 are active as chemotactic factors for stimulated, but not for resting, T cells, Studies done in vitro and in vivo have shown that rHuMig and rIP-10 share additional activities, including inhibition of neovascularization, inhibition of hematopoietic progenitor cells, and anti-tumor effects, rHuMig and rIP-10 show reciprocal desensitization on activated T cells and have been demonstrated to share a receptor, CXCR3, The genes for both MuMig, and Crg-2 are highly expressed in multiple tissues during experimental viral and protozoan infections in mice, but their patterns of expression differ, This suggests that the Migs and IP-10/Crg-2 may play roles in host defense and that, despite their similar activities assayed in vitro, Mig and IP-10/Crg-2 may serve non-redundant functions in vivo. RP Farber, JM (reprint author), NIAID,CLIN INVEST LAB,NIH,BLDG 10,RM 11N-228,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 45 TC 569 Z9 578 U1 3 U2 7 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 1997 VL 61 IS 3 BP 246 EP 257 PG 12 WC Cell Biology; Hematology; Immunology SC Cell Biology; Hematology; Immunology GA WN150 UT WOS:A1997WN15000002 PM 9060447 ER PT J AU Purdon, D Arai, T Rapoport, S AF Purdon, D Arai, T Rapoport, S TI No evidence for direct incorporation of esterified palmitic acid from plasma into brain lipids of awake adult rat SO JOURNAL OF LIPID RESEARCH LA English DT Article DE lipoprotein; unesterified fatty acid; phospholipid; triglyceride lipase; incorporation ID DENSITY-LIPOPROTEIN RECEPTOR; FATTY-ACIDS; ENERGY-METABOLISM; ARACHIDONIC-ACID; LIPASE; TRANSPORT; PHOSPHOLIPIDS; CAPILLARIES; INTESTINE; MEMBRANE AB Awake adult rats were given a solution of [9,10-H-3[palmitate ([H-3]PAM) by gavage. The appearance of radiolabel in plasma lipid fractions was monitored by thin-layer chromatography at fixed intervals thereafter. At 2 h, the rats were killed by microwave irradiation and radioactivity in whole brain and individual brain phospholipids was determined. In plasma, esterified [H-3]PAM was mainly associated with triglyceride, phospholipid, and cholesterol ester. Radioactivity appeared to a larger extent in triglyceride than in unesterified fatty acid, suggesting that unesterified [H-3]PAM in plasma was largely due to release from esterified [H-3]PAM by lipoprotein lipase hydrolysis. Brain radioactivity could be accounted for entirely by incorporation of unesterified plasma [H-3]PAM. Esterified [H-3]PAM in chylomicrons or lipoproteins was calculated to make no measurable contribution using a published value for the incorporation coefficient of [H-3]PAM into brain in the evaluation. These results suggest that ingested palmitic acid (PAM) in adult rats enters blood as esterified triglyceride within chylomicrons and lipoproteins and, in part, eventually is converted to circulating unesterified PAM. It is the circulating unesterified PAM that is incorporated into brain from blood, whereas esterified PAM within plasma chlomicrons and lipoproteins makes no measurable direct contribution. RP Purdon, D (reprint author), NIA, NEUROSCI LAB, NIH, BLDG 10, ROOM 6C-103, BETHESDA, MD 20892 USA. NR 24 TC 56 Z9 56 U1 0 U2 1 PU LIPID RESEARCH INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0022-2275 J9 J LIPID RES JI J. Lipid Res. PD MAR PY 1997 VL 38 IS 3 BP 526 EP 530 PG 5 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA WT525 UT WOS:A1997WT52500011 PM 9101433 ER PT J AU Wen, H Denison, TJ Singerman, RW Balaban, RS AF Wen, H Denison, TJ Singerman, RW Balaban, RS TI The intrinsic signal-to-noise ratio in human cardiac imaging at 1.5, 3, and 4 T SO JOURNAL OF MAGNETIC RESONANCE LA English DT Article ID FIELD PENETRATION; POWER DEPOSITION; NMR; BODY; SAMPLES; COIL; DEPENDENCE; DESIGN; PHASE AB Cardiac imaging is inherently demanding on the signal-to-noise performance of the MR scanner and may benefit from high field strengths. However, the complex behavior of the radiofrequency field in the human body at high frequencies makes model-based analyses difficult. This study aims to obtain reliable comparisons of the signal-to-noise profile in the human chest in vivo at 1.5, 3, and 4 T. By using an RF-field-mapping method, it is shown that the intrinsic signal-to-noise increases with the field strength up to 4 T with a less than linear relation. The RF held profile is markedly distorted at 4 T, and the onset of this distortion is dependent on the body size. The high power deposition and the consequences of the RF field distortion are discussed. (C) 1997 Academic Press. RP Wen, H (reprint author), NHLBI,LAB CARDIAC ENERGET,NIH,BLDG 10,BETHESDA,MD 20892, USA. RI Balaban, Robert/A-7459-2009; Wen, Han/G-3081-2010 OI Balaban, Robert/0000-0003-4086-0948; Wen, Han/0000-0001-6844-2997 FU Intramural NIH HHS [Z01 HL004606-11] NR 31 TC 85 Z9 85 U1 0 U2 3 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 1090-7807 J9 J MAGN RESON JI J. Magn. Reson. PD MAR PY 1997 VL 125 IS 1 BP 65 EP 71 DI 10.1006/jmre.1996.1072 PG 7 WC Biochemical Research Methods; Physics, Atomic, Molecular & Chemical; Spectroscopy SC Biochemistry & Molecular Biology; Physics; Spectroscopy GA WT450 UT WOS:A1997WT45000008 PM 9245361 ER PT J AU Singerman, RW Denison, TJ Wen, H Balaban, RS AF Singerman, RW Denison, TJ Wen, H Balaban, RS TI Simulation of B-1 field distribution and intrinsic signal-to-noise in cardiac MRI as a function of static magnetic field SO JOURNAL OF MAGNETIC RESONANCE LA English DT Article ID POWER DEPOSITION; NMR; COIL; PENETRATION; FREQUENCIES; DEPENDENCE; RESONANCE; SAMPLES AB Two issues that pertain to the optimal static magnetic field for cardiac MRI were addressed: intrinsic signal-to-noise ratio (ISNR) and radiofrequency power deposition. From 1.5 to 9.5 T, proton Larmor frequencies of 63 to 400 MHz, numerical simulations were performed of the RF fields from a surface coil and a body coil loaded by a heterogeneous, three-dimensional, symmetric model of the human chest. The RF field distribution, the power required to produce the RF field, and the ISNR at the center of the heart were computed. The model was validated by comparison with experimental data up to 4 T. The RF held distortion was quantified and found to increase linearly up to 6 T due mostly to dielectric resonance modes. Body coil simulations beyond 6 T showed the onset of higher-order modes at the center of the heart. A range of expected RF power requirements was constructed as a function of held up to 9.5 T for surface coils and up to 6.8 T for body coils. Over this range of static field, ISNR for a constant coil geometry was bracketed by an upper limit that was slightly greater than linear with field and a lower limit that was slightly less than linear with field. The RF power and ISNR showed a strong dependence on chest thickness at 1.5 and 4.0 T. Additionally, independent of chest thickness, the model predicts a lower limit of a factor of 5 increase in RF power as the static field is increased from 1.5 to 4 T. Implications for imaging with other nuclei are discussed. Methods for checking the self-consistency of electrodynamic simulations are presented. (C) 1997 Academic Press. RP Singerman, RW (reprint author), NHLBI,CARDIAC ENERGET LAB,NIH,BLDG 10,BETHESDA,MD 20892, USA. RI Balaban, Robert/A-7459-2009; Wen, Han/G-3081-2010 OI Balaban, Robert/0000-0003-4086-0948; Wen, Han/0000-0001-6844-2997 NR 23 TC 39 Z9 39 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 1090-7807 J9 J MAGN RESON JI J. Magn. Reson. PD MAR PY 1997 VL 125 IS 1 BP 72 EP 83 DI 10.1006/jmre.1996.1073 PG 12 WC Biochemical Research Methods; Physics, Atomic, Molecular & Chemical; Spectroscopy SC Biochemistry & Molecular Biology; Physics; Spectroscopy GA WT450 UT WOS:A1997WT45000009 PM 9245362 ER PT J AU Kuszewski, J Gronenborn, AM Clore, GM AF Kuszewski, J Gronenborn, AM Clore, GM TI Improvements and extensions in the conformational database potential for the refinement of NMR and X-ray structures of proteins and nucleic acids SO JOURNAL OF MAGNETIC RESONANCE LA English DT Article ID 3-DIMENSIONAL STRUCTURES; CRYSTAL-STRUCTURE; TUMOR-SUPPRESSOR; INTERLEUKIN-4; DOMAIN; IMPACT; P53 C1 NIDDKD,PHYS CHEM LAB,NIH,BETHESDA,MD 20892. RI Clore, G. Marius/A-3511-2008 OI Clore, G. Marius/0000-0003-3809-1027 NR 14 TC 158 Z9 159 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 1090-7807 J9 J MAGN RESON JI J. Magn. Reson. PD MAR PY 1997 VL 125 IS 1 BP 171 EP 177 DI 10.1006/jmre.1997.1116 PG 7 WC Biochemical Research Methods; Physics, Atomic, Molecular & Chemical; Spectroscopy SC Biochemistry & Molecular Biology; Physics; Spectroscopy GA WT450 UT WOS:A1997WT45000024 PM 9245376 ER PT J AU Walsh, TJ Kasai, M Francesconi, A Landsman, D Chanock, SJ AF Walsh, TJ Kasai, M Francesconi, A Landsman, D Chanock, SJ TI New evidence that Candida albicans possesses additional ATP-binding cassette MDR-like genes: Implications for antifungal azole resistance SO JOURNAL OF MEDICAL AND VETERINARY MYCOLOGY LA English DT Article DE ATP binding cassette; C-albicans; MDR-like proteins ID MULTIDRUG-RESISTANCE; FLUCONAZOLE; IDENTIFICATION; AGENTS; SEARCH; AIDS AB Emergence of resistance of Candida albicans to antifungal triazoles is increasingly recognized as an important cause of refractory mucosal candidiasis in HIV-infected patients. Recently, CDR1, which is thought to be analogous to the human MDR-1 P-glycoprotein, has been cloned in C. albicans. It has been proposed that its expression is partially responsible for fluconazole resistance in C. albicans. This gene is characterized by the presence of an ATP binding cassette (ABC) region and is distinct from the BENr gene which does not encode such a functional domain. As the molecular basis for fluconazole resistance appears to be multifactorial, we considered that there may be other ATP binding cassette-containing MDR genes that may potentially contribute to antifungal azole resistance in C. albicans. We therefore sought to identify potential target sequences that may be derived from candidate genes that share homology with the ATP binding cassette region of the human MDR-1 P-glycoprotein. Degenerate oligonucleotide primers based on the known sequence from the ATP binding cassette region of the human MDR-1 P-glycoprotein were used to amplify PCR products within the range of 100 bp in length from C. albicans isolates (3 fluconazole-susceptible and 3 fluconazole-resistant). Sequence analysis of individually subcloned PCR products, derived from the six isolates revealed 34 sequences in total. The results of our study identified 14 clones (with at least one per isolate) with a high degree of homology to the ATP binding cassette of the human MDR-1 P-glycoprotein. The BLAST search did not disclose homology of these new sequences to the C. albicans CDR1 gene, suggesting that C. albicans may possess more than one MDR-like gene. We conclude that C. albicans may possess one or more additional genes encoding ATP binding cassette MDR-like proteins that are distinct from CDR1 and which could participate in the development of fluconazole resistance. C1 NATL LIB MED,NATL CTR BIOTECHNOL INFORMAT,BETHESDA,MD 20894. RP Walsh, TJ (reprint author), NCI,INFECT DIS SECT,PEDIAT BRANCH,BLDG 10,ROOM 13N-240,BETHESDA,MD 20892, USA. RI Landsman, David/C-5923-2009; OI Landsman, David/0000-0002-9819-6675 NR 22 TC 23 Z9 25 U1 0 U2 0 PU BLACKWELL SCIENCE LTD PI OXFORD PA P O BOX 88, OSNEY MEAD, OXFORD, OXON, ENGLAND OX2 0NE SN 0268-1218 J9 J MED VET MYCOL JI J. Med. Vet. Mycol. PD MAR-APR PY 1997 VL 35 IS 2 BP 133 EP 137 PG 5 WC Mycology SC Mycology GA WV884 UT WOS:A1997WV88400007 PM 9147273 ER PT J AU MacLean, PD AF MacLean, PD TI The brain and subjective experience: Question of multilevel role of resonance SO JOURNAL OF MIND AND BEHAVIOR LA English DT Article ID NEUROLOGICAL POSITIVISM; SYSTEMS THINKING AB Everything we experience and do as individuals is assumed to be a function of the nervous system. It is as though we were born with a total supply of algorithms for all given forms of psychic states and solutions for immediate or eventual actions. There is evidence that the forebrain is, so to speak, the central processor for psychic experience and psychologically directed behavior. Since information itself is immaterial, all forms of psychic experience represent immaterial emanations of the forebrain, including sensations, perceptions, drives, affects, thoughts, and the precisely measured, cold hard facts of science. But it is to be emphasized that there can be no manufacture or communication of information without the intermediary of behaving entities. Because of the immateriality of information and the Godel-like problem of self-reference, a central question arises as to whether or not we can ever rely on the brain with its viscoelastic properties to achieve a reliable yardstick for measuring time and space and the general nature of things. Most needed at the present time is a refined picture of the anatomy and chemistry of the brain's circuitry accounting for its particular species of algorithms. Emphasis is given to the basic role of various proteins in generating subjective experience. Because of the role of resonance in contributing to the dynamical excitability of neural circuits, examples are given here of how it might play an algorithmic role at macroscopic, microscopic, molecular, and atomic levels. To describe this idea attention is focused on three evolutionary types of cortex that have developed in the triune evolution of the mammalian forebrain from the mammal-like reptiles (therapsids) to human beings. RP MacLean, PD (reprint author), NIMH,CTR NEUROSCI,ROOM 503,2700 MARTIN LUTHER KING JR AVE SE,WASHINGTON,DC 20032, USA. NR 29 TC 2 Z9 2 U1 1 U2 2 PU INST MIND BEHAVIOR INC PI NEW YORK PA PO BOX 522 VILLAGE STATION, NEW YORK, NY 10014 SN 0271-0137 J9 J MIND BEHAV JI J. Mind Behav. PD SPR-SUM PY 1997 VL 18 IS 2-3 BP 247 EP 267 PG 21 WC Psychology, Multidisciplinary; Psychology, Experimental SC Psychology GA YF124 UT WOS:A1997YF12400009 ER PT J AU Kleinman, JE AF Kleinman, JE TI Advances in the neurobiology of schizophrenia - DenBoer,JA, Westenberg,HGM, VanPraag,HM SO JOURNAL OF NERVOUS AND MENTAL DISEASE LA English DT Book Review RP Kleinman, JE (reprint author), NIMH,CLIN BRAIN DISORDERS BRANCH,WASHINGTON,DC 20032, 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 1997 VL 185 IS 3 BP 204 EP 204 DI 10.1097/00005053-199703000-00013 PG 1 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA WN398 UT WOS:A1997WN39800013 ER PT J AU Zhao, HM Wenthold, RJ Wang, YX Petralia, RS AF Zhao, HM Wenthold, RJ Wang, YX Petralia, RS TI delta-glutamate receptors are differentially distributed at parallel aad climbing fiber synapses on Purkinje cells SO JOURNAL OF NEUROCHEMISTRY LA English DT Article DE AMPA; kainate; delta receptors; NMDA; metabotropic glutamate receptors; long-term depression ID SUBUNIT MESSENGER-RNAS; CENTRAL-NERVOUS-SYSTEM; AMINO-ACID RECEPTORS; LONG-TERM DEPRESSION; DEVELOPING RAT-BRAIN; NMDA RECEPTOR; HIPPOCAMPAL-NEURONS; CEREBELLAR CORTEX; IMMUNOCYTOCHEMICAL LOCALIZATION; ULTRASTRUCTURAL-LOCALIZATION AB Neurons containing multiple excitatory inputs may sort and target glutamate receptor subtypes to subsets of synapses. A good model for testing this hypothesis is the Purkinje cell, which expresses significant levels of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate, kainate, N-methyl-D-aspartate, delta-, and metabotropic glutamate receptors. Purkinje cells receive two excitatory inputs, the parallel and climbing fibers; the combined effect of stimulation of these two inputs is to produce longterm depression of parallel fiber/Purkinje cell neurotransmission. Distribution of glutamate receptors in these two synapse populations in rat cerebella was studied using preembedding immunocytochemistry with antibodies to GluR1, GluR2/3, GluR5-7, NR1, delta 1/2, and mGluR1 alpha. Moderate/dense postsynaptic staining was most frequent in postsynaptic densities and spines of both parallel and climbing fiber synapses with mGluR1 alpha antibody, was intermediate in frequency with GluR2/3 and GluR5-7 antibodies, and was least frequent with GluR1 and NR1 antibodies. The most striking finding was the absence of significant postsynaptic staining with delta 1/2 antibody in climbing fiber synapses in adult animals, even though postsynaptic staining was prevalent in parallel fiber synapses with this antibody. In contrast to adults, moderate/dense postsynaptic immunolabeling of climbing fiber synapses with delta 1/2 antibody was common in rats at 10 days postnatal. This study provides direct morphological evidence that delta-glutamate receptors are differentially targeted to synapse populations. Our results support previous suggestions that delta 2 is involved in development of parallel and climbing fiber synapses and in long-term depression of parallel fiber/Purkinje synaptic responses in adults. C1 NIDCD,NEUROCHEM LAB,NIH,BETHESDA,MD 20892. NR 83 TC 66 Z9 67 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PD MAR PY 1997 VL 68 IS 3 BP 1041 EP 1052 PG 12 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA WJ842 UT WOS:A1997WJ84200017 PM 9048749 ER PT J AU Chik, CL Liu, QY Li, B Klein, DC Zylka, M AF Chik, CL Liu, QY Li, B Klein, DC Zylka, M TI alpha(1D)L-type Ca2+-channel currents: Inhibition by a beta-adrenergic agonist and pituitary adenylate cyclase-activating polypeptide (PACAP) in rat pinealocytes SO JOURNAL OF NEUROCHEMISTRY LA English DT Article DE Ca2+ channel; cyclic AMP; norepinephrine; PACAP ID PROTEIN KINASE-C; N-ACETYLTRANSFERASE ACTIVITY; SENSITIVE CALCIUM-CHANNEL; CA2+ CHANNELS; CYCLIC-AMP; ALPHA-1-ADRENERGIC STIMULATION; CGMP ACCUMULATION; ALPHA-1 SUBUNIT; MOLECULAR-BASIS; MAMMALIAN CNS AB In this study the subunits of the dihydropyridine-sensitive L-type Ca2+ channels (L-channels) expressed in rat pinealocytes were characterized using reverse transcription (RT)-PCR analysis, and the modulation of these channels by adrenergic agonists and by pituitary adenylate cyclase-activating polypeptide (PACAP) was studied using the patch-clamp technique. RT-PCR analysis showed that rat pinealocytes expressed alpha(1D), alpha(2b), beta(2), and beta(4) Ca2+-channel subunit mRNAs. Other alpha(1) subunit transcripts were either not expressed or present at very low levels, indicating that the pinealocytes express predominantly alpha(1D) L-channels. Electrophysiological studies confirmed that the pineal expressed a single population of L-channels. The L-channel currents were inhibited by two agonists that elevate cyclic AMP: the beta-adrenergic agonist isoproterenol and PACAP. Similar inhibition was observed with a cyclic AMP analogue, 8-bromo-cyclic AMP. The presence of a cyclic AMP antagonist, Rp-adenosine 3',5'-cyclic monophosphorothioate, blocked the inhibition by isoproterenol and PACAP. Norepinephrine, a mixed alpha- and beta-adrenergic agonist, also inhibited the L-channel currents, but the inhibition was smaller. The smaller inhibition by norepinephrine was secondary to the simultaneous activation of alpha- and beta-adrenergic receptors. These results indicate that (a) pinealocytes express predominantly alpha(1D) L-channels, and (b) the beta-adrenergic agonist isoproterenol and PACAP inhibit the L-channel currents through elevation of cyclic AMP. However, an alpha-adrenergic-mediated mechanism also appears to be involved in the effect of norepinephrine on the L-channel currents. C1 UNIV ALBERTA,DEPT PHYSIOL,EDMONTON,AB T6G 2H7,CANADA. NICHHD,DEV NEUROBIOL LAB,SECT NEUROENDOCRINOL,BETHESDA,MD 20892. NINCDS,NEUROCHEM LAB,NIH,BETHESDA,MD 20892. RP Chik, CL (reprint author), UNIV ALBERTA,DEPT MED,ROOM 733,MED SCI BLDG,EDMONTON,AB T6G 2H7,CANADA. NR 41 TC 41 Z9 42 U1 2 U2 2 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PD MAR PY 1997 VL 68 IS 3 BP 1078 EP 1087 PG 10 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA WJ842 UT WOS:A1997WJ84200021 PM 9048753 ER PT J AU Bencsics, A Elenkov, IJ Vizi, ES AF Bencsics, A Elenkov, IJ Vizi, ES TI Effect of morphine on lipopolysaccharide-induced tumor necrosis factor-alpha production in vivo: Involvement of the sympathetic nervous system SO JOURNAL OF NEUROIMMUNOLOGY LA English DT Article DE morphine; opioid receptors; lipopolysaccharide; tumor necrosis factor alpha; sympathetic nervous system; norepinephrine; neuroimmunomodulation; in vivo ID IMMUNE-SYSTEM; MAST-CELLS; OPIOID RECEPTORS; BLOOD; MODULATION; RELEASE; MICE; TNF; NOREPINEPHRINE; NORADRENALINE AB Morphine treatment modulates a variety of immunological parameters, including tumor necrosis factor-alpha (TNF-alpha) production by activated macrophages in vitro. The aim of our study was to clarify the effect of morphine on lipopolysaccharide (LPS)-induced TNF-alpha production in vivo. Plasma TNF-alpha levels of mice were determined by ELISA. Subcutaneous injection of morphine decreased LPS-induced TNF-alpha production throughout the response, an effect that was dose-dependent and reversible by naloxone. Blockade of the sympathetic transmission by chlorisondamine prevented the inhibitory effect of morphine on TNF-alpha production. It is concluded that (i) systemic administration of morphine inhibits LPS-induced TNF-alpha production in vivo via 'classic' opioid receptors; (ii) this effect requires intact sympathetic outflow. Since the increased incidence of bacterial and viral infections in opioid addicts is well documented, it is suggested that the inhibitory effect of morphine on TNF-alpha production might play a substantial role in the increased vulnerability of these individuals to certain infections. C1 HUNGARIAN ACAD SCI,INST EXPT MED,H-1450 BUDAPEST,HUNGARY. NICHHD,DEV ENDOCRINOL BRANCH,NIH,BETHESDA,MD 20892. NIAMSD,ARTHRIT & RHEUMATISM BRANCH,NIH,BETHESDA,MD 20892. NR 44 TC 41 Z9 42 U1 1 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-5728 J9 J NEUROIMMUNOL JI J. Neuroimmunol. PD MAR PY 1997 VL 73 IS 1-2 BP 1 EP 6 DI 10.1016/S0165-5728(96)00163-4 PG 6 WC Immunology; Neurosciences SC Immunology; Neurosciences & Neurology GA WM882 UT WOS:A1997WM88200001 PM 9058753 ER PT J AU Honma, K Parker, KC Becker, KG McFarland, HF Coligan, JE Biddison, WE AF Honma, K Parker, KC Becker, KG McFarland, HF Coligan, JE Biddison, WE TI Identification of an epitope derived from human proteolipid protein that can induce autoreactive CD8(+) cytotoxic T lymphocytes restricted by HLA-A3: Evidence for cross-reactivity with an environmental microorganism SO JOURNAL OF NEUROIMMUNOLOGY LA English DT Article DE autoimmunity; multiple sclerosis; cytotoxic T cells; HLA; molecular mimicry ID MYELIN BASIC-PROTEIN; EXPERIMENTAL ALLERGIC ENCEPHALOMYELITIS; INFLUENZA-VIRUS PROTEINS; MULTIPLE-SCLEROSIS; CLASS-I; ANTIGEN EXPRESSION; CELL EPITOPES; PEPTIDES; AUTOIMMUNITY; FREQUENCY AB The demyelination process that occurs in the central nervous system (CNS) of patients with multiple sclerosis (MS) is in part due to an inflammatory response in which CD4(+) and CD8(+) T cells and macrophages infiltrate white matter. In this study, we have identified a peptide sequence derived from the CNS-specific myelin protein proteolipid protein (PLP) which could bind to HLA-A3 and induce a HLA-AS-restricted CD8(+) CTL response from HLA-A3(+) donors. These PLP peptide-specific CTL could lyse HLA-A3(+) target cells pulsed with a homologous peptide derived from the CRM1 protein of Saccharomyces cerevisae. These findings demonstrate the immunogenic potential of a PLP-derived peptide for generation of autoreactive HLA-A3-restricted CD8(+) CTL, and further show that these CTL can be activated by a peptide derived from a common environmental microorganism. C1 NINCDS,NEUROIMMUNOL BRANCH,BETHESDA,MD 20892. NIAID,MOL STRUCT LAB,NIH,BETHESDA,MD 20892. OI Parker, Kenneth/0000-0002-6282-2478; Becker, Kevin/0000-0002-6794-6656 NR 35 TC 44 Z9 44 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-5728 J9 J NEUROIMMUNOL JI J. Neuroimmunol. PD MAR PY 1997 VL 73 IS 1-2 BP 7 EP 14 DI 10.1016/S0165-5728(96)00161-0 PG 8 WC Immunology; Neurosciences SC Immunology; Neurosciences & Neurology GA WM882 UT WOS:A1997WM88200002 PM 9058754 ER PT J AU Das, KP Hong, JS Sanders, VM AF Das, KP Hong, JS Sanders, VM TI Ultralow concentrations of proenkephalin and [met(5)]-enkephalin differentially affect IgM and IgG production by B cells SO JOURNAL OF NEUROIMMUNOLOGY LA English DT Article DE opioid peptides; immunoglobulin; B lymphocyte; mouse; enkephalins ID DELTA-OPIOID RECEPTOR; METHIONINE-ENKEPHALIN; DEXTRAN SULFATE; MET-ENKEPHALIN; IMMUNE-SYSTEM; MESSENGER-RNA; LYMPHOCYTES-T; ACTIVATION; GROWTH; LIPOPOLYSACCHARIDE AB Resting mouse splenic B cells were activated with lipopolysaccharide/dextran sulfate (LPS/DxS) to measure both B cell proliferation and IgM/IgG isotype production when increasing concentrations of [Met(5)]-enkephalin (MENK) and proenkephalin (PENK) (10(-16) to 10(-8) M) were added at increasing times after B cell activation (0, 3, 6, or 24 h). Results show that proliferation was not affected by either peptide, but that IgM, IgG3 and IgG2a production were inhibited in a concentration- and time-dependent manner by MENK. IgG1 production was unaffected by MENK. In contrast, PENK induced no change in the production of Ig isotypes at any time point of addition, with the exception of IgG1 and IgG2a that were enhanced when PENK was added 6 h after cell activation. In the absence of LPS/DxS activation, no change in the level of any Ig isotype was induced by either peptide. C1 LOYOLA UNIV,STRITCH SCH MED,DEPT CELL BIOL NEUROBIOL & ANAT,MAYWOOD,IL 60153. NIEHS,SYST TOXICOL BRANCH,NEUROPHARMACOL SECT,RES TRIANGLE PK,NC 27709. NR 38 TC 6 Z9 6 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-5728 J9 J NEUROIMMUNOL JI J. Neuroimmunol. PD MAR PY 1997 VL 73 IS 1-2 BP 37 EP 46 DI 10.1016/S0165-5728(96)00165-8 PG 10 WC Immunology; Neurosciences SC Immunology; Neurosciences & Neurology GA WM882 UT WOS:A1997WM88200005 PM 9058757 ER PT J AU Oyanagi, K Makifuchi, T Ohtoh, T Chen, KM Gajdusek, DC Chase, TN AF Oyanagi, K Makifuchi, T Ohtoh, T Chen, KM Gajdusek, DC Chase, TN TI Distinct pathological features of the gallyas- and tau-positive glia in the parkinsonism-dementia complex and amyotrophic lateral sclerosis of Guam SO JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY LA English DT Article DE amyotrophic lateral sclerosis; astrocyte; guam; intracytoplasmic inclusion; oligodendroglia; Parkinsonism-dementia complex; tau ID PROGRESSIVE SUPRANUCLEAR PALSY; PAIRED HELICAL FILAMENTS; ALZHEIMERS-DISEASE; CORTICOBASAL DEGENERATION; NEUROFIBRILLARY TANGLES; FIBRILLARY TANGLES; STRAIGHT TUBULES; OLIVOPONTOCEREBELLAR ATROPHY; BRAIN; ASTROCYTES AB We examined 50 patients with parkinsonism-dementia complex of Guam (Guam PDC), 10 Guamanian patients with amyotrophic lateral sclerosis (ALS), 5 patients with combined PDC and ALS (PDC-ALS), and 20 non-PDC non-ALS Guamanians, who had been autopsied between 1979 and 1982, paying special attention to glial inclusions. Gallyas-positive and tau-immunopositive intracytoplasmic inclusions were observed in many of the glial cells, in addition to extensive neurofibrillary tangles (NFTs) in the brains of Guam PDC and PDC-ALS patients. Granular hazy inclusions were seen in the astrocytes, and some crescent/coiled inclusions were observed in the oligodendroglia. Many granular hazy inclusions were observed in the amygdaloid nucleus, inferior olivary nucleus, and lateral funiculus of the spinal cord. The crescent/coiled inclusions were observed predominantly in the anterior nucleus of the thalamus, motor cortex, midbrain tegmentum, pyramids of the medulla oblongata, and lateral funiculus of the spinal cord. The granular hazy inclusions have never been reported previously, and the topographic distribution of the crescent/coiled inclusions in Guam PDC and PDC-ALS differs from those reported previously in other NFT-forming diseases. These findings indicate that Guam PDC and PDC-ALS involve not only neurons but also glia, and that their morphological and topographic differences from other NFT-forming diseases may provide further insights into their distinct etiopathogenesis, and thus prove useful for diagnosis. C1 NIIGATA UNIV,BRAIN RES INST,BRAIN DIS RES CTR,NIIGATA 951,JAPAN. NATL SAIGATA HOSP,DEPT NEUROPATHOL,OOGATA,NIIGATA,JAPAN. NATL KOHRIYAMA HOSP,KORIYAMA,JAPAN. GUAM MEM HOSP,TAMUNING,GU. NINCDS,NIH,BETHESDA,MD 20892. RP Oyanagi, K (reprint author), TOKYO METROPOLITAN INST NEUROSCI,DEPT NEUROPATHOL,2-6 MUSASHIDAI,FUCHU,TOKYO 183,JAPAN. NR 41 TC 36 Z9 37 U1 1 U2 2 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 1997 VL 56 IS 3 BP 308 EP 316 DI 10.1097/00005072-199703000-00010 PG 9 WC Clinical Neurology; Neurosciences; Pathology SC Neurosciences & Neurology; Pathology GA WN140 UT WOS:A1997WN14000010 PM 9056545 ER PT J AU Collin, C Miyaguchi, K Segal, M AF Collin, C Miyaguchi, K Segal, M TI Dendritic spine density and LTP induction in cultured hippocampal slices SO JOURNAL OF NEUROPHYSIOLOGY LA English DT Article ID ORGANOTYPIC CULTURES; PYRAMIDAL NEURONS; RAT HIPPOCAMPUS; SYNAPTIC MODIFICATION; CALCIUM; STIMULATION; INCREASE; SYNAPSES; MODEL AB Transverse hippocampal slices were cut from 8- to 9-day-old rats and maintained in an interface chamber for periods of 1-4 wk, in tissue culture conditions. Neurons in the slice preserved their spatial organization and connectivity. Dendritic spine density in CA1 neurons was very low at 1 wk in culture, and long, filopodia-like structures were abundant. Spine density increased in these neurons nearly threefold during the course of 3 wk in vitro, to approach values of those of the normal, in vivo hippocampus. The magnitude of long-term potentiation (LTP) of reactivity of CA1 to stimulation of CA3 neurons also increased during weeks in culture in parallel with the change in spine density. Chronic exposure of slices to drugs that interact with synaptic activity caused changes in their dendritic spine density. Blockade of the N-methyl-D-aspartate (NMDA) receptors with the receptor antagonist 2-aminophosphonovalerate (D-APV) or blockade of action potential discharges with tetrodotoxin (TTX) prevented dendritic spine development in immature cultures. Enhancing synaptic activity by blockade of GABAergic inhibition with picrotoxin did not affect spins density to a significant degree. D-APV-treated slices expressed larger LTP than controls. TTX-treated slices expressed smaller LTP than controls. Picrotoxin treated slices did nor express LTP. It is proposed that LTP and dendritic spine density are correlated strongly during development, whereas they are not correlated in the more mature slice/culture of the hippocampus where spine density can be modulated by chronic exposure to blockers of synaptic activity, which will not affect LTP in a similar manner. C1 NIH,NINDS,NEUROBIOL LAB,BETHESDA,MD 20814. WEIZMANN INST SCI,DEPT NEUROBIOL,IL-76100 REHOVOT,ISRAEL. RP Collin, C (reprint author), NIH,NINDS,MOL BIOL LAB,BLDG 36,ROOM 3D02,BETHESDA,MD 20814, USA. RI yu, yan/C-2322-2012 NR 38 TC 78 Z9 78 U1 0 U2 1 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-3077 J9 J NEUROPHYSIOL JI J. Neurophysiol. PD MAR PY 1997 VL 77 IS 3 BP 1614 EP 1623 PG 10 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA WP116 UT WOS:A1997WP11600044 PM 9084624 ER PT J AU Liu, X Linnington, C Webster, HD Lassmann, S Yao, DL Hudson, LD Wekerle, H Kreutzberg, GW AF Liu, X Linnington, C Webster, HD Lassmann, S Yao, DL Hudson, LD Wekerle, H Kreutzberg, GW TI Insulin-like growth factor-I treatment reduces immune cell responses in acute non-demyelinative experimental autoimmune encephalomyelitis SO JOURNAL OF NEUROSCIENCE RESEARCH LA English DT Article ID EXPERIMENTAL ALLERGIC ENCEPHALOMYELITIS; GENE-EXPRESSION; OLIGODENDROCYTE DEVELOPMENT; TRANSGENIC MICE; BINDING-PROTEIN; LEWIS RAT; MYELINATION; ASTROCYTES; RECEPTOR; SIZE AB To test the effects of insulin-like growth factor-I (IGF-I) on clinical deficits, lesion severity, and immune cell responses in acute, non-demyelinative experimental autoimmune encephalomyelitis (EAE), we induced EAE in Lewis rats by passive transfer of an MBP-reactive T lymphocyte line, Four days after receiving 5 x 10(5) MBPL-1 T cells intravenously, ten pairs of rats had the same mild degree of tail and hind limb weakness, Ten were given 300 mu g IGF-I i.v. twice daily for 6 days, and the other 10 received the same volume of 0.89% NaCl, Pairs of rats were sacrificed after 4 days and 6 days of IGF-I and placebo treatment and spinal cord sections were processed for immunostaining, in situ hybridization, and morphological examination, IGF-I treatment decreased clinical deficits, lesion numbers, and lesion areas significantly, Numbers of CD4-positive T cells, alpha/beta TCR-positive cells, and ED-1-positive macrophages were also significantly reduced by IGF-I treatment, Similar reductions were found in our second trial, when 11 days of placebo and IGF-I injections began the day after transfer, No demyelination was observed in either toluidine blue-stained semithin sections or in sections immunostained with an antibody raised against myelin basic protein (MBP), We conclude that IGF-I-induced reductions in immune cell responses can occur in the absence of demyelination and are of major importance in decreasing clinical deficits and lesion severity in EAE, If IGF-I has similar effects in multiple sclerosis, we think that it will be useful therapeutically. (C) 1997 Wiley-Liss, Inc. C1 NINCDS,NIH,EXPT NEUROPATHOL LAB,BETHESDA,MD 20892. NINCDS,NIH,LAB DEV NEUROGENET,BETHESDA,MD 20892. MAX PLANCK INST PSYCHIAT,DEPT NEUROIMMUNOL,D-8033 MARTINSRIED,GERMANY. MAX PLANCK INST PSYCHIAT,DEPT NEUROMORPHOL,D-8033 MARTINSRIED,GERMANY. NR 31 TC 39 Z9 43 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 1997 VL 47 IS 5 BP 531 EP 538 DI 10.1002/(SICI)1097-4547(19970301)47:5<531::AID-JNR8>3.0.CO;2-I PG 8 WC Neurosciences SC Neurosciences & Neurology GA WL661 UT WOS:A1997WL66100008 PM 9067862 ER PT J AU Sparks, SM AF Sparks, SM TI Using the Internet for nursing administration SO JOURNAL OF NURSING ADMINISTRATION LA English DT Article RP Sparks, SM (reprint author), NATL LIB MED,DIV EXTRAMURAL PROGRAMS,BETHESDA,MD, USA. NR 2 TC 2 Z9 2 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0002-0443 J9 J NURS ADMIN JI J. Nurs. Adm. PD MAR PY 1997 VL 27 IS 3 BP 15 EP 20 DI 10.1097/00005110-199703000-00005 PG 6 WC Nursing SC Nursing GA WN861 UT WOS:A1997WN86100007 PM 9084468 ER PT J AU Buckley, RH Schiff, RI Schiff, SE Markert, ML Williams, LW Harville, TO Roberts, JL Puck, JM AF Buckley, RH Schiff, RI Schiff, SE Markert, ML Williams, LW Harville, TO Roberts, JL Puck, JM TI Human severe combined immunodeficiency: Genetic, phenotypic, and functional diversity in one hundred eight infants SO JOURNAL OF PEDIATRICS LA English DT Article ID STEM-CELL TRANSPLANTATION; BONE-MARROW CELLS; ADENOSINE-DEAMINASE; DEFECT; DEFICIENCY; IMMUNITY; MUTATION; DISEASE; KINASE; LYMPHOCYTES AB Objective: To determine the relative frequencies of the different genetic forms of severe combined immunodeficiency (SCID) and whether there are distinctive characteristics of the particular genotypes. Study design: The demographic, genetic, and immunologic features of 108 infants with SCID who were treated consecutively at Duke University Medical Center were analyzed. Results: Eighty-nine subjects were boys and 19 were girls; there were 84 white infants, 16 black infants, and 8 Hispanic infants, Forty-nine had X-linked SCID with mutations of common cytokine receptor gamma chain (gamma(c)), 16 had adenosine deaminase (ADA) deficiency, 8 had Janus kinase 3 (Jak3) deficiency, 21 had unknown autosomal recessive mutations, 1 had reticular dysgenesis, 1 had cartilage hair hypoplasia, and 12 (all boys) had SCID of undetermined type, Deficiency of ADA caused the most profound lymphopenia; gamma(c) or Jak3 deficiency resulted in the most B cells and fewest natural kilter (NK) cells; NK cells and function were highest in autosomal recessive and unknown types of SCID. Conclusions: Different SCID genotypes are associated with distinctive lymphocyte characteristics. The presence of NK function in ADA-deficient, autosomal recessive, and unknown type SCIDs, and low NK function in a majority of gamma(c) and Jak3 SCIDs indicates that some molecular lesions aff ect T, B, and NK cells (gamma(c) and Jak3), others primarily T cells (ADA deficiency), and others just T and B cells. C1 DUKE UNIV, MED CTR, DEPT IMMUNOL, DURHAM, NC 27710 USA. NIH, NATL CTR HUMAN GENOME RES, BETHESDA, MD 20892 USA. RP Buckley, RH (reprint author), DUKE UNIV, MED CTR, DEPT PEDIAT, BOX 2898, DURHAM, NC 27710 USA. FU NCRR NIH HHS [M01-RR-30]; NIAID NIH HHS [5R37AI18613, U19 AI38550] NR 48 TC 335 Z9 343 U1 2 U2 31 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0022-3476 EI 1097-6833 J9 J PEDIATR-US JI J. Pediatr. PD MAR PY 1997 VL 130 IS 3 BP 378 EP 387 DI 10.1016/S0022-3476(97)70199-9 PG 10 WC Pediatrics SC Pediatrics GA WM264 UT WOS:A1997WM26400011 PM 9063412 ER PT J AU Zhao, M Kleinman, HK Mokotoff, M AF Zhao, M Kleinman, HK Mokotoff, M TI Synthesis and activity of partial retro-inverso analogs of the antimetastatic laminin-derived peptide, YIGSR-NH2 SO JOURNAL OF PEPTIDE RESEARCH LA English DT Article DE antimetastatic activity; FABMS; retro-inverso peptides; YIGSR-NH2 ID BOMBARDMENT MASS-SPECTROMETRY; BASEMENT-MEMBRANE; PENTAPEPTIDE; ACID; METASTASES; RECEPTOR; AGENTS; ESTERS; CHAIN AB This paper describes the synthesis and biological evaluation of six partial retro-inverso peptidomimetic analogs of YIGSR-NH2, a synthetic peptide from the beta 1 chain of laminin, which has antimetastatic activity. The intent was to improve the antimetastatic potency of YIGSR-NH2 by limiting the in vivo enzymatic degradation through the incorporation of fraudulent peptide bonds. We have prepared the following retro-inverso peptides, Tyr-Ile-Gly-Ser-gArg-CHO (1), Tyr-gIle-mGly-Ser-Arg-NH2 (2), Tyr-gIle-mGly-Ser-gArg-CHO (3), gTyr-D-rIle-mGly-Ser-Arg-NH2 (4), Tyr-Ile-Gly-gSer-D-rArg-CHO (5) and Tyr-gIle-rGly-D-rSer-D-rArg-CHO (6). In vitro assays for B16F10 melanoma cell adhesion showed no significant activity for these six peptides. Peptides 1-3, 5 and 6 were further tested, in vivo, for their ability to inhibit tumor metastases to the lung in mice injected in the tail vein with B16F10 melanoma cells. All five of the retro-inverso peptides tested showed statistically significant inhibition of metastasis, but the most active peptides were 5 and 6, which showed 57 and 69% inhibition of metastasis, respectively. (C) Munksgaard 1997. C1 UNIV PITTSBURGH,SCH PHARM,DEPT PHARMACEUT SCI,PITTSBURGH,PA 15261. NIDR,DEV BIOL LAB,NIH,BETHESDA,MD 20892. FU NCRR NIH HHS [RR04664-01] NR 29 TC 11 Z9 11 U1 0 U2 7 PU MUNKSGAARD INT PUBL LTD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 1397-002X J9 J PEPT RES JI J. Pept. Res. PD MAR PY 1997 VL 49 IS 3 BP 240 EP 253 PG 14 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA WZ919 UT WOS:A1997WZ91900007 PM 9151257 ER PT J AU Matsuoka, N Aigner, TG AF Matsuoka, N Aigner, TG TI FK960 [N-(4-acetyl-1-piperazinyl)-p-fluorobenzamide monohydrate], a novel potential antidementia drug, improves visual recognition memory in rhesus monkeys: Comparison with physostigmine SO JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS LA English DT Article ID LONG-TERM POTENTIATION; SOMATOSTATIN-LIKE IMMUNOREACTIVITY; CENTRAL NERVOUS-SYSTEM; PUTATIVE COGNITIVE ENHANCER; EXCITATORY AMINO-ACIDS; ALZHEIMERS-DISEASE; RECEPTOR ANTAGONIST; BRAIN SOMATOSTATIN; PASSIVE-AVOIDANCE; RAT HIPPOCAMPUS AB Our previous studies demonstrated that FK960 [N-(4-acetyl-1-piperazinyl)-p-fluorobenzamide monohydrate], a novel antidementia piperazine derivative, exerts beneficial effects on memory deficits in various rodent models of amnesia, through activation of the somatostatin neuronal system. To extend the antiamnesic action of FK960 to nonhuman primates, FK960 was evaluated for its ability to reverse the deficits in visual recognition memory produced by muscarinic cholinergic receptor blockade by scopolamine or N-methyl-D-aspartate receptor blockade by dizocilpine (MK-801) in four rhesus monkeys performing a computer-automated version of delayed nonmatching to sample, with a list length of 20 trial-unique graphic symbols. Furthermore, the effects of FK960 were compared with those of physostigmine, a cholinesterase inhibitor. Doses of FK960 (1, 3.2, 10, 32, 100, 320 or 1000 mu g/kg) injected i.m. 30 min before testing minimally affected visual recognition memory when administered alone. FK960 (1, 3.2, 10 or 32 mu g/kg) significantly antagonized the deficits in visual recognition memory produced by scopolamine (10 mu g/kg); the same doses of the drug minimally affected the deficits produced by dizocilpine (32 mu g/kg). Similarly, physostigmine (3.2, 10 or 32 mu g/kg) significantly and dose-dependently restored the visual recognition memory deficits produced by scopolamine (10 mu g/kg) but not those produced by dizocilpine (32 mu g/kg). From these results, we conclude that FK960 improves deficits in recognition memory associated with central cholinergic hypofunction in nonhuman primates, and we suggest that the therapeutic potential of this drug for patients with dementia should be evaluated. C1 FUJISAWA PHARMACEUT CO LTD, EXPLORATORY RES LABS, TSUKUBA, IBARAKI 30026, JAPAN. NIMH, NEUROPSYCHOL LAB, BETHESDA, MD 20892 USA. NR 46 TC 30 Z9 30 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 1997 VL 280 IS 3 BP 1201 EP 1209 PG 9 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA WN709 UT WOS:A1997WN70900010 PM 9067304 ER PT J AU Rho, JM Donevan, SD Rogawski, MA AF Rho, JM Donevan, SD Rogawski, MA TI Barbiturate-like actions of the propanediol dicarbamates felbamate and meprobamate SO JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS LA English DT Article ID GAMMA-AMINOBUTYRIC-ACID; METHYL-D-ASPARTATE; MOUSE SPINAL-CORD; RAT HIPPOCAMPAL-NEURONS; KINETIC-PROPERTIES; RECEPTOR CHANNELS; CONDUCTANCE STATE; CHLORIDE CHANNELS; PARTIAL SEIZURES; CLINICAL-TRIAL AB Felbamate and meprobamate are structurally related propanediol dicarbamates that possess distinct pharmacological profiles. Felbamate is a minimally sedative, broad-spectrum anticonvulsant, whereas meprobamate is a strong sedative-anxiolytic agent. Previously, we reported that felbamate potentiates gamma-aminobutyric acid(A) (GABA(A)) receptor Cl- currents and inhibits N-methyl-D-aspartate (NMDA) receptor currents. Here we further characterized the interaction of the two dicarbamates with GABA(A) receptors to determine the basis for their pharmacological differences, In whole-cell voltage-clamp recordings from cultured rat hippocampal neurons, meprobamate enhanced GABA-evoked responses in a concentration-dependent manner and, at high concentrations (>1 mM), exhibited a separate channel-blocking effect that limited the magnitude of GABA(A) receptor potentiation. At equivalent concentrations, meprobamate produced substantially greater potentiation than did felbamate. Furthermore, meprobamate (but not felbamate), in the absence of GABA, directly activated Cl- currents that could be attenuated by the GABA(A) receptor antagonists bicuculline and picrotoxin. The mean deactivation time constant of whole-cell currents evoked by 10 mM meprobamate (110 ms) or 1 and 3 mu M GABA (180 ms) were faster than the deactivation time constant of 10 mM meprobamate (490 ms) or 3 mM felbamate (470 ms) in the presence of GABA. Meprobamate and felbamate prolonged the mean burst duration of GABA-activated unitary currents in excised outside-out membrane patches, In addition, at high (supratherapeutic) concentrations, meprobamate blocked NMDA-activated currents. We conclude that felbamate and meprobamate have barbiturate-like modulatory actions on GABA(A) receptors, but meprobamate has greater activity and, unlike felbamate, is able to directly activate the receptor. C1 NINCDS,NEURONAL EXCITABIL SECT,EPILEPSY RES BRANCH,NIH,BETHESDA,MD 20892. RI Rogawski, Michael/B-6353-2009 OI Rogawski, Michael/0000-0002-3296-8193 NR 44 TC 45 Z9 45 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 1997 VL 280 IS 3 BP 1383 EP 1391 PG 9 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA WN709 UT WOS:A1997WN70900033 PM 9067327 ER PT J AU Evans, RL Turner, RJ AF Evans, RL Turner, RJ TI Upregulation of Na+-K+-2Cl(-) cotransporter activity in rat parotid acinar cells by muscarinic stimulation SO JOURNAL OF PHYSIOLOGY-LONDON LA English DT Article ID K-CL COTRANSPORT; ARACHIDONATE METABOLITES; ION-TRANSPORT; ACTIVATION; CYTOCHROME-P450; SECRETION; CALCIUM; VOLUME; DRUGS; ACID AB 1. The effects of fluid secretory stimuli on the Na+-K+-2Cl(-) cotransporter in rat parotid acini were investigated. Cotransporter activity was measured using NH4+ as a K+ surrogate and following cotransporter-mediated NH4+ fluxes by monitoring intracellular pH. 2. A dramatic upregulation (15- to 20-fold) of acinar Na+-K+-2Cl(-) cotransporter activity was induced by muscarinic, alpha(1)-adrenergic and peptidergic stimuli. A half-maximal effect of the muscarinic agonist carbachol was observed at similar to 0.5 mu M. 3. Our results indicate that the rise in intracellular calcium concentration ([Ca2+](i)) which accompanies these stimuli is both a necessary and a sufficient condition for this effect; but it is not a consequence of the KCl loss and concomitant isotonic shrinkage caused by increased [Ca2+](i) as it persists when these effects are prevented. 4. The effect of muscarinic stimulation on the cotransporter can, however, be blocked by inhibitors of phospholipase A, (4-bromophenacylbromide and manoalide), by a general inhibitor of arachidonic acid metabolism (5,8,11,14-eicosatetraynoic acid) and by specific inhibitors of the cytochrome P450 pathway (methoxsalen and ketoconazole). 5. These latter results argue strongly for the involvement of a product of the cytochrome P450 pathway of arachidonic acid metabolism in upregulation of the salivary Na+-K+-2Cl(-) cotransporter. 6. Owing to the complexity of the arachidonic acid cascade a wide variety of agents could potentially interfere with this upregulation of the cotransporter, and thereby result in decreased salivary fluid production. We suggest that such an effect could underlie the dry mouth (xerostomia) that occurs as an unexplained side-effect of many commonly prescribed medications. C1 NIDR,CLIN INVEST & PATIENT CARE BRANCH,NIH,BETHESDA,MD 20892. NR 33 TC 48 Z9 51 U1 0 U2 0 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 40 WEST 20TH STREET, NEW YORK, NY 10011-4211 SN 0022-3751 J9 J PHYSIOL-LONDON JI J. Physiol.-London PD MAR 1 PY 1997 VL 499 IS 2 BP 351 EP 359 PG 9 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA WR165 UT WOS:A1997WR16500007 PM 9080365 ER PT J AU Bachus, SE Hyde, TM Herman, MM Egan, MF Kleinman, JE AF Bachus, SE Hyde, TM Herman, MM Egan, MF Kleinman, JE TI Abnormal cholecystokinin mRNA levels in entorhinal cortex of schizophrenics SO JOURNAL OF PSYCHIATRIC RESEARCH LA English DT Review ID NUCLEUS-ACCUMBENS NEURONS; CEREBRAL BLOOD-FLOW; DORSOLATERAL PREFRONTAL CORTEX; GLUTAMIC-ACID DECARBOXYLASE; CULTURED CORTICAL-NEURONS; HYDROXYLASE MESSENGER-RNA; EXCITATORY NERVE-ENDINGS; MEDIAL TEMPORAL-LOBE; GABA UPTAKE SITES; HIPPOCAMPAL-FORMATION AB Limbic cortical regions, including anterior cingulate cortex (ACC), prefrontal cortex (PFC) and entorhinal cortex (ERC), have been implicated in the neuropathology of schizophrenia. Glutamate projection neurons connect these limbic cortical regions to each other, as well as to the terminal fields of the striatal/accumbens dopamine neurons. Subsets of these glutamate projection neurons, and of the GABA interneurons in cortex, contain the neuropeptide cholecystokinin (CCK). In an effort to study the limbic cortical glutamate projection neurons and GABA interneurons in schizophrenia, we have measured CCK mRNA with in situ hybridization histochemistry in postmortem samples of dorsolateral (DL)PFC, ACC and ERC of seven schizophrenics, nine nonpsychotic suicides and seven normal controls. CCK mRNA is decreased in ERC (especially layers iii-vi) and subiculum in schizophrenics relative to controls. Cellular analysis indicates that there is a decrease in density of CCK mRNA in labelled neurons. In so far as ERC CCK mRNA is not reduced in rats treated chronically with haloperidol, this decrease in schizophrenics does not appear to be related to neuroleptic treatment. In contrast, in DLPFC, where schizophrenics do not differ from normals, the suicide victims have elevated CCK mRNA (especially in layers v and vi), and increased cellular density of CCK mRNA, relative to both normals and schizophrenics. These results lend further support for the involvement of ERC and hippocampus in schizophrenia, suggesting that neurons that utilize CCK may be particularly important. Similarly, an increase in CCK mRNA levels in the PFC of suicides adds to a growing body of evidence implicating this structure in this pathological state. In so far as CCK is co-localized with GABA or glutamate in cortical neurons, both of these neuronal populations need to be studied further in schizophrenia and suicide. (C) 1997 Elsevier Science Ltd. RP Bachus, SE (reprint author), NIMH, ST ELIZABETHS HOSP,CTR NEUROSCI,NEUROPATHOL SECT, CLIN BRAIN DISORDERS BRANCH,IRP, NIH, WASHINGTON, DC 20032 USA. NR 166 TC 49 Z9 51 U1 1 U2 2 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0022-3956 J9 J PSYCHIATR RES JI J. Psychiatr. Res. PD MAR-APR PY 1997 VL 31 IS 2 BP 233 EP 256 DI 10.1016/S0022-3956(96)00041-6 PG 24 WC Psychiatry SC Psychiatry GA XP637 UT WOS:A1997XP63700006 PM 9278188 ER PT J AU Boyer, GS Templin, DW Bowler, A Lawrence, RC Heyse, SP Everett, DF CornoniHuntley, JC Goring, WP AF Boyer, GS Templin, DW Bowler, A Lawrence, RC Heyse, SP Everett, DF CornoniHuntley, JC Goring, WP TI Class I HLA antigens in spondyloarthropathy: Observations in Alaskan Eskimo patients and controls SO JOURNAL OF RHEUMATOLOGY LA English DT Article DE MHC class I antigens; HLA-B27; spondyloarthropathy; ankylosing spondylitis; reactive arthritis ID ANKYLOSING-SPONDYLITIS; REITERS-SYNDROME; RHEUMATOID-ARTHRITIS; HLA-B27; HOMOZYGOSITY; PREVALENCE; POPULATION; CRITERIA; CLASSIFICATION; INDIANS AB Objective. To assess the role of HLA-B27 and other class I histocompatibility antigens in overall risk and clinical manifestations of spondyloarthropathy (SpA) in Alaskan Eskimos, Methods. Class I antigens were studied in 104 patients with SpA and in 111 controls. The frequencies of HLA-A, B, and Cw antigens were determined in patients with SpA with various clinical manifestations and compared to frequencies observed in controls. Results. Only HLA-B27 differed significantly in cases and controls. Except for B27, no association of particular antigens with specific syndromes or disease features was found. Patients with B27 had more extraarticular manifestations than patients who lacked B27 antigen, Patients putatively homozygous for B27 did not appear to have more severe disease than those who were heterozygotic. B27 was most closely associated with ankylosing spondylitis [odds ratio (OR)=210], less so with reactive arthritis (OR=12.9) and undifferentiated SpA (OR=4.6), Conclusion. Observations in other population groups that implicated B27 cross reactive group (CREG) and other A, B, and Cw antigens as risk factors for developing SpA were not confirmed in Alaskan Eskimos. Nor were CREG or other B antigens either alone or in combination with B27 associated with specific clinical syndromes. Only HLA-B27 was strongly associated with disease and with extraarticular manifestations. C1 NIAMSD,BETHESDA,MD. NEI,BETHESDA,MD 20892. DUKE UNIV,SCH PUBL HLTH,NIAID,DURHAM,NC 27706. UNIV ARIZONA,TUCSON,AZ 85721. NR 40 TC 10 Z9 10 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 1997 VL 24 IS 3 BP 500 EP 506 PG 7 WC Rheumatology SC Rheumatology GA WM001 UT WOS:A1997WM00100016 PM 9058656 ER PT J AU Fabsitz, RR Sholinsky, P Goldberg, J AF Fabsitz, RR Sholinsky, P Goldberg, J TI Correlates of sleep problems among men: The Vietnam Era Twin Registry SO JOURNAL OF SLEEP RESEARCH LA English DT Article DE behaviour; insomnia; lifestyle; morbidity; prevalence; race; sleep ID VET REGISTRY; PREVALENCE; DISTURBANCES; POPULATION; DISORDERS; INSOMNIA AB The Vietnam Era Twin (VET) Registry includes 14 800 male twins born 1939-55 and in military service in 1964-75. A mailed health survey including the Jenkins Sleep Questionnaire was sent to 11 959 members and 8870 (74.2%) provided responses on the frequency of sleep problems in the previous month. Prevalence of those experiencing conditions at least 1 day per month was 67.2% for waking often, 61.5% for waking tired/worn out, 48.1% for trouble falling asleep and 48.6% for awakening early. Ordinal logistic regression analysis was used to estimate sleep problems from demographic, behaviour and lifestyle characteristics, and morbid conditions. Black (vs. white) race, older age, church/religious group participation, social support, employment, cigarette smoking, light physical activity, and strenuous physical activity were associated with lower risk of one or more sleep problems. Eleven morbid conditions with a prevalence of 1% or more, coffee consumption, heavy alcohol consumption, and Framingham Type A behaviour pattern were associated with a higher risk of sleep problems. These analyses suggest that sleep problems may be one of the mechanisms relating reduced quality of life to many physical and behavioural characteristics. Fortunately, a number of the risk factors associated with sleep problems are lifestyle characteristics which, if modified, may reduce sleep problems. C1 UNIV ILLINOIS,SCH PUBL HLTH,EPIDEMIOL BIOSTAT PROGRAM,CHICAGO,IL. EDWARD HINES JR VET ADM HOSP,VET ADM COOPERAT STUDIES PROGRAM,HINES,IL 60141. NHLBI,FIELD STUDIES & CLIN EPIDEMIOL SCI RES GRP,DIV EPIDEMIOL & CLIN APPLICAT,BETHESDA,MD. NR 22 TC 32 Z9 32 U1 0 U2 7 PU BLACKWELL SCIENCE LTD PI OXFORD PA P O BOX 88, OSNEY MEAD, OXFORD, OXON, ENGLAND OX2 0NE SN 0962-1105 J9 J SLEEP RES JI J. Sleep Res. PD MAR PY 1997 VL 6 IS 1 BP 50 EP 56 DI 10.1046/j.1365-2869.1997.00026.x PG 7 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA WU256 UT WOS:A1997WU25600007 PM 9125699 ER PT J AU Heishman, SJ Kozlowski, LT Henningfield, JE AF Heishman, SJ Kozlowski, LT Henningfield, JE TI Nicotine addiction: Implications for public health policy SO JOURNAL OF SOCIAL ISSUES LA English DT Article ID LOW-YIELD CIGARETTES; DRUG-USE; SMOKELESS TOBACCO; SMOKING URGES; ALCOHOL; DEPENDENCE; ABSTINENCE; KINETICS; CAFFEINE; IMAGERY AB Although the morbidity and mortality caused by cigarette smoking occur in adulthood, the initiation of tobacco use and the development of nicotine addiction typically occur during adolescence. The purpose of this paper is to examine the determinants of nicotine addiction, focusing on the development of addiction in youth, and to explore implications for public health policy. An understanding of the pharmacological and nonpharmacological factors that determine the course of nicotine addiction is critical in developing rational policies regarding tobacco products. The Food and Drug Administration's rule to regulate cigarettes and smokeless tobacco products is discussed. The fact that smokers typically make the transition from casual use To nicotine addiction during adolescence argues for developing and implementing effective prevention efforts and smoking cessation treatment programs that are youth-oriented. C1 NIDA, Addict Res Ctr, Biol Dependence Sect, Baltimore, MD 21224 USA. Penn State Univ, Coll Hlth & Human Dev, University Pk, PA 16802 USA. Johns Hopkins Univ, Sch Med, Dept Psychiat & Behav Sci, Baltimore, MD 21205 USA. RP Heishman, SJ (reprint author), NIDA, Addict Res Ctr, Biol Dependence Sect, POB 5180, Baltimore, MD 21224 USA. EM sheish@irp.nida.nih.gov NR 82 TC 8 Z9 8 U1 2 U2 3 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0022-4537 EI 1540-4560 J9 J SOC ISSUES JI J. Soc. Issues PD SPR PY 1997 VL 53 IS 1 BP 13 EP 33 DI 10.1111/0022-4537.319973 PG 21 WC Social Issues; Psychology, Social SC Social Issues; Psychology GA ZN064 UT WOS:000073605100003 ER PT J AU Ashery, RS Wild, J Zhao, ZX Rosenshine, N Young, P AF Ashery, RS Wild, J Zhao, ZX Rosenshine, N Young, P TI The WHEEL project - Women Helping to Empower and Enhance Lives SO JOURNAL OF SUBSTANCE ABUSE TREATMENT LA English DT Article DE HIV/AIDS; female sexual partners; women; HIV/AIDS education; drug abuse AB The Women Helping to Empower and Enhance Lives (WHEEL) Project focused on female sexual partners of injection drug users (IDUs). It was conducted in five sires, three within and two outside the continental United States. The study's two main intervention goals were to (a) reduce HIV-related sexual risk behaviors, and (b) reduce HIV-related drug risk behaviors. The Project also featured needs assessment, planning, and staff training components. Baseline data were collected on 2,794 women, which made this the largest study of noninjecting female sexual partners of IDUs in the United Stares. Six-month follow-lip data If ere obtained on 1,953 women. The Wheel Project tested two interventions: an individual intervention and a group intervention. The study found significant reductions in drug use and risky sexual behaviors for the 6-month follow-up sample for both interventions. These changes were substantial and point to the viability of both interventions for this population of sexual partners of injection drug users. (C) 1997 Elsevier Science Inc. C1 NIDA,PREVENT RES BRANCH,ROCKVILLE,MD. NOVA RES CO,BETHESDA,MD. FU NIDA NIH HHS [N01DA-0-8405] NR 8 TC 7 Z9 7 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0740-5472 J9 J SUBST ABUSE TREAT JI J. Subst. Abus. Treat. PD MAR-APR PY 1997 VL 14 IS 2 BP 113 EP 121 DI 10.1016/S0740-5472(96)00129-8 PG 9 WC Psychology, Clinical; Substance Abuse SC Psychology; Substance Abuse GA XN904 UT WOS:A1997XN90400002 PM 9258855 ER PT J AU Vitiello, B Stoff, DM AF Vitiello, B Stoff, DM TI Subtypes of aggression and their relevance to child psychiatry SO JOURNAL OF THE AMERICAN ACADEMY OF CHILD AND ADOLESCENT PSYCHIATRY LA English DT Article DE aggression; subtypes; children ID DISRUPTIVE BEHAVIOR DISORDERS; CEREBROSPINAL-FLUID MONOAMINE; CONDUCT DISORDER; HOSTILE AGGRESSION; OVERT; METABOLITES; IMPULSIVITY; PATTERNS; HUMANS; SCALE AB Objective: To review the evidence for qualitatively distinct subtypes of human aggression as they relate to childhood psychopathology. Method: Critical review of the pertinent literature. Results: In humans, as well as in animals, the term aggression encompasses a variety of behaviors that are heterogeneous for clinical phenomenology and neurobiological features. No simple extrapolation of animal subtypes to humans is possible, mainly because of the impact of complex cultural variables on behavior. On the whole, research into subtypes of human aggression has been rather limited. A significant part of it has been conducted in children. Clinical observation, experimental paradigms in the laboratory, and cluster/factor-analytic statistics have all been used in an attempt to subdivide aggression. A consistent dichotomy can be identified between an impulsive-reactive-hostile-affective subtype and a controlled-proactive-instrumental-predatory subtype. Although good internal consistency and partial descriptive validity have been shown, these constructs still need full external validation, especially regarding their predicting power of comorbidity, treatment response, and longterm prognosis. Conclusions: Our understanding and treatment of children and adolescents with aggressive behavior can benefit from research on subtypes of aggression. The differentiation between the impulsive-affective and controlled-predatory subtype as qualitatively different forms of aggressive behavior has emerged as the most promising construct. Specific therapeutic hypotheses could be tested in this context and contribute to a full validation of these concepts. C1 NIMH,MOOD ANSIETY & PERSONAL DISORDERS RES BRANCH,DIV CLIN & TREATMENT RES,ROCKVILLE,MD 20857. RP Vitiello, B (reprint author), NIMH,CHILD & ADOLESCENT DISORDERS RES BRANCH,ROOM 18C-17,5600 FISHERS LANE,ROCKVILLE,MD 20857, USA. NR 62 TC 207 Z9 208 U1 5 U2 23 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0890-8567 J9 J AM ACAD CHILD PSY JI J. Am. Acad. Child Adolesc. Psychiatr. PD MAR PY 1997 VL 36 IS 3 BP 307 EP 315 DI 10.1097/00004583-199703000-00008 PG 9 WC Psychology, Developmental; Pediatrics; Psychiatry SC Psychology; Pediatrics; Psychiatry GA WK274 UT WOS:A1997WK27400008 PM 9055510 ER PT J AU Casey, BJ Castellanos, FX Giedd, JN Marsh, WL Hamburger, SD Schubert, AB Vauss, YC Vaituzis, AC Dickstein, DP Sarfatti, SE Rapoport, JL AF Casey, BJ Castellanos, FX Giedd, JN Marsh, WL Hamburger, SD Schubert, AB Vauss, YC Vaituzis, AC Dickstein, DP Sarfatti, SE Rapoport, JL TI Implication of right frontostriatal circuitry in response inhibition and attention-deficit/hyperactivity disorder SO JOURNAL OF THE AMERICAN ACADEMY OF CHILD AND ADOLESCENT PSYCHIATRY LA English DT Article DE attention-deficit/hyperactivity disorder; basal ganglia; prefrontal cortex; response inhibition ID DEFICIT HYPERACTIVITY DISORDER; DISRUPTIVE BEHAVIOR DISORDERS; PSYCHIATRIC STATUS; QUANTITATIVE MORPHOLOGY; SPATIAL ATTENTION; BRAIN MORPHOLOGY; CORPUS-CALLOSUM; CHILDREN; PREVALENCE; CORTEX AB Objective: To examine the relation between specific frontostriatal structures (prefrontal cortex and basal ganglia) and response inhibition deficits observed in attention-deficit/hyperactivity disorder (ADHD). Method: Children with ADHD and age-matched normal controls were scanned using magnetic resonance imaging (MRI) and tested on three response inhibition tasks. Behavioral performance was correlated with MRI-based anatomical measures of frontostriatal circuitry (prefrontal cortex and basal ganglia) implicated in ADHD. Results: First, significant differences in performance by children with ADHD and normal volunteers were observed on all three response inhibition tasks. Second, performance on these tasks correlated only with those anatomical measures of frontostriatal circuitry observed to be abnormal in children with ADHD (e.g., the region of the prefrontal cortex, caudate, and globus pallidus, but not the putamen) in the authors' previous study. Third, significant correlations between task performance and anatomical measures of the prefrontal cortex and caudate nuclei were predominantly in the right hemisphere, supporting a role of right frontostriatal circuitry in response inhibition and ADHD. Conclusion: The data suggest a role of the right prefrontal cortex in suppressing responses to salient, but otherwise irrelevant events while the basal ganglia appear to be involved in executing these behavioral responses. C1 NIMH,CHILD PSYCHIAT BRANCH,ROCKVILLE,MD 20857. RP Casey, BJ (reprint author), UNIV PITTSBURGH,MED CTR,WESTERN PSYCHIAT INST & CLIN,E-519,3811 OHARA ST,PITTSBURGH,PA 15213, USA. RI Giedd, Jay/A-3080-2008; Giedd, Jay/B-7302-2012; Giedd, Jay/J-9644-2015; Dickstein, Daniel/L-3210-2016 OI Giedd, Jay/0000-0003-0827-3460; Giedd, Jay/0000-0003-2002-8978; Dickstein, Daniel/0000-0003-1647-5329 NR 53 TC 523 Z9 529 U1 11 U2 28 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0890-8567 J9 J AM ACAD CHILD PSY JI J. Am. Acad. Child Adolesc. Psychiatr. PD MAR PY 1997 VL 36 IS 3 BP 374 EP 383 DI 10.1097/00004583-199703000-00016 PG 10 WC Psychology, Developmental; Pediatrics; Psychiatry SC Psychology; Pediatrics; Psychiatry GA WK274 UT WOS:A1997WK27400016 PM 9055518 ER PT J AU Lish, KM Washenik, K Yancey, KB Yee, C Rico, MJ AF Lish, KM Washenik, K Yancey, KB Yee, C Rico, MJ TI Anti-epiligrin cicatricial pemphigoid in a patient with HIV SO JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY LA English DT Article ID AIDS-RELATED COMPLEX; INFECTION; AUTOANTIBODIES; AUTOIMMUNE; DISEASES C1 NEW YORK VET AFFAIRS MED CTR,DERMATOL SERV,NEW YORK,NY 10010. NYU,DEPT DERMATOL,NEW YORK,NY 10016. NATL CANC INST,DERMATOL BRANCH,NIH,BETHESDA,MD. NR 15 TC 20 Z9 20 U1 0 U2 0 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 SN 0190-9622 J9 J AM ACAD DERMATOL JI J. Am. Acad. Dermatol. PD MAR PY 1997 VL 36 IS 3 BP 486 EP 488 DI 10.1016/S0190-9622(97)80237-X PN 1 PG 3 WC Dermatology SC Dermatology GA WM433 UT WOS:A1997WM43300026 PM 9091490 ER PT J AU Slavkin, HC AF Slavkin, HC TI What's in a tooth? SO JOURNAL OF THE AMERICAN DENTAL ASSOCIATION LA English DT Article RP Slavkin, HC (reprint author), NIDR,31 CTR DR,MSC 2290,BLDG 31,ROOM 2C39,BETHESDA,MD 20892, USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU AMER DENTAL ASSN PI CHICAGO PA 211 E CHICAGO AVE, CHICAGO, IL 60611 SN 0002-8177 J9 J AM DENT ASSOC JI J. Am. Dent. Assoc. PD MAR PY 1997 VL 128 IS 3 BP 366 EP 369 PG 4 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA WM659 UT WOS:A1997WM65900024 PM 9066224 ER PT J AU Young, Y Brant, L German, P Kenzora, J Magaziner, J AF Young, Y Brant, L German, P Kenzora, J Magaziner, J TI A longitudinal examination of functional recovery among older people with subcapital hip fractures SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Article ID ELDERLY PATIENTS; EFFECTS MODELS; HEALTH; CARE AB OBJECTIVE: Few studies have examined the time-dependent change in functional recovery along with the factors that affect the change among older hip fracture patients. The focus of this study is to examine the predictors of functional recovery in community-dwelling older people with subcapital fractures using longitudinal data analysis methods. DESIGN: A 1-year prospective study. Information was obtained through structured interviews following surgery and at 2, 6, and 12 months after hospital discharge and from medical chart review. SETTING AND PATIENTS: The sample consisted of 312 community-dwelling older adults, admitted to one of the seven Baltimore area hospitals with a subcapital fracture, who received either internal fixation or hemiarthroplasty. RESULTS: The longitudinal data analysis using mixed-effects regression indicates that time and prefracture physical activities of daily living (PADL) had a significant association with PADL functional recovery over the course of 1 year. Among those 85 years and older, those who were disoriented after surgery had poorer PADL functional recovery over time than those who were not disoriented. Also, recovery in instrumental activities of daily living (IADL) was associated significantly with time, prefracture IADL function, unsteady gait prefracture, hospital length of stay, and discharge to an institution. The type of surgical procedure performed was not associated significantly with either PADL or IADL functional recovery. CONCLUSIONS: The factors that are related to functional recovery in this study shed light on the complexity of the recovery process in hip fracture patients. The rate of recovery in postsurgical PADL and IADL function is not constant over time; postsurgical IADL function among disoriented patients (without dementia) continues to deteriorate over time compared with the nondisoriented group; this difference in trends of deterioration on IADL function is most profound in the oldest-old aged group, those 85 and older. The types of surgical procedure performed was not significantly associated with postsurgical functional recovery. C1 UNIV MARYLAND,SCH MED,BALTIMORE,MD 21201. NIA,BALTIMORE,MD 21224. RP Young, Y (reprint author), JOHNS HOPKINS UNIV,SCH HYG & PUBL HLTH,HLTH SERV RES & DEV CTR,624 N BROADWAY,BALTIMORE,MD 21205, USA. FU AHRQ HHS [HS06658]; NIA NIH HHS [AG06322]; NICHD NIH HHS [HD0073] NR 34 TC 70 Z9 70 U1 1 U2 3 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 1997 VL 45 IS 3 BP 288 EP 294 PG 7 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA WL773 UT WOS:A1997WL77300005 PM 9063273 ER PT J AU Cohen, RM Andreason, PJ Sunderland, T AF Cohen, RM Andreason, PJ Sunderland, T TI The ratio of mesial to neocortical temporal lobe blood flow as a predictor of dementia SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Article ID POSITRON EMISSION TOMOGRAPHY; ALZHEIMERS-DISEASE; COMPUTED-TOMOGRAPHY; F-18 CYCLOFOXY; SYNAPSE LOSS; PERFORMANCE; METABOLISM; PERFUSION; CORRELATE; BINDING AB OBJECTIVE: The hypothesis tested was that an increased ratio of cerebral blood flow (rCBF) in the mesocortical temporal lobe to that of the neocortical temporal lobe (MES/NEO ratio) would be related to clinical measures of dementia severity and would help distinguish Alzheimer's patients from normal controls. DESIGN: The rCBF of nine Alzheimer's patients (5 males and 4 females; age = 65.9 +/- 6.0 years, range 55-71; Folstein Mini-Mental Status Examination = 18.6 +/- 7.4, range 9-28) and 10 age-matched normal controls (7 males, 3 females; age = 66.0 +/- 5.7 years, range 58-75) was determined by positron emission tomography (PET) using H(2)15O and the method of Alpert et al.(25) RESULTS: Alzheimer's disease patients had a significantly higher MES/NEO ratio (1.19 +/- .17) than the age-matched normal controls (.854 +/- 14; t = .-4.74, df = 17, P =.0002). Using a MES/NEO ratio of 1 as the cutoff point for discrimination between Alzheimer's patients and normal controls, the ratio demonstrated 100% sensitivity (no. of correctly identified Alzheimer's patients/no. of Alzheimer's patients) and 90% specificity (no. of correctly identified unaffected subects/no. of unaffected subjects). Further, those patients with the highest MES/NEO ratios had the lowest overall measures of cognitive function (Folstein Mini-Mental Status Examination: r = -.75, P < .02, 1-tail; Mattis Dementia Rating Scale: r = -0.655, P =.028, 1-tail) scores. CONCLUSIONS: The findings are consistent with other in vivo and postmortem studies, suggesting that functional and structural changes of the lateral temporal lobe in Alzheimer's disease occur relatively early in the disease process and appear to be distinguishable from those changes accompanying normal aging. In contrast, the memory loss and pathology of the mesial temporal lobe that is characteristic of the early stages of Alzheimer's patients do not appear to be associated with a reduction in cerebral blood flow in the resting Alzheimer's patient. Nevertheless, the clinical significance of the results must await findings of longitudinal studies of larger numbers of Alzheimer's patients and controls. C1 NIMH,SECT GERIATR PSYCHIAT,CLIN SCI LAB,NIH,BETHESDA,MD 20892. RP Cohen, RM (reprint author), NIMH,CEREBRAL METAB LAB,NIH,BLDG 36,ROOM 1A05,36 CONVENT DR,MSC 4030,BETHESDA,MD 20892, USA. NR 38 TC 10 Z9 10 U1 2 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 1997 VL 45 IS 3 BP 329 EP 333 PG 5 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA WL773 UT WOS:A1997WL77300011 PM 9063279 ER PT J AU Legler, JM Ryan, LM AF Legler, JM Ryan, LM TI Latent variable models for teratogenesis using multiple binary outcomes SO JOURNAL OF THE AMERICAN STATISTICAL ASSOCIATION LA English DT Article DE item response theory; random effects; teratology ID REPEATED CATEGORICAL MEASUREMENTS; EM ALGORITHM; LIKELIHOOD; TESTS AB Multiple outcomes are commonly measured in:the study of birth defects. The reason is that most teratogens do not cause a single, uniquely defined defect, but rather result in a range of effects, including major malformations, minor anomalies, and deficiencies in birth weight, length and head circumference. The spectrum of effects associated with a particular teratogen is sometimes described as a ''syndrome.'' In this article we develop a latent variable model to characterize exposure effects on multiple binary outcomes. Not only does the method allow comparisons of control and exposed infants with respect to multiple outcomes, but it also provides a measure of the ''severity'' of each child's condition. Data from a study of the teratogenic effects of anticonvulsants illustrate our results. C1 HARVARD UNIV, SCH PUBL HLTH, DEPT BIOSTAT, BOSTON, MA 02115 USA. DANA FARBER CANC INST, BOSTON, MA 02115 USA. RP Legler, JM (reprint author), NIH, BETHESDA, MD 20952 USA. RI Ryan, Louise/A-4562-2009 OI Ryan, Louise/0000-0001-5957-2490 NR 34 TC 41 Z9 42 U1 2 U2 2 PU AMER STATISTICAL ASSOC PI ALEXANDRIA PA 732 N WASHINGTON ST, ALEXANDRIA, VA 22314-1943 USA SN 0162-1459 EI 1537-274X J9 J AM STAT ASSOC JI J. Am. Stat. Assoc. PD MAR PY 1997 VL 92 IS 437 BP 13 EP 20 DI 10.2307/2291445 PG 8 WC Statistics & Probability SC Mathematics GA WL265 UT WOS:A1997WL26500002 ER PT J AU Couchman, GM Bentley, R Tsao, MS Raszmann, K McLachlan, JA Walmer, DK AF Couchman, GM Bentley, R Tsao, MS Raszmann, K McLachlan, JA Walmer, DK TI p53(lyn) and p56(lyn): A new signaling pathway in human endometrium and endometrial adenocarcinomas SO JOURNAL OF THE SOCIETY FOR GYNECOLOGIC INVESTIGATION LA English DT Article DE endometrium; lyn; endometrial adenocarcinoma; protein tyrosine kinase; Src family ID PROTEIN-TYROSINE KINASE; FAMILY; ASSOCIATION; EXPRESSION; RECEPTOR; CANCER; CELLS; RNA; LYN AB OBJECTIVE: To identify specific tyrosine kinases that are involved in endometrial signaling and to study their in vivo expression in normal and abnormal endometrium. We hypothesized that proteins that are differentially expressed would be more likely to be important in regulated cellular events. METHODS: Complementary DNA libraries, constructed from human secretory (n = 5) and proliferative (n = 5) endometrial specimens, were screened with a polyclonal anti-phosphotyrosine antibody. Positive clones were sequenced and screened for differential expression using immunoblotting and Northern analysis of samples from proliferative and secretory endometrium. The expression of one identified clone, lyn, a Src family member, was characterized further with Western and Northern blot analyses and immunolocalization. RESULTS: One protein identified by the above method was lyn, a member of the src family of protein tyrosine kinases, never before described in the human endometrium. Western blot analysis revealed two forms of lyn protein, p53(lyn) and p56(lyn), that were most abundant in the late secretory phase. Immunohistochemistry demonstrated uniform protein expression by all cells in normal glandular epithelium and suggested a correlation between lyn protein expression and cell differentiation for human endometrial adenocarcinomas, with markedly elevated levels noted in poorly differentiated adenocarcinomas compared with well-differentiated tumors (n = 3). Northern hybridization confirmed the presence of the expected 3.5-kb lyn transcript in normal and abnormal endometrium. CONCLUSIONS: Our data demonstrate that human cDNA libraries created from different phases of the menstrual cycle can be screened successfully using anti-phosphotyrosine antibodies to identify differentially expressed protein tyrosine kinases. Although p53(lyn) and p56(lyn) expression has been thought of as a predominantly lymphoid-specific tyrosine kinase, we show prominent expression of lyn protein and mRNA by normal and malignant epithelium of the human endometrium, suggesting a role in endometrial signaling and human reproduction. Copyright (C) 1997 by the Society for Gynecologic Investigation. C1 DUKE UNIV,MED CTR,DEPT PATHOL,DURHAM,NC 27710. MONTREAL GEN HOSP,DEPT PATHOL,MONTREAL,PQ H3G 1A4,CANADA. NIEHS,REPROD & DEV TOXICOL LAB,RES TRIANGLE PK,NC 27709. TULANE UNIV,DEPT PHARMACOL,TULANE XAVIER CTR BIOENVIRONM RES,NEW ORLEANS,LA 70118. RP Couchman, GM (reprint author), DUKE UNIV,MED CTR,DEPT OBSTET & GYNECOL,BOX 3143,DURHAM,NC 27710, USA. NR 21 TC 3 Z9 3 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 1071-5576 J9 J SOC GYNECOL INVEST JI J. Soc. Gynecol. Invest. PD MAR-APR PY 1997 VL 4 IS 2 BP 103 EP 109 DI 10.1016/S1071-5576(97)00011-7 PG 7 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA WT157 UT WOS:A1997WT15700010 PM 9101470 ER PT J AU Tang, Y Hugin, AW Giese, NA Gabriele, L Chattopadhyay, SK Fredrickson, TN Kagi, D Hartley, JW Morse, HC AF Tang, Y Hugin, AW Giese, NA Gabriele, L Chattopadhyay, SK Fredrickson, TN Kagi, D Hartley, JW Morse, HC TI Control of immunodeficiency and lymphoproliferation in mouse AIDS: Studies of mice deficient in CD8(+) T cells or perforin SO JOURNAL OF VIROLOGY LA English DT Article ID RETROVIRUS-INDUCED IMMUNODEFICIENCY; MURINE LEUKEMIA-VIRUS; DEFECTIVE RETROVIRUS; SYNDROME MAIDS; IN-VIVO; EXPRESSION; RESISTANCE; SUSCEPTIBILITY; DISEASE; STRAINS AB CD8(+) T cells were previously shown to be important in preventing lymphoproliferation and immunodeficiency following infection of murine AIDS (MAIDS)-resistant mice with the LP-BM5 mixture of murine leukemia viruses. To further evaluate the mechanisms contributing to MAIDS resistance, we studied mice lacking CD8(+) T cells or deficient in perforin due to knockout of the beta 2-microglobulin (beta 2M) or perforin gene, respectively, In contrast to wild-type, MAIDS-resistant controls, B10.A mice homozygous for the beta 2M mutation and B10.D2 mice homozygous for the perforin mutation were diagnosed as having MAIDS by 5 to 8 weeks after infection bg the criteria of lymphoproliferation, impaired proliferative responses to mitogens, and changes in cell populations as judged by histopathology and flow cytometry. Unexpectedly, there was no progression of lymphoproliferation through 24 weeks, even though immune functions were severely compromised. Expression of the defective virus responsible for MAIDS was enhanced in spleens of the knockouts in comparison with wild-type mice. These results demonstrate that perforin-dependent functions of CD8(+) T cells contribute to MAIDS resistance but that other, non-CD8-dependent mechanisms are of equal or greater importance. C1 NIAID,IMMUNOPATHOL LAB,NIH,BETHESDA,MD 20892. NCI,REGISTRY EXPT CANC,NIH,BETHESDA,MD 20892. UNIV HOSP GENEVA,DEPT DERMATOL,GENEVA,SWITZERLAND. UNIV ZURICH,DEPT PATHOL,INST EXPT IMMUNOL,CH-8006 ZURICH,SWITZERLAND. OI Morse, Herbert/0000-0002-9331-3705 FU NIAID NIH HHS [N01-AI-45203] NR 31 TC 15 Z9 15 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 1997 VL 71 IS 3 BP 1808 EP 1813 PG 6 WC Virology SC Virology GA WH172 UT WOS:A1997WH17200009 PM 9032310 ER PT J AU Low, KG Dorner, LF Fernando, DB Grossman, J Jeang, KT Comb, MJ AF Low, KG Dorner, LF Fernando, DB Grossman, J Jeang, KT Comb, MJ TI Human T-cell leukemia virus type 1 tax releases cell cycle arrest induced by p16(INK4a) SO JOURNAL OF VIROLOGY LA English DT Article ID NF-KAPPA-B; I TAX; DNA-BINDING; TRANSCRIPTION FACTOR; TRANSACTIVATOR TAX; RESPONSIVE ELEMENT; PROTEIN; GENE; EXPRESSION; INHIBITION AB The human T-cell leukemia virus type 1 (HTLV-1) Tax oncoprotein causes cellular transformation by deregulating important cellular processes such as DNA repair, transcription, signal transduction, proliferation, and growth. Although it is clear that normal cell cycle control is deregulated during HTLV-1-induced cellular transformation, the effects of Tax on cell cycle control are not well understood. Flow cytometric analyses of human T cells indicate that cell cycle arrest in late G(1), at or before the G(1)/S restriction point, by p16(INK4a) is relieved by Tax. Furthermore, Tax-dependent stimulation of 5-bromo-2'-deoxyuridine incorporation and transcriptional activation is inhibited by p16(INK4a) This result suggests that p16(INK4a) is able to block Tax-dependent stimulation of DNA synthesis and cell cycle progression into S phase, In vitro binding assays with recombinant glutathione S-transferase fusion proteins and [S-35] methionine-labeled proteins indicate that Tax binds specifically with p16(INK4a) but not with either p21(cip1) or p27(kip1), Furthermore, sequential immunoprecipitation assays with specific antisera and [S-35] methionine-labeled cell lysates subsequent to coexpression with Tax and p16(INK4a) indicate that the mo proteins form complexes in vivo. Immunocomplex kinase assays with cyclin-dependent kinase 4 antiserum indicate that Tax blocks the inhibition of cdk4 kinase activity by p16(INK4a). This study identifies p16(INK4a) as a novel cellular target for Tax and suggests that the inactivation of p16(INK4a) function is a mechanism of cell cycle deregulation by Tax. C1 NIAID,MOL MICROBIOL LAB,BETHESDA,MD 20892. RP Low, KG (reprint author), NEW ENGLAND BIOLABS INC,LAB CELL SIGNALING,32 TOZER RD,BEVERLY,MA 01915, USA. RI Jeang, Kuan-Teh/A-2424-2008 FU NIDA NIH HHS [DA00151, DA05706, DA07745] NR 45 TC 115 Z9 115 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 1997 VL 71 IS 3 BP 1956 EP 1962 PG 7 WC Virology SC Virology GA WH172 UT WOS:A1997WH17200026 PM 9032327 ER PT J AU Wonderling, RS Owens, RA AF Wonderling, RS Owens, RA TI Binding sites for adeno-associated virus rep proteins within the human genome SO JOURNAL OF VIROLOGY LA English DT Article ID ADENOASSOCIATED VIRUS; CELLULAR-TRANSFORMATION; TARGETED INTEGRATION; TERMINAL REPEATS; SUPPRESSOR GENE; GROWTH-FACTOR; GADD45 GENE; HUMAN-CELLS; IN-VITRO; DNA AB The Rep proteins of adeno-associated virus type 2 (AAV) are known to bind to Rep recognition sequences (RRSs) in the AAV inverted terminal repeats (ITRs), the AAV p5 promoter, and the preferred AAV integration site in human chromosome 19, called AAVS1. Integration of the AAV genome into AAVS1 appears to be mediated by an interaction between the Rep proteins of AAV and Rep binding sites within the viral genome and the integration Locus. In an attempt to identify potential alternate integration sites, we looked for recognition sites for AAV Rep proteins in the human genome by performing a BLASTN computerized homology search. We used the 16-mer core sequences of the RRSs in the AAV ITRs and AAVS1 separately as query sequences and identified 18 new RRSs in or flanking the genes coding for the following: tyrosine kinase activator protein I (TKA-1); colony stimulating factor-1; insulin-like growth factor binding protein 2 (IGFBP-2); histone H2B.1; basement membrane heparan sulfate proteoglycan, also known as perlecan; the AF-9 gene product, which is invoiced in the chromosomal translocation t (9:11)(p22:q23); the beta(B) subunit of the hormone known as inhibin; interleukin-2 enhancer binding factor; an endoplasmic reticulum-Golgi intermediate compartment resident protein called p63; a global transcription activator (hSNF2L); the beta-actin repair domain; a retinoic acid-inducible factor, also known as midkine; a breast tumor autoantigen; a growth-arrest- and DNA-damage-inducible protein called gadd45; the cyclin-dependent kinase inhibitor called KIP2, which inhibits several G(1) cyclin-cyclin-dependent kinase complexes; and the hereditary breast and ovarian cancer gene (BRAC1). RRSs were also identified in a newly discovered open reading frame on chromosome 10 and in the ERCC1 locus on human chromosome 19. The ability of a maltose binding protein-Rep68 fusion protein to bind to these sequences was confirmed by electrophoretic mobility shift assays. These sites may serve as alternate integration sites for AAV or play a role in Rep-mediated effects on human cells. C1 NIDDK,MOL & CELLULAR BIOL LAB,NIH,BETHESDA,MD 20892. NR 56 TC 36 Z9 36 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 1997 VL 71 IS 3 BP 2528 EP 2534 PG 7 WC Virology SC Virology GA WH172 UT WOS:A1997WH17200094 PM 9032395 ER PT J AU Cooke, A Ludlow, CL Hallett, N Selbie, WS AF Cooke, A Ludlow, CL Hallett, N Selbie, WS TI Characteristics of vocal fold adduction related to voice onset SO JOURNAL OF VOICE LA English DT Article DE adduction; onset; velocity; displacement ID LARYNGEAL AB This study examined whether vocal fold kinematics prior to phonation differed between hard (glottal), normal, or breathy onsets in men and women. Glottal landmarks were identified and digitized from videotape recorded with a rigid laryngoscope during different voice onset types. Significant linear relationships (p less than or equal to 0.0055) were found among onset types on measures of (a) gesture duration when moving from 80% to 20% of maximum distance during adduction, (b) maximum velocity, (c) duration between the completion of adduction and phonation onset, and (d) ratios of maximum velocity to maximum distance between the vocal processes, an estimate of stiffness. The gesture duration was greatest for breathy onsets and least for hard onsets, while the maximum velocity, latency between adduction and phonation onset, and estimated stiffness were greatest for hard onsets and least for breathy onsets. The results suggest that one trajectory seems to be used with increases in gesture duration being accompanied by decreases in articulator stiffness when moving from hard to normal to breathy voice onset types. C1 NIDCD,VOICE & SPEECH SECT,VSLB,NIH,BETHESDA,MD 20892. OI Ludlow, Christy/0000-0002-2015-6171 NR 15 TC 28 Z9 28 U1 0 U2 3 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0892-1997 J9 J VOICE JI J. Voice PD MAR PY 1997 VL 11 IS 1 BP 12 EP 22 DI 10.1016/S0892-1997(97)80019-7 PG 11 WC Otorhinolaryngology SC Otorhinolaryngology GA WM861 UT WOS:A1997WM86100002 PM 9075172 ER PT J AU Roth, GS Kowatch, MA Hengemihle, J Ingram, DK Spangler, EL Johnson, LK Lane, MA AF Roth, GS Kowatch, MA Hengemihle, J Ingram, DK Spangler, EL Johnson, LK Lane, MA TI Effect of age and caloric restriction on cutaneous wound closure in rats and monkeys SO JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL SCIENCES LA English DT Article ID DIETARY RESTRICTION; WISTAR RATS; LONGEVITY; EXERCISE; REPAIR; GROWTH; MODEL AB Cutaneous wounds close more slowly in rats and monkeys as age increases. Calorie restriction of 40% in rats and 30% in monkeys did not significantly affect healing rates, although it did exert a trend toward faster closure. Similarly, voluntary exercise did not significantly alter healing rates in rats. Thus, impaired wound healing appears to be a generalized physiological manifestation of aging, but its possible amelioration by ''anti-aging'' interventions remains to be established. RP Roth, GS (reprint author), NIA,MOL PHYSIOL & GENET SECT,CTR GERONTOL RES,HOPKINS BAYVIEW CTR,LAB CELLULAR & MOL BIOL,BALTIMORE,MD 21224, USA. NR 24 TC 17 Z9 17 U1 0 U2 2 PU GERONTOLOGICAL SOCIETY AMER PI WASHINGTON PA 1275 K STREET NW SUITE 350, WASHINGTON, DC 20005-4006 SN 1079-5006 J9 J GERONTOL A-BIOL JI J. Gerontol. Ser. A-Biol. Sci. Med. Sci. PD MAR PY 1997 VL 52 IS 2 BP B98 EP B102 PG 5 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA WL798 UT WOS:A1997WL79800002 PM 9060966 ER PT J AU Krall, EA DawsonHughes, B Hirst, K Gallagher, JC Sherman, SS Dalsky, G AF Krall, EA DawsonHughes, B Hirst, K Gallagher, JC Sherman, SS Dalsky, G TI Bone mineral density and biochemical markers of bone turnover in healthy elderly men and women SO JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL SCIENCES LA English DT Article ID LINKED N-TELOPEPTIDES; I COLLAGEN; AGE; OSTEOPOROSIS; RESORPTION; IMMUNOASSAY; URINE AB Background. Osteoporosis risk in middle-aged women is twofold greater than that in men, and the difference increases with age. Gender differences in bone mineral density, estimated rates of bone loss, and usefulness of markers of bone metabolism for predicting bone density have not been well described in healthy elders aged 65 and above. The purpose of this cross-sectional analysis was to describe associations of bone mineral density at the hip, spine, and whole body with age, serum osteocalcin, and urinary N-telopeptide crosslinks of Type I collagen in healthy elderly men and women. Methods. A total of 1,087 healthy adults (273 men and 814 women) aged 65 to 87 years were enrolled in a collaborative study at 3 sites: Tufts University (Boston, MA), University of Connecticut Health Center (Farmington, CT), and Creighton University (Omaha, NE). Bone mineral density (BMD) at three regions of the hip, the lumbar spine, and whole body was determined by dual-energy x-ray absorptiometry. Serum osteocalcin was measured by immunoassay, and measurement of N-telopeptide crosslinks (Ntx) in urine was made using an enzyme-linked radioimmunoassay (ELISA). Results. Among women, the age-related decline in BMD at all non-spine skeletal sites was significantly different from zero, with the largest decline seen at the femoral neck (-.0038 g/cm(2)/y, p <.001) and the smallest at the trochanter of the hip (-.0023 g/cm(2)/y, p = .03). Among men, the changes at all non-spine sites were not significant. In both sexes, spine BMD tended to increase with age (men, +.0045 g/cm(2)/y, women, +.0003 g/cm(2)/y). Serum osteocalcin and urinary Ntx were inversely related to BMD at all skeletal sites, but the weakest associations were observed at the spine. Individuals whose values of both osteocalcin and Ntx were in the lowest quartiles of the respective sex-specific distributions had mean femoral neck BMD that were 11% higher than individuals with marker values in the highest quartiles. Conclusions. These findings suggest that age-related decreases in BMD may vary by gender and skeletal site. Determinations of osteocalcin and N-telopeptide crosslinks at a single point in rime may potentially be used as indicators of current bone status, particularly at non-spine skeletal sites. C1 HENRY FORD HLTH SYST,DETROIT,MI. CREIGHTON UNIV,OMAHA,NE 68178. NIA,GERIATR PROGRAM,BETHESDA,MD 20892. UNIV CONNECTICUT,HLTH SCI CTR,FARMINGTON,CT. RP Krall, EA (reprint author), TUFTS UNIV,SCH MED,HUMAN NUTR RES CTR AGING,JEAN MAYER USDA,711 WASHINGTON ST,BOSTON,MA 02111, USA. FU NIA NIH HHS [AG-10353] NR 19 TC 36 Z9 37 U1 0 U2 0 PU GERONTOLOGICAL SOCIETY AMER PI WASHINGTON PA 1275 K STREET NW SUITE 350, WASHINGTON, DC 20005-4006 SN 1079-5006 J9 J GERONTOL A-BIOL JI J. Gerontol. Ser. A-Biol. Sci. Med. Sci. PD MAR PY 1997 VL 52 IS 2 BP M61 EP M67 PG 7 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA WL798 UT WOS:A1997WL79800007 PM 9060971 ER PT J AU Striker, LJ Esposito, C Striker, GE AF Striker, LJ Esposito, C Striker, GE TI Molecular biology of human glomerular diseases SO KIDNEY INTERNATIONAL LA English DT Article ID BASEMENT-MEMBRANE COLLAGEN; DIFFERENTIAL EXPRESSION; IV COLLAGEN; GLOMERULOSCLEROSIS; NEPHROPATHY; CHAINS; ADULT RP Striker, LJ (reprint author), NIDDK,NIH,RENAL CELL BIOL SECT,BLDG 10,ROOM 3N110,10 CTR DR MSC 1268,BETHESDA,MD 20892, USA. NR 13 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 SN 0085-2538 J9 KIDNEY INT JI Kidney Int. PD MAR PY 1997 SU 58 BP S62 EP S65 PG 4 WC Urology & Nephrology SC Urology & Nephrology GA WL569 UT WOS:A1997WL56900014 ER PT J AU Garnett, NL DeHaven, WR AF Garnett, NL DeHaven, WR TI OPRR and USDA animal care response on applicability of the Animal Welfare Regulations and the PHS Policy to dead animals and shared tissues SO LAB ANIMAL LA English DT Editorial Material C1 USDA,RIVERDALE,MD. RP Garnett, NL (reprint author), NIH,DIV ANIM WELF,OFF PROTECT RES RISKS,ROCKVILLE,MD, USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU NATURE PUBLISHING CO PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 SN 0093-7355 J9 LAB ANIMAL JI Lab Anim. PD MAR PY 1997 VL 26 IS 3 BP 21 EP 21 PG 1 WC Veterinary Sciences SC Veterinary Sciences GA WL990 UT WOS:A1997WL99000006 ER PT J AU Stokes, WS AF Stokes, WS TI Animal use alternatives in research and testing: Obligation and opportunity SO LAB ANIMAL LA English DT Article RP Stokes, WS (reprint author), NIEHS,ENVIRONM TOXICOL PROGRAM,POB 12233,RES TRIANGLE PK,NC 27709, USA. NR 25 TC 8 Z9 8 U1 0 U2 2 PU NATURE PUBLISHING CO PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 SN 0093-7355 J9 LAB ANIMAL JI Lab Anim. PD MAR PY 1997 VL 26 IS 3 BP 28 EP 32 PG 5 WC Veterinary Sciences SC Veterinary Sciences GA WL990 UT WOS:A1997WL99000008 ER PT J AU Phillips, KW Goldsworthy, SM Bennett, LM Brownlee, HA Wiseman, RW Davis, BJ AF Phillips, KW Goldsworthy, SM Bennett, LM Brownlee, HA Wiseman, RW Davis, BJ TI Brca1 is expressed independently of hormonal stimulation in the mouse ovary SO LABORATORY INVESTIGATION LA English DT Article ID CYCLIC MOUSE; PREGNANCY; BREAST; GROWTH; GENE AB BRCA1 mutations lead to cancer susceptibility in hormonally dependent tissues such as the ovary and breast. To test the hypothesis that Brca1 expression in the ovary is hormonally regulated and specifically regulated by a functional estrogen receptor, we examined its expression by in situ hybridization in ovaries from virgin, pregnant, and lactating mice, in hypophysectomized mice treated with hormones, and in estrogen-receptor-deficient mice. To determine the relationship between Brca1 expression and cell cycle, serial and adjacent sections of ovary were evaluated for proliferating cell nuclear antigen by immunohistochemistry. Regardless of the model, Brca1 was consistently expressed in granulosa and thecal cells of follicle populations that proliferate independently of hormonal stimulation. Expression was similar in these same follicle populations in the ovaries of estrogen-receptor-deficient mice, in which the lack of this estrogen receptor results in abnormal and incomplete follicular development. Brca1 expression was diminished in the granulosa and thecal cells of hormonally dependent antral follicles. Brca1 expression was also localized to luteal cells of recently formed corpora lutea and corpora lutea associated with pregnancy, but it was greatly diminished in regressing corpora lutea in cycling mice. In all cases, Brca1 expression correlated to S-phase proliferating cell nuclear antigen nuclear staining. Thus, Brca1 expression in the mouse ovary occurs independently of hormonal status and in the absence of a major estrogen receptor-mediated pathway; it is, however, closely correlated with cell cycle in mouse ovarian granulosa, thecal, and luteal cell. C1 NIEHS,RES TRIANGLE PK,NC 27709. PATHOL ASSOCIATES INT,DURHAM,NC. NR 21 TC 31 Z9 32 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 1997 VL 76 IS 3 BP 419 EP 425 PG 7 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA WQ659 UT WOS:A1997WQ65900012 PM 9121124 ER PT J AU Bunn, P Carbone, D Grim, J Harris, C Havemann, K Mabry, M Roth, J Saijo, N Poulsen, HS Stahel, R Takahashi, T AF Bunn, P Carbone, D Grim, J Harris, C Havemann, K Mabry, M Roth, J Saijo, N Poulsen, HS Stahel, R Takahashi, T TI 5th IASLC lung tumor biology workshop, August 13-17, 1996, Ermatingen, Switzerland SO LUNG CANCER LA English DT Editorial Material C1 UNIV COLORADO,CTR CANC,DIV MED ONCOL,DENVER,CO 80262. VANDERBILT UNIV,MED CTR,DIV MED ONCOL,NASHVILLE,TN. UNIV ALABAMA,CTR COMPREHENS CANC,GENE THERAPY PROGRAM,BIRMINGHAM,W MIDLANDS,ENGLAND. NCI,HUMAN CARCINOGENESIS LAB,NIH,BETHESDA,MD 20892. KLINIKUM PHILLIPPS UNIV MARBURG,ABT INNERE MED ONKOL SP HAMATOL ONKOL IMMUNOL,MARBURG,GERMANY. JOHNS HOPKINS UNIV,JOHNS HOPKINS ONCOL CTR,RADIOBIOL LAB,BALTIMORE,MD 21205. UNIV TEXAS,MD ANDERSON CANCER CTR,DEPT THORAC & CARDIOVASC SURG,HOUSTON,TX 77030. NATL CANC CTR,DEPT EXPT THERAPEUT & MED ONCOL,TOKYO,JAPAN. UNIV ZURICH HOSP,DEPT MED,DIV ONCOL,CH-8091 ZURICH,SWITZERLAND. AICHI CANC CTR,RES INST,LAB ULTRASTRUCT RES,NAGOYA,AICHI 464,JAPAN. MRC CTR,CLIN ONCOL & RADIOTHERAPEUT UNIT,CAMBRIDGE,ENGLAND. RP Bunn, P (reprint author), UNIV COPENHAGEN HOSP,SECT RADIAT BIOL,FINSEN CTR,DEPT ONCOL,9 BLEGDAMSVEJ,DK-2100 COPENHAGEN,DENMARK. NR 0 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 1997 VL 16 IS 2-3 BP 239 EP 257 DI 10.1016/S0169-5002(96)00618-6 PG 19 WC Oncology; Respiratory System SC Oncology; Respiratory System GA WW986 UT WOS:A1997WW98600011 PM 9152955 ER PT J AU Shearer, GM AF Shearer, GM TI Th1/Th2 changes in aging SO MECHANISMS OF AGEING AND DEVELOPMENT LA English DT Editorial Material DE Th1/Th2; cytokines; aging ID CELL RP Shearer, GM (reprint author), NCI,EXPT IMMUNOL BRANCH,NIH,BLDG 10,ROOM 4B-17,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 14 TC 123 Z9 127 U1 1 U2 1 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0047-6374 J9 MECH AGEING DEV JI Mech. Ageing. Dev. PD MAR PY 1997 VL 94 IS 1-3 BP 1 EP 5 PG 5 WC Cell Biology; Geriatrics & Gerontology SC Cell Biology; Geriatrics & Gerontology GA WX202 UT WOS:A1997WX20200002 PM 9147355 ER PT J AU Peacock, J Jones, T Tock, C Lutz, R AF Peacock, J Jones, T Tock, C Lutz, R TI An in vitro study on the effect of branch points on the stability of coronary artery flow SO MEDICAL ENGINEERING & PHYSICS LA English DT Article DE atherogenesis; turbulence; wall shear stress; coronary flow ID OSCILLATORY PIPE-FLOW; PULSATILE FLOW; WALL SHEAR; TURBULENCE; TRANSITION; PATTERNS; DIAMETER; VESSELS; STEADY AB Empirical correlations for the onset of turbulence in pulsatile flow through a straight tube and a 45 degrees T-bifurcation are presented We pumped three different test fluids of kinematic viscosity 0.008-0.035 cm(2) s(-1) through four straight tubes 0.4-3.0 cm in diameter and three 45 degree T-bifurcations 0.45-2.2 cm in diameter. A Scotch yoke mechanism provided an oscillatory sine wave flow component of known stroke volume and frequency. To determine transition to turbulence, we adjusted the mean flow independently until we detected signal instabilities from hot film or electrochemical wall shear probes. The critical peak Reynolds number was found to correlate with two independent dimensionless groups: the Womersley parameter and the Strouhal number. We derived power law functions of these groups to provide an accurate and convenient method of predicting transition in both straight and bifurcating tubes. When compared to pulsatile pou through the straight tube, the presence of flow separation within the 45 degrees 45 degrees T-bifurcation is also a suitable model for predicting transition at coronary branch points, which we previously atherogenesis. C1 NCI,BETHESDA,MD 20892. NR 39 TC 6 Z9 6 U1 0 U2 1 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, OXON, ENGLAND OX5 1GB SN 1350-4533 J9 MED ENG PHYS JI Med. Eng. Phys. PD MAR PY 1997 VL 19 IS 2 BP 101 EP 108 DI 10.1016/S1350-4533(96)00046-X PG 8 WC Engineering, Biomedical SC Engineering GA XD448 UT WOS:A1997XD44800001 PM 9203144 ER PT J AU Fisher, WR Venkatakrishnan, V Fisher, ES Stacpoole, PW Zech, LA AF Fisher, WR Venkatakrishnan, V Fisher, ES Stacpoole, PW Zech, LA TI The H-3-leucine tracer: Its use in kinetic studies of plasma lipoproteins SO METABOLISM-CLINICAL AND EXPERIMENTAL LA English DT Article; Proceedings Paper CT National-Institute-of-Health Symposium on In Vivo Tracer Kinetics and Modeling CY MAY 03, 1996 CL NATL INST OF HLTH, BETHESDA, MD SP NIH HO NATL INST OF HLTH ID LOW-DENSITY-LIPOPROTEIN; APOLIPOPROTEIN-A-I; SECRETORY PATHWAY; PROTEIN-SYNTHESIS; AMINO-ACIDS; METABOLISM; LEUCINE; HUMANS; MODEL; CELLS AB H-3-leucine administered as a bolus has been widely used as a tracer in kinetic investigations of protein synthesis and secretion. After intravenous injection, plasma specific radioactivity decays over several orders of magnitude during the first half-day, followed by a slow decay lasting a number of weeks that results from recycling of the leucine tracer as proteins are degraded and H-3-leucine reenters the plasma pool, In studies in which kinetic data are analyzed by mathematical compartmental modeling, plasma leucine activity is generally used as a forcing function to drive the input of H-3-leucine into the protein synthesis pathway. H-3-leucine is an excellent tracer during the initial hours of rapidly decreasing plasma activity; thereafter, reincorporation of recycled tracer into new protein synthesis obscures the tracer data from proteins with slower turnover rates. Thus, for proteins such as plasma albumin and apolipoprotein (apo) A-I, this tracer is unsatisfactory for measuring fractional catabolic (FCR) and turnover rates. By contrast, the kinetics of plasma very-low-density lipoprotein (VLDL)-apoB, a protein with a residence time of approximately 5 hours, are readily measured, since kinetic parameters of this protein can be determined by the time plasma leucine recycling becomes established. However, measurement of VLDL-apoB specific radioactivity extending up to 2 weeks provides further data on the kinetic tail of VLDL-apoB. Were plasma leucine a direct precursor for the leucine in VLDL-apoB, the kinetics of the plasma tracer should determine the kinetics of the protein. However, this is not the case, and the deviations from linearity are interpreted in terms of (1) the dilution of plasma leucine in the liver by unlabeled dietary leucine; (2) the recycling of hepatocellular leucine from proteins within the liver, where recycled cellular leucine does not equilibrate with plasma leucine; and (3) a ''hump'' in the kinetic data of VLDL-apoB, which we interpret to reflect recycling or retention of a portion of the apoB protein within the hepatocyte, with its subsequent secretion. Because hepatocellular tRNA is the immediate precursor for synthesis of these secretory proteins, its kinetics should be used as the forcing function to drive the modeling of this system. The VLDL-apoB tail contains the information needed to modify the plasma leucine data, to provide an appropriate forcing function when using H-3-leucine as a tracer of apolipoprotein metabolism. This correction is essential when using H-3-leucine as a tracer for measuring low-density lipoprotein (LDL)-apoB kinetics. The H-3-leucine tracer also highlights the importance of recognizing the difference between plasma and system residence times, the latter including the time the tracer resides within exchanging extravascular pools. The inability to determine these fractional exchange coefficients for apoA-I and albumin explains the failure of this tracer in kinetic studies of these proteins. For apoB-containing lipoproteins, plasma residence times are generally determined, and these measurements can be made satisfactorily with H-3-leucine. Copyright (C) 1997 by W.B. Saunders Company. C1 NIH,MATH BIOL LAB,BETHESDA,MD 20892. RP Fisher, WR (reprint author), UNIV FLORIDA,J HILLIS MILLER HLTH CTR,DEPT MED,BOX 100226,GAINESVILLE,FL 32610, USA. FU NCRR NIH HHS [M01RR00082]; NHLBI NIH HHS [NIH HL29394 NHLBI] NR 35 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 0026-0495 J9 METABOLISM JI Metab.-Clin. Exp. PD MAR PY 1997 VL 46 IS 3 BP 333 EP 342 DI 10.1016/S0026-0495(97)90262-6 PG 10 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA WL979 UT WOS:A1997WL97900017 PM 9054478 ER PT J AU Klier, CM Kolenbrander, PE Roble, AG Marco, ML Cross, S Handley, PS AF Klier, CM Kolenbrander, PE Roble, AG Marco, ML Cross, S Handley, PS TI Identification of a 95 kDa putative adhesin from Actinomyces serovar WVA963 strain PK1259 that is distinct from type 2 fimbrial subunits SO MICROBIOLOGY-UK LA English DT Article DE oral actinomyces; adhesin; fimbriae; coaggregation ID VISCOSUS T14V; ESCHERICHIA-COLI; ORAL BACTERIA; MEDIATED COAGGREGATION; PILUS-ADHESIN; CELL-SURFACE; STREPTOCOCCUS; NAESLUNDII; PROTEINS; BINDING AB The species Actinomyces serovar WVA963 is among the 20 bacteria most frequently isolated from human subgingival plaque. The interactions of this species with streptococci are inhibited by lactose, a function associated with type 2 fimbrial surface structures in Actinomyces naeslundii. Type 1 fimbriae mediate binding of cells to salivary proline-rich proteins. Specific polyclonal antisera against type 1 and type 2 fimbriae of A. naeslundii T14V revealed both types of fimbriae on Actinomyces serovar WVA963 strain PK1259, To investigate the role of type 2 fimbriae of strain PK1259 in Actinomyces-Streptococcus lactose-inhibitable coaggregations, spontaneous coaggregation-defective (Cog(-)) mutants that failed to coaggregate with streptococci were isolated; three were chosen for study. All three mutant strains synthesized type 1 fimbriae and a 59 kDa protein; mutant strains PK2415 and PK3092 synthesized type 2 fimbriae and a 57 kDa protein. In contrast, the Cog(-) strain PK2407 did not agglutinate with anti-type 2 antibodies or show the 57 kDa band, suggesting that the 57 kDa protein was the type 2 fimbrial subunit. Polyclonal antiserum raised against the Actinomyces serovar WVA963 strain PK2399, an antibiotic-resistant derivative of wild-type PK1259, blocked coaggregation between this strain and streptococci. Anti-PK2399 serum absorbed with mutant strain PK3092 bearing type 2 fimbriae retained its blocking ability. Surface sonicates of the parent and mutant strains were adsorbed to streptococcal cells and to lactose-agarose beads. Lactose eluates from both the streptococcal cells and the affinity beads were characterized by SDS-PAGE and corresponding immunoblots using anti-PK2399 serum absorbed with Cog(-) mutant PK3092, These blots revealed a 95 kDa putative adhesin in the parent strain PK2399 that was absent in the Cog(-) mutant strain PK3092. These results suggest the presence of a putative 95 kDa actinomyces adhesin distinct from the 57 kDa type 2 fimbrial subunit and that this adhesin mediates lactose-inhibitable coaggregation with streptococci. C1 NIDR,MICROBIAL ECOL LAB,NIH,BETHESDA,MD 20892. UNIV MANCHESTER,SCH BIOL SCI,MICROBIOL RES GRP,MANCHESTER M13 9PT,LANCS,ENGLAND. RI Marco, Maria/H-2322-2014 NR 48 TC 10 Z9 10 U1 0 U2 0 PU SOC GENERAL MICROBIOLOGY PI READING PA MARLBOROUGH HOUSE, BASINGSTOKE RD, SPENCERS WOODS, READING, BERKS, ENGLAND RG7 1AE SN 1350-0872 J9 MICROBIOL-UK JI Microbiology-(UK) PD MAR PY 1997 VL 143 BP 835 EP 846 PN 3 PG 12 WC Microbiology SC Microbiology GA WN280 UT WOS:A1997WN28000018 PM 9084167 ER PT J AU Williams, WM Chang, MCJ Hayakawa, T Grange, E Rapoport, SI AF Williams, WM Chang, MCJ Hayakawa, T Grange, E Rapoport, SI TI In vivo incorporation from plasma of radiolabeled palmitate and arachidonate into rat brain microvessels SO MICROVASCULAR RESEARCH LA English DT Article ID CAPILLARIES; TRANSPORT AB The microvascular endothelium must respond efficiently to the metabolic needs of the brain for normal brain function. To do this, endothelial cells have metabolic pathways that utilize substrates not primary to the metabolic needs of the brain as a whole. Thus, endothelial utilization of glucose is minimized, and saturated, long-chain fatty acids, such as palmitate, become a major source of fuel for oxidative metabolism and active transport processes (Goldstein, 1979). Previous assessment of fatty acid metabolism in cerebral microvessels has relied upon in vitro approaches involving cultured endothelial cells or isolated microvessels. The present study, utilizing radiolabeled fatty acids intravenously infused in vivo, is the first to report on fatty acid incorporation within cerebral microvessels of an awake animal. RP Williams, WM (reprint author), NIA,NEUROSCI LAB,NIH,BLDG 10,BETHESDA,MD 20892, USA. NR 8 TC 8 Z9 8 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 0026-2862 J9 MICROVASC RES JI Microvasc. Res. PD MAR PY 1997 VL 53 IS 2 BP 163 EP 166 DI 10.1006/mvre.1996.1984 PG 4 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA WU792 UT WOS:A1997WU79200008 PM 9143548 ER PT J AU Kleiner, DE Gaffey, MJ Sallie, R Tsokos, M Nichols, L McKenzie, R Straus, SE Hoofnagle, JH AF Kleiner, DE Gaffey, MJ Sallie, R Tsokos, M Nichols, L McKenzie, R Straus, SE Hoofnagle, JH TI Histopathologic changes associated with fialuridine hepatotoxicity SO MODERN PATHOLOGY LA English DT Article DE chronic hepatitis B; drug toxicity; fialuridine; hepatic failure; lactic acidosis; microvesicular steatosis; nucleoside analogue ID CHRONIC HEPATITIS-B; ACQUIRED-IMMUNODEFICIENCY-SYNDROME; HIV-INFECTED PATIENTS; REYES-SYNDROME; LACTIC-ACIDOSIS; MITOCHONDRIAL MYOPATHY; NUCLEOSIDE ANALOG; ANTIVIRAL AGENT; THERAPY; LIVER AB Chronic hepatitis B is a widespread viral illness with the serious sequelae of cirrhosis and hepatocellular carcinoma. Current therapy with interferon is not universally efficacious, and this has led to the evaluation of other antiviral agents. A recent Phase II trial of the nucleoside analogue, fluoroiodoarabinofuranosyluracil (fialuridine, FIAU) was halted because of the sudden development of severe multisystem toxicity characterized by hepatic failure, lactic acidosis, and pancreatitis, which resulted in the deaths of five patients. We systematically evaluated pre- and post-therapy biopsy, explant, and autopsy specimens from the 15 patients involved in this trial to define the hepatic changes of fialuridine toxicity and to determine whether the degree of pre-existing hepatitis contributed to the severity of toxicity. Severe hepatotoxicity from fialuridine was characterized by hepatomegaly with diffuse, predominantly microvesicular steatosis, hepatocellular glycogen depletion, marked bile ductular proliferation, and cholestasis. Ultrastructural examination revealed intracytoplasmic lipid droplets and marked mitochondrial injury. Patients in whom severe toxicity did not develop mainly showed changes caused by the underlying chronic hepatitis B alone. There was a subtle increase in the amount of microvesicular steatosis in two of six patients with mild or no symptoms of toxicity. The microscopic and ultrastructural pattern of injury and systemic symptoms in patients with fialuridine toxicity are consistent with severe mitochondrial and metabolic derangements. Similar hepatic pathologic findings have been reported rarely for other antiviral nucleoside analogues, which suggests that the mechanisms of toxicity might be related. C1 NIDDKD,DIGEST DIS BRANCH,LIVER DIS SECT,NIH,BETHESDA,MD 20892. NIAID,CLIN INVEST LAB,NIH,BETHESDA,MD 20892. UNIV VIRGINIA,MED CTR,DEPT PATHOL,CHARLOTTESVILLE,VA. UNIV PITTSBURGH,DEPT PATHOL,PITTSBURGH,PA. RP Kleiner, DE (reprint author), NCI,PATHOL LAB,NIH,BLDG 10,ROOM 2N212,BETHESDA,MD 20892, USA. OI Kleiner, David/0000-0003-3442-4453 NR 39 TC 42 Z9 43 U1 0 U2 6 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD MAR PY 1997 VL 10 IS 3 BP 192 EP 199 PG 8 WC Pathology SC Pathology GA WM999 UT WOS:A1997WM99900006 PM 9071726 ER PT J AU Tsuboi, T Cao, YM Kaslow, DC Shiwaku, K Torii, M AF Tsuboi, T Cao, YM Kaslow, DC Shiwaku, K Torii, M TI Primary structure of a novel ookinete surface protein from Plasmodium berghei SO MOLECULAR AND BIOCHEMICAL PARASITOLOGY LA English DT Article DE Plasmodium berghei; malaria; ookinete antigen; sequence ID TRANSMISSION-BLOCKING ANTIBODIES; SEXUAL STAGES; MALARIA; GALLINACEUM; FALCIPARUM; IMMUNITY; ANTIGENS C1 EHIME UNIV,SCH MED,DEPT PARASITOL,SHIGENOBU,EHIME 79102,JAPAN. NIAID,PARASIT DIS LAB,MALARIA VACCINES SECT,BETHESDA,MD 20892. SHIMANE MED UNIV,DEPT ENVIRONM MED,IZUMO,SHIMANE 693,JAPAN. NR 11 TC 22 Z9 23 U1 0 U2 0 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 1997 VL 85 IS 1 BP 131 EP 134 DI 10.1016/S0166-6851(96)02821-6 PG 4 WC Biochemistry & Molecular Biology; Parasitology SC Biochemistry & Molecular Biology; Parasitology GA WR492 UT WOS:A1997WR49200012 PM 9108555 ER PT J AU Sarrowa, J Chang, DY Maraia, RJ AF Sarrowa, J Chang, DY Maraia, RJ TI The decline in human Alu retroposition was accompanied by an asymmetric decrease in SRP9/14 binding to dimeric Alu RNA and increased expression of small cytoplasmic Alu RNA SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID SIGNAL RECOGNITION PARTICLE; SECONDARY STRUCTURE; REPEATED SEQUENCES; 7SL RNA; SRP-RNA; EVOLUTION; PROTEIN; FAMILY; TRANSCRIPTS; ELEMENTS AB Alu interspersed elements are inserted into the genome by a retroposition process that occurs via dimeric Alu RNA and causes genetic disorders in humans, Alu RNA is labile and can be diverted to a stable left monomer transcript known as small cytoplasmic AB (scAlu) RNA by RNA 3' processing, although the relationship between Alu RNA stability, scAlu RNA production, and retroposition has been unknown, In vivo, Aln and scAlu transcripts interact with the Alu RNA-binding subunit of signal recognition particle (SRP) known as SRP9/14. We examined RNAs corresponding to Alu sequences that were differentially active during primate evolution, as well as an Alu RNA sequence that is currently active in humans, Mutations that accompanied Alu RNA evolution led to changes in a conserved structural motif also found in SRP RNAs that are associated with thermodynamic destabilization and decreased affinity of the Alu right monomer for SRP9/14. In contrast to the right monomer, the Alu left monomer maintained structural integrity and high affinity for SRP9/14, indicating that scAlu RNA has been under selection during human evolution, Loss of Alu right monomer affinity for SRP9/14 is associated with scAlu RNA production from Alu elements in vivo. Moreover, the loss in affinity coincided with decreased rates of Alu amplification during primate evolution, This indicates that stability of the Alu right monomer is a critical determinant of Alu retroposition. These results provide insight into Alu mobility and evolution and into how retroposons may interact with host proteins during genome evolution. C1 NICHHD,NIH,LAB MOL GROWTH REGULAT,BETHESDA,MD 20892. NR 52 TC 35 Z9 35 U1 1 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD MAR PY 1997 VL 17 IS 3 BP 1144 EP 1151 PG 8 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA WJ164 UT WOS:A1997WJ16400012 PM 9032241 ER PT J AU GiorgettiPeraldi, S Ottinger, E Wolf, G Ye, B Burke, TR Shoelson, SE AF GiorgettiPeraldi, S Ottinger, E Wolf, G Ye, B Burke, TR Shoelson, SE TI Cellular effects of phosphotyrosine-binding domain inhibitors on insulin receptor signaling and trafficking SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID PROTEIN-TYROSINE-PHOSPHATASE; GROWTH-FACTOR RECEPTOR; SOLID-PHASE SYNTHESIS; SH2 DOMAIN; PHOSPHATIDYLINOSITOL 3-KINASE; JUXTAMEMBRANE REGION; TRANSMEMBRANE DOMAIN; NUCLEOTIDE EXCHANGE; HEMATOPOIETIC-CELLS; NPXY MOTIF AB She and insulin receptor substrate 1 (IRS-1) are cytoplasmic substrates of tyrosine kinase receptors that engage, localize, and activate downstream SH2 enzymes. Each contains a phosphotyrosine-binding (PTB) domain that is structurally unrelated to SH2 domains. We have designed high-affinity, cellular inhibitors of the She PTB domain by incorporating nonnatural, phosphatase-resistant amino acids into short peptides. None of the inhibitors bind the IRS-1 PTB domain, consistent with distinct specificities for domains. The best inhibitor of the She domain was introduced by electroporation into Rat1 fibroblasts that express human insulin receptors. Insulin-stimulated phosphorylation of She was inhibited, with no effect on IRS-I, and downstream effects on mitogen-activated protein kinase and DNA synthesis were both inhibited. The PTB domain inhibitor had less influence on epidermal growth factor-induced effects and essentially no impact on serum- or phorbol ester-induced effects. The inhibitor did not affect insulin internalization and its degradation. We conclude that the PTB domain of She is critical for its phosphorylation by the insulin receptor, that She is an important mediator of insulin's mitogenic effects, and that She is not central to insulin receptor cycling in these cells. PTB domains can be inhibited selectively in cells and represent potential targets for drug discovery. C1 HARVARD UNIV,SCH MED,JOSLIN DIABET CTR,BOSTON,MA 02215. HARVARD UNIV,SCH MED,DEPT MED,BOSTON,MA 02215. NCI,MED CHEM LAB,DIV BASIC SCI,NIH,BETHESDA,MD 20892. RI Burke, Terrence/N-2601-2014 FU NIDDK NIH HHS [DK36836, DK43123, DK51729] NR 66 TC 30 Z9 32 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD MAR PY 1997 VL 17 IS 3 BP 1180 EP 1188 PG 9 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA WJ164 UT WOS:A1997WJ16400016 PM 9032245 ER PT J AU PiseMasison, CA Dittmer, J Clemens, KE Brady, JN AF PiseMasison, CA Dittmer, J Clemens, KE Brady, JN TI Physical and functional interaction between the human T-cell lymphotropic virus type 1 Tax(1) protein and the CCAAT binding protein NF-Y SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID I-ASSOCIATED MYELOPATHY; PRIMARY HUMAN-LYMPHOCYTES; KAPPA-B-ALPHA; HTLV-I; DNA-BINDING; GENE-EXPRESSION; TRANSCRIPTIONAL ACTIVATION; TRANSACTIVATOR TAX; TRANSGENIC MICE; LEUKEMIA AB Tax(1), a potent activator of human T-cell lymphotropic virus type 1 (HTLV-1) transcription, has been shown to modulate expression of many cellular genes. Tax(1) does not bind DNA directly but regulates transcription through protein-protein interactions with sequence-specific transcription factors. Using the yeast two-hybrid system to screen for proteins which interact with Tax(1), we isolated the B subunit of the CCAAT binding protein NF-Y from a HeLa cDNA library. The interaction of Tax(1) with NF-YB was specific in that NF-YB did not interact with a variety of other transcription factors, including human immunodeficiency virus Tat, human papillomavirus E6, and Bicoid, or with the M7 (amino acids (CP)-C-29-AS) Tax(1) mutant. However, NF-YB did interact,vith the C-terminal Tax(1) mutants M22 ((130)TL-AS) and M47 ((319)LL-RS). We also show that in vitro-translated NF-YB specifically bound to a glutathione S-transferase-Tax(1) fusion protein. Further, Tax(1) coimmunoprecipitated with NF-Y from nuclear extracts of HTLV-1-transformed cells, providing evidence for in vivo interaction of Tax(1) and NF-YB. We further demonstrate that Tax(1) specifically activated the NF-Y-responsive DQ beta promoter, as well as a minimal promoter which contains only the Y-box element. In addition, mutation of the Y-box element alone abrogated Tax(1)-mediated activation. Taken together, these data indicate that Tax(1) interacts with NF-Y through the B subunit and that this interaction results in activation of the major histocompatibility complex class II promoter. Through activation of this and other NF-Y driven promoters, the Tax(1)-NF-Y interaction may play a critical role in causing cellular transformation and HTLV-1 pathogenesis. C1 NCI,TUMOR VIRUS BIOL SECT,MOL VIROL LAB,BETHESDA,MD 20892. RI Dittmer, Juergen/G-1160-2011 NR 93 TC 28 Z9 28 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD MAR PY 1997 VL 17 IS 3 BP 1236 EP 1243 PG 8 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA WJ164 UT WOS:A1997WJ16400021 PM 9032250 ER PT J AU Pavitt, GD Yang, WM Hinnebusch, AG AF Pavitt, GD Yang, WM Hinnebusch, AG TI Homologous segments in three subunits of the guanine nucleotide exchange factor eIF2B mediate translational regulation by phosphorylation of eIF2 SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID INITIATION FACTOR-II; PROTEIN-SYNTHESIS INITIATION; TRANSFER-RNA-SYNTHETASES; AMINO-ACID CONTROL; SACCHAROMYCES-CEREVISIAE; MALIGNANT TRANSFORMATION; SHUTTLE VECTORS; GCN4 EXPRESSION; KINASE GCN2; YEAST AB eIF2B is a five-subunit guanine nucleotide exchange factor that is negatively regulated by phosphorylation of the alpha subunit of its substrate, eIF2, leading to inhibition of translation initiation, To analyze this regulatory mechanism, we have characterized 29 novel mutations in the homologous eIF2B subunits encoded by GCD2, GCD7, and GCN3 that reduce or abolish inhibition of eIF2B activity by eIF2 phosphorylated on its ex subunit [eIF2(alpha P)]. Most, if not all, of the mutations decrease sensitivity to eIF2(alpha P) without excluding GCN3, the nonessential subunit, from eIF2B; thus, all three proteins are critical for regulation of eIF2B by eIF2(alpha P). The mutations are clustered at both ends of the homologous region of each subunit, within two segments each of approximately 70 amino acids in length, Several mutations alter residues at equivalent positions in two or all three subunits, These results imply that structurally similar segments in GCD2, GCD7, and GCN3 perform related functions in eIF2B regulation, We propose that these segments form a single domain in eIF2B that makes multiple contacts with the ex subunit of eIF2, around the phosphorylation site, allowing eIF2B to detect and respond to phosphoserine at residue 51, Most of the eIF2 is phosphorylated in certain mutants, suggesting that these substitutions allow eIF2B to accept phosphorylated eIF2 as a substrate for nucleotide exchange. C1 NICHHD, LAB EUKARYOT GENE REGULAT, NIH, BETHESDA, MD 20892 USA. RI Pavitt, Graham/A-1363-2010 OI Pavitt, Graham/0000-0002-8593-2418 NR 54 TC 72 Z9 73 U1 0 U2 4 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0270-7306 EI 1098-5549 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD MAR PY 1997 VL 17 IS 3 BP 1298 EP 1313 PG 16 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA WJ164 UT WOS:A1997WJ16400028 PM 9032257 ER PT J AU Lopez, JV Culver, M Stephens, JC Johnson, WE OBrien, SJ AF Lopez, JV Culver, M Stephens, JC Johnson, WE OBrien, SJ TI Rates of nuclear and cytoplasmic mitochondrial DNA sequence divergence in mammals SO MOLECULAR BIOLOGY AND EVOLUTION LA English DT Article DE Numt; mitochondrial DNA relative rates; selective retardation index ID MOLECULAR CLOCK; NUCLEOTIDE-SEQUENCE; SILENT SUBSTITUTION; FIN WHALE; D-LOOP; EVOLUTION; GENOME; GENES; PROTEIN; RECONSTRUCTION AB Differential rates of nucleotide substitution among different gene segments and between distinct evolutionary lineages is well documented among mitochondrial genes and is likely a consequence of locus-specific selective constraints that delimit mutational divergence over evolutionary time. We compared sequence variation of 18 homologous loci (15 coding genes and 3 parts of the control region) among 10 mammalian mitochondrial DNA genomes which allowed us to describe different mitochondrial evolutionary patterns and to produce an estimation of the relative order of gene divergence. The relative rates of divergence of mitochondrial DNA genes in the family Felidae were estimated by comparing their divergence from homologous counterpart genes included in nuclear mitochondrial DNA (Numt, pronounced ''new might''), a genomic fossil that represents an ancient transfer of 7.9 kb of mitochondrial DNA to the nuclear genome of an ancestral species of the domestic cat (Felis catus). Phylogenetic analyses of mitochondrial (mtDNA) sequences with multiple outgroup species were conducted to date the ancestral node common to the Numt and the cytoplasmic (Cymt) mtDNA genes and to calibrate the rate of sequence divergence of mitochondrial genes relative to nuclear homologous counterparts. By setting the fastest substitution rate as strictly mutational, an empirical ''selective retardation index'' is computed to quantify the sum of all constraints, selective and otherwise, that limit sequence divergence of mitochondrial gene sequences over time. C1 NCI, FREDERICK CANC RES & DEV CTR, LAB GENOM DIVERS, FREDERICK, MD 21702 USA. SAIC, INTRAMURAL RES SUPPORT PROGRAM, LAB GENOM DIVERS, FREDERICK, MD USA. UNIV MARYLAND, DEPT ZOOL, COLLEGE PK, MD 20742 USA. RI Lopez, Jose/F-8809-2011; Johnson, Warren/D-4149-2016 OI Lopez, Jose/0000-0002-1637-4125; Johnson, Warren/0000-0002-5954-186X NR 70 TC 109 Z9 114 U1 1 U2 6 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0737-4038 J9 MOL BIOL EVOL JI Mol. Biol. Evol. PD MAR PY 1997 VL 14 IS 3 BP 277 EP 286 PG 10 WC Biochemistry & Molecular Biology; Evolutionary Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Evolutionary Biology; Genetics & Heredity GA WM188 UT WOS:A1997WM18800007 PM 9066795 ER PT J AU Bengel, D Heils, A Petri, S Seemann, M Glatz, K Andrews, A Murphy, DL Lesch, KP AF Bengel, D Heils, A Petri, S Seemann, M Glatz, K Andrews, A Murphy, DL Lesch, KP TI Gene structure and 5'-flanking regulatory region of the murine serotonin transporter SO MOLECULAR BRAIN RESEARCH LA English DT Article DE serotonin transporter; mouse; gene organization; promoter; antidepressant; anxiety; alcoholism; affective disorder ID PLACENTAL CHORIOCARCINOMA CELLS; NEUROTRANSMITTER TRANSPORTERS; DEPENDENT REGULATION; EXPRESSION; PROMOTER; SEQUENCE; ELEMENTS; TRANSCRIPTION; LOCALIZATION; SILENCER AB By modulating the magnitude and duration of postsynaptic responses, carrier-facilitated serotonin (5-HT) transport into and release from the presynaptic neuron is central to the fine tuning of serotonergic neurotransmission. The 5-HT transporter (5-HTT) is the prime target for widely used antidepressants, psychostimulants, drugs of abuse and neurotoxins. We have isolated the gene encoding the murine 5-HTT and determined the sequence of all exons including adjacent intronic regions and similar to 3.6 kb of the 5'-flanking regulatory region. The murine 5-HTT gene is composed of 14 exons spanning similar to 34 kb. The single gene transcript after splicing is 2744 bp in length and it contains 186 bp of 5' untranslated region (5'-UTR) and 668 bp of 3'-UTR. A TATA-like motif and several potential binding sites for transcription factors including API, AP2, AP4, SPL as well as CRE- and GRE-like motifs are present in the GC-rich 5'-flanking region. The characterization of murine 5-HTT cDNA and genomic organization will facilitate studies of 5-HT uptake function with molecular pharmacologic and transgenic strategies as well as investigations of its role in quantitative traits and psychiatric disorders. C1 UNIV WURZBURG, DEPT PSYCHIAT, D-97080 WURZBURG, GERMANY. NIMH, NIH, LCS, CTR CLIN, BETHESDA, MD 20892 USA. RI Andrews, Anne/B-4442-2011; Lesch, Klaus-Peter/J-4906-2013 OI Andrews, Anne/0000-0002-1961-4833; Lesch, Klaus-Peter/0000-0001-8348-153X NR 35 TC 44 Z9 47 U1 0 U2 4 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0169-328X J9 MOL BRAIN RES JI Mol. Brain Res. PD MAR PY 1997 VL 44 IS 2 BP 286 EP 292 DI 10.1016/S0169-328X(96)00234-3 PG 7 WC Neurosciences SC Neurosciences & Neurology GA WM030 UT WOS:A1997WM03000012 ER PT J AU Kanuma, T Nishida, J Gima, T Barrett, JC Wake, N AF Kanuma, T Nishida, J Gima, T Barrett, JC Wake, N TI Alterations of the p16(INK4A) gene in human ovarian cancers SO MOLECULAR CARCINOGENESIS LA English DT Article DE p16(INK4A); ovarian cancer; mutation ID KINASE-4 INHIBITOR GENE; TUMOR-SUPPRESSOR GENE-1; SQUAMOUS-CELL CARCINOMA; HOMOZYGOUS DELETIONS; P16 MTS1; MUTATION; HETEROZYGOSITY; ADENOCARCINOMA; CHROMOSOME-9; PRODUCT AB The p16(INK4A) gene, which encodes the cell-cycle regulatory protein cyclin-dependent kinase 4 inhibitor, is a putative tumor-suppressor gene. We examined p16 gene alterations in 30 primary ovarian cancers and ii ovarian cancer cell lines. Five of the primary cancers (16.7%) had lost both p16(INK4A) genes. In addition, four cancers (13.3%) contained five kinds of missense mutations and a one-base deletion. Three cell lines had homozygous deletions of p16 genes, and one cell line had multiple intragenic mutations. There was also suppressed transcription of the p16 gene in one cell line. Some point mutations occurred in the conserved ankylin consensus region. These observations suggest that p16 is a functional target for ovarian carcinogenesis and that p16 alterations occurred in the primary cancers. (C) 1997 Wiley-Liss, Inc. C1 KYUSHU UNIV,MED INST BIOREGULAT,DEPT REPROD PHYSIOL & ENDOCRINOL,BEPPU,OITA 874,JAPAN. NIEHS,MOL CARCINOGENESIS LAB,RES TRIANGLE PK,NC 27709. NR 23 TC 16 Z9 17 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0899-1987 J9 MOL CARCINOGEN JI Mol. Carcinog. PD MAR PY 1997 VL 18 IS 3 BP 134 EP 141 DI 10.1002/(SICI)1098-2744(199703)18:3<134::AID-MC2>3.0.CO;2-F PG 8 WC Biochemistry & Molecular Biology; Oncology SC Biochemistry & Molecular Biology; Oncology GA WQ418 UT WOS:A1997WQ41800002 PM 9115583 ER PT J AU Shibata, MA Ward, JM Green, JE Merlino, G AF Shibata, MA Ward, JM Green, JE Merlino, G TI Enhanced sensitivity to tumor growth and development in multistage skin carcinogenesis by transforming growth factor-alpha-induced epidermal growth factor receptor activation but not p53 inactivation SO MOLECULAR CARCINOGENESIS LA English DT Article DE transforming growth factor-alpha; epidermal growth factor; tyrosine phosphorylation; Ha-ras; p53 ID TRANSGENIC MICE; MOUSE SKIN; TGF-ALPHA; HA-RAS; MALIGNANT PROGRESSION; HUMAN KERATINOCYTES; CELL-PROLIFERATION; PROTEIN-KINASE; PAPILLOMAS; OVEREXPRESSION AB Transforming growth factor-alpha (TGF alpha) can stimulate keratinocyte proliferation and function as an autocrine tumor promoter in 7,12-dimethylbenz[a]anthracene (DMBA)-initiated TGF alpha-transgenic mouse Skin. In this study, we examined the effect of ectopic TGF alpha transgene expression on skin tumor growth and progression after DMBA initiation in the presence of 12-O-tetradecanoylphorbol-13-acetate (TPA). Both the multiplicity and size of skin rumors arising in TGF alpha-transgenic mice were significantly higher than those of the nontransgenic parental CD-1 strain. There were more dysplastic papillomas and squamous cell carcinomas (SCCs) in the transgenic animals as well. ProTGF alpha protein was expressed in transgenic papillomas, hut mature TGF alpha was not detected. The epidermal growth factor receptor (EGFR) appeared to be downregulated and was associated with en ha need tyrosine phosphorylation of several substrates in TGF alpha-transgenic mouse tumors. Characteristic codon 61 mutations in the Ha-ras gene were found in most of the papillomas and SCCs Induced by DMBA and TPA in transgenic as well as nontransgenic mice. However, no p53 gene mutations were found in any skin tumors from either transgenic or control animals. Analysis of cellular proliferation in both DMBA-TPA-induced papillomas and in skin 48 h after TPA treatment alone revealed significantly more DNA synthesis in TGF alpha-transgenic mice relative to controls. These results demonstrate that TGF alpha, through EGFR overstimulation, can act synergistically with TPA to induce the formation, growth, and development of DMBA-initiated skin tumors containing classic Ha-ras gene mutations but not p53 gene inactivation. (C) 1997 Wiley-Liss, Inc.(dagger) C1 NCI,DIV BASIC SCI,MOL ONCOL LAB,FREDERICK,MD 21701. NCI,MOL BIOL LAB,MOL GENET SECT,BETHESDA,MD 20892. RP Shibata, MA (reprint author), NCI,OFF LAB ANIM SCI,VET TUMOR PATHOL SECT,DIV BASIC SCI,FREDERICK,MD 21702, USA. NR 43 TC 15 Z9 15 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0899-1987 J9 MOL CARCINOGEN JI Mol. Carcinog. PD MAR PY 1997 VL 18 IS 3 BP 160 EP 170 DI 10.1002/(SICI)1098-2744(199703)18:3<160::AID-MC5>3.0.CO;2-J PG 11 WC Biochemistry & Molecular Biology; Oncology SC Biochemistry & Molecular Biology; Oncology GA WQ418 UT WOS:A1997WQ41800005 PM 9115586 ER PT J AU Lash, A Rabkin, C EmmertBuck, M Merino, MJ Liotta, L Zhuang, ZP AF Lash, A Rabkin, C EmmertBuck, M Merino, MJ Liotta, L Zhuang, ZP TI Presence of human herpesvirus 8 is specific to Kaposi's sarcoma lesion SO MOLECULAR DIAGNOSIS LA English DT Article DE Kaposi's sarcoma-associated herpesvirus; Kaposi's sarcoma; molecular pathology ID DNA-SEQUENCES; HIV-INFECTION AB Background: Human herpesvirus 8 (HHV8) has previously been shown to be associated with Kaposi's sarcoma (KS) skin lesions in HIV-positive and negative patients. This study was designed to test, on a microscopic level, using the microdissection technique in frozen and formalin-fixed tissue, whether HHV8 DNA is specific to the KS lesion. Methods and Results: Thirty-seven evaluable KS lesions were microdissected and DNA extracted, and HHV8-specific polymerase chain reaction (PCR) was performed. All of the KS lesions showed a PCR product; none of the microscopically adjacent normal tissue samples showed a PCR product. One of the PCR products was sequenced, confirming the presence of HHV8 DNA. Conclusions: HHV8 was shown to be specific to the KS lesion at the microscopic level. C1 NCI,PATHOL LAB,NIH,BETHESDA,MD 20892. NCI,VIRAL EPIDEMIOL BRANCH,NIH,BETHESDA,MD 20892. OI Lash, Alex/0000-0003-3787-1590 NR 11 TC 0 Z9 0 U1 0 U2 0 PU CHURCHILL LIVINGSTONE INC MEDICAL PUBLISHERS PI NEW YORK PA 650 AVENUE OF THE AMERICAS, NEW YORK, NY 10011 SN 1084-8592 J9 MOL DIAGN JI Mol. Diagn. PD MAR PY 1997 VL 2 IS 1 BP 11 EP 14 DI 10.1016/S1084-8592(97)80004-5 PG 4 WC Biotechnology & Applied Microbiology; Medical Laboratory Technology; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Medical Laboratory Technology; Research & Experimental Medicine GA XW605 UT WOS:A1997XW60500003 ER PT J AU Rodland, KD Wersto, RP Hobson, S Kohn, EC AF Rodland, KD Wersto, RP Hobson, S Kohn, EC TI Thapsigargin-induced gene expression in nonexcitable cells is dependent on calcium influx SO MOLECULAR ENDOCRINOLOGY LA English DT Article ID PROTEIN-KINASE-C; EPIDERMAL GROWTH-FACTOR; SMOOTH-MUSCLE CELLS; CIS-TRANS ISOMERASE; INTRACELLULAR CALCIUM; ALTERNATIVE MECHANISM; SIGNAL-TRANSDUCTION; INOSITOL PHOSPHATES; FOS TRANSCRIPTION; COLLAGENASE GENE AB Agents such as thapsigargin and endothelin elevate intracellular calcium levels by a combination of calcium release from intracellular stores and calcium influx across the plasma membrane; however, the relative contribution of influx vs. release in modulating calcium-dependent gene expression is not as well understood in nonexcitable cells as in excitable cells, In this report we have been able to separate thapsigargin-induced elevation of intracellular calcium into release and influx components, using carboxyamido-triazole (CAI), a known inhibitor of calcium influx with antiproliferative activity against a number of human carcinomas, to selectively inhibit influx without affecting release, The results of these experiments indicate that the ability of thapsigargin to induce calcium-dependent gene expression in nonexcitable cells is dependent on the induction of calcium influx, presumably through store-operated calcium channels. CAI treatment specifically inhibited thapsigargin- or endothelin-stimulated expression from the c-fos promoter in Rat-1 cells and in epithelial cell lines derived from ovary and breast, Use of the VL30 model system confirmed the ability of CAI to inhibit calcium-dependent gene expression and further demonstrated that the ability of elevated calcium to synergize with other signaling pathways required close temporal coupling, In addition to inhibiting endothelin-induced calcium influx, CAI treatment also resulted in a partial inhibition of IP3 production and calcium release, CAI treatment also blocked the increase in ERK1 kinase activity observed in response to either endothelin or thapsigargin, suggesting a role for calcium influx in the activation of mitogen-activated protein kinase pathways. C1 NCI, PATHOL LAB, BETHESDA, MD 20892 USA. RP Rodland, KD (reprint author), OREGON HLTH SCI UNIV, DEPT CELL & DEV BIOL, PORTLAND, OR 97201 USA. FU NCI NIH HHS [CA-60738] NR 56 TC 26 Z9 28 U1 0 U2 1 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0888-8809 J9 MOL ENDOCRINOL JI Mol. Endocrinol. PD MAR PY 1997 VL 11 IS 3 BP 281 EP 291 DI 10.1210/me.11.3.281 PG 11 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA WK710 UT WOS:A1997WK71000003 PM 9058375 ER PT J AU Tremblay, GB Tremblay, A Copeland, NG Gilbert, DJ Jenkins, NA Labrie, F Giguere, V AF Tremblay, GB Tremblay, A Copeland, NG Gilbert, DJ Jenkins, NA Labrie, F Giguere, V TI Cloning, chromosomal localization, and functional analysis of the murine estrogen receptor beta SO MOLECULAR ENDOCRINOLOGY LA English DT Article ID LIGAND-DEPENDENT PHOSPHORYLATION; THYROID-HORMONE RECEPTOR; TRANSCRIPTIONAL ACTIVATION; RESPONSIVE ELEMENT; BINDING-PROPERTIES; RETINOIC ACID; CO-REPRESSOR; SEQUENCE; IDENTIFICATION; EXPRESSION AB Estrogen receptor beta (ER beta) is a novel steroid receptor that is expressed in rat prostate and ovary. We have cloned the mouse homolog of ER beta and mapped the gene, designated Estrb, to the central region of chromosome 12. The cDNA encodes a protein of 485 amino acids that shares, respectively, 97% and 60% identity with the DNA- and ligand-binding domains of mouse (m) ER alpha. Mouse ER beta binds to an inverted repeat spaced by three nucleotides in a gel mobility shift assay and transactivates promoters containing synthetic or natural estrogen response elements in an estradiol (E(2))-dependent manner. Scatchard analysis indicates that mER beta has slightly lower affinity for E(2) [dissociation constant (K-d) = 0.5 nM] when compared with mER alpha (K-d = 0.2 nM). Antiestrogens, including 4-hydroxytamoxifen (OHT), ICI 182,780, and a novel compound, EM-800, inhibit E(2)-dependent transactivation efficiently. However, while OHT displays partial agonistic activity with ER alpha on a basal promoter linked to estrogen response elements in Cos-1 cells, this effect is not observed with mER beta. Cotransfection of mER beta and H-Ras(V12) causes enhanced activation in the presence of E(2). Mutagenesis of a serine residue (position 60), located within a mitogen-activated protein kinase consensus phosphorylation site abolishes the stimulatory effect of Ras, suggesting that the activity of mER beta is also regulated by the mitogen-activated protein kinase pathway. Surprisingly, the coactivator SRC-1 up-regulates mER beta transactivation both in the absence and presence of E(2), and in vitro interaction between SRC-1 and the ER beta ligand-binding domain is enhanced by E(2). Moreover, the ligand-independent stimulatory effect of SRC-1 on ER beta transcriptional activity is abolished by ICI 182,780, but not by OHT. Our results demonstrate that while ER beta shares many of the functional characteristics of ER alpha, the molecular mechanisms regulating the transcriptional activity of mER beta may be distinct from those of ER alpha. C1 ROYAL VICTORIA HOSP, MOL ONCOL GRP, MONTREAL, PQ H3A 1A1, CANADA. MCGILL UNIV, DEPT BIOCHEM, MONTREAL, PQ H3A 1A1, CANADA. MCGILL UNIV, DEPT MED, MONTREAL, PQ H3A 1A1, CANADA. MCGILL UNIV, DEPT ONCOL, MONTREAL, PQ H3A 1A1, CANADA. NCI, MAMMALIAN GENET LAB, ABL BASIC RES PROGRAM, FREDERICK CANC RES & DEV CTR, FREDERICK, MD 21702 USA. CHU LAVAL, RES CTR, MOL ENDOCRINOL LAB, ST FOY, PQ G1V 4G2, CANADA. NR 53 TC 733 Z9 747 U1 0 U2 9 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0888-8809 J9 MOL ENDOCRINOL JI Mol. Endocrinol. PD MAR PY 1997 VL 11 IS 3 BP 353 EP 365 DI 10.1210/me.11.3.353 PG 13 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA WK710 UT WOS:A1997WK71000010 PM 9058381 ER PT J AU Ripp, SL Overby, LH Philpot, RM Elfarra, AA AF Ripp, SL Overby, LH Philpot, RM Elfarra, AA TI Oxidation of cysteine S-conjugates by rabbit liver microsomes and cDNA-expressed flavin-containing mono-oxygenases: Studies with S-(1,2-dichlorovinyl)-L-cysteine, S-(1,2,2-trichlorovinyl)-L-cysteine, S-allyl-L-cysteine, and S-benzyl-L-cysteine SO MOLECULAR PHARMACOLOGY LA English DT Article ID ADULT HUMAN LIVER; CONTAINING MONOOXYGENASE; ESCHERICHIA-COLI; KIDNEY MICROSOMES; AMINO-ACID; SULFOXIDATION; GLUTATHIONE; OXIDASE; FMO3; NEPHROTOXICITY AB Rabbit liver microsomes catalyzed the highly stereoselective, NADPH- and time-dependent S-oxidation of S-benzyl-L-cysteine (SBC), S-allyl-L-cysteine (SAC), S-(1,2-dichlorovinyl)-L-cysteine (DCVC), and S-(1,2,2-trichlorovinyl)-L-cysteine (TCVC) to their respective sulfoxides. Methimazole, a flavin-containing mono-oxygenase (FMO) substrate, inhibited S-oxidation of all four conjugates. The cytochrome P450 inhibitor 1-benzylimidazole did not affect SAC, SBC, or DCVC S-oxidation but inhibited the S-oxidation of TCVC. Solubilization of microsomes also inhibited TCVC activity, whereas SBC, SAC, and DCVC activities were not affected. Because these results suggested that FMOs were the major catalysts of SBC, SAC, and DCVC sulfoxidations, the four conjugates were evaluated as substrates for cDNA-expressed rabbit FMO isoforms FMO1, FMO2, FMO3, and FMO5. At equimolar concentrations (10 mM), FMO1 S-oxidized SBC and SAC, but no sulfoxides were detected with DCVC or TCVC. FMO3 S-oxidized all four conjugates. K-m values determined with FMO3 were comparable to K-m values from rabbit liver microsomes. S-Oxidation by FMO2 was detected only with SAC, and no sulfoxides were detected in incubations with FMO5. These results show that FMO isoforms can catalyze cysteine conjugate S-oxidation and that the specific isoform involved depends on the structure of the cysteine conjugate. The cysteine conjugates with more nucleophilic sulfur atoms, SAC and SBC, were much better FMG substrates than those having the less nucleophilic sulfur atoms DCVC and TCVC. The sulfoxides of TCVC and DCVC were reactive toward GSH, whereas the sulfoxides of SBC and SAC were not reactive. These results provide evidence for different chemical reactivities of these sulfoxides. C1 UNIV WISCONSIN,SCH VET MED,DEPT COMPARAT BIOSCI,MADISON,WI 53706. UNIV WISCONSIN,CTR ENVIRONM TOXICOL,MADISON,WI 53706. NIEHS,CELLULAR & MOL PHARMACOL LAB,NIH,RES TRIANGLE PK,NC 27709. FU NIDDK NIH HHS [DK44295] NR 32 TC 49 Z9 51 U1 1 U2 2 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0026-895X J9 MOL PHARMACOL JI Mol. Pharmacol. PD MAR PY 1997 VL 51 IS 3 BP 507 EP 515 PG 9 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA WN009 UT WOS:A1997WN00900020 PM 9058607 ER PT J AU Casavola, V Guerra, L Reshkin, SJ Jacobson, KA Murer, H AF Casavola, V Guerra, L Reshkin, SJ Jacobson, KA Murer, H TI Polarization of adenosine effects on intracellular pH in A(6) renal epithelial cells SO MOLECULAR PHARMACOLOGY LA English DT Article ID CORTICAL COLLECTING TUBULE; PROTEIN-KINASE-C; NA+/H+-EXCHANGE; HORMONAL-REGULATION; STIMULATED CAMP; NA/H-EXCHANGE; RECEPTORS; TRANSPORT; INHIBITOR; LINE AB The effect of adenosine on Na+/H+ exchange activity was examined in cultured A(6) renal epithelial cells. Adenosine and its analogue N-6-cyclopentyladenosine (CPA) had different effects on Na+/H+ exchange activity depending on the side of addition. Basolateral CPA induced a stimulation of Na+/H+ exchange activity that was completely prevented by preincubation with an A(2A)-selective antagonist, 8-(3-chlorostyryl)caffeine, whereas apical CPA induced a slight but significant inhibition of Na+/H+ exchange activity that was significantly reduced by the A(1)-receptor antagonist 1,3-dipropyl-8-cyclopentylxanthine. Protein kinase C activation may be involved in mediating the apical CPA inhibition of Na+/H+ exchange activity; this inhibition was prevented by the protein kinase C inhibitor calphostin C. Treatment with either forskolin or 8-bromo-cAMP significantly stimulated Na+/H+ exchange activity; only basolateral CPA addition induced an increase in cAMP level. These observations together with the finding that the CPA-dependent stimulation of exchange activity was prevented by the protein kinase A inhibitor H-89 support the hypothesis that basolateral CPA stimulates Na+/H+ exchange via adenylate cyclase/protein kinase A activation, Basolateral CPA also increased transepithelial Na+ transport, and this stimulation was prevented by the Na+/H+ exchange inhibitor HOE-694, suggesting that changes in pH(i) during hormone action can act as an intermediate in the second-messenger cascade. C1 UNIV ZURICH,DEPT PHYSIOL,CH-8057 ZURICH,SWITZERLAND. NIH,BIOORGAN CHEM LAB,BETHESDA,MD 20892. RP Casavola, V (reprint author), UNIV BARI,INST GEN PHYSIOL,VIA AMENDOLA 165-A,I-70126 BARI,ITALY. RI Jacobson, Kenneth/A-1530-2009 OI Jacobson, Kenneth/0000-0001-8104-1493 FU Intramural NIH HHS [Z01 DK031127-01, Z99 DK999999] NR 40 TC 16 Z9 16 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0026-895X J9 MOL PHARMACOL JI Mol. Pharmacol. PD MAR PY 1997 VL 51 IS 3 BP 516 EP 523 PG 8 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA WN009 UT WOS:A1997WN00900021 PM 9058608 ER PT J AU Licinio, J Wong, ML AF Licinio, J Wong, ML TI Interleukin 1 receptor antagonist gene expression in rat pituitary in the systemic inflammatory response syndrome: Pathophysiological implications SO MOLECULAR PSYCHIATRY LA English DT Editorial Material DE interleukin 1 beta; interleukin 1 receptor antagonist; pituitary gland; sepsis; systemic inflammatory response syndrome; lipopolysaccharide; in situ hybridization ID MESSENGER-RNA; BACTERIAL LIPOPOLYSACCHARIDE; LOCALIZATION; BRAIN; SECRETION; ENZYME; GROWTH; CELLS; GLAND; SHOCK AB The systemic inflammatory response syndrome (SIRS) is characterized by endothelial cell activation causing a generalized inflammatory response and cytokine-mediated pathophysiological alterations.(1-2) The pathophysiology of SIRS involves changes in the functioning of several endocrine glands, including the pituitary.(1-3) SIRS-induced alterations in pituitary function include activation of the hypothalamic-pituitary adrenal (HPA) axis causing hypercortisolemia, the euthyroid sick syndrome, and cessation of reproductive function. These changes are in part mediated by cytokines, such as tumor necrosis factor alpha (TNF-alpha) and interleukin 1 (IL-1).(4,5) IL-1 function depends on the local ratio of bioactive IL-1 and IL-1 receptor antagonist.(6,7) Here we review our studies on IL-1 beta and IL-1ra mRNA levels in the pituitary in a rat model of SIRS.(8,9) We have found that IL-1 beta mRNA peaked at 2 h after lipopolysaccharide (LPS) administration, increasing twelvefold over control values in the posterior pituitary and fivefold over controls in the anterior pituitary. IL-1ra mRNA levels peaked at 6 h post-LPS administration, later than those of IL-1 beta mRNA. IL-1ra mRNA levels increased tenfold in the anterior pituitary, but were induced only threefold in the posterior pituitary. IL-1ra gene expression is profoundly induced in the pituitary in vivo during systemic inflammation and its induction follows that of IL-1 beta, but it is differentially regulated and tissue-specific, occurring predominantly in the anterior pituitary. Future studies of the effects of IL-1 in the pituitary should take into account the local levels of IL-1ra. RP Licinio, J (reprint author), NIMH,CLIN NEUROENDOCRINOL BRANCH,INTRAMURAL RES PROGRAM,NIH,BLDG 10,RM 2D46,BETHESDA,MD 20892, USA. RI Wong, Ma-Li/D-7903-2011; Licinio, Julio/L-4244-2013 OI Licinio, Julio/0000-0001-6905-5884 NR 27 TC 15 Z9 16 U1 0 U2 0 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE, HAMPSHIRE, ENGLAND RG21 6XS SN 1359-4184 J9 MOL PSYCHIATR JI Mol. Psychiatr. PD MAR PY 1997 VL 2 IS 2 BP 99 EP 103 DI 10.1038/sj.mp.4000251 PG 5 WC Biochemistry & Molecular Biology; Neurosciences; Psychiatry SC Biochemistry & Molecular Biology; Neurosciences & Neurology; Psychiatry GA WT692 UT WOS:A1997WT69200006 PM 9106226 ER PT J AU Vitkovic, L AF Vitkovic, L TI Neuropathogenesis of HIV-1 infection: Interactions between interleukin-1 and transforming growth factor-1 beta SO MOLECULAR PSYCHIATRY LA English DT Editorial Material ID FACTOR-BETA; EXPRESSION; ASTROCYTES; GROWTH-FACTOR-BETA-1; INDUCTION; BRAIN AB Cytokines are widely considered to function as major mediators of neuropathogenesis of HIV-1 infection. This view is based on a large amount of data obtained in vitro, in animal models and in human brain tissue obtained postmortem. Evidence for the involvement of interleukin-1 and transforming growth factor-beta 1, summarized here, indicates that these cytokines likely control HIV-1 expression in the brain and astrocytosis, the two hallmarks of brain in AIDS patients. Although the data do not reveal the precise time course of molecular and cellular changes in vivo, they strongly suggest a complex pattern of interactions whose ordering in time determines when and where HIV-1 is expressed in the brain. Further kinetic data are therefore urgently needed to shed light on the heterogeneity of HIV-1 expression in the brain. RP Vitkovic, L (reprint author), NIMH, DIV NEUROSCI & BEHAV SCI, NIH, 5600 FISHERS LANE, ROOM 11C-06, ROCKVILLE, MD 20856 USA. NR 16 TC 8 Z9 8 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1359-4184 J9 MOL PSYCHIATR JI Mol. Psychiatr. PD MAR PY 1997 VL 2 IS 2 BP 111 EP 112 DI 10.1038/sj.mp.4000220 PG 2 WC Biochemistry & Molecular Biology; Neurosciences; Psychiatry SC Biochemistry & Molecular Biology; Neurosciences & Neurology; Psychiatry GA WT692 UT WOS:A1997WT69200009 PM 9106229 ER PT J AU Gibbs, CJ Bolis, CL AF Gibbs, CJ Bolis, CL TI Normal isoform of amyloid protein (PrP) in brains of spawning salmon SO MOLECULAR PSYCHIATRY LA English DT Article DE spongiform encephalopathy; prion protein; fish AB The transmissible spongiform encephalopathies are a group of subacute progressive degenerative diseases of the nervous system which are always fatal in their outcome. These diseases appear to be caused by the abnormal isoform of the precursor protein of amyloid designated prion protein. The normal isoform has been identified in the tissues of all mammalian species thus far tested as well as in Drosophila. We report the presence of this protein for the first time in the brains of fish. C1 UNIV MILAN,INST PHARMACOL SCI,LAB COMPARAT BIOL,MILAN,ITALY. RP Gibbs, CJ (reprint author), NINCDS,CENT NERVOUS SYST STUDIES LAB,NIH,BLDG 36,RM 4D04,BETHESDA,MD 20892, USA. NR 3 TC 10 Z9 10 U1 0 U2 0 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE, HAMPSHIRE, ENGLAND RG21 6XS SN 1359-4184 J9 MOL PSYCHIATR JI Mol. Psychiatr. PD MAR PY 1997 VL 2 IS 2 BP 146 EP 147 PG 2 WC Biochemistry & Molecular Biology; Neurosciences; Psychiatry SC Biochemistry & Molecular Biology; Neurosciences & Neurology; Psychiatry GA WT692 UT WOS:A1997WT69200019 PM 9106239 ER PT J AU Simon, ES AF Simon, ES TI Phenotypic heterogeneity and disease course in three murine strains with mutations in genes encoding for alpha 1 and beta glycine receptor subunits SO MOVEMENT DISORDERS LA English DT Article DE glycine; spinal cord; spasticity; myoclonus; hyperekplexia; chloride channel ID INDUCED MYOCLONUS; MUTANT MOUSE; HYPEREKPLEXIA AB Impaired glycinergic inhibition causes human hyperekplexia, and may be involved in the pathogenesis of movement disorders associated with uremia, spinal cord lesions, DDT poisoning, and tetanus. Three autosomal recessive mutant mouse strains with single-gene mutations affecting either the arl (spasm odic and oscillator) or beta (spastic) subunits of the glycine receptor were studied. Serial videotaped examinations assessed the severity of hyperkinetic features. Homozygote oscillator mice appeared normal until postnatal day (P) 11-14, when decreased exploratory movements, spastic gait, stimulus-induced myoclonic bouts, rigidity, and tremor were noticeable. All symptoms gradually worsened until death by P21-P23. In contrast, spastic and spasmodic mice were most severely affected by the 3rd-5th week of life and had a lessening of symptom severity in adulthood. Within each mutant strain, there was marked interanimal variation of severity of the other motor abnormalities, possibly because of stochastic variability in developmental processes. These mutants represent good animal models for elucidation of molecular and cellular issues regarding the glycine receptor and for the study of pathogenetic mechanisms of movement disorders. C1 NINCDS,NEURAL CONTROL LAB,NIH,BETHESDA,MD 20892. NR 24 TC 12 Z9 14 U1 0 U2 1 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0885-3185 J9 MOVEMENT DISORD JI Mov. Disord. PD MAR PY 1997 VL 12 IS 2 BP 221 EP 228 DI 10.1002/mds.870120213 PG 8 WC Clinical Neurology SC Neurosciences & Neurology GA WP482 UT WOS:A1997WP48200011 PM 9087981 ER PT J AU KwonChung, KJ Chang, YC Penoyer, L AF KwonChung, KJ Chang, YC Penoyer, L TI Species of the genus Filobasidiella differ in the organization of their 5S rRNA genes SO MYCOLOGIA LA English DT Article DE Filobasidiella depauperata; Filobasidiella neoformans; ribosomal RNA ID RIBOSOMAL-RNA GENES; CRYPTOCOCCUS-NEOFORMANS; SCHIZOSACCHAROMYCES-POMBE; BASIDIOMYCETOUS YEASTS; NUCLEOTIDE-SEQUENCES; NEUROSPORA-CRASSA; FUNGI IMPERFECTI; DNA; EVOLUTION; HETEROGENEITY AB The genus Filobasidiella contains two species, F. neoformans and F. depauperata. The 5S ribosomal RNA genes in the two species were found to have completely different genomic arrangements. We previously reported that the 5S rRNA gene of F. neoformans, the type species of genus Filobasidiella, is located 1 kb upstream from the 18S rRNA gene within the 8.6-kb HindIII fragment of the ribosomal DNA repeat unit. The present study demonstrates the 5S rRNA gene to be absent from the rDNA repeat in F. depauperata, but is dispersed in the genome. Analysis of the nucleotide sequence from five randomly isolated 5S rDNA clones of F. depauperata showed heterogeneity at six different positions of the putative transcription region. The genus Filobasidiella is the first genus of Eumycota reported to have the 5S rRNA with two different genomic arrangements. RP KwonChung, KJ (reprint author), NIAID,CLIN INVEST LAB,MOL MICROBIOL SECT,NIH,BLDG 10,BETHESDA,MD 20892, USA. NR 35 TC 5 Z9 5 U1 1 U2 1 PU NEW YORK BOTANICAL GARDEN PI BRONX PA PUBLICATIONS DEPT, BRONX, NY 10458 SN 0027-5514 J9 MYCOLOGIA JI Mycologia PD MAR-APR PY 1997 VL 89 IS 2 BP 244 EP 249 DI 10.2307/3761078 PG 6 WC Mycology SC Mycology GA WT214 UT WOS:A1997WT21400008 ER PT J AU Sikorski, R Peters, R AF Sikorski, R Peters, R TI Transgenics on the Internet SO NATURE BIOTECHNOLOGY LA English DT Editorial Material C1 MASSACHUSETTS GEN HOSP,DEPT MED,BOSTON,MA 02114. RP Sikorski, R (reprint author), NCI,HOWARD HUGHES MED INST,BETHESDA,MD 20892, USA. NR 0 TC 3 Z9 6 U1 0 U2 0 PU NATURE PUBLISHING CO PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 SN 1087-0156 J9 NAT BIOTECHNOL JI Nat. Biotechnol. PD MAR PY 1997 VL 15 IS 3 BP 289 EP 289 DI 10.1038/nbt0397-289 PG 1 WC Biotechnology & Applied Microbiology SC Biotechnology & Applied Microbiology GA WM050 UT WOS:A1997WM05000037 PM 9062932 ER PT J AU Allikmets, R Singh, N Sun, H Shroyer, NE Hutchinson, A Chidambaram, A Gerrard, B Baird, L Stauffer, D Peiffer, A Rattner, A Smallwood, P Li, YX Anderson, KL Lewis, RA Nathans, J Leppert, M Dean, M Lupski, JR AF Allikmets, R Singh, N Sun, H Shroyer, NE Hutchinson, A Chidambaram, A Gerrard, B Baird, L Stauffer, D Peiffer, A Rattner, A Smallwood, P Li, YX Anderson, KL Lewis, RA Nathans, J Leppert, M Dean, M Lupski, JR TI A photoreceptor cell-specific ATP-binding transporter gene (ABCR) is mutated in recessive Stargardt macular dystrophy SO NATURE GENETICS LA English DT Article ID FUNDUS-FLAVIMACULATUS; MULTIDRUG-RESISTANCE; RETINAL DEGENERATION; MOLECULAR-GENETICS; CYSTIC-FIBROSIS; POINT MUTATIONS; NORRIE DISEASE; CLONING; SEQUENCE; MAPS AB Stargardt disease (STGD, also known as fundus flavimaculatus; FFM) is an autosomal recessive retinal disorder characterized by a juvenile-onset macular dystrophy, alterations of the peripheral retina, and subretinal deposition of lipofuscin-like material. A gene encoding an ATP-binding cassette (ABC) transporter was mapped to the 2-cM (centiMorgan) interval at 1p13-p21 previously shown by linkage analysis to harbour the STGD gene. This gene, ABCR, is expressed exclusively and at high levels in the retina, in rod but not cone photoreceptors, as detected by in situ hybridization. Mutational analysis of ABCR in STGD families revealed a total of 19 different mutations including homozygous mutations in two families with consanguineous parentage. These data indicate that ABCR is the causal gene of STGD/FFM. C1 NCI,FREDERICK CANC RES & DEV CTR,SAIC FREDERICK,LAB GEN DIVERS,FREDERICK,MD 21702. NCI,FREDERICK CANC RES & DEV CTR,SAIC FREDERICK,INTRAMURAL RES SUPPORT PROGRAM,FREDERICK,MD 21702. UNIV UTAH,DEPT HUMAN GENET,SALT LAKE CITY,UT 84112. JOHNS HOPKINS UNIV,SCH MED,DEPT MOL BIOL & GENET,BALTIMORE,MD 21205. JOHNS HOPKINS UNIV,SCH MED,DEPT NEUROSCI,BALTIMORE,MD 21205. JOHNS HOPKINS UNIV,SCH MED,DEPT OPHTHALMOL,BALTIMORE,MD 21205. JOHNS HOPKINS UNIV,SCH MED,HOWARD HUGHES MED INST,BALTIMORE,MD 21205. BAYLOR COLL MED,DEPT MOL & HUMAN GENET,HOUSTON,TX 77030. BAYLOR COLL MED,DEPT PEDIAT,HOUSTON,TX 77030. BAYLOR COLL MED,DEPT OPHTHALMOL,HOUSTON,TX 77030. BAYLOR COLL MED,DEPT MED,HOUSTON,TX 77030. RI Dean, Michael/G-8172-2012; OI Dean, Michael/0000-0003-2234-0631; Shroyer, Noah/0000-0002-5934-2852 FU NCI NIH HHS [5P30CA42014] NR 77 TC 766 Z9 789 U1 0 U2 28 PU NATURE PUBLISHING CO PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 SN 1061-4036 J9 NAT GENET JI Nature Genet. PD MAR PY 1997 VL 15 IS 3 BP 236 EP 246 DI 10.1038/ng0397-236 PG 11 WC Genetics & Heredity SC Genetics & Heredity GA WK386 UT WOS:A1997WK38600011 PM 9054934 ER PT J AU Kang, S Graham, JM Olney, AH Biesecker, LG AF Kang, S Graham, JM Olney, AH Biesecker, LG TI GLI3 frameshift mutations cause autosomal dominant Pallister-Hall syndrome SO NATURE GENETICS LA English DT Article ID CONGENITAL HYPOTHALAMIC HAMARTOBLASTOMA; GREIG CEPHALOPOLYSYNDACTYLY SYNDROME; IMPERFORATE ANUS; GENE; HYPOPITUITARISM; LOCALIZATION; DELETION; 7P13 AB Pallister-Hail syndrome (PHS, M146510) was first described in 1980 in six newborns. It is a pleiotropic disorder of human development that comprises hypothalamic hamartoma, central polydactyly, and other malformations(1,2). This disorder is inherited as an autosomal dominant trait and has been mapped to 7p13 (S. Kang et al. Autosomal dominant Pallister-Hail syndrome maps to 7p13. Am. J. Hum. Genet. 59, A81 (1996)). colocalizing the PHS locus and the GLI3 zinc finger transcription factor gene(3). Large deletions or translocations resulting in haploinsufficiency of the GLI3 gene have been associated with Greig cephalopolysyndactyly syndrome (GCPS; M175700)(4-6) although no mutations have been identified in GCPS patients with normal karyotypes. Both PHS and GCPS have polysyndactyly, abnormal craniofacial features and are inherited in an autosomal dominant pattern, but they are clinically distinct(7,8). The polydactyly of CCPS is commonly preaxial and that of PHS is typically central or postaxial. No reported cases of CCPS have hypothalamic hamartoma and PHS does not cause hypertelorism or broadening of the nasal root or forehead. The co-localization of the loci for PHS and GCPS led us to investigate GLI3 as a candidate gene for PHS. Herein we report two PHS families with frameshift mutations in GLI3 that are 3' of the zinc finger-encoding domains, including one family with a de novo mutation. These data implicate mutations in GLI3 as the cause of autosomal dominant PHS, and suggest that frameshift mutations of the GLI3 transcription factor gene can alter the development of multiple organ systems in vertebrates. C1 NIH,NATL HUMAN GENOME RES INST,LAB GENET DIS RES,BETHESDA,MD 20892. CEDARS SINAI MED CTR,DEPT PEDIAT,CTR MED GENET BIRTH DEFECTS,LOS ANGELES,CA 90048. UNIV CALIF LOS ANGELES,SCH MED,LOS ANGELES,CA 90048. UNIV NEBRASKA,SCH MED,CTR HUMAN GENET,OMAHA,NE 68198. NR 18 TC 309 Z9 316 U1 3 U2 7 PU NATURE PUBLISHING CO PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 SN 1061-4036 J9 NAT GENET JI Nature Genet. PD MAR PY 1997 VL 15 IS 3 BP 266 EP 268 DI 10.1038/ng0397-266 PG 3 WC Genetics & Heredity SC Genetics & Heredity GA WK386 UT WOS:A1997WK38600015 PM 9054938 ER PT J AU Sternberg, EM AF Sternberg, EM TI Emotions and disease: From balance of humors to balance of molecules SO NATURE MEDICINE LA English DT Editorial Material ID CORTICOTROPIN-RELEASING FACTOR; PITUITARY-ADRENAL AXIS; CENTRAL-NERVOUS-SYSTEM; MESSENGER-RNA; RAT-BRAIN; INTERLEUKIN-1 RECEPTOR; LEWIS RATS; LOCALIZATION; CYTOKINES; MICE AB A new field of research investigates how the immune and nervous systems communicate with each other. RP Sternberg, EM (reprint author), NIMH,SECT NEUROENDOCRINE IMMUNOL & BEHAV,NIH,BLDG 10,RM 2D-46,10 CTR DR,MSC 1284,BETHESDA,MD 20892, USA. NR 45 TC 45 Z9 45 U1 1 U2 3 PU NATURE PUBLISHING CO PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 SN 1078-8956 J9 NAT MED JI Nat. Med. PD MAR PY 1997 VL 3 IS 3 BP 264 EP 267 DI 10.1038/nm0397-264 PG 4 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA WL305 UT WOS:A1997WL30500019 PM 9055845 ER PT J AU Rice, WG Turpin, JA Huang, MJ Clanton, D Buckheit, RW Covell, DG Wallqvist, A McDonnell, NB DeGuzman, RN Summers, MF Zalkow, L Bader, JP Haugwitz, RD Sausville, EA AF Rice, WG Turpin, JA Huang, MJ Clanton, D Buckheit, RW Covell, DG Wallqvist, A McDonnell, NB DeGuzman, RN Summers, MF Zalkow, L Bader, JP Haugwitz, RD Sausville, EA TI Azodicarbonamide inhibits HIV-1 replication by targeting the nucleocapsid protein SO NATURE MEDICINE LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; ACID-BINDING-PROTEINS; REVERSE TRANSCRIPTION; STRAND TRANSFER; ZINC FINGERS; INFECTIVITY; DNA; RNA AB Nucleocapsid p7 (NCp7) proteins of human immunodeficiency virus type 1 (HIV-1) contain two zinc binding domains of the sequence Cys-(X)(2)-Cys-(X)(4)-His-(X)(4)-Cys (CCHC)(1,2). The spacing pattern and metal-chelating residues (3 Cys, 1 His) of these nucleocapsid CCHC zinc fingers are highly conserved among retroviruses(1,3,4). These CCHC domains are required during both the early(5,6) and late(7,8) phases of retroviral replication, making them attractive targets for antiviral agents. Toward that end, we have identified a number of antiviral chemotypes that electrophilically attack the sulfur atoms of the zinc-coordinating cysteine residues of the domains(9-14). Such nucleocapsid inhibitors were directly virucidal by preventing the initiation of reverse transcription(15) and blocked formation of infectious virus from cells through modification of CCHC domains within Gag precursors(16). Herein we report that azodicarbonamide (ADA) represents a new compound that inhibits HIV-1 and a broad range of retroviruses by targeting the the nucleocapsid CCHC domains. Vandevelde et al.(17) also recently disclosed that ADA inhibits HIV-1 infection via an unidentified mechanism and that ADA was introduced into Phase I/II clinical trials in Europe for advanced AIDS. These studies distinguish ADA as the first known nucleocapsid inhibitor to progress to human trials and provide a lead compound for drug optimization. C1 NCI,FREDERICK CANC RES & DEV CTR,SAIC FREDERICK,ANTI AIDS VIRUS DRUG SCREENING LAB,FREDERICK,MD 21702. FREDERICK RES CTR,SO RES INST,VIROL RES GRP,FREDERICK,MD 21701. SAIC FREDERICK,NCI,FREDERICK CANC RES & DEV CTR,DIV BASIC SCI,FREDERICK,MD 21702. UNIV MARYLAND BALTIMORE CTY,HOWARD HUGHES MED INST,BALTIMORE,MD 21228. UNIV MARYLAND BALTIMORE CTY,DEPT CHEM & BIOCHEM,BALTIMORE,MD 21228. GEORGIA INST TECHNOL,DEPT CHEM,ATLANTA,GA 30332. NCI,DEV THERAPEUT PROGRAM,DIV CANC TREATMENT,DIAG & CTR,BETHESDA,MD 20892. RP Rice, WG (reprint author), NCI,FREDERICK CANC RES & DEV CTR,SAIC FREDERICK,LAB ANTIVIRAL DURG MECHANISMS,FREDERICK,MD 21702, USA. OI wallqvist, anders/0000-0002-9775-7469 FU NCI NIH HHS [N01-CO-56000] NR 20 TC 84 Z9 89 U1 0 U2 3 PU NATURE PUBLISHING CO PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 SN 1078-8956 J9 NAT MED JI Nat. Med. PD MAR PY 1997 VL 3 IS 3 BP 341 EP 345 DI 10.1038/nm0397-341 PG 5 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA WL305 UT WOS:A1997WL30500039 PM 9055865 ER PT J AU Wlodawer, A AF Wlodawer, A TI Deposition of macromolecular coordinates resulting from crystallographic and NMR studies SO NATURE STRUCTURAL BIOLOGY LA English DT Editorial Material ID DNA-POLYMERASE-BETA; CRYSTAL-STRUCTURE; ESCHERICHIA-COLI; 3-DIMENSIONAL STRUCTURE; HIV-1; MECHANISM; PROTEASE; DOMAIN; MOTIF RP Wlodawer, A (reprint author), NCI,FREDERICK CANC RES & DEV CTR,MACROMOL STRUCT LAB,ABL,BASIC RES PROGRAM,FREDERICK,MD 21702, USA. NR 25 TC 3 Z9 3 U1 0 U2 0 PU NATURE PUBLISHING CO PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 SN 1072-8368 J9 NAT STRUCT BIOL JI Nat. Struct. Biol. PD MAR PY 1997 VL 4 IS 3 BP 173 EP 174 DI 10.1038/nsb0397-173 PG 2 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA WM071 UT WOS:A1997WM07100006 PM 9164453 ER PT J AU Bebenek, K Beard, WA Darden, TA Li, LP Prasad, R Luxon, BA Gorenstein, DG Wilson, SH Kunkel, TA AF Bebenek, K Beard, WA Darden, TA Li, LP Prasad, R Luxon, BA Gorenstein, DG Wilson, SH Kunkel, TA TI A minor groove binding track in reverse transcriptase SO NATURE STRUCTURAL BIOLOGY LA English DT Letter ID CRYSTAL-STRUCTURE; ANGSTROM RESOLUTION; THUMB SUBDOMAIN; DNA; POLYMERASE; VIRUS; FRAGMENT; FORMS; HELIX AB Evidence is presented indicating that processive synthesis by HIV-1 reverse transcriptase involves interactions between the minor groove of the template-primer and a discrete protein structural element, the minor groove binding track (MGBT). C1 NIEHS,STRUCT BIOL LAB,RES TRIANGLE PK,NC 27709. NIEHS,LAB COMPUTAT BIOL & RISK ANAL,RES TRIANGLE PK,NC 27709. SEALY CTR MOL SCI,GALVESTON,TX 77555. UNIV TEXAS,MED BRANCH,SEALY CTR STRUCT BIOL,GALVESTON,TX 77555. RI Luxon, Bruce/C-9140-2012 NR 27 TC 109 Z9 109 U1 1 U2 2 PU NATURE PUBLISHING CO PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 SN 1072-8368 J9 NAT STRUCT BIOL JI Nat. Struct. Biol. PD MAR PY 1997 VL 4 IS 3 BP 194 EP 197 DI 10.1038/nsb0397-194 PG 4 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA WM071 UT WOS:A1997WM07100012 PM 9164459 ER PT J AU Zhang, L Roth, GS AF Zhang, L Roth, GS TI The effect of aging on rat striatal D-1 receptor mRNA-containing neurons SO NEUROBIOLOGY OF AGING LA English DT Article DE aging; D-1 receptor mRNA-containing neurons; striatum; nonradioactive in situ hybridization; digoxigenin; computer assisted image assessment ID MESSENGER-RNA; DOPAMINE-RECEPTORS; D2 RECEPTORS; WISTAR RATS; IN-SITU; BRAIN; RECOVERY; HYBRIDIZATION; MECHANISMS; BLOCKADE AB In situ hybridization of a digoxigenin-labeled oligonucleotide probe combined with computer assisted image assessment was used to directly visualize D-1 dopamine receptor mRNA-containing neurons in rat striata, and quantify age-related changes in the sizes and relative mRNA content of these neurons. It was found that: 1) numbers of D-1 mRNA-containing neurons appear to decrease in striata of aged rats; 2) relative amounts of D-1 receptor mRNA in individual striatal neurons do not change during aging; and 3) neurons of all sizes appear to be lost, with the greatest absolute decrease in those larger than 150 mu m(2). These data confirm the age associated loss of D-1 dopamine receptors reported for some other rat strains in that species, and further suggest that neuronal loss is responsible for the decrement. The latter finding contrasts with the aging associated loss of D-2 dopamine receptors, which additionally involves decreased amounts of mRNA per cell. (C) 1997 Elsevier Science Inc. RP Zhang, L (reprint author), NIA,NIH,CTR GERONTOL RES,MOL PHYSIOL & GENET SECT,4940 EASTERN AVE,RM 4E05,BALTIMORE,MD 21224, USA. NR 21 TC 10 Z9 10 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0197-4580 J9 NEUROBIOL AGING JI Neurobiol. Aging PD MAR-APR PY 1997 VL 18 IS 2 BP 251 EP 255 DI 10.1016/S0197-4580(97)00011-0 PG 5 WC Geriatrics & Gerontology; Neurosciences SC Geriatrics & Gerontology; Neurosciences & Neurology GA XP013 UT WOS:A1997XP01300016 PM 9258904 ER PT J AU Alkon, DL Elbaum, D Etcheberrigaray, R AF Alkon, DL Elbaum, D Etcheberrigaray, R TI Peripheral membrane abnormalities in Alzheimer's disease SO NEUROBIOLOGY OF AGING LA English DT Letter ID FIBROBLASTS RP Alkon, DL (reprint author), NINCDS,NIH,LAB ADAPT SYST,36 CONVENT DR,MSC 4124,BETHESDA,MD 20892, USA. NR 8 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0197-4580 J9 NEUROBIOL AGING JI Neurobiol. Aging PD MAR-APR PY 1997 VL 18 IS 2 BP 262 EP 262 PG 1 WC Geriatrics & Gerontology; Neurosciences SC Geriatrics & Gerontology; Neurosciences & Neurology GA XP013 UT WOS:A1997XP01300019 ER PT J AU Cimini, V Isaacs, KR Jacobowitz, DM AF Cimini, V Isaacs, KR Jacobowitz, DM TI Calretinin in the rat pituitary: Colocalization with thyroid-stimulating hormone SO NEUROENDOCRINOLOGY LA English DT Article DE calcium-binding protein; immunocytochemistry; in situ hybridization; thyrotropes; catecholamines; calretinin; neurointermediate lobe ID CALCIUM-BINDING PROTEIN; IMMUNOHISTOCHEMICAL LOCALIZATION; INSITU HYBRIDIZATION; TYROSINE-HYDROXYLASE; CELLS; BRAIN; CALBINDIN-D28K; NEURONS; CALMODULIN; EXPRESSION AB The purpose of this study was to examine the distribution of calretinin immunoreactivity (CR) in the male rat pituitary gland by immunofluorescence microscopy. CR was found in cells of the anterior pituitary and in granules in the posterior pituitary. In the intermediate lobe, nerve fibers in close proximity to the melanotropes were CR-immunoreactive (CR-ir). Fine CR-ir varicose fibers were also observed in the anterior and posterior pituitary. Colocalization studies revealed that the majority of the CR-containing cells of the anterior pituitary also contained thyroid-stimulating hormone (TSH). These CR/TSH cells represented about 32% of the thyrotrope population. Following thyroidectomy, a massive increase in both the number of CR-ir cells and in the expression of CR mRNA was observed in the anterior pituitary. Thyroxine treatment, however, resulted in a reduction in the number and size of the CR-ir cells in the same lobe. In the intermediate lobe, CR-ir was colocalized with tyrosine hydroxylase (TH) immunoreactive dopaminergic fibers. These intermediate lobe fibers disappeared following pituitary stalk section, as did the CR/TH fibers and the CR-ir granular material in the posterior pituitary. The findings in the anterior pituitary suggest that consideration be given to the idea that CR might function in the synthesis and/or release mechanism of TSH in thyrotropes and that its expression is modulated by the hypothalamopituitary-thyroid axis. C1 NIMH,CLIN SCI LAB,BETHESDA,MD 20892. NR 42 TC 9 Z9 9 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0028-3835 J9 NEUROENDOCRINOLOGY JI Neuroendocrinology PD MAR PY 1997 VL 65 IS 3 BP 179 EP 188 DI 10.1159/000127179 PG 10 WC Endocrinology & Metabolism; Neurosciences SC Endocrinology & Metabolism; Neurosciences & Neurology GA WN271 UT WOS:A1997WN27100004 PM 9087999 ER PT J AU Epstein, LG Brown, P AF Epstein, LG Brown, P TI Bovine spongiform encephalopathy and a new variant of Creutzfeldt-Jakob disease SO NEUROLOGY LA English DT Editorial Material ID PRION PROTEIN; SCRAPIE; SERIES; MICE C1 UNIV ROCHESTER,SCH MED & DENT,DEPT PEDIAT,ROCHESTER,NY 14642. UNIV ROCHESTER,SCH MED & DENT,DEPT MICROBIOL,ROCHESTER,NY 14642. UNIV ROCHESTER,SCH MED & DENT,DEPT IMMUNOL,ROCHESTER,NY 14642. NINCDS,CNS STUDIES LAB,NIH,BETHESDA,MD 20892. RP Epstein, LG (reprint author), UNIV ROCHESTER,SCH MED & DENT,DEPT NEUROL,BOX 631,601 ELMWOOD AVE,ROCHESTER,NY 14642, USA. NR 24 TC 13 Z9 13 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0028-3878 J9 NEUROLOGY JI Neurology PD MAR PY 1997 VL 48 IS 3 BP 569 EP 571 PG 3 WC Clinical Neurology SC Neurosciences & Neurology GA XC475 UT WOS:A1997XC47500003 PM 9065527 ER PT J AU Stewart, WF Kawas, C Corrada, M Metter, EJ AF Stewart, WF Kawas, C Corrada, M Metter, EJ TI Risk of Alzheimer's disease and duration of NSAID use SO NEUROLOGY LA English DT Article ID NONSTEROIDAL ANTIINFLAMMATORY DRUGS; DEMENTIA; PROTEIN AB In a longitudinal study of 1,686 participants in the Baltimore Longitudinal Study of Aging, we examined whether the risk of Alzheimer's disease (AD) was reduced among reported users of aspirin or other nonsteroidal anti-inflammatory drugs (NSAIDs), In addition, we examined use of acetaminophen, a pain-relief medication with little or no anti-inflammatory activity, to assess the specificity of the association between AD risk and self-reported medications, Information on use of medications was collected during each biennial examination between 1980 and 1995. The relative risk (RR) for AD decreased with increasing duration of NSAID use. Among those with 2 or more years of reported NSAID use, the RR was 0.40 (95% confidence interval [CI]: 0.19-0.843 compared with 0.65 (95% CI: 0.33-1.29) for those with less use, The overall RR for AD among aspirin users was 0.74 (95% CI: 0.46-1.18), and no trend of. decreasing risk of AD was observed Kith increasing duration Of aspirin use, No association was found between AD risk and use of acetaminophen (RR = 1.35; 95% CI: 0.79-2.30), and there was no trend of decreasing risk with increasing duration of use. These findings are consistent with evidence from cross-sectional studies indicating protection against AD risk among NSAID users and with evidence suggesting that one stage of the pathophysiology leading to AD is characterized by an inflammatory process. C1 JOHNS HOPKINS UNIV, SCH MED, DEPT NEUROL, BALTIMORE, MD 21205 USA. NIA, GERONTOL RES CTR, BALTIMORE, MD 21224 USA. RP Stewart, WF (reprint author), JOHNS HOPKINS UNIV, SCH HYG & PUBL HLTH, DEPT EPIDEMIOL, 615 N WOLFE ST, BALTIMORE, MD 21205 USA. OI corrada, maria/0000-0002-8168-8593 FU NIA NIH HHS [R01AG08325] NR 37 TC 797 Z9 821 U1 4 U2 33 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0028-3878 J9 NEUROLOGY JI Neurology PD MAR PY 1997 VL 48 IS 3 BP 626 EP 632 PG 7 WC Clinical Neurology SC Neurosciences & Neurology GA XC475 UT WOS:A1997XC47500013 PM 9065537 ER PT J AU Dalakas, MC Sonies, B Dambrosia, J Sekul, E Cupler, E Sivakumar, K AF Dalakas, MC Sonies, B Dambrosia, J Sekul, E Cupler, E Sivakumar, K TI Treatment of inclusion-body myositis with IVIg: A double-blind, placebo-controlled study SO NEUROLOGY LA English DT Article ID DOSE INTRAVENOUS IMMUNOGLOBULIN; CONTROLLED TRIAL; DERMATOMYOSITIS; POLYMYOSITIS; MYOPATHIES; DISEASES; THERAPY; RISK AB We randomized 19 patients with inclusion-body myositis (IBM) to a double-blind, placebo-controlled, crossover study using monthly infusions of 2 g/kg intravenous immunoglobulin (Mg) or placebo for 3 months. Patients crossed over to the alternate treatment after a washout period. We evaluated responses at baseline and at the end of each treatment period using expanded (0-10) MRC scales, the Maximum Voluntary Isometric Contraction (MVIC) method, symptom and disability scores, and quantitative swallowing studies. We calculated the differences in scores between IVIg and placebo from baseline to end of treatment, Of the 19 patients, 9 (mean age, 61.2 years; mean disease duration, 5.6 years) were randomized to IVIg and 10 (mean age, 66.1 years; mean disease duration. 7.4 years) to placebo. During IVIg the patients gained a mean of 4.2 (-16 to +39.8) MRC points, and during placebo lost 2.7 (-10 to +8) points (p < 0.1). These gains were not significant. Similar results were obtained with the MRC and MVIC scores when the patients crossed to the alternate treatment. Six patients had a functionally important improvement by more than 10 MRC points that declined when crossed over to placebo. Limb-by-limb analysis demonstrated that during Mg the muscle strength in 39% of the lower extremity limbs significantly increased compared with placebo (p < 0.05), while a simultaneous decrease in 28% of other limbs was detected. The clinical importance of these minor gains is unclear. The duration of swallowing functions measured in seconds with ultrasound improved statistically in the IVIg-randomized patients (p < 0.05) compared with placebo. Although the study did not establish efficacy of Mg, possibly because of the small sample size, the drug induced functionally important improvement in 6 (28%) of the 19 patients. Whether the modest gains noted in certain muscle groups justify the high cost of trying IVIg in IBM patients at a given stage of the disease remains unclear. C1 NINCDS,MED NEUROL BRANCH,BETHESDA,MD 20892. NINCDS,SPEECH PATHOL SECT,CTR CLIN,NIH,BETHESDA,MD 20892. NINCDS,BIOMETRY & FIELD STUDIES BRANCH,NIH,BETHESDA,MD 20892. RP Dalakas, MC (reprint author), NINCDS,NEUROMUSCULAR DIS SECT,NIH,BLDG 10,ROOM 4N248,10 CTR DR MSC 1382,BETHESDA,MD 20892, USA. NR 21 TC 204 Z9 205 U1 0 U2 5 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0028-3878 J9 NEUROLOGY JI Neurology PD MAR PY 1997 VL 48 IS 3 BP 712 EP 716 PG 5 WC Clinical Neurology SC Neurosciences & Neurology GA XC475 UT WOS:A1997XC47500029 PM 9065553 ER PT J AU Polymeropoulos, MH Hurko, O Hsu, F Rubenstein, J Basnet, S Lane, K Dietz, H Spetzler, RF Rigamonti, D AF Polymeropoulos, MH Hurko, O Hsu, F Rubenstein, J Basnet, S Lane, K Dietz, H Spetzler, RF Rigamonti, D TI Linkage of the locus for cerebral cavernous hemangiomas to human chromosome 7q in four families of Mexican-American descent SO NEUROLOGY LA English DT Article ID CENTRAL-NERVOUS-SYSTEM; VASCULAR MALFORMATIONS; NATURAL-HISTORY; CEREBROVASCULAR MALFORMATIONS; HUNTINGTON DISEASE; MYOTONIC-DYSTROPHY; BRAIN-STEM; CAG-REPEAT; ANGIOMAS; GENE AB Objective: To determine with greater precision the map location of the locus associated with familial cavernous hemangiomas. Background: Cavernous malformations of the brain are a significant cause of seizures, progressive or apoplectic neurologic deficit, and headache. Prevalence estimates from autopsy series vary from 0.39 to 0.9%. This disorder (OMIM #116860) can be inherited as an autosomal dominant trait with variable penetrance, Linkage to markers on the long arm of chromosome 7 was recently reported in separate reports in three apparently unrelated Hispanic kindreds as well as in two kindreds of non-Hispanic descent, Design/Methods: We examined clinically, by MRI scanning, and by pathologic examination of surgical specimens, members of four large Mexican-American families segregating cavernous hemangiomas of the brain. Linkage analysis was performed with use of blood specimens from morphologically proven cases, Two-point linkage analysis was performed with the MLINK program of the LINKAGE package, Multipoint analysis was performed between two markers and the disease locus with LINKMAP in the FASTLINKAGE package. Allele frequencies were set as described by the Genome Database (GDB). Maximum penetrance for the disease allele was set to 0.75. Results: The highest lod score was observed for marker D7S652 with Z(max) = 6.66 at theta(max) = 0.00. Multipoint LOD score analysis placed the disease locus in the 11 cM interval between markers D7S630 and D7S527 with Z(max) = 9.19. Haplotype analysis is in agreement with the placement of the disease gene between D7S630 and D7S527 and further shows a minimal shared region within this interval, indicating a founder effect in the establishment of the mutation in these families. Conclusions: We confirmed the linkage of cavernous hemangioma to markers on the long arm of chromosome 7q, and the estimate of the map location has been refined to a region of shared haplotype between markers D7S630 and D7S527 in four Mexican-American families who may be descended From a common ancestor in Sonora County, Mexico. C1 JOHNS HOPKINS UNIV,SCH MED,DEPT NEUROL,BALTIMORE,MD 21205. JOHNS HOPKINS UNIV,SCH MED,DEPT PEDIAT,BALTIMORE,MD 21205. JOHNS HOPKINS UNIV,SCH MED,DEPT MED,BALTIMORE,MD 21205. JOHNS HOPKINS UNIV,SCH MED,DEPT NEUROL SURG,BALTIMORE,MD 21205. JOHNS HOPKINS UNIV,SCH MED,CTR GENET MED,BALTIMORE,MD 21205. BARROW NEUROL INST,DEPT NEUROSURG,PHOENIX,AZ 85013. RP Polymeropoulos, MH (reprint author), NIH,LAB GENET DIS RES,NATL CTR HUMAN GENOME RES,BETHESDA,MD 20892, USA. NR 63 TC 50 Z9 63 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0028-3878 J9 NEUROLOGY JI Neurology PD MAR PY 1997 VL 48 IS 3 BP 752 EP 757 PG 6 WC Clinical Neurology SC Neurosciences & Neurology GA XC475 UT WOS:A1997XC47500036 PM 9065560 ER PT J AU Doudet, DJ Chan, GLY Holden, JE Morrison, KS Wyatt, RJ Ruth, TJ AF Doudet, DJ Chan, GLY Holden, JE Morrison, KS Wyatt, RJ Ruth, TJ TI Effects of catechol-O-methyltransferase inhibition on the rates of uptake and reversibility of 6-fluoro-L-dopa trapping in MPTP-induced parkinsonism in monkeys SO NEUROPHARMACOLOGY LA English DT Article DE FDOPA; PET; tolcapone; COMT inhibitor; MPTP-induced parkinsonism ID POSITRON EMISSION TOMOGRAPHY; MONOAMINE-OXIDASE-A; L-DOPA; STRIATAL METABOLISM; COMT INHIBITION; DISEASE; BRAIN; PET; 6-FLUORO-L-DOPA; NITECAPONE AB The uptake rate constant and the loss rate constant that expresses the reversibility of the uptake process of 6-[F-18]fluoro-L-Dopa (FDOPA) were measured by positron emission tomography in the striatum of normal rhesus monkeys and in monkeys with unilateral lesions of the dopaminergic nigro-striatal pathway, induced by intracarotid injection of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Each animal was studied twice: with and without pretreatment of the catechol-O-methyltransferase (COMT) inhibitor Po 40-7592, tolcapone. After pretreatment with tolcapone, there was a very significant increase in plasma FDOPA throughout the course of the study, accompanied by a significant decrease in its main metabolite, 3-O-methylfluorodopa. Tolcapone did not induce a significant change in the uptake rate constant in either the normal or the MPTP-treated striatum. However, after tolcapone pretreatment, there was a significant decrease in the loss rate constant in the MPTP-treated striatum (25%) and a smaller, non-significant decrease in the normal striatum (13%). It is concluded that the COMT inhibitor tolcapone exhibits clear peripheral and central activity. As compared to peripheral COMT inhibitors, this central effect may help preserve and stabilize the synaptic levels of DA and, thus, further improve the effects of L-DOPA therapy in parkinsonian patients. (C) 1997 Elsevier Science Ltd. C1 UNIV BRITISH COLUMBIA,CTR NEURODEGENERAT DISORDERS,VANCOUVER,BC V6T 2B5,CANADA. UNIV BRITISH COLUMBIA,TRIUMF,VANCOUVER,BC V6T 2B5,CANADA. UNIV WISCONSIN,DEPT MED PHYS,MADISON,WI 53706. NIMH,NEUROPSYCHIAT BRANCH,NIH,IRP,BETHESDA,MD 20892. RP Doudet, DJ (reprint author), UNIV BRITISH COLUMBIA,DEPT MED,DIV NEUROL,RM M36,PURDY PAVIL,2211 WESTBROOK MALL,VANCOUVER,BC V6T 2B5,CANADA. NR 31 TC 26 Z9 26 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0028-3908 J9 NEUROPHARMACOLOGY JI Neuropharmacology PD MAR PY 1997 VL 36 IS 3 BP 363 EP 371 DI 10.1016/S0028-3908(97)00017-8 PG 9 WC Neurosciences; Pharmacology & Pharmacy SC Neurosciences & Neurology; Pharmacology & Pharmacy GA WZ228 UT WOS:A1997WZ22800011 PM 9175615 ER PT J AU McCann, UD Slate, SO Geraci, M RoscowTerrill, D Uhde, TW AF McCann, UD Slate, SO Geraci, M RoscowTerrill, D Uhde, TW TI A comparison of the effects of intravenous pentagastrin on patients with social phobia, panic disorder and healthy controls SO NEUROPSYCHOPHARMACOLOGY LA English DT Article DE CCK; chemical models; panic; social interaction ID CHOLECYSTOKININ-TETRAPEPTIDE; PSYCHIATRIC-DISORDERS; ENHANCED SENSITIVITY; UNITED-STATES; INFUSIONS; ANXIETY; PREVALENCE; BEHAVIOR; ATTACKS; WOMEN AB The present study sought to determine whether social phobics, like patients with panic disorder, have increased sensitivity to the panicogenic effects of pentagastrin. Intravenous pentagastrin in and placebo were administered in a double-blind fashion to 19 social phobics, 11 patients with panic disorder, and 19 healthy controls while they participated in a structured social interaction task. Behavioral, cardiovascular, and neuroendocrine responses were obtained. Pentagastrin led to panic attacks in 47% of the social phobics, 64% of the panic disorder patients, and 11% of the healthy controls. The social interaction itself increased anxiety, blood pressure, and pulse in all three groups. These findings suggest that the panicogenic effects of pentagastrin are not limited to patients with panic disorder and provide further evidence for shaved neurobiology in social phobia and panic disorder. (C) 1997 American College of Neuropsychopharmacology. C1 WAYNE STATE UNIV,SCH MED,DEPT PSYCHIAT,DETROIT,MI 48202. RP McCann, UD (reprint author), NIMH,UNIT ANXIETY DISORDERS,BIOL PSYCHIAT BRANCH,NIH,BLDG 10,ROOM 3N-212,MSC 1272,10 CTR DR,BETHESDA,MD 20892, USA. NR 26 TC 42 Z9 42 U1 2 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0893-133X J9 NEUROPSYCHOPHARMACOL JI Neuropsychopharmacology PD MAR PY 1997 VL 16 IS 3 BP 229 EP 237 DI 10.1016/S0893-133X(96)00197-2 PG 9 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA WK132 UT WOS:A1997WK13200006 PM 9138439 ER PT J AU Chen, G Yan, PX Hawver, DB Potter, WZ Manji, HK AF Chen, G Yan, PX Hawver, DB Potter, WZ Manji, HK TI Increase in AP-1 transcription factor DNA binding activity by valproic acid SO NEUROPSYCHOPHARMACOLOGY LA English DT Article DE valproic acid; transcription factors; AP-1; CREB; c-fos; c-jun; mania; depression; lithium; anticonvulsant; bipolar affective disorder ID SIGNAL-TRANSDUCTION PATHWAYS; PROTEIN-KINASE-C; SODIUM VALPROATE; RAT-BRAIN; LITHIUM; FOS; EXPRESSION; PILOCARPINE; MECHANISMS; EFFICACY AB Valproic acid (VPA), a simple branched fatty acid anticonvulsant, had been demonstrated to have clinical efficacy in the treatment of manic-depressive illness (Bowden et al., 1994), but the mechanism(s) by which VPA produces its therapeutic effects remain to be elucidated. VPA's clinical antimanic action require a lag period for onset and are not immediately reversed upon discontinuation of treatment, effects that suggest alternations at the genomic level; we therefore investigated the effects of VPA on the modulation of the DNA binding activity of key transcription factors. DNA binding activities of activator protein 1(AP-1) and cAMP responsive element binding protein (CREB) were studied in acute (hours) and chronic (days) VPA-treated rat C6 glioma cells. VPA did not affect CREB DNA binding activity, but concentration- and time-dependantly increased AP-1 DNA binding activity. The activity was raised at 2 hours (the shortest time examined) and remained high after 6 days (the longest time used) of continuing VPA treatment. VPA was also enhanced AP-1 DNA binding activity in human neuroblastoma (SH-SY5Y) cells. Because the effects of VPA were markedly inhibited by cycloheximide, they appear to require new protein synthesis. Taken together, the data suggest that antimanic agents may affect gene expression by modulation of the activity of major transcription factors; in view of the key roles of these nuclear transcription regulatory factors in long-term neuronal plasticity and cellular responsiveness, these effects may play a major role in VPA's therapeutic efficacy and are worthy of further study. (C) 1997 American College of Neuropsychopharmacology. C1 WAYNE STATE UNIV,SCH MED,DEPT PSYCHIAT & BEHAV NEUROSCI,MOL PATHOPHYSIOL PROGRAM,DETROIT,MI 48201. WAYNE STATE UNIV,SCH MED,DEPT PSYCHIAT & BEHAV NEUROSCI,DETROIT,MI 48201. DETROIT RECEIVING HOSP & UNIV HLTH CTR,NEUROPSYCHIAT RES UNIT,DETROIT,MI. NIMH,CLIN PHARMACOL SECT,BETHESDA,MD 20892. RI Chen, Guang/A-2570-2017 NR 25 TC 63 Z9 64 U1 0 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0893-133X J9 NEUROPSYCHOPHARMACOL JI Neuropsychopharmacology PD MAR PY 1997 VL 16 IS 3 BP 238 EP 245 PG 8 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA WK132 UT WOS:A1997WK13200007 PM 9138440 ER PT J AU Zhang, LX Li, XL Smith, MA Post, RM Han, JS AF Zhang, LX Li, XL Smith, MA Post, RM Han, JS TI Lipofectin-facilitated transfer of cholecystokinin gene corrects behavioral abnormalities of rats with audiogenic seizures SO NEUROSCIENCE LA English DT Article DE CCK; gene transfer; gene therapy; epilepsy; analgesia; liposome ID SEPTOHIPPOCAMPAL CELL-CULTURES; BRAIN-CELLS; ADENOVIRUS VECTORS; OCTAPEPTIDE CCK-8; VIRUS VECTORS; EXPRESSION; INVIVO; SYSTEM; ANALGESIA; LONG AB To evaluate the potential for lipofectin-mediated central nervous system gene transfer, the plasmid coding for cholecystokinin was administered intracerebroventricularly to rats, which have congenital audiogenic seizures and high responses to peripheral electric stimulation-induced analgesia. Previous studies had shown that low brain cholecystokinin levels may be the neurochemical variable of rat's audiogenic seizure and high responses to the analgesia because cholecystokinin is an anticonvulsant and anti-opioid neuropeptide. Gene transfer of cholecystokinin corrected the increased susceptibility to audiogenic seizures and the high responses to analgesia for about one week. Similar administration of plasmid expressing beta-galactosidase indicated that the vector mainly transfected ependymal cells lining the ventricle and pia mater cells. The increased cholecystokinin messenger RNA and immunoreactivity in the hippocampus following stereotactic intrahippocampal administration of cholecystokinin plasmid was also demonstrated with in situ hybridization and immunohistochemistry techniques. These results suggest that lipofectin-mediated gene transfer will be useful for studies of brain function, the modification of behavior and gene therapy for central nervous system disorders. C1 NIMH,BIOL PSYCHIAT BRANCH,BETHESDA,MD 20892. RP Zhang, LX (reprint author), BEIJING MED UNIV,NEUROSCI RES CTR,BEIJING 100083,PEOPLES R CHINA. NR 36 TC 15 Z9 21 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0306-4522 J9 NEUROSCIENCE JI Neuroscience PD MAR PY 1997 VL 77 IS 1 BP 15 EP 22 DI 10.1016/S0306-4522(96)00420-4 PG 8 WC Neurosciences SC Neurosciences & Neurology GA WF712 UT WOS:A1997WF71200002 PM 9044370 ER PT J AU Acri, JB Wong, G Lyon, T Witkin, JM Basile, AS AF Acri, JB Wong, G Lyon, T Witkin, JM Basile, AS TI Localization and pharmacological characterization of pigeon diazepam-insensitive GABA(A) receptors SO NEUROSCIENCE LA English DT Article DE benzodiazepine; diazepam-insensitive; Ro 15-4513; alpha 6 subunit; alpha 4 subunit; autoradiography ID DISCRIMINATIVE STIMULUS PROPERTIES; H-3 RO 15-4513; BENZODIAZEPINE RECEPTORS; ALCOHOL ANTAGONIST; RO 15-4513; BINDING; INVERSE; BRAIN; CELLS; HETEROGENEITY AB Transduction mechanisms associated with ligand binding at diazepam-insensitive subtypes of GABA(A) receptors remain largely unknown, but unique behavioral effects of ligands binding at these sites have been reported in pigeons. The present study further evaluated the pharmacological characteristics of diazepam-insensitive GABA(A) receptors in pigeon brain, using [H-3]Ro 15-4513. Autoradiography detected diazepam-insensitive benzodiazepine sites on GABA(A) receptors in a number of brain regions, with the highest densities present in the olfactory bulb, hippocampus, thalamic nuclei and cerebellar granule cell layers, with densities of similar to 10-20% of total benzodiazepine receptor binding. Saturation analysis revealed significant densities (similar to 10% of total benzodiazepine receptor binding) of extracerebellar diazepam-insensitive benzodiazepine receptors in optic lobe, hippocampus, and brainstem compared to 27% in cerebellum. As reported for mammalian diazepam-sensitive benzodiazepine receptors, GABA (50 mu M) generally increased the affinities of agonists and partial agonists, had little effect on the affinities of antagonists, and decreased the affinity of an inverse agonist for pigeon cerebellar diazepam-sensitive benzodiazepine receptors. GABA modulation of ligand binding to diazepam-insensitive benzodiazepine receptors was less than that observed for diazepam-sensitive sites, and no positive modulation was observed. These results demonstrate the presence of cerebellar and extracerebellar diazepam-insensitive benzodiazepine receptors in pigeon brain, with distribution patterns and pharmacology similar to those reported in mammals. The comparable central localization and pharmacological properties of drugs at diazepam-sensitive and -insensitive benzodiazepine receptors in pigeons and rats attests to the evolutionary conservation of GABA(A) systems. C1 NIDA, ADDICT RES CTR, PSYCHOBIOL SECT, DRUG DEV GRP, NIH, BALTIMORE, MD 21224 USA. NIDDK, NEUROSCI LAB, NIH, BETHESDA, MD 20892 USA. NR 34 TC 6 Z9 6 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0306-4522 J9 NEUROSCIENCE JI Neuroscience PD MAR PY 1997 VL 77 IS 2 BP 371 EP 378 DI 10.1016/S0306-4522(96)00469-1 PG 8 WC Neurosciences SC Neurosciences & Neurology GA WK428 UT WOS:A1997WK42800008 PM 9472397 ER PT J AU Freeman, SPHT King, JC Vieira, NE Woodhouse, LR Yergey, AL AF Freeman, SPHT King, JC Vieira, NE Woodhouse, LR Yergey, AL TI Human calcium metabolism including bone resorption measured with Ca-41 tracer SO NUCLEAR INSTRUMENTS & METHODS IN PHYSICS RESEARCH SECTION B-BEAM INTERACTIONS WITH MATERIALS AND ATOMS LA English DT Article; Proceedings Paper CT 7th Conference on Accelerator Mass Spectrometry CY MAY 20-24, 1996 CL TUCSON, AZ SP AMS AB Accelerator mass spectrometry is so sensitive to small quantities of Ca-41 that it might be used as a tracer in the study of human calcium kinetics to generate unique kinds of data. In contrast with the use of other Ca isotopic tracers, Ca-41 tracer can be so administered that the tracer movements between the various body pools achieve a quasi steady state, Resorbing bone may thus be directly measured, We have tested such a protocol against a conventional stable isotope experiment with good agreement. C1 LAWRENCE LIVERMORE NATL LAB,CTR ACCELERATOR MASS SPECTROMETRY,LIVERMORE,CA 94551. UNIV CALIF BERKELEY,DEPT NUTR SCI,BERKELEY,CA 94720. NICHHD,BETHESDA,MD 20892. RI Freeman, Stewart/C-3290-2012 OI Freeman, Stewart/0000-0001-6148-3171 NR 5 TC 45 Z9 46 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0168-583X J9 NUCL INSTRUM METH B JI Nucl. Instrum. Methods Phys. Res. Sect. B-Beam Interact. Mater. Atoms PD MAR PY 1997 VL 123 IS 1-4 BP 266 EP 270 DI 10.1016/S0168-583X(96)00701-X PG 5 WC Instruments & Instrumentation; Nuclear Science & Technology; Physics, Atomic, Molecular & Chemical; Physics, Nuclear SC Instruments & Instrumentation; Nuclear Science & Technology; Physics GA WT653 UT WOS:A1997WT65300055 ER PT J AU Grady, PA AF Grady, PA TI News from NINR SO NURSING OUTLOOK LA English DT News Item RP Grady, PA (reprint author), NINR,NIH,BETHESDA,MD 20892, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 SN 0029-6554 J9 NURS OUTLOOK JI Nurs. Outlook PD MAR-APR PY 1997 VL 45 IS 2 BP 72 EP 72 DI 10.1016/S0029-6554(97)90082-8 PG 1 WC Nursing SC Nursing GA WV236 UT WOS:A1997WV23600005 ER PT J AU Grady, PA Harden, JT Moritz, P Amende, LM AF Grady, PA Harden, JT Moritz, P Amende, LM TI Incorporating environmental sciences and nursing research: An NINR initiative SO NURSING OUTLOOK LA English DT Article AB The environment is a pivotal determinant of human health and well-being; and understanding its impact is essential to improving public health. This article reflects the deliberations of a panel convened by the National Institute of Nursing Research to identify gaps in environmental sciences, along with research opportunities and challenges that could be explored through investigator-initiated clinical studies. RP Grady, PA (reprint author), NINR,NIH,DIV EXTRAMURAL ACT,BETHESDA,MD 20892, USA. NR 3 TC 11 Z9 11 U1 0 U2 0 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 SN 0029-6554 J9 NURS OUTLOOK JI Nurs. Outlook PD MAR-APR PY 1997 VL 45 IS 2 BP 73 EP 75 DI 10.1016/S0029-6554(97)90083-X PG 3 WC Nursing SC Nursing GA WV236 UT WOS:A1997WV23600006 PM 9127346 ER PT J AU Toporoff, EG French, SA Story, M Himes, JH Snyder, MP DuBray, M Rock, BH Hunsberger, S AF Toporoff, EG French, SA Story, M Himes, JH Snyder, MP DuBray, M Rock, BH Hunsberger, S TI Do children eat what they say? Validity of intended food choices among Native American school children SO OBESITY RESEARCH LA English DT Article DE food intentions; food choices; self-reported measures; cafeteria observation; school-aged children ID PHYSICAL-ACTIVITY; PREFERENCES; BEHAVIORS; CONSUMPTION; PROMOTION; OUTCOMES; MODEL AB Objective, To examine the agreement between school children's intended food choices and observed food choices. Design. Native American students in the second through fifth grade completed a questionnaire that asked them to select from 10 paired food choices for a given meal or snack. Three weeks later students chose among foods identical to those on the questionnaire as part of their usual school lunch or breakfast over three consecutive days; afternoon snacks were also offered. Results, Agreement between students' intended food choices and observed food choices was examined across 10 food pairs. The composite kappa coefficient between intended and observed food choices was 0.09 (95% confidence interval 0.06, 0.12), indicating virtually no agreement above that expected by chance. There were no differences in agreement by sex or grade. Conclusions, Intended food choices were not significantly associated with observed food choices. It is unclear whether intended food choices reflect nutrition knowledge, socially desirable responses, food preferences, or some other dimension of eating behavior. Although responsive to school-based nutrition interventions, the interpretation of changes in intended food choices must be clarified in future research. C1 UNIV MINNESOTA,DIV EPIDEMIOL,MINNEAPOLIS,MN 55454. NIH,OFF BIOSTAT RES,BETHESDA,MD 20892. FU NHLBI NIH HHS [5U01 HL50885-02] NR 18 TC 5 Z9 5 U1 0 U2 2 PU NORTH AMER ASSOC STUDY OBESITY PI BATON ROUGE PA 6400 PERKINS RD, BATON ROUGE, LA 70808 SN 1071-7323 J9 OBES RES JI Obes. Res. PD MAR PY 1997 VL 5 IS 2 BP 87 EP 92 PG 6 WC Endocrinology & Metabolism; Nutrition & Dietetics SC Endocrinology & Metabolism; Nutrition & Dietetics GA WR888 UT WOS:A1997WR88800001 PM 9112242 ER PT J AU Kahle, EB Butz, KG Chua, SC Kershaw, EE Leibel, RL Fenger, TW Hansen, CT Michaelis, OE AF Kahle, EB Butz, KG Chua, SC Kershaw, EE Leibel, RL Fenger, TW Hansen, CT Michaelis, OE TI The rat corpulent (cp) mutation maps to the same interval on (Pgm1-Glut1) rat chromosome 5 as the fatty (fa) mutation SO OBESITY RESEARCH LA English DT Article DE inherited; single-gene; obesity; genes ID GENETICALLY-OBESE RAT; SUCROSE; INSULIN; MOUSE; GLUCOSE; LOCUS; MICE AB The autosomal recessive obesity mutations fatty (fa) and corpulent (cp) arose in separate rat strains, 13M and Koletsky, respectively. By complementation analysis, the two mutations appear to be in the same gene. The somewhat different phenotypes of fa/fa and cp/cp animals probably reflect the fact that the mutations are segregating on different rat strains. The fa mutation has been mapped to the interval between Pgm1 and Glut1 on rat Chr 5, but cp has not been mapped genetically. We mapped cp in 30 obese progeny of a LA/N-BN cp/+ intercross using microsatellite markers for these flanking genes. Cp maps to the same genetic interval as rat fa and mouse db. Cp is flanked by Glut1 and Pgm1: [GRAPHICS] Thus, cp and fa map to the same similar to 8 cM interval of the rat genome. In conjunction with the complementation studies alluded to above, these findings indicate that cp and fa are mutations in the same gene (Lepr). C1 MARSHALL UNIV,DEPT MICROBIOL,HUNTINGTON,WV 25755. ROCKEFELLER UNIV,HUMAN BEHAV & METAB LAB,NEW YORK,NY 10021. NIH,DIV RES SERV,BETHESDA,MD 20892. USDA,BELTSVILLE HUMAN NUTR RES CTR,BELTSVILLE,MD 20705. RP Kahle, EB (reprint author), MARSHALL UNIV,DEPT BIOL,HUNTINGTON,WV 25755, USA. RI Kershaw, Erin/G-9587-2013 FU NICHD NIH HHS [HD28047]; NIDDK NIH HHS [DK28867, DK47473] NR 36 TC 11 Z9 11 U1 0 U2 0 PU NORTH AMER ASSOC STUDY OBESITY PI BATON ROUGE PA 6400 PERKINS RD, BATON ROUGE, LA 70808 SN 1071-7323 J9 OBES RES JI Obes. Res. PD MAR PY 1997 VL 5 IS 2 BP 142 EP 145 PG 4 WC Endocrinology & Metabolism; Nutrition & Dietetics SC Endocrinology & Metabolism; Nutrition & Dietetics GA WR888 UT WOS:A1997WR88800008 PM 9112249 ER PT J AU Bowman, ED Shields, PG Caporaso, NE Tucker, MA Hoover, RN Trump, BF Harris, CC AF Bowman, ED Shields, PG Caporaso, NE Tucker, MA Hoover, RN Trump, BF Harris, CC TI Chromosome 13 poly(ADP-ribose) polymerase polymorphisms and lung cancer risk SO ONCOLOGY REPORTS LA English DT Article DE chromosome 13; poly(ADP-ribose) polymerase; lung cancer ID GENE; DNA AB A 193 base pair repeat polymorphism in the human poly(ADP-ribose) polymerase (PADPRP) pseudogene found on chromosome 13 has been associated with lung cancer, endemic Burkitt lymphoma, B-cell lymphoma, breast cancer and colorectal carcinoma. We investigated the frequency of the PADPRP genetic polymorphism in a hospital-based case-control study of lung cancer for 54 cases and 47 controls. There was a statistically significant difference in allelic frequency between Caucasians and African Americans (p<0.001). For African Americans, the odds ratio for lung cancer and the 'B' allele was 2.38 (95% C.I.=0.73, 7.69) and for Caucasians 0.44 (95% C.I.=0.11, 1.77). The results for the African Americans, however, were not in Hardy-Weinberg equilibrium, although the Caucasians were. Thus, this study, albeit small, does not find that the PADPRP pseudogene duplicated region located on chromosome 13 is a risk factor for lung cancer. C1 NCI,HUMAN CARCINOGENESIS LAB,DIV BASIC SCI,NIH,BETHESDA,MD 20892. NCI,GENET EPIDEMIOL BRANCH,DIV EPIDEMIOL & GENET,NIH,BETHESDA,MD 20892. UNIV MARYLAND,DEPT PATHOL,BALTIMORE,MD 21201. RI Shields, Peter/I-1644-2012; Tucker, Margaret/B-4297-2015 NR 13 TC 0 Z9 0 U1 0 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 1021-335X J9 ONCOL REP JI Oncol. Rep. PD MAR-APR PY 1997 VL 4 IS 2 BP 269 EP 272 PG 4 WC Oncology SC Oncology GA WJ450 UT WOS:A1997WJ45000002 PM 21590040 ER PT J AU Lenz, FA Gracely, RH Zirh, AT Romanoski, AJ Dougherty, PM AF Lenz, FA Gracely, RH Zirh, AT Romanoski, AJ Dougherty, PM TI The sensory-limbic model of pain memory - Connections from thalamus to the limbic system mediate the learned component of the affective dimension of pain SO PAIN FORUM LA English DT Article DE neurophysiology; pain measurement; memory; affect; emotion; ventral posterior thalamic nucleus ID CORONARY-ARTERY OCCLUSION; MONKEY LATERAL THALAMUS; INTRACARDIAC INJECTION; ELECTRICAL-STIMULATION; NOCICEPTIVE RESPONSES; SOMATOSENSORY FIELDS; SPINOTHALAMIC TRACT; HEAT STIMULI; NEURONS; NUCLEUS AB Stimulation in the human somatosensory thalamus, posteroinferior to the human principal sensory nucleus (ventralis caudalis), has been reported to reproduce previously experienced pain associated with a strong affective dimension. In these reports, pains with a strong affective dimension were reproduced by stimulation within and posteroinferior to the core (posteroinferior region) of the ventralis caudalis only in patients with previous experience of such pain. Similar vivid experiential responses have been reported with stimulation over the parasylvian cortex. Thus, the connection from the posteroinferior region to the secondary somatosensory cortex and insular cortex may explain the reproduction, by thalamic stimulation, of pain with a strong affective dimension. The secondary somatosensory and insular cortex are involved in nociceptive pathways that have similar characteristics to cortical areas known to be involved in visual memory through corticolimbic connections. Therefore, stimulation-evoked pain with a strong affective dimension may be explained by a model in which limbic structures are altered by previous experience of pain with a strong affective dimension and triggered, through thalamic corticolimbic connections, to reproduce that pain. This sensory-limbic model could form the framework for testable hypotheses regarding the anatomic and physiologic substrates of learning processes involved in,the affective dimension of pain. C1 JOHNS HOPKINS UNIV HOSP,DEPT NEUROSURG,BALTIMORE,MD 21205. JOHNS HOPKINS UNIV HOSP,DEPT PSYCHIAT,BALTIMORE,MD 21205. NIDR,NEUROBIOL & ANESTHESIOL BRANCH,NIH,BETHESDA,MD 20892. OI Dougherty, Patrick/0000-0002-2177-2734 NR 78 TC 24 Z9 24 U1 0 U2 2 PU CHURCHILL LIVINGSTONE INC MEDICAL PUBLISHERS PI NEW YORK PA 650 AVENUE OF THE AMERICAS, NEW YORK, NY 10011 SN 1058-9139 J9 PAIN FORUM JI Pain Forum PD SPR PY 1997 VL 6 IS 1 BP 22 EP 31 PG 10 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA WQ443 UT WOS:A1997WQ44300006 ER PT J AU Lenz, FA Gracely, RH Zirh, AT Romanoski, AJ Staats, P Dougherty, PM AF Lenz, FA Gracely, RH Zirh, AT Romanoski, AJ Staats, P Dougherty, PM TI The sensory-limbic model suggests testable hypotheses about the learned component of the affective dimension of pain SO PAIN FORUM LA English DT Editorial Material ID STIMULATION; THALAMUS; NUCLEUS C1 JOHNS HOPKINS UNIV HOSP,DEPT NEUROSURG,BALTIMORE,MD 21205. JOHNS HOPKINS UNIV HOSP,DEPT PSYCHIAT,BALTIMORE,MD 21205. NIDR,NEUROBIOL & ANESTHESIOL BRANCH,NIH,BETHESDA,MD 20892. NR 28 TC 1 Z9 1 U1 0 U2 1 PU CHURCHILL LIVINGSTONE INC MEDICAL PUBLISHERS PI NEW YORK PA 650 AVENUE OF THE AMERICAS, NEW YORK, NY 10011 SN 1058-9139 J9 PAIN FORUM JI Pain Forum PD SPR PY 1997 VL 6 IS 1 BP 41 EP 43 PG 3 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA WQ443 UT WOS:A1997WQ44300010 ER PT J AU Teigen, PM AF Teigen, PM TI A catalogue of printed books in the Wellcome Historical Medical Library, Vol 4: Books from 1641-1850 - Symons,HJM, Denham,HR SO PAPERS OF THE BIBLIOGRAPHICAL SOCIETY OF AMERICA LA English DT Book Review RP Teigen, PM (reprint author), NATL LIB MED,DIV HIST MED,BETHESDA,MD 20894, USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU BIBLIOGRAPHICAL SOC AMER PI NEW YORK PA BOX 397 GRAND CENTRAL STATION, NEW YORK, NY 10163 SN 0006-128X J9 PAP BIBLIOGR SOC AM JI Pap. Bibliogra. Soc. Am. PD MAR PY 1997 VL 91 IS 1 BP 110 EP 112 PG 3 WC Humanities, Multidisciplinary SC Arts & Humanities - Other Topics GA WP707 UT WOS:A1997WP70700012 ER PT J AU Cooper, PJ Guderian, RH Proano, R Taylor, DW AF Cooper, PJ Guderian, RH Proano, R Taylor, DW TI The pathogenesis of chorioretinal disease in onchocerciasis SO PARASITOLOGY TODAY LA English DT Review ID IMMUNOLOGICAL CROSS-REACTIVITY; OCULAR ONCHOCERCIASIS; IMMUNE-COMPLEXES; SIERRA-LEONE; AUTOANTIBODIES; IVERMECTIN; VOLVULUS; INTENSITY; INFECTION; COMMUNITY AB The pathogenesis of onchocercal chorioretinopathy is poorly understood. In this article, Philip Cooper, Ronald Gudarian, Roberto Proano and David Taylor discuss the important clinical, histological and epidemiological features of the resulting lesions that cause blindness, and review the numberous mechanisms that have been put forward to explain its pathogenesis. The pathogenesis of anterior segment disease, particularly sclerosing keratitis, has been reviewed in depth previously(1) and will not be discussed here. C1 HOSP VOZANDES,ONCHOCERCIASIS CONTROL PROGRAMME,QUITO,ECUADOR. UNIV EDINBURGH,CTR TROP VET MED,EDINBURGH EH25 9RG,MIDLOTHIAN,SCOTLAND. RP Cooper, PJ (reprint author), NIH,PARASIT DIS LAB,BLDG 4,ROOM 126,BETHESDA,MD 20892, USA. NR 59 TC 4 Z9 4 U1 0 U2 0 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, OXON, ENGLAND OX5 1GB SN 0169-4758 J9 PARASITOL TODAY JI Parasitol. Today PD MAR PY 1997 VL 13 IS 3 BP 94 EP 98 DI 10.1016/S0169-4758(97)01005-3 PG 5 WC Parasitology SC Parasitology GA WJ629 UT WOS:A1997WJ62900007 PM 15275111 ER PT J AU Cizza, G Chrousos, GP AF Cizza, G Chrousos, GP TI Anxiety and short stature SO PEDIATRICS LA English DT Letter ID STRESS RP Cizza, G (reprint author), NICHHD,SECT PEDIAT ENDOCRINOL,DEV ENDOCRINOL BRANCH,NIH,BETHESDA,MD 20892, USA. NR 7 TC 0 Z9 0 U1 0 U2 0 PU AMER ACAD PEDIATRICS PI ELK GROVE VILLAGE PA 141 NORTH-WEST POINT BLVD, ELK GROVE VILLAGE, IL 60007-1098 SN 0031-4005 J9 PEDIATRICS JI Pediatrics PD MAR PY 1997 VL 99 IS 3 BP 500 EP 500 PG 1 WC Pediatrics SC Pediatrics GA WR147 UT WOS:A1997WR14700044 PM 9041314 ER PT J AU Vautrin, J Kriebel, ME AF Vautrin, J Kriebel, ME TI Giant and sub-miniature end-plate potentials SO PFLUGERS ARCHIV-EUROPEAN JOURNAL OF PHYSIOLOGY LA English DT Letter ID SUBUNITS; CURRENTS; MOUSE C1 NINCDS,LNP,NIH,BETHESDA,MD 20892. SUNY HLTH SCI CTR,COLL MED,DEPT PHYSIOL,SYRACUSE,NY 13210. RP Vautrin, J (reprint author), USTL MONTPELLIER,INSERM,U432,MONTPELLIER,FRANCE. NR 12 TC 2 Z9 2 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0031-6768 J9 PFLUG ARCH EUR J PHY JI Pflugers Arch. PD MAR PY 1997 VL 433 IS 5 BP 669 EP 670 DI 10.1007/s004240050329 PG 2 WC Physiology SC Physiology GA WM211 UT WOS:A1997WM21100017 PM 9049154 ER PT J AU SamsDodd, F Newman, JD AF SamsDodd, F Newman, JD TI Effects of administration regime on the psychotomimetic properties of d-amphetamine in the squirrel monkey (Saimiri sciureus) SO PHARMACOLOGY BIOCHEMISTRY AND BEHAVIOR LA English DT Article DE animal model; primates; psychosis; schizophrenia ID PSYCHOSIS; BEHAVIOR AB Studies have reported that d-amphetamine can induce a schizophreniform psychosis in humans and can induce abnormal behaviour patterns in monkeys that resemble the psychotic symptoms observed in man. The purpose of the present study was to identify a drug administration regime that in squirrel monkeys reliably could induce such behaviours in order to use this as a model of schizophrenia. The behavioural effects of acute, subchronic and continuous administration of d-amphetamine were determined in male and female squirrel monkeys during short term separation from the colony and in the home cage. It was found that abnormal behaviours developed in both male and female subjects and that they were most evident in the home cage. The number of subjects responding was highest during continuous infusion followed by subchronic treatment. The study indicated that prolonged administration of high doses of d-amphetamine is necessary for the development of abnormal behaviours. These findings suggest that animal models of schizophrenia based on d-amphetamine should be based on chronic administration or continuous infusion of d-amphetamine instead of acute injections. Copyright (C) 1997 Elsevier Science Inc. C1 NICHHD, COMPARAT ETHOL LAB, NIH, POOLESVILLE, MD 20837 USA. NR 28 TC 11 Z9 11 U1 1 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0091-3057 J9 PHARMACOL BIOCHEM BE JI Pharmacol. Biochem. Behav. PD MAR PY 1997 VL 56 IS 3 BP 471 EP 480 DI 10.1016/S0091-3057(96)00332-2 PG 10 WC Behavioral Sciences; Neurosciences; Pharmacology & Pharmacy SC Behavioral Sciences; Neurosciences & Neurology; Pharmacology & Pharmacy GA WQ103 UT WOS:A1997WQ10300019 PM 9077585 ER PT J AU Baptista, T Lopez, ME Teneud, L Contreras, Q Alastre, T deQuijada, M deBaptista, EA Alternus, M Weiss, SRB Musseo, E Paez, X Hernandez, L AF Baptista, T Lopez, ME Teneud, L Contreras, Q Alastre, T deQuijada, M deBaptista, EA Alternus, M Weiss, SRB Musseo, E Paez, X Hernandez, L TI Amantadine in the treatment of neuroleptic-induced obesity in rats: Behavioral, endocrine and neurochemical correlates SO PHARMACOPSYCHIATRY LA English DT Article ID STIMULATES FOOD-INTAKE; BODY-WEIGHT; LATERAL HYPOTHALAMUS; SYSTEMIC SULPIRIDE; PROLACTIN; DOPAMINE; SCHIZOPHRENIA; RECEPTORS; INHIBITION; INCREASE AB The efficacy of the antiviral agent Amantadine (AM, 5-100 mg/kg/sc, ip or intrahypothalamically, 12.5 - 100 mu g bilaterally) in influencing body weight and food intake in drug-free rats, and in preventing neuroleptic-induced weight gain, was assessed in adult female rats. In drug-free rats, acute administration of systemic AM or directly injected in the lateral hypothalamus (LH) displayed a significant dose-dependent anorectic effect (p < 0.001). This effect could be mediated by the brain monoaminergic system, because systemic or local injections of AM increased dopamine and serotonin overflow in the nucleus accumbens and in the LH. Chronic administration of AM significantly decreased body weight gain in drug-free rats only at the dose of 100 mg/kg/sc. Similarly, obesity induced by the neuroleptic drug sulpiride (SUL, 20 mg/kg/ip for 21 days) was prevented by AM only at the dose of 100 mg/kg. AM did not prevent SUL-induced hyperprolactinemia, disruption of the vaginal cycle and a decrement in the weight of the uterus and ovaries at any dosage. This lack of efficacy of AM contrasts with that of bromocriptine, which completely prevented SUL-induced weight gain and hyperprolactinemia. The results show that despite a potent acute anorectic effect, AM displays a weak antagonistic action on SUL-induced obesity in rats, in contrast to the preliminary results obtained in humans. As AM metabolism differs in humans and rats, additional research is needed before its systematic testing in counteracting neuroleptic-induced obesity in patients with mental disorders. C1 UNIV LOS ANDES, SCH MED, DEPT PHYSIOL, MERIDA, VENEZUELA. UNIV LOS ANDES, SCH MED, DEPT PSYCHIAT, MERIDA, VENEZUELA. UNIV LOS ANDES, SCH PHARM, DEPT MICROBIOL, MERIDA, VENEZUELA. NIMH, BETHESDA, MD 20892 USA. NR 59 TC 28 Z9 28 U1 0 U2 1 PU GEORG THIEME VERLAG KG PI STUTTGART PA RUDIGERSTR 14, D-70469 STUTTGART, GERMANY SN 0176-3679 J9 PHARMACOPSYCHIATRY JI Pharmacopsychiatry PD MAR PY 1997 VL 30 IS 2 BP 43 EP 54 DI 10.1055/s-2007-979482 PG 12 WC Pharmacology & Pharmacy; Psychiatry SC Pharmacology & Pharmacy; Psychiatry GA WU645 UT WOS:A1997WU64500002 PM 9131724 ER PT J AU Sloand, EM AF Sloand, EM TI Viral risks associated with blood transfusion SO PHOTOCHEMISTRY AND PHOTOBIOLOGY LA English DT Article ID HEPATITIS-B VIRUS; RECOMBINANT IMMUNOBLOT ASSAY; POLYMERASE CHAIN-REACTION; C VIRUS; POSTTRANSFUSION HEPATITIS; HTLV-II; CYTOMEGALOVIRUS-INFECTION; TRANSMITTED VIRUSES; DNA AMPLIFICATION; TYPE-1 INFECTION AB Great strides have been made within the last decade to help ensure the safety of the blood supply. Additional tests to detect infectious agents, as well as development of improved donor screening and deferral techniques have helped make the risk of transfusion-transmitted disease very low. Currently, blood banks perform seven tests to detect infectious agents. Prospective donors are carefully questioned about factors that place them at risk for transfusion-transmitted disease and donors known to test positive for certain viruses are permanently deferred, The risks of receiving a human immunodeficiency virus (HIV)-infected unit is now estimated to be 1 in 493000, while the risk of hepatitis B is 1 in 63000. However, changes in prevalence within the blood donor population brought about by changes in the factors that place an individual at risk for a transfusion-transmitted disease could significantly alter these risks. The American public continues to be concerned about the safety of blood transfusion, These concerns coupled with the fears that new viruses or new strains of viruses will be identified that escape detection has created the impetus for development of methods that will remove or inactivate viruses in cellular blood products. C1 NHLBI,BETHESDA,MD 20892. NR 54 TC 10 Z9 10 U1 1 U2 1 PU AMER SOC PHOTOBIOLOGY PI AUGUSTA PA BIOTECH PARK, 1021 15TH ST, SUITE 9, AUGUSTA, GA 30901-3158 SN 0031-8655 J9 PHOTOCHEM PHOTOBIOL JI Photochem. Photobiol. PD MAR PY 1997 VL 65 IS 3 BP 428 EP 431 DI 10.1111/j.1751-1097.1997.tb08583.x PG 4 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA WP722 UT WOS:A1997WP72200013 PM 9077125 ER PT J AU Martinez, LJ Li, G Chignell, CF AF Martinez, LJ Li, G Chignell, CF TI Photogeneration of fluoride by the fluoroquinolone antimicrobial agents lomefloxacin and fleroxacin SO PHOTOCHEMISTRY AND PHOTOBIOLOGY LA English DT Article ID QUINOLONE ANTIBACTERIAL AGENTS; REACTIVITY; PHOTOLYSIS; OXYGEN; MICE AB The photolysis (>320 nm) of the fluoroquinolone antibacterial agents lomefloxacin and fleroxacin results in the loss of their Fs atoms as fluoride. The quantum yield for lomefloxacin was 0.98 at pH 7.4. The mechanism probably involves aryl-F heterolysis from the S-1 state with the concomitant generation of a carbene at C-8, In contrast, the monofluorinated fluoroquinolones norfloxacin and ciprofloxacin do not generate fluoride upon irradiation. Carbenes are highly reactive species that undergo addition, insertion and abstraction reactions and can cause DNA cleavage. These findings may explain why lomefloxacin and fleroxacin are more photomutagenic and photocarcinogenic than fluoroquiuolones in which C-8 is either unsubstituted or bears a substituent other than fluorine. C1 NIEHS,LAB PHARMACOL & CHEM,NIH,RES TRIANGLE PK,NC 27709. NR 22 TC 95 Z9 98 U1 4 U2 8 PU AMER SOC PHOTOBIOLOGY PI AUGUSTA PA BIOTECH PARK, 1021 15TH ST, SUITE 9, AUGUSTA, GA 30901-3158 SN 0031-8655 J9 PHOTOCHEM PHOTOBIOL JI Photochem. Photobiol. PD MAR PY 1997 VL 65 IS 3 BP 599 EP 602 DI 10.1111/j.1751-1097.1997.tb08612.x PG 4 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA WP722 UT WOS:A1997WP72200042 PM 9077147 ER PT J AU Shrader, JA Siegel, KL AF Shrader, JA Siegel, KL TI Postsurgical hindfoot deformity of a patient with rheumatoid arthritis treated with custom-made foot orthoses and shoe modifications SO PHYSICAL THERAPY LA English DT Article DE foot orthoses; rehabilitation; rheumatoid arthritis; shoe modifications; triple arthrodesis ID GAIT; ANKLE AB This case report describes the treatment of a 73-year-old woman with long-standing, severe rheumatoid arthritis, using custom-made foot orthoses and shoe modifications. The patient was referred for physical therapy 4 weeks after triple arthrodesis of her right foot. Her primary complaint was periodic unsteadiness during gait, which necessitated the use of a cane at all times. Other problems included a lower-extremity length discrepancy and right foot pain. Physical therapy included fabrication of bilateral semirigid foot orthoses, shoe modifications, gait training, and instruction in strengthening exercises. After treatment, the patient reported feeling steady during walking without a cane, and she was able to resume community activities without right foot pain. Computerized movement analysis of gait revealed that the use of orthoses and modified footwear reduced weight bearing and movement-pattern abnormalities, as compared with barefoot walking. The findings in this case show that physical therapy including foot orthoses, shoe modifications, gait training, and strengthening exercises can be instrumental in the postsurgical rehabilitation of a patient with severe rheumatoid arthritis. C1 NIH,WARREN GRANT MAGNUSON CLIN CTR,DEPT REHABIL MED,BIOMECH LAB,BETHESDA,MD 20892. RP Shrader, JA (reprint author), NIH,WARREN GRANT MAGNUSON CLIN CTR,DEPT REHABIL MED,BLDG 10,ROOM 6S235,9000 WISCONSIN AVE,BETHESDA,MD 20892, USA. RI Siegel, Karen Lohmann/B-5898-2008; OI Siegel, Karen Lohmann/0000-0002-0788-6612 NR 21 TC 4 Z9 4 U1 0 U2 2 PU AMER PHYSICAL THERAPY ASSOC PI ALEXANDRIA PA 1111 N FAIRFAX ST, ALEXANDRIA, VA 22314 SN 0031-9023 J9 PHYS THER JI Phys. Ther. PD MAR PY 1997 VL 77 IS 3 BP 296 EP 305 PG 10 WC Orthopedics; Rehabilitation SC Orthopedics; Rehabilitation GA WL837 UT WOS:A1997WL83700008 PM 9062571 ER PT J AU Breslow, RA Sorkin, JD Frey, CM Kessler, LG AF Breslow, RA Sorkin, JD Frey, CM Kessler, LG TI Americans' knowledge of cancer risk and survival SO PREVENTIVE MEDICINE LA English DT Article ID BREAST-CANCER; AGE; MAMMOGRAPHY; WOMEN; ATTITUDES AB Background. There are more than 500,000 deaths from cancer each year in the United States. This study examines Americans' knowledge of risk factors for breast, cervical, colon, and prostate cancers, which account for over 130,000 of these deaths, and their knowledge of the prospects of surviving these cancers following early detection. Methods. Data were obtained from 12,035 subjects who completed the 1992 National Health interview Survey Cancer Control Supplement which includes questions about cancer risk factors and survival. Results. The majority of respondents were unable to identify major cancer risk factors when prompted with a list. Approximately two-thirds did not recognize that age increased the risk for breast and colon cancer, that diet increased the risk for colon cancer, or that multiple sex partners increased the risk for cervical cancer. Knowledge about survival was also poor. Only about half thought they had a good chance of survival following early detection of colon and cervical cancers, for which 5-year relative survival exceeds 90%. Conclusions. Americans lack knowledge about major risk factors for common cancers and about the prospects of survival following early detection. Knowledge about risk factors and about survival from cervical and colon cancers was poor at all ages, among all races, at all income levels, and at all educational levels, it was poorest among blacks and Hispanics and among those with the lowest income and least education. Americans need education about cancer risk factors and survival. C1 NIA, EPIDEMIOL DEMOG & BIOMETRY PROGRAM, BETHESDA, MD 20892 USA. RP Breslow, RA (reprint author), NCI, APPL RES BRANCH, EPN-313, BETHESDA, MD 20892 USA. NR 25 TC 99 Z9 101 U1 1 U2 2 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0091-7435 J9 PREV MED JI Prev. Med. PD MAR-APR PY 1997 VL 26 IS 2 BP 170 EP 177 DI 10.1006/pmed.1996.0136 PG 8 WC Public, Environmental & Occupational Health; Medicine, General & Internal SC Public, Environmental & Occupational Health; General & Internal Medicine GA WP351 UT WOS:A1997WP35100003 PM 9085385 ER PT J AU Devetten, MP Liu, JM Ling, V Weichold, FF Yu, JL Medof, ME Young, NS Dunn, DE AF Devetten, MP Liu, JM Ling, V Weichold, FF Yu, JL Medof, ME Young, NS Dunn, DE TI Paroxysmal nocturnal hemoglobinuria: New insights from murine Pig-a-deficient hematopoiesis SO PROCEEDINGS OF THE ASSOCIATION OF AMERICAN PHYSICIANS LA English DT Article DE glycosylphosphatidyl inositol-anchored proteins; embryonic stem cells; aplastic anemia; knock-out mice; hematopoietic stem cells ID GPI-ANCHOR BIOSYNTHESIS; APLASTIC-ANEMIA PATIENTS; PERIPHERAL-BLOOD CELLS; GLYCOSYL-PHOSPHATIDYLINOSITOL; GLYCOSYLPHOSPHATIDYLINOSITOL ANCHOR; PHOSPHOLIPASE-C; MOLECULAR-BASIS; PROTEINS; COMPLEMENT; GENE AB A large fraction of the hematopoietic cells of patients with paroxysmal nocturnal hemoglobinuria (PNH) are deficient in membrane expression of glycosylphosphatidylinositol-anchored proteins (GPI-APs). Current evidence suggests that this deficiency is sufficient to account for the hemolytic and thrombotic manifestations of this disease but not for its frequent association with aplastic anemia, an autoimmune disorder in which the patient's own hematopoietic progenitor cells are the target. Mutations in the X-linked gene PIG-A, encoding one of several enzymes required for the biosynthesis of the glycophosphatidylinositol anchor, have been found in all PNH patients studied to date. Recent experiments with murine Pig-a knock-out embryonic stem cells show that although embryogenesis is critically dependent on normal GPI-AP expression, Pig-a-deficient cells can undergo apparently normal hematopoietic differentiation if they develop in a GPI-AP-replete environment. Thus, in an in vitro mouse model of PNH, Pig-a mutations confer no gross proliferative or differentiative advantage or disadvantage, suggesting an unidentified process selecting for these mutations in the bone marrow of patients with the PNH-aplastic anemia syndrome. The rescue of hematopoiesis observed in chimeric cultures of knock-out and normal cells was accompanied by intercellular transfer of GPI AP, suggesting exciting new possibilities for future therapeutic manipulations in PNH patients. C1 NHLBI,HEMATOL BRANCH,NIH,BETHESDA,MD 20892. INST GENET,CAMBRIDGE,MA. CASE WESTERN RESERVE UNIV,INST PATHOL,CLEVELAND,OH 44106. NR 68 TC 3 Z9 3 U1 0 U2 1 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 SN 1081-650X J9 P ASSOC AM PHYSICIAN JI Proc. Assoc. Am. Phys. PD MAR PY 1997 VL 109 IS 2 BP 99 EP 110 PG 12 WC Medicine, General & Internal; Medicine, Research & Experimental SC General & Internal Medicine; Research & Experimental Medicine GA WM203 UT WOS:A1997WM20300001 PM 9069578 ER PT J AU Medin, JA Karlsson, S AF Medin, JA Karlsson, S TI Selection of retrovirally transduced cells to enhance the efficiency of gene therapy SO PROCEEDINGS OF THE ASSOCIATION OF AMERICAN PHYSICIANS LA English DT Article DE retroviridae; cell-surface antigens; drag resistance; flow cytometry ID HEAT-STABLE ANTIGEN; HEMATOPOIETIC STEM-CELLS; DIHYDROFOLATE-REDUCTASE CDNA; RESISTANT BONE-MARROW; PERIPHERAL-BLOOD LYMPHOCYTES; HUMAN MDR1 GENE; MULTIDRUG-RESISTANCE; P-GLYCOPROTEIN; DRUG-RESISTANCE; PROGENITOR CELLS AB Retrovirally mediated gene transfer is the approach of choice for many laboratories interested in gene therapy. One problem, however, is that the efficiency of therapeutic gene transfer to some important target cells is low. A strategy employed by a number of investigators to overcome this shortcoming is to construct recombinant viruses that employ selection modalities. These strategies can be classified broadly into either metabolic or cell-surface selection strategies. This article examines each selection approach and notes their important strengths and weaknesses. Further, the various gene products used in each approach to effect sorting of transduced cells is detailed. RP Medin, JA (reprint author), NINCDS,DEV & METAB NEUROL BRANCH,NIH,BLDG 10,ROOM 3D04,10 CTR DR MSC 1260,BETHESDA,MD 20892, USA. NR 67 TC 10 Z9 10 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 SN 1081-650X J9 P ASSOC AM PHYSICIAN JI Proc. Assoc. Am. Phys. PD MAR PY 1997 VL 109 IS 2 BP 111 EP 119 PG 9 WC Medicine, General & Internal; Medicine, Research & Experimental SC General & Internal Medicine; Research & Experimental Medicine GA WM203 UT WOS:A1997WM20300002 PM 9069579 ER PT J AU Cifone, MG Alesse, E DiMarzio, L Ruggeri, B Zazzeroni, F Moretti, S Famularo, G Steinberg, SM Vullo, E DeSimone, C AF Cifone, MG Alesse, E DiMarzio, L Ruggeri, B Zazzeroni, F Moretti, S Famularo, G Steinberg, SM Vullo, E DeSimone, C TI Effect of L-carnitine treatment in vivo on apoptosis and ceramide generation in peripheral blood lymphocytes from AIDS patients SO PROCEEDINGS OF THE ASSOCIATION OF AMERICAN PHYSICIANS LA English DT Article DE HIV infection; CD4; CD8; anti-apoptotic drug ID PROGRAMMED CELL-DEATH; TUMOR-NECROSIS-FACTOR; T-CELLS; HIV-1 TAT; ACTIVATION; INDIVIDUALS; CYTOTOXICITY; STIMULATION; EXPRESSION; DEFICIENCY AB Lymphocyte apoptosis in HIV-infected individuals may play a role in T-cell depletion and therefore favor progression to AIDS. In this study, we examined the effects of a short-term (5-day) intravenous treatment with L-carnitine (6 g/day) on apoptosis of CD4 and CD8 cells from 10 AIDS patients. L-carnitine administration has been shown to induce a strong reduction in the percentage of both CD4 and CD8 cells undergoing apoptosis. Interestingly, the L-carnitine treatment, which did not show relevant side effects in our patients, led to a strong and significant reduction of peripheral blood mononuclear cell-associated ceramide, an intracellular messenger of apoptosis, that positively correlated with the decrease of apoptotic CD4- and CD8-positive cells. These results suggest that L-carnitine could be an effective antiapoptotic drug in the treatment of AIDS patients. C1 UNIV AQUILA,DEPT EXPT MED,I-67100 LAQUILA,ITALY. NCI,NIH,BETHESDA,MD 20892. UNIV ROMA LA SAPIENZA,DEPT INFECT DIS,ROME,ITALY. RI Di Marzio, Luisa/H-9969-2012; OI Zazzeroni, Francesca/0000-0002-4474-3274; CIFONE, Maria Grazia/0000-0002-9923-5445 NR 42 TC 46 Z9 46 U1 0 U2 1 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 SN 1081-650X J9 P ASSOC AM PHYSICIAN JI Proc. Assoc. Am. Phys. PD MAR PY 1997 VL 109 IS 2 BP 146 EP 153 PG 8 WC Medicine, General & Internal; Medicine, Research & Experimental SC General & Internal Medicine; Research & Experimental Medicine GA WM203 UT WOS:A1997WM20300006 PM 9069583 ER PT J AU Lin, SL Yan, B AF Lin, SL Yan, B TI Three-dimensional model of sensory rhodopsin I reveals important restraints between the protein and the chromophore SO PROTEIN ENGINEERING LA English DT Article DE membrane; modeling; rhodopsin; sensory; structure ID RETINAL-BINDING POCKET; PROTON TRANSLOCATION; MOLECULAR-DYNAMICS; BACTERIORHODOPSIN; RECEPTOR; FAMILY; INTERMEDIATE; TRANSDUCER; MECHANISM; PIGMENTS AB A structural model is constructed for the integral membrane protein, sensory rhodopsin I (SRI), the phototaxis receptor of the archaeon Halobacterium salinarium. The model is built on the template of the homologous bacteriorhodopsin (BR), The modeling procedure includes sequence alignment, a side chain rotamer search and simulated annealing by restricted molecular dynamics, The structure is in general agreement with previous results from mutagenesis experiments, chromophore substitution and room and cryogenic temperature spectroscopy, In particular, a residue near the beta-ionone ring of the retinylidene chromophore is found to be critical in maintaining the proper isomeric conformation of the chromophore; a layer of residues lying on the cytoplasmic side of the chromophore pocket is found to modulate the restraints around the C-13 region of the chromophore, affecting the isomerizations around its 13 = 14 bond that are important to the protein's activity, The restraints in these regions are more stringent in SRI than in BR, The tightened restraints are chiefly due to van der Waals interactions, where the attractive and repulsive components play separable roles, Aromatic residues account for a majority of the restrictive interactions, It is hypothesized that the enhanced barriers due to these restrictions regulate the progress of SRI's photocycle, so that it can couple,vith the phototaxis reaction chain in the bacterium, A possibility is also suggested that conformational changes of the protein provide the signal recognized by the transducer. C1 SANDOZ PHARMACEUT CORP,E HANOVER,NJ 07936. RP Lin, SL (reprint author), NCI,FREDERICK CANC RES & DEV CTR,MATH BIOL LAB,BLDG 469,ROOM 151,FREDERICK,MD 21702, USA. RI Yan, Bing/B-7903-2009 OI Yan, Bing/0000-0002-7970-6764 NR 36 TC 13 Z9 15 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD, ENGLAND OX2 6DP SN 0269-2139 J9 PROTEIN ENG JI Protein Eng. PD MAR PY 1997 VL 10 IS 3 BP 197 EP 206 DI 10.1093/protein/10.3.197 PG 10 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology GA WX736 UT WOS:A1997WX73600003 PM 9153084 ER PT J AU Smith, GR Fischer, EP Nordquist, CR Mosley, CL Ledbetter, NS AF Smith, GR Fischer, EP Nordquist, CR Mosley, CL Ledbetter, NS TI Implementing outcomes management systems in mental health settings SO PSYCHIATRIC SERVICES LA English DT Article ID CARE; QUALITY AB Outcomes management has received considerable attention in the literature on mental health services delivery. However, relatively little practical information is available on how to implement an outcomes management system in the mental health care setting. The authors review seven key issues that must be addressed in planning such a system: involving senior organizational leaders in ownership of the project, securing the support of clinicians and patients, selecting personnel to operate the system, choosing outcomes assessment instruments, developing data collection procedures, selecting techniques for data management, and using the data to improve outcomes. Ultimately, an outcomes management system is intended to generate data that can be used to stimulate discussion, to guide clinicians in tailoring treatments, and to identify efficient treatment approaches. C1 UNIV ARKANSAS MED SCI HOSP,DEPT PSYCHIAT & BEHAV SCI,DEV FIELD PROGRAM MENTAL HLTH,LITTLE ROCK,AR 72205. NIMH,CTR RURAL MENTAL HEALTHCARE RES,BETHESDA,MD 20892. UNIV ARKANSAS MED SCI HOSP,DEPT VET AFFAIRS HLTH SERV RES,LITTLE ROCK,AR 72205. NR 38 TC 33 Z9 33 U1 1 U2 3 PU AMER PSYCHIATRIC ASSOCIATION PI WASHINGTON PA 1400 K ST NW, WASHINGTON, DC 20005 SN 1075-2730 J9 PSYCHIATR SERV JI Psychiatr. Serv. PD MAR PY 1997 VL 48 IS 3 BP 364 EP 368 PG 5 WC Health Policy & Services; Public, Environmental & Occupational Health; Psychiatry SC Health Care Sciences & Services; Public, Environmental & Occupational Health; Psychiatry GA WL843 UT WOS:A1997WL84300012 PM 9057239 ER PT J AU Wyatt, RJ Green, MF Tuma, AH AF Wyatt, RJ Green, MF Tuma, AH TI Long-term morbidity associated with delayed treatment of first admission schizophrenic patients: A re-analysis of the Camarillo State Hospital data SO PSYCHOLOGICAL MEDICINE LA English DT Editorial Material ID 1ST-EPISODE SCHIZOPHRENIA; 1ST EPISODES; PSYCHOSIS; DURATION AB Background. The authors examined data from a follow-up study of first admission schizophrenic patients treated with and without antipsychotic medications, who were discharged from the hospital within 6 months. It was predicted that patients who did not require antipsychotic medications for discharge would have a more favourable long-term outcome. Methods. The subjects were part of the Camarillo State Hospital study conducted by May and colleagues in the late 1950s and early 1960s. Patients had been randomly assigned to treatment with and without antipsychotic medications. The number of rehospitalization days and total prescribed chlorpromazine equivalents were calculated for each patient for the 2 years following discharge. In order to assess patients' continuing ability to function, 11 patients from each group who met DSM-IV criteria for schizophrenia were matched for age, educational status at first admission, race, and gender; their Global Assessment of Functioning Scale (GAF) score was estimated across a period of 6-7 years following discharge. Results. During the second year following discharge, patients initially treated with antipsychotic medications required fewer rehospitalization days than the initially non-medicated patients. Furthermore, 6-7 years following initial discharge, those patients initially treated with medications were functioning at a higher level, as measured by GAF scores, than patients not initially treated with antipsychotic medications. Conclusions. The results of this study suggest that, at least for this subgroup of patients, early treatment with antipsychotic medications both decreases the immediate morbidity associated with schizophrenia, and prevents detrimental changes possibly related to prolonged untreated psychosis. C1 UNIV CALIF LOS ANGELES,DEPT PSYCHIAT & BIOBEHAV SCI,CAMARILLO,CA. W LOS ANGELES VET AFFAIRS MED CTR,CAMARILLO,CA. UNIV PITTSBURGH,SCH MED,WESTERN PSYCHIAT INST & CLIN,DEPT PSYCHIAT,PITTSBURGH,PA. RP Wyatt, RJ (reprint author), NIMH,INTRAMURAL RES PROGRAM,NEUROPSYCHIAT BRANCH,NEUROPSYCHIAT HOSP,WASHINGTON,DC 20032, USA. NR 25 TC 86 Z9 88 U1 1 U2 3 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 40 WEST 20TH STREET, NEW YORK, NY 10011-4211 SN 0033-2917 J9 PSYCHOL MED JI Psychol. Med. PD MAR PY 1997 VL 27 IS 2 BP 261 EP 268 DI 10.1017/S0033291796004345 PG 8 WC Psychology, Clinical; Psychiatry; Psychology SC Psychology; Psychiatry GA WT612 UT WOS:A1997WT61200002 PM 9089819 ER PT J AU Grober, E Kawas, C AF Grober, E Kawas, C TI Learning and retention in preclinical and early Alzheimer's disease SO PSYCHOLOGY AND AGING LA English DT Article; Proceedings Paper CT Scientific Meeting of the International-Neuropsychology-Society CY FEB, 1996 CL CHICAGO, IL SP Int Neuropsychol Soc ID CUED-RECALL; KORSAKOFFS SYNDROME; MEMORY; DEMENTIA; RATES AB Accelerated forgetting has been proposed as the first sign in preclinical and early Alzheimer's disease (AD). The authors investigated learning and retention in participants who later developed AD with free and cued selective reminding (FCSR; H. Buschke, 1984; E. Grober & H. Buschke, 1987), a test that maximizes learning by inducing deep semantic processing and by controlling study and test conditions. AD patients in the preclinical stage recalled significantly fewer words than did matched control participants, indicating an impairment of learning; nonetheless, patients' retention was identical to that of control participants. A retention deficit was documented 3 years later for AD patients but not for control participants, whose retention was still perfect. Thus, a retention deficit is not present in preclinical AD when hallmark learning deficits can be documented. Detection of preclinical and very early AD may be best accomplished by using robust learning tests that control cognitive processing. C1 NIA,BALTIMORE LONGITUDINAL STUDY AGING,BALTIMORE,MD 21224. JOHNS HOPKINS SCH MED,DEPT NEUROL,BALTIMORE,MD. RP Grober, E (reprint author), YESHIVA UNIV ALBERT EINSTEIN COLL MED,DEPT NEUROL,1300 MORRIS PK AVE,ROUSSO ROOM 336,BRONX,NY 10461, USA. FU NIA NIH HHS [5P01 AG03949, 2PO AG05146, R01 AG08325] NR 35 TC 115 Z9 119 U1 1 U2 5 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 SN 0882-7974 J9 PSYCHOL AGING JI Psychol. Aging PD MAR PY 1997 VL 12 IS 1 BP 183 EP 188 DI 10.1037/0882-7974.12.1.183 PG 6 WC Gerontology; Psychology, Developmental SC Geriatrics & Gerontology; Psychology GA WM565 UT WOS:A1997WM56500017 PM 9100279 ER PT J AU Preston, K deWit, H AF Preston, K deWit, H TI Bridging the information gap: Assimilating preclinical and clinical findings SO PSYCHOPHARMACOLOGY LA English DT Editorial Material C1 UNIV CHICAGO,DEPT PSYCHIAT,CHICAGO,IL 60637. RP Preston, K (reprint author), NIDA,INTRAMURAL RES PROGRAM,POB 5180,BALTIMORE,MD 21224, USA. RI Preston, Kenzie/J-5830-2013 OI Preston, Kenzie/0000-0003-0603-2479 NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0033-3158 J9 PSYCHOPHARMACOLOGY JI Psychopharmacology PD MAR PY 1997 VL 130 IS 1 BP 1 EP 1 DI 10.1007/s002130050206 PG 1 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA WN932 UT WOS:A1997WN93200001 ER PT J AU Dykstra, LA Preston, KL Bigelow, GE AF Dykstra, LA Preston, KL Bigelow, GE TI Discriminative stimulus and subjective effects of opioids with mu and kappa activity: Data from laboratory animals and human subjects SO PSYCHOPHARMACOLOGY LA English DT Review DE opioids; discriminative stimulus; humans ID AGONIST-ANTAGONIST OPIOIDS; MIXED ACTION OPIOIDS; DRUG DISCRIMINATION; RHESUS-MONKEYS; SQUIRREL-MONKEY; NALTREXONE ANTAGONISM; BETA-FUNALTREXAMINE; INTRINSIC EFFICACY; DEPENDENT HUMANS; OPIATE RECEPTOR AB Although a large and rich body of data is available regarding the discriminative stimulus effects of opioids in laboratory animals and human subjects, it has been difficult to reconcile the data obtained from these two different sources. Therefore, the purpose of this review is to bring together data from both animal and human laboratories and systematically to compare the discriminative stimulus effects of opioids, in particular those with activity at both mu and kappa opioid receptor types (i.e., the mixed action opioids). The data that can be collected from laboratory animals differ from the data that can be collected in human subjects, In general, the advantage of studies in laboratory animals is that they can investigate very broad dose ranges of opioids as well as some very selective opioids that are not available for investigation in human subjects, Although investigations in human subjects are limited by the compounds and doses available for examination,;he advantage of these studies is that they can examine the subjective as well as the discriminative stimulus effects of opioids. Taken together, studies conducted in laboratory animals and human subjects indicate that the mixed action opioids are best classified as intermediate efficacy mu agonists with additional activity through other non-mlr, possibly kappa opioid systems. C1 NIDA,NIH,INTRAMURAL RES PROGRAM,BALTIMORE,MD 21224. JOHNS HOPKINS UNIV,SCH MED,DEPT PSYCHIAT & BEHAV SCI,BALTIMORE,MD 21224. RP Dykstra, LA (reprint author), UNIV N CAROLINA,DEPT PSYCHOL,CB 3270,DAVIE HALL,CHAPEL HILL,NC 27599, USA. RI Preston, Kenzie/J-5830-2013 OI Preston, Kenzie/0000-0003-0603-2479 FU NIDA NIH HHS [DA-02749, DA-04089, DA-00050] NR 79 TC 46 Z9 46 U1 1 U2 3 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0033-3158 J9 PSYCHOPHARMACOLOGY JI Psychopharmacology PD MAR PY 1997 VL 130 IS 1 BP 14 EP 27 DI 10.1007/s002130050208 PG 14 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA WN932 UT WOS:A1997WN93200003 PM 9089845 ER PT J AU Broocks, A Briggs, NC Pigott, TA Hill, JL Canter, SK Tolliver, TJ Baldemore, D Murphy, DL AF Broocks, A Briggs, NC Pigott, TA Hill, JL Canter, SK Tolliver, TJ Baldemore, D Murphy, DL TI Behavioral, physiological and neuroendocrine responses in healthy volunteers to m-chlorophenylpiperazine (m-CPP) with and without ondansetron pretreatment SO PSYCHOPHARMACOLOGY LA English DT Article DE serotonin receptors; anxiety; temperature; blood pressure; adrenocorticotropic hormone; cortisol; growth hormone; prolactin; norepinephrine ID 5-HT3 RECEPTOR ANTAGONISTS; PIG HIPPOCAMPAL SYNAPTOSOMES; META-CHLOROPHENYLPIPERAZINE; SEROTONIN RECEPTOR; ACETYLCHOLINE-RELEASE; PSYCHOTROPIC-DRUGS; NUCLEUS-ACCUMBENS; ANXIOLYTIC DRUGS; DOPAMINE RELEASE; CONSCIOUS RATS AB Several serotonin3 (5-HT3) antagonists have been shown to attenuate the anxiogenic effects of the serotonergic agent, m-chlorophenylpiperazine (m-CPP), in animal models, but little data regarding possible effects of 5-HT3 antagonists on responses to m-CPP are available from studies in humans. Therefore, we studied the behavioral, physiological and neuroendocrine responses of 12 healthy volunteers to IV administered placebo and m-CPP (0.08 mg/kg), with and without IV pretreatment with the selective 5-HT3 antagonist, ondansetron (0.15 mg/kg). Compared to placebo, m-CPP given alone significantly increased ratings of anxiety and several other behavioral measures. m-CPP also produced statistically significant increases in temperature, systolic and diastolic blood pressure, heart rate, and in plasma concentrations of adrenocorticotropic hormone, cortisol, prolactin and norepinephrine. Responses to ondansetron given alone were no different from those of placebo. Pretreatment with ondansetron did not affect peak behavioral responses to m-CPP, but was associated with a significantly earlier return to baseline levels of ratings of anxiety and functional deficit as well as a summary measure of overall behavioral effects. Following ondansetron pretreatment, the increases produced by m-CPP in systolic and diastolic blood pressure and heart rate were no longer significantly different from placebo. Ondansetron pretreatment significantly reduced their plasma cortisol response to m-CPP without affecting the other plasma hormone responses. Plasma concentrations of m-CPP were unaffected by ondansetron pretreatment. These findings suggest that in normal human subjects some behavioral, cardiovascular and neuroendocrine effects of m-CPP may be partially modulated by 5-HT3 receptor-mediated mechanisms. C1 NIMH, CLIN SCI LAB, NIH, CTR CLIN SCI, BETHESDA, MD 20892 USA. UNIV TEXAS, MED BRANCH, DEPT PSYCHIAT, GALVESTON, TX 77550 USA. NATL INST DRUG ABUSE, ROCKVILLE, MD USA. NR 94 TC 25 Z9 25 U1 0 U2 3 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0033-3158 J9 PSYCHOPHARMACOLOGY JI Psychopharmacology PD MAR PY 1997 VL 130 IS 2 BP 91 EP 103 DI 10.1007/s002130050215 PG 13 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA WQ445 UT WOS:A1997WQ44500003 PM 9106905 ER EF