FN Thomson Reuters Web of Science™ VR 1.0 PT J AU Kraft, T Xu, S Brenner, B Yu, LC AF Kraft, T Xu, S Brenner, B Yu, LC TI Does lowering ionic strength change weak cross-bridge binding from a non-stereospecific to a stereospecific conformation? SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 NIAMS,NIH,BETHESDA,MD. SCH MED,HANNOVER,GERMANY. NR 0 TC 0 Z9 0 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 FEB PY 1996 VL 70 IS 2 BP TU156 EP TU156 PN 2 PG 1 WC Biophysics SC Biophysics GA TZ682 UT WOS:A1996TZ68201675 ER PT J AU Lohret, TA Murphy, RC Drgon, T Kinnally, KW AF Lohret, TA Murphy, RC Drgon, T Kinnally, KW TI Evidence that the adenine nucleotide translocator is not responsible for the mitochondrial multiple conductance channel, MCC. SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 NEW YORK STATE DEPT HLTH,WADSWORTH CTR LABS & RES,ALBANY,NY 12201. RENSSELAER POLYTECH INST,DEPT BIOL,TROY,NY 12180. NIDDK,NIH,LBM,BETHESDA,MD. COMENIUS UNIV BRATISLAVA,DEPT BIOCHEM,BRATISLAVA,SLOVAKIA. SUNY ALBANY,DEPT BIOMED SCI,ALBANY,NY. SUNY ALBANY,DEPT BIOL SCI,ALBANY,NY 12222. NR 0 TC 0 Z9 0 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 FEB PY 1996 VL 70 IS 2 BP TUAM2 EP TUAM2 PN 2 PG 1 WC Biophysics SC Biophysics GA TZ682 UT WOS:A1996TZ68201406 ER PT J AU Merezhinskaya, N Kuijpers, G Pollard, H Raviv, Y AF Merezhinskaya, N Kuijpers, G Pollard, H Raviv, Y TI Reversible penetration of glutathione-S-transferase into the cell plasma membrane revealed by site directed photosensitized labeling SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 NIDDK,NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 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 FEB PY 1996 VL 70 IS 2 BP TU428 EP TU428 PN 2 PG 1 WC Biophysics SC Biophysics GA TZ682 UT WOS:A1996TZ68201949 ER PT J AU Mienville, JM Clay, JR AF Mienville, JM Clay, JR TI Intracellular K+ alters flicker gating of BK channels from embryonic rat telencephalon. SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 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 FEB PY 1996 VL 70 IS 2 BP TUAM5 EP TUAM5 PN 2 PG 1 WC Biophysics SC Biophysics GA TZ682 UT WOS:A1996TZ68201380 ER PT J AU Millar, DB Darawshe, S Minton, AP AF Millar, DB Darawshe, S Minton, AP TI Equilibrium dissociation of tryptophan synthase subunits studied by sedimentation equilibrium SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 NIDDK,NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 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 FEB PY 1996 VL 70 IS 2 BP TU250 EP TU250 PN 2 PG 1 WC Biophysics SC Biophysics GA TZ682 UT WOS:A1996TZ68201772 ER PT J AU Minetti, CA Tai, JY Liang, SM Remeta, DP AF Minetti, CA Tai, JY Liang, SM Remeta, DP TI Conformational, stability of outer membrane proteins from Neisseria meningitidis: Comparison of class 2 and class 3 proteins SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 N AMER VACCINE INC,BELTSVILLE,MD 20705. NHLBI,NIH,BETHESDA,MD 20892. RI Minetti, Conceicao/B-5077-2009 OI Minetti, Conceicao/0000-0002-9682-2898 NR 0 TC 0 Z9 0 U1 0 U2 1 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD FEB PY 1996 VL 70 IS 2 BP TUPM2 EP TUPM2 PN 2 PG 1 WC Biophysics SC Biophysics GA TZ682 UT WOS:A1996TZ68201482 ER PT J AU Nossal, R AF Nossal, R TI Rigidity analysis of activated PMN leukocytes SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 DCRT,NIH,PHYS SCI LAB,BETHESDA,MD 20892. NR 2 TC 0 Z9 0 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 FEB PY 1996 VL 70 IS 2 BP TU406 EP TU406 PN 2 PG 1 WC Biophysics SC Biophysics GA TZ682 UT WOS:A1996TZ68201925 ER PT J AU Nosworthy, NJ Ginsburg, A AF Nosworthy, NJ Ginsburg, A TI Thermal unfolding of E-coli dodecameric glutamine synthetase in 3M urea. SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 NHLBI,NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 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 FEB PY 1996 VL 70 IS 2 BP TU237 EP TU237 PN 2 PG 1 WC Biophysics SC Biophysics GA TZ682 UT WOS:A1996TZ68201757 ER PT J AU Nussinov, R Lin, SL Fischer, D Norel, R Wolfson, H AF Nussinov, R Lin, SL Fischer, D Norel, R Wolfson, H TI Highly efficient docking and matching by computer-vision and robotics based techniques SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 NCI,FREDERICK CANC RES & DEV CTR,FREDERICK,MD. TEL AVIV UNIV,IL-69978 TEL AVIV,ISRAEL. RI Wolfson, Haim/A-1837-2011 NR 0 TC 0 Z9 0 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 FEB PY 1996 VL 70 IS 2 BP TU199 EP TU199 PN 2 PG 1 WC Biophysics SC Biophysics GA TZ682 UT WOS:A1996TZ68201716 ER PT J AU Peng, S Rapoport, SI Galdzicki, Z AF Peng, S Rapoport, SI Galdzicki, Z TI Reduced membrane resistance and increased inward chloride conductance in cultured trisomy 16 mouse tongue muscle cells suggest a mechanism for the hypotonia in human Down Syndrome SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 NIA,NIH,NEUROSCI LAB,BETHESDA,MD 20892. NR 0 TC 1 Z9 1 U1 1 U2 2 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD FEB PY 1996 VL 70 IS 2 BP TU137 EP TU137 PN 2 PG 1 WC Biophysics SC Biophysics GA TZ682 UT WOS:A1996TZ68201659 ER PT J AU Ritter, AR Shi, Y Fisher, A Ferretti, JA Taniuchi, H AF Ritter, AR Shi, Y Fisher, A Ferretti, JA Taniuchi, H TI On the nature of the partially unfolded state of yeast iso-2-cytochrome C proteins. SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 NHLBI,BIOPHYS CHEM LAB,BETHESDA,MD 20892. NIDDK,NIH,BIOL CHEM LAB,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 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 FEB PY 1996 VL 70 IS 2 BP TU231 EP TU231 PN 2 PG 1 WC Biophysics SC Biophysics GA TZ682 UT WOS:A1996TZ68201751 ER PT J AU Ross, PD Rekharsky, MV AF Ross, PD Rekharsky, MV TI Thermodynamic comparison of a hydrogen bond and a hydrophobic interaction at a common site SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 NIH,BETHESDA,MD 20892. NIST,GAITHERSBURG,MD 20899. NR 0 TC 1 Z9 1 U1 0 U2 1 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD FEB PY 1996 VL 70 IS 2 BP TU225 EP TU225 PN 2 PG 1 WC Biophysics SC Biophysics GA TZ682 UT WOS:A1996TZ68201745 ER PT J AU Schoenberg, M AF Schoenberg, M TI Active muscle force, the weakly-to-strongly binding conformational change, and labeling SH1 and SH2. SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 NIAMS,NIH,LPB,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 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 FEB PY 1996 VL 70 IS 2 BP TU152 EP TU152 PN 2 PG 1 WC Biophysics SC Biophysics GA TZ682 UT WOS:A1996TZ68201670 ER PT J AU Sidorova, NY Yarmola, EG Rau, DC AF Sidorova, NY Yarmola, EG Rau, DC TI Linking energetics and structure of DNA-protein binding through water release SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 ENGELHARDT INST MOL BIOL,MOSCOW,RUSSIA. NIDDK,NIH,DCRT,LSB,BETHESDA,MD 20892. NIDDK,NIH,ODIR,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 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 FEB PY 1996 VL 70 IS 2 BP TU461 EP TU461 PN 2 PG 1 WC Biophysics SC Biophysics GA TZ682 UT WOS:A1996TZ68201981 ER PT J AU Vargas, J Arispe, N Rojas, E AF Vargas, J Arispe, N Rojas, E TI Asymmetrical displacement currents associated with the incorporation of amyloid beta-protein [A beta P(1-40)] into planar bilayers SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 UNIV CHILE,FAC MED,DEPT PHYSIOL BIOPHYS,SANTIAGO,CHILE. NIDDK,NIH,BETHESDA,MD. NR 0 TC 0 Z9 0 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 FEB PY 1996 VL 70 IS 2 BP TUAM4 EP TUAM4 PN 2 PG 1 WC Biophysics SC Biophysics GA TZ682 UT WOS:A1996TZ68201388 ER PT J AU Weiler, S Tsao, D Gruschus, J Yu, L Wang, LH Nirenberg, M Ferretti, J AF Weiler, S Tsao, D Gruschus, J Yu, L Wang, LH Nirenberg, M Ferretti, J TI Role of amino acid residues in the recognition helix of the NK-2 homeodomain on structure, function and thermal stability SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 NHLBI,NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 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 FEB PY 1996 VL 70 IS 2 BP TU463 EP TU463 PN 2 PG 1 WC Biophysics SC Biophysics GA TZ682 UT WOS:A1996TZ68201982 ER PT J AU Xiao, RP Lakatta, EG Cheng, HP AF Xiao, RP Lakatta, EG Cheng, HP TI Alteration of the elementary calcium release events by FK506 binding protein in cardiac myocytes SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 NIA,NIH,GRC,LCS,BALTIMORE,MD 21224. NR 0 TC 0 Z9 0 U1 1 U2 2 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD FEB PY 1996 VL 70 IS 2 BP TUAM4 EP TUAM4 PN 2 PG 1 WC Biophysics SC Biophysics GA TZ682 UT WOS:A1996TZ68201417 ER PT J AU Xu, D Lin, SL Nussinov, R AF Xu, D Lin, SL Nussinov, R TI Role of hydrophilic bridges in protein associations: A difference between protein-protein interfaces and the interior of proteins. SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 NCI,FREDERICK CANC RES & DEV CTR,MATH BIOL LAB,FREDERICK,MD 21702. NR 0 TC 0 Z9 0 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 FEB PY 1996 VL 70 IS 2 BP TU193 EP TU193 PN 2 PG 1 WC Biophysics SC Biophysics GA TZ682 UT WOS:A1996TZ68201710 ER PT J AU Xu, S Malinchik, S Kraft, T Brenner, B Yu, LC AF Xu, S Malinchik, S Kraft, T Brenner, B Yu, LC TI X-ray diffraction evidence that attachment conformation of weakly bound crossbridges in muscle is highly variable (nonstereospecific). SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 HANNOVER MED SCH,W-3000 HANNOVER,GERMANY. NIAMS,NIH,BETHESDA,MD. NR 0 TC 0 Z9 0 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 FEB PY 1996 VL 70 IS 2 BP TU155 EP TU155 PN 2 PG 1 WC Biophysics SC Biophysics GA TZ682 UT WOS:A1996TZ68201677 ER PT J AU Zolkiewski, M Redowicz, MJ Korn, ED Hammer, JA Ginsburg, A AF Zolkiewski, M Redowicz, MJ Korn, ED Hammer, JA Ginsburg, A TI Thermal unfolding and dissociation of the Acanthamoeba myosin II coiled-coil rod. SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 NHLBI,NIH,BETHESDA,MD 20892. RI Redowicz, Maria Jolanta/R-4083-2016 NR 0 TC 0 Z9 0 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 FEB PY 1996 VL 70 IS 2 BP TU244 EP TU244 PN 2 PG 1 WC Biophysics SC Biophysics GA TZ682 UT WOS:A1996TZ68201766 ER PT J AU BarNoy, S McPhie, P Wang, Y Sorscher, E Lee, G Eidelman, O Pollard, HB AF BarNoy, S McPhie, P Wang, Y Sorscher, E Lee, G Eidelman, O Pollard, HB TI Interactions of the NBF-1 domain of CFTR with phospholipid membranes. SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 NIDDK,NIH,LCBG,BETHESDA,MD. NIDDK,NIH,LBP,BETHESDA,MD. UNIV ALABAMA,DEPT PHYSIOL,BIRMINGHAM,AL 35294. UNIV ALABAMA,DEPT MED,BIRMINGHAM,AL 35294. NR 0 TC 0 Z9 0 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 FEB PY 1996 VL 70 IS 2 BP WP249 EP WP249 PN 2 PG 1 WC Biophysics SC Biophysics GA TZ682 UT WOS:A1996TZ68202435 ER PT J AU Batenjany, MM Mason, JT Levin, IW OLeary, TJ AF Batenjany, MM Mason, JT Levin, IW OLeary, TJ TI Thermal phase behavior and packing characteristics of fully hydrated bilayers composed of DHPC and DPPE. SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 ARMED FORCES INST PATHOL,DEPT CELLULAR PATHOL,WASHINGTON,DC 20306. NIDDK,NIH,CHEM PHYS LAB,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 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 FEB PY 1996 VL 70 IS 2 BP WP242 EP WP242 PN 2 PG 1 WC Biophysics SC Biophysics GA TZ682 UT WOS:A1996TZ68202428 ER PT J AU Brzeska, H Szczepanowska, J Hoey, J Martin, B Korn, ED AF Brzeska, H Szczepanowska, J Hoey, J Martin, B Korn, ED TI Catalytic domain of myosin I heavy chain kinase (MIHC kinase) cloning expression and characterization SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 NHLBI,LCB,BETHESDA,MD 20892. NIMH,CNB,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 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 FEB PY 1996 VL 70 IS 2 BP WP315 EP WP315 PN 2 PG 1 WC Biophysics SC Biophysics GA TZ682 UT WOS:A1996TZ68202502 ER PT J AU Cerritelli, ME Cheng, N Rosenberg, AH Simon, MN Steven, AC AF Cerritelli, ME Cheng, N Rosenberg, AH Simon, MN Steven, AC TI Organization of dsDNA in bacteriophage T7 capsids: Support for the coaxial-spool model SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract ID HEADS C1 NIAMS,NIH,LSB,BETHESDA,MD 20892. BROOKHAVEN NATL LAB,UPTON,NY 11973. NR 3 TC 0 Z9 0 U1 1 U2 1 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD FEB PY 1996 VL 70 IS 2 BP WAMC1 EP WAMC1 PN 2 PG 1 WC Biophysics SC Biophysics GA TZ682 UT WOS:A1996TZ68202100 ER PT J AU Cheng, HP Xiao, RP Spurgeon, H Lakatta, EG AF Cheng, HP Xiao, RP Spurgeon, H Lakatta, EG TI Calcium sparks in mouse cardiocytes originate at terminal SR and reveal anisotropy in calcium diffusion SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 NIA,GERONTOL RES CTR,CARDIOVASC SCI LAB,NIH,BALTIMORE,MD 21224. NR 0 TC 0 Z9 0 U1 1 U2 2 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD FEB PY 1996 VL 70 IS 2 BP WAMI2 EP WAMI2 PN 2 PG 1 WC Biophysics SC Biophysics GA TZ682 UT WOS:A1996TZ68202153 ER PT J AU Clay, JR AF Clay, JR TI Nerve axon excitability revisited. SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 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 FEB PY 1996 VL 70 IS 2 BP WP150 EP WP150 PN 2 PG 1 WC Biophysics SC Biophysics GA TZ682 UT WOS:A1996TZ68202336 ER PT J AU Clay, JR Ogbaghebriel, A Paquette, T Sasyniuk, B Shrier, A AF Clay, JR Ogbaghebriel, A Paquette, T Sasyniuk, B Shrier, A TI Unusual kinetic and ion transfer properties of the E-4031 sensitive repolarization current (I-Kr) in rabbit ventricular SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 NIH,BETHESDA,MD 20892. MCGILL UNIV,DEPT PHYSIOL,MONTREAL,PQ H3G 1Y6,CANADA. MCGILL UNIV,DEPT PHARMACOL,MONTREAL,PQ H3G 1Y6,CANADA. NR 0 TC 0 Z9 0 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 FEB PY 1996 VL 70 IS 2 BP WAMA6 EP WAMA6 PN 2 PG 1 WC Biophysics SC Biophysics GA TZ682 UT WOS:A1996TZ68202091 ER PT J AU Holte, LL Gawrisch, K AF Holte, LL Gawrisch, K TI The location of ethanol in a lipid bilayer investigated with 2-D NMR and magic angle sample spinning. SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 NIAAA,NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 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 FEB PY 1996 VL 70 IS 2 BP WP235 EP WP235 PN 2 PG 1 WC Biophysics SC Biophysics GA TZ682 UT WOS:A1996TZ68202424 ER PT J AU Holte, LL Gawrisch, K AF Holte, LL Gawrisch, K TI Influence of lipid hydration on hydrocarbon chain order - A H-2 NMR study. SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 NIAAA,NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 1 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD FEB PY 1996 VL 70 IS 2 BP WP228 EP WP228 PN 2 PG 1 WC Biophysics SC Biophysics GA TZ682 UT WOS:A1996TZ68202415 ER PT J AU Horsky, J Pitha, J AF Horsky, J Pitha, J TI Effect of cyclodextrins on aggregation and refolding of proteins in molten globule state. SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 NIA,NIH,BALTIMORE,MD 21224. RI Horsky, Jiri/G-3442-2014 NR 0 TC 0 Z9 0 U1 0 U2 1 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD FEB PY 1996 VL 70 IS 2 BP WP354 EP WP354 PN 2 PG 1 WC Biophysics SC Biophysics GA TZ682 UT WOS:A1996TZ68202542 ER PT J AU Huster, D Jin, AJ Gawrisch, K AF Huster, D Jin, AJ Gawrisch, K TI Water permeation across unsaturated bilayers measured by O-17 NMR SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 NIAAA,NIH,LMBB,BETHESDA,MD 20892. UNIV LEIPZIG,D-04103 LEIPZIG,GERMANY. NIH,PSL,DCRT,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 1 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD FEB PY 1996 VL 70 IS 2 BP WP230 EP WP230 PN 2 PG 1 WC Biophysics SC Biophysics GA TZ682 UT WOS:A1996TZ68202416 ER PT J AU Jin, AJ Nossal, R Ghirlando, R Greene, L Eisenberg, E AF Jin, AJ Nossal, R Ghirlando, R Greene, L Eisenberg, E TI Dynamic light scattering studies suggest that the binding of hsp70 induces a conformational change in clathrin. SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 DCRT,PHYS SCI LAB,BETHESDA,MD 20892. NIDDK,MOLEC BIOL LAB,BETHESDA,MD 20892. NHLBI,NIH,CELL BIOL LAB,BETHESDA,MD 20892. RI Ghirlando, Rodolfo/A-8880-2009 NR 1 TC 0 Z9 0 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 FEB PY 1996 VL 70 IS 2 BP WP319 EP WP319 PN 2 PG 1 WC Biophysics SC Biophysics GA TZ682 UT WOS:A1996TZ68202507 ER PT J AU Keller, SL Strey, HH Podgornik, R Rau, DC Parsegian, VA AF Keller, SL Strey, HH Podgornik, R Rau, DC Parsegian, VA TI Single DNA mesophases observed by electron and polarization microscopy. SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 UNIV CALIF SANTA BARBARA,SANTA BARBARA,CA 93106. NIH,NIDDK,DCRT,LSB,BETHESDA,MD 20892. RI Podgornik, Rudolf/C-6209-2008 OI Podgornik, Rudolf/0000-0002-3855-4637 NR 0 TC 1 Z9 1 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 FEB PY 1996 VL 70 IS 2 BP WP378 EP WP378 PN 2 PG 1 WC Biophysics SC Biophysics GA TZ682 UT WOS:A1996TZ68202565 ER PT J AU Koenig, BW Gawrisch, K Krueger, S Orts, W Majkrzak, CF Berk, N Silverton, JV AF Koenig, BW Gawrisch, K Krueger, S Orts, W Majkrzak, CF Berk, N Silverton, JV TI Membrane structure at the solid/water interface studied with neutron reflectivity and atomic force microscopy SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 NIAAA,BETHESDA,MD 20892. NHLBI,NIH,BETHESDA,MD 20892. NIST,DIV REACTOR RADIAT,GAITHERSBURG,MD 20899. NR 0 TC 2 Z9 2 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 FEB PY 1996 VL 70 IS 2 BP WP229 EP WP229 PN 2 PG 1 WC Biophysics SC Biophysics GA TZ682 UT WOS:A1996TZ68202418 ER PT J AU Lee, J Barry, JA AF Lee, J Barry, JA TI Influence of toluene and membrane lipid chain packing on T-2-weighted MRI of brain SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 LDDR,NIH,BETHESDA,MD. NIAAA,NIH,BETHESDA,MD. NR 0 TC 0 Z9 0 U1 0 U2 1 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD FEB PY 1996 VL 70 IS 2 BP WP175 EP WP175 PN 2 PG 1 WC Biophysics SC Biophysics GA TZ682 UT WOS:A1996TZ68202363 ER PT J AU Lewis, EN Levin, IW Hanig, JP Lester, DS AF Lewis, EN Levin, IW Hanig, JP Lester, DS TI Infrared chemical imaging of drug-induced neurotoxicity in the rat cerebellum SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 NIDDK,NIH,CHEM PHYS LAB,BETHESDA,MD 20892. US FDA,CTR DRUG EVALUAT & RES,LAUREL,MD 20708. NR 0 TC 2 Z9 2 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 FEB PY 1996 VL 70 IS 2 BP WP180 EP WP180 PN 2 PG 1 WC Biophysics SC Biophysics GA TZ682 UT WOS:A1996TZ68202366 ER PT J AU Lyubchenko, YL Aki, T Choy, HE Adhya, S AF Lyubchenko, YL Aki, T Choy, HE Adhya, S TI AFM studies of protein-induced DNA looping. SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 ARIZONA STATE UNIV,DEPT MICROBIOL,TEMPE,AZ 85287. NCI,NIH,MOLEC BIOL LAB,BETHESDA,MD 20892. RI Aki, Tsunehiro/B-6719-2012 OI Aki, Tsunehiro/0000-0001-9753-2043 NR 0 TC 0 Z9 0 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 FEB PY 1996 VL 70 IS 2 BP WAMG7 EP WAMG7 PN 2 PG 1 WC Biophysics SC Biophysics GA TZ682 UT WOS:A1996TZ68202139 ER PT J AU Mears, D Sheppard, NF Rojas, E Atwater, I Bertram, R Sherman, A AF Mears, D Sheppard, NF Rojas, E Atwater, I Bertram, R Sherman, A TI A role for calcium release-activated current in pancreatic beta-cell biphasic electrical activity SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 JOHNS HOPKINS UNIV,DEPT BIOMED ENGN,BALTIMORE,MD 21218. NIH,LCBG,BETHESDA,MD 20892. NIDDK,NIH,MRB,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 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 FEB PY 1996 VL 70 IS 2 BP WAMB3 EP WAMB3 PN 2 PG 1 WC Biophysics SC Biophysics GA TZ682 UT WOS:A1996TZ68202094 ER PT J AU Mitchell, DC Litman, BJ AF Mitchell, DC Litman, BJ TI The reduction of acyl chain packing free volume by cholesterol depends on acyl chain unsaturation SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 NIAAA,NIH,ROCKVILLE,MD 20892. NR 0 TC 0 Z9 0 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 FEB PY 1996 VL 70 IS 2 BP WP231 EP WP231 PN 2 PG 1 WC Biophysics SC Biophysics GA TZ682 UT WOS:A1996TZ68202419 ER PT J AU MyersPayne, SC Mitchell, DC Litman, BJ AF MyersPayne, SC Mitchell, DC Litman, BJ TI Rhodopsin photoactivation is modulated by water activity. SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 NIAAA,NIH,BETHESDA,MD 20892. NR 0 TC 1 Z9 1 U1 1 U2 1 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD FEB PY 1996 VL 70 IS 2 BP WPO95 EP WPO95 PN 2 PG 1 WC Biophysics SC Biophysics GA TZ682 UT WOS:A1996TZ68202285 ER PT J AU Niebylski, CD Litman, BJ AF Niebylski, CD Litman, BJ TI Phase separation in bilayers containing disaturated and dipolyunsaturated acyl chains. SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 NIAAA,NIH,DICBR,LMBB,SECT FLUORESCENCE STUDIES,ROCKVILLE,MD 20892. NR 0 TC 0 Z9 0 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 FEB PY 1996 VL 70 IS 2 BP WP232 EP WP232 PN 2 PG 1 WC Biophysics SC Biophysics GA TZ682 UT WOS:A1996TZ68202417 ER PT J AU Parthum, KA Phillips, KM Tomellini, SA Levin, IW AF Parthum, KA Phillips, KM Tomellini, SA Levin, IW TI Comparison of the interactions of conjugated and unconjugated bile salts with model membranes. SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 UNIV NEW HAMPSHIRE,DEPT CHEM,DURHAM,NH 03824. NIDDKD,NIH,CHEM PHYS LAB,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 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 FEB PY 1996 VL 70 IS 2 BP WP241 EP WP241 PN 2 PG 1 WC Biophysics SC Biophysics GA TZ682 UT WOS:A1996TZ68202430 ER PT J AU Podgornik, R Parsegian, A Fuller, N Rand, P AF Podgornik, R Parsegian, A Fuller, N Rand, P TI The vapor pressure paradox - Postulated, formulated and observed SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 BROCK UNIV,NIH,BETHESDA,MD. RI Podgornik, Rudolf/C-6209-2008 OI Podgornik, Rudolf/0000-0002-3855-4637 NR 0 TC 0 Z9 0 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 FEB PY 1996 VL 70 IS 2 BP WP364 EP WP364 PN 2 PG 1 WC Biophysics SC Biophysics GA TZ682 UT WOS:A1996TZ68202552 ER PT J AU Raviv, Y Eidelman, O AF Raviv, Y Eidelman, O TI The membrane domain of the human erythrocyte anion exchanger revealed by specific substrate induced photosensitized labeling. SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 NIDDK,NIH,LCBG,BETHESDA,MD. NR 0 TC 0 Z9 0 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 FEB PY 1996 VL 70 IS 2 BP WP200 EP WP200 PN 2 PG 1 WC Biophysics SC Biophysics GA TZ682 UT WOS:A1996TZ68202389 ER PT J AU Strey, HH Podgornik, R Wang, J Sirota, E Rau, DC Rupprecht, A Yu, L Parsegian, VA AF Strey, HH Podgornik, R Wang, J Sirota, E Rau, DC Rupprecht, A Yu, L Parsegian, VA TI DNA mesophases: An osmotic stress study SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 DCRT,LSB,BETHESDA,MD. NIDDK,OD,BETHESDA,MD. NIAMS,LCP,BETHESDA,MD. EXXON RES & ENGN CO,FLORHAM PK,NJ. RI Sirota, Eric/A-7633-2009; Podgornik, Rudolf/C-6209-2008 OI Podgornik, Rudolf/0000-0002-3855-4637 NR 0 TC 0 Z9 0 U1 0 U2 3 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD FEB PY 1996 VL 70 IS 2 BP WP379 EP WP379 PN 2 PG 1 WC Biophysics SC Biophysics GA TZ682 UT WOS:A1996TZ68202563 ER PT J AU Wimley, WC Creamer, TP Gawrish, K White, SH AF Wimley, WC Creamer, TP Gawrish, K White, SH TI Solvation energies of amino acid residues and salt-bridges in proteins. SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 UNIV CALIF IRVINE,DEPT PHYSIOL & BIOPHYS,IRVINE,CA 92717. JOHNS HOPKINS UNIV,SCH MED,DEPT BIOPHYS & BIOPHYS CHEM,BALTIMORE,MD 21205. NIH,NIAAA,MEMBRANE BIOPHYS & BIOCHEM LAB,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 1 U2 1 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD FEB PY 1996 VL 70 IS 2 BP WP368 EP WP368 PN 2 PG 1 WC Biophysics SC Biophysics GA TZ682 UT WOS:A1996TZ68202554 ER PT J AU Yang, J Wang, L CameriniOtero, RD AF Yang, J Wang, L CameriniOtero, RD TI The physical mechanism of the close-packing of membrane-bound DNA in solution SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 UNIV VERMONT,DEPT PHYS,BURLINGTON,VT 05405. NIDDK,NIH,GENET & BIOCHEM BRANCH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 1 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD FEB PY 1996 VL 70 IS 2 BP WAMG5 EP WAMG5 PN 2 PG 1 WC Biophysics SC Biophysics GA TZ682 UT WOS:A1996TZ68202138 ER PT J AU Zlotnick, A Cheng, N Conway, JF Booy, FP Steven, AC Stahl, SJ Wingfield, PT AF Zlotnick, A Cheng, N Conway, JF Booy, FP Steven, AC Stahl, SJ Wingfield, PT TI Regulation of Hepatitis B Virus core assembly and polymorphism. SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 NIAMS,NIH,STRUCT BIOL LAB,BETHESDA,MD 20892. NIH,PROT EXPRESS LAB,BETHESDA,MD 20892. NR 2 TC 0 Z9 0 U1 1 U2 2 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD FEB PY 1996 VL 70 IS 2 BP WAMC7 EP WAMC7 PN 2 PG 1 WC Biophysics SC Biophysics GA TZ682 UT WOS:A1996TZ68202105 ER PT J AU Zorov, DB Camp, M Filburn, CR Hansford, RG AF Zorov, DB Camp, M Filburn, CR Hansford, RG TI Mitochondrial, retention of nucleic acids. SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 NIA,NIH,GERONTOL RES CTR,BALTIMORE,MD 21224. INST MOSCOW STATE UNIV,MOSCOW,RUSSIA. NR 0 TC 0 Z9 0 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 FEB PY 1996 VL 70 IS 2 BP WP208 EP WP208 PN 2 PG 1 WC Biophysics SC Biophysics GA TZ682 UT WOS:A1996TZ68202396 ER PT J AU Barchi, JJ Nomizu, M Otaka, A Roller, PP Burke, TR AF Barchi, JJ Nomizu, M Otaka, A Roller, PP Burke, TR TI Conformational analysis of cyclic hexapeptides designed as constrained ligands for the SH2 domain of the p85 subunit of phosphatidylinositol-3-OH kinase SO BIOPOLYMERS LA English DT Article ID AFFINITY PHOSPHOTYROSYL PEPTIDE; RESTRAINED MOLECULAR-DYNAMICS; SRC HOMOLOGY-2 DOMAIN; SOLID-PHASE SYNTHESIS; NMR-SPECTROSCOPY; CROSS-RELAXATION; ROTATING-FRAME; BIOLOGICAL-ACTIVITY; 2-DIMENSIONAL NMR; RGD PEPTIDES AB The structures of the cyclic hexapeptide cycle (-Gly-Tyr-Val-Pro-Met-Leu-) (1) and its phosphotyrosyl (pTyr) derivative cycle [-Gly-Tyr(PO3H2)-Val-Pro-Met-Leu-] (2), designed as constrained models of a sequence that interacts with the src homology, 2 (SH2) region of the p85 subunit of phosphatidylinositol-3-ON kinase (PI-3 kinase), were studied in methanol/water solutions by 500 MHz nmr spectroscopy. Compound 1 was found to exist as a 2:1 mixture of isomers about the Val-Pro bond (trans and cis prolyl) between 292-330 K in 75% CD3O(D,H)/ (D,H)(2)O solutions. A third species of undetermined undetermined structure (etc. 5%) was also observed Compound 2, a model of phosphorylated peptide ligand that binds to the PI-3 kinase SH2 domain, exhibited similar conformational isomerism. When either compound was dissolved in pure solvent [i.e., 100% CD3O(H,D) or (H.D)(2)O] the ratio of cis to trans isomers was ca 1:1. A battery of one- and two-dimensional nmr experiments at different temperatures and solvent compositions allowed a complete assignment of both the cis and trans forms of 1 and indicated the trans compound to be the major. isomer. The spectral properties of the phophorylated derivative 2 paralleled those of 1, indicating like conformations for the two compounds. Analysis of rotating frame Overhauser spectrosropy data, coupling constants, amide proton temperature dependence and amide proton exchange rates generated a set of constraints that were employed in energy minimization and molecular dynamics calculations using the CHARMM force field. The trans isomer exists with the tyrosine and C-terminal Tyr(+3) (Met) residues at opposite corners of the 18-membered ring separated by a distance of 16-18 Angstrom, in contrast with the cis isomer where the side chains of these residues are much closer in space (7-14 Angstrom). It was previously shown that the pTyr and the third amino acid C-terminal to this residue are the critical recognition elements for pTyr-peptide binding to the PI-3 kinase SH2 domain. Such cyclic structures may offer appropriate scaffolding for positioning important amino acid side chains of pTyr containing peptides as a means of increasing their binding affinities to SH2 domains, and in trim provide a conceptual approach toward the design of SH2 domain directed peptidomimetics. (C) 1996 John Wiley & Sons, Inc. RP Barchi, JJ (reprint author), NCI,DIV CANC TREATMENT,MED CHEM LAB,DEV THERAPEUT PROGRAM,BETHESDA,MD 20892, USA. RI Barchi Jr., Joseph/N-3784-2014; Burke, Terrence/N-2601-2014 NR 57 TC 6 Z9 6 U1 0 U2 0 PU JOHN WILEY & SONS INC PI NEW YORK PA 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0006-3525 J9 BIOPOLYMERS JI Biopolymers PD FEB PY 1996 VL 38 IS 2 BP 191 EP 208 DI 10.1002/(SICI)1097-0282(199602)38:2<191::AID-BIP6>3.0.CO;2-Q PG 18 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA TR391 UT WOS:A1996TR39100006 PM 8589253 ER PT J AU Brady, JP AF Brady, JP TI Combined protocol for selection and isolation of recombinant plasmids using multiwell plates SO BIOTECHNIQUES LA English DT Article RP Brady, JP (reprint author), NEI,MOLEC & DEV BIOL LAB,BG 6,RM 2A04,BETHESDA,MD 20892, USA. NR 3 TC 0 Z9 0 U1 0 U2 0 PU EATON PUBLISHING CO PI NATICK PA 154 E. CENTRAL ST, NATICK, MA 01760 SN 0736-6205 J9 BIOTECHNIQUES JI Biotechniques PD FEB PY 1996 VL 20 IS 2 BP 172 EP 174 PG 3 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA TT955 UT WOS:A1996TT95500001 PM 8825142 ER PT J AU Fucharoen, S Siritanaratkul, N Winichagoon, P Chowthaworn, J Siriboon, W Muangsup, W Chaicharoen, S Poolsup, N Chindavijak, B Pootrakul, P Piankijagum, A Schechter, AN Rodgers, GP AF Fucharoen, S Siritanaratkul, N Winichagoon, P Chowthaworn, J Siriboon, W Muangsup, W Chaicharoen, S Poolsup, N Chindavijak, B Pootrakul, P Piankijagum, A Schechter, AN Rodgers, GP TI Hydroxyurea increases hemoglobin F levels and improves the effectiveness of erythropoiesis in beta-thalassemia hemoglobin E disease SO BLOOD LA English DT Article ID SICKLE-CELL DISEASE; ANEMIA; SEVERITY AB Hydroxyurea (HU) is one of several agents that have been shown to enhance hemoglobin (Hb) F levels in patients with sickle cell disease and may be useful as a therapy for beta-globinopathies. However, limited information exists on the effects of HU in patients with thalassemia. Accordingly, we examined the hematologic effects of orally administered HU in 13 patients with beta-thalassemia/Hb E, including four patients who had been splenectomized. These patients were treated with escalating doses (final range, 10 to 20 mg/kg/d) for 5 months and were observed in the outpatient hematology clinic every 2 to 4 weeks. Complete blood counts including reticulocyte counts, amounts of Hb E and Hb F, (G) gamma:(A) gamma and alpha:non-alpha globin biosynthetic ratios were evaluated before and during treatment. Almost all patients responded with an average increase of 33% in Hb F levels, from a mean (+/-SD) of 42% +/- 11% to 56% +/- 8% (P < .0001), and a reciprocal decline in the percentage of Hb E from 59% +/- 9% to 49% +/- 8% (P < .001). Reticulocytosis was decreased from a mean (+/-SD) of 18.0% +/- 15.6% to 11.7% +/- 9.1% (P < .05); there was also a slight (10%) but statistically significant increase in hemoglobin levels and an improved balance in alpha:non-alpha globin chains ratios. The side effects were minimal in most patients, although these patients tended to tolerate a lower dose of HU before significant myelosuppression than has been our previous experience in sickle cell disease. One splenectomized patient died of sepsis during the trial. We conclude that increased Hb F production in beta-thalassemia/Hb E patients, with an improvement in the alpha:non-alpha globin ratios and, probably, the effectiveness of erythropoiesis, can be achieved using HU. Longer trials of HU in this population, including at other doses and in combination with other agents, appear warranted. C1 NIDDKD,BIOL CHEM LAB,MOLEC HEMATOL SECT,BETHESDA,MD 20895. SIRIRAJ HOSP,FAC MED,DEPT MED,DIV HEMATOL,THALASSEMIA CTR,BANGKOK,THAILAND. INST SCI & TECHNOL RES & DEV,BANGKOK,THAILAND. MAHIDOL UNIV,FAC PHARM,DEPT PHARM,BANGKOK 10700,THAILAND. OI Schechter, Alan N/0000-0002-5235-9408 NR 31 TC 88 Z9 91 U1 0 U2 2 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 FEB 1 PY 1996 VL 87 IS 3 BP 887 EP 892 PG 6 WC Hematology SC Hematology GA TT484 UT WOS:A1996TT48400007 PM 8562958 ER PT J AU Spivak, JL Avedissian, LS Pierce, JH Williams, D Hankins, WD Jensen, RA AF Spivak, JL Avedissian, LS Pierce, JH Williams, D Hankins, WD Jensen, RA TI Isolation of the full-length murine erythropoietin receptor using a baculovirus expression system SO BLOOD LA English DT Article ID COLONY-STIMULATING FACTOR; TYROSINE PHOSPHORYLATION; EXTRACELLULAR DOMAIN; CROSS-LINKING; CELL-MEMBRANE; PROTEIN; ACTIVATION; COMPLEX; BINDING; GROWTH AB The full-length murine erythropoietin receptor was expressed in Spodoptera frugiperda (Sf9) cells using a recombinant baculovirus vector. Erythropoietin receptor protein production was maximal 48 hours after infection, as determined by metabolic labeling and immunoblotting; receptor protein varied in molecular mass from 62 to 76 kD. Erythropoietin receptors produced in Sf9 cells could be solubilized using CHAPS in a form capable of binding erythropoietin, and the solubilized receptor bound to immobilized Concanavalin A (Con A) and wheat germ agglutinin, as well as to immobilized recombinant human erythropoietin. Analysis of the distribution of erythropoietin receptors in Sf9 plasma membrane and cytosol fractions using lectin affinity chromatography revealed that membrane-bound receptor had a higher apparent molecular mass and contained the bulk of receptors that bound to wheat germ agglutinin, The receptor was purified by sequential affinity chromatography on Con A-Sepharose and immobilized erythropoietin. Erythropoietin receptors expressed in Sf9 cells were inserted into the plasma membrane in the correct orientation, bound I-125-erythropoietin with a single affinity (kD, 330 pmol/L), and were internalized after ligand binding. However, kD varied inversely with the number of cell surface receptors. Solubilized erythropoietin receptors in whole-cell lysates and isolated plasma membranes exhibited high-affinity binding, with kD values of 92 and 57 pmol/L, respectively. Erythropoietin bound to the surface of infected Sf9 cells could be cross-linked to two proteins with molecular masses of 90 and 65 kD using the homobifunctional cross-linker, disuccinimidyl suberate (DSS). Similar results were obtained with solubilized receptors in whole-cell lysates, and both proteins could be immunoprecipitated by an antiserum to the erythropoietin receptor carboxyl-terminal domain. (C) 1996 by The American Society of Hematology. C1 NCI, CELLULAR & MOLEC BIOL LAB, BETHESDA, MD 20892 USA. RP JOHNS HOPKINS UNIV, SCH MED, DIV HEMATOL, TRAYLOR 924, 720 RUTLAND AVE, BALTIMORE, MD 21205 USA. FU NIDDK NIH HHS [DK16702] NR 45 TC 4 Z9 4 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA SN 0006-4971 EI 1528-0020 J9 BLOOD JI Blood PD FEB 1 PY 1996 VL 87 IS 3 BP 926 EP 937 PG 12 WC Hematology SC Hematology GA TT484 UT WOS:A1996TT48400013 PM 8562964 ER PT J AU Himmelmann, A Thevenin, C Harrison, K Kehrl, JH AF Himmelmann, A Thevenin, C Harrison, K Kehrl, JH TI Analysis of the Bruton's tyrosine kinase gene promoter reveals critical PU1 and SP1 sites SO BLOOD LA English DT Article ID X-LINKED AGAMMAGLOBULINEMIA; PU.1 REGULATES EXPRESSION; ENHANCER ACTIVITY; CD11B PROMOTER; ETS ONCOGENE; CHAIN GENE; TRANSCRIPTION; BINDS; ACTIVATION; PROTEINS AB The gene defective in X-linked agammaglobulinemia (XLA) encodes a novel protein kinase termed Bruton's tyrosine kinase (Btk). Whereas the XLA phenotype is confined to abnormalities of B-cell development and function, Btk is expressed not only in B-lymphocyte lineage but also in myeloid lineage cells. The first 450 basepairs of the Btk promoter fused to a luciferase gene displayed a similar cell-type specificity. Critical binding sites for the transcription factors PU.1 and Spl were identified in the proximal portion of the Btk promoter upstream of a cluster of transcriptional start sites, Mutation of either the PU.1 or Sp1 site markedly reduced the activity of a Btk promoter-luciferase reporter construct in transfection experiments, In addition, PU.1 directly transactivated the Btk promoter, and deletion of the PU.1 binding site abolished this effect, This study implicates PU.1 and Sp1 as major regulators of Btk expression and provides a foundation for further study of the regulation of this gene in XLA patients that lack Btk mRNA. This is a US government work, There are no restrictions on its use. C1 NIAID,IMMUNOREGULAT LAB,BETHESDA,MD 20892. OI Kehrl, John/0000-0002-6526-159X NR 39 TC 50 Z9 50 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD FEB 1 PY 1996 VL 87 IS 3 BP 1036 EP 1044 PG 9 WC Hematology SC Hematology GA TT484 UT WOS:A1996TT48400026 PM 8562928 ER PT J AU Harris, CC AF Harris, CC TI The 1995 Walter Hubert lecture - Molecular epidemiology of human cancer: Insights from the mutational analysis of the p53 tumour-suppressor gene SO BRITISH JOURNAL OF CANCER LA English DT Review DE cancer susceptibility genes; cancer risk assessment; aflatoxin B-1; ultraviolet light; liver cancer; skin cancer ID HEPATITIS-B VIRUS; WILD-TYPE P53; HUMAN HEPATOCELLULAR-CARCINOMA; TATA-BINDING PROTEIN; TRANSCRIPTIONAL ACTIVATION; X-PROTEIN; DNA; ONCOGENE; GROWTH; TRANSACTIVATOR RP Harris, CC (reprint author), NCI,HUMAN CARCINOGENESIS LAB,BLDG 37,RM 2CO1,37 CONVENT DR,BETHESDA,MD 20892, USA. NR 84 TC 109 Z9 112 U1 0 U2 0 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE, HAMPSHIRE, ENGLAND RG21 6XS SN 0007-0920 J9 BRIT J CANCER JI Br. J. Cancer PD FEB PY 1996 VL 73 IS 3 BP 261 EP 269 DI 10.1038/bjc.1996.47 PG 9 WC Oncology SC Oncology GA TR165 UT WOS:A1996TR16500001 PM 8562328 ER PT J AU Klaiman, MD Gerber, LH AF Klaiman, MD Gerber, LH TI General considerations for managing tendon injuries SO BULLETIN ON THE RHEUMATIC DISEASES LA English DT Article ID OVERUSE INJURIES; SPORTS RP Klaiman, MD (reprint author), NIH,DEPT REHABIL MED,BETHESDA,MD 20892, USA. NR 25 TC 1 Z9 1 U1 0 U2 0 PU ARTHRITIS FOUNDATION PI ATLANTA PA 1314 SPRING STREET NW, ATLANTA, GA 30309 SN 0007-5248 J9 B RHEUM DIS JI Bull. Rheum. Dis. PD FEB PY 1996 VL 45 IS 1 BP 1 EP 6 PG 8 WC Rheumatology SC Rheumatology GA TU172 UT WOS:A1996TU17200001 PM 8834996 ER PT J AU Massaquoi, S Hallett, M AF Massaquoi, S Hallett, M TI Kinematics of initiating a two-joint arm movement in patients with cerebellar ataxia SO CANADIAN JOURNAL OF NEUROLOGICAL SCIENCES LA English DT Article ID DYSFUNCTION; DYSMETRIA; NEURONS; MONKEY; ELBOW; FORCE AB Objective: To characterize kinematically any systematic aberration in multi-joint movements in cerebellar ataxia. Methods: Nine patients with cerebellar degeneration and nine normal subjects, mobile only at the shoulder and elbow of the right arm, were required to produce left-to-right cross-body linear hand trajectories on the horizontal surface of a digitizing tablet. Nonlinearity indicated failure of precise coordination of the two joints. A wide range of hand speeds was studied: Data analysis was restricted primarily to the first 130 ms of movement, Results: As hand velocities increased, normal subjects and, especially, patients produced misdirected, curved paths. Normal subjects had significant curvature when peak speeds exceeded 100 cm/s and a trend toward significant bi-directional angular deviation at velocities greater than 300 cm/s. In patients, peak path curvature was significantly greater than normal at peak velocities of 50 to 200 cm/s, By 3.3 cm, their paths deviated significantly outward at all but the slowest speeds. Overall, patients' maximal hand velocities and shoulder angular velocities, as well as maximal angular accelerations at both joints, were significantly lower than normal. Conclusions: The patients' trajectory aberrations were attributed to a deficient rate of rotation at the shoulder relative to that at the elbow. Relative to task requirements, their rate of torque development was apparently deficient at both joints, but to a greater degree at the shoulder. Joint torque-rate impairment may contribute to the ataxia in both multi- and single-joint movements of patients with cerebellar disorders. A similar, but smaller impairment may produce milder nonlinearity in high-velocity movements of normal subjects. RP Massaquoi, S (reprint author), NINCDS,MED NEUROL BRANCH,HUMAN MOTOR CONTROL SECT,NIH,BLDG 10,ROOM 5N226,10 CTR DR MSC 1428,BETHESDA,MD 20892, USA. NR 32 TC 40 Z9 40 U1 0 U2 3 PU CANADIAN J NEUROL SCI INC PI CALGARY PA PO BOX 4220, STATION C EDITORIAL & SUBSCRIPTION SERV, CALGARY AB T2T 5N1, CANADA SN 0317-1671 J9 CAN J NEUROL SCI JI Can. J. Neurol. Sci. PD FEB PY 1996 VL 23 IS 1 BP 3 EP 14 PG 12 WC Clinical Neurology SC Neurosciences & Neurology GA TW394 UT WOS:A1996TW39400002 PM 8673959 ER PT J AU Boyd, J Takahashi, H Waggoner, SE Jones, LA Hajek, RA Wharton, JT Liu, FS Fujino, T Barrett, JC McLachlan, JA AF Boyd, J Takahashi, H Waggoner, SE Jones, LA Hajek, RA Wharton, JT Liu, FS Fujino, T Barrett, JC McLachlan, JA TI Molecular genetic analysis of clear cell adenocarcinomas of the vagina and cervix associated and unassociated with diethylstilbestrol exposure in utero SO CANCER LA English DT Article DE vaginal neoplasm; cervical neoplasm; estrogen; diethylstilbestrol; DNA repair; ras; p53; WT1; estrogen receptor; mutation ID DNA DAMAGE; ENDOMETRIAL CARCINOMA; GENOMIC ORGANIZATION; COLORECTAL-CANCER; BREAST-CANCER; WT1 GENE; CARCINOGENESIS; MUTATIONS; MICE; EXPRESSION AB BACKGROUND. Prenatal exposure to the synthetic estrogen diethylstilbestrol (DES) is associated with the subsequent development of clear cell adenocarcinoma of the lower reproductive tract in young women, and data concerning the molecular genetic alterations involved in the etiology of this tumor type have not previously been reported. Such knowledge would be of potential value by providing insight into the molecular mechanisms of hormonal carcinogenesis in general, as well as by suggesting molecular markers for risk assessment in the estrogen-exposed population. METHODS. A total of 24 samples of clear cell adenocarcinoma of the vagina or cervix, 16 associated with exposure in utero to DES and 8 with no history of DES exposure, were obtained as archival fixed and embedded tissue specimens. DNA was purified from these tissues and used to examine a number of biologically plausible molecular genetic endpoints for tumor specific alterations. RESULTS. No evidence was found for mutations in the K-ras or H-ras protooncogenes, the Wilms' tumor (WT1) tumor suppressor gene, or the estrogen receptor gene. Sporadic overexpression of the p53 tumor suppressor gene was detected in some tumor cell nuclei by immunohistochemistry, but in the absence of detectable p53 gene mutation. Genetic instability as manifested by somatic mutation of microsatellite repeats was widespread in these tumors, with evidence of microsatellite instability in all DES-associated tumors examined, and in 50% of those tumors not associated with DES exposure. CONCLUSIONS. These data are consistent with the hypothesis that the induction of genomic instability may be an important mechanism of DES-induced carcinogenesis. (C) American Cancer Society. C1 NIEHS,MOLEC CARCINOGENESIS LAB,RES TRIANGLE PK,NC 27709. NIEHS,REPROD & DEV TOXICOL LAB,RES TRIANGLE PK,NC 27709. UNIV CHICAGO,MED CTR,DEPT OBSTET & GYNECOL,GYNECOL ONCOL SECT,CHICAGO,IL 60637. UNIV TEXAS,MD ANDERSON CANC CTR,DEPT GYNECOL ONCOL,HOUSTON,TX. RP Boyd, J (reprint author), UNIV PENN,MED CTR,DEPT OBSTET & GYNECOL,DIV GYNECOL ONCOL,778 CLIN RES BLDG,415 CURIE BLVD,PHILADELPHIA,PA 19104, USA. NR 55 TC 56 Z9 58 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 0008-543X J9 CANCER JI Cancer PD FEB 1 PY 1996 VL 77 IS 3 BP 507 EP 513 DI 10.1002/(SICI)1097-0142(19960201)77:3<507::AID-CNCR12>3.0.CO;2-8 PG 7 WC Oncology SC Oncology GA TR916 UT WOS:A1996TR91600012 PM 8630958 ER PT J AU Heineman, EF Bernstein, L Stark, AD Spirtas, R AF Heineman, EF Bernstein, L Stark, AD Spirtas, R TI Mesothelioma, asbestos, and reported history of cancer in first-degree relatives SO CANCER LA English DT Article DE mesothelioma; occupational exposure; family; asbestos; etiology; case-control studies; risk factors; Li-Fraumeni cancer syndrome ID MALIGNANT MESOTHELIOMA; FAMILIAL MESOTHELIOMA AB BACKGROUND. Although malignant mesothelioma is known to be strongly related to asbestos exposure, its relationship to familial factors is unclear. METHODS. We compared reported histories of cancer in first-degree relatives, obtained from telephone interviews with the next-of-kin of 196 patients who had a pathologic diagnosis of mesothelioma, and with those from 511 deceased controls. RESULTS. Among men exposed to asbestos, we found a statistically significant twofold elevation in the risk of mesothelioma for patients reporting cancer in two or more first-degree relatives. We found no significant elevation in women or among the small number of men without asbestos exposure. The next-of-kin of three patients (but no controls) reported a possible mesothelioma in a first-degree relative; asbestos exposure could not be ruled out in those relatives. Associations of asbestos with pleural mesothelioma were stronger among men with a reported family history of cancer than men without, although no statistical evidence of an interaction was detected. CONCLUSIONS. These results provide suggestive, but limited, evidence that a family history of cancer may be a risk factor for mesothelioma, or may indicate an increased susceptibility to mesothelioma given asbestos exposure. (C) 1996 American Cancer Society. C1 UNIV SO CALIF,SCH MED,DEPT PREVENT MED,LOS ANGELES,CA 90033. NEW YORK STATE DEPT HLTH,CTR ENVIRONM HLTH,BUR ENVIRONM & OCCUPAT EPIDEMIOL,ALBANY,NY. RP Heineman, EF (reprint author), NCI,EPIDEMIOL & BIOSTAT PROGRAM,ENVIRONM EPIDEMIOL BRANCH,OCCUPAT STUDIES SECT,EPN ROOM 418,BETHESDA,MD 20892, USA. NR 15 TC 28 Z9 28 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 0008-543X J9 CANCER JI Cancer PD FEB 1 PY 1996 VL 77 IS 3 BP 549 EP 554 DI 10.1002/(SICI)1097-0142(19960201)77:3<549::AID-CNCR18>3.0.CO;2-4 PG 6 WC Oncology SC Oncology GA TR916 UT WOS:A1996TR91600018 PM 8630964 ER PT J AU Chow, WH Hsing, AW McLaughlin, JK Fraumeni, JF AF Chow, WH Hsing, AW McLaughlin, JK Fraumeni, JF TI Smoking and adrenal cancer mortality among United States veterans SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article AB Adrenal cancer is a rare and heterogenous group of tumors the etiology of which is largely unknown, Tobacco use was suggested as a potential risk factor in a recent case-control study of adults dying from adrenal cancers, most of which were adrenocortical carcinomas, In a cohort study of nearly 250,000 United States veterans whose mortality was followed for up to 26 years, we evaluated the risk of adrenal cancer associated with tobacco use, Relative risks and corresponding 95% confidence intervals were calculated, A total of 27 adrenal cancer deaths were observed during the followup period, Relative to nonusers of any tobacco, risk was elevated 5-fold (relative risk = 5.1; confidence interval = 1.1-22.4) among current cigarette smokers, with risks further increased among those who smoked > 20 cigarettes/day (P for trend < 0.01), Nonsignificant increases in risk occurred among smokers of other forms of tobacco, This cohort study provides support for an etiological relationship between tobacco smoking and adrenal cancer, although further confirmatory studies are needed. C1 NCI,DIV CANC EPIDEMIOL & GENET,BETHESDA,MD. RP Chow, WH (reprint author), INT EPIDEMIOL INST,1550 RES BLVD,ROCKVILLE,MD 20850, USA. NR 13 TC 5 Z9 5 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA PUBLIC LEDGER BLDG, SUITE 816, 150 S. INDEPENDENCE MALL W., PHILADELPHIA, PA 19106 SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD FEB PY 1996 VL 5 IS 2 BP 79 EP 80 PG 2 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA TU885 UT WOS:A1996TU88500001 PM 8850265 ER PT J AU DeBenedetti, VMG Travis, LB Welsh, JA vanLeeuwen, FE Stovall, M Clarke, EA Boice, JD Bennett, WP AF DeBenedetti, VMG Travis, LB Welsh, JA vanLeeuwen, FE Stovall, M Clarke, EA Boice, JD Bennett, WP TI p53 mutations in lung cancer following radiation therapy for Hodgkin's disease SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID IONIZING-RADIATION; ESCHERICHIA-COLI; HUMAN LYMPHOBLASTS; GAMMA-RADIATION; HUMAN-CELLS; RISK; DNA; LYMPHOMA; SPECTRUM AB High risks of lung cancer occur after successful treatment of Hodgkin's disease. In addition to tobacco smoking, other risk factors include radiotherapy, chemotherapy, and immunosuppression, although the relative contributions of each are unknown, We conducted p53 mutational spectrum analysis in second lung cancers after radiation therapy for Hodgkin's disease in the Netherlands and in Ontario, Canada, Lung cancer tissues from 11 patients were analyzed by p53 immunohistochemistry and DNA sequence analysis. All were male cigarette smokers, all received radiation therapy, and six also received chemotherapy. The lung cancers occurred 9.8 years (mean) after treatment, Radiation doses to lung lobes that developed the tumors averaged 5.7 Gy (range, 3.7-11.7 Gy), Sequence analysis showed four missense and two silent p53 point mutations in five patients, There were four G:C --> A:T transitions; three of four mutated deoxyguanines occurred on the coding strand, and one was a CPG site, There were two transversions: one G:C --> C:G and one A:T --> C:G. Despite moderate or heavy smoking histories in all patients, the mutational spectrum appears to differ from usual smoking-related lung cancers in which G:C --> T:A transversions predominate, The absence of G:C --> T:A mutations and the prominence of G:C --> A:T transitions, which are characteristic of radiation and oxidative damage, suggest that radiotherapy might have caused some of the p53 mutations, These data illustrate the potential of mutation analysis to determine causes of human cancer, If confirmed in a larger series, these results imply that some radiation-induced cancers can be distinguished from those caused by other factors. C1 NCI,HUMAN CARCINOGENESIS LAB,BETHESDA,MD 20892. NCI,RADIAT EPIDEMIOL BRANCH,BETHESDA,MD 20892. NETHERLANDS CANC INST,DEPT EPIDEMIOL,1066 CX AMSTERDAM,NETHERLANDS. UNIV TEXAS,MD ANDERSON CANC CTR,DEPT RADIAT PHYS,HOUSTON,TX 77030. ONTARIO CANC TREATMENT & RES FDN,TORONTO,ON,CANADA. NR 47 TC 27 Z9 28 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 FEB PY 1996 VL 5 IS 2 BP 93 EP 98 PG 6 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA TU885 UT WOS:A1996TU88500004 PM 8850268 ER PT J AU Michalova, K Lemez, P Bartsch, O Brezinova, J Zemanova, Z Jelinek, J Horak, ID Burke, PJ AF Michalova, K Lemez, P Bartsch, O Brezinova, J Zemanova, Z Jelinek, J Horak, ID Burke, PJ TI Derivative (6)t(1;6)(q22;p21) revealed in bone marrow cells by FISH 9 months before diagnosis of acute T-lymphoblastic leukemia SO CANCER GENETICS AND CYTOGENETICS LA English DT Article ID CHROMOSOMES AB A chromosomal clone with unbalanced translocation resulting in partial trisomy of segment 1q22-qter and partial monosomy of segment 6p21-pter was revealed by fluorescence in situ hybridization (FISH) using a panel of different whole chromosome painting probes. The pathologic clone appeared after sequential chemotherapy treatment for AML-M5 when the patient was in complete remission before development of T-ALL. However, this clone was present during the whole period of treatment for T-ALL. The clone remained the only chromosomal aberration found. Breakpoints were detected more easily and more precisely with the use of the FISH technique than with G-banding only. C1 INST HEMATOL & BLOOD TRANSFUS,PRAGUE,CZECH REPUBLIC. TECH UNIV DRESDEN,INST CLIN GENET,O-8027 DRESDEN,GERMANY. NIH,US DEPT HHS,BETHESDA,MD. JOHNS HOPKINS ONCOL CTR,BALTIMORE,MD. RP Michalova, K (reprint author), CHARLES UNIV,GEN FAC HOSP,DEPT MED 3,FAC MED 1,U NEMOCNICE 1,CR-12808 PRAGUE 2,CZECH REPUBLIC. RI Jelinek, Jaroslav/A-8476-2008; Jelinek, Jaroslav/D-2282-2012; Zemanova, Zuzana/D-8041-2017; Michalova, Kyra/D-8081-2017 OI Jelinek, Jaroslav/0000-0002-2533-0220; Zemanova, Zuzana/0000-0002-7538-6601; Michalova, Kyra/0000-0003-0259-8475 NR 10 TC 4 Z9 4 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0165-4608 J9 CANCER GENET CYTOGEN JI Cancer Genet. Cytogenet. PD FEB PY 1996 VL 86 IS 2 BP 131 EP 135 DI 10.1016/0165-4608(95)00199-9 PG 5 WC Oncology; Genetics & Heredity SC Oncology; Genetics & Heredity GA UC163 UT WOS:A1996UC16300008 PM 8603339 ER PT J AU Novakovic, B Fears, TR Wexler, LH McClure, LL Wilson, DL McCalla, JL Tucker, MA AF Novakovic, B Fears, TR Wexler, LH McClure, LL Wilson, DL McCalla, JL Tucker, MA TI Experiences of cancer in children and adolescents SO CANCER NURSING LA English DT Article DE cancer experiences; adolescents ID CHILDHOOD-CANCER; SURVIVORS; ADAPTATION; LIFE AB In an effort to understand the effect of cancer diagnosis and treatment in children and adolescents, and to identify issues that should be addressed with newly diagnosed patients, 85 patients with Ewing's sarcoma family tumors (ESFT) were interviewed about their experience of having cancer. This represents 90% of all eligible patients who survived at least 3 years since their diagnosis and who were treated for ESFT at the National Cancer Institute (NCI) from 1965-1993. The mean age of patients at the time of diagnosis was 15.8 +/- 5.3 years, and mean rime since diagnosis was 13.6 +/- 6.4 years. Patients from this cohort had a disease usually related to poor outcome. Patients answered five open-ended written questions. Negative experiences that they described included transient and permanent discomfort and disabilities related to cancer; disruption of life or relationships; and emotional aspects of cancer diagnosis or treatment. Positive aspects of having cancel included changed attitudes about self and life, improved relationships with others, or better job performance. Advice for newly diagnosed patients most often dealt with the emotional aspects of cancer. The importance of patient-to-patient support was frequently described. Overall, having cancer was not an entirely negative experience, and it may result in introspection and improved relationships with others. C1 NCI,GENET EPIDEMIOL BRANCH,BETHESDA,MD 20892. NCI,BIOSTAT BRANCH,BETHESDA,MD 20892. GEORGETOWN UNIV,MED CTR,WASHINGTON,DC 20007. NCI,PEDIAT BRANCH,BETHESDA,MD 20892. RI Tucker, Margaret/B-4297-2015 NR 19 TC 34 Z9 34 U1 0 U2 3 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0162-220X J9 CANCER NURS JI Cancer Nurs. PD FEB PY 1996 VL 19 IS 1 BP 54 EP 59 DI 10.1097/00002820-199602000-00007 PG 6 WC Oncology; Nursing SC Oncology; Nursing GA TV443 UT WOS:A1996TV44300007 PM 8904387 ER PT J AU DeLaPena, L Tomaszewski, JG Bernato, DL Kryk, JA Molenda, J Gantz, S AF DeLaPena, L Tomaszewski, JG Bernato, DL Kryk, JA Molenda, J Gantz, S TI Programmed instruction: Biotherapy: Module IV. Interleukins SO CANCER NURSING LA English DT Article ID CYTOKINE RP DeLaPena, L (reprint author), NIH,CTR CLIN,DEPT NURSING,BETHESDA,MD 20892, USA. NR 14 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0162-220X J9 CANCER NURS JI Cancer Nurs. PD FEB PY 1996 VL 19 IS 1 BP 60 EP 73 DI 10.1097/00002820-199602000-00008 PG 14 WC Oncology; Nursing SC Oncology; Nursing GA TV443 UT WOS:A1996TV44300008 ER PT J AU Gorospe, M Holbrook, NJ AF Gorospe, M Holbrook, NJ TI Role of p21 in prostaglandin A(2)-mediated cellular arrest and death SO CANCER RESEARCH LA English DT Article ID GROWTH-INHIBITION; ANTINEOPLASTIC PROSTAGLANDINS; CYCLOPENTENONE PROSTAGLANDINS; MECHANISM; SITE; MODULATION; CISPLATIN; CELLS AB Prostaglandin A(2) (PGA(2)) treatment induces growth arrest of most cells, and we have recently shown that, for breast carcinoma MCF-7 cells, this is correlated with an induction of the cyclin-dependent kinase inhibitor p21 and reduced cyclin-dependent kinase 2 activity, In this study, we demonstrate that, in RKO cells, PGA(2) treatment fails to induce growth arrest, but rather results in significant cell death, These effects are correlated with lack of p21 induction and enhanced cyclin-dependent kinase 2 activity. Reduction of endogenous p21 expression in MCF-7 cells through expression of antisense p21 resulted in a response pattern approaching that seen in RKO cells, characterized by diminished growth arrest and increased death. These findings support a role for p21 in PGA(2)-mediated growth arrest, which we propose serves to prevent cell death caused by inappropriate cell cycle progression. C1 NIA,GERONTOL RES CTR,SECT GENE EXPRESS & AGING,BALTIMORE,MD 21224. NR 22 TC 65 Z9 65 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA PUBLIC LEDGER BLDG, SUITE 816, 150 S. INDEPENDENCE MALL W., PHILADELPHIA, PA 19106 SN 0008-5472 J9 CANCER RES JI Cancer Res. PD FEB 1 PY 1996 VL 56 IS 3 BP 475 EP 479 PG 5 WC Oncology SC Oncology GA TR324 UT WOS:A1996TR32400012 PM 8564956 ER PT J AU Li, JJ Dong, ZG Dawson, MI Colburn, NH AF Li, JJ Dong, ZG Dawson, MI Colburn, NH TI Inhibition of tumor promoter-induced transformation by retinoids that transrepress AP-1 without transactivating retinoic acid response element SO CANCER RESEARCH LA English DT Article ID ORNITHINE DECARBOXYLASE ACTIVITY; ANCHORAGE-INDEPENDENT GROWTH; EPIDERMAL-CELLS; TERMINAL DIFFERENTIATION; RECEPTOR-GAMMA; DNA-BINDING; X RECEPTOR; VITAMIN-A; C-JUN; MOUSE AB Both retinoic acid (RA) treatment and dominant-negative c-Jun mutant expression effectively inhibit phorbol ester-induced AP-1 activity and induced neoplastic transformation in mouse epidermal JB6 cells, However, both reagents also target non-AP-1 molecules in addition, Because liganded retinoic acid receptors interact with and transactivate RA response elements (RAREs) on DNA, as well as interact with Jun protein to block AP-1 activity, the question arises as to which of these two activities of retinoids is responsible for antitumor-promoting activity, To address this question we generated JB6 promotion-sensitive (P+) cell lines that are stably transfected with a construct containing the collagenase promoter bearing one AP-1-binding site that drives a luciferase reporter gene. The stable collagenase-luciferase-transfected cell lines showed 1.5-3.5-fold enhanced AP-1 activity when treated with 12-O-tetradecanoyl-phorbol-13-acetate (TPA). Up to 90% of TPA-induced AP-1 activity was blocked by retinoids SR11238, SR11302, or trans-RA, but not by retinoid SR11235, Of these retinoids, only RA and SR11235 were able to transactivate RARE-dependent gene expression. Transrepression of TPA-induced AP-1 and transactivation of RARE by RA, SR11238, and SR11302 were concentration dependent at 10(-10) to 10(-6) M retinoid, When tested for activity in inhibiting tumor promoter-induced transformation in JB6 P+ cells, the retinoids specific for AP-1 transrepression were inhibitory, whereas SR11235, which only activated RARE, showed little effect, We thus conclude that the AP-1-blocking activity of retinoids is likely to be responsible for the antitumor-promoting activity, This result, together with the observation that dominant-negative Jun blocks transformation, argues for a requirement of induced AP-1 in the tumor promoter-induced transformation process. C1 UNIV MINNESOTA,HORMEL INST,AUSTIN,MN 55912. SRI INT,MENLO PK,CA 94025. RP Li, JJ (reprint author), NCI,VIRAL CARCINOGENESIS LAB,CELL BIOL SECT,POB B,BLDG 560,ROOM 21-27,FREDERICK,MD 21702, USA. NR 41 TC 131 Z9 132 U1 0 U2 2 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA PUBLIC LEDGER BLDG, SUITE 816, 150 S. INDEPENDENCE MALL W., PHILADELPHIA, PA 19106 SN 0008-5472 J9 CANCER RES JI Cancer Res. PD FEB 1 PY 1996 VL 56 IS 3 BP 483 EP 489 PG 7 WC Oncology SC Oncology GA TR324 UT WOS:A1996TR32400014 PM 8564958 ER PT J AU Kohn, EC Reed, E Sarosy, G Christian, M Link, CJ Cole, K Figg, WD Davis, PA Jacob, J Goldspiel, B Liotta, LA AF Kohn, EC Reed, E Sarosy, G Christian, M Link, CJ Cole, K Figg, WD Davis, PA Jacob, J Goldspiel, B Liotta, LA TI Clinical investigation of a cytostatic calcium influx inhibitor in patients with refractory cancers SO CANCER RESEARCH LA English DT Article ID INOSITOL PHOSPHATES; SIGNAL TRANSDUCTION; RECEPTOR; ACTIVATION; L651582; ENTRY; AGENT AB Carboxyamido-triazole (CAI) is a synthetic inhibitor of non-excitable calcium channels that reversibly inhibits angiogenesis, tumor cell proliferation, and metastatic potential, Inhibition of calcium influx and calcium-dependent events is a potential common mechanism underlying these effects of CAI, The cytostatic and antiangiogenic properties of CAI led to its development for clinical investigation, In a Phase I clinical trial open to patients with refractory solid tumors, 49 patients received p.o. administered CAI daily or every other day, Two oral formulations, a PEG-400 CAI solution and a gelatin capsule containing CAI in PEG-400, were tested, All administered dosages of CAI yielded plasma concentrations at or above the range demonstrated to be effective in inhibiting signaling and cancer progression in vitra and in preclinical models (1 mu g/ml, 2.3 mu M). Toxicity of p.o. administered CAI most commonly consisted of dose-related grade 1-2 nausea, vomiting, and occasional anorexia, CAI administration at bedtime ameliorated gastrointestinal complaints in many patients; others required addition of simple antiemetic regimens, usually consisting of metoclopropamide or prochlorperazine, Gastrointestinal complaints were the cause for compliance-limiting toxicity at 175 mg/m(2)/day of the liquid formulation and 125 mg/m(2)/day of the gelatin capsule formulation, Reversible and rare sensory axonal neuropathy (grade 3, 1 patient) and neutropenia (grade 4, 1 patient) were dose-limiting toxicities observed at the 330 mg/m(2) every-other-day liquid CAI dose Level, No evidence of cumulative end organ damage or central nervous system injury was observed, Disease stabilization and improvement in performance status was observed in 49% of evaluable patients who had disease progression before CAI, Disease stabilization and associated improvement in performance status was seen in patients with renal cell carcinoma (7 months), pancreaticobiliary carcinomas (3, 5, and 5 months), melanoma (7 months), ovarian cancer (7 months), and non-small cell lung cancer (3 months), The recommended Phase II doses from this trial are 150 mg/m(2)/day in the liquid formulation and 100 mg/m(2)/day in the gelatin capsule formulation. C1 NCI,CLIN PHARMACOL BRANCH,BETHESDA,MD 20892. NIH,WARREN G MAGNUSON CLIN CTR,DEPT PHARM,BETHESDA,MD 20892. RP Kohn, EC (reprint author), NCI,SIGNAL TRANSDUCTR & PREVENT UNIT,PATHOL LAB,BLDG 10,ROOM 2A33,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. RI Cole, Kristina/M-3922-2015; Figg Sr, William/M-2411-2016 NR 24 TC 88 Z9 89 U1 0 U2 2 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA PUBLIC LEDGER BLDG, SUITE 816, 150 S. INDEPENDENCE MALL W., PHILADELPHIA, PA 19106 SN 0008-5472 J9 CANCER RES JI Cancer Res. PD FEB 1 PY 1996 VL 56 IS 3 BP 569 EP 573 PG 5 WC Oncology SC Oncology GA TR324 UT WOS:A1996TR32400029 PM 8564973 ER PT J AU OBrien, ML Rangwala, SM Henry, KW Weinberger, C Crick, DC Waechter, CJ Feller, DR Noonan, DJ AF OBrien, ML Rangwala, SM Henry, KW Weinberger, C Crick, DC Waechter, CJ Feller, DR Noonan, DJ TI Convergence of three steroid receptor pathways in the mediation of nongenotoxic hepatocarcinogenesis SO CARCINOGENESIS LA English DT Article ID PEROXISOMAL 3-KETOACYL-COA THIOLASE; PROLIFERATOR-ACTIVATED RECEPTOR; BETA-OXIDATION PATHWAY; ACID-BINDING-PROTEIN; RAT-LIVER; FATTY-ACIDS; GLUCOCORTICOID RECEPTOR; RETINOIC ACID; GENE; CLONING AB The mechanisms by which peroxisome proliferators are able to regulate metabolic processes such as fat metabolism, while at the same time creating an environment for the development of hepatocellular carcinomas, is a central issue in the non-genotoxic carcinogenesis field, The convergence of two members of the steroid receptor family (peroxisome proliferator-activated receptor, PPAR; and retinoid X receptor, RXR) has provided strong support for an oxidative stress component in this carcinogenesis process, but has yet to define clearly a pathway for the classical tumor promotion events associated with peroxisome proliferation, The findings presented here integrate a third member of the steroid receptor family into this process and suggest a novel autocrine loop and mechanism for creating both oxidative stress and tumor promotion. A central regulatory component in this pathway is farnesol which has recently been shown to induce transcription mediated by the steroid receptor family member, farnesoid X receptor (FXR), In this report, it is clearly demonstrated that farnesol can also upregulate the transcriptional events of PPAR, but most likely through a different farnesoid metabolite, resulting in the regulation of an entirely different set of genetic components, Deregulation of the activities of these receptors offers a provocative mechanism for explaining the hepatocarcinogenic effects of peroxisome proliferators in chronically treated rodents. C1 UNIV KENTUCKY,DEPT BIOCHEM,LEXINGTON,KY 40536. OHIO STATE UNIV,COLL PHARM,DIV PHARMACOL,COLUMBUS,OH 43270. NIEHS,REPROD & DEV TOXICOL LAB,RES TRIANGLE PK,NC 27709. UNIV MISSISSIPPI,SCH PHARM,DEPT PHARMACOL,UNIVERSITY,MS 38677. FU NIDDK NIH HHS [DK47132]; NIGMS NIH HHS [GM36065] NR 51 TC 29 Z9 29 U1 0 U2 1 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0143-3334 J9 CARCINOGENESIS JI Carcinogenesis PD FEB PY 1996 VL 17 IS 2 BP 185 EP 190 DI 10.1093/carcin/17.2.185 PG 6 WC Oncology SC Oncology GA UC149 UT WOS:A1996UC14900002 PM 8625436 ER PT J AU Wang, TTY Sathyamoorthy, N Phang, JM AF Wang, TTY Sathyamoorthy, N Phang, JM TI Molecular effects of genistein on estrogen receptor mediated pathways SO CARCINOGENESIS LA English DT Article ID INHIBITOR; GROWTH AB Genistein, a component of soy products, may play a role in the prevention of breast and prostate cancer, However, little is known about the molecular mechanisms involved, In the present study, we examined the effects of genistein on the estrogen receptor positive human breast cancer cell line MCF-7. We observed that genistein stimulated estrogen-responsive pS2 mRNA expression at concentrations as low as 10(-8) M and these effects can be inhibited by tamoxifen, We also showed that genistein competed with [H-3]estradiol binding to the estrogen receptor with 50% inhibition at 5 x 10(-7) M. Thus, the estrogenic effect of genistein would appear to be a result of an interaction with the estrogen receptor, The effect of genistein on growth of MCF-7 cells was also examined, Genistein produced a concentration-dependent effect on the growth of MCF-7 cells, At lower concentrations (10(-8)-10(-6) M) genistein stimulated growth, but at higher concentrations (>10(-5) M) genistein inhibited growth. The effects of genistein on growth at lower concentrations appeared to be via the estrogen receptor pathway, while the effects at higher concentrations were independent of the estrogen receptor, We also found that genistein, though estrogenic, can interfere with the effects of estradiol, In addition, prolonged exposure to genistein resulted in a decrease in estrogen receptor mRNA level as well as a decreased response to stimulation by estradiol. RP Wang, TTY (reprint author), NCI, LAB NUTR & MOLEC REGULAT, FREDERICK CANC RES & DEV CTR, NIH, FREDERICK, MD 21701 USA. NR 17 TC 347 Z9 361 U1 2 U2 12 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0143-3334 J9 CARCINOGENESIS JI Carcinogenesis PD FEB PY 1996 VL 17 IS 2 BP 271 EP 275 DI 10.1093/carcin/17.2.271 PG 5 WC Oncology SC Oncology GA UC149 UT WOS:A1996UC14900015 PM 8625449 ER PT J AU Page, JE Ross, HL Bigger, CAH Dipple, A AF Page, JE Ross, HL Bigger, CAH Dipple, A TI Mutagenic specificities and adduct distributions for 7-bromomethylbenz[a]anthracenes SO CARCINOGENESIS LA English DT Article ID BENZOPHENANTHRENE DIHYDRODIOL EPOXIDES; SHUTTLE VECTOR PLASMID; ESCHERICHIA-COLI; CHEMICAL CARCINOGENESIS; SUPF GENE; DNA; MUTATIONS; 1,2-EPOXIDES; ADENINE; CELLS AB Mutation induction in the supF gene of the plasmid pS189 by 7-bromomethylbenz[a]anthracene and 7-bromomethyl-12-methylbenz[a]anthracene was examined. The former compound was substantially more mutagenic than the latter but a much greater proportion of the total mutations were located at mutation hotspots for the 12-methyl derivative. The overall correlation between sites of mutation and sites of polymerase arrest (an indicator of adduct formation) through the supF gene was poor. Although these bromo-compounds should form only a single guanine adduct (unlike dihydrodiol epoxides that form both cis and trans adducts) more than one mutational change was found at a given site, although the predominant base substitution was G-->T for either compound. C1 NCI,CHEM CARCINOGENESIS LAB,ABL,BASIC RES PROGRAM,FREDERICK CANC RES & DEV CTR,FREDERICK,MD 21702. NR 38 TC 8 Z9 8 U1 0 U2 0 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0143-3334 J9 CARCINOGENESIS JI Carcinogenesis PD FEB PY 1996 VL 17 IS 2 BP 283 EP 288 DI 10.1093/carcin/17.2.283 PG 6 WC Oncology SC Oncology GA UC149 UT WOS:A1996UC14900017 PM 8625451 ER PT J AU Pereira, MA Barnes, LH Steele, VE Kelloff, GV Lubet, RA AF Pereira, MA Barnes, LH Steele, VE Kelloff, GV Lubet, RA TI Piroxicam-induced regression of azoxymethane-induced aberrant crypt foci and prevention of colon cancer in rats SO CARCINOGENESIS LA English DT Article ID PUTATIVE PRENEOPLASTIC LESIONS; FAMILIAL ADENOMATOUS POLYPOSIS; LARGE-BOWEL CANCER; F344 RATS; HEXOSAMINIDASE ACTIVITY; RECTAL ADENOMAS; SULINDAC; ASPIRIN; CARCINOGENESIS AB Piroxicam has been shown to prevent azoxymethane (AOM)-induced aberrant crypt foci and colon cancer in rats. In this communication we evaluate whether piroxicam can also cause regression of precancerous lesions identified as aberrant crypt foci, thus preventing the occurrence of cancer. Male Fischer-344 rats were administered 0.125 g/kg piroxicam in their diet starting either 1 week prior to or 12 weeks after a single subcutaneous injection of AOM (30 mg/kg body wt). The yield of aberrant crypt foci and of colon adenomas and adenocarcinomas was determined at 5, 12, 27 and 37 weeks after administering the AOM respectively. When piroxicam was administered starting 1 week prior to AOM the yield of aberrant crypt foci at the three initial time points was reduced. When the administration of piroxicam was delayed until 12 weeks after AOM the yield of aberrant crypt foci was reduced from 53.8 +/- 8.1 foci/colon at 12 weeks to 11.1 +/- 2.0 at 27 weeks. At 37 weeks after administering AOM the yield of colon tumors was 0.59 +/- 0.11 tumors/animal, while in rats administered piroxicam beginning either 1 week prior to or 12 weeks after AOM the yield was similarly reduced to 0.14 +/- 0.07 and 0.17 +/- 0.07 tumors/animal respectively. Thus piroxicam was demonstrated not only to prevent, but also to cause regression of aberrant crypt foci, both of which were associated with the prevention of colon tumors. C1 ENVIRONM HLTH RES & TESTING INC,LEXINGTON,KY 40503. NCI,DIV CANC PREVENT & CONTROL,BETHESDA,MD 20856. RP Pereira, MA (reprint author), MED COLL OHIO,CTR ENVIRONM MED,3000 ARLINGTON AVE,TOLEDO,OH 43614, USA. FU NCI NIH HHS [N01-CN-25495-01] NR 22 TC 31 Z9 32 U1 0 U2 0 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0143-3334 J9 CARCINOGENESIS JI Carcinogenesis PD FEB PY 1996 VL 17 IS 2 BP 373 EP 376 DI 10.1093/carcin/17.2.373 PG 4 WC Oncology SC Oncology GA UC149 UT WOS:A1996UC14900032 PM 8625466 ER PT J AU Bagrov, AY Fedorova, OV Dmitrieva, RI French, AW Anderson, DE AF Bagrov, AY Fedorova, OV Dmitrieva, RI French, AW Anderson, DE TI Plasma marinobufagenin-like and ouabain-like immunoreactivity during saline volume expansion in anesthetized dogs SO CARDIOVASCULAR RESEARCH LA English DT Article DE dog, anesthetized; plasma volume expansion; Na+/K+ ATPase inhibitors; bufodienolide; marinobufagenin; ouabain; endogenous digitalis-like factor (EDLF) ID DIGITALIS-LIKE-FACTOR; DIGOXIN-LIKE FACTORS; EXPERIMENTAL-HYPERTENSION; EXPANDED DOGS; CINOBUFAGIN; SUBSTANCES; ANTIBODIES; INHIBITOR; TRANSPORT; BUFALIN AB Objectives: This study investigated effects of acute plasma volume expansion on plasma levels and urinary output of two endogenous Na,K-ATPase inhibitors, marinobufagenin-like and ouabain-like immunoreactive substances. Methods: Plasma volume was expanded for 3 h via intravenous saline infusion in three groups of anesthetized dogs - nontreated (n = 5); pretreated with rabbit antidigoxin (n = 5); and pretreated with rabbit antimouse (control) antibody (n = 4). Results: Plasma marinobufagenin-like immunoreactivity increased to 11.87 +/- 3.16 nmol . l(-1) (vs. 0.30 +/- 0.16 nmol . l(-1)) within 10 min of volume expansion, in parallel with a 15% increase in LVdP/dt, then decreased to 2.21 +/- 0.59 nmol . l(-1), and in 90 min increased to 11.8 +/- 2.8 nmol . l(-1) 1-', in parallel with the maximal natriuretic response. Plasma concentrations of ouabain-like immunoreactive material were increased after 90 min of saline infusion (0.019 +/- 0.004 nmol . l(-1) vs. 0.139 +/- 0.056 nmol 1-'). Pretreatment of the animals with antidigoxin antibody blocked the positive inotropic and reduced natriuretic response to volume expansion, and decreased the urinary release of marinobufagenin-like, but not ouabain-like, material. Conclusions: These results show the presence of marinobufagenin-like immunoreactive substance in dog plasma and suggest that mammalian EDLF may have a bufodienolide nature. Endogenous marinobufagenin-like immunoreactive substance, which is likely to cross-react with antidigoxin antibody, is involved in the natriuretic and positive inotropic responses to plasma volume expansion. C1 NIA,BEHAV SCI LAB,NIH,BALTIMORE,MD 21224. RP Bagrov, AY (reprint author), IM SECHENOV EVOLUTIONARY PHYSIOL & BIOCHEM INST,PHARMACOL LAB,THOREZ PR 44,ST PETERSBURG 194223,RUSSIA. OI Dmitrieva, Renata/0000-0002-3073-7914 NR 57 TC 80 Z9 80 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0008-6363 J9 CARDIOVASC RES JI Cardiovasc. Res. PD FEB PY 1996 VL 31 IS 2 BP 296 EP 305 PG 10 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA UL026 UT WOS:A1996UL02600015 PM 8730407 ER PT J AU Martinez, A Unsworth, EJ Cuttitta, F AF Martinez, A Unsworth, EJ Cuttitta, F TI Adrenomedullin-like immunoreactivity in the nervous system of the starfish Marthasterias glacialis SO CELL AND TISSUE RESEARCH LA English DT Article DE adrenomedullin; nitric oxide; nervous system; gut; immunocytochemistry; Marthasterias glacialis (Echinodermata) ID ASTERIAS-RUBENS; ENDOCRINE-CELLS; ECHINODERMATA AB The nervous system of the starfish Marthasterias glacialis was investigated immunocytochemically using an antiserum specific for adrenomedullin (AM), a new regulatory peptide. Immunoreactivity was only found in nerves of the basiepithelial plexus of cardiac and pyloric stomachs and pyloric caeca, while the radial nerve cords and the other digestive organs were negative. The strongest AM-like immunoreactivity was located in the current-producing areas of the cardiac stomach. The distribution of this peptide suggests different functions in echinoderms involving regulation of muscle movement and neurotransmission. The presence of an AM like substance in echinoderms points to an early phylogenetic origin for this regulatory system. RP Martinez, A (reprint author), NCI,NATL INST HLTH,BIOMARKERS & PREVENT RES BRANCH,9610 MED CTR DR,ROCKVILLE,MD 20850, USA. RI Martinez, Alfredo/A-3077-2013 OI Martinez, Alfredo/0000-0003-4882-4044 NR 24 TC 27 Z9 28 U1 0 U2 4 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0302-766X J9 CELL TISSUE RES JI Cell Tissue Res. PD FEB PY 1996 VL 283 IS 2 BP 169 EP 172 DI 10.1007/s004410050526 PG 4 WC Cell Biology SC Cell Biology GA TU683 UT WOS:A1996TU68300002 PM 8593645 ER PT J AU IshizuyaOka, A Ueda, S Shi, YB AF IshizuyaOka, A Ueda, S Shi, YB TI Transient expression of stromelysin-3 mRNA in the amphibian small intestine during metamorphosis SO CELL AND TISSUE RESEARCH LA English DT Article DE matrix metalloproteinase; intestine, small; metamorphosis; in situ hybridization; basement membrane; Xenopus laevis (Anura) ID GENE-EXPRESSION; CONNECTIVE-TISSUE; THYROID-HORMONE; XENOPUS-LAEVIS; CELLS; CARCINOMAS; INVITRO AB It has been suggested that a matrix metalloproteinase, stromelysin-3 (ST3), is an important enzyme for epithelial transformation; the ST3 gene is known to be regulated by thyroid hormone during Xenopus metamorphosis. In this study, we have examined the distribution of ST3 mRNA in the small intestine of Xenopus during metamorphosis by using in situ hybridization. Around stage 58, ST3 mRNA is first detectable in larval fibroblasts near the muscular layer, and then increases in amount throughout the entire region of connective tissue. By stage 61, when connective tissue cells are rapidly increasing in number, ST3 mRNA is localized in fibroblasts just beneath the epithelium. This localization of ST3 mRNA is in good temporal accordance with modification of the basement membrane and epithelial transformation from the larval to adult form. Thereafter, ST3 mRNA gradually decreases and is no longer detected after stage 63 when the adult epithelium has completely replaced the larval type. The transient expression of ST3 mRNA in the fibroblasts of connective tissue during metamorphosis indicates that it plays an important role in epithelial transformation by changing the basement membrane. C1 NICHHD,MOLEC EMBRYOL LAB,NATL INST HLTH,BETHESDA,MD 20892. RP IshizuyaOka, A (reprint author), DOKKYO UNIV,SCH MED,DEPT ANAT,MIBU,TOCHIGI 32102,JAPAN. NR 21 TC 47 Z9 47 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0302-766X J9 CELL TISSUE RES JI Cell Tissue Res. PD FEB PY 1996 VL 283 IS 2 BP 325 EP 329 DI 10.1007/s004410050542 PG 5 WC Cell Biology SC Cell Biology GA TU683 UT WOS:A1996TU68300018 PM 8593661 ER PT J AU Yang, CL Chang, J Gorospe, M Passaniti, A AF Yang, CL Chang, J Gorospe, M Passaniti, A TI Protein tyrosine phosphatase regulation of endothelial cell apoptosis and differentiation SO CELL GROWTH & DIFFERENTIATION LA English DT Article ID CAPILLARY-LIKE STRUCTURES; FIBROBLAST GROWTH-FACTOR; TUMOR-NECROSIS-FACTOR; ANGIOGENESIS INVITRO; BASEMENT-MEMBRANE; DEATH; PHOSPHORYLATION; ADHESION; PATHWAYS; MITOGEN AB Apoptosis, or programmed cell death, occurs during development and may also be an important factor in many diseases, However, little is known about the signal transduction pathways regulating apoptosis, In these studies, loss of endothelial cell-substrate attachment and apoptosis after removal of growth factors was associated with dephosphorylation of tyrosine residues at the cell periphery, Dephosphorylation of total cellular proteins accompanied apoptosis and was reduced by orthovanadate, an inhibitor of protein tyrosine phosphatases. Orthovanadate blocked the fragmentation of nuclear DNA, inhibited DNA laddering, and suppressed the expression of TRPM-2, an apoptosis-associated gene. The tyrosine phosphorylation levels of FAK(125), erk1 (mitogen-activated kinase kinase), and cdc-2 were reduced during apoptosis, FAK(125) dephosphorylation was inhibited by orthovanadate, but premature activation (tyrosine dephosphorylation) of cdc-2 was not. Orthovanadate was as effective as basic fibroblast growth factor in activating erk1 without increasing cell proliferation and in preventing the apoptosis of endothelial cells after treatment with tumor necrosis factor alpha. Endothelial cell differentiation on extracellular matrix (Matrigel) was also stimulated by orthovanadate in the absence of basic fibroblast growth factor without affecting growth arrest and inhibition of DNA synthesis, Expression of the cyclin-dependent kinase inhibitor p21 (Waf1/Cip1/Sdi1) was down-regulated during the early stages of differentiation, remained low for at least 6 hours as differentiation proceeded, and increased upon completion of differentiation. Cells that failed to down-regulate p21 mRNA on Matrigel in the absence of angiogenic factors underwent apoptosis. These results suggest that protein tyrosine phosphatases are actively involved in signal transduction during apoptosis and may regulate p21 expression to inhibit endothelial cell differentiation. C1 NIA,GERONTOL RES CTR,BIOL CHEM LAB,BALTIMORE,MD 21224. NIA,GERONTOL RES CTR,GENE EXPRESS UNIT,BALTIMORE,MD 21224. NR 69 TC 49 Z9 50 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA PUBLIC LEDGER BLDG, SUITE 816, 150 S. INDEPENDENCE MALL W., PHILADELPHIA, PA 19106 SN 1044-9523 J9 CELL GROWTH DIFFER JI Cell Growth Differ. PD FEB PY 1996 VL 7 IS 2 BP 161 EP 171 PG 11 WC Cell Biology SC Cell Biology GA TU887 UT WOS:A1996TU88700003 PM 8822199 ER PT J AU Kowtha, VC Bryant, HJ Krauthamer, V Iwasa, KH Stenger, DA AF Kowtha, VC Bryant, HJ Krauthamer, V Iwasa, KH Stenger, DA TI Spontaneous firing of NG108-15 cells induced by transient exposure to ammonium chloride SO CELLULAR AND MOLECULAR NEUROBIOLOGY LA English DT Article DE NG108-15; serum-free media; ammonium chloride; intracellular pH ID INTRACELLULAR PH; NEURONS; INACTIVATION; AXONS AB 1. We report that NG108-15 (neuroblastoma x glioma) cells differentiated in defined serum-free media are capable of exhibiting stable automaticity (the spontaneous occurrence of regenerative action potentials) following exposure to extracellular perfusates containing NH4Cl. 2. Membrane depolarization (4-5 mV) concomitant with an increased pH(i) during NH4Cl exposure are followed by hyperpolarization (5-7 mV), subthreshold oscillations, and spontaneous firing after the removal of NH4Cl. 3. Cells cultured in 10% serum did not exhibit automaticity. Cells cultured in serum-free media are twice as likely to show automaticity as those cultured in reduced (1.5%) serum media. 4. We have examined factors that contribute to the events following NH4Cl exposure, namely, membrane depolarization and hyperpolarization, subthreshold oscillations, and automaticity, The inward currents activated at more negative potentials and the ionic currents associated with pronounced afterhyperpolarization in NG108-15 cells cultured in serum-free media provide a basis for the repetitive activity in general and automaticity in particular. C1 USN,RES LAB,CTR BIOMOLEC SCI & ENGN,WASHINGTON,DC 20375. UNIFORMED SERV UNIV HLTH SCI,DEPT PHYSIOL,BETHESDA,MD 20814. US FDA,ELECTROPHYS BRANCH,DPS,OST,CDRH,ROCKVILLE,MD 20857. NIDCD,NATL INST HLTH,SECT BIOPHYS SENSORY PROC,LCB,BETHESDA,MD 20892. OI Iwasa, Kuni/0000-0002-9397-7704 NR 14 TC 5 Z9 5 U1 0 U2 0 PU PLENUM PUBL CORP PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 SN 0272-4340 J9 CELL MOL NEUROBIOL JI Cell. Mol. Neurobiol. PD FEB PY 1996 VL 16 IS 1 BP 1 EP 9 DI 10.1007/BF02578382 PG 9 WC Cell Biology; Neurosciences SC Cell Biology; Neurosciences & Neurology GA TV608 UT WOS:A1996TV60800001 PM 8714555 ER PT J AU Xu, NZ Coso, O Mahadevan, D DeBlasi, A Goldsmith, PK Simonds, WF Gutkind, JS AF Xu, NZ Coso, O Mahadevan, D DeBlasi, A Goldsmith, PK Simonds, WF Gutkind, JS TI The PH domain of Ras-GAP is sufficient for in vitro binding to beta gamma subunits of heterotrimeric G proteins SO CELLULAR AND MOLECULAR NEUROBIOLOGY LA English DT Article DE G proteins; ras-GAP; PH domain; beta gamma subunits; ras ID ADRENERGIC-RECEPTOR KINASE; TRANSLOCATION; DIMERS AB 1. The noncatalytic domain of Ras-GAP can affect signaling through G protein-coupled receptors by a poorly understood mechanism. 2. In this study, fusion proteins containing elements of the noncatalytic domain of ras-GAP were examined for their ability to bind beta gamma subunits of heterotrimeric G proteins and phosphotyrosine-containing polypeptides. 3. Our results demonstrate that purified beta gamma dimers associated with bacterially expressed GAP proteins and that this association does not require SH2 or SH3 domains but is dependent on the presence of the GAP pleckstrin-homology (PH) domain. In contrast, only the SH2 domains are necessary for binding to tyrosine phosphorylated proteins. 4. These findings raise the possibility that heterotrimeric G proteins might affect functioning of ras-like proteins through beta gamma subunits acting on their regulatory molecules. C1 NIDR,NIH,MOL SIGNALING UNIT,CELLULAR DEV & ONCOL LAB,BETHESDA,MD 20892. NATL CANC INST,CELLULAR & MOLEC BIOL LAB,BETHESDA,MD. IST RIC FARMACOL MARIO NEGRI,CONSORZIO MARIO NEGRI SUD,I-66030 SANTA MARIA IMBAR,ITALY. NIDDK,NATL INST HLTH,METAB DIS BRANCH,BETHESDA,MD 20892. RI Gutkind, J. Silvio/A-1053-2009 NR 25 TC 6 Z9 6 U1 0 U2 0 PU PLENUM PUBL CORP PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 SN 0272-4340 J9 CELL MOL NEUROBIOL JI Cell. Mol. Neurobiol. PD FEB PY 1996 VL 16 IS 1 BP 51 EP 59 DI 10.1007/BF02578386 PG 9 WC Cell Biology; Neurosciences SC Cell Biology; Neurosciences & Neurology GA TV608 UT WOS:A1996TV60800005 PM 8714559 ER PT J AU Murray, RP Bailey, WC Daniels, K Bjornson, WM Kurnow, K Connett, JE Nides, MA Kiley, JP AF Murray, RP Bailey, WC Daniels, K Bjornson, WM Kurnow, K Connett, JE Nides, MA Kiley, JP TI Safety of nicotine polacrilex gum used by 3,094 participants in the lung health study SO CHEST LA English DT Article DE cardiovascular illness; clinical trial; nicotine gum; side effects; smoking cessation ID CHEWING-GUM; SMOKING CESSATION; INTERVENTION; DESIGN; TRIAL AB Study objective: To assess cardiovascular conditions and other side effects associated with the use of nicotine polacrilex (NP), 2 mg. Design: A multicentered randomized control trial of early intervention for the prevention of COPD. Setting: Ten university medical centers in the United States and Canada. Participants: Adult smoking volunteers with evidence of early COPD; 3,923 in intervention and 1,964 controls. Intervention: Smoking cessation program, including NP. Measurements: Data on hospitalizations were collected annually. Data on reported NP side effects were collected at 4-month intervals for intervention participants. Results: The rates of hospitalization for cardiovascular conditions and cardiovascular deaths during the 5 years of the study were not related to use of NP, to dose of NP, or to concomitant use of NP and cigarettes. About 25% of NP users reported at least one side effect, but most were very minor and transient. Side effects associated with discontinuance of NP in 5% or more of users included headache, indigestion, mouth irritation, mouth ulcers, and nausea. There was no evidence that concomitant use of NP and cigarettes was associated with elevated rates of reported side effects. Participants in the smoking cessation intervention who received intensive levels of instruction, and monitoring of NP use (initially at 12 meetings during 3 months) appeared to report significantly lower rates of side effects (dizziness, headache, and throat irritation) than control participants, presumed to have less instruction and monitoring. Conclusions: NP, as used in the Lung Health Study, appears to be safe and unrelated to any cardiovascular illnesses or other serious side effects. C1 UNIV MANITOBA,WINNIPEG,MB R3T 2N2,CANADA. UNIV ALABAMA,BIRMINGHAM,AL. UNIV MINNESOTA,MINNEAPOLIS,MN 55455. OREGON HLTH SCI UNIV,PORTLAND,OR 97201. UNIV CALIF LOS ANGELES,LOS ANGELES,CA 90024. NHLBI,BETHESDA,MD 20892. FU NHLBI NIH HHS [N01-HR-46002] NR 13 TC 115 Z9 118 U1 0 U2 3 PU AMER COLL CHEST PHYSICIANS PI NORTHBROOK PA 3300 DUNDEE ROAD, NORTHBROOK, IL 60062-2348 SN 0012-3692 J9 CHEST JI Chest PD FEB PY 1996 VL 109 IS 2 BP 438 EP 445 DI 10.1378/chest.109.2.438 PG 8 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA TV429 UT WOS:A1996TV42900030 PM 8620719 ER PT J AU Boerwinkle, E Sharrett, AR Ballantyne, CM Davis, CE Gotto, A Smith, L AF Boerwinkle, E Sharrett, AR Ballantyne, CM Davis, CE Gotto, A Smith, L TI Circulating adhesion molecules predict atherosclerosis and incident CHD in the ARIC study. SO CIRCULATION LA English DT Meeting Abstract C1 UNIV TEXAS,HLTH SCI CTR,DALLAS,TX 75235. NHLBI,BETHESDA,MD 20892. BAYLOR COLL MED,HOUSTON,TX 77030. UNIV N CAROLINA,CHAPEL HILL,NC 27515. RI Ballantyne, Christie/A-6599-2008 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD FEB 1 PY 1996 VL 93 IS 3 BP 7 EP 7 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA TR330 UT WOS:A1996TR33000047 ER PT J AU Shiota, T Jones, M Yamada, I Heinrich, RS Ishii, M Sinclair, B Holcomb, S Yoganathan, AP Sahn, DJ AF Shiota, T Jones, M Yamada, I Heinrich, RS Ishii, M Sinclair, B Holcomb, S Yoganathan, AP Sahn, DJ TI Effective regurgitant orifice area by the color Doppler flaw convergence method for evaluating the severity of chronic aortic regurgitation - An animal study SO CIRCULATION LA English DT Article DE aortic regurgitation; echocardiography; blood flow; hemodynamics ID PROXIMAL FLOW CONVERGENCE; MITRAL REGURGITATION; QUANTITATIVE ASSESSMENT; CONTINUOUS-WAVE; QUANTIFICATION; VOLUME; REGION; INSUFFICIENCY AB Background The aim of the present study was to evaluate dynamic changes in aortic regurgitant (AR) orifice area with the use of calibrated electromagnetic (EM) flowmeters and to validate a color Doppler flow convergence (FC) method for evaluating effective AR orifice area and regurgitant volume. Methods and Results In 6 sheep, 8 to 20 weeks after surgically induced AR, 22 hemodynamically different states were studied. Instantaneous regurgitant flow rates were obtained by aortic and pulmonary EM flowmeters balanced against each other. Instantaneous AR orifice areas were determined by dividing these actual AR flow rates by the corresponding continuous wave velocities (over 25 to 40 points during each diastole) matched for each steady state. Echo studies were performed to obtain maximal aliasing distances of the FC in a low range (0.20 to 0.32 m/s) and a high range (0.70 to 0.89 m/s) of aliasing velocities; the corresponding maximal AR flow rates were calculated using the hemispheric flow convergence assumption for the FC isovelocity surface. AR orifice areas were derived by dividing the maximal flow rates by the maximal continuous wave Doppler velocities. AR orifice sizes obtained with the use of EM flowmeters showed little change during diastole, Maximal and time-averaged AR orifice areas during diastole obtained by EM flowmeters ranged from 0.06 to 0.44 cm(2) (mean, 0.24+/-0.11 cm(2)) and from 0.05 to 0.43 cm(2) (mean, 0.21+/-0.06 cm(2)), respectively. Maximal AR orifice areas by FC using low aliasing velocities overestimated reference EM orifice areas; however, at high AV, FC predicted the reference areas more reliably (0.25+/-0.16 cm(2), r=.82, difference=0.04+/-0.07 cm(2)). The product of the maximal orifice area obtained by the FC method using high AV and the velocity time integral of the regurgitant orifice velocity showed good agreement with regurgitant volumes per beat (r=.81, difference=0.9+/-7.9 mL/beat). Conclusions This study, using strictly quantified AR volume, demonstrated little change in AR orifice size during diastole. When high aliasing velocities are chosen, the FC method can be useful for determining effective AR orifice size and regurgitant volume. C1 OREGON HLTH SCI UNIV,PORTLAND,OR 97201. NIH,AMIN MED & SURG LAB,BETHESDA,MD. GEORGIA INST TECHNOL,SCH CHEM ENGN,ATLANTA,GA 30332. FU NHLBI NIH HHS [HL-43287] NR 34 TC 37 Z9 39 U1 0 U2 1 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD FEB 1 PY 1996 VL 93 IS 3 BP 594 EP 602 PG 9 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA TR330 UT WOS:A1996TR33000028 PM 8565180 ER PT J AU Burchfiel, CM Curb, JD Sharp, DS Rodriguez, BL Arakaki, R Abbott, RD Yano, K AF Burchfiel, CM Curb, JD Sharp, DS Rodriguez, BL Arakaki, R Abbott, RD Yano, K TI Insulin resistance syndrome and cardiovascular disease in elderly men: The Honolulu Heart Program SO CIRCULATION LA English DT Meeting Abstract C1 KUAKINI MED CTR,NHLBI,HONOLULU,HI. UNIV HAWAII,HONOLULU,HI 96822. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD FEB 1 PY 1996 VL 93 IS 3 BP P55 EP P55 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA TR330 UT WOS:A1996TR33000127 ER PT J AU Levy, D Larson, M Vasan, R Kannel, W Ho, K AF Levy, D Larson, M Vasan, R Kannel, W Ho, K TI Population attributable risk of hypertension for heart failure SO CIRCULATION LA English DT Meeting Abstract C1 FRAMINGHAM HEART DIS EPIDEMIOL STUDY,FRAMINGHAM,MA. NHLBI,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 0009-7322 J9 CIRCULATION JI Circulation PD FEB 1 PY 1996 VL 93 IS 3 BP P50 EP P50 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA TR330 UT WOS:A1996TR33000122 ER PT J AU Obarzanek, E Hunsberger, SA VanHorn, L Franklin, FA Stevens, VJ Hartmuller, VV Barton, BA Kimm, SYS Lasser, NL Kwiterovich, PO AF Obarzanek, E Hunsberger, SA VanHorn, L Franklin, FA Stevens, VJ Hartmuller, VV Barton, BA Kimm, SYS Lasser, NL Kwiterovich, PO TI Adequacy and safety of a reduced fat diet: The dietary intervention study in children (DISC) SO CIRCULATION LA English DT Meeting Abstract C1 NHLBI,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 0009-7322 J9 CIRCULATION JI Circulation PD FEB 1 PY 1996 VL 93 IS 3 BP P33 EP P33 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA TR330 UT WOS:A1996TR33000105 ER PT J AU Rodriguez, BL Curb, JD Burchfiel, CM Chyou, PH Fong, KO Masaki, K Huang, BJ Yano, K Sharp, D AF Rodriguez, BL Curb, JD Burchfiel, CM Chyou, PH Fong, KO Masaki, K Huang, BJ Yano, K Sharp, D TI The relationships between cardiovascular diseases (CM), total mortality and measures of socioeconomic statue (SES); The Honolulu Heart Program SO CIRCULATION LA English DT Meeting Abstract C1 UNIV HAWAII,JOHN A BURNS SCH MED,HONOLULU,HI 96822. NHLBI,HONOLULU,HI. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD FEB 1 PY 1996 VL 93 IS 3 BP P42 EP P42 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA TR330 UT WOS:A1996TR33000114 ER PT J AU Wheaton, PK He, J Cutler, JA Brancati, FL Appel, LJ Follmann, D Klag, MJ AF Wheaton, PK He, J Cutler, JA Brancati, FL Appel, LJ Follmann, D Klag, MJ TI Effects of oral potassium on blood pressure. A quantitative overview of randomized, controlled clinical trials. SO CIRCULATION LA English DT Meeting Abstract C1 JOHNS HOPKINS MED INST,BALTIMORE,MD 21205. NHLBI,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD FEB 1 PY 1996 VL 93 IS 3 BP P28 EP P28 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA TR330 UT WOS:A1996TR33000100 ER PT J AU Wilson, PWF Kannel, WB DAgostino, R AF Wilson, PWF Kannel, WB DAgostino, R TI Coronary disease risk factor clusters: Prevalence and impact on 16 year incidence of CHD in framingham offspring SO CIRCULATION LA English DT Meeting Abstract C1 NHLBI,FRAMINGHAM,MA. BOSTON UNIV,BOSTON,MA 02215. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD FEB 1 PY 1996 VL 93 IS 3 BP P1 EP P1 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA TR330 UT WOS:A1996TR33000073 ER PT J AU Engler, HD Selepak, ST Callaway, J AF Engler, HD Selepak, ST Callaway, J TI Effects of sonication of clinical specimens on detection of cytomegalovirus in shell vial cultures SO CLINICAL AND DIAGNOSTIC VIROLOGY LA English DT Article DE centrifugation; cytomegalovirus; shell vial culture; sonication ID VIRUS; CENTRIFUGATION; INFECTION AB Background: The centrifugation-enhanced shell vial (SV) method of virus culturing has decreased the time to laboratory detection of many viruses, and has become the principal method for the rapid detection of cytomegalovirus (CMV) in clinical specimens. Objectives: To examine the use of sonication and centrifugation of clinical specimens as a means of optimizing the sensitivity of SV detection of CMV, decreasing the toxicity of specimens to the SV monolayer, and facilitating the examination and interpretation of SV monolayers. Study design: A total of 350 clinical specimens submitted for CMV culture were processed and then divided in half with one-half sonicated for 1 min in a cup-horn-equipped sonicator, and the other half left unsonicated. Sonicated specimens were centrifuged to recover a cell-free supernatant. SVs containing MRC-5 fibroblast monolayers were inoculated with either the unsonicated whole specimen or the cell-free supernatant, and were stained with monoclonal antibodies directed against the immediate-early antigen of CMV after 24 and 48 h of incubation. Results: While no significant difference was observed in the overall number of specimens in which CMV was detected following sonication, sonication did afford a 31% increase in the number of CMV-positive specimens detected at 24 h. A significant reduction in toxicity of all specimens except for blood was observed for the sonicated specimens, although sonication of blood increased the number of blood specimens toxic to the monolayer by 40%. Use of the cell-free inoculum following sonication facilitated microscopic examination and interpretation of SV monolayers without adversely affecting the sensitivity of the culture. Conclusions: Sonication of clinical specimens prior to shell vial culturing for CMV is beneficial and can help to reduce specimen toxicity, facilitate interpretation of monolayers, and allow the earlier detection of a positive specimen. RP Engler, HD (reprint author), NIH,WARREN GRANT MAGNUSON CLIN CTR,DEPT CLIN PATHOL,MICROBIOL SERV,BLDG 10,ROOM 2C-385,BETHESDA,MD 20892, USA. NR 9 TC 1 Z9 1 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0928-0197 J9 CLIN DIAGN VIROL JI Clin. Diagn. Virol. PD FEB PY 1996 VL 5 IS 1 BP 67 EP 71 DI 10.1016/0928-0197(95)00152-2 PG 5 WC Virology SC Virology GA UD772 UT WOS:A1996UD77200010 PM 15566863 ER PT J AU Goldstein, DS McRae, A Holmes, C Dalakas, MC AF Goldstein, DS McRae, A Holmes, C Dalakas, MC TI Autoimmune autonomic failure in a patient with myeloma-associated Shy-Drager syndrome SO CLINICAL AUTONOMIC RESEARCH LA English DT Article DE Shy-Drager syndrome; dysautonomia; sympathetic nervous system; norepinephrine; dihydroxyphenylglycol ID SYMPATHETIC-NERVOUS-SYSTEM; ORTHOSTATIC HYPOTENSION; NOREPINEPHRINE AB We report here the case of a patient with the Shy-Drager syndrome and multiple myeloma who had evidence consistent with a central neural autoimmune basis for sympathetic autonomic failure. Autonomic function testing showed no recordable peroneal skeletal muscle sympathoneural traffic, normal arterial norepinephrine (NE) spillover during supine rest and no increment in NE spillover during exposure to lower body negative pressure. The patient's cerebrospinal fluid and serum contained an immunoglobulin G that bound to rat locus ceruleus (LC) in an in vitro test system. The myeloma protein was of the lambda subtype and bound in the rat LC, without binding in the substantia nigra, as demonstrated with anti-lambda antiserum. Since in this case the monoclonal antibody produced by the myeloma bound specifically to LC cells, the results are consistent with the hypothesis that in this patient the Shy-Drager syndrome may have had an immune-mediated basis. C1 NINCDS,CLIN NEUROSCI BRANCH,BETHESDA,MD 20892. GOTHENBURG UNIV,DEPT ANAT,GOTHENBURG,SWEDEN. NINCDS,MED NEUROL BRANCH,BETHESDA,MD 20892. NR 16 TC 4 Z9 4 U1 0 U2 1 PU RAPID SCIENCE PUBLISHERS PI LONDON PA 2-6 BOUNDARY ROW, LONDON, ENGLAND SE1 8NH SN 0959-9851 J9 CLIN AUTON RES JI Clin. Auton. Res. PD FEB PY 1996 VL 6 IS 1 BP 17 EP 21 DI 10.1007/BF02291401 PG 5 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA UC924 UT WOS:A1996UC92400002 PM 8924751 ER PT J AU Reiter, Y Pastan, I AF Reiter, Y Pastan, I TI Antibody engineering of recombinant Fv immunotoxins for improved targeting of cancer: Disulfide-stabilized Fv immunotoxins SO CLINICAL CANCER RESEARCH LA English DT Article ID SINGLE-CHAIN IMMUNOTOXIN; PSEUDOMONAS EXOTOXIN-A; MONOCLONAL-ANTIBODIES; DIPHTHERIA-TOXIN; TRANSFERRIN RECEPTOR; ESCHERICHIA-COLI; CHIMERIC TOXINS; FUSION PROTEINS; CELLS; MACROMOLECULES AB Recombinant immunotoxins are chimeric proteins in which a truncated toxin is fused to a recombinant antigen-binding domain such as a recombinant Fv or Fab, Recombinant immunotoxins target cell surface receptors and other antigens on tumor cells. The antigen-binding and -targeting domains in recombinant immunotoxins are usually single-chain Fvs (scFv), which are the antibody variable regions connected by a flexible peptide linker and fused directly to a bacterial toxin. However, Fabs have also been used, Recombinant immunotoxins have very good activity in vitro on cultured human tumor cell lines and have produced complete regressions and cures of established tumor xenografts in nude mouse models, Problems with the stability and binding of some scFv immunotoxins as well as scFvs not linked to toxin led to the development of a new type of recombinant Fv immunotoxin in which the targeting variable domains of the Fv are stabilized by an interchain disulfide bond located in structurally conserved framework positions of the V-H and V-L domains. These are termed disulfide-stabilized Fvs (dsFv) or dsFv immunotoxins. dsFvs and dsFv immunotoxins have several advantages over scFv immunotoxins. This review summarizes the design, construction, activities in vitro and in vivo, and biochemical characteristics of dsFv immunotoxins and compares them with scFv immunotoxins. C1 NCI, DIV CANC BIOL DIAG & CTR, MOLEC BIOL LAB, NIH, BETHESDA, MD 20892 USA. NR 62 TC 47 Z9 51 U1 0 U2 7 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 EI 1557-3265 J9 CLIN CANCER RES JI Clin. Cancer Res. PD FEB PY 1996 VL 2 IS 2 BP 245 EP 252 PG 8 WC Oncology SC Oncology GA TU875 UT WOS:A1996TU87500002 PM 9816166 ER PT J AU Shetty, HU Holloway, HW Schapiro, MB AF Shetty, HU Holloway, HW Schapiro, MB TI Cerebrospinal fluid and plasma distribution of myo-inositol and other polyols in Alzheimer disease SO CLINICAL CHEMISTRY LA English DT Article DE carbohydrate metabolism; gas chromatography mass spectrometry ID NERVOUS-SYSTEM; MYOINOSITOL TRANSPORT; DIAGNOSIS AB Previous studies suggest the presence of increased concentrations of cerebral myo-inositol in Alzheimer disease (AD). To characterize this abnormality further, we quantified myo-inositol and several other polyols in cerebrospinal fluid (CSF) and plasma from 10 AD subjects and 10 healthy age-matched controls by using a gas chromatographic-mass spectrometric technique. The mean CSF concentration and CSF/plasma concentration ratio of myo-inositol in AD were not significantly different from those determined in control subjects. Also, concentration profiles of other polyols were not significantly altered in AD. CSF and plasma myo-inositol concentrations were correlated in control subjects but not in AD subjects. However, a significant correlation between CSF and plasma 1,5-anhydrosorbitol (a polyol internal control) concentrations observed in control subjects was retained in AD subjects. RP Shetty, HU (reprint author), NIA, NEUROSCI LAB, BLDG 10, ROOM 6C 103, 10 CTR DR MSC 1582, BETHESDA, MD 20892 USA. NR 28 TC 23 Z9 23 U1 0 U2 1 PU AMER ASSOC CLINICAL CHEMISTRY PI WASHINGTON PA 2101 L STREET NW, SUITE 202, WASHINGTON, DC 20037-1526 USA SN 0009-9147 J9 CLIN CHEM JI Clin. Chem. PD FEB PY 1996 VL 42 IS 2 BP 298 EP 302 PG 5 WC Medical Laboratory Technology SC Medical Laboratory Technology GA TV950 UT WOS:A1996TV95000017 PM 8595727 ER PT J AU Buyon, JP Nelson, JL Lockshin, MD AF Buyon, JP Nelson, JL Lockshin, MD TI The effects of pregnancy on autoimmune diseases SO CLINICAL IMMUNOLOGY AND IMMUNOPATHOLOGY LA English DT Review ID SYSTEMIC LUPUS-ERYTHEMATOSUS; RHEUMATOID-ARTHRITIS; ANTIPHOSPHOLIPID ANTIBODIES; NEONATAL LUPUS; APOLIPOPROTEIN-H; HUMAN-PLATELETS; BETA-2-GLYCOPROTEIN-I; WOMEN; NEPHROPATHY; COAGULATION C1 FRED HUTCHINSON CANC RES CTR,SEATTLE,WA 98104. NIAMSD,NIH,BETHESDA,MD 20892. RP Buyon, JP (reprint author), NYU,HOSP JOINT DIS,SCH MED,DEPT RHEUMAT DIS,NEW YORK,NY 10003, USA. NR 57 TC 25 Z9 25 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 0090-1229 J9 CLIN IMMUNOL IMMUNOP JI Clin. Immunol. Immunopathol. PD FEB PY 1996 VL 78 IS 2 BP 99 EP 104 DI 10.1006/clin.1996.0018 PG 6 WC Immunology; Pathology SC Immunology; Pathology GA TX989 UT WOS:A1996TX98900001 PM 8625564 ER PT J AU Vistica, BP Chanaud, NP Felix, N Caspi, RR Rizzo, LV Nussenblatt, RB Gery, I AF Vistica, BP Chanaud, NP Felix, N Caspi, RR Rizzo, LV Nussenblatt, RB Gery, I TI CD8 T-cells are not essential for the induction of ''low-dose'' oral tolerance SO CLINICAL IMMUNOLOGY AND IMMUNOPATHOLOGY LA English DT Article ID EXPERIMENTAL AUTOIMMUNE UVEORETINITIS; MYELIN BASIC-PROTEIN; IMMUNE-RESPONSES; S-ANTIGEN; INVITRO; ENCEPHALOMYELITIS; TOLERIZATION; SUPPRESSION; MECHANISMS; DISEASE AB To examine whether CD8 T-cells are essential for the induction of ''low-dose'' oral tolerance, we tested animals deficient in CD8 T-cells, i.e., Lewis rats in which CD8 cells were eliminated by injections of specific antibodies and beta 2m(-/-) mice in which the CD8 cells are scarce and poorly functional. Oral tolerance was induced in the rats by repeated feedings with the uveitogenic retinal S-antigen, while in the mice the fed antigen was ovalbumin. Feeding reduced in both species the specific cellular immune response, measured by the lymphocyte proliferation assay. In the rats, this treatment also inhibited the development of the inflammatory eye disease, experimental autoimmune uveoretinitis. In addition, the levels of specific antibodies in the fed animals were moderately lower than those in their controls. Both the CD8-depleted rats and the beta 2m(-/-) mice resembled their normal controls in demonstrating reduced immune responses following feeding with the corresponding antigen. This observation thus indicates that CD8 T-cells are not essential for the induction of low-dose oral tolerance. (C) 1996 Academic Press, Inc. C1 NEI,IMMUNOL LAB,NIH,BETHESDA,MD 20892. AUTOIMMUNE INC,LEXINGTON,MA 02173. RI Rizzo, Luiz Vicente/B-4458-2009 NR 35 TC 26 Z9 27 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 0090-1229 J9 CLIN IMMUNOL IMMUNOP JI Clin. Immunol. Immunopathol. PD FEB PY 1996 VL 78 IS 2 BP 196 EP 202 DI 10.1006/clin.1996.0029 PG 7 WC Immunology; Pathology SC Immunology; Pathology GA TX989 UT WOS:A1996TX98900012 PM 8625562 ER PT J AU Wagner, RP Tian, HS McPherson, MJ Latham, PS Orenstein, JM AF Wagner, RP Tian, HS McPherson, MJ Latham, PS Orenstein, JM TI AIDS - Associated infections in salivary glands: Autopsy survey of 60 cases SO CLINICAL INFECTIOUS DISEASES LA English DT Article ID HIV-INFECTION; MANIFESTATIONS AB We reviewed the autopsy findings for the submandibular glands of 60 patients with AIDS who were autopsied at the George Washington University Medical Center (Washington, DC) from 1982 to 1992. AIDS-associated infections in the submandibular glands were compared with those in the pancreas and lung. Cytomegalovirus intranuclear inclusions were found in 10 cases, and Pneumocystis carinii infection was found in one case, Disseminated mycobacterial and fungal infections were not identified in the submandibular gland, even in the presence of documented pancreatic and pulmonary infection (P < .05). Overall, the major salivary glands of patients with AIDS are less frequently involved with disseminated opportunistic infections than is either the lung or the pancreas (P < .01 and P < .001, respectively). C1 GEORGE WASHINGTON UNIV,SCH MED,DEPT PATHOL,WASHINGTON,DC 20037. NIH,NIDR,IMMUNOL LAB,BETHESDA,MD 20892. RP Wagner, RP (reprint author), GEORGE WASHINGTON UNIV,MED CTR,DEPT MED,DIV PULM DIS & ALLERGY,SCH MED,ROOM 4-511,WASHINGTON,DC 20037, USA. OI Latham, Patricia/0000-0003-2782-9444 FU NIDCR NIH HHS [DE-12585] NR 15 TC 18 Z9 18 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 FEB PY 1996 VL 22 IS 2 BP 369 EP 371 PG 3 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA TU876 UT WOS:A1996TU87600027 PM 8838199 ER PT J AU Castro, KG Blinkhorn, RJ Ellner, JJ Chaisson, RE Horsburgh, CR Masur, H Holmes, KK Kaplan, JE AF Castro, KG Blinkhorn, RJ Ellner, JJ Chaisson, RE Horsburgh, CR Masur, H Holmes, KK Kaplan, JE TI Secondary prophylaxis for tuberculosis in patients infected with human immunodeficiency virus - Reply SO CLINICAL INFECTIOUS DISEASES LA English DT Letter C1 EMORY UNIV, ATLANTA, GA 30322 USA. NIAID, BETHESDA, MD 20892 USA. JOHNS HOPKINS UNIV, BALTIMORE, MD USA. CASE WESTERN RESERVE UNIV, CLEVELAND, OH 44106 USA. UNIV WASHINGTON, SEATTLE, WA USA. RP Castro, KG (reprint author), CTR DIS CONTROL & PREVENT, DIV TB ELIMINAT, 1600 CLIFTON RD, MAILSTOP E-10, ATLANTA, GA 30333 USA. NR 10 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1058-4838 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD FEB PY 1996 VL 22 IS 2 BP 399 EP 400 PG 2 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA TU876 UT WOS:A1996TU87600056 ER PT J AU Ollo, C Alim, TN Rosse, RB Lindquist, T Green, T Gillis, T Ricci, J Khan, M Deutsch, SI AF Ollo, C Alim, TN Rosse, RB Lindquist, T Green, T Gillis, T Ricci, J Khan, M Deutsch, SI TI Lack of neurotoxic effect of diethylpropion in crack-cocaine abusers SO CLINICAL NEUROPHARMACOLOGY LA English DT Review DE crack-cocaine abuse; neuropsychology; cognition; stimulants; diethylpropion ID AMPHETAMINE ANALOGS; CORTEX ABLATION; FRONTAL-CORTEX; RAT-BRAIN; BROMOCRIPTINE; DOPAMINE; METHAMPHETAMINE; AMANTADINE; DEGENERATION; STIMULANTS AB Dopamine agonists have been used with some success in treating cocaine addiction. However, both cocaine and psychostimulants have been reported to produce neurotoxic effects. We evaluated the effect of the stimulant diethylpropion on cognitive performance in a double-blind, placebo-controlled trial. Forty-six abstinent crack-cocaine users received either placebo, 25-mg, 50-mg, or 75-mg doses of diethylpropion. Patients were tested at baseline and again after 9-14 days of medication. There were no differences between placebo and medication groups on any test, indicating that, within the time frame studied, diethylpropion does not produce neurotoxic effects that can be detected with standardized neuropsychological tests. C1 GEORGETOWN UNIV, PSYCHIAT SERV 116A,RES UNIT,NIDA, DEPT VET AFFAIRS MED CTR,SCH MED, WASHINGTON, DC 20422 USA. GEORGETOWN UNIV, SCH MED, DEPT PSYCHIAT, WASHINGTON, DC USA. HOWARD UNIV, MED CTR, DEPT PSYCHIAT, WASHINGTON, DC 20059 USA. FU ONDIEH CDC HHS [RA-ND-90-10] NR 47 TC 6 Z9 6 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0362-5664 J9 CLIN NEUROPHARMACOL JI Clin. Neuropharmacol. PD FEB PY 1996 VL 19 IS 1 BP 52 EP 58 DI 10.1097/00002826-199619010-00003 PG 7 WC Clinical Neurology; Pharmacology & Pharmacy SC Neurosciences & Neurology; Pharmacology & Pharmacy GA TQ803 UT WOS:A1996TQ80300003 PM 8867517 ER PT J AU Yu, KC Fraker, DL Ziessman, HA AF Yu, KC Fraker, DL Ziessman, HA TI Atlas of iodocholesterol scintigraphy (NP-59) in Cushing's syndrome with CT and MR correlation SO CLINICAL NUCLEAR MEDICINE LA English DT Article ID DIAGNOSIS AB An atlas of I-131 iodocholesterol scintigraphy, each with correlative CT or MRI illustrates the findings in 12 patients with biochemically proven Cushing's syndrome and ultimate surgical cure, Included are patients with both ACTH dependent and independent disease, as well as patients with postoperative functional adrenal remnants. Emphasis will be on the concordance or discordance of the anatomical and functional imaging modalities. C1 NCI,SURG BRANCH,SURG METAB SECT,NATL INST HLTH,BETHESDA,MD 20892. GEORGETOWN UNIV HOSP,DEPT RADIOL,WASHINGTON,DC 20007. GEORGETOWN UNIV HOSP,DIV NUCL MED,WASHINGTON,DC 20007. NR 8 TC 3 Z9 3 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0363-9762 J9 CLIN NUCL MED JI Clin. Nucl. Med. PD FEB PY 1996 VL 21 IS 2 BP 136 EP 141 DI 10.1097/00003072-199602000-00013 PG 6 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA TV628 UT WOS:A1996TV62800013 PM 8697685 ER PT J AU Pikis, A Kavaliotis, J Tsikoulas, J Andrianopoulos, P Venzon, D Manios, S AF Pikis, A Kavaliotis, J Tsikoulas, J Andrianopoulos, P Venzon, D Manios, S TI Long-term sequelae of pneumococcal meningitis in children SO CLINICAL PEDIATRICS LA English DT Article ID HEMOPHILUS-INFLUENZAE MENINGITIS; CHILDHOOD BACTERIAL-MENINGITIS; CHLORAMPHENICOL; AMPICILLIN; RESISTANCE; MORTALITY; OUTCOMES; THERAPY AB The purpose of this study was to assess the long-term effects of pneumococcal meningitis in children. From 1967 to 1988, a total of 90 children were admitted to the Hospital for Infectious Diseases, Thessaloniki, Greece, with the diagnosis of pneumococcal meningitis. Sixteen patients died in the hospital as a direct result of meningitis. Eleven others were excluded from the study (neurologic deficits prior to onset of meningitis, two; death subsequent to hospitalization, two; recurrent meningitis, seven), Of the remaining 63 survivors, we were able to evaluate 47 patients (75%). Evaluation was performed il to 23 years (mean 12.3 +/- 5.8 years) after discharge. Forty patients returned to hospital for evaluation, and seven were evaluated by their primary physicians, who sent information by a standardized questionnaire, The following examinations were carried out: history, physical and neurologic examination, ophthalmologic and hearing evaluation, and psychometric testing, Fourteen patients (30%) had at least one neurologic handicap; nine (19%) had mental retardation, eight (17%) hearing loss, seven (15%) seizure disorder, five (11%) motor defects, and one each (2%) behavioral problems and visual impairment, The presence of coma was the strongest predictor of increased morbidity. The high frequency of long-term sequelae observed in our study supports the need of an effective vaccine. C1 HOSP INFECT DIS,DEPT PEDIAT,THESSALONIKI,GREECE. UNIV THESSALONIKI,DEPT PEDIAT 1,GR-54006 THESSALONIKI,GREECE. KENTRIKON HOSP,THESSALONIKI,GREECE. NCI,BIOSTAT & DATA MANAGEMENT SECT,BETHESDA,MD 20892. RI Venzon, David/B-3078-2008 NR 31 TC 39 Z9 39 U1 0 U2 0 PU WESTMINSTER PUBL INC PI GLEN HEAD PA 708 GLEN COVE AVE, GLEN HEAD, NY 11545 SN 0009-9228 J9 CLIN PEDIATR JI Clin. Pediatr. PD FEB PY 1996 VL 35 IS 2 BP 72 EP 78 DI 10.1177/000992289603500204 PG 7 WC Pediatrics SC Pediatrics GA TW379 UT WOS:A1996TW37900004 PM 8775479 ER PT J AU Dionne, RA Max, MB Parada, S Gordon, SM MacLean, DB AF Dionne, RA Max, MB Parada, S Gordon, SM MacLean, DB TI Evaluation of a neurokinin(1) antagonist, CP-99,994, in comparison to ibuprofen and placebo in the oral surgery model SO CLINICAL PHARMACOLOGY & THERAPEUTICS LA English DT Meeting Abstract C1 NIDR,NIH,BETHESDA,MD. PFIZER INC,PFIZER CENT RES,GROTON,CT 06340. 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 0009-9236 J9 CLIN PHARMACOL THER JI Clin. Pharmacol. Ther. PD FEB PY 1996 VL 59 IS 2 BP OIII1 EP OIII1 PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA TX001 UT WOS:A1996TX00100350 ER PT J AU George, DT Phillips, M Linnoila, M AF George, DT Phillips, M Linnoila, M TI Effects of intravenous procaine on alcoholics with and without panic disorder and controls SO CLINICAL PHARMACOLOGY & THERAPEUTICS LA English DT Meeting Abstract C1 NIAAA,BETHESDA,MD 20892. 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 0009-9236 J9 CLIN PHARMACOL THER JI Clin. Pharmacol. Ther. PD FEB PY 1996 VL 59 IS 2 BP PII89 EP PII89 PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA TX001 UT WOS:A1996TX00100324 ER PT J AU Holtzmann, JL Zhou, LX Zheng, W Ganz, R Pihlstrom, B Dansen, V Park, SS Potter, J AF Holtzmann, JL Zhou, LX Zheng, W Ganz, R Pihlstrom, B Dansen, V Park, SS Potter, J TI Possible role of CYPS 1A1, 1A2 and 2E1 in the initiation of human oropharyngeal, esophageal and gastric cancers. SO CLINICAL PHARMACOLOGY & THERAPEUTICS LA English DT Meeting Abstract C1 VET ADM MED CTR,MINNEAPOLIS,MN. NCI,FREDERICK,MD 21701. 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 0009-9236 J9 CLIN PHARMACOL THER JI Clin. Pharmacol. Ther. PD FEB PY 1996 VL 59 IS 2 BP PII53 EP PII53 PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA TX001 UT WOS:A1996TX00100172 ER PT J AU Piscitelli, SC Forrest, A Vogel, S Metcalf, J Baseler, M Stevens, R Kovacs, JA AF Piscitelli, SC Forrest, A Vogel, S Metcalf, J Baseler, M Stevens, R Kovacs, JA TI A novel PK/PD model for infused interleukin-2 (IL2), in HIV-infected patients SO CLINICAL PHARMACOLOGY & THERAPEUTICS LA English DT Meeting Abstract C1 CTR CLIN,DEPT PHARM,BETHESDA,MD. CTR CLIN,DEPT CRIT CARE MED,BETHESDA,MD. NIAID,BETHESDA,MD 20892. SUNY BUFFALO,SCH PHARM,BUFFALO,NY. CLIN PHARMACOKINET LAB,BUFFALO,NY. SAIC,FREDERICK,MD. 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 0009-9236 J9 CLIN PHARMACOL THER JI Clin. Pharmacol. Ther. PD FEB PY 1996 VL 59 IS 2 BP PI92 EP PI92 PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA TX001 UT WOS:A1996TX00100092 ER PT J AU Preston, KL Silverman, K Schuster, CR Cone, EJ AF Preston, KL Silverman, K Schuster, CR Cone, EJ TI Baseline cocaine use predicts outcome in cocaine treatment SO CLINICAL PHARMACOLOGY & THERAPEUTICS LA English DT Meeting Abstract C1 NATL INST DRUG ABUSE,INTRAMURAL RES PROGRAM,BALTIMORE,MD. 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 0009-9236 J9 CLIN PHARMACOL THER JI Clin. Pharmacol. Ther. PD FEB PY 1996 VL 59 IS 2 BP PII88 EP PII88 PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA TX001 UT WOS:A1996TX00100323 ER PT J AU Takimoto, C Lu, Z Zhang, R Diasio, R Liang, M Larson, L Cantilena, L Grem, J Allegra, C Chu, E AF Takimoto, C Lu, Z Zhang, R Diasio, R Liang, M Larson, L Cantilena, L Grem, J Allegra, C Chu, E TI Reversible 5-fluorouracil-associated encephalopathy in a dihydropyrimidine dehydrogenase (DPD) deficient patient. SO CLINICAL PHARMACOLOGY & THERAPEUTICS LA English DT Meeting Abstract C1 NCI,NMOB,BETHESDA,MD 20892. UNIFORMED SERV UNIV HLTH SCI,DIV CLIN PHARM,BETHESDA,MD. UNIV ALABAMA,DEPT PHARMACOL & TOXICOL,DIV CLIN PHARM,BIRMINGHAM,AL. 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 0009-9236 J9 CLIN PHARMACOL THER JI Clin. Pharmacol. Ther. PD FEB PY 1996 VL 59 IS 2 BP PII9 EP PII9 PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA TX001 UT WOS:A1996TX00100128 ER PT J AU Tracy, TS Marra, C Wrighton, SA Gonzalez, FJ Korzekwa, KR AF Tracy, TS Marra, C Wrighton, SA Gonzalez, FJ Korzekwa, KR TI Involvement of multiple cytochrome P450 isoforms in naproxen demethylation. SO CLINICAL PHARMACOLOGY & THERAPEUTICS LA English DT Meeting Abstract C1 W VIRGINIA UNIV,DEPT BASIC PHARMACEUT SCI,MORGANTOWN,WV 26506. ELI LILLY & CO,INDIANAPOLIS,IN 46285. NCI,BETHESDA,MD 20892. UNIV PITTSBURGH,PITTSBURGH,PA. 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 0009-9236 J9 CLIN PHARMACOL THER JI Clin. Pharmacol. Ther. PD FEB PY 1996 VL 59 IS 2 BP PII51 EP PII51 PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA TX001 UT WOS:A1996TX00100169 ER PT J AU Snider, TG Luther, DG Jenny, BF Hoyt, PG Battles, JK Ennis, WH Balady, J BlasMachado, U Lemarchand, TX Gonda, MA AF Snider, TG Luther, DG Jenny, BF Hoyt, PG Battles, JK Ennis, WH Balady, J BlasMachado, U Lemarchand, TX Gonda, MA TI Encephalitis, lymphoid tissue depletion and secondary diseases associated with bovine immunodeficiency virus in a dairy herd SO COMPARATIVE IMMUNOLOGY MICROBIOLOGY AND INFECTIOUS DISEASES LA English DT Article DE bovine immunodeficiency virus; lentivirus; immunodeficiency; lymphoid tissue; encephalitis; secondary infections; pododermatitis; mastitis; bovine leukemia virus; polymerase chain reaction ID MULTIPLE RETROVIRAL INFECTIONS; BRUCELLA-ABORTUS; LEUKEMIA-VIRUS; CATTLE; CALVES; TYPE-1; ENCEPHALOPATHY; APOPTOSIS; STRAINS; MICE AB Encephalitis, lymphoid tissue depletion and secondary infections occurred over a 5-yr-period in Holstein cows infected with bovine inmunodeficiency virus (BIV). There were 59 cattle studied, the majority during 1991, when a severe environmental stress occurred, each with one or more primary causes of death, natural or by euthanasia, and most with several secondary diseases. The encephalitis was characterized by meningeal, perivascular and parenchymal infiltration with lymphocytes, occasional plasma cells and macrophages with perivascular edema in some cows. Affected areas included the cerebrum, cerebellum, and spinal cord with no particular distribution pattern recognized. The lymphoid depletion was primarily an absence of follicular development in nodes draining regions with secondary infections such as chronic mastitis and chronic suppurative pododermatitis. Paucity of lymphocytes in thymic-dependent regions of lymph nodes and the spleen suggested a primary depletion of T cells. Secondary infections were often multiple with each cow having several minor conditions, usually considered short-term and treatable. These included mastitis and pododermatitis, with many cows having non-responding abscesses, cellulitis and myositis attributed to injection site infections. A large number of the cattle had parturition difficulties such as dystocia, obturator paralysis, and metritis. Pulmonary, cardiovascular, and intestinal disease were recognized as both primary and secondary disease conditions. There was a high level of infection with bovine leukemia virus with 4 of the 59 cattle having lymphosarcoma. Under practical conditions, the infection with BIV has a different effect on the host than has been observed under experimental conditions. The presence of BIV combined with the stresses associated with parturition and a modern dairy production system were considered causal for the development of untreatable secondary diseases in immunocompromised cattle. The peak incidence in 1991 was attributed to increased environmental stress during renovation of the barn facility. During this time the cattle were kept on open pasture, exposed to an extremely wet winter, and spring weather conditions. The effect of co-infection with bovine leukemia virus, the influence of immunocompromise on the chronicity of mastitis, the relationship with laminitis and pododermatitis, and several questions related to viral transmission, complementarism with bovine leukemia virus, viral reactivation and immunoprophylaxis all remain as viable avenues for future investigations. C1 LOUISIANA STATE UNIV & A&M COLL, DEPT VET CLIN SCI, BATON ROUGE, LA 70803 USA. LOUISIANA AGR EXPT STN, DEPT DAIRY SCI, BATON ROUGE, LA 70803 USA. LOUISIANA STATE UNIV, AGR EXPT STN, BATON ROUGE, LA 70803 USA. NCI, FREDERICK CANC RES & DEV CTR, SAIC FREDERICK, FREDERICK, MD 21702 USA. RP Snider, TG (reprint author), LOUISIANA STATE UNIV & A&M COLL, SCH VET MED, DEPT VET PATHOL, BATON ROUGE, LA 70803 USA. NR 47 TC 49 Z9 49 U1 1 U2 2 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0147-9571 EI 1878-1667 J9 COMP IMMUNOL MICROB JI Comp. Immunol. Microbiol. Infect. Dis. PD FEB PY 1996 VL 19 IS 2 BP 117 EP 131 DI 10.1016/0147-9571(95)00032-1 PG 15 WC Immunology; Microbiology; Veterinary Sciences SC Immunology; Microbiology; Veterinary Sciences GA UB977 UT WOS:A1996UB97700003 PM 8814974 ER PT J AU Mezzetti, M Ferraroni, M Decarli, A LaVecchia, C Benichou, J AF Mezzetti, M Ferraroni, M Decarli, A LaVecchia, C Benichou, J TI Software for attributable risk and confidence interval estimation in case-control studies SO COMPUTERS AND BIOMEDICAL RESEARCH LA English DT Article ID LOGISTIC-MODELS; FRACTION; CANCER AB The increasing interest in obtaining model-based estimates of attributable risk (AR) and corresponding confidence intervals, in particular when more than one risk factor and/or several confounding factors are jointly considered,led us to develop a program based on the procedure described by Benichou and Call for case-control data. This program is structured as an SAS-macro. It is suited to analysis of the relationship between risk factors and disease in case-control studies with simple random sampling of controls, in terms of relative risks and ARs, by means of unconditional logistic regression analysis. The variance of the AR is obtained by the delta method and is based on three components, namely, (i) the variance-covariance matrix of the vector of the estimated probabilities of belonging to joint levels of the exposure and confounding factors conditional on being a case, (ii) the variance-covariance matrix of the odds ratio parameter estimates from the logistic model, and (iii) the covariances between these probability and parameter estimates. Only a limited number of commands is requested from the user (i.e., the name of the work file and the names of the variables considered). The estimated relative risks for all the factors included in the model, the attributable risk for the exposure factor under consideration, and the corresponding 95% confidence intervals are given as outputs by the macro. Computational problems, if any, may arise for large numbers of covariates because of the resulting large size of vectors and matrices. The macro was tested for reliability and consistency on published data sets of case-control studies. (C) 1996 Academic Press, Inc. C1 IST NAZL STUDIO & CURA TUMORI,I-20133 MILAN,ITALY. IST RIC FARMACOL MARIO NEGRI,MILAN,ITALY. NCI,EPIDEMIOL METHODS SECT,ROCKVILLE,MD. RP Mezzetti, M (reprint author), UNIV MILAN,IST STAT MED & BIOMETRIA,I-20122 MILAN,ITALY. RI Decarli, Adriano/C-3129-2017; Ferraroni, Monica/D-6548-2017; OI Decarli, Adriano/0000-0003-1451-8292; Ferraroni, Monica/0000-0002-4542-4996; La Vecchia, Carlo/0000-0003-1441-897X NR 21 TC 60 Z9 61 U1 0 U2 4 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0010-4809 J9 COMPUT BIOMED RES JI Comput. Biomed. Res. PD FEB PY 1996 VL 29 IS 1 BP 63 EP 75 DI 10.1006/cbmr.1996.0006 PG 13 WC Computer Science, Interdisciplinary Applications; Medical Informatics SC Computer Science; Medical Informatics GA UA227 UT WOS:A1996UA22700006 PM 8689875 ER PT J AU Hertert, S Bailey, G Cottinghan, V Carmody, S Egan, D Johnson, P Probstfield, J AF Hertert, S Bailey, G Cottinghan, V Carmody, S Egan, D Johnson, P Probstfield, J TI Community volunteers as recruitment staff in a clinical trial: The systolic hypertension in the elderly program (SHEP) experience SO CONTROLLED CLINICAL TRIALS LA English DT Article DE recruitment; clinical trials; volunteer staff; SHEP ID CHURCHES AB During the recruitment phase of a trial it is often found that recruitment is not proceeding as quickly as projected. Budget limitations require innovative methods, such as use of volunteers, to increase recruitment yields without increasing cost. In the Systolic Hypertension in the Elderly Program (SHEP), volunteer staff at 12 of the 16 clinical centers (CCs) performed a range of tasks such as mailings, telephoning, and clerical work. SHEP volunteers donated almost 40,000 hours, at an estimated cost savings to the program of more than $368, 000. Staff volunteers appear to require more training and supervision than regular staff and may require flexible work schedules. These limitations can be obviated by careful planning. This paper describes the SHEP experience with staff volunteers and provides suggestions for their use in other trials. C1 CLIN STUDIES CTR,SHEP,CTR CLIN,SAN FRANCISCO,CA. UNIV ALABAMA,SHEP,CTR CLIN,BIRMINGHAM,AL. WASHINGTON UNIV,SHEP,CTR CLIN,ST LOUIS,MO. NHLBI,CLIN TRIALS BRANCH,SHEP,PROJECT OFF,BETHESDA,MD 20892. RP Hertert, S (reprint author), KAISER FDN HOSP,CTR HLTH RES,3800 N KAISER CTR DR,PORTLAND,OR 97227, USA. NR 16 TC 7 Z9 7 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0197-2456 J9 CONTROL CLIN TRIALS JI Controlled Clin. Trials PD FEB PY 1996 VL 17 IS 1 BP 23 EP 32 DI 10.1016/0197-2456(95)00074-7 PG 10 WC Medicine, Research & Experimental; Pharmacology & Pharmacy SC Research & Experimental Medicine; Pharmacology & Pharmacy GA UA398 UT WOS:A1996UA39800003 PM 8721799 ER PT J AU Gorkin, L Schron, EB Handshaw, K Shea, S Kinney, MR Branyon, M Campion, J Bigger, JT Sylvia, SC Duggan, J Stylianou, M Lancaster, S Ahern, DK Follick, MJ AF Gorkin, L Schron, EB Handshaw, K Shea, S Kinney, MR Branyon, M Campion, J Bigger, JT Sylvia, SC Duggan, J Stylianou, M Lancaster, S Ahern, DK Follick, MJ TI Clinical trial enrollers vs nonenrollers: The cardiac arrhythmia suppression trial (CAST) recruitment and enrollment assessment in clinical trials (REACT) project SO CONTROLLED CLINICAL TRIALS LA English DT Article DE clinical trial; enrollment; cardiac arrhythmia; CAST REACT ID CORONARY-ARTERY DISEASE AB The Recruitment and Enrollment Assessment in Clinical Trials (REACT) was a National Heart, Lung, and Blood Institute (NHLBI)-sponsored substudy to the Cardiac Arrhythmia Suppression Trial (CAST). Two-hundred-sixty (260) patients who enrolled in CAST and 140 partially or fully eligible patients who did not enroll were compared across several parameters, including demographic variables, disease severity, psychosocial functioning, health beliefs, recruitment experience, and understanding of informed consent procedures used in CAST. Significant predictors of enrollment included several demographic variables (e.g., being male, not having medical insurance), episodes of ventricular tachycardia, and health beliefs (e.g., extra beats are harmful, a higher degree of general health concern). Enrollment was higher for those who read and understood the informed consent and those who were initially recruited after hospital discharge, particularly nondepressed patients. In the multivariate model, the key variables that emerged were the patient's reading of the informed consent form and the patient's lack of medical insurance. These results suggest that (1) the clinical trial staffs interaction with the patient and the time when recruitment is initiated contribute significantly to the decision to enroll; and (2) it may be a greater challenge to motivate patients to enroll in future clinical trials if health care reform improves access to medical insurance coverage. Some of the significant variables are modifiable, suggesting interventions that may increase enrollment rates in future trials. C1 INST BEHAV MED,CRANSTON,RI. NHLBI,DIV EPIDEMIOL & CLIN APPLICAT,WASHINGTON,DC. RHODE ISL HOSP,OFF RES ADM,PROVIDENCE,RI 02902. COLUMBIA UNIV,DEPT MED,NEW YORK,NY. UNIV ALABAMA,SCH NURSING,BIRMINGHAM,AL. PRESBYTERIAN HOSP,NEW YORK,NY. UNIV WASHINGTON,SEATTLE,WA 98195. RI Duggan, Jennie/I-2267-2015 NR 18 TC 47 Z9 47 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0197-2456 J9 CONTROL CLIN TRIALS JI Controlled Clin. Trials PD FEB PY 1996 VL 17 IS 1 BP 46 EP 59 DI 10.1016/0197-2456(95)00089-5 PG 14 WC Medicine, Research & Experimental; Pharmacology & Pharmacy SC Research & Experimental Medicine; Pharmacology & Pharmacy GA UA398 UT WOS:A1996UA39800005 PM 8721801 ER PT J AU Abernathy, GT Abrams, J Akhtar, S Albitar, I Amidi, M Anand, IS Arnold, JMO Ashton, T Aubrey, B Auger, P Babb, J Baigrie, R Baird, MG Baitz, T Barber, NC Barbour, DJ Barr, DM Basu, AK Baughman, KL Beckham, V BekheitSaad, S Berkson, DM Bertoglio, M Bessoudo, R Beaudoin, J Bhaskar, G Binder, A Bloomfield, D Bodine, K Boehmer, JP Borgersen, K Borts, D Bouchard, G Bourassa, MG Boutros, G Bozek, B Brisbin, D Brophy, J Brossoit, R Brown, E Brown, J Bruinsma, N Burton, G Cameron, A Campbell, R Campeau, J Campos, EE Cardello, FP Carter, RP Chan, YK Charles, FR Chaudhry, MA Chiaramida, A Chiaramida, S Chohan, A Christie, LG Clemson, BS Collin, R Cook, TH Copen, DL Cossett, J Costantino, T Crawford, MH Croke, RP Crowell, R DAmours, G Dagenais, GR Danisa, K Davidson, S Davies, ML Davies, R Davies, RA DeLarochelliere, R DeLeon, AC Delage, F Denes, P Dennish, GW Denny, DM DeVilla, MA DeYoung, JP Dhurandhar, RW DibnerDunlap, M Dodek, A Doherty, JE Dominguez, J Dubbin, J Dufton, J Effron, MB ElSherif, N Eladasari, B Fly, D Ericson, K Fahrenholtz, D Fast, A Fell, DA Fishman, S Fitchett, D Fleg, JL Flint, E Folger, JS Folkins, D Forker, AD Fowles, RE Fraker, TD Francis, G Frerking, TR Friesinger, GC Fulop, JC Gagnon, J Gamble, L Ganjavi, F Garrou, BW Gervais, PB Gheorghiade, M Gilbert, L Gillie, E Glatter, TR Godley, ML Goeres, M Goldberger, MH Gollapudi, A Goode, JE Goodman, LS Gordon, R Gossard, D Gosselin, G Goulet, C Grant, C Graettinger, WF Greene, JG Greenwood, PV Gregoratos, G Gregory, JJ Groden, DL Grover, J Gudapati, R Guess, MA Gupta, SC Habib, N Hack, I Hamilton, WP Hankey, TL Hanna, M Harper, D Harris, DE Hassapoyannes, CA Hatheway, RJ Heinsimer, J Pequignot, MH Heiselman, DE Hess, AR Hickner, J Hickey, JE Higgins, T Higginson, L Hill, L Hobbs, RE Honos, G Horner, BA Horwitz, L Hsieh, A Hsueh, JT Hubbard, J Hughes, DF Hui, W Imrie, JR Jacobs, MH Jarmukli, N Johnson, TH Johnstone, D Jutila, CK Kadri, N Kahl, FR Kaimal, PK Karnegis, J Kay, R Kelly, KJ Kenefick, G Kennelly, BM Kent, E Khan, AH Khanijo, V Khouri, M Kinloch, D Kirlin, PC Kiwan, GS Kline, MD Kohn, RM Koilpillai, C Kornder, JM Kouz, S Kumar, VA Kumar, U Kuntz, A Kuritzky, RA Kuruvilla, G Kwok, KK Lader, E Laforest, M LaForge, D Lalonde, G Lalonde, L Lang, RM Latour, Y Lawal, O LeBlanc, MH Lee, AB Lee, RW Legault, C Lemay, M Lenis, JHF Lepage, S Letarte, P Levesque, C LevinoffRoth, SN Lewis, BK Lipshutz, H Loungani, RR Lowery, ML Lubell, DL Lucariello, R LugoRodriguez, JE Lui, C Lutterodt, AT Lutz, L Machel, T Macina, G MacLellan, K Magnan, O Mansuri, M Manyari, DE Mallis, GI Marr, D Mast, DJ Mathew, J McBarron, FD McIntyre, KM McLean, RW McMahon, DP Mercier, M Methe, M Miller, AB Minkowitz, J Milton, JR Mizgala, HF Mohanty, PK Mohiuddin, S Montero, A Mookherjee, S Morris, A Morris, L Morrison, J Moten, M Nafziger, A Nair, PH Nawaz, S Neiman, JC Nutting, P NguyenPho, HT OBrien, TK OKelly, RL OReilly, MV Okerson, D Patel, G Pande, PN Papa, LA Patrick, L Payne, RM Perry, G Philbin, EF Pierpont, G Pitt, WA Poirier, C Pollak, EM Popio, K Poulin, JF Probst, PA Pruneau, G Pu, C Puram, BS Putatunda, B Quinn, B Rabkin, SW Racine, N Raco, DL Radant, L Radford, MJ Radwany, S Rajachar, M Ramanathan, KB Rashkow, A Rausch, DC Read, L Reddy, KR Reid, R Rich, MW Ricci, AJ Richman, HG Riley, A Rim, DA Rinne, C Roberge, G Roberts, DK Robinson, V Rodeheffer, RT Rosenstein, R Roth, DL Rothbart, R Rouleau, JL Ruble, P Sacco, J Safford, RE Salmon, D Sahay, BM Sarma, RJ Sayeed, MAR Schick, EC Schroeder, GS Seifert, M Senaratne, MPJ Sestier, F Shah, A Shanes, JG Sheesley, K Silverman, A Shiva, T Shrestha, DD Silver, MA Silverberg, L Simard, L Singh, BN Small, RS Smith, MR Smith, S Sochowski, RA Southern, RF Sridharan, MR StHilaire, R Stein, M Stewart, JW Stillabower, ME Sullivan, BHM Sturrock, WA Sussex, BA Swan, J Swenson, L Talbot, P Talibi, T Tamilia, M Tan, A Tanser, PH Tarry, L Teo, KK Thadani, U Thagirisa, S Thompson, B Thornton, R Timmis, GC Tobin, M Tommaso, C Toren, M Tsuyuki, R Turek, M Utley, K Vanderbush, EJ VanVoorhees, L Ventura, H Vertes, G Vizel, S Wagner, KR Wagner, S Weeks, A Weingert, ME Weinstein, C Weiss, MM Weiss, R Wickemeyer, W Wielgoz, A Willens, HJ Williams, WL Wong, D Yarows, SA Yao, L Shalev, Y Young, JB Yousefian, M Zajac, EJ Zatuchni, J Ziperman, DB Zoble, RG Zoneraich, S Gorlin, R Sleight, P Cohn, JN Collins, R Deykin, D Hennekens, C Kjekshus, J Smith, TW Tognoni, G Collins, JF Williford, WO Fye, C Sather, R Jolly, MK Held, CP Verter, J Yusuf, S Egan, D Garg, R Johnstone, DE Montague, T Bristow, D Engelhardt, HT Gent, M Hood, WB Jones, S Meier, P Pitt, B Waters, D Arnold, JMO Baker, A Barnhill, S Carew, B Hagar, S Liuni, C Martin, S Miles, R Arthur, MM Feldbush, MW Highfield, DA Hobbins, TE Kurz, R Leviton, SP Libonati, JP Moore, M Perez, E Mills, P Geller, N Hunsberger, S Gold, J Huang, PC Burns, A Caleb, H Cline, DR Harris, S Hockenbrock, R Horney, RA Jadwin, LM King, J Sexton, P Spence, ME Chacon, F Gagne, W Maple, S Martinez, G AF Abernathy, GT Abrams, J Akhtar, S Albitar, I Amidi, M Anand, IS Arnold, JMO Ashton, T Aubrey, B Auger, P Babb, J Baigrie, R Baird, MG Baitz, T Barber, NC Barbour, DJ Barr, DM Basu, AK Baughman, KL Beckham, V BekheitSaad, S Berkson, DM Bertoglio, M Bessoudo, R Beaudoin, J Bhaskar, G Binder, A Bloomfield, D Bodine, K Boehmer, JP Borgersen, K Borts, D Bouchard, G Bourassa, MG Boutros, G Bozek, B Brisbin, D Brophy, J Brossoit, R Brown, E Brown, J Bruinsma, N Burton, G Cameron, A Campbell, R Campeau, J Campos, EE Cardello, FP Carter, RP Chan, YK Charles, FR Chaudhry, MA Chiaramida, A Chiaramida, S Chohan, A Christie, LG Clemson, BS Collin, R Cook, TH Copen, DL Cossett, J Costantino, T Crawford, MH Croke, RP Crowell, R DAmours, G Dagenais, GR Danisa, K Davidson, S Davies, ML Davies, R Davies, RA DeLarochelliere, R DeLeon, AC Delage, F Denes, P Dennish, GW Denny, DM DeVilla, MA DeYoung, JP Dhurandhar, RW DibnerDunlap, M Dodek, A Doherty, JE Dominguez, J Dubbin, J Dufton, J Effron, MB ElSherif, N Eladasari, B Fly, D Ericson, K Fahrenholtz, D Fast, A Fell, DA Fishman, S Fitchett, D Fleg, JL Flint, E Folger, JS Folkins, D Forker, AD Fowles, RE Fraker, TD Francis, G Frerking, TR Friesinger, GC Fulop, JC Gagnon, J Gamble, L Ganjavi, F Garrou, BW Gervais, PB Gheorghiade, M Gilbert, L Gillie, E Glatter, TR Godley, ML Goeres, M Goldberger, MH Gollapudi, A Goode, JE Goodman, LS Gordon, R Gossard, D Gosselin, G Goulet, C Grant, C Graettinger, WF Greene, JG Greenwood, PV Gregoratos, G Gregory, JJ Groden, DL Grover, J Gudapati, R Guess, MA Gupta, SC Habib, N Hack, I Hamilton, WP Hankey, TL Hanna, M Harper, D Harris, DE Hassapoyannes, CA Hatheway, RJ Heinsimer, J Pequignot, MH Heiselman, DE Hess, AR Hickner, J Hickey, JE Higgins, T Higginson, L Hill, L Hobbs, RE Honos, G Horner, BA Horwitz, L Hsieh, A Hsueh, JT Hubbard, J Hughes, DF Hui, W Imrie, JR Jacobs, MH Jarmukli, N Johnson, TH Johnstone, D Jutila, CK Kadri, N Kahl, FR Kaimal, PK Karnegis, J Kay, R Kelly, KJ Kenefick, G Kennelly, BM Kent, E Khan, AH Khanijo, V Khouri, M Kinloch, D Kirlin, PC Kiwan, GS Kline, MD Kohn, RM Koilpillai, C Kornder, JM Kouz, S Kumar, VA Kumar, U Kuntz, A Kuritzky, RA Kuruvilla, G Kwok, KK Lader, E Laforest, M LaForge, D Lalonde, G Lalonde, L Lang, RM Latour, Y Lawal, O LeBlanc, MH Lee, AB Lee, RW Legault, C Lemay, M Lenis, JHF Lepage, S Letarte, P Levesque, C LevinoffRoth, SN Lewis, BK Lipshutz, H Loungani, RR Lowery, ML Lubell, DL Lucariello, R LugoRodriguez, JE Lui, C Lutterodt, AT Lutz, L Machel, T Macina, G MacLellan, K Magnan, O Mansuri, M Manyari, DE Mallis, GI Marr, D Mast, DJ Mathew, J McBarron, FD McIntyre, KM McLean, RW McMahon, DP Mercier, M Methe, M Miller, AB Minkowitz, J Milton, JR Mizgala, HF Mohanty, PK Mohiuddin, S Montero, A Mookherjee, S Morris, A Morris, L Morrison, J Moten, M Nafziger, A Nair, PH Nawaz, S Neiman, JC Nutting, P NguyenPho, HT OBrien, TK OKelly, RL OReilly, MV Okerson, D Patel, G Pande, PN Papa, LA Patrick, L Payne, RM Perry, G Philbin, EF Pierpont, G Pitt, WA Poirier, C Pollak, EM Popio, K Poulin, JF Probst, PA Pruneau, G Pu, C Puram, BS Putatunda, B Quinn, B Rabkin, SW Racine, N Raco, DL Radant, L Radford, MJ Radwany, S Rajachar, M Ramanathan, KB Rashkow, A Rausch, DC Read, L Reddy, KR Reid, R Rich, MW Ricci, AJ Richman, HG Riley, A Rim, DA Rinne, C Roberge, G Roberts, DK Robinson, V Rodeheffer, RT Rosenstein, R Roth, DL Rothbart, R Rouleau, JL Ruble, P Sacco, J Safford, RE Salmon, D Sahay, BM Sarma, RJ Sayeed, MAR Schick, EC Schroeder, GS Seifert, M Senaratne, MPJ Sestier, F Shah, A Shanes, JG Sheesley, K Silverman, A Shiva, T Shrestha, DD Silver, MA Silverberg, L Simard, L Singh, BN Small, RS Smith, MR Smith, S Sochowski, RA Southern, RF Sridharan, MR StHilaire, R Stein, M Stewart, JW Stillabower, ME Sullivan, BHM Sturrock, WA Sussex, BA Swan, J Swenson, L Talbot, P Talibi, T Tamilia, M Tan, A Tanser, PH Tarry, L Teo, KK Thadani, U Thagirisa, S Thompson, B Thornton, R Timmis, GC Tobin, M Tommaso, C Toren, M Tsuyuki, R Turek, M Utley, K Vanderbush, EJ VanVoorhees, L Ventura, H Vertes, G Vizel, S Wagner, KR Wagner, S Weeks, A Weingert, ME Weinstein, C Weiss, MM Weiss, R Wickemeyer, W Wielgoz, A Willens, HJ Williams, WL Wong, D Yarows, SA Yao, L Shalev, Y Young, JB Yousefian, M Zajac, EJ Zatuchni, J Ziperman, DB Zoble, RG Zoneraich, S Gorlin, R Sleight, P Cohn, JN Collins, R Deykin, D Hennekens, C Kjekshus, J Smith, TW Tognoni, G Collins, JF Williford, WO Fye, C Sather, R Jolly, MK Held, CP Verter, J Yusuf, S Egan, D Garg, R Johnstone, DE Montague, T Bristow, D Engelhardt, HT Gent, M Hood, WB Jones, S Meier, P Pitt, B Waters, D Arnold, JMO Baker, A Barnhill, S Carew, B Hagar, S Liuni, C Martin, S Miles, R Arthur, MM Feldbush, MW Highfield, DA Hobbins, TE Kurz, R Leviton, SP Libonati, JP Moore, M Perez, E Mills, P Geller, N Hunsberger, S Gold, J Huang, PC Burns, A Caleb, H Cline, DR Harris, S Hockenbrock, R Horney, RA Jadwin, LM King, J Sexton, P Spence, ME Chacon, F Gagne, W Maple, S Martinez, G TI Rationale, design, implementation, and baseline characteristics of patients in the DIG trial: A large, simple, long-term trial to evaluate the effect of digitalis on mortality in heart failure SO CONTROLLED CLINICAL TRIALS LA English DT Article DE design; large simple trial; randomized clinical trial; digoxin; heart failure ID CLINICAL-TRIALS; NEED AB This article provides a detailed overview of the rationale for key aspects of the protocol of the Digitalis Investigation Group (DIG) trial. It also highlights unusual aspects of the study implementation and the baseline characteristics. The DIG trial is a large, simple, international placebo-controlled trial whose primary objective is to determine the effect of digoxin on all cause mortality in patients with clinical heart failure who are in sinus rhythm and whose ejection fraction is less than or equal to 0.45. An ancillary study examines the effect in those with an ejection fraction > 0.45. Key aspects of the trial include the simplicity of the design, broad eligibility criteria, essential data collection, and inclusion of various types of centers. A total of 302 centers in the United States and Canada enrolled 7788 patients between February 1991 and September 1993. Follow-up continued until December 1995 with the results available in Spring 1996. C1 ST JOSEPHS HOSP, TAMPA, FL USA. UNIV NEW MEXICO, SCH MED, ALBUQUERQUE, NM 87131 USA. VAMC, TOPEKA, KS USA. SINAI SAMARITAN MED CTR, MILWAUKEE, WI USA. VAMC, PITTSBURGH, PA USA. VAMC, MINNEAPOLIS, MN USA. VICTORIA HOSP, LONDON, ON N6A 4G5, CANADA. PENTICTON REG HOSP, PENTICTON, BC, CANADA. OTTAWA CIVIC HOSP, OTTAWA, ON K1Y 4E9, CANADA. HOTEL DIEU DELEVIS, QUEBEC CITY, PQ, CANADA. BRIDGEPORT HOSP, BRIDGEPORT, CT USA. SUNNYBROOK HSC, TORONTO, ON, CANADA. GR BAKER MEM HOSP, QUESNEL, BC, CANADA. MERCY MED CTR, BALTIMORE, MD USA. JOHNS HOPKINS MED INST, BALTIMORE, MD 21205 USA. JEWISH HOSP ST LOUIS, ST LOUIS, MO 63110 USA. VAMC, BROOKLYN, NY USA. ST JOSEPH HOSP & HLTH CARE CTR, CHICAGO, IL USA. OROVILLE HOSP, OROVILLE, CA USA. ST JOHNS HOSP, ST JOHN, NB, CANADA. HOP ENFANTS JESUS, QUEBEC CITY, PQ, CANADA. VAMC, LAKE CITY, FL USA. CARDIOL CONSULTANTS, HICKSVILLE, NY USA. ST VINCENTS MED CTR, STATEN ISL, NY USA. USN HOSP, OAKLAND, CA USA. MILTON S HERSHEY MED CTR, HERSHEY, PA USA. HOP SEPT ILES, SEPT ILES, PQ, CANADA. INST CARDIOL MONTREAL, MONTREAL, PQ, CANADA. CTR HOP REG, BAIE COMEAU, PQ, CANADA. CTR HOP, VERDUN, PQ, CANADA. CTR HOP, JONQUIERE, PQ, CANADA. VAMC, BIRMINGHAM, AL USA. COLUMBIA UNIV COLL PHYS & SURG, HARLEM HOSP CTR, NEW YORK, NY 10032 USA. VICTORIA HOSP, LONDON, ON N6A 4G5, CANADA. ST LUKES ROOSEVELT HOSP, NEW YORK, NY 10025 USA. METHODIST HOSP, INDIANAPOLIS, IN USA. CTR HOP REG AMIANTE, THETFORD MINES, PQ, CANADA. VAMC, BUFFALO, NY USA. VAMC, PHOENIX, AZ USA. VAMC, ALBANY, NY USA. RARITAN BAY MED CTR, PERTH AMBOY, NJ USA. OUR LADY MERCY MED CTR, BRONX, NY USA. UNIV OKLAHOMA, HLTH SCI CTR, VAMC, OKLAHOMA CITY, OK USA. SACRED HEART GEN HOP, EUGENE, OR USA. CTR HOP, GATINEAU, PQ, CANADA. FT MADISON COMMUNITY HOSP, FT MADISON, IA USA. DANBURY HOSP, DANBURY, CT USA. VICTORIA GEN HOSP, HALIFAX, NS B3H 2Y9, CANADA. STATEN ISL U HOSP, STATEN ISL, NY USA. HOP NOTRE DAME DE BON SECOURS, MONTREAL, PQ H2L 4K8, CANADA. VAMC, ALBUQUERQUE, NM USA. LOVELACE MED CTR, ALBUQUERQUE, NM USA. CAMP HILL MED CTR, HALIFAX, NS, CANADA. HOP LAVAL, ST FOY, PQ, CANADA. VAMC, MUSKOGEE, OK USA. COOK CTY HOSP, CHICAGO, IL 60612 USA. VAMC, FT MEADE, SD USA. UNIV OTTAWA, INST HEART, OTTAWA, ON, CANADA. HOP CHICOUTIMI, CHICOUTIMI, PQ, CANADA. ST JOHNS HOSP, TULSA, OK USA. ST PAUL RAMSEY MED CTR, ST PAUL, MN 55101 USA. SPECIALTY MED CLIN, ENCINITAS, CA USA. AUDUBON REG MED CTR, LOUISVILLE, KY USA. TOURO INFIRM, NEW ORLEANS, LA USA. VAMC, CLEVELAND, OH USA. ST PAULS HOSP, VANCOUVER, BC V6Z 1Y6, CANADA. VAMC, LITTLE ROCK, AR USA. PROVIDENCE HOSP, SOUTHFIELD, MI 48037 USA. SINAI HOSP, BALTIMORE, MD 21215 USA. VAMC, BROOKLYN, NY USA. VAMC, FARGO, ND USA. UNIV TENNESSEE, MED CTR, KNOXVILLE, TN USA. EASTERN MAINE MED CTR, BANGOR, ME USA. NO COLORADO MED CTR, GREELEY, CO USA. VAMC, LOS ANGELES, CA USA. ROYAL VICTORIA HOSP, MONTREAL, PQ H3A 1A1, CANADA. FRANCIS SCOTT KEY MED CTR, BALTIMORE, MD 21224 USA. MT AUBURN HOSP, CAMBRIDGE, MA USA. VAMC, NEWINGTON, CT USA. COLCHESTER REG HOSP ANNEX, TRURO, NS, CANADA. UNIV MISSOURI, TRUMAN MED CTR, KANSAS CITY, MO 64108 USA. SALT LAKE CLIN RES, SALT LAKE CITY, UT USA. MED COLL OHIO, TOLEDO, OH 43699 USA. UNIV MINNESOTA, MINNEAPOLIS, MN 55455 USA. GOOD SAMARITAN HOSP, ZANESVILLE, OH USA. VANDERBILT UNIV SCH MED, NASHVILLE, TN USA. CTR HOP, VERDUN, PQ, CANADA. SUDBURY MEM HOSP, SUDBURY, ON, CANADA. VALDESE GEN HOSP, VALDESE, NC USA. HOP ST JOSEPH, TROIS RIVIERES, PQ, CANADA. HENRY FORD HOSP, DETROIT, MI 48202 USA. VAMC, MANCHESTER, NH USA. MARICOPA CTY GEN HOSP, PHOENIX, AZ USA. ST FRANCES CABRINI HOSP, ALEXANDRIA, LA USA. GREY NUNS HOSP, EDMONTON, AB, CANADA. MONTEFIORE MED CTR, BRONX, NY 10467 USA. VAMC, MURFREESBORO, TN USA. MEM MED CTR, SAVANNAH, GA USA. NO COLORADO MED CTR, GREELEY, CO USA. HOP MAISON NEUVE ROSEMONT, MONTREAL, PQ H1T 2M4, CANADA. INST CARDIOL, MONTREAL, PQ, CANADA. VAMC, ALLEN PK, MI USA. VAMC, RENO, NV USA. VAMC, CASTLE POINT, NY USA. MISERICORDIA HOSP, EDMONTON, AB, CANADA. UNIV CALIF DAVIS, SACRAMENTO, CA 95817 USA. OVERLOOK HOSP, SUMMIT, NJ USA. MARSHFIELD CLIN FDN MED RES & EDUC, MARSHFIELD, WI USA. BESS KAISER MED CTR, PORTLAND, OR USA. AURORA COMMUNITY HOSP, AURORA, CO USA. VAMC, MARION, IL USA. VAMC, DAYTON, OH USA. PLAINS HLTH CTR, REGINA, SK, CANADA. ABERDEEN HOSP, NEW GLASGOW, NS, CANADA. ST JOHNS MERCY MED CTR, ST LOUIS, MO 63141 USA. BUFFALO GEN HOSP, BUFFALO, NY 14203 USA. DUNES FAMILY HLTH CARE, REEDSPORT, OR USA. DORNS VET HOSP, COLUMBIA, SC USA. S SHORE REG HOSP, BRIDGEWATER, MA USA. ST JOSEPH MERCY HOSP, PONTIAC, MI USA. AKRON GEN MED CTR, AKRON, OH USA. BAY DE NOC FAMILY HLTH CTR, ESCANABA, MI USA. QUEEN ELIZABETH HOSP, CHARLOTTETOWN, PE, CANADA. UNIV ALBERTA, EDMONTON, AB, CANADA. CLEVELAND CLIN, CLEVELAND, OH 44106 USA. HOP GEN JUIF SIR MORTIMER B DAVIS, MONTREAL, PQ, CANADA. NANAIMO REG GEN HOSP, NAINAMO, BC, CANADA. UNIV COLORADO, HLTH SCI CTR, DENVER, CO USA. LAKESIDE VAMC, CHICAGO, IL USA. FLUSHING HOSP & MED CTR, FLUSHING, NY USA. VAMC, TUSCALOOSA, AL USA. ROYAL ALEXANDRA HOSP, EDMONTON, AB, CANADA. N SHORE CARDIOL LAB, N VANCOUVER, BC, CANADA. VAMC, SALEM, VA USA. VAMC, OMAHA, NE USA. WAKE FOREST UNIV, BOWMAN GRAY SCH MED, WINSTON SALEM, NC USA. RAPIDES REG MED CTR, ALEXANDRIA, LA USA. NEW YORK MED COLL, VALHALLA, NY 10595 USA. FT WAYNE CARDIOL, FT WAYNE, IN USA. HOAG MEM HOSP, NEWPORT BEACH, CA USA. ST JOSEPHS HOSP, HAMILTON, ON, CANADA. MEM HOSP, PAWTUCKET, RI USA. VAMC, ROSEBURG, OR USA. ROYAL U HOSP, SASKATOON, SK, CANADA. CARDIAC RES CTR, VICTORIA, BC, CANADA. METHODIST HOSP, INDIANAPOLIS, IN USA. CHRDL, JOLIETTE, PQ, CANADA. SURREY MEM HOSP, SURREY, ENGLAND. VAMC, HOT SPRINGS, SD USA. VAMC, MONTROSE, NY USA. ROYAL COLUMBIAN HOSP, NEW WESTMINSTER, BC, CANADA. GREY BRUCE REG HLTH CTR, OWEN SOUND, ON, CANADA. MID HUDSON FAMILY HLTH SERV INST, KINGSTON, NY USA. HOP SACRE COEUR, MONTREAL, PQ H4J 1C5, CANADA. UNIV CHICAGO HOSP, CHICAGO, IL USA. COLUMBIA UNIV COLL PHYS & SURG, HARLEM HOSP CTR, NEW YORK, NY 10032 USA. HARRISON MEM HOSP, BREMERTON, WA USA. MAYO CLIN, SCOTTSDALE, AZ USA. HOP NOTRE DAME DE BON SECOURS, MONTREAL, PQ H2L 4K8, CANADA. INVASCOR, LONGUEUIL, PQ, CANADA. UNIV SHERBROOKE, CTR HOP, SHERBROOKE, PQ J1K 2R1, CANADA. SYDENHAM DIST HOP, WALLACEBURG, ON, CANADA. HOP CHICOUTIMI, CHICOUTIMI, PQ, CANADA. SACRED HEART HOSP & REHABIL CTR, NORRISTOWN, PA USA. VAMC, DES MOINES, IA USA. MT SINAI HOSP MED CTR, CHICAGO, IL USA. OUR LADY MERCY MED CTR, BRONX, NY USA. SAN JUAN CITY HOSP, RIO PIEDRAS, PR USA. VAMC, SALEM, VA USA. WILLIAMS FAMILY MED CTR, DENVER, CO USA. HANTS COMMUNITY HOSP, WINDSOR, NS, CANADA. ST JOHNS QUEENS HOSP, ELMHURST, NY USA. UNIV CALGARY, FOOTHILLS PROV GEN HOSP, CALGARY, AB, CANADA. VAMC, NORTHPORT, NY USA. ST JOHNS HOSP, ST JOHN, NB, CANADA. DULUTH CLIN, DULUTH, MN USA. COOK CTY HOSP, CHICAGO, IL 60612 USA. PROVIDENCE MED CTR, PORTLAND, OR USA. VAMC, BROCKTON, MA USA. DUNES FAMILY HLTH CARE, REEDSPORT, OR USA. HOTEL DIEU ARTHABASKA, ARTHABASKA, PQ, CANADA. UNIV FLORIDA, HLTH SCI CTR, JACKSONVILLE, FL 32209 USA. CARLETON MEM HOSP, WOODSTOCK, NB, CANADA. VANCOUVER HOSP & HSC, VANCOUVER, BC, CANADA. VAMC, RICHMOND, VA USA. CREIGHTON UNIV, CARDIAC CTR, OMAHA, NE 68178 USA. VAMC, HOUSTON, TX USA. VAMC, SYRACUSE, NY USA. ST BONIFACE GEN HOSP, WINNIPEG, MB R2H 2A6, CANADA. LEHIGH VALLEY HOSP, ALLENTOWN, PA USA. N SHORE U HOSP, MANHASSET, NY USA. VAMC, ALLEN PK, MI USA. MARY IMOGENE BASSETT HOSP, COOPERSTOWN, NY 13326 USA. COFFEE REG HOSP, DOUGLAS, GA USA. SUDBURY MEM HOSP, SUDBURY, ON, CANADA. ST VINCENTS MED CTR, JACKSONVILLE, FL USA. CHELSEA COMMUNITY HOSP, CHELSEA, MI USA. VALLEY REG HOSP, HUNTSVILLE, NS, CANADA. VAMC, WILKES BARRE, PA USA. VAMC, ASHEVILLE, NC USA. ROCHESTER GEN HOSP, ROCHESTER, NY 14621 USA. UMDNJ, AMBULATORY HLTH CARE CTR, STRATFORD, NJ USA. UNIV TEXAS, CTR HLTH, TYLER, TX 75710 USA. VAMC, MINNEAPOLIS, MN USA. SO CALIF CARDIOL, SAN DIEGO, CA USA. CAPE FEAR VALLEY MED CTR, FAYETTEVILLE, AR USA. HOSP ST SACREMENT, QUEBEC CITY, PQ, CANADA. IOWA HEART CTR, DES MOINES, IA USA. CTR HOSP REG AMIANTE, THETFORD MINES, PQ, CANADA. UNIV BRITISH COLUMBIA, VANCOUVER, BC V5Z 1M9, CANADA. GUELPH CARDIOL ASSOCIATES, GUELPH, ON, CANADA. HESS MEM HOSP, MILE BLUFF CLIN, MAUSTON, WI USA. VAMC, NEWINGTON, CT USA. AKRON CITY HOSP, AKRON, OH USA. VAMC, BUTLER, PA USA. VAMC, MEMPHIS, TN USA. GRIFFIN HOSP, DERBY, CT USA. GRANDIN MED CTR, ST ALBERT, AB, CANADA. VAMC, TUSKEGEE, AL USA. ROYAL INLAND HOSP, KAMLOOPS, BC, CANADA. RAVENSWOOD HOSP, MED CTR, CHICAGO, IL USA. VAMC, BATTLE CREEK, MI USA. LINCOLN MED & MENTAL HLTH CTR, BRONX, NY 10451 USA. HOSP ST LUC, MONTREAL, PQ, CANADA. USN HOSP, OAKLAND, CA USA. MONCTON MED CLIN, MONCTON, NB, CANADA. ST MARYS HOSP, DECATUR, IL USA. CALGARY GEN HOSP, CALGARY, AB, CANADA. UNIV COLORADO, HLTH SCI CTR, DENVER, CO USA. HOSP GOOD SAMARITAN, BALTIMORE, MD USA. UNIV SO CALIF, RANCHO LOS AMIGOS MED CTR, DOWNEY, CA 90242 USA. LAHEY CLIN MED CTR, BURLINGTON, MA 01803 USA. PLYMOUTH FAMILY PHYSICIANS, PLYMOUTH, WI USA. EAGLE MED, EXCELSIOR, MN USA. WASHINGTON HOSP CTR, WASHINGTON, DC 20010 USA. VAMC, TUSCALOOSA, AL USA. BAY MED CTR, BAY CITY, MI USA. MIDW CTR HEART FAILURE, LOMBARD, IL USA. HOP CHRIST ROI, VANIER, PQ, CANADA. VAMC, LOS ANGELES, CA USA. CARDIOVASC ASSOCIATES, LANCASTER, PA USA. MERCY HOSP ANDERSON, CINCINNATI, OH USA. HENRY FORD HOSP, DETROIT, MI 48202 USA. ST JOSEPHS HLTH CTR, LONDON, ON, CANADA. VAMC, AUGUSTA, GA USA. CTR HOP ST GEORGES DE BEAUCE, ST GEORGES OUEST, PQ, CANADA. CHRISTIANA HOSP, MED CTR DELAWARE, NEWARK, DE USA. SULLIVAN CARDIOL ASSOCIATES, HAMILTON, ON, CANADA. EASTERN MAINE MED CTR, BANGOR, ME USA. GEN HOSP CORP, HSC, ST JOHN, NF, CANADA. ST PAUL RAMSEY MED CTR, ST PAUL, MN 55101 USA. NO ALBERTA CARDIAC REHABIL INST, EDMONTON, AB, CANADA. CTR HOP REG, BAIE COMEAU, PQ, CANADA. VAMC, ROSEBURG, OR USA. ST JOSEPHS HOSP, HAMILTON, ON, CANADA. UNIV ALBERTA, EDMONTON, AB, CANADA. UNIV OKLAHOMA, HLTH SCI CTR, VAMC, OKLAHOMA CITY, OK USA. VAMC, CLARKSBURG, MD USA. BEAUMONT HOSP, ROYAL OAK, MI USA. HILLSBORO CARDIOL, HILLSBORO, OR USA. ROYAL COLUMBIAN HOSP, NEW WESTMINSTER, BC, CANADA. SINAI HOSP, BALTIMORE, MD 21215 USA. COLUMBIA UNIV COLL PHYS & SURG, HARLEM HOSP CTR, NEW YORK, NY 10032 USA. WASHINGTON HOSP CTR, WASHINGTON, DC 20010 USA. ALTON OCHSNER MED FDN & OCHSNER CLIN, NEW ORLEANS, LA 70121 USA. CAMBRIDGE MEM HOSP, CAMBRIDGE, ON, CANADA. TRAIL REG HOSP, TRAIL, BC, CANADA. UNIV LOUISVILLE, VAMC, LOUISVILLE, KY 40292 USA. FT WILLIAM CLIN, THUNDER BAY, ON, CANADA. JAMAICA HOSP, JAMAICA, NY USA. JEWISH HOSP HEART & LUNG INST, LOUISVILLE, KY USA. ANDROSCOGGIN CARDIOL ASSOCIATES, AUBURN, AL USA. OTTAWA GEN HOSP, OTTAWA, ON K1H 8L6, CANADA. BURNS CLIN MED CTR, PETOSKEY, MI USA. EDMONTON GEN HOSP, EDMONTON, AB, CANADA. SINAI SAMARITAN MED CTR, MILWAUKEE, WI USA. METHODIST HOSP, HOUSTON, TX 77030 USA. FAMILY MED ASSOCIATES, RICHBURG, SC USA. UNIV ILLINOIS, CHICAGO, IL USA. PENN HOSP, PHILADELPHIA, PA 19107 USA. COMMUNITY HOSP, INDIANAPOLIS, IN USA. JAMES A HALEY VET HOSP, TAMPA, FL 33612 USA. FLUSHING HOSP & MED CTR, FLUSHING, NY USA. MT SINAI HOSP, NEW YORK, NY 10029 USA. JOHN RADCLIFFE HOSP, OXFORD OX3 9DU, ENGLAND. VAMC, BOSTON, MA USA. VAMC, MINNEAPOLIS, MN USA. HARVARD UNIV, BOSTON, MA 02115 USA. BAIRUM HOSP, SANDVIKA, NORWAY. BRIGHAM & WOMENS HOSP, BOSTON, MA 02115 USA. IST M NEGRI, MILAN, ITALY. VAMC, COORD CTR, PERRY POINT, MD USA. VA CLIN RES PHARM COORD CTR, ALBUQUERQUE, NM USA. BURROUGHS WELLCOME CO, RES TRIANGLE PK, NC 27709 USA. NHLBI, CLIN TRIALS BRANCH, PROJECT OFF, BETHESDA, MD 20892 USA. UNIV ALBERTA HOSP, EDMONTON, AB T6G 2B7, CANADA. HAMILTON GEN HOSP, HAMILTON, ON, CANADA. OREGON HLTH SCI UNIV, PORTLAND, OR 97201 USA. BAYLOR COLL MED, HOUSTON, TX 77030 USA. HAMILTON CIV HOSP, RES CTR, HAMILTON, ON, CANADA. UNIV MICHIGAN, SCH MED, ANN ARBOR, MI USA. HARTFORD HOSP, HARTFORD, CT 06115 USA. RI Tsuyuki, Ross/E-2462-2016; Effron, Mark/P-9300-2015 OI Tsuyuki, Ross/0000-0002-3724-598X; NR 27 TC 65 Z9 66 U1 0 U2 6 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0197-2456 EI 1879-050X J9 CONTROL CLIN TRIALS JI Controlled Clin. Trials PD FEB PY 1996 VL 17 IS 1 BP 77 EP 97 PG 21 WC Medicine, Research & Experimental; Pharmacology & Pharmacy SC Research & Experimental Medicine; Pharmacology & Pharmacy GA UA398 UT WOS:A1996UA39800009 ER PT J AU Vaagenes, P Ginsberg, M Ebmeyer, U Ernster, L Fischer, M Gisvold, SE Gurvitch, A Hossmann, KA Nemoto, EM Radovsky, A Severinghaus, JW Safar, P Schlichtig, R Sterz, F Tonnessen, T White, RJ Xiao, F Zhou, Y AF Vaagenes, P Ginsberg, M Ebmeyer, U Ernster, L Fischer, M Gisvold, SE Gurvitch, A Hossmann, KA Nemoto, EM Radovsky, A Severinghaus, JW Safar, P Schlichtig, R Sterz, F Tonnessen, T White, RJ Xiao, F Zhou, Y TI Cerebral resuscitation from cardiac arrest: Pathophysiologic mechanisms SO CRITICAL CARE MEDICINE LA English DT Article; Proceedings Paper CT International Resuscitation Research Conference (IRRC 94) CY MAY 07-09, 1994 CL PITTSBURGH, PA DE anoxia; cardiopulmonary resuscitation; hypothermia; cardiac arrest; cerebral ischemia; cerebral blood flow; reoxygenation injury; cerebral excitotoxicity; angiogenesis; histopathology ID ISCHEMIC BRAIN-DAMAGE; DECREASES PLASMA-CATECHOLAMINES; BLOOD-FLOW; GLOBAL-ISCHEMIA; POSTRESUSCITATION SYNDROME; CARDIOPULMONARY BYPASS; ARTERY OCCLUSION; DOGS; RAT; RELEASE AB Both the period of total circulatory arrest to the brain and postischemic-anoxic encephalopathy (cerebral postresuscitation syndrome or disease), after normothermic cardiac arrests of between 5 and 20 mins (no flow), contribute to complex physiologic and chemical derangements. The best documented derangements include the delayed protracted inhomogeneous cerebral hypoperfusion (despite controlled normotension), excitotoxicity as an explanation for selectively vulnerable brain regions and neurons, and free radical triggered chemical cascades to lipid peroxidation of membranes. Protracted hypoxemia without cardiac arrest (e.g., very high altitude) can cause angiogenesis; the trigger of it, which lyses basement membranes, might be a factor in post-cardiac arrest encephalopathy. Questions to be explored include: What are the changes and effects on outcome of neurotransmitters (other than glutamate), of catecholamines, of vascular changes (microinfarcts seen after asphyxia), osmotic gradients, free radical reactions, DNA cleavage, and transient extracerebral organ malfunction? For future mechanism oriented studies of the brain after cardiac arrest and innovative cardiopulmonary cerebral resuscitation, increasingly reproducible outcome models of temporary global brain ischemia in rats and dogs are now available. Disagreements exist between experienced investigative groups on the most informative method for quantitative evaluation of morphologic brain damage. There is agreement on the desirability of using not only functional deficit and chemical changes, but also morphologic damage as end points. C1 UNIV MIAMI, SCH MED, DEPT NEUROL D45, MIAMI, FL 33101 USA. UNIV PITTSBURGH, SAFAR CTR RESUSCITAT RES, PITTSBURGH, PA 15260 USA. UNIV MAGDEBURG, DEPT ANESTHESIOL & CRIT CARE MED, D-39120 MAGDEBURG, GERMANY. UNIV STOCKHOLM, ARRHENIUS LAB, DEPT BIOCHEM, S-10691 STOCKHOLM, SWEDEN. REG UNIV HOSP TRONDEIM, DEPT ANESTHESIOL, N-7006 TRONDHEIM, NORWAY. RUSSIAN ACAD MED SCI, INST GEN REANIMATOL, MOSCOW 103031, RUSSIA. MAX PLANCK INST NEUROL RES, ABT EXPT NEUROL, D-50866 COLOGNE, GERMANY. UNIV PITTSBURGH, MED CTR, DEPT ANESTHESIOL, CCM, PITTSBURGH, PA 15261 USA. NIEHS, RES TRIANGLE PK, NC 27709 USA. UNIV CALIF SAN FRANCISCO, DEPT ANESTHESIOL, SAN FRANCISCO, CA 94143 USA. UNIV PITTSBURGH, DEPT CRIT CARE MED, PITTSBURGH, PA 15261 USA. LOUISIANA STATE UNIV, MED CTR, DEPT EMERGENCY MED, SHREVEPORT, LA 71130 USA. BEIJING MED UNIV, HOSP 1, DEPT ANESTHESIOL, BEIJING, PEOPLES R CHINA. STADT WIEN UNIV KLIN, ALLGEMEINES KRANKENHAUS, ABT NOTFALLMED, A-1090 VIENNA, AUSTRIA. CASE WESTERN RESERVE UNIV, CLEVELAND, OH 44109 USA. METROHLTH MED CTR, CLEVELAND, OH 44109 USA. RP Vaagenes, P (reprint author), AKERSHUS CENT HOSP, DEPT ANESTHESIA, 1474 NORDBYHAGEN, OSLO, NORWAY. NR 89 TC 38 Z9 45 U1 0 U2 6 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0090-3493 J9 CRIT CARE MED JI Crit. Care Med. PD FEB PY 1996 VL 24 IS 2 SU S BP S57 EP S68 PG 12 WC Critical Care Medicine SC General & Internal Medicine GA TW260 UT WOS:A1996TW26000006 PM 8608707 ER PT J AU delPilarValencia, M Miller, LH Mazur, P AF delPilarValencia, M Miller, LH Mazur, P TI Permeability of intact and dechorionated eggs of the Anopheles mosquito to water vapor and liquid water: A comparison with Drosophila SO CRYOBIOLOGY LA English DT Article ID EMBRYOS AB As an initial step in the development of cryopreservation methods for Allopheles gambiae embryos, we determined the permeability of intact and dechorionated A. gambiae embryos to water and ethylene glycol and compared those permeabilities with those of Drosophila melanogaster embryos. Most studies were conducted on embryos allowed to develop For 8 h at 26 degrees C or 15 h at 17 degrees C. Intact A. gambiae embryos are some 50 times more permeable to water vapor than are D. melanogaster embryos; e.g., when air dried, half of 15 h/17 degrees C A. gambiae embryos become severely dehydrated in 3.5-4.0 min, whereas comparably aged D. melanogaster embryos require similar to 4 h or more. Comparable differences between the two species exist with respect to the loss of liquid water under an osmotic driving force. After 90 min in 0.75 M sucrose in 0.26 osmolal D-20 Drosophila medium, 25-40% of intact A. gambiae embryos underwent extensive shrinkage, whereas D. melanogaster embryos showed no shrinkage. The chorion of both species can be removed by a 2.5-min exposure to 50% household bleach (Clorox). Dechorionation increases the rate of water loss two- to sixfold during air drying in both species and during exposure to hyperosmotic sucrose in A. gambiae. Dechorionated D. melanogaster embryos, however, show no shrinkage in hyperosmotic sucrose even after 6 h. The water permeability of dechorionated A. gambiae embryos thus remains many-fold higher than that of dechorionated D. melanogaster embryos. Although moderately permeable to water, neither intact nor dechorionated A. gambiae embryos are permeable to ethylene glycol, as evidenced by the failure of dehydrated embryos to reexpand in 120-180 min in that solution. (C) 1996 Academic Press. Inc. C1 OAK RIDGE NATL LAB, DIV BIOL, OAK RIDGE, TN 37831 USA. RP delPilarValencia, M (reprint author), NIH, PARASIT DIS LAB, BETHESDA, MD 20892 USA. NR 14 TC 20 Z9 20 U1 0 U2 5 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0011-2240 EI 1090-2392 J9 CRYOBIOLOGY JI Cryobiology PD FEB PY 1996 VL 33 IS 1 BP 142 EP 148 DI 10.1006/cryo.1996.0014 PG 7 WC Biology; Physiology SC Life Sciences & Biomedicine - Other Topics; Physiology GA UH228 UT WOS:A1996UH22800014 PM 8812093 ER PT J AU delPilarValencia, M Miller, LH Mazur, P AF delPilarValencia, M Miller, LH Mazur, P TI Permeabilization of eggs of the malaria mosquito Anopheles gambiae SO CRYOBIOLOGY LA English DT Article ID DROSOPHILA-MELANOGASTER EMBRYOS; CRYOPRESERVATION AB Although Anopheles gambiae embryos that have developed for 15 h at 17 degrees C are slightly permeable to water, they are impermeable to ethylene glycol, the cryoprotectant used in the cryopreservation of Drosophila melanogaster embryos. Success in cryopreservation requires that they be made permeable to protective solutes. Permeabilization of D. melanogaster was achieved by 1) dechorionation with 50% Clorox (household bleach) followed by 2) a water flush; 3) immersion in isopropyl alcohol to remove most extraembryonic water; 4) 2 min air drying to remove most isopropyl alcohol; 5) 90-s exposure to n-heptane containing 0.3% 1-butanol; and 6) 15-s exposure to pure n-heptane. The permeability of A. gambiae embryos was assessed by determining the times required for the initial dehydration of embryos in 1 M ethylene glycol in 260 mOsm Drosophila culture medium (permeability to water) and the times required for their return to normal volume (permeability to ethylene glycol). Based on these criteria, the above D. melanogaster procedure effectively permeabilizes 15 h/17 degrees C to 19 h/17 degrees C A. gambiae embryos. Nearly all collapsed in <5 min, and most returned to normal volume in similar to 40 min. Although permeable, all were killed by the permeabilization procedure. In analyzing the effect of each step on viability, 50% Clorox caused some lethality, and Clorox followed by isopropyl alcohol was 100% lethal. Decreasing the Clorox concentration to 10% still dechorionated eggs, but with reduced toxicity; substitution of a 10% solution of reagent-grade sodium hypochlorite for Clorox further decreased toxicity. The isopropyl alcohol step was also toxic. Consequently, the removal of residual surface water was achieved by substituting air drying for isopropyl alcohol. The drying took place under direct microscope observation and was continued until the embryos began to shrink. The combination of this modified method for dechorionation and controlled air drying before exposure to heptane resulted in permeabilization of all embryos in most runs and in similar to 30% survival of the permeabilized embryos. (C) 1996 Academic Press, Inc. C1 OAK RIDGE NATL LAB, DIV BIOL, OAK RIDGE, TN 37831 USA. RP delPilarValencia, M (reprint author), NIH, PARASIT DIS LAB, BETHESDA, MD 20892 USA. NR 16 TC 16 Z9 16 U1 0 U2 1 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0011-2240 EI 1090-2392 J9 CRYOBIOLOGY JI Cryobiology PD FEB PY 1996 VL 33 IS 1 BP 149 EP 162 DI 10.1006/cryo.1996.0015 PG 14 WC Biology; Physiology SC Life Sciences & Biomedicine - Other Topics; Physiology GA UH228 UT WOS:A1996UH22800015 PM 8812094 ER PT J AU Lunsford, RD Nguyen, N London, J AF Lunsford, RD Nguyen, N London, J TI DNA-binding activities in Streptococcus gordonii: Identification of a receptor-nickase and a histonelike protein SO CURRENT MICROBIOLOGY LA English DT Article ID ESCHERICHIA-COLI; MOLECULAR-CLONING; HU; PURIFICATION; GENE AB Extraction of Streptococcus gordonii cells with the mild chaotropic agent, LiCl, drastically decreased DNA transforming ability, had little effect on viability, and released both DNA nicking and binding activities, Both activities were Mg2+ and Ca2+ independent and were not competence specific. Southwestern blot analysis of the extract identified putative surface proteins of 56 kDa and 68 kDa in strain Challis and Wicky, respectively. Extracts also contained a 10-kDa DNA-binding protein, designated HSgo, that belongs to the eubacterial histonelike class of proteins. C1 US FDA,CTR BIOL EVALUAT & RES,BETHESDA,MD 20892. RP Lunsford, RD (reprint author), NIDR,MICROBIAL ECOL LAB,BLDG 30,RM 312,30 CONVENT DR,BETHESDA,MD 20892, USA. NR 28 TC 14 Z9 14 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0343-8651 J9 CURR MICROBIOL JI Curr. Microbiol. PD FEB PY 1996 VL 32 IS 2 BP 95 EP 100 DI 10.1007/s002849900017 PG 6 WC Microbiology SC Microbiology GA TM932 UT WOS:A1996TM93200008 PM 8574134 ER PT J AU Baxevanis, AD Makalowski, W Ouellette, BFF Recipon, H AF Baxevanis, AD Makalowski, W Ouellette, BFF Recipon, H TI The biologist and the World Wide Web SO CURRENT OPINION IN BIOTECHNOLOGY LA English DT Article RP Baxevanis, AD (reprint author), NIH,NATL CTR BIOTECHNOL INFORMAT,BLDG 38A,ROOM 8N-805,BETHESDA,MD 20894, USA. RI Makalowski, Wojciech/I-2843-2016 NR 2 TC 3 Z9 3 U1 0 U2 0 PU CURRENT BIOLOGY LTD PI LONDON PA 34-42 CLEVELAND STREET, LONDON, ENGLAND W1P 6LB SN 0958-1669 J9 CURR OPIN BIOTECH JI Curr. Opin. Biotechnol. PD FEB PY 1996 VL 7 IS 1 BP 99 EP 101 DI 10.1016/S0958-1669(96)80104-2 PG 3 WC Biochemical Research Methods; Biotechnology & Applied Microbiology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology GA TX114 UT WOS:A1996TX11400018 ER PT J AU Parsegian, VA Evans, EA AF Parsegian, VA Evans, EA TI Long and short range intermolecular and intercolloidal forces SO CURRENT OPINION IN COLLOID & INTERFACE SCIENCE LA English DT Review ID ELECTRICAL DOUBLE-LAYER; PHOSPHOLIPID-BILAYERS; SURFACE FORCES; LIPID BILAYERS; MOLECULAR-DYNAMICS; COLLOIDAL FORCES; HYDRATION FORCES; GLASS SURFACES; MICROSCOPY; TEMPERATURE AB The way we now automatically speak of directly measured intermolecular or intercolloidal forces represents a qualitative change from the indirect way such forces used to be inferred from aggregation kinetics or from measurements on much larger or smaller systems. The big change is in the way colloids or macromolecules can now be observed, confined, manipulated, put under collective stress or subjected to discrete forces. C1 NIDDKD,DIV INTRAMURAL RES,NIH,BETHESDA,MD 20892. UNIV BRITISH COLUMBIA,DEPT PHYS,VANCOUVER,BC V6T 1W5,CANADA. UNIV BRITISH COLUMBIA,DEPT PATHOL,VANCOUVER,BC V6T 1W5,CANADA. RP Parsegian, VA (reprint author), NIDDKD,STRUCT BIOL LAB,DIV COMP RES & TECHNOL,NIH,BETHESDA,MD 20892, USA. NR 60 TC 28 Z9 28 U1 2 U2 9 PU CURRENT SCIENCE LTD PI LONDON PA 34-42 CLEVELAND STREET, LONDON, ENGLAND W1P 6LB SN 1359-0294 J9 CURR OPIN COLLOID IN JI Curr. Opin. Colloid Interface Sci. PD FEB PY 1996 VL 1 IS 1 BP 53 EP 60 PG 8 WC Chemistry, Physical SC Chemistry GA VE480 UT WOS:A1996VE48000010 ER PT J AU Bates, S Vousden, KH AF Bates, S Vousden, KH TI p53 in signaling checkpoint arrest or apoptosis SO CURRENT OPINION IN GENETICS & DEVELOPMENT LA English DT Article ID WILD-TYPE P53; DNA-DAMAGING AGENTS; GROWTH ARREST; CELLS; INDUCTION; CYCLE; SUPPRESSION AB The cell cycle arrest and apoptotic functions of p53 both contribute to the role of this tumour suppressor protein in preventing replication of cells suffering DNA damage. Although the ability of p53 to function as a sequence-specific transcription factor appears to be directly and causally linked to the implementation of an arrest at the G(1) stage of the cell cycle, the contribution of transcriptional activation to the apoptotic response is less clear. It seems likely that several p53 activities, both transcriptionally dependent and transcriptionally independent, can play a role in mediating cell death. The requirement for each of these functions appears to depend on the cell type, the cell environment and other genetic alterations already sustained by the cell in which p53 function is activated. RP Bates, S (reprint author), NCI,FREDERICK CANC RES & DEV CTR,ABL BASIC RES PROGRAM,W 7TH ST,FREDERICK,MD 21702, USA. NR 68 TC 274 Z9 281 U1 0 U2 5 PU CURRENT BIOLOGY LTD PI LONDON PA 34-42 CLEVELAND STREET, LONDON, ENGLAND W1P 6LB SN 0959-437X J9 CURR OPIN GENET DEV JI Curr. Opin. Genet. Dev. PD FEB PY 1996 VL 6 IS 1 BP 12 EP 18 DI 10.1016/S0959-437X(96)90004-0 PG 7 WC Cell Biology; Genetics & Heredity SC Cell Biology; Genetics & Heredity GA TU879 UT WOS:A1996TU87900003 PM 8791489 ER PT J AU Rice, P Craigie, R Davies, DR AF Rice, P Craigie, R Davies, DR TI Retroviral integrases and their cousins SO CURRENT OPINION IN STRUCTURAL BIOLOGY LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; HIV-1 REVERSE-TRANSCRIPTASE; DNA-BINDING DOMAIN; ESCHERICHIA-COLI; CRYSTAL-STRUCTURE; RIBONUCLEASE-H; PROTEIN INVITRO; POLYNUCLEOTIDYL TRANSFER; ANGSTROM RESOLUTION; MU-TRANSPOSASE AB The recently determined structures of the catalytic domains of HIV integrase, avian sarcoma virus integrase and the Mu transposase are strikingly similar to each other and also exhibit significant similarity to several nucleases. All these enzymes cut polynucleotides, leaving 3'OH and 5'PO4 groups. The integrase and transposase also possess a strand-transfer activity that splices DNA. The structural similarities among members of this superfamily of polynucleotidyl transferases suggest that they share a similar mechanism of catalysis. RP Rice, P (reprint author), NIDDK,MOLEC BIOL LAB,NIH,BLDG 5,BETHESDA,MD 20892, USA. NR 65 TC 166 Z9 167 U1 0 U2 2 PU CURRENT BIOLOGY LTD PI LONDON PA 34-42 CLEVELAND STREET, LONDON, ENGLAND W1P 6LB SN 0959-440X J9 CURR OPIN STRUC BIOL JI Curr. Opin. Struct. Biol. PD FEB PY 1996 VL 6 IS 1 BP 76 EP 83 DI 10.1016/S0959-440X(96)80098-4 PG 8 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA TW573 UT WOS:A1996TW57300012 PM 8696976 ER PT J AU Sievers, ML Nelson, RG Bennett, PH AF Sievers, ML Nelson, RG Bennett, PH TI Sequential trends in overall and cause-specific mortality in diabetic and nondiabetic Pima Indians SO DIABETES CARE LA English DT Article ID PREVALENCE; TABLES; DEATH AB OBJECTIVE - To compare sequential trends in overall and cause-specific death rates for diabetic and nondiabetic Pima Indians. RESEARCH DESIGN AND METHODS - Underlying causes of death in Pimas aged greater than or equal to 15 years old were determined for the years 1975-1989 From review of death certificates and medical records. Overall and cause-specific death rates were compared for consecutive intervals. RESULTS - The all-causes death rate, age- and sex-adjusted, did not change significantly between the first and second halves of the study for diabetic (death rate ratio [DRR] = 0.99, 95% CI 0.70-1.4) or nondiabetic Pimas (DRR = 0.92, 95% CI 0.74-1.1). Among diabetic Pimas, however, the death rate For diabetic nephropathy declined from 2.7 to 1.5/1,000 person-years (DRR = 0.55, 95% CI 0.33-0.93), with ischemic heart disease (IHD) replacing diabetic nephropathy as the leading cause in the second half (DRR = 1.5, 95% CI 0.91-2.6). For diabetic and nondiabetic Pimas combined, the death rate in three consecutive 5-year periods declined progressively for alcoholic liver disease (P = 0.024) and external causes of death (P = 0.016), the largest component of which was automobile accidents. CONCLUSIONS - The decrease in death rate for diabetic nephropathy may be a result of greater access to and improvements in renal replacement therapy. Because of shared risk factors, however, the IHD death rate increased and largely offset the decrease in diabetic nephropathy deaths. The decline in deaths from alcoholic liver disease and from automobile accidents parallels the national trend. RP Sievers, ML (reprint author), NIDDKD,PHOENIX EPIDEMIOL & CLIN RES BRANCH,1550 E INDIAN SCH RD,PHOENIX,AZ 85014, USA. RI Nelson, Robert/B-1470-2012 NR 29 TC 35 Z9 35 U1 0 U2 0 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1660 DUKE ST, ALEXANDRIA, VA 22314 SN 0149-5992 J9 DIABETES CARE JI Diabetes Care PD FEB PY 1996 VL 19 IS 2 BP 107 EP 111 DI 10.2337/diacare.19.2.107 PG 5 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA TR892 UT WOS:A1996TR89200001 PM 8718428 ER PT J AU Gagneten, D Hijazi, YM Jaffe, ES Solomon, D AF Gagneten, D Hijazi, YM Jaffe, ES Solomon, D TI Mantle cell lymphoma: A cytopathological and immunocytochemical study SO DIAGNOSTIC CYTOPATHOLOGY LA English DT Article DE mantle cell lymphoma; cytopathology; immunocytochemistry ID LYMPHOCYTIC LYMPHOMA; INTERMEDIATE DIFFERENTIATION; MALIGNANT-LYMPHOMA; CENTROCYTIC LYMPHOMA; BCL-1 AB Mantle cell lymphoma (MCL) is a rare type of non-Hodgkin's lymphoma which is thought to derive from the cuff of the lymphoid follicle. The histopathologic and immunophenotypic features of MCL are well described. The literature contains few cytopathologic studies of collected cases of MCL. Review of files from the National Institutes of Health from 1989 through June 1993 revealed a total of 24 positive specimens from eight patients with a diagnosis of MCL. The specimens consisted often pleural effusions, ten cerebrospinal fluids (CSF), and four fine-needle aspirations CSF involvement was noted in 3 of 8 (37.5%) patients and was associated with disease progression. The cardinal morphologic features on air-dried, Diff-Quik-stained material are a monotonous population of relatively small atypical lymphoid cells with enlarged, frequently grooved nuclei, coarse chromatin and small nucleoli, scant cytoplasm, and an absence of large or ''transformed'' lymphoid cells. Immunocytochemistry is characterized by expression of one or more pan-B-cell markers, immunoglobulin light-chain restriction, and positivity for the pan-T-cell antigen CD5. When these morphologic and immunocytochemical characteristics are present, the specific diagnosis of MCL can be suggested on cytologic specimens. (C) 1996 Wiley-Liss, Inc.* C1 NATL INST HLTH,PATHOL LAB,BETHESDA,MD 20892. NR 24 TC 18 Z9 19 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 8755-1039 J9 DIAGN CYTOPATHOL JI Diagn. Cytopathol. PD FEB PY 1996 VL 14 IS 1 BP 32 EP 37 DI 10.1002/(SICI)1097-0339(199602)14:1<32::AID-DC7>3.3.CO;2-4 PG 6 WC Medical Laboratory Technology; Pathology SC Medical Laboratory Technology; Pathology GA TT502 UT WOS:A1996TT50200007 PM 8834074 ER PT J AU Ekbom, A Yuen, J Karlsson, BM McLaughlin, JK Adami, HO AF Ekbom, A Yuen, J Karlsson, BM McLaughlin, JK Adami, HO TI Risk of pancreatic and periampullar cancer following cholecystectomy - A population-based cohort study SO DIGESTIVE DISEASES AND SCIENCES LA English DT Article DE cholecystectomy; pancreatic cancer periampullar cancer; epidemiology ID MEDICAL HISTORY; DISEASE; CARCINOMA; ALCOHOL; HAMSTER AB An increased risk of pancreatic cancer following cholecystectomy has been reported in some studies but not in others. In order to settle this question, a population-based cohort consisting of 62,615 patients who had undergone cholecystectomy was followed up for the occurrence of pancreatic and periampullar cancer up to 23 years. After excluding the first year after operation, there were 261 pancreatic cancers vs 216.8 expected [standardized incidence ratio (SIR) = 1.20; 95% confidence interval (CI) = 1.06-1.37]; and 11 periampullar cancers vs 7.2 expected (SIR = 1.52; 95% CI = 0.76-2.72). The increased risk of pancreatic cancer was most prominent up to four years after operation, but was also significantly increased 15 years or more after operation (SIR = 1.35; 95% CI = 1.00-1.78). We conclude that there is a modest excess risk of pancreatic and periampullar cancer following cholecystectomy, most prominent up to four pears after operation, but that also exists 15 years or more after operation. C1 UNIV UPPSALA HOSP,DEPT SURG,S-75185 UPPSALA,SWEDEN. NCI,DIV CANC ETIOL,EPIDEMIOL & BIOSTAT PROGRAM,BETHESDA,MD 20892. HARVARD UNIV,SCH PUBL HLTH,DEPT EPIDEMIOL,BOSTON,MA 02115. RP Ekbom, A (reprint author), UNIV UPPSALA HOSP,DEPT CANC EPIDEMIOL,S-75185 UPPSALA,SWEDEN. NR 25 TC 35 Z9 36 U1 0 U2 0 PU PLENUM PUBL CORP PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 SN 0163-2116 J9 DIGEST DIS SCI JI Dig. Dis. Sci. PD FEB PY 1996 VL 41 IS 2 BP 387 EP 391 DI 10.1007/BF02093833 PG 5 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA TX944 UT WOS:A1996TX94400024 PM 8601387 ER PT J AU Norflus, F Yamanaka, S Proia, RL AF Norflus, F Yamanaka, S Proia, RL TI Promoters for the human beta-hexosaminidase genes, HEXA and HEXB SO DNA AND CELL BIOLOGY LA English DT Article ID CATHEPSIN-D-GENE; ALPHA-GALACTOSIDASE-A; STRUCTURAL ORGANIZATION; N-ACETYLHEXOSAMINIDASE; LYSOSOMAL-ENZYME; CELLS; SEQUENCE; EXPRESSION; HOMOLOGY; CHAIN AB Human lysosomal beta-hexosaminidases are encoded by two genes, HEXA and HEXB, specifying an alpha- and a beta-subunit, respectively. The subunits dimerize to form beta-hexosaminidase A (alpha beta), beta-hexosaminidase B (beta beta), and beta-hexosaminidase S (alpha alpha). This enzyme system has the capacity to degrade a variety of cellular substrates: oligosaccharides, glycosaminoglycans, and glycolipids containing beta-linked N-acetylglucosaminyl or N-galactosaminyl residues, Mutations in either the HEXA gene or HEXB gene lead to an accumulation of G(M2) ganglioside in neurons, resulting in the severe neurodegenerative disorders termed the G(M2) gangliosidoses. To identify the DNA elements responsible for hexosaminidase expression, we ligated the 5'-flanking sequences of both the human and mouse hexosaminidase genes to a chloramphenicol acetyltransferase (CAT) gene. The resulting plasmids were transfected into NIH-3T3 cells and CAT activity was determined as a measure of promoter strength, By 5' deletion analysis, it was found that essential sequences for HEXA expression resided within a 40-bp region between 100 bp and 60 bp upstream of the ATG initiation codon. This area contained two potential estrogen response element half-sites as well as potential binding sites for transcription factors NF-E1 and AP-2. Similarly, important HEXB promoter sequences were localized to a 60-bp region between 150 bp and 90 bp upstream of the ATG codon, By performing scanning mutagenesis on a 60-bp region within the 150-bp HEXB construct, we defined an essential promoter element of 12 bp that contained two potential AP-1 sites. The mouse Hexa and Herb 5'-flanking sequences were found to contain regions similar in sequence, location, and activity to the essential promoter elements defined in the cognate human genes. No sequence similarity was found, however, between 5'-flanking regions of the HEXA and HEXB genes. These essential promoter elements represent potential sites for HEXA and HEXB mutations that could alter enzyme expression in Tay-Sachs and Sandhoff diseases, respectively. RP Norflus, F (reprint author), NIDDKD,NIH,GENET & BIOCHEM BRANCH,SECT BIOCHEM GENET,BLDG 10,ROOM 9D-15,BETHESDA,MD 20892, USA. RI Proia, Richard/A-7908-2012 NR 31 TC 16 Z9 16 U1 1 U2 4 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 FEB PY 1996 VL 15 IS 2 BP 89 EP 97 DI 10.1089/dna.1996.15.89 PG 9 WC Biochemistry & Molecular Biology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Cell Biology; Genetics & Heredity GA TV867 UT WOS:A1996TV86700001 PM 8634145 ER PT J AU Lee, YI Kim, SJ AF Lee, YI Kim, SJ TI Transcriptional repression of human insulin-like growth factor-II P4 promoter by Wilms' tumor suppressor WT1 SO DNA AND CELL BIOLOGY LA English DT Article ID FACTOR-A-CHAIN; GENE-PRODUCT; 3T3 CELLS; EXPRESSION; DELETION; TRANSACTIVATION; SEQUENCES; PROTEINS; BINDING; REGION AB The Wilms' tumor suppressor gene wt1 encodes a zinc finger-containing protein that binds to the same DNA sequence as Egr-1, a mitogen-inducible immediate-early gene product that activates transcription. In this study, we investigated whether the human insulin-like growth factor-II (IGF-II) P4 promoter might be a target for transcriptional repression mediated by WT1. Using constructs of the IGF-II P4 promoter linked to the chloramphenicol acetyltransferase gene, we have demonstrated that the WT1 protein represses expression of the IGF-II gene through a GCGGGGGAG response element spanning nucleotides -87 to -65 of the IGF-II P4 promoter. Conversely, we have shown that the Egr-1 activates transcription of the IGF-II gene through the same response element. WT1 and Egr-1 proteins interact directly with the WT1/Egr-1 response element of the IGF-II promoter 4 in gel mobility-shift assays. These findings demonstrate the importance of the WT1/Egr-1 consensus element for the expression of the IGF-II gene in response to positive or negative transcription signals. C1 KIST,KOREA RES INST BIOSCI & BIOTECHNOL,BIOMED RES GRP,TAEJON 305606,SOUTH KOREA. NCI,CHEMOPREVENT LAB,BETHESDA,MD 20892. NR 28 TC 9 Z9 10 U1 0 U2 0 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 SN 1044-5498 J9 DNA CELL BIOL JI DNA Cell Biol. PD FEB PY 1996 VL 15 IS 2 BP 99 EP 104 DI 10.1089/dna.1996.15.99 PG 6 WC Biochemistry & Molecular Biology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Cell Biology; Genetics & Heredity GA TV867 UT WOS:A1996TV86700002 PM 8634146 ER PT J AU Mercuri, B Wassermann, EM Manganotti, P Ikoma, K Samii, A Hallett, M AF Mercuri, B Wassermann, EM Manganotti, P Ikoma, K Samii, A Hallett, M TI Cortical modulation of spinal excitability: An F-wave study SO ELECTROMYOGRAPHY AND MOTOR CONTROL-ELECTROENCEPHALOGRAPHY AND CLINICAL NEUROPHYSIOLOGY LA English DT Article DE F-wave; motor evoked potentials; transcranial magnetic stimulation; spinal cord; motor cortex; human ID MOTOR CORTEX STIMULATION; MAGNETIC STIMULATION; NEURON EXCITABILITY; SURFACE EMG; H-REFLEXES; INTACT MAN; RESPONSES; MUSCLES; POTENTIATION; MOTONEURONS AB F-waves are known to be highly sensitive to changes in the excitatory state of the spinal cord. This paper describes the effects of subthreshold transcranial magnetic stimulation on the F-waves evoked in hand and foot muscles. In the abductor pollicis brevis muscle, the F-wave was significantly enhanced when the cortical stimulus was given with a delay corresponding approximately to the expected time of collision, i.e., the difference between the mean latency of the F-wave and the mean latency of the motor evoked potential. A second, usually larger facilitatory phase followed the first phase after 2-3 msec, and later peaks of enhancement often occurred. After the enhancement periods, a significant inhibition of the F-wave was usually observed. in the extensor digitorum brevis muscle, the first facilitatory phase was observed some milliseconds earlier than expected in 4 of 5 subjects, and the inhibitory phase was less pronounced. We argue that the sequential arrival of I-waves at the spinal segment could be responsible for the changes observed in the F-wave recorded from the small hand muscle. In the foot muscle, anatomical and technical factors could contribute to the generation of a D-wave. The strong inhibition observed in the F-wave recorded from the hand muscle is likely to be due to the arrival on cu-motoneurons of inhibitory postsynaptic potentials (IPSPs) generated by the cortical stimulus. Our data show that the F-wave is a probe for changes in the spinal cord excitatory state. C1 NINCDS,NIH,MED NEUROL BRANCH,HUMAN MOTOR CONTROL SECT,BETHESDA,MD 20892. RI Ikoma, Katsunori/D-8158-2012 NR 44 TC 52 Z9 53 U1 0 U2 2 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0924-980X J9 ELECTROMYOGR MOTOR C JI Electromyogr. Mot. Control-Electroencephalogr. Clin. Neurophysiol. PD FEB PY 1996 VL 101 IS 1 BP 16 EP 24 DI 10.1016/0013-4694(95)00164-6 PG 9 WC Engineering, Biomedical; Neurosciences SC Engineering; Neurosciences & Neurology GA UB642 UT WOS:A1996UB64200003 PM 8625873 ER PT J AU Belsham, DD Wetsel, WC Mellon, PL AF Belsham, DD Wetsel, WC Mellon, PL TI NMDA and nitric oxide act through the cGMP signal transduction pathway to repress hypothalamic gonadotropin-releasing hormone gene expression SO EMBO JOURNAL LA English DT Article DE cGMP-dependent protein kinase; glutamate; gonadotropin-releasing hormone; nitric oxide; transcriptional repression ID DEPENDENT PROTEIN-KINASE; EXCITATORY AMINO-ACIDS; MESSENGER-RNA; NERVOUS-SYSTEM; CYCLIC-AMP; RELAXING FACTOR; CDNA CLONES; C-FOS; NEURONS; TRANSCRIPTION AB The key roles of the excitatory neurotransmitter glutamate and its second messengers, nitric oxide (NO) and cGMP, in long-term potentiation and neural plasticity are well documented. However, complex functions such as memory are likely to require long term changes in synaptic efficacy which require gene expression and protein synthesis, Here we demonstrate that the glutamate receptor agonist, N-methyl-D-aspartic acid (NMDA), nitric oxide (NO) and cGMP each repress expression of the gonadotropin-releasing hormone (GnRH) gene in the hypothalamic cell line, GT1, This repression is dependent upon signals from NMDA receptors activating NO synthase to synthesize NO, In turn NO induces guanylyl cyclase to synthesize cGMP, activating cGMP-dependent protein kinase, Repression requires elevation of calcium because it only occurs in the presence of a calcium ionophore or with release of intracellular calcium, Repression also requires protein synthesis, Activation of this pathway specifically represses expression of a reporter gene containing the regulatory region of the GnRH gene in transfected GT1 cells, indicating that repression occurs at the transcriptional level. Furthermore the target for transcriptional repression is a 300 bp neuron-specific enhancer found 1.5 kb upstream of the GnRH gene which is sufficient to confer repression to a heterologous promoter. Thus the NMDA/NO/cGMP neurotransmitter signal transduction pathway controls not only synaptic function but also neuron-specific gene expression. C1 UNIV CALIF SAN DIEGO,CTR MOLEC GENET,DEPT REPROD MED & NEUROSCI,LA JOLLA,CA 92093. NIEHS,CELLULAR & MOLEC PHARMACOL LAB,RES TRIANGLE PK,NC 27709. FU NICHD NIH HHS [P50 HD012303, R01 HD072754]; NIDDK NIH HHS [DK44838, R01 DK044838] NR 87 TC 59 Z9 61 U1 0 U2 0 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0261-4189 J9 EMBO J JI Embo J. PD FEB 1 PY 1996 VL 15 IS 3 BP 538 EP 547 PG 10 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA TU925 UT WOS:A1996TU92500010 PM 8599937 ER PT J AU Nightingale, K Dimitrov, S Reeves, R Wolffe, AP AF Nightingale, K Dimitrov, S Reeves, R Wolffe, AP TI Evidence for a shared structural role for HMG1 and linker histones B4 and H1 in organizing chromatin SO EMBO JOURNAL LA English DT Review DE chromatin; histone B4; HMG1; nucleosome; Xenopus ID MOBILITY GROUP PROTEIN-1; NONHISTONE CHROMOSOMAL PROTEIN; MAJOR DEVELOPMENTAL TRANSITION; NONSPECIFIC DNA-BINDING; EARLY XENOPUS-EMBRYOS; RAT-LIVER HMG1; NUCLEOTIDE-SEQUENCE; DROSOPHILA-MELANOGASTER; CRYSTAL-STRUCTURE; H1-LIKE PROTEIN AB The high mobility group proteins 1 and 2 (HMG1/2) and histone B4 are major components of chromatin within the nuclei assembled during the incubation of Xenopus sperm chromatin in Xenopus egg extract, To investigate their potential structural and functional roles, we have cloned and expressed Xenopus HMG1 and histone B4. Purified histone B4 and HMG1 form stable complexes with nucleosomes including Xenopus 5S DNA. Both proteins associate with linker DNA and stabilize it against digestion with micrococcal nuclease, in a similar manner to histone H1, However, neither histone B4 nor HMG1 influence the DNase I or hydroxyl radical digestion of DNA within the nucleosome core. We suggest that HMG1/2 and histone B4 have a shared structural role in organizing linker DNA in the nucleosome. C1 NICHHD,NIH,MOLEC EMBRYOL LAB,BETHESDA,MD 20892. RI dimitrov, stefan/M-7697-2013 NR 106 TC 134 Z9 138 U1 0 U2 0 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0261-4189 J9 EMBO J JI Embo J. PD FEB 1 PY 1996 VL 15 IS 3 BP 548 EP 561 PG 14 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA TU925 UT WOS:A1996TU92500011 PM 8599938 ER PT J AU Hohjoh, H Singer, MF AF Hohjoh, H Singer, MF TI Cytoplasmic ribonucleoprotein complexes containing human LINE-1 protein and RNA SO EMBO JOURNAL LA English DT Article DE human LINE-1 (L1Hs); leucine zipper; retrotransposon; ribonucleoprotein complex; RNA-binding protein ID EMBRYONAL CARCINOMA-CELLS; HUMAN TRANSPOSABLE ELEMENT; OPEN READING FRAMES; DNA-BINDING DOMAIN; LEUCINE ZIPPER; DROSOPHILA-MELANOGASTER; REVERSE TRANSCRIPTION; RETROVIRAL PROTEINS; MAMMALIAN LINES; REPETITIVE DNA AB P40 is the protein encoded by the first open reading frame (ORF1) of the human LINE-1 (L1Hs) retrotransposon; it is 338 amino acids long, has a leucine zipper motif and has been found in human teratocarcinoma cell lines and some tumor cells. In this report, we describe properties of p40 in the human teratocarcinoma cell lines NTera2D1 and 2102Ep. The results indicate that: (i) most of p40 occurs in large multimeric cytoplasmic complexes, (ii) L1Hs RNA is associated with the p40 complexes, (iii) the complexes are dissociated by ribonuclease and (iv) p40 is a novel RNA-binding protein. Cross-linking experiments with full-length and truncated p40 produced in Escherichia coli also showed that: (i) p40 itself can form a multimeric complex larger than 250 kDa, (ii) the leucine zipper motif and the region conserved among the predicted ORF1 polypeptides of mammalian LINE-1s participate in complex formation and (iii) the amino terminal region is important for the stability of complex formation. Analysis of the amino acid sequence of p40 suggests that long segments of the molecule can assume an alpha-helical configuration including the leucine zipper and the conserved region. The evidence presented here suggests that the p40 complex is a ribonucleoprotein complex containing L1Hs RNA(s) and that protein-protein interactions in which alpha-helix structures participate, for example coiled-coils, may occur in the complex. C1 CARNEGIE INST WASHINGTON,WASHINGTON,DC 20005. RP Hohjoh, H (reprint author), NCI,BIOCHEM LAB,NATL INST HLTH,BETHESDA,MD 20892, USA. NR 60 TC 211 Z9 212 U1 0 U2 2 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0261-4189 J9 EMBO J JI Embo J. PD FEB 1 PY 1996 VL 15 IS 3 BP 630 EP 639 PG 10 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA TU925 UT WOS:A1996TU92500019 PM 8599946 ER PT J AU Blakesley, VA Kalebic, T Helman, LJ Stannard, B Faria, TN Roberts, CT LeRoith, D AF Blakesley, VA Kalebic, T Helman, LJ Stannard, B Faria, TN Roberts, CT LeRoith, D TI Tumorigenic and mitogenic capacities are reduced in transfected fibroblasts expressing mutant insulin-like growth factor (IGF)-I receptors. The role of tyrosine residues 1250, 1251, and 1316 in the carboxy-terminus of the IGF-I receptor SO ENDOCRINOLOGY LA English DT Article ID RAPID COLORIMETRIC ASSAY; KINASE-ACTIVITY; ANTIBODY; SURVIVAL; BINDING AB Regulation of ligand-mediated signal transduction through transmembrane tyrosine kinase growth factor receptors involves phosphorylation of tyrosine residues in the intracellular domain of the receptor. The insulin-like growth factor-I (IGF-I) receptor contains three tyrosine residues in the carboxy-terminal domain at positions 1250, 1251, and 1316. Of these, only the tyrosine at position 1316 is conserved in the homologous position of the insulin receptor. Mutational analysis was used to study the role of these tyrosines in specific outcomes of IGF-I-mediated signal transduction. Mutations in the human IGF-I receptor were either replacement of tyrosines 1250 and 1251 with phenylalanine and histidine (yyFH), respectively, or replacement of the conserved distal tyrosine (position 1316) with phenylalanine (yCF). The yyFH mutation results in an IGF-I receptor with the amino acids found in the homologous position of the human insulin receptor. Cells overexpressing mutated IGF-I receptors were compared with cells expressing only endogenous IGF-I receptors or overexpressing wild-type IGF-I receptors. The ability of yyFH mutant IGF-I receptors to autophosphorylate the beta-subunit or phosphorylate insulin receptor substrate-1 was not significantly different from wild-type IGF-I receptors. However, one or both of the proximal tyrosine residues (positions 1250 and 1251) in the carboxy-terminus of the IGF-I receptor are essential for IGF-I-stimulation of mitogenic and tumorigenic pathways. IGF-I-induced mitog enesis, measured as thymidine incorporation and cellular proliferation, was abrogated in cells overexpressing mutant IGF-I receptors with replacement of the proximal double tyrosines (positions 1250 and 1251). Fibroblasts expressing this mutant IGF-I receptor formed fewer tumors than the negative control cells, whereas cells expressing wild-type IGF-I receptors formed large tumors in all recipient mice injected. Conversely, cells expressing mutant IGF-I receptors viith only the conserved distal tyrosine (position 1316) replaced had slightly reduced IGF-I-stimulated beta-subunit autophosphorylation, thymidine incorporation, and cellular proliferation when compared with cells expressing wild-type receptors. Phosphorylation of insulin receptor substrate-1 by the yCF mutant receptors was not impaired. Despite the ability of these mutant receptors to stimulate mitogenic growth, fibroblasts expressing this mutant receptor were also incapable of forming tumors in recipient nude mice. The distal tyrosine (position 1316) of the IGF-I receptor is crucial for tumor formation but is not essential for IGF-I stimulated mitogenesis. Thus, the tyrosine moieties in the carboxy-terminus of the IGF-I receptor participate in the signal transduction pathways that affect the mitogenic and tumorigenic potentials of cells expressing mutant IGF-I receptors. C1 NCI,PEDIAT BRANCH,MOLEC ONCOL SECT,BETHESDA,MD 20892. RP Blakesley, VA (reprint author), NIDDK,DIABET BRANCH,SECT MOLEC & CELLULAR PHYSIOL,BLDG 10,ROOM 8S235A,10 CTR DR MSC 1770,BETHESDA,MD 20892, USA. OI Roberts, Charles/0000-0003-1756-5772 NR 19 TC 57 Z9 58 U1 0 U2 1 PU ENDOCRINE SOC PI BETHESDA PA 4350 EAST WEST HIGHWAY SUITE 500, BETHESDA, MD 20814-4110 SN 0013-7227 J9 ENDOCRINOLOGY JI Endocrinology PD FEB PY 1996 VL 137 IS 2 BP 410 EP 417 DI 10.1210/en.137.2.410 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA TR826 UT WOS:A1996TR82600004 PM 8593783 ER PT J AU Makara, GB Kiss, A Lolait, SJ Aguilera, G AF Makara, GB Kiss, A Lolait, SJ Aguilera, G TI Hypothalamic-pituitary corticotroph function after shunting of magnocellular vasopressin and oxytocin to the hypophyseal portal circulation SO ENDOCRINOLOGY LA English DT Article ID ARGININE-VASOPRESSIN; RAT INTERMEDIATE; GENE-EXPRESSION; MESSENGER-RNA; SECRETION; STRESS; ADRENOCORTICOTROPIN; ACTH; LOCALIZATION; RESPONSES AB Surgical pituitary stalk compression (PSC) causes neural lobe denervation and development of ectopic magnocellular terminals in the external zone of the median eminence, resulting in shunting of magnocellular vasopressin (VP) and oxytocin (OT) to the pituitary portal circulation. To determine the effects of PSC on hypothalamic and pituitary function, VP and CRH receptors and POMC messenger RNA (mRNA) in the pituitary, and CRH, VP, and OT mRNA levels in the PVN were examined in 7-day PSC and sham-operated rats. Immunohistochemical staining revealed marked accumulation of immunoreactive VP in the swollen pituitary stalk and the external zone of the distal median eminence of PSC rats. Plasma ACTH and corticosterone levels were significantly increased by PSC, an effect that was attenuated by minipump infusion of desamino-[D-Arg(8)]-vasopressin (DDAVP) given to correct the diabetes insipidus. [H-3]VP binding to anterior pituitary membranes from PSC rats was reduced by 50% compared to that in sham-operated controls, but VP V1b receptor mRNA levels measured by in situ hybridization were unchanged. Pituitary CRH receptors measured by binding autoradiography and CRH receptor mRNA levels did not change after PSC. POMC mRNA was unchanged in the anterior pituitary lobe, but markedly increased in the intermediate lobe of PSC rats, with or without DDAVP infusion. In the hypothalamic supraoptic and paraventricular nuclei, PSC resulted in reduction of Srp mRNA (-83%) and OT mRNA (-38%) levels, probably reflecting retrograde degeneration of magnocellular neurons. This decrease was more pronounced for VP mRNA than for OT mRNA. CRH mRNA levels in parvicellular cells of the paraventricular nuclei of PSC rats were reduced by 55%. Correction of the diabetes insipidus by DDAVP treatment further decreased hypothalamic VP mRNA levels, but restored CRH mRNA to control levels. The data show that continuous exposure of the pituitary to high VP levels from ectopic magnocellular fibers in the median eminence results in VP, but not CRH, receptor loss. Pituitary VP receptor down-regulation and decreased hypothalamic CRH expression are likely to contribute to the reduced corticotroph responsiveness to VP reported in this experimental model. C1 NICHHD,DEV ENDOCRINOL BRANCH,SECT ENDOCRINE PHYSIOL,BETHESDA,MD 20892. NIMH,CELL BIOL LAB,BETHESDA,MD 20892. HUNGARIAN ACAD SCI,INST EXPTL MED,BUDAPEST,HUNGARY. RI Makara, Gabor/H-8397-2013 OI Makara, Gabor/0000-0001-9220-0373 NR 37 TC 17 Z9 17 U1 0 U2 2 PU ENDOCRINE SOC PI BETHESDA PA 4350 EAST WEST HIGHWAY SUITE 500, BETHESDA, MD 20814-4110 SN 0013-7227 J9 ENDOCRINOLOGY JI Endocrinology PD FEB PY 1996 VL 137 IS 2 BP 580 EP 586 DI 10.1210/en.137.2.580 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA TR826 UT WOS:A1996TR82600027 PM 8593805 ER PT J AU Zhu, XG Yu, CL McPhie, P Wong, R Cheng, SY AF Zhu, XG Yu, CL McPhie, P Wong, R Cheng, SY TI Understanding the molecular mechanism of dominant negative action of mutant thyroid hormone beta(1)-receptors: The important role of the wild-type mutant receptor heterodimer SO ENDOCRINOLOGY LA English DT Article ID LIGAND-BINDING DOMAIN; RETINOIC ACID; GENERALIZED RESISTANCE; RESPONSE ELEMENT; TRANSCRIPTIONAL ACTIVITY; NUCLEAR RECEPTOR; RXR-BETA; DNA; 3,5,3'-TRIIODOTHYRONINE; GENES AB The clinical manifestations of patients with resistance to thyroid hormone result from inhibition of the functions of wild-type thyroid hormone receptors (wTRs) by the dominant negative effect of mutant TR beta 1 receptors (mTR beta 1). One of the proposed mechanisms by which mTR beta 1 exerts its dominant negative action is via formation of the putative inactive wTR beta 1/mTR beta 1 heterodimer. However, the nature of the wTR beta 1/mTR beta 1 heterodimer is poorly understood. The present study characterizes the wTR beta 1/mTR beta 1 heterodimer by electrophoretic mobility shift assay. The mutant TR beta 1 used was PV, which contains a frame shift mutation in the C-terminal part of TR beta 1 and has less than 1% of the T-3 binding affinity of the wTR beta 1. Because of the difficulty in resolving wTR beta 1 and mutant PV dimers, we used a truncated wTR beta 1 in which the A/B domain was deleted (Delta TR beta 1) to demonstrate the formation of the heterodimer on thyroid hormone response elements (TREs) in which the half-site binding motifs are oriented in an inverted repeat (F2), a direct repeat separated by four nucleotides (DR4), or an inverted repeat (Pal). Deletion of the A/B domain had no effect on the binding of T-3 and TREs to wTR beta 1. In the presence of equal amounts of Delta TR beta 1 and PV, three types of molecular complexes, Delta TR beta 1 homodimer, Delta TR beta 1/PV heterodimer, and PV homodimer bound to each TRE in a ratio of approximately 1:2:1. The identities of these complexes were confirmed by their ability to be supershifted by anti-TR beta 1 and/or anti-PV antibodies. Delta TR beta 1/PV heterodimer formation varied with different TREs. The ratio of apparent affinity constant (K-a) in the binding of Delta TR beta 1/PV to TREs was F2:DR4:Pal = approximately 6:2:1. The effect of T-3 on Delta TR beta 1/PV heterodimer formation was TRE dependent. No T-3-induced dissociation was observed for the Delta TR beta 1/PV heterodimer when bound to F2 and Pal. In contrast, the Delta TR beta 1/PV heterodimer bound to DR4 was dissociated by T-3 with an ED(50) of 3.9 +/- 0.9 nM. The T-3-induced dissociation of Delta TR beta 1 homodimer bound to F2, DR4, and Pal had ED(50) values of 4.1 +/- 1.2, 1.3 +/- 0.3, and more than 100 nM, respectively. By transfection assays, the dominant negative action of PV was found to be TRE dependent with the rank order of F2 much greater than Pal > ME (a DR4-like TRE in the rat malic enzyme gene). Taken together, these results indicate a strong correlation between wTR beta 1/mTR beta 1 heterodimer formation and the dominant negative potency of PV. These results suggest that the wTR beta 1/mTR beta 1 het erodimer could play an important role in the dominant negative action of mTR beta 1. C1 NCI, DIV CANC BIOL DIAG & CTR, MOLEC BIOL LAB, BETHESDA, MD 20892 USA. NIDDKD, BIOCHEM PHARMACOL LAB, BETHESDA, MD 20892 USA. NIDDKD, MOLEC & CELLULAR ENDOCRINOL BRANCH, BETHESDA, MD 20892 USA. NR 38 TC 19 Z9 20 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 FEB PY 1996 VL 137 IS 2 BP 712 EP 721 DI 10.1210/en.137.2.712 PG 10 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA TR826 UT WOS:A1996TR82600044 PM 8593822 ER PT J AU Sheridan, PH Jacobs, MP AF Sheridan, PH Jacobs, MP TI The development of antiepileptic drugs for children - Report from the NIH workshop, Bethesda, Maryland, February 17-18, 1994 SO EPILEPSY RESEARCH LA English DT Editorial Material DE pediatric seizure types and syndromes; childhood epilepsy; antiepileptic drug development; clinical trial design RP Sheridan, PH (reprint author), NINCDS,EPILEPSY BRANCH,NIH,BETHESDA,MD 20892, USA. NR 4 TC 16 Z9 16 U1 1 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0920-1211 J9 EPILEPSY RES JI Epilepsy Res. PD FEB PY 1996 VL 23 IS 1 BP 87 EP 92 DI 10.1016/0920-1211(95)00043-7 PG 6 WC Clinical Neurology SC Neurosciences & Neurology GA UD446 UT WOS:A1996UD44600007 PM 8925806 ER PT J AU Tomarev, SI Piatigorsky, J AF Tomarev, SI Piatigorsky, J TI Lens crystallins of invertebrates - Diversity and recruitment from detoxification enzymes and novel proteins SO EUROPEAN JOURNAL OF BIOCHEMISTRY LA English DT Review DE glutathione S-transferase; crystallin; lens; invertebrates; aldehyde dehydrogenase ID GLUTATHIONE S-TRANSFERASES; ANIMAL-BACTERIAL MUTUALISM; HOMEOBOX-CONTAINING GENE; AMINO-ACID-SEQUENCE; ALDEHYDE DEHYDROGENASE; ALPHA-CRYSTALLIN; EYE LENS; PHYSICOCHEMICAL CHARACTERIZATION; CUBOMEDUSAN JELLYFISH; STRUCTURAL PROTEIN AB The major proteins (crystallins) of the transparent, refractive eye lens of vertebrates are a surprisingly diverse group of multifunctional proteins. A number of lens crystallins display taxon-specificity. In general, vertebrate crystallins have been recruited from stress-protective proteins (i.e. the small heat-shock proteins) and a number of metabolic enzymes by a gene-sharing mechanism. Despite the, existence of refractive lenses in the complex and compound eyes of many invertebrates, relatively little is known about their crystallins. Here we review for the first time the state of knowledge of invertebrate crystallins. The major cephalopod (squid, octopus; and cuttlefish) crystallins (S-crystallins) have, like vertebrate crystallins, been recruited from a stress protective metabolic enzyme, glutathione S-transferase. The presence of overlapping AP-1 and antioxidant responsive-like sequences that appear functional in transfected vertebrate cells suggests that the recruitment of glutathione S-transferase to S-crystallins involved response to oxidative stress. Cephalopods also have at least two taxon-specific crystallins: Omega-crystallin, related to aldehyde dehydrogenase, and O-crystallin, related to a superfamily of lipid-binding proteins. L-crystallin (probably identical to Omega-crystallin) is the major protein of the lens of the squid photophore, a specialized structure for emitting light, The use of L/Omega-crystallin in the ectodermal lens of the eye and the mesodermal lens of the photophore of the squid contrasts with the recruitment of different crystallins in the ectodermal lenses of the eye and photophore of fish. S- and Omega-crystallins appear to be lens-specific (some S-crystallins are also expressed in corneal and, except for one S-crystallin polypeptide (SL11/Lops4; possibly a molecular fossil), lack enzymatic activity. The S-crystallins (except SL11/Lops4) contain a variable peptide that has been inserted by exon shuffling. The only other invertebrate crystallins that have been examined are in one marine gastropod (Aplysia, a sea hare), in jellyfish and in the compound eyes of some arthropods; all are different and novel proteins. Drosocrystallin is one of three calcium binding taxon-specific crystallins found selectively in the acellular corneal lens of Drosophilia, while antigen 3G6 is a highly conserved protein present in the ommatidial crystallin cone and central nervous system of numerous arthropods. Cubomedusan jellyfish have three novel crystallin families (the J-crystallins); the J1-crystallins are encoded in three very similar intronless genes with markedly different 5' flanking sequences despite their almost identical encoded proteins and high lens expression. The numerous refractive structures that have evolved in the eyes of invertebrates contrast markedly with the limited information on their protein composition, making this field as exciting as it is underdeveloped. The similar requirement of Pax-6 (and possibly other common transcription factors) for eye development as well as the diversity? taxon-specificity and recruitment of stress-protective enzymes as crystallins suggest that borrowing multifunctional proteins for refraction by a gene sharing strategy may have occurred in invertebrates as it did in vertebrates. C1 NEI, MOLEC & DEV BIOL LAB, NIH, BETHESDA, MD 20892 USA. NR 225 TC 92 Z9 92 U1 3 U2 22 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0014-2956 J9 EUR J BIOCHEM JI Eur. J. Biochem. PD FEB 1 PY 1996 VL 235 IS 3 BP 449 EP 465 DI 10.1111/j.1432-1033.1996.00449.x PG 17 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA TU397 UT WOS:A1996TU39700001 PM 8654388 ER PT J AU Nesterova, M Yokozaki, H McDuffie, E ChoChung, YS AF Nesterova, M Yokozaki, H McDuffie, E ChoChung, YS TI Overexpresson of RII(beta) regulatory subunit of protein kinase A in human colon carcinoma cell induces growth arrest and phenotypic changes that are abolished by site-directed mutation of RII(beta) SO EUROPEAN JOURNAL OF BIOCHEMISTRY LA English DT Article DE protein kinase A; gene transfer; site-directed mutation; growth inhibition; human cancer cells ID MAMMARY EPITHELIAL-CELLS; SELECTIVE CAMP ANALOGS; HL-60 LEUKEMIA-CELLS; AMINO-ACID SEQUENCE; RI-ALPHA-SUBUNIT; CATALYTIC SUBUNIT; HUMAN TESTIS; ANTISENSE OLIGODEOXYNUCLEOTIDE; MOLECULAR-CLONING; GENE-EXPRESSION AB LS-174T human colon carcinoma cells that contain approximately equal amounts of cAMP-dependent protein kinase (PKA) isozymes, PKA-I and PKA-II, were infected with retroviral vectors coding for regulatory (R) and catalytic (C) subunits of human PKA. In cells overexpressing RII(mu) RII(beta), and RII(beta)-P (a RII(beta) mutant at the autophosphorylation site), PKA-II levels increased while PKA-I levels decreased. PKA-I was almost completely eliminated in cells overexpressing RII(beta) or RII(beta)-P. In contrast, overexpression of either RI(alpha) or C-alpha had little or no effect on PKA isozyme levels. Although all infectants expressed high levels of PKA subunit mRNAs in accordance with gene introduction, the R subunit protein expression was reflected in PKA isozyme levels rather than in subunit mRNA levels. Only RII(beta) infectants demonstrated marked growth inhibition in monolayer culture, reduced thymidine incorporation into DNA, and inability to grow in semisolid medium or in serum-free medium. Conversely, all other infectants displayed growth properties similar to uninfected parental cells. The growth-retardation properties of RII(beta) infectants were reflected in their altered phenotypic appearances. Our findings that the mutant RII(beta)-P could not mimic the growth-inhibitory effect of RII(beta) suggest the functional importance of the autophosphorylation site in RII(beta). Our results suggest a role for RII(beta) in the suppression of neoplastic cell growth, and thus abnormal expression of R subunit isoforms of PKA may be involved in neoplastic transformation. C1 NCI,TUMOR IMMUNOL & BIOL LAB,CELLULAR BIOCHEM SECT,NIH,BETHESDA,MD 20892. NR 48 TC 55 Z9 56 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0014-2956 J9 EUR J BIOCHEM JI Eur. J. Biochem. PD FEB 1 PY 1996 VL 235 IS 3 BP 486 EP 494 DI 10.1111/j.1432-1033.1996.00486.x PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA TU397 UT WOS:A1996TU39700005 PM 8654392 ER PT J AU BallardBarbash, R Graubard, I KrebsSmith, SM Schatzkin, A Thompson, FE AF BallardBarbash, R Graubard, I KrebsSmith, SM Schatzkin, A Thompson, FE TI Contribution of dieting to the inverse association between energy intake and body mass index SO EUROPEAN JOURNAL OF CLINICAL NUTRITION LA English DT Article DE body weight; dieting; energy; fat; obesity; physical activity ID NORMAL-WEIGHT INDIVIDUALS; MIDDLE-AGED MEN; DIETARY-FAT; PHYSICAL-ACTIVITY; FOOD-INTAKE; FUNDAMENTAL PRINCIPLES; CALORIC-INTAKE; OBESE SUBJECTS; ADULT FEMALES; SELF-REPORTS AB Objective: To examine the association of energy and % energy from fat with body mass index (BMI) and determine if self-reported dieting altered observed associations. Design: Dietary intake data based on dietary recalls from four nonconsecutive days over a 1 year period were examined relative to BMI. The relation between energy intake and % energy from fat and BMI was examined by linear regression analysis. Subjects: The sample included 1854 free-living women aged 19-50 years who participated in the 1985-6 Continuing Surveys of Food Intakes by Individuals conducted by the United States Department of Agriculture, Results: Reported energy intake was inversely associated with BMI (regression coefficient (beta) = -0.001 24, standard error (s.e.) = 0.000 31). Controlling for low energy dieting alone reduced the inverse energy intake-BMI association by approximately 20% (beta = -0.001 00, s.e. = 0.000 31), compared to reductions of 16%, 13% and 10%, respectively, when health status, age and education were added individually to the energy intake - BMI linear regression. Physical activity, smoking status, % energy from fat and report of low fat dieting did not reduce the energy intake - BMI association. Controlling for nondietary factors related to BMI and potentially influencing energy intake reduced the inverse energy intake - BMI association by similar to 22% (beta = -0.000 97, s.e. = 0.000 25). Further adjustment for low energy dieting on day 1 reduced the inverse energy intake - BMI association by 40% (beta = -0.000 74, s.e. = 0.000 26), suggesting that intermittent energy restriction was a significant factor in the reduced energy intake reported among overweight women. Percent energy from fat was not associated with BMI (beta = 0.049, s.e. = 0.025, P = 0.055). Exclusion of 37 women reporting poor health status further attenuated the inverse association between energy intake and BMI (beta = -0.000 64, s.e. = 0.000 26), while it strengthened the previously non-significant positive association between % energy from fat and BMI (beta = 0.062; s.e. = 0.024). Conclusion: Intermittent energy restriction appeared to be a significant factor in the reduced energy intake reported among overweight women in this sample. Adequate assessment of energy expenditure is required to correctly interpret the association of energy intake to body weight. Sponsorship: National Cancer Institute, National Institutes of Health. Descriptors: body weight, dieting, energy, fat, obesity, physical activity C1 NCI,NIH,DIV CANC PREVENT & CONTROL,CANC PREVENT STUDIES BRANCH,BETHESDA,MD 20892. NCI,NIH,DIV CANC PREVENT & CONTROL,APPL RES BRANCH,BETHESDA,MD 20892. NCI,NIH,DIV CANC PREVENT & CONTROL,BIOMETRY BRANCH,BETHESDA,MD 20892. RI Biguzzi, Felipe/E-4724-2015 NR 56 TC 75 Z9 75 U1 0 U2 11 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE, HAMPSHIRE, ENGLAND RG21 6XS SN 0954-3007 J9 EUR J CLIN NUTR JI Eur. J. Clin. Nutr. PD FEB PY 1996 VL 50 IS 2 BP 98 EP 106 PG 9 WC Nutrition & Dietetics SC Nutrition & Dietetics GA TV641 UT WOS:A1996TV64100004 PM 8641252 ER PT J AU Abrams, SI Stanziale, SF Lunin, SD Zaremba, S Schlom, J AF Abrams, SI Stanziale, SF Lunin, SD Zaremba, S Schlom, J TI Identification of overlapping epitopes in mutant ras oncogene peptides that activate CD4(+) and CD8(+)T cell responses SO EUROPEAN JOURNAL OF IMMUNOLOGY LA English DT Article DE CD8(+) T cell; mutated ras p21; peptide; cytoxicity; immunotherapy ID SYNTHETIC PEPTIDES; LYMPHOCYTES-T; TUMOR-CELLS; FUNCTIONAL-PROPERTIES; LYMPHOKINE SECRETION; BINDING MOTIF; PROTEINS; IMMUNIZATION; PROTOONCOGENES; RECOGNITION AB Mutant ras p21 proteins contain sequences which distinguish them from normal endogenous rats and. thus, may represent unique epitopes for T cell recognition of antigen bearing tumor cells. Here. we examined the capacity of a mutant K-ras 9-mer peptide to induce in vivo CDS cytotoxic T lymphocytes (CTL). The peptide chosen reflected positions 4-12 of the point-mutated sequence of the K-ras oncogene encoding the Gly to Val substitution at codon 12. The overall rationale for selecting this particular 9-mer sequence was threefold: the mutant peptide contained a putative major histocompatibility complex (MHC) class I consensus anchor motif for murine H-2K(1): specific binding to MHC class I may then create an immunogenic complex for the induction of anti-ras CD8(+) CTL: and finally. the mutant sequence overlapped with a newly characterized anti-ras CD4(+) T helper type I epitope. which may have implications for the coordination and activation of both anti-ras immune mechanisms against the same target cell antigenic determinant. A functional interaction with H-2K(d) was demonstrated with the mutant ras4-12(V12) peptide. but not the normal ras4-12(G12) peptide. which specifically inhibited an H-2K(d)-restricted. anti-nucleoprotein NP147-155 CTL response in a dose-dependent fashion. An anti-ras CD8(+) T cell line was then established from immune splenocytes of BALB/c (H-2(d)) mice injected with ras4-12(V12) in adjuvant. which mediated peptide-specific lysis of syngeneic P815 tumor targets. Cytotoxicity was restricted by H-2K(d) and strongly specific for the mutant ras peptide. Importantly, these anti-ras CTL specifically lysed a syngeneic tumor line (i.e. A20 lymphoma) transduced with the corresponding point-mutated ras oncogene. suggesting T cell receptor recognition of endogenously derived antigen. Overall, these data demonstrated that mutant ras p21 at codon 12 (Gly --> Val) contained a peptide sequence which exhibited specific functional binding to a murine MHC class I molecule: the ability of the mutant. but not the normal sequence to bind selectively to murine MHC class I likely reflected the generation of a C-terminal anchor residue: and the ras 4-12(V12) peptide was immunogenic for the production of antigen-specific CD8(+) CTL. which lysed in vitro a syngeneic tumor cell line harboring the mutant K-ras oncogene. C1 NCI,TUMOR IMMUNOL & BIOL LAB,BETHESDA,MD 20892. HOWARD HUGHES MED INST,RES SCHOLARS PROGRAM,BETHESDA,MD. NR 36 TC 47 Z9 47 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 FEB PY 1996 VL 26 IS 2 BP 435 EP 443 DI 10.1002/eji.1830260225 PG 9 WC Immunology SC Immunology GA UJ662 UT WOS:A1996UJ66200024 PM 8617315 ER PT J AU Doucet, JP Nakabeppu, Y Bedard, PJ Hope, BT Nestler, EJ Jasmin, BJ Chen, JS Iadarola, MJ StJean, M Wigle, N Blanchet, P Grondin, R Robertson, GS AF Doucet, JP Nakabeppu, Y Bedard, PJ Hope, BT Nestler, EJ Jasmin, BJ Chen, JS Iadarola, MJ StJean, M Wigle, N Blanchet, P Grondin, R Robertson, GS TI Chronic alterations in dopaminergic neurotransmission produce a persistent elevation of Delta FosB-like protein(s) in both the rodent and primate striatum SO EUROPEAN JOURNAL OF NEUROSCIENCE LA English DT Article DE immediate-early genes; 6-hydroxydopamine; MPTP; striatonigral neurons; striatopallidal neurons; dyskinesia ID TRANSCRIPTION FACTOR AP-1; IMMEDIATE-EARLY GENE; DNA-BINDING ACTIVITY; C-FOS; SUBSTANCE-P; 6-HYDROXYDOPAMINE LESIONS; STRIATOPALLIDAL NEURONS; IMMUNOHISTOCHEMICAL EVIDENCE; RECEPTOR AGONISTS; GLOBUS PALLIDUS AB Using an antibody that recognizes the products of all known members of the fos family of immediate early genes, it was demonstrated that destruction of the nigrostriatal pathway by 6-hydroxydopamine (6-OHDA) lesions of the medial forebrain bundle produces a prolonged (>3 months) elevation of Fos-like immunoreactivity in the striatum. Using retrograde tract tracing techniques, we have previously shown that this increase in Fos-like immunoreactivity is located predominantly in striatal neurons that project to the globus pallidus. In the present study, Western blots were performed on nuclear extracts from the intact and denervated striatum of 6-OHDA-lesioned rats to determine the nature of Fos-immunoreactive protein(s) responsible for this increase. Approximately 6 weeks after the 6-OHDA lesion, expression of two Fos-related antigens with apparent molecular masses of 43 and 45 kDa was enhanced in the denervated striatum. Chronic haloperidol administration also selectively elevated expression of these Fos-related antigens, suggesting that their induction after dopaminergic denervation is mediated by reduced activation of De-like dopamine receptors. Western blot immunostaining using an antibody which recognizes the N-terminus of FosB indicated that the 43 and 45 kDa Fos-related antigens induced by dopaminergic denervation and chronic haloperidol administration may be related to a truncated from of FosB known as Delta FosB. Consistent with this proposal, retrograde tracing experiments confirmed that Delta FosB-like immunoreactivity in the deafferented striatum was located predominantly in striatopallidal neurons. Gel shift experiments demonstrated that elevated AP-1 binding activity in denervated striata contained FosB-like protein(s), suggesting that enhanced Delta FosB levels may mediate some of the effects of prolonged dopamine depletion on AP-l-regulated genes in striatopallidal neurons. In contrast, chronic administration of the D1-like receptor agonist CY 208-243 to 6-OHDA-lesioned rats dramatically enhanced Delta FosB-like immunoreactivity in striatal neurons projecting to the substantia nigra. Western blot immunostaining revealed that Delta FosB and, to a lesser extent, FosB are elevated by chronic D1-like agonist administration. Both the quantitative reverse transcriptase-polymerase chain reaction and the ribonuclease protection assay demonstrated that Delta fosB mRNA levels were substantially enhanced in the denervated striatum by chronic D1-like agonist administration. Lastly, we examined the effects of chronic administration of D1-like and D2-like dopamine receptor agonists on striatal Delta FosB expression in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) primate model of Parkinson's disease. In monkeys rendered Parkinsonian by MPTP, there was a modest increase in Delta FosB-like protein(s), while the development of dyskinesia produced by chronic D1-like agonist administration was accompanied by large increases in Delta FosB-like protein(s). In contrast, administration of the long-acting D2-like agonist cabergoline, which alleviated Parkinsonian symptoms without producing dyskinesia reduced Delta FosB levels to near normal. Taken together, these results demonstrate that chronic alterations in dopaminergic neurotransmission produce a persistent elevation of Delta FosB-like protein(s) in both the rodent and primate striatum. C1 UNIV OTTAWA,DEPT PHARMACOL,OTTAWA,ON K1H 8M5,CANADA. UNIV OTTAWA,DEPT PHYSIOL,OTTAWA,ON K1H 8M5,CANADA. KYUSHU UNIV 69,MED INST BIOREGULAT,DEPT BIOCHEM,FUKUOKA 812,JAPAN. HOP ENFANTS JESUS,CTR RECH NEUROBIOL,QUEBEC CITY,PQ G1J 1Z4,CANADA. YALE UNIV,DEPT PSYCHIAT,NEW HAVEN,CT 06508. YALE UNIV,DEPT PHARMACOL,NEW HAVEN,CT 06508. NIDR,NIH,NEUROBIOL & ANESTHESIA BRANCH,BETHESDA,MD 20892. RI Hope, Bruce/A-9223-2010; Nakabeppu, Yusaku/A-8902-2011 OI Hope, Bruce/0000-0001-5804-7061; NR 70 TC 161 Z9 162 U1 0 U2 10 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0953-816X J9 EUR J NEUROSCI JI Eur. J. Neurosci. PD FEB PY 1996 VL 8 IS 2 BP 365 EP 381 DI 10.1111/j.1460-9568.1996.tb01220.x PG 17 WC Neurosciences SC Neurosciences & Neurology GA TV906 UT WOS:A1996TV90600013 PM 8714707 ER PT J AU Abdo, KM Kari, FW AF Abdo, KM Kari, FW TI The sensitivity of the NTP bioassay for carcinogen hazard evaluation can be modulated by dietary restriction SO EXPERIMENTAL AND TOXICOLOGIC PATHOLOGY LA English DT Article; Proceedings Paper CT 2nd Conference of the International-Federation-of-Societies-of-Toxicologic-Pathologists (IFSTP) CY APR 23-26, 1995 CL TOURS, FRANCE SP IFSTP DE carcinogen hazard evaluation; NTP bioassay; bioassay, NTP; dietary restriction, carcinogen hazard evaluation ID NUTRITIONAL INFLUENCES; FISCHER-344 RATS; TUMOR TRENDS; F344/N RATS; BODY-WEIGHT; TUMORIGENESIS; SURVIVAL; GROWTH; PERIOD AB Studies were undertaken to compare outcomes when four chemicals were evaluated under typical NTP bioassay conditions as well as by protocols employing dietary restriction. Four Chemicals, using three different routes of exposure (in utero [accomplished by feeding the dam dosed feed], dosed feed, and gavage) were used to 1) evaluate the effect of diet restriction on the sensitivity of the bioassay toward chemically-induced chronic toxicity and carcinogenicity; and 2) evaluate the effect of weight-matched control groups on the sensitivity of the bioassays. Control and chemical exposed F344 rats and B6C3F1 mice (50-60/group) were fed NIH-07 diet either ad libitum or at restricted levels such that body weights were similar to 80 % of ad libitum control weights. The dietary restricted groups were either sacrificed at the end of two or 3-years. Results consistently show that feed restriction decreased the incidence of neoplastic and non-neoplastic lesions at a variety of anatomic sites in both control and chemical exposed animals. Furthermore, the sensitivity of the bioassay to detect chemical carcinogenic response were altered by dietary restriction: three of the four chemicals were found to increase the incidence of neoplastic lesions at four sites when evaluated under standard ad libitum conditions for 104 weeks. When unexposed and exposed groups were both subjected to dietary restriction, none of these 4 sites were detected as a target for carcinogenesis after two or three years. Rather, two different sites of carcinogenesis were detected. When the top dosed ad libitum fed animals were compared against their weight-matched control groups, a total of 10 sites were identified as targets for carcinogenesis. These included all four sites identified under the ad libitum protocol, both sites identified unter the feed restricted protocol, and an additional four sites that were not identified under the other two protocols. These studies show that dietary restriction of all animals can be expected of decrease the sensitivity of carcinogenesis bioassays. However, restricting only unexposed groups (weight matching) of control for non-specific weight loss in chemical exposed groups yielded the most sensitivity among our comparisons. RP Abdo, KM (reprint author), NIEHS,POB 12233,RES TRIANGLE PK,NC 27709, USA. NR 23 TC 16 Z9 16 U1 0 U2 1 PU GUSTAV FISCHER VERLAG JENA PI JENA PA VILLENGANG 2, D-07745 JENA, GERMANY SN 0940-2993 J9 EXP TOXICOL PATHOL JI Exp. Toxicol. Pathol. PD FEB PY 1996 VL 48 IS 2-3 BP 129 EP 137 PG 9 WC Pathology; Toxicology SC Pathology; Toxicology GA TY331 UT WOS:A1996TY33100006 PM 8672866 ER PT J AU Spivak, JL Ferris, DK Fisher, J Noga, SJ Isaacs, M Connor, E Hankins, WD AF Spivak, JL Ferris, DK Fisher, J Noga, SJ Isaacs, M Connor, E Hankins, WD TI Cell cycle-specific behavior of erythropoietin SO EXPERIMENTAL HEMATOLOGY LA English DT Article; Proceedings Paper CT 1995 Annual Meeting of the ISEH CY 1995 CL DUSSELDORF, GERMANY SP Int Soc Exptl Hematol DE erythropoietin; cell cycle; p34cdc2; erythropoietin receptor ID ERYTHROID PROGENITOR CELLS; COLONY-FORMING-UNITS; INDUCED-DIFFERENTIATION; PRECURSOR CELLS; TYROSINE KINASE; GENE-EXPRESSION; PROTEIN-KINASE; BONE-MARROW; S-PHASE; RECEPTOR AB The murine erythropoietin-dependent erythroleukemia cell line, HCD-57, was employed to study the cell cycle-specific behavior of erythropoietin. Cell cycle duration for HCD-57 cells was approximately 12 hours and was uninfluenced by erythropoietin. Populations of HCD-57 cells synchronized in G(1) by centrifugal elutriation were able to pass through one complete cell cycle in the absence of erythropoietin but, thereafter, arrested in G(1) as identified by propidium iodide staining and flow cytometry. Analysis of cell cycle behavior using the metachromic dye acridine orange, however, revealed that HCD-57 cells pass through a G(0) cell cycle phase and, like serum-deprived 3T3 cells, actually arrest in G(0) when deprived of erythropoietin. Expression of the cell cycle regulatory protein p34cdc2 was invariant throughout the cell cycle in HCD-57 cells. p34cdc2 was constitutively phosphorylated in G(0) cells, and this effect was not modified by erythropoietin. Erythropoietin receptor distribution was log normal in HCD-57 cells in each phase of the cell cycle. The affinity of these surface receptors for erythropoietin was essentially invariant throughout the cell cycle, but receptor expression was upregulated in G(2)M cells as compared with cells in G(1) or S phase. Taken together, these data indicate that erythropoietin has an important role in the G(0)-G(1) to S phase transition but, based on receptor expression, is involved in other phases of the cell cycle as well. C1 JOHNS HOPKINS UNIV,SCH MED,CTR ONCOL,BALTIMORE,MD 21205. NCI,FREDERICK CANC RES & DEV CTR,BIOL CARCINOGENESIS & DEV PROGRAM,FREDERICK,MD. RP Spivak, JL (reprint author), JOHNS HOPKINS UNIV,SCH MED,DIV HEMATOL,TRAYLOR 924,720 RUTLAND AVE,BALTIMORE,MD 21205, USA. FU NIDDK NIH HHS [DK16702] NR 65 TC 11 Z9 12 U1 1 U2 2 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 FEB PY 1996 VL 24 IS 2 BP 141 EP 150 PG 10 WC Hematology; Medicine, Research & Experimental SC Hematology; Research & Experimental Medicine GA TX753 UT WOS:A1996TX75300009 PM 8641335 ER PT J AU Crosier, PS Freeman, SA Orlic, D Bodine, DM Crosier, KE AF Crosier, PS Freeman, SA Orlic, D Bodine, DM Crosier, KE TI The Dtk receptor tyrosine kinase, which binds protein S, is expressed during hematopoiesis SO EXPERIMENTAL HEMATOLOGY LA English DT Article; Proceedings Paper CT 1995 Annual Meeting of the ISEH CY 1995 CL DUSSELDORF, GERMANY SP Int Soc Exptl Hematol DE receptor tyrosine kinases; Dtk; Ufo; hematopoiesis ID GENE AB Dtk (Tyro 3/Sky/Rse/Brt/Tif) belongs to a recently recognized subfamily of receptor tyrosine kinases that also includes Ufo (Axl/Ark) and Mer (Eyk). Ligands for Dtk and Ufo have been identified as protein S and the related molecule Gas6, respectively. This study examined expression of Dtk during ontogeny of the hematopoietic system and compared the pattern of expression with that of Ufo. Both receptors were abundantly expressed in differentiating embryonic stem cells, yolk sac blood islands, para-aortic splanchnopleural mesoderm, fractionated AA4(+) fetal liver cells, and fetal thymus from day 14 until birth. Although Ufo was expressed at moderate levels in adult bone marrow, expression of Dtk in this tissue was barely detectable. In adult bone marrow subpopulations fractionated using counterflow centrifugal elutriation, immunomagnetic bead selection for lineage-depletion and FAGS sorting for c-kit expression, very low levels of Dtk and/or Ufo were detected in some cell fractions. These results suggest that Dtk and Ufo are likely to be involved in the regulation of hematopoiesis, particularly during the embryonic stages of blood cell development. C1 UNIV AUCKLAND,SCH MED,DEPT MOLEC MED,AUCKLAND,NEW ZEALAND. NIH,NATL CTR HUMAN GENOME RES,HEMATOPOIESIS SECT,BETHESDA,MD 20892. NR 27 TC 27 Z9 28 U1 0 U2 0 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 FEB PY 1996 VL 24 IS 2 BP 318 EP 323 PG 6 WC Hematology; Medicine, Research & Experimental SC Hematology; Research & Experimental Medicine GA TX753 UT WOS:A1996TX75300034 PM 8641360 ER PT J AU Kaufmann, WK Paules, RS AF Kaufmann, WK Paules, RS TI DNA damage and cell cycle checkpoints SO FASEB JOURNAL LA English DT Review DE mutation; cyclin-dependent kinase; carcinogenesis; DNA repair; DNA replication; mitosis ID ATAXIA-TELANGIECTASIA; HUMAN FIBROBLASTS; REPAIR; REPLICATION; INHIBITION; INVITRO AB DNA is prone to numerous forms of damage that can injure cells and impair fitness, Cells have evolved an array of mechanisms to repair these injuries, Proliferating cells are especially vulnerable to DNA damage due to the added demands of cellular growth and division. Cell cycle checkpoints represent integral components of DNA repair that coordinate cooperation between the machinery of the cell cycle and several biochemical pathways that respond to damage and restore DNA structure, By delaying progression through the cell cycle, checkpoints provide more time for repair before the critical phases of DNA replication, when the genome is replicated, and of mitosis, when the genome is segregated, Loss or attenuation of checkpoint function may increase spontaneous and induced gene mutations and chromosomal aberrations by reducing the efficiency of DNA repair, Defects in checkpoint control have been seen in certain hereditary cancer syndromes and at early stages of cell transformation, Mutations in checkpoint control genes therefore may contribute to the genetic instability that appears to drive neoplastic evolution. C1 UNIV N CAROLINA,DEPT PATHOL,CHAPEL HILL,NC 27599. NIEHS,GROWTH CONTROL & CANC GRP,RES TRIANGLE PK,NC 27709. RP Kaufmann, WK (reprint author), UNIV N CAROLINA,LINEBERGER COMPREHENS CANC CTR,CB 7295,RM 351,CHAPEL HILL,NC 27599, USA. FU NCI NIH HHS [CA42765] NR 44 TC 206 Z9 214 U1 0 U2 6 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0892-6638 J9 FASEB J JI Faseb J. PD FEB PY 1996 VL 10 IS 2 BP 238 EP 247 PG 10 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA TY962 UT WOS:A1996TY96200008 PM 8641557 ER PT J AU Sei, Y Whitesell, L Kustova, Y Paul, IA Morse, HC Skolnick, P Basile, AS AF Sei, Y Whitesell, L Kustova, Y Paul, IA Morse, HC Skolnick, P Basile, AS TI Altered brain fyn kinase in a murine acquired immunodeficiency syndrome SO FASEB JOURNAL LA English DT Article DE AIDS; animal model; brain; dementia; fyn; glutamate; murine leukemia virus; tyrosine phosphorylation ID RETROVIRUS-INDUCED IMMUNODEFICIENCY; LONG-TERM POTENTIATION; CENTRAL-NERVOUS-SYSTEM; TYROSINE KINASES; RECEPTOR; ACTIVATION; AIDS; MICE; HIPPOCAMPUS; PROTEIN AB Mice infected with the replication-defective virus (BM5def) in the LP-BM5 murine leukemia virus (MuLV) mixture develop an immune deficiency syndrome and encephalopathy characterized by impaired spatial learning and memory as demonstrated in the Morris water maze. However, the molecular mechanism (or mechanisms) underlying this cognitive deficit remains unknown. Here we report that brain fyn kinase, which has been proposed to be involved in spatial learning and memory, was unresponsive to glutamatergic stimulation in mice with MAIDS. Thus, whereas application of glutamate to hippocampal slices from control mice increased fyn protein tyrosine kinase (PTK) activity more than 2.5-fold, these changes were significantly impaired in LP-BM5 MuLV-infected mice. Moreover, mice with MAIDS exhibited an abnormal histological distribution of fyn PTK in the hippocampus, These findings suggest that virus-associated disruption of fyn kinase-mediated signaling contributes to the cognitive deficits observed in mice with MAIDS and other retrovirus-induced encephalopathies. C1 NIDDKD,NEUROSCI LAB,NIH,BETHESDA,MD 20892. NCI,CLIN PHARMACOL BRANCH,TUMOR CELL BIOL SECT,NIH,BETHESDA,MD 20892. NIAID,IMMUNOPATHOL LAB,NIH,BETHESDA,MD 20892. OI Morse, Herbert/0000-0002-9331-3705 FU NIAID NIH HHS [N01 AI 45203] NR 32 TC 12 Z9 12 U1 2 U2 2 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0892-6638 J9 FASEB J JI Faseb J. PD FEB PY 1996 VL 10 IS 2 BP 339 EP 344 PG 6 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA TY962 UT WOS:A1996TY96200019 PM 8641568 ER PT J AU Morrow, PE Haseman, JK Hobbs, CH Driscoll, KE Vu, V Oberdorster, G AF Morrow, PE Haseman, JK Hobbs, CH Driscoll, KE Vu, V Oberdorster, G TI The maximum tolerated dose for inhalation bioassays: Toxicity vs overload SO FUNDAMENTAL AND APPLIED TOXICOLOGY LA English DT Editorial Material ID MACROPHAGE-MEDIATED INDUCTION; OXYGEN RADICAL SCAVENGERS; DIESEL-ENGINE EMISSIONS; PULMONARY RESPONSE; TITANIUM-DIOXIDE; RATS; EXPOSURE; ASBESTOS; FIBERS; HAMSTERS C1 UNIV ROCHESTER, DEPT ENVIRONM MED, ROCHESTER, NY 14642 USA. NIEHS, STAT & BIOMATH BRANCH, RES TRIANGLE PK, NC 27709 USA. INHALAT TOXICOL RES INST, ALBUQUERQUE, NM 87185 USA. PROCTER & GAMBLE CO, MIAMI VALLEY LABS, CINCINNATI, OH 45253 USA. US EPA, OFF POLLUT PREVENT & TOX, WASHINGTON, DC 20460 USA. NR 68 TC 23 Z9 23 U1 1 U2 2 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0272-0590 J9 FUND APPL TOXICOL JI Fundam. Appl. Toxicol. PD FEB PY 1996 VL 29 IS 2 BP 155 EP 167 DI 10.1006/faat.1996.0017 PG 13 WC Toxicology SC Toxicology GA TX206 UT WOS:A1996TX20600001 PM 8742311 ER PT J AU Hawk, E Prindiville, S Kelloff, G AF Hawk, E Prindiville, S Kelloff, G TI NSAID trials, sporadic adenomas, and conservative inferences SO GASTROENTEROLOGY LA English DT Letter RP Hawk, E (reprint author), NCI,DIV CANC PREVENT & CONTROL,BETHESDA,MD 20892, USA. NR 3 TC 3 Z9 3 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD FEB PY 1996 VL 110 IS 2 BP 654 EP 654 DI 10.1053/gast.1996.v110.agast960654 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA TT975 UT WOS:A1996TT97500047 PM 8566622 ER PT J AU Tio, TL AF Tio, TL TI The TNM staging system SO GASTROINTESTINAL ENDOSCOPY LA English DT Article; Proceedings Paper CT 10th International Symposium on Endoscopic Ultrasonography CY OCT 25-27, 1995 CL CLEVELAND, OH SP Univ Hosp Cleveland, Div Gastroenterol, Univ Hosp Cleveland, Digest Dis Ctr, Case Western Reserve Univ, Amer Endosonog Club, Amer Soc Gastrointestinal Endoscopy ID CLASSIFICATION; CARCINOMA; ENDOSONOGRAPHY C1 NIH,BETHESDA,MD 20892. RP Tio, TL (reprint author), GEORGETOWN UNIV,MED CTR,DIV GASTROENTEROL,2W,ROOM 212Z,3800 RESERVOIR RD NW,WASHINGTON,DC 20007, USA. NR 16 TC 9 Z9 9 U1 0 U2 1 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 SN 0016-5107 J9 GASTROINTEST ENDOSC JI Gastrointest. Endosc. PD FEB PY 1996 VL 43 IS 2 SU S BP S19 EP S24 PN 2 PG 6 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA TX115 UT WOS:A1996TX11500007 PM 8929802 ER PT J AU Muhlhauser, J Jones, M Yamada, I Cirielli, C Lemarchand, P Gloe, TR Bewig, B Signoretti, S Crystal, RG Capogrossi, MC AF Muhlhauser, J Jones, M Yamada, I Cirielli, C Lemarchand, P Gloe, TR Bewig, B Signoretti, S Crystal, RG Capogrossi, MC TI Safety and efficacy of in vivo gene transfer into the porcine heart with replication-deficient, recombinant adenovirus vectors SO GENE THERAPY LA English DT Article DE adenovirus; gene therapy; myocardium; minipig ID HUMAN ENDOTHELIAL-CELLS; MEDIATED TRANSFER; DIRECT-INJECTION; INVIVO; EXPRESSION; MYOCARDIUM; DELIVERY; CDNA; DNA AB Gene transfer with replication-deficient recombinant adenovirus (Ad) vectors may provide a novel approach to the treatment of some cardiac disorders. The relative efficiency of intramyocardial vs intracoronary Ad vector injection in transducing myocardial cells remains to be determined. Further, Ad vectors are associated with localized inflammation, and this could be associated with clinically significant side-effects. Female minipigs underwent open chest surgery and the Ad vector AdCMV.NLS beta-gal was injected into the circumflex coronary artery (IC;2x10(10) p.f.u.; n=5) or the posterobasal wall of the left ventricle (i.m.; 5x10(9) p.f.u., n=4; 2x10(10) p.f.u., n=18). The minipigs were killed after 2-31 days and the hearts examined for evidence of beta-galactosidase activity. Minipigs underwent epicardial echocardiography immediately before, within 15 min following the i.m. injection of AdCMV.NLS beta-gal and again at the time of death. Blood samples for white blood cell count, alkaline phosphatase, total bilirubin, blood urea nitrogen, creatinine and electrolytes were obtained before i.m. and i.c. injection of the Ad vector and before death. Intramuscular injection of the Ad vector was more efficient than i.c. infusion in infecting cells in a localized area of the heart. Myocardial beta-gal activity peaked at 3-6 days after i.m. injection and returned to its control value within 1 month. Although inflammatory cells were present at the injection site, echocardiograms did not show any evidence of either segmental or global left ventricular dysfunction. No minipigs died and all blood tests remained within normal limits following either i.m. or i.c. exposure to the Ad vector. In summary, direct i.m. administration of replication-deficient, recombinant Ad vectors provides a safe and effective approach for short-term gene transfer into the heart of large mammals. C1 NHLBI,NIH,PULM BRANCH,BETHESDA,MD 20892. NHLBI,NIH,LAB ANIM MED & SURG,BETHESDA,MD 20892. CORNELL UNIV,MED CTR,NEW YORK HOSP,DIV PULM & CRIT CARE MED,NEW YORK,NY 10021. IST DERMOPAT IMMACOLATA,LAB PATOL VASC,ROME,ITALY. RI lemarchand, patricia/C-3247-2011 NR 30 TC 95 Z9 97 U1 0 U2 2 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE, HAMPSHIRE, ENGLAND RG21 6XS SN 0969-7128 J9 GENE THER JI Gene Ther. PD FEB PY 1996 VL 3 IS 2 BP 145 EP 153 PG 9 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA TZ787 UT WOS:A1996TZ78700007 PM 8867862 ER PT J AU Aki, T Choy, HE Adhya, S AF Aki, T Choy, HE Adhya, S TI Histone-like protein HU as a specific transcriptional regulator: Co-factor role in repression of gal transcription by GAL repressor SO GENES TO CELLS LA English DT Article ID OPEN COMPLEX-FORMATION; DNA-BINDING PROTEINS; ESCHERICHIA-COLI; GALACTOSE OPERON; RNA-POLYMERASE; STRAND SEPARATION; LAC OPERATORS; CYCLIC-AMP; PROMOTER; INVITRO AB Background: Transcription initiation from the two overlapping promoters of the gal operon in Escherichia coli is negatively regulated by binding of Gal repressor (GalR) to bipartite operators, which encompass the promoters, Coordinated repression of the two promoters requires GalR binding to both operators. In a purified system, GalR, nevertheless, fails to show the coordinated repression, predicting the participation of an additional factor(s) in the regulation in vivo. Results: We have purified a protein that restored the expected GalR-mediated repression for the in vitro system and have identified this factor to be the bacterial histone-like protein HU. In vitro transcription assays in the presence of GalR and HU show that, just as in vivo, the coordinated repression of the two gal promoters requires GalR binding to both operators and is sensitive to the inducer, D-galactose. The GalR and HU dependent repression also requires supercoiled DNA template and prevents open complex formation. Conclusion: We propose that HU, acting as a co-factor, brings about the GalR-mediated repression by forming a distinct nucleoprotein complex of higher order structure. Although how HU participates in the assembly process is unknown, there may be a cooperative effect in the formation of the repression complex. C1 NCI,MOL BIOL LAB,NIH,BETHESDA,MD 20892. RI Aki, Tsunehiro/B-6719-2012 OI Aki, Tsunehiro/0000-0001-9753-2043 NR 50 TC 78 Z9 78 U1 0 U2 1 PU BLACKWELL SCIENCE LTD PI OXFORD PA OSNEY MEAD, OXFORD, OXON, ENGLAND OX2 0EL SN 1356-9597 J9 GENES CELLS JI Genes Cells PD FEB PY 1996 VL 1 IS 2 BP 179 EP 188 DI 10.1046/j.1365-2443.1996.d01-236.x PG 10 WC Cell Biology; Genetics & Heredity SC Cell Biology; Genetics & Heredity GA VC843 UT WOS:A1996VC84300004 PM 9140062 ER PT J AU Chattoraj, DK Ghirlando, R Park, K Dibbens, JA Lewis, MS AF Chattoraj, DK Ghirlando, R Park, K Dibbens, JA Lewis, MS TI Dissociation kinetics of RepA dimers: Implications for mechanisms of activation of DNA binding by chaperones SO GENES TO CELLS LA English DT Article ID SHOCK PROTEINS DNAJ; CIRCULAR-DICHROISM SPECTRA; P1 PLASMID REPLICATION; SECONDARY-STRUCTURE; INITIATOR PROTEIN; ORIGIN; GRPE; MONOMERIZATION; PREDICTION; ELEMENTS AB Background: The replication initiator of plasmid P1, RepA, binds DNA as monomer. The binding is stimulated by the chaperones DnaJ, DnaK and GrpE of Escherichia coli. Two models of chaperone action have been proposed. (i) Chaperones dissociate RepA dimers, which are inactive in DNA binding, into active monomers. (ii) The dissociation occurs spontaneously but the monomeric products require the chaperones for refolding into the active form. The latter model was based on the observation that RepA diluted 1000-fold below the KD for dimer dissociation, still required the chaperones for DNA binding. Results: We have confirmed that under condition of DNA binding experiments, the RepA dimers dissociate reversibly into monomers with a K-D value of 1.1 +/- 0.1 mu M. In the vicinity of this concentration, the sedimentation coefficient of RepA was concentration dependent, allowing estimation of s(20,w) coefficients for the RepA monomer (2.95 S) and dimer (4.01 S). Dynamic light scattering experiments indicated an increase of the monomer fraction within 5 min of RepA dilution. Circular dichroism (CD) measurements were consistent with these results. Conclusion: RepA monomerization is efficient without the mediation of chaperones. They are required to activate RepA most likely because they are needed to re-fold RepA monomers. C1 NCI,BIOCHEM LAB,NIH,BETHESDA,MD 20892. NIDDK,MOL BIOL LAB,NIH,BETHESDA,MD 20892. NIH,NCRR,BIOMED ENGN & INSTRUMENTAT PROGRAM,BETHESDA,MD 20892. RI Ghirlando, Rodolfo/A-8880-2009 NR 30 TC 16 Z9 16 U1 0 U2 0 PU BLACKWELL SCIENCE LTD PI OXFORD PA OSNEY MEAD, OXFORD, OXON, ENGLAND OX2 0EL SN 1356-9597 J9 GENES CELLS JI Genes Cells PD FEB PY 1996 VL 1 IS 2 BP 189 EP 199 DI 10.1046/j.1365-2443.1996.d01-235.x PG 11 WC Cell Biology; Genetics & Heredity SC Cell Biology; Genetics & Heredity GA VC843 UT WOS:A1996VC84300005 PM 9140063 ER PT J AU Blanco, JCG Dey, A Leid, M Minucci, S Park, BK Jurutka, PW Haussler, MR Ozato, K AF Blanco, JCG Dey, A Leid, M Minucci, S Park, BK Jurutka, PW Haussler, MR Ozato, K TI Inhibition of ligand induced promoter occupancy in vivo by a dominant negative RXR SO GENES TO CELLS LA English DT Article ID THYROID-HORMONE RECEPTOR; RETINOIC ACID RECEPTOR; EMBRYONAL CARCINOMA-CELLS; D-RESPONSIVE ELEMENT; X-RECEPTOR; TRANSCRIPTIONAL ACTIVATION; IN-VIVO; V-ERBA; DEPENDENT TRANSACTIVATION; ESTROGEN-RECEPTOR AB Background: Retinoid X receptors (RXRs) heterodimerize with other nuclear hormone receptors and control ligand mediated transcription. To address how RXRs function as heterodimers, we investigated activities of truncated RXR alpha. and RXR beta that lack approximate to 20 conserved C-terminal amino acids. Results: The truncated RXRs formed heterodimers and bound to respective DNA elements in vitro. By transient reporter assays we found that these RXRs act as dominant negative receptors and inhibit ligand dependent transcription by the retinoic acid receptor (RAR) and vitamin D receptor. P19 embryonal carcinoma cells stably expressing the truncated RXR beta (termed Delta C2) were deficient in activating the endogenous RAR beta gene and an RA responsive reporter. To study the dominant negative activity of Delta C2 further, genomic footprinting analysis was performed for the RAR beta(2) promoter. In control P19 clones, the RA responsive element (RARE) and other elements in the promoter were protected after RA treatment. However, in Delta C2 clones RA-induced protection was markedly inhibited at all elements. Conclusions: These results indicate that the C-terminal region of RXR is required for full RARE occupancy in vivo, a RA dependent process that leads to the recruitment of other factors to the promoter and the subsequent transcriptional activation. Thus, RXRs play an integral role in ligand dependent transcription. C1 NICHHD,LAB MOL GROWTH REGULAT,NIH,BETHESDA,MD 20892. OREGON STATE UNIV,COLL PHARM,CORVALLIS,OR 97331. UNIV ARIZONA,COLL MED,DEPT BIOCHEM,TUCSON,AZ 85724. RI Minucci, Saverio/J-9669-2012; OI Jurutka, Peter/0000-0002-4950-9161 NR 52 TC 21 Z9 22 U1 0 U2 1 PU BLACKWELL SCIENCE LTD PI OXFORD PA OSNEY MEAD, OXFORD, OXON, ENGLAND OX2 0EL SN 1356-9597 J9 GENES CELLS JI Genes Cells PD FEB PY 1996 VL 1 IS 2 BP 209 EP 221 DI 10.1046/j.1365-2443.1996.d01-229.x PG 13 WC Cell Biology; Genetics & Heredity SC Cell Biology; Genetics & Heredity GA VC843 UT WOS:A1996VC84300007 PM 9140065 ER PT J AU Hong, GZ Deleersnijder, V Kozak, CA VanMarck, E Tylzanowski, P Merregaert, J AF Hong, GZ Deleersnijder, V Kozak, CA VanMarck, E Tylzanowski, P Merregaert, J TI Molecular cloning of a highly conserved mouse and human integral membrane protein (Itm1) and genetic mapping to mouse chromosome 9 SO GENOMICS LA English DT Article ID DIFFERENTIATION; TRANSPORTER; EXPRESSION; SEQUENCES; ONCOGENE; ACID AB We have isolated and characterized a novel cDNA coding for a highly hydrophobic protein (B5) from a fetal mouse mandibular condyle cDNA library, The full-length mouse B5 cDNA is 3095 nucleotides long and contains a potential open reading frame coding for a protein of 705 amino acids with a calculated molecular weight of 80.5 kDa, The B5 mRNA is differentially polyadenylated, with the most abundant transcript having a length of 2.7 kb, The human homolog of B5 was isolated from a cDNA testis library, The predicted amino acid sequence of the human B5 is 98.5% identical to that of mouse, The most striking feature of the B5 protein is the presence of numerous (10-14) potential transmembrane domains, characteristic of an integral membrane protein, Similarity searches in public databanks reveal that B5 is 58% similar to the T12A2,2 gene of Caenorhabditis elegans and 60% similar to the STT3 gene of Saccharomyces cerevisiae, Furthermore, the report of an EST sequence (Accession No, Z13858) related to the human B5, but identical to the STT3 gene, indicates that B5 belongs to a larger gene family coding for novel putative transmembrane proteins, This family exhibits a remarkable degree of conservation in different species, The gene for B5, designated Itm1 (Integral membrane protein 1), is located on mouse chromosome 9. (C) 1996 Academic Press, Inc. C1 UNIV ANTWERP,DEPT BIOCHEM,LAB MOLEC BIOTECHNOL,B-2610 WILRIJK,BELGIUM. NV INNOGENET SA,B-9052 GHENT,BELGIUM. NIAID,NIH,BETHESDA,MD 20892. UNIV ANTWERP,DEPT PATHOL,B-2610 WILRIJK,BELGIUM. RI Tylzanowski, Przemko/G-8881-2013 NR 28 TC 13 Z9 15 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0888-7543 J9 GENOMICS JI Genomics PD FEB 1 PY 1996 VL 31 IS 3 BP 295 EP 300 DI 10.1006/geno.1996.0051 PG 6 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA TU592 UT WOS:A1996TU59200004 PM 8838310 ER PT J AU Elkahloun, AG Meltzer, PS Guan, XY McNinch, JS Trent, JM deJong, PJ AF Elkahloun, AG Meltzer, PS Guan, XY McNinch, JS Trent, JM deJong, PJ TI Isolation of a cosmid sublibrary for a region of chromosome 12 frequently amplified in human cancers using a complex chromosome microdissection probe SO GENOMICS LA English DT Article ID MALIGNANT-MELANOMA; RAPID GENERATION; HUMAN SARCOMAS; GENE; IDENTIFICATION; AMPLIFICATION; DNA; LIBRARIES; CLONES AB Chromosome-specific cosmid libraries are an extremely useful resource for positional cloning projects. Once a particular region of interest has been identified, it would be of value to have an approach for isolating chromosome band-specific cosmids that could be assembled into a sublibrary for rapid screening. We constructed a region-specific sublibrary of 700 cosmids by screening a chromosome la-specific cosmid library with a complex probe generated by degenerate oligonucleotide-primed PCR of a microdissected homogeneously staining region containing sequences amplified from chromosome 12q13-q15. Based on fluorescence in situ hybridization, approximately 60% of the cosmids in the sublibrary were derived from the microdissected region. To demonstrate further the utility of this sublibrary, a 150-kb contig containing the SAS and CDK4 genes was constructed, as well as several additional contigs between CDK4 and MDM2. This study demonstrates the possibility of utilizing probes generated by microdissection for assembling band-specific sublibraries that are amenable to rapid screening with multiple markers. (C) 1996 Academic Press, Inc. C1 NIH,NCHGR,CANC GENET LAB,BETHESDA,MD 20892. LAWRENCE LIVERMORE NATL LAB,LIVERMORE,CA 94551. ROSWELL PK CANC INST,DEPT HUMAN GENET,BUFFALO,NY 14263. RI Guan, Xin-Yuan/A-3639-2009 OI Guan, Xin-Yuan/0000-0002-4485-6017 NR 20 TC 17 Z9 17 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0888-7543 J9 GENOMICS JI Genomics PD FEB 1 PY 1996 VL 31 IS 3 BP 343 EP 347 DI 10.1006/geno.1996.0057 PG 5 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA TU592 UT WOS:A1996TU59200010 PM 8838316 ER PT J AU Elson, A Kozak, CA Morton, CC Weremowicz, S Leder, P AF Elson, A Kozak, CA Morton, CC Weremowicz, S Leder, P TI The protein tyrosine phosphatase epsilon gene maps to mouse chromosome 7 and human chromosome 10q26 SO GENOMICS LA English DT Article ID RECEPTOR AB We have mapped the mouse protein tyrosine phosphatase epsilon (PTP epsilon, gene symbol Ptpre) gene to the distal region of chromosome 7 by linkage analysis using two sets of multilocus genetic crosses. The human PTP epsilon gene (gene symbol PTPRE) was mapped to chromosome 10q26 by fluorescence in situ hybridization. We have previously documented the existence of two isoforms of PTP epsilon-a transmembranal, receptor-type isoform and a shorter, cytoplasmic one. Both isoforms have been suggested to arise from a single gene through the use of alternative promoters and 5' exons. The identification of a single PTP epsilon locus in both organisms is consistent with this suggestion. (C) 1996 Academic Press, Inc. C1 NIAID,NIH,BETHESDA,MD 20892. HARVARD UNIV,SCH MED,BRIGHAM & WOMENS HOSP,DEPT PATHOL,BOSTON,MA 02115. RP Elson, A (reprint author), HARVARD UNIV,SCH MED,HOWARD HUGHES MED INST,DEPT GENET,BOSTON,MA 02115, USA. NR 14 TC 8 Z9 8 U1 0 U2 1 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0888-7543 J9 GENOMICS JI Genomics PD FEB 1 PY 1996 VL 31 IS 3 BP 373 EP 375 DI 10.1006/geno.1996.0061 PG 3 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA TU592 UT WOS:A1996TU59200014 PM 8838320 ER PT J AU Blazer, DG Hays, JC Salive, ME AF Blazer, DG Hays, JC Salive, ME TI Factors associated with paranoid symptoms in a community sample of older adults SO GERONTOLOGIST LA English DT Article DE community survey; black race; sensory impairment; elderly ID DEPRESSION; IMPAIRMENT AB Symptoms of paranoia were found in 9.5% of a community sample of older adults in North Carolina. In cross-sectional analyses, these symptoms were associated most strongly with black race, lower income and education, less exercise, and more depressive symptoms. In longitudinal analysis, paranoid symptoms three years following initial interview were predicted by baseline paranoid symptoms, education and depressive symptoms at the initial interview. In blacks, paranoid symptoms may represent an appropriate response to a hostile environment rather than a psychopathic trait. C1 DUKE UNIV,MED CTR,CTR STUDY AGING & HUMAN DEV,DURHAM,NC 27710. NIH,DEMOG & BIOMETRY PROGRAM,BETHESDA,MD 20892. RP Blazer, DG (reprint author), DUKE UNIV,MED CTR,DEPT PSYCHIAT & BEHAV SCI,BOX 3005,DURHAM,NC 27710, USA. FU NIA NIH HHS [N01-AG-42110] NR 21 TC 18 Z9 18 U1 1 U2 4 PU GERONTOLOGICAL SOCIETY AMER PI WASHINGTON PA 1275 K STREET NW SUITE 350, WASHINGTON, DC 20005-4006 SN 0016-9013 J9 GERONTOLOGIST JI Gerontologist PD FEB PY 1996 VL 36 IS 1 BP 70 EP 75 PG 6 WC Gerontology SC Geriatrics & Gerontology GA TV975 UT WOS:A1996TV97500015 PM 8932412 ER PT J AU Wang, ZY Lubin, JH Wang, LD Conrath, S Zhang, SZ Kleinerman, R Shang, B Gao, SX Gao, PY Lei, SW Boice, JD AF Wang, ZY Lubin, JH Wang, LD Conrath, S Zhang, SZ Kleinerman, R Shang, B Gao, SX Gao, PY Lei, SW Boice, JD TI Radon measurements in underground dwellings from two prefectures in China SO HEALTH PHYSICS LA English DT Article DE Rn-222; cancer; epidemiology; exposure, radiation ID LUNG-CANCER; RESIDENTIAL RADON; WOMEN AB Radon, an established lung carcinogen, remains the single most important environmental radiation exposure. Yet, an excess of lung cancer from breathing radon in homes has not been consistently demonstrated in studies conducted to date. To address several major problems that have hindered previous studies of lung cancer and radon in homes, we have embarked upon a lung cancer case-control study in Gansu Province, China, where a substantial proportion of the population live in underground dwellings. In this paper, we report on results of a pilot study in which radon measurements were made for 3 days in the summer in 40 homes under normal occupancy conditions using short-term E-PERM detectors and for 6 months from February through August in 49 homes using long-term alpha-track detectors. Useable E-PERM data were obtained from 38 homes and useable alpha-track data from 47 homes. For both types of detectors, measurements were approximately log-normally distributed. Arithmetic and geometric means were 233 and 185 Bq m(-3) (range 74-1,590 Bq m(-3)) for E-PERM measurements and 165 and 158 Bq m(-3) (range 74-592 Bq m(-3)) for alpha-track measurements, respectively; 68% of E-PERM measured homes and 55% of alpha-track measured homes exceeded 148 Bq m(-3). Alpha-track measurements made at the entry, middle, and rear areas of the underground dwellings did not differ significantly (arithmetic means of 168, 162, and 165 Bq m(-3) with standard deviations 63, 73, and 48, respectively), which suggests that air circulation may be minimal. The underground dwellings measured in the pilot study had high radon levels and the underground dwellers may provide an excellent population for studying indoor radon and risk of lung cancer. C1 NCI, BIOSTAT BRANCH, BETHESDA, MD 20892 USA. NCI, DIV CANC & GENET EPIDEMIOL, BETHESDA, MD 20892 USA. MINIST PUBL HLTH, LAB IND HYG, BEIJING, PEOPLES R CHINA. US EPA, DIV RADON, WASHINGTON, DC 20460 USA. OI Kleinerman, Ruth/0000-0001-7415-2478 NR 23 TC 27 Z9 35 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0017-9078 EI 1538-5159 J9 HEALTH PHYS JI Health Phys. PD FEB PY 1996 VL 70 IS 2 BP 192 EP 198 DI 10.1097/00004032-199602000-00006 PG 7 WC Environmental Sciences; Public, Environmental & Occupational Health; Nuclear Science & Technology; Radiology, Nuclear Medicine & Medical Imaging SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Nuclear Science & Technology; Radiology, Nuclear Medicine & Medical Imaging GA TT677 UT WOS:A1996TT67700008 PM 8567286 ER PT J AU Shimizu, YK Feinstone, SM Kohara, M Purcell, RH Yoshikura, H AF Shimizu, YK Feinstone, SM Kohara, M Purcell, RH Yoshikura, H TI Hepatitis C virus: Detection of intracellular virus particles by electron microscopy SO HEPATOLOGY LA English DT Article ID NON-B HEPATITIS; NON-A; CHIMPANZEES; INDUCTION AB We previously demonstrated that a human T-cell Line, HPBMa10-2 derived from HPBALL, was capable of supporting a productive infection of hepatitis C virus (HCV). We subsequently found Daudi cells, a human B-cell line, to be susceptible to HCV infection. Employing these cell Lines infected with HCV as well as liver obtained during the acute phase of hepatitis C from a chimpanzee, we observed intracellular HCV particles by electron microscopy (EM). We detected viruslike particles with a diameter of approximately 50 nm in the cytoplasmic vesicles. In Daudi cells harvested 15 days after virus inoculation, the appearance of cytoplasmic tubular structures which we originally described for chimpanzee hepatocytes in association with HCV infection was noted. Immunoperoxidase EM using antibodies against HCV core and envelope demonstrated that the particles contained the viral antigens. C1 TOKYO METROPOLITAN INST MED SCI,DEPT MICROBIOL,TOKYO 113,JAPAN. NIH,INFECT DIS LAB,BETHESDA,MD. US FDA,DIV VIROL,BETHESDA,MD. RP Shimizu, YK (reprint author), UNIV TOKYO,FAC MED,DEPT BACTERIOL,BUNKYO KU,7-3-1 HONGO,TOKYO 113,JAPAN. NR 14 TC 140 Z9 143 U1 0 U2 5 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 FEB PY 1996 VL 23 IS 2 BP 205 EP 209 PG 5 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA TU856 UT WOS:A1996TU85600002 PM 8591842 ER PT J AU Oberhammer, F Nagy, P Tiefenbacher, R Froschl, G Bouzahzah, B Thorgeirsson, SS Carr, B AF Oberhammer, F Nagy, P Tiefenbacher, R Froschl, G Bouzahzah, B Thorgeirsson, SS Carr, B TI The antiandrogen cyproterone acetate induces synthesis of transforming growth factor beta 1 in the parenchymal cells of the liver accompanied by an enhanced sensitivity to undergo apoptosis and necrosis without inflammation SO HEPATOLOGY LA English DT Article ID RAT-LIVER; DEATH APOPTOSIS; MESSENGER-RNA; REGRESSING LIVER; PROGRAMMED DEATH; EPITHELIAL-CELLS; C-FOS; PROLIFERATION; INDUCTION; FACTOR-BETA-1 AB Recently, cases of liver damage and liver tumors have been reported after treatment of prostate cancer patients with the antiandrogen cyproterone acetate (CPA). In rat liver, CPA initiates a wave of DNA synthesis that is accompanied by apoptosis. In apoptotic hepatocytes, a latent form of transforming growth factor beta 1 (TGF-beta 1) is detectable by immunohistochemistry. Injection of a single dose of TGF-beta 1 induces apoptosis in the liver of animals pretreated with CPA but has an insignificant effect in untreated animals. In this study, we show by Northern analysis that there is increased expression of TGF-beta 1 in the liver after CPA treatment. Detection of TGF-beta 1 with in situ hybridization showed that TGF-beta 1 was synthesized in the parenchymal cells. Time course and dose-response experiments performed 48 hours after the last application of CPA showed that apoptotic nuclei with chromatin condensed at the nuclear periphery (AN) were already visible 2 hours after injection (0.13%), and apoptotic bodies (ABs) increased 2 to 9 hours after the injection (from 1.28% to 6.67%) after 25 mu g TGP-beta 1/kg. At 4.5 hours after injection, an induction of apoptosis could be detected with 0.25 mu g TGF-beta 1/kg and after the maximum dose (250 mu g TGF-beta 1/kg) ANs (0.24%) and ABs (16.74%) were homogeneously distributed throughout the liver lobe. Irrespective of the dose or time after injection of TGF-beta 1, 82% of the ABs were localized within hepatocytes, Liver enzymes were detected in high amounts in the serum (eightfold elevation of glutamate dehydrogenase, fivefold elevation of alanine transaminase [ALT]) 7 hours after the first visible sign of apoptosis. After an additional 20 hours, the Liver contained many necrotic figures. These results suggest that the combination of TGF-beta 1 expression coupled with a strikingly enhanced sensitivity to the induction of apoptosis could be responsible both for the liver damage and the development of liver tumors observed after treatment with CPA. C1 INST TUMORBIOL,VIENNA,AUSTRIA. NCI,EXPTL CARCINOGENESIS LAB,BETHESDA,MD 20892. UNIV PITTSBURGH,SCH MED,DEPT SURG,PITTSBURGH,PA. NR 50 TC 33 Z9 34 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 FEB PY 1996 VL 23 IS 2 BP 329 EP 337 PG 9 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA TU856 UT WOS:A1996TU85600020 PM 8591860 ER PT J AU Schrock, E Badger, P Larson, D Erdos, M WynshawBoris, A Ried, T Brody, L AF Schrock, E Badger, P Larson, D Erdos, M WynshawBoris, A Ried, T Brody, L TI The murine homolog of the human breast and ovarian cancer susceptibility gene Brca1 maps to mouse chromosome 11D SO HUMAN GENETICS LA English DT Article ID NUCLEOTIDE AB The recently cloned human breast and ovarian cancer suseptibility gene, BRCA1, is located on human chromosome 17q21. We have isolated murine genomic clones containing Brca1 as a first step in generating a mouse model for the loss of BRCA1 function. A mouse genomic library was screened using probes corresponding to exon 11 of the human BRCA1 gene. Two overlapping mouse clones were identified that hybridized to human BRCA1 exons 9-12. Sequence analysis of 1.4 kb of the region of these clones corresponding to part of human exon 11 revealed 72% nucleic acid identity but only 50% amino acid identity with the human gene. The longest of the mouse Brcal genomic clones maps to chromosome 11D, as determined by two-color fluorescence in situ hybridization. The synteny to human chromosome 17 was confirmed by cohybridization with the mouse probe for the NF1-gene. This comparative study confirms that the relative location of the BRCA1 gene has been conserved between mice and humans. C1 NIH,NATL CTR HUMAN GENOME RES,LAB GENE TRANSFER,BETHESDA,MD 20892. NIH,NATL CTR HUMAN GENOME RES,DIAGNOST DEV BRANCH,BETHESDA,MD 20892. NIH,NATL CTR HUMAN GENOME RES,LAB GENET DIS RES,BETHESDA,MD 20892. NR 13 TC 14 Z9 15 U1 0 U2 2 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0340-6717 J9 HUM GENET JI Hum. Genet. PD FEB PY 1996 VL 97 IS 2 BP 256 EP 259 DI 10.1007/BF02265277 PG 4 WC Genetics & Heredity SC Genetics & Heredity GA TR669 UT WOS:A1996TR66900025 PM 8566965 ER PT J AU Zhuang, ZP Emmertbuck, MR Roth, MJ Gnarra, J Linehan, WM Liotta, LA Lubensky, IA AF Zhuang, ZP Emmertbuck, MR Roth, MJ Gnarra, J Linehan, WM Liotta, LA Lubensky, IA TI Von Hippel-Lindau disease gene deletion detected in microdissected sporadic human colon carcinoma specimens SO HUMAN PATHOLOGY LA English DT Article DE VHL gene; LOH; colon cancer ID TUMOR SUPPRESSOR GENES; RENAL-CELL CARCINOMA; COLORECTAL CARCINOMAS; MOLECULAR ANALYSIS; SHORT ARM; IDENTIFICATION; CHROMOSOME-3; CANCER AB The progression of human malignancies is thought to involve the inactivation or loss of tumor suppressor genes. Previous studies have suggested that inactivation of tumor suppressor genes on chromosomes 5q, 17p, 18q, and 8p play a role in the development of colorectal carcinoma. However, chromosome 3p at the von Hippel-Lindan disease (VHL) gene locus (3p25-26) has not been previously implicated in the development or progression of sporadic colorectal carcinoma. The authors have analyzed VHL gene alterations on chromosome 3p in sporadic human colon carcinomas and adenomas using modified microdissection techniques. These techniques allow for procurement and analysis of selected subpopulations of cells from both paraffin-embedded and frozen human tumor specimens. MIL disease gene deletion was detected by polymerase chain reaction (PCR) and single-strand conformation polymorphism (SSCP) analysis in microdissected colon carcinoma specimens. Allelic loss of VHL gene was detected in 7 of 11 (64%) informative patients who underwent colectomy for primary sporadic colon carcinoma. However, no allelic loss of VHL gene was shown in colonic adenomas of eight informative patients. These results indicate that VHL disease gene deletion frequently occurs in sporadic colon carcinoma. Because this deletion was not present in adenomas, VHL gene may play a role in colonic carcinogenesis and represent a relatively late event in colonic neoplasia progression. Additionally, microdissection of tissue sections may be especially useful in detecting allelic loss in PCR-based studies of infiltrating tumors, particularly when the tumor cells represent a relatively small percentage of the total cell population. This is a US government work. There are no restrictions on its use. C1 NCI,NIH,PATHOL LAB,BETHESDA,MD 20892. NCI,NIH,SURG BRANCH,BETHESDA,MD 20892. NR 19 TC 39 Z9 40 U1 0 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0046-8177 J9 HUM PATHOL JI Hum. Pathol. PD FEB PY 1996 VL 27 IS 2 BP 152 EP 156 DI 10.1016/S0046-8177(96)90368-8 PG 5 WC Pathology SC Pathology GA TU855 UT WOS:A1996TU85500008 PM 8617456 ER PT J AU Chuaqui, RF Zhuang, ZP Emmertbuck, MR Bryant, BR Nogales, F Tavassoli, FA Merino, MJ AF Chuaqui, RF Zhuang, ZP Emmertbuck, MR Bryant, BR Nogales, F Tavassoli, FA Merino, MJ TI Genetic analysis of synchronous mucinous tumors of the ovary and appendix SO HUMAN PATHOLOGY LA English DT Article DE ovarian mucinous tumors; appendiceal mucinous lesions; pseudomyxoma peritonei; microdissection; loss of heterozygosity ID PSEUDOMYXOMA PERITONEI; CANCER; CHROMOSOME-17; ORIGIN AB The coexistence of mucinous ovarian and appendiceal tumors in association with pseudomyxoma peritonei (PP) is well established. However, it has not been determined whether they represent independent or metastatic neoplasms. The authors analyzed microsatellites on chromosome 17q 21.3-22 (nm23), 3p 25-26 (von Hippel Lindau disease [VHL] gene), and 5q 21-22 (D5S346 locus) in 12 synchronous ovarian and appendiceal mucinous lesions. Loss of heterozygosity (LOH) at the nm23 locus has been shown previously in ovarian carcinomas, and genetic alterations at both the 3p and 5q loci have been reported in colorectal carcinomas. The ovarian lesions consisted of nine mucinous tumors of low malignant potential and three invasive adenocarcinomas, and the appendiceal leisons consisted of eight carcinomas without invasion, two invasive carcinomas, and two mucosal hyperplasias. DNA was extracted from microdissected cells obtained from formalin-fixed, paraffin-embedded tissue sections and amplified by polymerase chain reaction. In three specimens, genetic alterations occurred at 17q 21.3-22 in only the ovarian tumors. One of these cases showed LOH on chromosome 5q 21-22 in only the appendiceal tumor. In three other specimens, LOH at the same locus was found in both tumors. Six specimens did not show LOH at any locus. These results suggest that a subset of synchronous mucinos ovarian and appendiceal lesions showing different LOH patterns in both sites most likely represent patients with two separate primary lesions. Another group of specimens with the same allelic loss in both tumors most likely represent patients with a single primary and metastatic spread. Thus, genetic analysis of these lesions may be useful in investigating the origin of histologically similar synchronous tumors. This is a US government work. There are no restrictions on its use. C1 NCI,PATHOL LAB,BETHESDA,MD 20892. UNIV GRANADA,GRANADA,SPAIN. FAIRFAX HOSP,FAIRFAX,VA. NR 31 TC 53 Z9 57 U1 0 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0046-8177 J9 HUM PATHOL JI Hum. Pathol. PD FEB PY 1996 VL 27 IS 2 BP 165 EP 171 DI 10.1016/S0046-8177(96)90370-6 PG 7 WC Pathology SC Pathology GA TU855 UT WOS:A1996TU85500010 PM 8617458 ER PT J AU Basta, M Miletic, VD Hammer, CH Frank, MM AF Basta, M Miletic, VD Hammer, CH Frank, MM TI Production and characterization of the monoclonal antibody against SGP120, a novel serum protein SO HYBRIDOMA LA English DT Article AB A monoclonal antibody designated B1.9.E-2 was produced and characterized to facilitate study of the immunizing antigen-a serum glycoprotein of 120 kDa (sgp 120) of unknown function. The antibody, produced in mice, reacts with 1-2 epitopes located in the N-terminal region of the sgp 120 molecule, The affinity of the reaction, as determined by Scatchard analysis, is K-a = 1.13 x 10(10) l/M and is of a hydrophobic nature, The monoclonal antibody can be purified to a high degree by a modified caprylic acid method and by protein G FPLC chromatography column. B1.9.E-2 does not trigger the complement cascade, as determined by C3 RIA and immune complex solubilization assays, Both affinity purified (C4b Sepharose) and chromatographically isolated (using jacqualine agarose) sgp 120 were recognized by B1.9.E-2. The monoclonal antibody can be utilized for affinity purification of sgp 120, for detection of intact or cleaved sgp 120 in biological samples of healthy and ill individuals, and for the number of functional and neutralization assays aimed at resolving the physiologic role of sgp 120. C1 NIAID,NIH,MOLEC STRUCT LAB,BETHESDA,MD 20892. DUKE UNIV,MED CTR,DEPT PEDIAT,DURHAM,NC 27710. RP Basta, M (reprint author), NIAID,CLIN INVEST LAB,NIH,BLDG 10,RM 4N248,BETHESDA,MD 20892, USA. OI Basta, Milan/0000-0001-5958-9241 NR 14 TC 0 Z9 2 U1 0 U2 0 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 SN 0272-457X J9 HYBRIDOMA JI Hybridoma PD FEB PY 1996 VL 15 IS 1 BP 69 EP 75 DI 10.1089/hyb.1996.15.69 PG 7 WC Biochemical Research Methods; Biotechnology & Applied Microbiology; Immunology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Immunology GA TY436 UT WOS:A1996TY43600009 PM 9064288 ER PT J AU Wang, HY Paul, WE Keegan, AD AF Wang, HY Paul, WE Keegan, AD TI IL-4 function can be transferred to the IL-2 receptor by tyrosine containing sequences found in the IL-4 receptor alpha chain SO IMMUNITY LA English DT Article ID HUMAN INTERLEUKIN-4 RECEPTOR; SIGNAL-TRANSDUCTION; HEMATOPOIETIC-CELLS; GAMMA-CHAIN; PROTEIN; PHOSPHORYLATION; SUPERFAMILY; ACTIVATION; PATHWAYS; CLONING AB IL-4 binds to a cell surface receptor complex that consists of the IL-4-binding protein (IL-4R alpha) and the gamma chain of the IL-2 receptor complex (gamma c). The receptors for IL-4 and IL-2 have several features in common; both use the gamma c as a receptor component, and both activate the Janus kinases JAK-1 and JAK-3. In spite of these similarities, IL-4 evokes specific responses, including the tyrosine phosphorylation of 4PS/IRS-2 and the induction of CD23. To determine whether sequences within the cytoplasmic domain of the IL-4R alpha specify these IL-4-specific responses, we transplanted the insulin IL-4 receptor motif (14R motif) of the huIL-4R alpha to the cytoplasmic domain of a truncated IL-2R beta. In addition, we transplanted a region that contains peptide sequences shown to block State binding to DNA. We analyzed the ability of cells expressing these IL-2R-IL-4R chimeric constructs to respond to IL-2. We found that IL-4 function could be transplanted to the IL-2 receptor by these regions and that proliferative and differentiative functions can be induced by different receptor sequences. C1 NIAID,IMMUNOL LAB,BETHESDA,MD 20892. RP Wang, HY (reprint author), AMER RED CROSS,JEROME H HOLLAND LAB,IMMUNOL LAB,15601 CRABBS BRANCH WAY,ROCKVILLE,MD 20855, USA. NR 57 TC 66 Z9 66 U1 0 U2 0 PU CELL PRESS PI CAMBRIDGE PA 1050 MASSACHUSETTES AVE, CIRCULATION DEPT, CAMBRIDGE, MA 02138 SN 1074-7613 J9 IMMUNITY JI Immunity PD FEB PY 1996 VL 4 IS 2 BP 113 EP 121 DI 10.1016/S1074-7613(00)80676-7 PG 9 WC Immunology SC Immunology GA TX225 UT WOS:A1996TX22500002 PM 8624802 ER PT J AU Ryan, JJ McReynolds, LJ Keegan, A Wang, LH Garfein, E Rothman, P Nelms, K Paul, WE AF Ryan, JJ McReynolds, LJ Keegan, A Wang, LH Garfein, E Rothman, P Nelms, K Paul, WE TI Growth and gene expression are predominantly controlled by distinct regions of the human IL-4 receptor SO IMMUNITY LA English DT Article ID STIMULATORY FACTOR-I; MAST-CELL LINES; HUMAN INTERLEUKIN-4 RECEPTOR; FC-EPSILON; T-CELL; SUPERFAMILY; DEFINES; IRS-1 AB IL-4 causes hematopoietic cells to proliferate and express a series of genes, including CD23. We examined whether IL-4-mediated growth, as measured by 4PS phosphorylation, and gene induction were similarly controlled. Studies of M12.4.1 cells expressing human IL-4R truncation mutants indicated that the region between amino acids 557-657 is necessary for full gene expression, which correlated with State DNA binding activity. This region was not required for 4PS phosphorylation. Tyrosine-to-phenylalanine mutations in the interval between amino acids 557-657 revealed that as long as one tyrosine remained unmutated, CD23 was fully induced. When all three tyrosines were mutated, the receptor was unable to induce CD23. The results indicate that growth regulation and gene expression are principally controlled by distinct regions of IL-4R. C1 AMER RED CROSS,JEROME H HOLLAND LAB,ROCKVILLE,MD 20855. CUNY MT SINAI SCH MED,DEPT MICROBIOL,NEW YORK,NY 10029. COLUMBIA UNIV COLL PHYS & SURG,DEPT MED,NEW YORK,NY 10032. COLUMBIA UNIV COLL PHYS & SURG,DEPT MICROBIOL,NEW YORK,NY 10032. RP Ryan, JJ (reprint author), NIAID,IMMUNOL LAB,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. FU NIAID NIH HHS [R01AI33540] NR 34 TC 135 Z9 141 U1 0 U2 0 PU CELL PRESS PI CAMBRIDGE PA 1050 MASSACHUSETTES AVE, CIRCULATION DEPT, CAMBRIDGE, MA 02138 SN 1074-7613 J9 IMMUNITY JI Immunity PD FEB PY 1996 VL 4 IS 2 BP 123 EP 132 DI 10.1016/S1074-7613(00)80677-9 PG 10 WC Immunology SC Immunology GA TX225 UT WOS:A1996TX22500003 PM 8624803 ER PT J AU Rocken, M Shevach, EM AF Rocken, M Shevach, EM TI Immune deviation - The third dimension of nondeletional T cell tolerance SO IMMUNOLOGICAL REVIEWS LA English DT Review ID EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS; RECEPTOR TRANSGENIC MICE; PANCREATIC BETA-CELLS; GROWTH-FACTOR-BETA; INTERFERON-GAMMA; CLONAL ANERGY; MURINE LEISHMANIASIS; IL-4-PRODUCING CELLS; MONOCLONAL-ANTIBODY; DOWN-REGULATION C1 NIAID,NIH,IMMUNOL LAB,BETHESDA,MD 20892. UNIV MUNICH,DEPT DERMATOL,D-80337 MUNICH,GERMANY. NR 104 TC 63 Z9 65 U1 0 U2 0 PU MUNKSGAARD INT PUBL LTD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0105-2896 J9 IMMUNOL REV JI Immunol. Rev. PD FEB PY 1996 VL 149 BP 175 EP 194 DI 10.1111/j.1600-065X.1996.tb00904.x PG 20 WC Immunology SC Immunology GA UC521 UT WOS:A1996UC52100008 PM 9005214 ER PT J AU Long, EO Colonna, M Lanier, LL AF Long, EO Colonna, M Lanier, LL TI Inhibitory MHC class I receptors on NK and T cells: A standard nomenclature SO IMMUNOLOGY TODAY LA English DT Letter C1 BASEL INST IMMUNOL,CH-4005 BASEL,SWITZERLAND. DNAX RES INST MOLEC & CELLULAR BIOL INC,PALO ALTO,CA 94304. RP Long, EO (reprint author), NIAID,IMMUNOGENET LAB,TWINBROOKE II,12441 PARKLAWN DR,ROCKVILLE,MD 20852, USA. RI Long, Eric/G-5475-2011 OI Long, Eric/0000-0002-7793-3728 NR 4 TC 77 Z9 77 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 FEB PY 1996 VL 17 IS 2 BP 100 EP 100 DI 10.1016/0167-5699(96)80590-1 PG 1 WC Immunology SC Immunology GA TU506 UT WOS:A1996TU50600017 PM 8808061 ER PT J AU Hoffman, WD Danner, RL Quezado, ZMN Banks, SM Elin, RJ Hosseini, JM Natanson, C AF Hoffman, WD Danner, RL Quezado, ZMN Banks, SM Elin, RJ Hosseini, JM Natanson, C TI Role of endotoxemia in cardiovascular dysfunction and lethality: Virulent and nonvirulent Escherichia coli challenges in a canine model of septic shock SO INFECTION AND IMMUNITY LA English DT Article ID GRAM-NEGATIVE BACTEREMIA; INTESTINAL PERMEABILITY; NEISSERIA-MENINGITIDIS; LIBERATION; INFECTION; STRAINS; HUMANS; BLOOD AB We investigated whether the severity of septic shock is determined by virulence factors associated with or the levels of endotoxemia produced by two Escherichia coli strains. Canines were challenged intraperitoneally with an E. coli strain (06:H1:K-2) that has virulence factors associated with human disease or with an equal dose of a nonvirulent strain (086:H8) that lacks these factors. Both strains were administered in viable, heat-killed, and purified endotoxin forms. Median survival times with the virulent strain compared with the nonvirulent strain were shorter with viable bacteria (5 x 10(9) CFU/kg) (144 h versus >672 h; Wilcoxon, P = 0.03), longer with heat-killed bacteria (5 x 10(10) CFU/kg) (> 676 h versus 26 h; P = 0.03), and similar with purified endotoxin (15 mg/kg) (28 h versus 48 h; P = 0.71). However, whether the challenge contained viable bacteria, heat-killed bacteria, or purified endotoxin, the virulent strain produced less endotoxemia (P = 0.001). Hence, the changing outcomes with differing forms of the two strains cannot be attributed solely to endotoxin levels. The viable virulent strain caused less endotoxemia but more harm, and this does not appear to be explained by a more potent endotoxin or other heat-stable component. This study suggests that circulating endotoxin levels per se are less important in the outcome of septic shock than virulence factors associated with E. coli strains. Furthermore, the data call into question the significance of the endotoxin concentration in the blood in predicting the severity of shock and the lethality of gram-negative infections. C1 NIH,DEPT CRIT CARE MED,BETHESDA,MD 20892. NIH,WARREN G MAGNUSON CLIN CTR,BETHESDA,MD 20892. NIH,DEPT CLIN PATHOL,BETHESDA,MD 20892. RI Quezado, Zenaide/O-4860-2016 OI Quezado, Zenaide/0000-0001-9793-4368 NR 47 TC 25 Z9 25 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 FEB PY 1996 VL 64 IS 2 BP 406 EP 412 PG 7 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA TQ486 UT WOS:A1996TQ48600004 PM 8550184 ER PT J AU Gu, ML Gordon, VM Fitzgerald, DJP Leppla, SH AF Gu, ML Gordon, VM Fitzgerald, DJP Leppla, SH TI Furin regulates both the activation of Pseudomonas exotoxin A and the quantity of the toxin receptor expressed on target cells SO INFECTION AND IMMUNITY LA English DT Article ID CELLULAR PROTEASE; DIPHTHERIA-TOXIN; MOUSE FURIN; ENDOPROTEASE; AERUGINOSA; RESISTANT; SEQUENCE; FRAGMENT; CLEAVAGE; VIRUSES AB Pseudomonas exotoxin A (PE) binds and enters mammalian cells via the alpha(2)-macroglobulin receptor/low density lipoprotein receptor-related protein (LRP). The toxin then requires proteolytic cleavage to generate an enzymatically active fragment which translocates to the cell cytosol and inhibits protein synthesis. To assess the role of furin in determining toxin susceptibility, CHO cells were transfected with a mouse furin gene (CHO+fur cells) and maintained under neomycin selection. Cells expressing the transfected gene were about two- to threefold more sensitive to PE than were cells expressing only a neomycin resistance gene (CHO+neo cells). Possible reasons for the increased toxin sensitivity include the cleavage of a greater number of PE molecules and/or the conversion of more single-chain LRP to the processed, two-chain form. Processing of LRP appears to be necessary to allow the surface display of this receptor. Results of ligand binding studies indicated that the CHO+fur cells displayed about twofold more surface-expressed LRP than did CHO+neo cells. In addition, the in vitro cleavage of PE by recombinant furin enhanced toxin potency about threefold for CHO+neo cells but enhanced it very little for CHO+fur cells. This suggested that CHO+fur cells were processing PE at close to the maximum usable rate. Together these findings suggest that furin is involved in at least two separate protein processing pathways that each contribute to the sensitivity of cells to PE. C1 NIDR,MICROBIAL ECOL LAB,BETHESDA,MD 20892. NCI,MOLEC BIOL LAB,BETHESDA,MD 20892. NR 29 TC 26 Z9 28 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 FEB PY 1996 VL 64 IS 2 BP 524 EP 527 PG 4 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA TQ486 UT WOS:A1996TQ48600022 PM 8550202 ER PT J AU Balaji, PV Qasba, PK Rao, VSR AF Balaji, PV Qasba, PK Rao, VSR TI Molecular dynamics simulations of hybrid and complex type oligosaccharides SO INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES LA English DT Article DE carbohydrates; conformation; Asn-linked oligosaccharide; hybrid type; complex type; oligosaccharide processing ID ASPARAGINE-LINKED OLIGOSACCHARIDES; HAMSTER OVARY CELLS; N-ACETYLGLUCOSAMINYLTRANSFERASE; CONFORMATIONAL-ANALYSIS; CONCANAVALIN-A; BIANTENNARY OCTASACCHARIDE; 3-DIMENSIONAL STRUCTURES; ENERGY CALCULATIONS; BRANCH SPECIFICITY; FORCE-FIELD AB Conformational preferences of hybrid (GlcNAc(1)Man(5)GlcNAc(2)) and complex (GlcNAc(1)Man(3)GlcNAc(2); GlcNAc(2)Man(3)GlcNAc(2)) type asparagine-linked oligosaccharides and the corresponding bisected oligosaccharides have been studied by molecular dynamics simulations for 2.5 ns. The fluctuations of the core Man-alpha 1,3-Man fragment are restricted to a region around (-30 degrees, -30 degrees) due to a 'face-to-face' arrangement of bisecting GlcNAc and the beta 1,2-GlcNAc on the 1,3-arm. However, conformations where such a 'face-to-face' arrangement is disrupted are also accessed occasionally. The orientation of the 1,6-arm is affected not only by changes in chi, but also by changes in Phi and Psi around the core Man-alpha 1,6-Man linkage. The conformation around the core Man-alpha 1,6-Man linkage is different in the hybrid and the two complex types suggesting that the preferred values of Phi, Psi, and chi are affected by the addition or deletion of saccharides to the alpha 1,6-linked mannose. The conformational data are in agreement with the available experimental studies and also explain the branch specificity of galactosyltransferases. C1 NCI,MATH BIOL LAB,NATL INST HLTH,BETHESDA,MD 20892. OI Balaji, Petety/0000-0002-6018-6957 NR 55 TC 7 Z9 7 U1 0 U2 0 PU BUTTERWORTH-HEINEMANN LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, OXON, ENGLAND OX5 1GB SN 0141-8130 J9 INT J BIOL MACROMOL JI Int. J. Biol. Macromol. PD FEB PY 1996 VL 18 IS 1-2 BP 101 EP 114 DI 10.1016/0141-8130(95)01064-5 PG 14 WC Biochemistry & Molecular Biology; Chemistry, Applied; Polymer Science SC Biochemistry & Molecular Biology; Chemistry; Polymer Science GA TY867 UT WOS:A1996TY86700014 PM 8852759 ER PT J AU Yu, JJ Dabholkar, M Bennett, WP Welsh, JA Mu, CJ BostickBruton, F Reed, E AF Yu, JJ Dabholkar, M Bennett, WP Welsh, JA Mu, CJ BostickBruton, F Reed, E TI Platinum-sensitive and platinum-resistant ovarian cancer tissues show differences in the relationships between mRNA levels of p53, ERCC1 and XPA SO INTERNATIONAL JOURNAL OF ONCOLOGY LA English DT Article DE p53; ERCC1; XPA; DNA repair; ovarian cancer ID TUMOR-SUPPRESSOR GENE; PIGMENTOSUM GROUP-F; EXCISION REPAIR; DNA; EXPRESSION; MUTATIONS; ACCUMULATION; COMPLEXES; ACID AB We investigated the association between p53 mRNA expression and clinically relevant surrogates of nucleotide excision repair (ERCC1 and XPA) in 28 ovarian cancer specimens. We observed that platinum-resistant tumors showed higher mRNA levels of p53, ERCC1, and XPA than platinum-sensitive tumors; mRNA expression patterns in responders differed substantially from nonresponders; and p53 expression showed a strong correlation with the expression of ERCC1, and of XPA in platinum-sensitive tumor tissues, but not with platinum-resistant tumors. 47% of the mutations from p53 sequence analysis were not related to clinical response to chemotherapy. We conclude that the p53 influence on DNA repair in human malignancy may vary substantially from tumor to tumor, and that such differences are not necessarily related to the mutational status of p53. C1 NCI,DIV CANC TREATMENT,CLIN PHARMACOL BRANCH,MED OVARIAN CANC SECT,BETHESDA,MD 20892. NCI,DIV CANC ETIOL,HUMAN CARCINOGENESIS LAB,BETHESDA,MD 20892. NR 33 TC 16 Z9 16 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 FEB PY 1996 VL 8 IS 2 BP 313 EP 317 PG 5 WC Oncology SC Oncology GA TR618 UT WOS:A1996TR61800012 PM 21544361 ER PT J AU Burger, AM Li, H Panayiotakis, A Salesiotis, AN Seth, A AF Burger, AM Li, H Panayiotakis, A Salesiotis, AN Seth, A TI Identification of differentially expressed genes in breast cancer SO INTERNATIONAL JOURNAL OF ONCOLOGY LA English DT Article DE MSS1; E2A; SEC13R; breast cancer; differential expression; tumor marker ID DNA-BINDING; PROTEINS; LOCALIZATION; ONCOGENE; E2A AB A number of genes differentially expressed in breast cancer were isolated using a subtractive cloning technique. DNA sequence analysis and GenBank searches of T4F10, T2H7, and T2E5 cDNA clones found them to be identical with E2A, MSS1, and SEC13R genes. Their expression in a variety of primary breast tumor and cancer cell lines was compared with c-ERB-B2 and pS2 by Northern blot analysis. In breast cancer cell lines, the genes that we isolated are more frequently expressed than the previously described c-ERB-B2 and pS2. C1 UNIV TORONTO,DEPT PATHOL,FAC MED,TORONTO,ON,CANADA. UNIV TORONTO,FAC DENT,TORONTO,ON,CANADA. UNIV TORONTO,WOMENS COLL HOSP,TORONTO,ON,CANADA. UNIV BRADFORD,CLIN ONCOL UNIT,BRADFORD BD7 1DP,W YORKSHIRE,ENGLAND. MEM SLOAN KETTERING CANC CTR,NEW YORK,NY. NCI,MOLEC ONCOL LAB,FREDERICK,MD. NR 35 TC 8 Z9 8 U1 0 U2 0 PU INT JOURNAL ONCOLOGY PI ATHENS PA C/O PROFESSOR D A SPANDIDOS, EDITORIAL OFFICE, 1, S MERKOURI ST, ATHENS 116 35, GREECE SN 1019-6439 J9 INT J ONCOL JI Int. J. Oncol. PD FEB PY 1996 VL 8 IS 2 BP 395 EP 400 PG 6 WC Oncology SC Oncology GA TR618 UT WOS:A1996TR61800026 PM 21544375 ER PT J AU Ruble, G Wu, CC Squire, RA Gansow, OA Strand, M AF Ruble, G Wu, CC Squire, RA Gansow, OA Strand, M TI The use of Pb-212-labeled monoclonal antibody in the treatment of murine erythroleukemia SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Article DE radioimmunotherapy; (212)lead; alpha-emitter; monoclonal antibody; erythroleukemia ID CHELATING-AGENTS; MICE; RADIOIMMUNOTHERAPY; BIODISTRIBUTION; STABILITY; EXCRETION; MODEL AB Purpose: The goals of this study were to learn whether the DOTA chelator was useful for targeting lead radionuclides (Pb-203,Pb-212) to cells and tissues invaded by the Rauscher leukemia virus (RVB3) and to investigate the therapeutic efficacy of targeted Pb-212 in treating the murine leukemia. Methods and Materials: Five to 6-week-old BALB/c mice were inoculated i.v. with RVB3, This virus causes marked splenomegaly and death by day 13 and day 70 postinfection, respectively, Biodistribution, tumor targeting, and toxicity studies were performed using varying doses of Pb-212-DOTA-103A. A heavy metal chelator, DMPS, was administered orally and parenterally in two phases of the toxicity study. Results: Biodistribution studies showed marked tumor targeting (58% ID/g spleen) in mice treated with Pb-203-103A as compared to mice treated with control antibody B3 (4.6% ID/g spleen), Histologic cure was achieved in all leukemic mice treated with 20 mu Ci Pb-212-103A; however, all of the mice died with leukopenia and secondary bacterial infections due to severe bone marrow toxicity. Nonleukemic mice and mice treated with 20 mu Ci Pb-212-B3 experienced less marrow toxicity and longer survival, Coadministration of the heavy metal chelator did not diminish the bone marrow toxicity. Conclusion: An effective, nonlethal dose could not be established to treat this tumor, The severe bone marrow toxicity associated with this radionuclide may limit its usefulness in systemic radioimmunotherapy. C1 JOHNS HOPKINS UNIV,SCH MED,DEPT PHARMACOL,BALTIMORE,MD 21205. JOHNS HOPKINS UNIV,SCH MED,DIV COMPARAT MED,BALTIMORE,MD 21205. NCI,RADIAT ONCOL BRANCH,INORGAN & RADIOIMMUNE CHEM SECT,BETHESDA,MD 20892. FU NCRR NIH HHS [RR00130, RR07002] NR 27 TC 25 Z9 26 U1 0 U2 2 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0360-3016 J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD FEB 1 PY 1996 VL 34 IS 3 BP 609 EP 616 DI 10.1016/0360-3016(95)02119-1 PG 8 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA TW660 UT WOS:A1996TW66000011 PM 8621285 ER PT J AU Oonishi, T Sakashita, K Suematsu, N Schechter, AN Uyesaka, N AF Oonishi, T Sakashita, K Suematsu, N Schechter, AN Uyesaka, N TI Quantitative characterization of P-glycoprotein-mediated transport in mdr1-gene-transfected lymphoma cells SO JAPANESE JOURNAL OF PHYSIOLOGY LA English DT Article DE P-glycoprotein; flow cytometry; L5178Y cell; verapamil; vanadate ID RESISTANT TUMOR-CELLS; MULTIDRUG TRANSPORTER; FLOW-CYTOMETRY; CHANNEL; LINES AB We have established a quantitative flow cytometry system to elucidate the causal role of P-glycoprotein in the phenomenon of multidrug resistance. We have used this method to analyze the accumulation and release of adriamycin (ADM) in intact L5178Y and L5178Y/VMDR/C.06 (L5178Y/R) cells, by determining the effect of sodium orthovanadate (Na3VO4), verapamil, bovine serum albumin (BSA) and physiologically operative materials on the cells. Based on the experiments, we prepared a standard solution that contained NaCl, D-glucose, L-cysteine, HCO3- and BSA, which was sufficient to perform transport experiments. In particular, BSA caused a decrease in ADM accumulation and a facilitation of the rate of ADM release in both L5178Y and L5178Y/R cells, probably due to its relatively high affinity for ADM as compared to the cell membrane. In multidrug-resistant L5178Y/R cells, sodium orthovanadate, a strong ATP-binding inhibitor, caused a marked increase in the accumulation of ADM, whereas vanadate-treated drug-sensitive L5178Y cells showed little increase in ADM accumulation. In a release (0-trans exit) experiment, vanadate-treated L5178Y/R cells exhibited an apparent decrease in ADM release (increase in ADM retention), to a level which was almost the same as L5178Y cells. We thus confirmed that the P-glycoprotein-mediated efflux system is coupled with P-glycoprotein-associated ATP-hydrolysis, Further, verapamil, a potent inhibitor of P-glycoprotein-mediated transport, facilitated the ADM accumulation in L5178Y/R cells up to the level of L5178Y and vanadate-treated L5178Y/R cells. A more important finding is that, in the release experiment, verapamil-treated L5178Y/R cells exhibited a much greater ADM retention than drug-sensitive L5178Y and vanadate-treated L5178Y/R cells. These findings, in particular the potent effect of verapamil on drug-resistant cells, may afford new insight into the pathophysiology of the phenomenon of multidrug resistance and the mechanism of action of the multidrug transporter. C1 YOKUFUKAI HOSP,DEPT PATHOL,TOKYO 168,JAPAN. NIDDKD,BIOL CHEM LAB,NIH,BETHESDA,MD 20892. NIPPON MED COLL,DEPT PHYSIOL,BUNKYO KU,TOKYO 113,JAPAN. RP Oonishi, T (reprint author), KANTO TEISHIN HOSP,MED INFORMAT INST,SHINAGAWA KU,5-9-22 HIGASHI GOTANDA,TOKYO 141,JAPAN. OI Schechter, Alan N/0000-0002-5235-9408 NR 22 TC 2 Z9 2 U1 0 U2 0 PU CENTER ACAD PUBL JAPAN PI TOKYO PA C/O BUSINESS CTR ACAD SOC JPN, 16-9 HONKOMAGOME 5-CHOME BUNKYO-KU, TOKYO 113, JAPAN SN 0021-521X J9 JPN J PHYSIOL JI Jpn. J. Physiol. PD FEB PY 1996 VL 46 IS 1 BP 33 EP 41 DI 10.2170/jjphysiol.46.33 PG 9 WC Physiology SC Physiology GA VF821 UT WOS:A1996VF82100003 PM 8743716 ER PT J AU RubioStipec, M Shrout, PE Canino, G Bird, HR Jensen, P Dulcan, M SchwabStone, M AF RubioStipec, M Shrout, PE Canino, G Bird, HR Jensen, P Dulcan, M SchwabStone, M TI Empirically defined symptom scales using the DISC 2.3 SO JOURNAL OF ABNORMAL CHILD PSYCHOLOGY LA English DT Article ID COMMUNITY SURVEY; PREVALENCE; CHILDREN AB Empirically defined scales of depressive, attention deficit hyperactivity disorder, oppositional-defiant disorder, and conduct symptoms from the lay-administered National Institute of Mental Health (NIMH) Diagnostic Interview Schedule for Children (DISC), version 2.3, and evidence of their reliability and validity are presented. The scales were developed using factor analyses of data obtained from an epidemiologic survey of over 1,200 children drawn from four sites across the U.S. and Puerto Rico (the NIMH Methods for the Epidemiology of Child and Adolescent Mental Disorders, or MECA Study). Their psychometric properties were rested in a subsample of children reinterviewed by clinicians. The findings support the use of these continuous measures. The scales are strongly related to the diagnostic categories and show good test-retest reliability. The scales can be used to characterize severity in children with diagnoses and to describe problems and symptoms in children without diagnoses. Because these scales can measure gradations in symptomatology, they may be more useful than categorical measures. Like categorical measures the scales based on the DISC are greatly influenced by the informant, whether child or parent. C1 NYU,DEPT PSYCHOL,NEW YORK,NY 10003. UNIV PUERTO RICO,BEHAV SCI RES INST,ASSMCA,SAN JUAN,PR 00936. NEW YORK STATE PSYCHIAT INST & HOSP,DIV CHILD & ADOLESCENT PSYCHIAT,NEW YORK,NY. COLUMBIA UNIV,COLL PHYS & SURG,NEW YORK,NY. NIMH,ROCKVILLE,MD 20857. CHILDRENS MEM HOSP,DEPT CHILD PSYCHIAT,CHICAGO,IL 60614. NORTHWESTERN UNIV,CHICAGO,IL 60611. YALE UNIV,SCH MED,YALE CHILD STUDY CTR,NEW HAVEN,CT. RP RubioStipec, M (reprint author), UNIV PUERTO RICO,BEHAV SCI RES INST,DEPT ECON,MED SCI CAMPUS,POB 365067,SAN JUAN,PR 00936, USA. OI Jensen, Peter/0000-0003-2387-0650 FU NIMH NIH HHS [MH46732] NR 18 TC 13 Z9 13 U1 3 U2 4 PU PLENUM PUBL CORP PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 SN 0091-0627 J9 J ABNORM CHILD PSYCH JI J. Abnorm. Child Psychol. PD FEB PY 1996 VL 24 IS 1 BP 67 EP 83 DI 10.1007/BF01448374 PG 17 WC Psychology, Clinical; Psychology, Developmental SC Psychology GA TZ290 UT WOS:A1996TZ29000005 PM 8833029 ER PT J AU Leidy, NK Traver, GA AF Leidy, NK Traver, GA TI Adjustment and social behaviour in older adults with chronic obstructive pulmonary disease: The family's perspective SO JOURNAL OF ADVANCED NURSING LA English DT Article ID SICKNESS IMPACT PROFILE; CHRONIC ILLNESS; LIFE; REHABILITATION; DEPRESSION; QUALITY; HEALTH; CARE; COPD AB This study employed secondary data analysis to explore family perceptions of adjustment and social behaviour in older adults (n = 51) with chronic obstructive pulmonary disease (COPD) and their relationship to published norms and patient self-report, According to the Katz Adjustment Scale for Relatives, these COPD patients had significantly higher levels of belligerence, negativism, helplessness, withdrawal, psychopathology, nervousness and confusion than reports from relatives of older adults from the general population, No differences were found in performance, expectation or dissatisfaction with socially expected activities, or performance of free-time activities, However, family members of COPD patients were significantly more dissatisfied with their relative's free-time activities, Although family perceptions of socially expected activities corresponded to patient descriptions of general and physical functioning (Sickness Impact Profile), patient perceptions of psychosocial functioning were independent of the family's. The results supported the tenet that older adults with COPD have difficulties with adjustment that may adversely affect social relationships, but were not consistent with the belief that the performance of socially expected or free-time activities is more impaired than in others of this age group, The data also suggested there may be some perceptual discrepancy between family and patient views of social behaviour. C1 UNIV ARIZONA,MED CTR,TUCSON,AZ. RP Leidy, NK (reprint author), NINR,LAB STUDY HUMAN RESPONSES HLTH & ILLNESS,BLDG 31,ROOM 5B25,31 CTR DR,BETHESDA,MD 20892, USA. NR 38 TC 20 Z9 20 U1 1 U2 5 PU BLACKWELL SCIENCE LTD PI OXFORD PA OSNEY MEAD, OXFORD, OXON, ENGLAND OX2 0EL SN 0309-2402 J9 J ADV NURS JI J. Adv. Nurs. PD FEB PY 1996 VL 23 IS 2 BP 252 EP 259 DI 10.1111/j.1365-2648.1996.tb02664.x PG 8 WC Nursing SC Nursing GA TR588 UT WOS:A1996TR58800006 PM 8708236 ER PT J AU Sledjeski, DD Gottesman, S AF Sledjeski, DD Gottesman, S TI Osmotic shock induction of capsule synthesis in Escherichia coli K-12 SO JOURNAL OF BACTERIOLOGY LA English DT Article ID KDP OPERON EXPRESSION; POLYSACCHARIDE SYNTHESIS; REGULATOR; GENE AB The genes (cps) involved in the synthesis of the colanic acid capsular polysaccharide in Escherichia coli K-12 are transcriptionally regulated by numerous proteins. Two of these, RcsB and RcsC, share homology with two-component regulatory elements that respond to environmental stimuli. Osmotic shock by sucrose or NaCl transiently increased transcription of a cpsB::lacZ fusion. RcsC and RcsB were essential for osmotic induction of colanic acid synthesis. In contrast to observations in some other osmotically regulated systems, addition of glycine betaine enhanced the osmotic induction of cps::lacZ by both sucrose and NaCl but had no effect alone. C1 NCI,MOLEC BIOL LAB,BETHESDA,MD 20892. OI Sledjeski, Darren/0000-0001-9882-6625 NR 21 TC 122 Z9 124 U1 0 U2 5 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 FEB PY 1996 VL 178 IS 4 BP 1204 EP 1206 PG 3 WC Microbiology SC Microbiology GA TU511 UT WOS:A1996TU51100035 PM 8576059 ER PT J AU Tanimura, A Turner, RJ AF Tanimura, A Turner, RJ TI Calcium release in HSY cells conforms to a steady-state mechanism involving regulation of the inositol 1,4,5-trisphosphate receptor Ca2+ channel by luminal [Ca2+] SO JOURNAL OF CELL BIOLOGY LA English DT Article ID INTRACELLULAR STORES; PERMEABILIZED HEPATOCYTES; FLUORESCENT INDICATOR; INTRALUMINAL CA2+; CA-2+ STORES; TRISPHOSPHATE; POOLS; MOBILIZATION; OSCILLATIONS; GENERATION AB In many cell types, low concentrations of inositol 1,4,5-trisphosphate (IP3) release only a portion of the intracellular IP3-sensitive Ca2+ store, a phenomenon known as ''quantal'' Ca2+ release. It has been suggested that this effect is a result of reduced activity of the IP3-dependent Ca2+ channel with decreasing calcium concentration within the IP3-sensitive store ([Ca2+]s). To test this hypothesis, the properties of IP3-dependent Ca2+ release in single saponin-permeabilized HSY cells were studied by monitoring [Ca2+]s using the Ca2+-sensitive fluorescent dye mag-fura-2. In permeabilized cells, blockade of the sarco/ER Ca2+-ATPase pump in stores partially depleted by IP3 induced further Ca2+ release via an IP3-dependent route, indicating that Ca2+ entry via the sarco/ER Ca2+-ATPase pump had been balanced by Ca2+ loss via the IP3-sensitive channel before pump inhibition. IP3-dependent Mn2+ entry, monitored via quenching of luminal mag-fura-2 fluorescence, was readily apparent in filled stores but undetectable in Ca2+-depleted stores, indicating markedly reduced IP3-sensitive channel activity in the latter. Also consistent with reduced responsiveness of Ca2+-depleted stores to IP3, the initial rate of refilling of these stores was unaffected by the presence of 0.3 mu M IP3, a concentration that was clearly effective in eliciting Ca2+ release from filled stores. Analysis of the rate of Ca2+ release at various IP3 concentrations indicated a significant shift of the IP3 dose response toward higher [IP3] with decreasing [Ca2+]s. We conclude that IP3-dependent Ca2+ release in HSY cells is a steady-state process wherein Ca2+ efflux via the IP3 receptor Ca2+ channel is regulated by [Ca2+]s, apparently via changes in the sensitivity of the channel to IP3. C1 NIDR,NIH,CLIN INVEST & PATIENT CARE BRANCH,BETHESDA,MD 20892. NR 46 TC 52 Z9 52 U1 0 U2 0 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 222 E 70TH STREET, NEW YORK, NY 10021 SN 0021-9525 J9 J CELL BIOL JI J. Cell Biol. PD FEB PY 1996 VL 132 IS 4 BP 607 EP 616 DI 10.1083/jcb.132.4.607 PG 10 WC Cell Biology SC Cell Biology GA TX172 UT WOS:A1996TX17200010 PM 8647892 ER PT J AU Ryeom, SW Sparrow, JR Silverstein, RL AF Ryeom, SW Sparrow, JR Silverstein, RL TI CD36 participates in the phagocytosis of rod outer segments by retinal pigment epithelium SO JOURNAL OF CELL SCIENCE LA English DT Article DE CD36; rod outer segment; retinal pigment epithelium ID MANNOSE RECEPTOR; PLATELET-MONOCYTE; MEMBRANE-PROTEIN; GLYCOPROTEIN-IV; RAT; CELLS; BINDING; INVITRO; CULTURE; CYTOADHERENCE AB Mechanisms of phagocytosis are complex and incompletely understood. The retinal pigment epithelium provides an ideal system to study the specific aspects of phagocytosis since an important function of this cell is the ingestion of packets of membranous discs that are normally discarded at the apical ends of rod and cone cells during outer segment renewal. Here we provide evidence that rod outer segment phagocytosis by retinal pigment epithelium is mediated by CD36, a transmembrane glycoprotein which has been previously characterized on hematopoietic cells as a receptor for apoptotic neutrophils and oxidized low density lipoprotein. Immunocytochemical staining with monoclonal and polyclonal antibodies demonstrated CD36 expression by both human and rat retinal pigment epithelium in transverse cryostat sections of normal retina and in primary cultured cells. By western blot analysis of retinal pigment epithelial cell lysates, polyclonal and monoclonal antibodies to CD36 recognized an 88 kDa protein which comigrated with platelet CD36. Furthermore, the synthesis of CD36 mRNA by retinal pigment epithelium was confirmed by reverse transcriptase-PCR using specific CD36 oligonucleotides. The addition of CD36 antibodies to cultured retinal pigment epithelial cells reduced the binding and internalization of I-125-labeled rod outer segments by 60%. Immunofluorescence confocal microscopy confirmed that outer segment uptake was significantly diminished by an antibody to CD36. Moreover, we found that transfection of a human melanoma cell line with CD36 cDNA enabled these cells to bind and internalize isolated photoreceptor outer segments as seen by double immunofluorescent staining for surface bound and total cell-associated rod outer segments, and by measurement of cell-associated I-125-labeled rod outer segments. We conclude that the multifunctional scavenger receptor CD36 participates in the clearance of photoreceptor outer segments by retinal pigment epithelium and thus, participates in the visual process. C1 CORNELL UNIV,COLL MED,CELL BIOL & GENET PROGRAM,DIV HEMATOL ONCOL,NEW YORK,NY 10021. CORNELL UNIV,COLL MED,NIH,SPECIALIZED CTR THROMBOSIS RES,NEW YORK,NY 10021. CORNELL UNIV,COLL MED,DEPT OPHTHALMOL,NEW YORK,NY 10021. FU NEI NIH HHS [EY 10967]; NHLBI NIH HHS [HL18828, HL46403] NR 55 TC 139 Z9 144 U1 1 U2 5 PU COMPANY OF BIOLOGISTS LTD PI CAMBRIDGE PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE, CAMBS, ENGLAND CB4 4DL SN 0021-9533 J9 J CELL SCI JI J. Cell Sci. PD FEB PY 1996 VL 109 BP 387 EP 395 PN 2 PG 9 WC Cell Biology SC Cell Biology GA TV543 UT WOS:A1996TV54300012 PM 8838662 ER PT J AU Zafarullah, M Su, SM MartelPelletier, J DiBattista, JA Costello, BG StetlerStevenson, WG Pelletier, JP AF Zafarullah, M Su, SM MartelPelletier, J DiBattista, JA Costello, BG StetlerStevenson, WG Pelletier, JP TI Tissue inhibitor of metalloproteinase-2 (TIMP-2) mRNA is constitutively expressed in bovine, human normal, and osteoarthritic articular chondrocytes SO JOURNAL OF CELLULAR BIOCHEMISTRY LA English DT Article DE cartilage; osteoarthritis; metalloproteinases; inhibitors; mRNA ID RHEUMATOID SYNOVIAL-FLUID; MESSENGER-RNA EXPRESSION; DEVELOPMENTAL EXPRESSION; DIFFERENTIAL REGULATION; POTENTIATING ACTIVITY; GENE-EXPRESSION; COLLAGENASE; CARTILAGE; FIBROBLASTS; COMPLEX AB Tissue inhibitors of metalloproteinases (TIMPs) inhibit the extracellular matrix (ECM) metalloproteinases (MMPs). To determine the source of TIMPs in synovial fluids of patients with osteoarthritis (OA), the ability of chondrocytes to express TIMP-2 and its regulation by agents found in inflammed joints was investigated. The constitutive TIMP-2 mRNA expression was demonstrated in chondrocytes from normal bovine, human OA and normal cartilage. The cross-hybridization of human and bovine TIMP-2 suggested its evolutionary conservation. Serum, IL-1, IL-6 and TGF-beta were unable to augment considerably the basal expression of TIMP-2 mRNA. TIMP-1 RNA expression in chondrocytes from human OA cartilage was elevated compared to non-OA chondrocytes, while TIMP-2 mRNA levels were similar in both. IL-1 beta, IL-6 and TGF-beta did not affect TIMP-2 expression but TGF-beta induced TIMP-1 mRNA in human OA chondrocytes. TIMP-2 and TIMP-1 are therefore differentially regulated in chondrocytes and the basal TIMP-2 levels may be needed for the cartilage ECM integrity. (C) 1996 Wiley-Liss, Inc. C1 ROYAL VICTORIA HOSP,DEPT ORTHOPAED SURG,MONTREAL,PQ H3A 1A1,CANADA. NCI,BETHESDA,MD 20892. RP Zafarullah, M (reprint author), UNIV MONTREAL,HOP NOTRE DAME DE BON SECOURS,CTR RECH LOUIS CHARLES SIMARD,UNITE RHUMATISMALE,MONTREAL,PQ H2L 4K8,CANADA. RI Stetler-Stevenson, William/H-6956-2012 OI Stetler-Stevenson, William/0000-0002-5500-5808 NR 43 TC 29 Z9 31 U1 0 U2 2 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0730-2312 J9 J CELL BIOCHEM JI J. Cell. Biochem. PD FEB PY 1996 VL 60 IS 2 BP 211 EP 217 DI 10.1002/(SICI)1097-4644(19960201)60:2<211::AID-JCB5>3.0.CO;2-# PG 7 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA TW085 UT WOS:A1996TW08500005 PM 8655631 ER PT J AU Merchan, M Roos, BO McDiarmid, R Xing, X AF Merchan, M Roos, BO McDiarmid, R Xing, X TI A combined theoretical and experimental determination of the electronic spectrum of acetone SO JOURNAL OF CHEMICAL PHYSICS LA English DT Article ID 3P RYDBERG STATES; 2ND-ORDER PERTURBATION-THEORY; ABSORPTION PROPERTIES; ACETALDEHYDE; TRANSITION; SPECTROSCOPY; ASSIGNMENTS; IMPACT; SHIFTS AB A combined ab initio and experimental investigation has been performed of the main features of the electronic spectrum of acetone. Vertical transition energies have been calculated from the ground to the n(y) --> pi*, pi --> pi*, sigma --> pi*, and the n = 3 Rydberg states. In addition, the (1)A(1) energy surfaces have been studied as functions of the CO bond length. The (1)A(1) 3p and 3d states were found to be heavily perturbed by the pi --> pi* state. Resonant multiphoton ionization and polarization-selected photoacoustic spectra of acetone have been measured and observed transitions were assigned on internal criteria. The calculated vertical transition energies to the n(y) --> pi* and all Rydberg states were found to be in agreement with experiment. This includes the 3s-, all three 3p-, and the A(1), B-1, and B-2 3d-Rydberg states. By contrast, there is little agreement between the calculated and experimental relative intensities of the A, and B, 3d-Rydberg transitions. In addition, anomalously intense high vibrational overtone bands of one of the 3p-Rydberg transitions have been observed. These results confirm the strong perturbation of the 3p- and 3d-Rydberg states by the pi --> pi* state found in the theoretical calculation and support the calculated position of this unobserved state. (C) 1996 American Institute of Physics. C1 CHEM CTR LUND,DEPT THEORET CHEM,S-22100 LUND,SWEDEN. NIDDK,PHYS CHEM LAB,BETHESDA,MD 20892. RP Merchan, M (reprint author), UNIV VALENCIA,DEPT QUIM FIS,DR MOLINER 50,E-46100 VALENCIA,SPAIN. NR 43 TC 82 Z9 83 U1 1 U2 6 PU AMER INST PHYSICS PI WOODBURY PA CIRCULATION FULFILLMENT DIV, 500 SUNNYSIDE BLVD, WOODBURY, NY 11797-2999 SN 0021-9606 J9 J CHEM PHYS JI J. Chem. Phys. PD FEB 1 PY 1996 VL 104 IS 5 BP 1791 EP 1804 PG 14 WC Chemistry, Physical; Physics, Atomic, Molecular & Chemical SC Chemistry; Physics GA TT361 UT WOS:A1996TT36100004 ER PT J AU Ghizzoni, L Mastorakos, G Vottero, A Magiakou, MA Chrousos, GP Bernasconi, S AF Ghizzoni, L Mastorakos, G Vottero, A Magiakou, MA Chrousos, GP Bernasconi, S TI Spontaneous cortisol and growth hormone secretion interactions in patients with nonclassic 21-hydroxylase deficiency (NCCAH) and control children SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID CORTICOTROPIN-RELEASING FACTOR; SOMATOSTATIN; CELLS; GENE AB Both exogenous and endogenous hypercortisolism result in reduced GH secretion and decreased somatic growth. However, little is known about the relation between endogenous cortisol and GH secretion under physiological or slightly disturbed conditions. To examine this, we measured and evaluated the pulsatility and circadian rhythmicity, and we cross-correlated the secretory patterns of cortisol and GH in six prepubertal patients with nonclassic 21-hydroxylase deficiency (NCCAH) and seven age-matched short-normal children. Cortisol and GH were secreted in a pulsatile fashion in both the NCCAH and control groups. The nocturnal peak cortisol increment and time-integrated area were lower in the NCCAH patients than in controls, whereas there was no difference in the total 24-h cortisol secretion between the two groups. The nocturnal increase of GH in NCCAH children, on the other hand, was associated with a significant augmentation of the pulse amplitude, whereas in control children there was an elevation of the baseline component. The crosscorrelation analysis of the 24-h raw data showed that cortisol and GH were negatively correlated at brief lag times of 0-30 min, and positively correlated at long lag times of 12-12.5 h in both groups, with cortisol leading GH. The negative correlation might reflect either the negative effect of glucocorticoids on the adrenergic system, which stimulates GH secretion through GH-releasing hormone (GHRH) elevations and somatostatin (SRIH) decreases, or the absence of an inhibitory effect of CRH on SRIH. The positive correlation may reflect the positive effect of glucocorticoids on the GH gene. In conclusion, NCCAH children have a mild nocturnal cortisol deficiency compared with control children, as previously reported, and a distinct circadian pattern of pulsatile GH secretion. The hypothalamic-pituitary-adrenal (HPA) axis exerts both negative and positive influences on GH secretion, with mild disturbances in cortisol biosynthesis associated with slight alterations of GH secretion. C1 UNIV MODENA, DEPT PEDIAT, I-41100 MODENA, ITALY. UNIV ATHENS, EVGENIDION HOSP, SCH MED, ENDOCRINE UNIT, GR-11528 ATHENS, GREECE. UNIV ATHENS, AGHIA SOPHIA HOSP,SCH MED,DEPT PEDIAT 1, ENDOCRINE UNIT, GR-11527 ATHENS, GREECE. NICHHD, DEV ENDOCRINOL BRANCH, NIH, BETHESDA, MD 20892 USA. RP Ghizzoni, L (reprint author), UNIV PARMA, DEPT PEDIAT, VIA GRAMSCI 14, I-43100 PARMA, ITALY. NR 28 TC 12 Z9 12 U1 0 U2 0 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X EI 1945-7197 J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD FEB PY 1996 VL 81 IS 2 BP 482 EP 487 DI 10.1210/jc.81.2.482 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA TU981 UT WOS:A1996TU98100011 PM 8636254 ER PT J AU Thompson, DB DeGregorio, M Sommercorn, J AF Thompson, DB DeGregorio, M Sommercorn, J TI Insulin regulation of multiple ribonucleic acid species in human skeletal muscle in insulin-sensitive and insulin-resistant subjects SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID DEPENDENT DIABETIC-PATIENTS; GENE-EXPRESSION; GROWTH-FACTOR; GLYCOGEN-SYNTHASE; HEPATOMA-CELLS; RECEPTOR-GENE; PROTEIN; FIBROBLASTS; INDUCTION; KINASE AB In, vivo short term (2 h) insulin-regulated gene expression was examined in skeletal muscle of persons with differing insulin sensitivities. Nine genes were analyzed by a S1 nuclease protection assay with multiple probes (multiple S1 nuclease protection assay) to allow the simultaneous examination of RNA abundances from the multiple genes. In insulin-sensitive individuals, 5 of these 9 genes were insulin responsive. RNA from the proto-oncogenes c-Ha-ras, c-myc, and c-src transiently increased 2- to 4-fold within 30 min of insulin infusion. In addition, the RNA abundance of myf-5, a muscle specific differentiation factor, increased 3-fold with a time course similar to that of c-Ha-ras, c-myc, and c-src. In contrast, type 1 protein phosphatase alpha (PPP1A) RNA levels decreased by 50% within 30 min. In insulin-resistant individuals, the RNA levels of c-Ha-ras and myf-5 did not increase, whereas c-src RNA did increase within 30 min of insulin infusion. RNA encoding c-myc transiently increased in both groups; however, this response was lower in insulin-resistant individuals than in insulin-sensitive individuals in a pattern similar to c-Ha-ras and myf-5. PPP1A RNA levels slightly increased in insulin-resistant individuals. In both insulin-sensitive and insulin-resistant persons, RNA quantities of GLUT4, c-jun, c-fos, and the insulin receptor did not change over the period of insulin infusion. However, overall RNA levels of the insulin receptor and c-jun were lower in insulin-resistant individuals. RP Thompson, DB (reprint author), NIDDKD, CLIN DIABET & NUTR SECT, NIH, 4212 N 16TH ST, PHOENIX, AZ 85016 USA. NR 36 TC 9 Z9 9 U1 0 U2 0 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD FEB PY 1996 VL 81 IS 2 BP 519 EP 523 DI 10.1210/jc.81.2.519 PG 5 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA TU981 UT WOS:A1996TU98100018 PM 8636261 ER PT J AU White, AD Folsom, AR Chambless, LE Sharret, AR Yang, K Conwill, D Higgins, M Williams, OD Tyroler, HA AF White, AD Folsom, AR Chambless, LE Sharret, AR Yang, K Conwill, D Higgins, M Williams, OD Tyroler, HA TI Community surveillance of coronary heart disease in the atherosclerosis risk in communities (ARIC) study: Methods and initial two years' experience SO JOURNAL OF CLINICAL EPIDEMIOLOGY LA English DT Article DE coronary heart disease; community surveillance; mortality; case fatality ID CARDIOVASCULAR-DISEASE; MYOCARDIAL-INFARCTION; UNITED-STATES; GEOGRAPHIC-VARIATION; MORTALITY; DECLINE; TRENDS; RATES AB The community surveillance component of the Atherosclerosis Risk in Communities (ARIC) Study is designed to estimate patterns and trends of coronary heart disease (CHD) incidence, case fatality, and mortality in four U.S. communities, Community surveillance involves ongoing review of death certificates and hospital discharge records to identify CHD events in community residents aged 35-74 years. Interviews with next of kin and questionnaires completed by physicians and medical examiners or coronets were used to collect information on deaths, and review and abstraction of hospital records were used to collect information on possible fatal and nonfatal myocardial infarctions (MIs). Events were classified using standardized criteria. The initial 2-years' experience with case ascertainment and availability of information needed for classification of events is described, Average annual age-adjusted attack rates of definite MI and CHD mortality rates for blacks in two communities and whites in the four communities are presented and compared with rates based on unvalidated hospital discharge data and vital statistics. Age adjusted rates based on ARIC classification of definite MI were lower than those based on hospital discharge diagnosis code 410 (e.g., 5.60/1000 and 11.50/1000 among Forsyth County white men, respectively). Age adjusted rates of definite fatal CHD based on ARIC classification were similarly lower than rates based on underlying cause of death code 410; for example, Jackson black men had rates of 2.82/1000 and 4.52/1000 for definite fatal CHD and UCOD 410-414 or 429.2, respectively. C1 UNIV MINNESOTA,SCH PUBL HLTH,DIV EPIDEMIOL,MINNEAPOLIS,MN 55455. UNIV N CAROLINA,SCH PUBL HLTH,DEPT BIOSTAT,CHAPEL HILL,NC. NHLBI,DIV EPIDEMIOL & CLIN APPLICAT,NIH,BETHESDA,MD 20892. UNIV MISSISSIPPI,MED CTR,DEPT PREVENT MED,DIV EPIDEMIOL,JACKSON,MS 39216. UNIV ALABAMA,SCH PUBL HLTH,BIRMINGHAM,AL 35294. RP White, AD (reprint author), UNIV N CAROLINA,SCH PUBL HLTH,DEPT EPIDEMIOL,CHAPEL HILL,NC 27599, USA. NR 26 TC 393 Z9 395 U1 2 U2 10 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0895-4356 J9 J CLIN EPIDEMIOL JI J. Clin. Epidemiol. PD FEB PY 1996 VL 49 IS 2 BP 223 EP 233 DI 10.1016/0895-4356(95)00041-0 PG 11 WC Health Care Sciences & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA UC799 UT WOS:A1996UC79900012 PM 8606324 ER PT J AU Baird, DD Wilcox, AJ Herbst, AL AF Baird, DD Wilcox, AJ Herbst, AL TI Self-reported allergy, infection, and autoimmune diseases among men and women exposed in utero to diethylstilbestrol SO JOURNAL OF CLINICAL EPIDEMIOLOGY LA English DT Article DE diethylstilbestrol; allergy; asthma; infection; autoimmunity; rheumatoid arthritis; epidemiology ID INUTERO; ASSOCIATION AB Immunotoxicology studies of prenatal or neonatal exposure to diethylstilbestrol (DES) show effects on immune function of the adult animal. Prenatally exposed humans are known to be at increased risk of vaginal adenocarcinoma, but little research has been done to assess immunologic function. A placebo controlled clinical trial of DES was conducted in the early 1950s. The sons and daughters born to participants of this clinical trial were traced and interviewed about immune-related health problems. Symptom and disease rates for the DES exposed (253 sons and 296 daughters) were compared with rates for the unexposed (241 men and 246 women). DES-exposed men and women reported rates of allergy, infection, and autoimmune disease similar to the unexposed. However, because autoimmune diseases are rare, a larger sample is needed to evaluate further DES-associated risk of autoimmunity. C1 UNIV CHICAGO,DEPT OBSTET & GYNECOL,CHICAGO,IL 60637. RP Baird, DD (reprint author), NIEHS,EPIDEMIOL BRANCH,POB 12233,A3-05,RES TRIANGLE PK,NC 27709, USA. OI Wilcox, Allen/0000-0002-3376-1311; Baird, Donna/0000-0002-5544-2653 NR 17 TC 20 Z9 21 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0895-4356 J9 J CLIN EPIDEMIOL JI J. Clin. Epidemiol. PD FEB PY 1996 VL 49 IS 2 BP 263 EP 266 DI 10.1016/0895-4356(95)00521-8 PG 4 WC Health Care Sciences & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA UC799 UT WOS:A1996UC79900017 PM 8606329 ER PT J AU Stratakis, CA Carney, JA Lin, JP Papanicolaou, DA Karl, M Kastner, DL Pras, E Chrousos, GP AF Stratakis, CA Carney, JA Lin, JP Papanicolaou, DA Karl, M Kastner, DL Pras, E Chrousos, GP TI Carney complex, a familial multiple neoplasia and lentiginosis syndrome - Analysis of 11 kindreds and linkage to the short arm of chromosome 2 SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article DE Carney complex; multiple endocrine neoplasia (MEN); myxomas linkage; chromosome 2p ID ADRENOCORTICAL NODULAR DYSPLASIA; PSAMMOMATOUS MELANOTIC SCHWANNOMA; ENDOCRINE OVERACTIVITY; CARDIAC MYXOMA; SPOTTY PIGMENTATION; CUSHINGS-SYNDROME; COLORECTAL-CANCER; MUCOCUTANEOUS LENTIGINES; SPECIAL ASSOCIATIONS; CUTANEOUS MYXOMAS AB Carney complex is an autosomal dominant syndrome characterized by multiple neoplasias, including myxomas at various sites and endocrine rumors, and lentiginosis. The generic defect(s) responsible for the complex remain(s) unknown. We studied 101 subjects, including 51 affected members, from 11 North American kindreds with Carney complex. Blood samples were collected from patients and their family members. Hospital records, photographs, and tissue specimens of deceased individuals were reviewed. DNA was extracted from blood samples, patient-derived cell lines, and/ or paraffin-embedded tissues. Linkage analysis was performed with highly polymorphic microsatellite markers, distributed over areas of the human genome harboring the most likely candidate genes. The most prevalent clinical manifestation in patients with Carney complex was spotty skin pigmentation, similar to that observed in Peutz-Jeghers and other lentiginosis syndromes. Skin and cardiac myxomas, Cushing syndrome, and acromegaly were present in 62, 30, 31, and 8 percent of the patients, respectively. Linkage was obtained for three markers on the short arm of chromosome 2 (2p16), with a maximum two-point lod score of 5.97 at theta = 0.03 for the marker CA-2 (odds in favor of linkage 10(6):1). The flanking markers CA7 and D2S378 defined a region of similar to 6.4 cM that is likely to contain the gene(s) associated with Carney complex. Candidate genes in the proximity, including the propiomelanocortin and the DNA-mismatch repair hMSH2 genes, were excluded. We conclude that the genetic defect(s) responsible for Carney complex map(s) to the short arm of chromosome 2 (2p16). This region has exhibited cytogenetic aberrations in atrial myxomas associated with the complex, and has been characterized by microsatellite instability in human neoplasias. C1 MAYO CLIN,DEPT LAB MED & PATHOL,ROCHESTER,MN 55905. NIAMSD,GENET STUDIES SECT,SKIN BIOL LAB,ARTHRIT & RHEUMATISM BRANCH,NIH,BETHESDA,MD 20892. RP Stratakis, CA (reprint author), NICHHD,SECT PEDIAT ENDOCRINOL,DEV ENDOCRINOL BRANCH,NIH,BLDG 10,ROOM 10 N 262,BETHESDA,MD 20892, USA. NR 76 TC 261 Z9 273 U1 0 U2 3 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 222 E 70TH STREET, NEW YORK, NY 10021 SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD FEB 1 PY 1996 VL 97 IS 3 BP 699 EP 705 DI 10.1172/JCI118467 PG 7 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA UB656 UT WOS:A1996UB65600017 PM 8609225 ER PT J AU Wang, MH Skeel, A Leonard, EJ AF Wang, MH Skeel, A Leonard, EJ TI Proteolytic cleavage and activation of pro-macrophage-stimulating protein by resident peritoneal macrophage membrane proteases SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article DE chemotaxis; kringles; inflammation; plasma; activation analysis ID HEPATOCYTE GROWTH-FACTOR; AMINO-ACID-SEQUENCE; MOLECULAR-CLONING; HUMAN-SERUM; EXPRESSION; FAMILY; MSP; PLASMINOGEN; PROTHROMBIN; UROKINASE AB Macrophage stimulating protein (MSP), which is secreted as biologically inactive pro-MSP. is activated to MSP by cleat:age at a single peptide bond. Our objectives were to determine the form of MSP in circulating blood and to study proteolytic activation of pro-MSP by its target cell. Western blot of immunoaffinity-purified serum MSP showed that all the protein was pro-MSP, without detectable MSP. The circulating form of the protein is therefore pro-MSP, and conversion to MSP does not occur when blood is shed. Incubation of radiolabeled pro-MSP with murine peritoneal macrophages caused proteolytic cleavage to predominantly inactive fragments. Among several protease inhibitors, soybean trypsin inhibitor was one of two that inhibited nonspecific cleavage and revealed a macrophage activity that cleaved pro-MSP to biologically active MSP. Mouse or human serum also inhibited macrophage proteolysis of pro-MSP, and certain concentrations enhanced cleavage to mature MSP. Macrophage membranes had nonspecific and specific pro-MSP proteolytic activity, which was not present in macrophage culture fluids. The results suggest that control of MSP activity can occur at the level of the target cell by proteolytic cleavage of pro-MSP to mature MSP or to inactive fragments. RP Wang, MH (reprint author), NCI,FREDERICK CANC RES & DEV CTR,IMMUNOPATHOL SECT,IMMUNOBIOL LAB,NIH,BLDG 560,RM 12-71,FREDERICK,MD 21702, USA. NR 35 TC 67 Z9 68 U1 0 U2 2 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 222 E 70TH STREET, NEW YORK, NY 10021 SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD FEB 1 PY 1996 VL 97 IS 3 BP 720 EP 727 DI 10.1172/JCI118470 PG 8 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA UB656 UT WOS:A1996UB65600020 PM 8609228 ER PT J AU ApplebaumBowden, D Kobayashi, J Kashyap, VS Brown, DR Berard, A Meyn, S Parrott, C Maeda, N Shamburek, R Brewer, HB SantamarinaFojo, S AF ApplebaumBowden, D Kobayashi, J Kashyap, VS Brown, DR Berard, A Meyn, S Parrott, C Maeda, N Shamburek, R Brewer, HB SantamarinaFojo, S TI Hepatic lipase gene therapy in hepatic lipase-deficient mice - Adenovirus-mediated replacement of a lipolytic enzyme to the vascular endothelium SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article DE gene therapy; Adenoviridae; hepatic lipase; HDL; phospholipid ID CELL-DERIVED CHOLESTEROL; ESTER TRANSFER PROTEIN; APOLIPOPROTEIN-A-I; RAT-LIVER CELLS; LIPOPROTEIN-LIPASE; DENSITY-LIPOPROTEIN; TRIGLYCERIDE LIPASE; POSTHEPARIN PLASMA; FIREFLY LUCIFERASE; MAMMALIAN-CELLS AB Hepatic lipase (HL) is an endothelial-bound lipolytic enzyme which functions as a phospholipase as well as a triacylglycerol hydrolase and is necessary for the metabolism of IDL and HDL. To evaluate the feasibility of replacing an enzyme whose in vivo physiologic function depends on its localization on the vascular endothelium, we have infused recombinant replication-deficient adenovirus vectors expressing either human HL (HL-rAdV; n = 7) or luciferase cDNA (Lucif-rAdV; n = 4) into HL-deficient mice with pretreatment plasma cholesterol, phospholipid, and HDL cholesterol values of 176+/-9, 314+/-12, and 129+/-9, respectively. After infusion of HL-rAdV. HL could be detected in the post-heparin plasma of HL-deficient mice by and postheparin plasma HL activities were 25,700+/-4,810 and 1,510+/-688 nmol/min/ml on days 5 and 15, respectively. Unlike the mouse HL, 97% of the newly synthesized human HL was heparin releasable, indicating that the human enzyme was virtually totally bound to the mouse vascular endothelium. Infusion of HL-rAdV in HL-deficient mice was associated with a 50-80% decrease in total cholesterol, tri- glyceride, phospholipids, cholesteryl ester, and HDL cholesterol (P < 0.001) as well as normalization of the plasma fast protein liquid chromatography lipoprotein profile by day 8. These studies demonstrate successful expression and delivery of a lipolytic enzyme to the vascular endothelium for ultimate correction of the HL gene defect in HL-deficient mice and indicate that recombinant adenovirus vectors may be useful in the replacement of endothelial-bound lipolytic enzymes in human lipolytic deficiency states. C1 NHLBI,NIH,MOLEC DIS BRANCH,BETHESDA,MD 20892. BOWMAN GRAY SCH MED,WINSTON SALEM,NC 27103. UNIV N CAROLINA,CHAPEL HILL,NC. NR 53 TC 56 Z9 56 U1 0 U2 0 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 222 E 70TH STREET, NEW YORK, NY 10021 SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD FEB 1 PY 1996 VL 97 IS 3 BP 799 EP 805 DI 10.1172/JCI118479 PG 7 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA UB656 UT WOS:A1996UB65600029 PM 8609237 ER PT J AU Avis, IM Jett, M Boyle, T Vos, MD Moody, T Treston, AM Martinez, A Mulshine, JL AF Avis, IM Jett, M Boyle, T Vos, MD Moody, T Treston, AM Martinez, A Mulshine, JL TI Growth control of lung cancer by interruption of 5-lipoxygenase-mediated growth factor signaling SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article DE lipoxygenase pathway; 5-HETE; signal transduction; growth inhibition; apoptosis ID LEUKOTRIENE BIOSYNTHESIS INHIBITOR; ARACHIDONIC-ACID; CELLS; BOMBESIN AB Signal transduction pathways shared by different autocrine growth factors may provide an efficient approach to accomplish clinically significant control of lung cancer growth. In this study, we demonstrate that two autocrine growth factors activate 5-lipoxygenase action of the arachidonic acid metabolic pathway in lung cancer cell lines. Both growth factors increased the production of 5(S)-hydrooxyeicosa-6E,8Z,11Z,14Z-tetraenoic acid (5-HETE), a major early 5-lipoxygenase metabolic product. Exogenously added 5-HETE stimulated lung cancer cell growth in vitro. Inhibition of 5-lipoxygenase metabolism by selective antagonists resulted in significant growth reduction for a number of lung cancer cell lines. Primary clinical specimens and lung cancer cell lines express the message for the 5-lipoxygenase enzymes responsible for the generation of active metabolites. In vivo evaluation demonstrated that interruption of 5-lipoxygenase signaling resulted in enhanced levels of programmed cell death. These findings demonstrate that 5-lipoxygenase activation is involved with growth factor-mediated growth stimulation for lung cancer cell lines. Pharmacological intervention with lipoxygenase inhibitors may be an important new clinical strategy to regulate growth factor-dependent stages of lung carcinogenesis. C1 NCI,BIOMARKERS & PREVENT RES BRANCH,ROCKVILLE,MD 20850. WALTER REED ARMY INST RES,DIV PATHOL,WASHINGTON,DC 20307. RI Martinez, Alfredo/A-3077-2013; OI Martinez, Alfredo/0000-0003-4882-4044; Mulshine, James/0000-0002-4648-9177 NR 39 TC 195 Z9 198 U1 0 U2 0 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 222 E 70TH STREET, NEW YORK, NY 10021 SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD FEB 1 PY 1996 VL 97 IS 3 BP 806 EP 813 DI 10.1172/JCI118480 PG 8 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA UB656 UT WOS:A1996UB65600030 PM 8609238 ER PT J AU Conville, PS Andrews, JWB Witebsky, FG AF Conville, PS Andrews, JWB Witebsky, FG TI Additional data about the influence of an inhibitory factor on growth of Mycobacterium kansasii in BACTEC 12B medium - Reply SO JOURNAL OF CLINICAL MICROBIOLOGY LA English DT Letter RP Conville, PS (reprint author), NIH,MICROBIOL SERV,BLDG 10,ROOM 2C-385,10 CTR DR,MSC 1508,BETHESDA,MD 20892, USA. NR 2 TC 0 Z9 0 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 FEB PY 1996 VL 34 IS 2 BP 484 EP 484 PG 1 WC Microbiology SC Microbiology GA TQ538 UT WOS:A1996TQ53800057 ER PT J AU Wexler, LH Andrich, MP Venzon, D Berg, SL WeaverMcClure, L Chen, CC Dilsizian, V Avila, N Jarosinski, P Balis, FM Poplack, DG Horowitz, ME AF Wexler, LH Andrich, MP Venzon, D Berg, SL WeaverMcClure, L Chen, CC Dilsizian, V Avila, N Jarosinski, P Balis, FM Poplack, DG Horowitz, ME TI Randomized trial of the cardioprotective agent ICRF-187 in pediatric sarcoma patients treated with doxorubicin SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID ACUTE LYMPHOBLASTIC-LEUKEMIA; CONGESTIVE HEART-FAILURE; EWINGS-SARCOMA; ANTHRACYCLINE THERAPY; CARDIAC TOXICITY; RADIONUCLIDE ANGIOCARDIOGRAPHY; MULTIMODAL THERAPY; CARDIOTOXICITY; ADRIAMYCIN; CHILDREN AB Purpose: We conducted an open-label, randomized trial to determine whether ICRF-187 would reduce doxorubicin-induced cardiotoxicity in pediatric sarcoma patients. Methods: Thirty-eight patients were randomized to receive doxorubicin-containing chemotherapy (given as an intravenous bolus) with or without ICRF-187, Resting left ventricular ejection fraction (LVEF) was monitored serially with multigated radionuclide angiography (MUGA) scan, The two groups were compared for incidence and degree of cardiotoxicity, response rates to four cycles of chemotherapy, event-free and overall survival, and incidence and severity of noncardiac toxicities. Results: Eighteen ICRF-187-treated and 15 control patients were assessable for cardiac toxicity, ICRF-187-treated patients were less likely to develop subclinical cardiotoxicity (22% v 67%, P<.01), had a smaller decline in LVEF per 100 mg/m(2) of doxorubicin (1,0 v 2.7 percentage points, P=.02), and received a higher median cumulative dose of doxorubicin (410 v 310 mg/m(2), P<.05) than did control patients, Objective response rates were identical in the two groups, with no significant differences seen in event-free or overall survival, ICRF-187-treated patients had a significantly higher incidence of transient grade 1 serum transaminase elevations and a trend toward increased hematologic toxicity. Conclusion: ICRF-187 reduces the risk of developing short-term subclinical cardiotoxicity in pediatric sarcoma patients who receive vp to 410 mg/m(2) of doxorubicin, Response rates to chemotherapy, event-free and overall survival, and noncardiac toxicities appear to be unaffected by the use of ICRF-187, Additional clinical trials with larger numbers of patients are needed to determine if the short-term cardioprotection afforded by ICRF-187 will reduce the incidence of late cardiac complications in long-term survivors of childhood cancer. C1 NCI,BIOSTAT & DATA MANAGEMENT SECT,BETHESDA,MD 20892. NIH,CTR CLIN,DEPT PHARM,BETHESDA,MD 20892. NIH,CTR CLIN,DEPT RADIOL,BETHESDA,MD 20892. NIH,CTR CLIN,DEPT NUCL MED,BETHESDA,MD 20892. RP Wexler, LH (reprint author), NCI,PEDIAT BRANCH,9000 ROCKVILLE PIKE,BLDG 10,ROOM 13N240,10 CTR DR,BETHESDA,MD 20892, USA. RI Venzon, David/B-3078-2008 NR 49 TC 147 Z9 153 U1 0 U2 3 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD FEB PY 1996 VL 14 IS 2 BP 362 EP 372 PG 11 WC Oncology SC Oncology GA TU998 UT WOS:A1996TU99800008 PM 8636745 ER PT J AU Fraker, DL Alexander, HR Andrich, M Rosenberg, SA AF Fraker, DL Alexander, HR Andrich, M Rosenberg, SA TI Treatment of patients with melanoma of the extremity using hyperthermic isolated limb perfusion with melphalan, tumor necrosis factor, and interferon gamma: Results of a tumor necrosis factor dose-escalation study SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID MALIGNANT-MELANOMA; FACTOR-ALPHA; COMBINATION AB Purpose: To evaluate response rates and systemic and regional toxicity of hyperthermic isolated limb perfusion (ILP) for treatment of in-transit metastases of extremity melanoma using escalating-dose tumor necrosis factor (TNF) in conjunction with melphalan and interferon gamma (IFN). Patients and Methods: All patients received IFN 0.2 mg(2) for 2 days followed by a 90-minute ILP with TNF and IFN (0.2 mg) given at time 0 and melphalan (10 mg/L limb volume) given at 30 minutes, Twenty-six patients were treated with 4 mg of TNF and 12 patients received 6 mg of TNF, All patients herd assessable disease in the perfusion field and all but two patients were assessable for response at 1 month after treatment. Results: Mean peak perfusate TNF levels in the 4-mg group were 4.8 mu g/mL, compared with 7.4 mu g/mL for the 6-mg group (P = .03), The complete response rate in the 4-mg TNF group was 76%, with an overall objective response rate of 92%, compared with 36% and 100% for the 6-mg group. Subgroup analyses showed that the lower complete response rate in the 6-mg TNF group was not explained by differences in disease burden or prior regional therapy. Systemic drug toxicity was short-lived, easily managed, and related to perfusate leak more than to TNF perfusate dose, Regional toxicity, particularly painful myopathy and neuropathy, wets greater with the 6-mg dose level and was considered dose-limiting. Conclusion: ILP with 4 mg TNF, IFN, and melphalan can lead to complete local responses in the majority of patients with extremity melanoma, Escalating the TNF dose to 6 mg did not increase the complete response rate and increased regional toxicity. C1 NCI,SURG BRANCH,BETHESDA,MD 20892. NIH,CTR CLIN,DEPT NUCL MED,BETHESDA,MD 20892. NR 19 TC 149 Z9 151 U1 0 U2 3 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD FEB PY 1996 VL 14 IS 2 BP 479 EP 489 PG 11 WC Oncology SC Oncology GA TU998 UT WOS:A1996TU99800024 PM 8636761 ER PT J AU Travis, LB Weeks, J Curtis, RE Chaffey, JT Stovall, M Banks, PM Boice, JD AF Travis, LB Weeks, J Curtis, RE Chaffey, JT Stovall, M Banks, PM Boice, JD TI Leukemia following low-dose total body irradiation and chemotherapy for non-Hodgkin's lymphoma SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID ACUTE NONLYMPHOCYTIC LEUKEMIA; COMBINATION CHEMOTHERAPY; ADVANCED LYMPHOSARCOMA; LYMPHOCYTIC LYMPHOMA; CYCLOPHOSPHAMIDE; VINCRISTINE; PREDNISONE; ADRIAMYCIN; THERAPY; RISK AB Purpose: Low-dose total body irradiation (TBI) is used to treat non-Hodgkin's lymphoma (NHL) and several other malignancies. Large volumes of bone marrow and other tissue receive considerable exposure, but few studies have quantified late carcinogenic sequelae. Patients and Methods: A cohort of 61 2-year survivors of NHL treated with low-dose TBI was monitored for second cancer occurrence, Data on primary and subsequent therapy were collected, and cumulative dose of radiation to active bone marrow (ABM) (median, 5.2 Gy) was reconstructed. Results: Thirteen second primary cancers occurred, Four patients developed acute nonlymphocytic leukemia (ANLL), which represents a relative risk (90) of 117(95% confidence interval [Cl], 31.5 to 300) compared with population rates. A fifth patient was diagnosed with myelodysplastic syndrome (MDS). All five patients with secondory hematologic malignancies subsequently received salvage treatment, with either alkylating agents alone (n = 1) or combined modality therapy (CMT) (n = 4). Overall, eight solid tumors were observed (RR = 2.0; 95% Cl, 0.9 to 4.0). The 15-year cumulative risks of all second cancers and secondary ANLL were 37% and 17%, respectively. Conclusions: Despite the small number of subjects, a considerable risk of leukemia was observed among patients treated with low-dose TBI in combination with CMT including alkylating agents. Based on these results, approximately eight to nine excess ANLLs might be expected to occur among 100 NHL patients treated with low-dose TBI and salvage treatment and followed-up for 15 years. C1 DANA FARBER CANC INST,BOSTON,MA 02115. HARVARD JOINT CTR RADIOTHERAPY,BOSTON,MA. UNIV TEXAS,MD ANDERSON CANC CTR,HOUSTON,TX. UNIV TEXAS,HLTH SCI CTR,SAN ANTONIO,TX. RP Travis, LB (reprint author), NCI,RADIAT EPIDEMIOL BRANCH,NIH,UNITED STATES DEPT HLTH & HUMAN SERV,EXECUT PLAZA N,SUITE 408,BETHESDA,MD 20892, USA. NR 46 TC 69 Z9 78 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD FEB PY 1996 VL 14 IS 2 BP 565 EP 571 PG 7 WC Oncology SC Oncology GA TU998 UT WOS:A1996TU99800035 PM 8636772 ER PT J AU Smith, M Bleyer, A Crist, W Murphy, S Sallan, SE AF Smith, M Bleyer, A Crist, W Murphy, S Sallan, SE TI Uniform criteria for childhood acute lymphoblastic leukemia risk classification SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Letter C1 CHILDRENS CANC GRP, ARCADIA, CA USA. ST JUDE CHILDRENS RES HOSP, MEMPHIS, TN 38105 USA. PEDIAT ONCOL GRP, CHICAGO, IL USA. DANA FARBER CANC INST, BOSTON, MA 02115 USA. RP Smith, M (reprint author), NCI, CANC THERAPY EVALUAT PROGRAM, BETHESDA, MD 20892 USA. NR 2 TC 23 Z9 23 U1 1 U2 2 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD FEB PY 1996 VL 14 IS 2 BP 680 EP 681 PG 2 WC Oncology SC Oncology GA TU998 UT WOS:A1996TU99800051 PM 8636788 ER PT J AU Frye, MA Altshuler, LL Bitran, JA AF Frye, MA Altshuler, LL Bitran, JA TI Clozapine in rapid cycling bipolar disorder SO JOURNAL OF CLINICAL PSYCHOPHARMACOLOGY LA English DT Letter ID PROPHYLAXIS C1 UNIV CALIF LOS ANGELES,SCH MED,DEPT PSYCHIAT & BEHAV SCI,INST NEUROPSYCHIAT,LOS ANGELES,CA 90024. UNIV CALIF LOS ANGELES,SCH MED,DEPT PSYCHIAT & BEHAV SCI,W LOS ANGELES VET ADM MED CTR,LOS ANGELES,CA 90024. RP Frye, MA (reprint author), NIMH,BIOL PSYCHIAT BRANCH,BETHESDA,MD 20892, USA. NR 19 TC 29 Z9 31 U1 1 U2 2 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0271-0749 J9 J CLIN PSYCHOPHARM JI J. Clin. Psychopharmacol. PD FEB PY 1996 VL 16 IS 1 BP 87 EP 90 DI 10.1097/00004714-199602000-00022 PG 4 WC Pharmacology & Pharmacy; Psychiatry SC Pharmacology & Pharmacy; Psychiatry GA TU193 UT WOS:A1996TU19300022 PM 8834431 ER PT J AU Callahan, AM Ketter, TA Crumlish, J Parekh, P Brown, DW Post, RM AF Callahan, AM Ketter, TA Crumlish, J Parekh, P Brown, DW Post, RM TI Mania and lower serum cholesterol levels - Reply SO JOURNAL OF CLINICAL PSYCHOPHARMACOLOGY LA English DT Letter ID DISORDER RP Callahan, AM (reprint author), NIMH,BIOL PSYCHIAT BRANCH,BETHESDA,MD 20892, USA. NR 11 TC 1 Z9 1 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0271-0749 J9 J CLIN PSYCHOPHARM JI J. Clin. Psychopharmacol. PD FEB PY 1996 VL 16 IS 1 BP 95 EP 97 DI 10.1097/00004714-199602000-00029 PG 3 WC Pharmacology & Pharmacy; Psychiatry SC Pharmacology & Pharmacy; Psychiatry GA TU193 UT WOS:A1996TU19300029 PM 8834437 ER PT J AU Cowan, PA Cohn, DA Cowan, CP Pearson, JL AF Cowan, PA Cohn, DA Cowan, CP Pearson, JL TI Parents' attachment histories and children's externalizing and internalizing behaviors: Exploring family systems models of linkage SO JOURNAL OF CONSULTING AND CLINICAL PSYCHOLOGY LA English DT Article ID CHILDHOOD ATTACHMENT; MATERNAL ATTACHMENT; MARITAL CONFLICT; WORKING MODELS; ADJUSTMENT; MOTHERS; PREDICT; QUALITY AB Twenty-seven mothers and 27 fathers were given the Adult Attachment Interview (M. Main & R. Goldwyn, in press) when their children were 3.5 years old. Continuous ratings of narrative coherence, probable experience quality (parents perceived as loving), and state of mind (current anger at parents) were entered as latent variables in partial least squares structural equation models that included observational measures of marital quality and parenting style. Models that include fathers' attachment histories predicted more variance in kindergarten teachers' descriptions of children's externalizing behavior, whereas models that include mothers' attachment histories predicted more variance in children's internalizing behavior. Marital data added predictive power to the equations. Discussion is focused on the importance of integrating attachment and family systems approaches, and of parents' gender and marital quality, in understanding specific links between parents' attachment histories and their young children's externalizing and internalizing behaviors. C1 UNIV VIRGINIA,CHARLOTTESVILLE,VA 22903. NIMH,ROCKVILLE,MD 20857. RP Cowan, PA (reprint author), UNIV CALIF BERKELEY,DEPT PSYCHOL,3210 TOLMAN HALL,BERKELEY,CA 94720, USA. FU NIMH NIH HHS [MH-31109] NR 52 TC 115 Z9 118 U1 3 U2 30 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 SN 0022-006X J9 J CONSULT CLIN PSYCH JI J. Consult. Clin. Psychol. PD FEB PY 1996 VL 64 IS 1 BP 53 EP 63 DI 10.1037/0022-006X.64.1.53 PG 11 WC Psychology, Clinical SC Psychology GA TX437 UT WOS:A1996TX43700006 PM 8907084 ER PT J AU Kleinman, DV Drury, TF AF Kleinman, DV Drury, TF TI Oral health in the United States, 1988-1991: The first three years of the Third National Health and Nutrition Examination Survey SO JOURNAL OF DENTAL RESEARCH LA English DT Editorial Material C1 NIDR,DIV EPIDEMIOL & ORAL DIS PREVENT,BETHESDA,MD 20892. RP Kleinman, DV (reprint author), NIDR,OFF DIRECTOR,NIH,US PUBL HLTH SERV,NIH BLDG 31,ROOM 2C39,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 0 TC 4 Z9 4 U1 0 U2 0 PU AMER ASSOC DENTAL RESEARCH PI ALEXANDRIA PA 1619 DUKE ST, ALEXANDRIA, VA 22314 SN 0022-0345 J9 J DENT RES JI J. Dent. Res. PD FEB PY 1996 VL 75 SI SI BP 617 EP 617 PG 1 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA UB209 UT WOS:A1996UB20900001 PM 8594085 ER PT J AU Drury, TF Winn, DM Snowden, CB Kingman, A Kleinman, DV Lewis, B AF Drury, TF Winn, DM Snowden, CB Kingman, A Kleinman, DV Lewis, B TI An overview of the oral health component of the 1988-1991 national health and nutrition examination survey (NHANES III-Phase 1) SO JOURNAL OF DENTAL RESEARCH LA English DT Article DE NHANES III; oral health survey AB As part of a Federal consortium, the National Institute of Dental Research's (NIDR) Division of Epidemiology and Oral Disease Prevention (DEODP) staff and consultants collaborated with the National Center for Health Statistics (NCHS) to conduct a national oral health examination as a component of the 1988-94 National Health and Nutrition Examination Survey (NHANES III). The NHANES III was designed to be fielded in two phases. Phase 1 took place between October 18, 1988, and October 24, 1991, at 44 survey locations; Phase 2, between September 20, 1991, and October 15, 1994, at 45 sites. This article provides general background information on the NHANES III and its oral health examination component which pertains to all six years of the full survey. It also focuses on particular aspects of the first three years of the survey (NHANES III-Phase 1)-the database for the articles in this peer-reviewed Special Issue--and provides the essential context for the substantively oriented analyses of the Phase 1 database which are presented in the articles which follow this overview. RP Drury, TF (reprint author), NIDR,NIH,US PUBL HLTH SERV,NATCHER BLDG,45 CTR DR,ROOM 3AN-44A,BETHESDA,MD 20892, USA. NR 9 TC 94 Z9 94 U1 0 U2 4 PU AMER ASSOC DENTAL RESEARCH PI ALEXANDRIA PA 1619 DUKE ST, ALEXANDRIA, VA 22314 SN 0022-0345 J9 J DENT RES JI J. Dent. Res. PD FEB PY 1996 VL 75 SI SI BP 620 EP 630 PG 11 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA UB209 UT WOS:A1996UB20900002 PM 8594086 ER PT J AU Kaste, LM Selwitz, RH Oldakowski, RJ Brunelle, JA Winn, DM Brown, LJ AF Kaste, LM Selwitz, RH Oldakowski, RJ Brunelle, JA Winn, DM Brown, LJ TI Coronal caries in the primary and permanent dentition of children and adolescents 1-17 years of age: United States, 1988-1991 SO JOURNAL OF DENTAL RESEARCH LA English DT Article DE caries; children and adolescents; survey; oral health; race; ethnicity; female; male ID PERIODONTAL-DISEASE; DENTAL-CARIES; PREVALENCE; HHANES AB The Third National Health and Nutrition Examination Survey-Phase 1, conducted from 1988 to 1991 in the United States, included an assessment of dental caries in US children and adolescents and provided the opportunity for differences in dental caries status to be viewed by age, sex, race, and race-ethnicity. The measurement of dental caries in children and adolescents from 2 to 17 years of age included the number of decayed, missing, and filled permanent tooth surfaces and teeth, and the number of decayed and filled primary tooth surfaces and teeth. Additionally, a brief visual inspection for the presence or absence of early childhood caries in the maxillary incisors was conducted for children 12 to 23 months of age. The survey yielded weighted estimates for 1988-1991 for over 58 million US children and adolescents 1 to 17 years of age. For infants aged 12 to 23 months, 0.8% were scored positive for early childhood caries. Over 60% (62.1%) of the children aged 2 to 9 years were caries-free in their primary dentition. Over half (54.7%) of the children 5 to 17 years were caries-free in their permanent dentition. The occurrence of caries in the permanent dentition is clustered: A quarter of the children and adolescents ages 5 to 17 with at least one permanent tooth accounted for about 80% of the caries experienced in permanent teeth. Differences in caries experience were found among race and race-ethnicity subpopulations, and caries patterns for the primary and permanent dentition were dissimilar. Further analyses are needed to explore other potential determinants of caries in children. RP Kaste, LM (reprint author), NIDR,DIV EPIDEMIOL & ORAL DIS PREVENT,NIH,US PUBL HLTH SERV,NATCHER BLDG,ROOM 4AS-25B,BETHESDA,MD 20892, USA. RI de la Flor, Maria/B-9212-2015 NR 17 TC 248 Z9 253 U1 6 U2 12 PU AMER ASSOC DENTAL RESEARCH PI ALEXANDRIA PA 1619 DUKE ST, ALEXANDRIA, VA 22314 SN 0022-0345 J9 J DENT RES JI J. Dent. Res. PD FEB PY 1996 VL 75 SI SI BP 631 EP 641 PG 11 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA UB209 UT WOS:A1996UB20900003 PM 8594087 ER PT J AU Winn, DM Brunelle, JA Selwitz, RH Kaste, LM Oldakowski, RJ Kingman, A Brown, LJ AF Winn, DM Brunelle, JA Selwitz, RH Kaste, LM Oldakowski, RJ Kingman, A Brown, LJ TI Coronal and root caries in the dentition of adults in the United States, 1988-1991 SO JOURNAL OF DENTAL RESEARCH LA English DT Article DE coronal caries; root caries; adults; oral health surveys ID ORAL HEALTH-STATUS; POPULATION; PREVALENCE; DISEASE AB Dental public health policy planning requires accurate and current information about the extent of caries in the United States population. These data are available from the caries examination from Phase 1 of the Third National Health and Nutrition Examination Survey, which found that 94% of adults in the United States show evidence of past or present coronal caries. Among the dentate, the mean number of decayed and filled coronal surfaces per person was 21.5. Dentate females had a lower number of untreated coronal tooth surfaces with caries (1.5), but a higher mean number of treated and untreated surfaces per person (22.7) than males, with scores of 2.1 and 20.2, respectively. Estimates for race-ethnicity groups were standardized by age and gender to control for population differences among them. Dentate non-Hispanic blacks (11.9) and Mexican-Americans (14.1) had half the number of decayed and filled coronal surfaces as non-Hispanic whites (24.3), but more untreated surfaces (non-Hispanic whites, 1.5; non-Hispanic blacks, 3.4; Mexican-Americans, 2.8). Mexican-Americans were most likely to be dentate, had the highest average number of teeth, and had 25% fewer decayed, missing, and filled coronal surfaces (37.6) than non-Hispanic blacks (49.2) and non-Hispanic whites (51.0). Root caries affected 22.5% of the dentate population. Blacks had the most treated and untreated root surfaces with caries (1.6), dose to the value for Mexican-Americans (1.4). The store for non-Hispanic whites was 1.1. Untreated root caries is most common in dentate non-Hispanic blacks (1.5), followed by Mexican-Americans (1.2), with non-Hispanic whites (0.6) having the fewest untreated carious root surfaces. Race-ethnicity groups were disparate with respect to dental caries; effort is needed to treat active caries common in some population subgroups. RP Winn, DM (reprint author), NIDR,DIV EPIDEMIOL & ORAL DIS PREVENT,NIH,US PUBL HLTH SERV,NATCHER BLDG,ROOM 4AS-19F,BETHESDA,MD 20892, USA. NR 18 TC 117 Z9 121 U1 4 U2 8 PU AMER ASSOC DENTAL RESEARCH PI ALEXANDRIA PA 1619 DUKE ST, ALEXANDRIA, VA 22314 SN 0022-0345 J9 J DENT RES JI J. Dent. Res. PD FEB PY 1996 VL 75 SI SI BP 642 EP 651 PG 10 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA UB209 UT WOS:A1996UB20900004 PM 8594088 ER PT J AU Selwitz, RH Winn, DM Kingman, A Zion, GR AF Selwitz, RH Winn, DM Kingman, A Zion, GR TI The prevalence of dental sealants in the US population: Findings from NHANES III, 1988-91 SO JOURNAL OF DENTAL RESEARCH LA English DT Article DE dental sealants; dental health surveys; prevalence ID FISSURE SEALANTS; CARIES; SCHOOLCHILDREN; PATTERNS; CHILDREN; PIT AB Over the past decade, dental sealants have become recognized as an important adjunct to the use of fluorides in the prevention of dental caries. The most recent national survey of oral health in children conducted in 1986-1987 found that only 7.6% of children had any sealed teeth. As part of the oral health component of the 1988-1991 Third National Health and Examination Survey (NHANES III-Phase 1), the prevalence of dental sealants in children, adolescents, and adults was determined. The presence of dental sealants on posterior teeth (excluding third molars) and maxillary lateral incisors was recorded by visual and tactile methods during the dental caries examination. Findings in this paper are based on those examined persons having at least one sealable primary tooth for children aged 2-11 years (n = 3,792); at least one sealable permanent tooth for persons aged 5-17 years (n = 2,989); and at least one sealable permanent tooth for persons aged 18 years and over (n = 7,146). During 1988-1991, about 18.5% of US children and youth ages 5-17 had one or more sealed permanent teeth. A significantly higher percentage of non-Hispanic whites had sealants in comparison with their non-Hispanic black and Mexican-American counterparts (for all contrasts, p < 0.001). As expected, molar teeth were the most frequently sealed tooth type. Only 1.4% of US children ages 2-11 had at least one sealed primary tooth. The prevalence of dental sealants decreased in the US adult population with increasing age; 5.5% of adults ages 18-24 had at least one sealed permanent tooth. Data collected from NHANES III-Phase 2 (1991-1994) will be analyzed to determine if the upward trend in sealant use continues. RP Selwitz, RH (reprint author), NIDR,DIV EPIDEMIOL & ORAL DIS PREVENT,NIH,US PUBL HLTH SERV,NATCHER BLDG,ROOM 3AN-44J,BETHESDA,MD 20892, USA. NR 48 TC 32 Z9 32 U1 0 U2 1 PU AMER ASSOC DENTAL RESEARCH PI ALEXANDRIA PA 1619 DUKE ST, ALEXANDRIA, VA 22314 SN 0022-0345 J9 J DENT RES JI J. Dent. Res. PD FEB PY 1996 VL 75 SI SI BP 652 EP 660 PG 9 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA UB209 UT WOS:A1996UB20900005 PM 8594089 ER PT J AU White, BA Albertini, TF Brown, LJ LarachRobinson, D Redford, M Selwitz, RH AF White, BA Albertini, TF Brown, LJ LarachRobinson, D Redford, M Selwitz, RH TI Selected restoration and tooth conditions: United States, 1988-1991 SO JOURNAL OF DENTAL RESEARCH LA English DT Article DE dental restorations; health services needs; oral health surveys; adults; United States ID RECOMMENDATIONS; LONGEVITY AB The DMF index provides one source of information on past and present dental caries experience; however, important limitations hinder its ability to characterize fully the impact of dental caries. The purpose of this paper is to describe a measure of selected restoration and tooth conditions that supplements information from the DMF index and to report on the application of this measure as part of the Third National Health and Nutrition Examination Survey, Phase 1, conducted between 1988 and 1991. Data from this survey were used to estimate the prevalence and severity of selected disaggregated physical and biological oral conditions among dentate adults aged 18 to 74 years. Trained, standardized, and calibrated dentist examiners assessed 28 permanent teeth or tooth spaces for each of 6,767 subjects. Teeth or tooth spaces were classified based on criteria for: defective intracoronal restorations, crowns, or bridges; gross loss of tooth structure associated with a restoration; pulpal involvement; or retained roots. Approximately 40.5%, or 61.6 million, dentate adults had at least one tooth or tooth space that met the criteria. Among all persons, an average of 0.9 teeth or tooth spaces met the criteria for at least one category. Adults with at least one scored tooth or tooth space had an average of 2.2 such teeth or tooth spaces. Data from this assessment supplement information available from the DMF index to provide a broader profile of the impact of dental caries on permanent teeth of US adults. C1 NIDR,DIV EPIDEMIOL & ORAL DIS PREVENT,NIH,US PUBL HLTH SERV,BETHESDA,MD 20892. KAISER PERMANENTE,CTR HLTH RES,PORTLAND,OR. NR 23 TC 13 Z9 13 U1 0 U2 0 PU AMER ASSOC DENTAL RESEARCH PI ALEXANDRIA PA 1619 DUKE ST, ALEXANDRIA, VA 22314 SN 0022-0345 J9 J DENT RES JI J. Dent. Res. PD FEB PY 1996 VL 75 SI SI BP 661 EP 671 PG 11 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA UB209 UT WOS:A1996UB20900006 PM 8594090 ER PT J AU Brown, LJ Brunelle, JA Kingman, A AF Brown, LJ Brunelle, JA Kingman, A TI Periodontal status in the United States, 1988-91: Prevalence, extent and demographic variation SO JOURNAL OF DENTAL RESEARCH LA English DT Article DE periodontal; prevalence; survey; pocket depth ID DISEASE; SEVERITY; ERRORS AB This paper reports estimates of the periodontal status of US population derived from data from Phase 1 of the Third National Health and Nutrition Examination Survey conducted by the National Center for Health Statistics in collaboration with the National institute of Dental Research from 1988 to 1991. A total of 7,447 dentate individuals 13 years of age and older, representing approximately 160.3 million civilian non-institutionalized Americans, received a periodontal assessment Measurements of gingival bleeding gingival recession level, periodontal pocket depth, and calculus were made by dental examiners. Assessments were made at the mesiobuccal and mid-buccal sites of all fully erupted permanent teeth present in two randomly selected quadrants, one maxillary and one mandibular. All data were weighted and standard errors calculated by special software to adjust for the effect of sample design. Although over 90% of persons 13 years of age or older had experienced some clinical loss of attachment (LA), only 15% exhibited more severe destruction (LA greater than or equal to 5 mm). Prevalence of moderate and severe LA and gingival recession increased with age, while prevalence of pockets greater than or equal to 4 mm or greater than or equal to 6 mm did not. These data suggest that the increasing prevalence of LA with age is more associated with increasing prevalence of recession than with changes in the prevalence of pockets or age. The extent or number of affected sites with advanced conditions for loss of attachment, pocket depth, or recession was not large for: any age group. Differences in prevalence of moderate and severe loss of attachment, moderate and deep pockets, and recession were found among gender and race-ethnicity groups. Females exhibited better periodontal health than males, and non-Hispanic whites exhibited better periodontal health than either non-Hispanic blacks or Mexican-Americans. RP Brown, LJ (reprint author), NIDR,DIV EPIDEMIOL & ORAL DIS PREVENT,NIH,US PUBL HLTH SERV,NATCHER BLDG,ROOM 4AS-13E,BETHESDA,MD 20892, USA. NR 13 TC 185 Z9 192 U1 1 U2 4 PU AMER ASSOC DENTAL RESEARCH PI ALEXANDRIA PA 1619 DUKE ST, ALEXANDRIA, VA 22314 SN 0022-0345 J9 J DENT RES JI J. Dent. Res. PD FEB PY 1996 VL 75 SI SI BP 672 EP 683 PG 12 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA UB209 UT WOS:A1996UB20900007 PM 8594091 ER PT J AU Marcus, SE Drury, TF Brown, LJ Zion, GR AF Marcus, SE Drury, TF Brown, LJ Zion, GR TI Tooth retention and tooth loss in the permanent dentition of adults: United States, 1988-1991 SO JOURNAL OF DENTAL RESEARCH LA English DT Article DE tooth loss; edentulism; prevalence; epidemiology ID PERIODONTAL-DISEASE; DENTAL-CARIES; PREVALENCE; HHANES; PATTERNS; HEALTH; OLDER AB While the overall prevalence of tooth loss and edentulism has been declining in the United States over the past several decades, important variations remain among subgroups of the population. Data from Phase 1 of the Third National Health and Nutrition Examination Survey (NHANES III) provide the most current estimates of the prevalence and distribution of tooth retention and tooth loss in the United States. Weighted analyses were conducted for all adults 18+ years of age (n = 8,366) and for selected age, gender, and race-ethnicity groups. In 1988-91, 89.5% of the population was dentate, and 30.5% had retained all 28 teeth. The mean number of teeth retained was 21.1 for all adults and 23.5 for dentate persons. The most commonly retained teeth in the mouth were the six anterior teeth in the lower arch. Conversely, 10.5% of the population was edentulous. Partial edentulism was much more common in the upper arch than in the lower arch. The most commonly missing teeth were the first and second molars. Age was strongly related to every measure of tooth retention and tooth loss. Gender was not related to any of these measures, after adjustment for age. Race-ethnicity was consistently related to these measures, after adjustment for age and gender. In general, Mexican-Americans had the lowest and black non-Hispanics the highest rates of tooth loss. Future research needs to examine a wide range of potential correlates of tooth retention and tooth loss before we can understand the complex interplay among the personal, dental, and environmental factors influencing tooth retention and tooth loss in the United States. RP Marcus, SE (reprint author), NIDR,DIV EPIDEMIOL & ORAL DIS PREVENT,NIH,US PUBL HLTH SERV,NATCHER BLDG,ROOM 4AS-25J,BETHESDA,MD 20892, USA. NR 41 TC 144 Z9 147 U1 1 U2 7 PU AMER ASSOC DENTAL RESEARCH PI ALEXANDRIA PA 1619 DUKE ST, ALEXANDRIA, VA 22314 SN 0022-0345 J9 J DENT RES JI J. Dent. Res. PD FEB PY 1996 VL 75 SI SI BP 684 EP 695 PG 12 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA UB209 UT WOS:A1996UB20900008 PM 8594092 ER PT J AU Kaste, LM Gift, HC Bhat, M Swango, PA AF Kaste, LM Gift, HC Bhat, M Swango, PA TI Prevalence of incisor trauma in persons 6 to 50 years of age: United States, 1988-1991 SO JOURNAL OF DENTAL RESEARCH LA English DT Article DE incisal trauma; prevalence; children; adults; demographic; race; ethnicity; NHANES III ID ANTERIOR DENTAL TRAUMA; PERMANENT INCISORS; SCHOOL-CHILDREN; AFTER-HOURS; INJURIES; TEETH; NEWCASTLE; PRIVATE; SYDNEY AB Traumatic injuries to the teeth are among the most serious of dental conditions, yet little is known about the prevalence of tooth or dental trauma at the national level. The National Institute of Dental Research (NIDR) modified existing indices for specific use in national epidemiologic studies of tooth trauma among both children and adults. The NIDR index was developed not only to track the status of the tooth from sound (no evidence of trauma) through missing due to trauma, but also to reflect selected sequelae of trauma. The index is based on clinical, non-radiographic evidence of tooth injury and treatment received in the eight permanent incisors, including a positive history of injury obtained from the subject. The trauma assessment index was applied immediately following the caries examination for dentate participants ages 6-50 years old (n = 7,707) in Phase 1 of the NHANES III oral examination. This article reports the first national overall and age-specific population-based prevalence (24.9%) of injury to incisor teeth among individuals ages 6-50 and examines differences in the prevalence of dental trauma among gender, racial, and ethnic groups. There is a higher prevalence of incisal trauma, of both maxillary and mandibular incisors, in males than females, in both the younger and older age groups. The prevalence of incisal trauma of both maxillary and mandibular incisors in whites and blacks in both younger and older age categories is similar. The study found that half of the individuals with trauma had only one incisor tooth classified as having trauma. Males and older age groups showed larger numbers of traumatized teeth. Further study and examination of methodological issues are desirable for additional understanding of incisal trauma in the general population. RP Kaste, LM (reprint author), NIDR,DIV EPIDEMIOL & ORAL DIS PREVENT,NIH,US PUBL HLTH SERV,NATCHER BLDG,ROOM 4AS-25B,BETHESDA,MD 20892, USA. NR 70 TC 95 Z9 95 U1 1 U2 5 PU AMER ASSOC DENTAL RESEARCH PI ALEXANDRIA PA 1619 DUKE ST, ALEXANDRIA, VA 22314 SN 0022-0345 J9 J DENT RES JI J. Dent. Res. PD FEB PY 1996 VL 75 SI SI BP 696 EP 705 PG 10 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA UB209 UT WOS:A1996UB20900009 PM 8594093 ER PT J AU Brunnelle, JA Bhat, M Lipton, JA AF Brunnelle, JA Bhat, M Lipton, JA TI Prevalence and distribution of selected occlusal characteristics in the US population, 1988-1991 SO JOURNAL OF DENTAL RESEARCH LA English DT Article DE occlusion; orthodontics; prevalence AB The inclusion of occlusal traits as part of the oral health component of the Third National Health and Nutrition Examination Survey, Phase 1, 1988-91, provided an opportunity to assess several occlusal characteristics in the US population: diastema greater than or equal to 2 mm, alignment of lower and upper anterior teeth, posterior crossbite, overbite, and overjet. Household questionnaires asked whether the individual had ever received orthodontic treatment. Prevalence of clinical measures of occlusal characteristics and orthodontic treatment was estimated for over 7,000 sample persons from 8 to 50 years of age, representing approximately 150 million non-institutionalized people in the United States. These findings present the first estimates of occlusal status of the US non-institutionalized population in more than 25 years. Eight percent of the population had severe overbite of 6 mm or more. The average overbite was 2.9 mm. Maxillary diastemas greater than or equal to 2 mm were observed in 19% of 8-11-year-olds, 6% of 12-17-year-olds, and 5% of adults 18-50 years old. Twenty-five percent and 22% of persons had zero mm of malalignment in maxillary and mandibular incisors, respectively. Conversely, 11% and 15% of persons had 6 mm or more displacement of maxillary and mandibular molars, respectively. Posterior crossbite affects less than 10% of this population, and less than 10% had overjet of 6 mm or more. Non-Hispanic black adults had the least amount of malalignment in mandibular incisors. Three times as many non-Hispanic blacks compared with non-Hispanic whites and Mexican-Americans had diastemas greater than or equal to 2 mm. Comparisons with published data from the National Health Examination Survey (1966-70) indicated a 20% increase of 12-17-year-olds with overbite in the normal range (0-3 mm). Almost 20% of adults ages 18-50, as well as 18% of children, have had orthodontic treatment. C1 DEPT ENERGY,OFF INT HLTH STUDIES EH63,GERMANTOWN,MD. NIDR,DIV EXTRAMURAL RES,NIH,US PUBL HLTH SERV,BETHESDA,MD 20892. RP Brunnelle, JA (reprint author), NIDR,DIV EPIDEMIOL & ORAL DIS PREVENT,NIH,US PUBL HLTH SERV,NATCHER BLDG,ROOM 4AS-25E,BETHESDA,MD 20892, USA. NR 12 TC 76 Z9 82 U1 2 U2 3 PU AMER ASSOC DENTAL RESEARCH PI ALEXANDRIA PA 1619 DUKE ST, ALEXANDRIA, VA 22314 SN 0022-0345 J9 J DENT RES JI J. Dent. Res. PD FEB PY 1996 VL 75 SI SI BP 706 EP 713 PG 8 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA UB209 UT WOS:A1996UB20900010 PM 8594094 ER PT J AU Redford, M Drury, TF Kingman, A Brown, LJ AF Redford, M Drury, TF Kingman, A Brown, LJ TI Denture use and the technical anality of dental prostheses among persons 18-74 years of age: United States, 1988-1991 SO JOURNAL OF DENTAL RESEARCH LA English DT Article DE oral health survey; denture use; denture quality; prosthodontics; NHANES III ID ORAL HEALTH-STATUS; ELDERLY POPULATION; TREATMENT NEEDS; PROSTHODONTIC TREATMENT; NORTHERN NORWAY; SERVICE AB For persons without all or some of their natural teeth in one or both arches, the use of a complete or partial denture and the quality of the denture used are important aspects of their oral health and functioning. This report of prosthodontic findings from the first three years of the 1988-94 National Health and Nutrition Examination Survey (NHANES III-Phase 1) provides estimates of denture use among the US civilian non-institutionalized population 18-74 years of age, as well as seminal information on the technical quality of dental prostheses nationwide. NHANES III-Phase 1 prosthodontic findings indicate that about one in five persons 18-74 years of age wears a removable prosthodontic appliance of some type. Overall, removable prosthodontic appliances are worn disproportionately more often by women than by men, and less frequently by whites than by blacks. Comparisons among race-ethnicity categories indicate that Mexican-Americans are less likely to use dentures than either of their non-Hispanic counterparts. Analyses of prosthodontic evaluation data indicate that approximately 60% of denture users have at least one problem with a denture. These findings from the oral component of NHANES III-Phase 1 provide clear indications that, despite increasing trends in tooth retention, dependence on removable prosthodontic appliances is still a reality of life for millions of Americans. RP Redford, M (reprint author), NIDR,DIV EPIDEMIOL & ORAL DIS PREVENT,NIH,US PUBL HLTH SERV,NATCHER BLDG,ROOM 3AN-44D,BETHESDA,MD 20892, USA. NR 42 TC 48 Z9 51 U1 0 U2 3 PU AMER ASSOC DENTAL RESEARCH PI ALEXANDRIA PA 1619 DUKE ST, ALEXANDRIA, VA 22314 SN 0022-0345 J9 J DENT RES JI J. Dent. Res. PD FEB PY 1996 VL 75 SI SI BP 714 EP 725 PG 12 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA UB209 UT WOS:A1996UB20900011 PM 8594095 ER PT J AU Carrera, L Gazzinelli, RT Badolato, R Hieny, S Muller, W Kuhn, R Sacks, DL AF Carrera, L Gazzinelli, RT Badolato, R Hieny, S Muller, W Kuhn, R Sacks, DL TI Leishmania promastigotes selectively inhibit interleukin 12 induction in bone marrow-derived macrophages from susceptible and resistant mice SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article ID INTERFERON-GAMMA-PRODUCTION; NATURAL-KILLER-CELLS; PROTEIN-KINASE-C; NECROSIS-FACTOR-ALPHA; GROWTH-FACTOR-BETA; CD4+ T-CELLS; IFN-GAMMA; MURINE LEISHMANIASIS; SIGNAL TRANSDUCTION; CYTOKINE PRODUCTION AB Leishmania major promastigotes were found to avoid activation of mouse bone marrow-derived macrophages (BMMo) in vitro for production of cytokines that are typically induced during infection with other intracellular pathogens. Coexposure of BMMo to the parasite and other microbial stimuli resulted in complete inhibition of interleukin (IL) 12 (p40) mRNA induction and IL-12 release. In contrast, mRNA and protein levels for IL-1 alpha, IL-1 beta, tumor necrosis factor (TNF) alpha, and inducible NO synthase (iNOS) were only partially reduced, and signals for IL-10 and monocyte chemoattractant protein (MCP-1/JE) were enhanced. The parasite could provide a detectable trigger for TNF-alpha and iNOS in BMMo primed with interferon (IFN) gamma, but still failed to induce IL-12. Thus IL-12 induction is selectively impaired after infection, whereas activation pathways for other monokine responses remain relatively intact. Selective and complete inhibition of IL-12(p40) induction was observed using BMMo from either genetically susceptible or resistant mouse strains, as well as IL-10 knockout mice, and was obtained using promastigotes from cutaneous, visceral, and lipophosphoglycan-deficient strains of Leishmania. The impaired production of the major physiologic inducer of IFN-gamma is suggested to underlie the relatively prolonged interval of parasite intracellular survival and replication that is typically associate with leishmanial infections, including those producing self-limiting disease. C1 NIAID,PARASIT DIS LAB,NIH,BETHESDA,MD 20892. NCI,DIV CANC TREATMENT,PROGRAM RESOURCES INC DYNCORP,BIOL CARCINOGENESIS & DEV PROGRAM,FREDERICK,MD 21702. UNIV COLOGNE,INST GENET,D-50923 COLOGNE,GERMANY. RI Badolato, Raffaele/A-8081-2010; Muller, Werner/B-9044-2008 OI Badolato, Raffaele/0000-0001-7375-5410; Muller, Werner/0000-0002-1297-9725 NR 66 TC 234 Z9 238 U1 0 U2 3 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 222 E 70TH STREET, NEW YORK, NY 10021 SN 0022-1007 J9 J EXP MED JI J. Exp. Med. PD FEB 1 PY 1996 VL 183 IS 2 BP 515 EP 526 DI 10.1084/jem.183.2.515 PG 12 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA TW109 UT WOS:A1996TW10900017 PM 8627163 ER PT J AU Weissman, D Barker, TD Fauci, AS AF Weissman, D Barker, TD Fauci, AS TI The efficiency of acute infection of CD4(+) T cells is markedly enhanced in the setting of antigen-specific immune activation SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article ID INCUBATION PERIOD; HIV-1 INFECTION; HTLV-III/LAV; LYMPHOCYTES; AIDS; DISEASE AB Human immunodeficiency virus (HIV) disease is sub-Saharan Africa generally differs from that observed in the United States and other developed countries in that the risk of seroconversion after exposure is greater and the rate of disease progression to AIDS and death is faster. One theory that could in part explain this difference is the increased state of immune activation associated with a relatively high rate of parasite infestation and other infections among inhabitants of these regions. Using a model based on the cellular microenvironment of lymphoid organs, the role of exposure to HIV during a state of antigen-specific immune activation was investigated. Dendritic cells and CD4(+) T cells are the major cellular components of the paracortical region of lymphoid tissue, the primary site of HIV replication. We analyzed cocultures of HIV-pulsed dendritic cells that had matured in the presence of tetanus toroid and CD4(+) T cells before and after inducing an antigen-specific response by in vivo immunization with tetanus toxoid. During antigen-specific immune activation, 100 times less HIV was needed to initiate a productive infection. These findings provide a model system to further delineate the relationship between immune activation and the propagation of HIV infection and suggest a mechanism for the epidemiologic observations of an increased ease of developing HIV infection and faster progression for HIV disease in geographic areas where immune activation is prevalent. RP Weissman, D (reprint author), NIAID, NIH,LIR,BLDG 10,ROOM 6A02, 10 CTR DR MSC 1576, BETHESDA, MD 20892 USA. NR 33 TC 98 Z9 98 U1 0 U2 1 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0022-1007 J9 J EXP MED JI J. Exp. Med. PD FEB 1 PY 1996 VL 183 IS 2 BP 687 EP 692 DI 10.1084/jem.183.2.687 PG 6 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA TW109 UT WOS:A1996TW10900037 PM 8627183 ER PT J AU Stuber, E Strober, W Neurath, M AF Stuber, E Strober, W Neurath, M TI Blocking the CD40L-CD40 interaction in vivo specifically prevents the priming of T helper 1 cells through the inhibition of interleukin 12 secretion SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article ID INTERFERON-GAMMA PRODUCTION; CD40; ANTIBODY; LIGAND; GP39 AB The recent finding that CD40L on activated T cells induces interleukin (IL) 12 secretion in human peripheral blood monocytes in vitro suggests that the CD40L-CD40 interaction may be of importance in the priming of T helper (Th) 1-type T cells. We therefore investigated the in vivo relevance of this interaction in an experimental model for a Th1-mediated disease, the hapten reagent (2,4,6-trinitrobenzene sulfonic acid [TNBS])-induced colitis. The administration of anti-gp39 (CD40L) antibodies during the induction phase of the Th1 response prevented interferon gamma production by lamina propria CD4(+) T cells and also clinical and histological evidence of disease. In contrast, the secretion of IL-4, a Th2-type cytokine, was increased after anti-gp39 treatment. In further studies we showed that the prevention of disease activity was caused by an inhibition of IL-12 secretion, as demonstrated by immunohistochemistry. In addition, the injection of recombinant IL-12 p70 heterodimer into TNBS + anti-gp39-treated mice reversed the effect of anti-gp39 and resulted in severe disease activity. When anti-gp39 was given after the disease was established, no effect on the disease activity was observed. In conclusion, we demonstrated that the CD40L-CD40 interaction is crucial for the in vivo priming of Th1 T cells via the stimulation of IL-12 secretion by antigen-presenting cells (APC). C1 NIAID,NIH,MUCOSAL IMMUN SECT,CLIN INVEST LAB,BETHESDA,MD 20892. NR 22 TC 289 Z9 292 U1 0 U2 2 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 222 E 70TH STREET, NEW YORK, NY 10021 SN 0022-1007 J9 J EXP MED JI J. Exp. Med. PD FEB 1 PY 1996 VL 183 IS 2 BP 693 EP 698 DI 10.1084/jem.183.2.693 PG 6 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA TW109 UT WOS:A1996TW10900038 PM 8627184 ER PT J AU Sandler, AB Baker, CC Spalholz, BA AF Sandler, AB Baker, CC Spalholz, BA TI Sp1 is critical for basal and E2-transactivated transcription from the bovine papillomavirus type 1 P-89 promoter SO JOURNAL OF GENERAL VIROLOGY LA English DT Article ID E1 REPLICATION PROTEIN; NUCLEAR FACTOR-I; TRANSFORMING REGION; BINDING-SITES; E2 PROTEIN; CONSTITUTIVE ENHANCER; DNA-REPLICATION; GENE-PRODUCT; C127 CELLS; ACTIVATION AB The bovine papillomavirus type 1 (BPV-1) long control region (LCR) contains at least three consensus binding sites for the transcription factor Spl at nucleotides (nt) 7800, 7833 and 7854. A high basal-level P-89 expression vector consisting of an origin-deleted LCR fused to the chloramphenicol acetyltransferase (CAT) gene was utilized to determine the role of these Spl sites in the regulation of transcription from the BPV-1 P-89 promoter. The three Spl sites were capable of binding Spl in vitro. Mutation of these sites in the background of the origin-deleted LCR-CAT or a wild-type LCR-CAT construct resulted in decreased basal expression from P-89. In addition, mutation of the Spl sites in the wild-type background caused a reduction in E2-transactivation potential. These data illustrate the importance of these Spl sites in regulating both basal and E2-transactivated P-89 expression. C1 NCI,TUMOR VIRUS BIOL LAB,BETHESDA,MD 20892. NR 40 TC 8 Z9 8 U1 0 U2 0 PU SOC GENERAL MICROBIOLOGY PI READING PA HARVEST HOUSE 62 LONDON ROAD, READING, BERKS, ENGLAND RG1 5AS SN 0022-1317 J9 J GEN VIROL JI J. Gen. Virol. PD FEB PY 1996 VL 77 BP 189 EP 198 DI 10.1099/0022-1317-77-2-189 PN 2 PG 10 WC Biotechnology & Applied Microbiology; Virology SC Biotechnology & Applied Microbiology; Virology GA TT842 UT WOS:A1996TT84200006 PM 8627222 ER PT J AU Roccella, EJ AF Roccella, EJ TI Considerations for evaluating community high blood pressure control programmes SO JOURNAL OF HUMAN HYPERTENSION LA English DT Article; Proceedings Paper CT World Conference on Hypertension Control - Hypertension Control - Worldwide Experience CY JUN 21-24, 1995 CL OTTAWA, CANADA SP World Hypertens League, Canadian Coalit High Blood Pressure Prevent & Control, Health Canada, Canadian Hypertens Soc DE programme evaluation; hypertension; community programmes; outcome evaluation AB A major reason for building evaluation procedures into community high blood pressure control programme is the potential to influence programme planning and operation positively. Evaluation can assist smooth, successful Implementation of programme plans on a continuous basis. Evaluation can provide for staff development and training and help administrators be accountable to themselves, their staffs, and their clients. Three basis types of evaluation are relevant to hypertension control programmes: process, outcome, and impact. Process evaluation measures programme efforts by assessing, modifying, and reassessing daily operations. This type of evaluation examines the use of resources, patterns of staff interaction, processes used in planning, decision making, or organization of staff to carry out these efforts. Outcome evaluation measures programme effects and extent to which programme achieve results in the target population. This activity helps determine how well programme objectives are achieved and whether activities should be continued, expanded, or redirected. Impact evaluation provides information on the long-term effects of the hypertension control programme on the community at large, such as morbidity and mortality changes. Because of the need for large sample sizes to detect these changes, impact evaluation is not usually conducted by a single community programme. As community programmes grow in number, the competition for resources becomes greater. Legislators will demand more information about programme costs and effectiveness, which will justify expenditures and compete for additional resources. RP Roccella, EJ (reprint author), NHLBI,NATL HIGH BLOOD PRESSURE EDUC PROGRAMME,BLDG 10,BETHESDA,MD 20892, USA. NR 3 TC 1 Z9 1 U1 0 U2 0 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE, HAMPSHIRE, ENGLAND RG21 6XS SN 0950-9240 J9 J HUM HYPERTENS JI J. Hum. Hypertens. PD FEB PY 1996 VL 10 SU 1 BP S17 EP S19 PG 3 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA UD154 UT WOS:A1996UD15400010 PM 8965281 ER PT J AU Khodarev, NN Ashwell, JD AF Khodarev, NN Ashwell, JD TI An inducible lymphocyte nuclear Ca2+/Mg2+-dependent endonuclease associated with apoptosis SO JOURNAL OF IMMUNOLOGY LA English DT Article ID CALCIUM-DEPENDENT ENDONUCLEASE; PROGRAMMED CELL-DEATH; POLYACRYLAMIDE-GEL-ELECTROPHORESIS; INTERNUCLEOSOMAL DNA CLEAVAGE; THYMOCYTE APOPTOSIS; FRAGMENTS PRIOR; RAT THYMOCYTES; HUMAN SPLEEN; CYCLE BLOCK; ACTIVATION AB Apoptotic cell death is typically accompanied by internucleosomal chromatin fragmentation, Although a number of candidate enzymes have been proposed, there is as yet no direct evidence for the involvement of any particular endonuclease in this process. Here we demonstrate the existence of an endonuclease(s) that is up-regulated during apoptotic T cell death, The endonuclease(s) is located in the nucleus, and its activity is increased up to eightfold by a variety of stimuli or conditions that induce apoptosis in T cell hybridomas and thymocytes. Treatments that prevent TCR-mediated apoptosis, such as cyclosporin A or concomitant administration of glucocorticoids, also prevent the induction of enzyme activity, The endonuclease activity is associated with three molecular forms, designated A, B, and C, with apparent M(r) of 49K, 47K, and 45K, respectively, and constitutes the major endonuclease activity in T hybridoma cells. Form A exists in resting cells, and its activity is increased threefold after the induction of apoptosis, Forms B and C are absent in resting cells and are induced up to 20-fold after stimuli that lead to apoptosis, All three forms are Ca2+/Mg2+ dependent and are inhibited by Zn2+. This enzyme(s) introduces double strand breaks and single strand nicks into supercoiled plasmid DNA, demonstrating the mode of DNA fragmentation characteristic of products of apoptotic chromatin degradation, The enzyme(s) produces DNA fragments with 5'-P and 3'-OH terminals, also consistent with apoptotic chromatin degradation. Finally, enzyme solubilized from cells activated to die cleaves chromatin in nuclei isolated from unstimulated T hybridoma cells, yielding the classic DNA ladder, Because of its biologic properties, we named this enzyme(s) inducible lymphocyte Ca2+/Mg2+-dependent endonuclease, or ILCME. Because inducible lymphocyte Ca2+/Mg2+-dependent endonuclease possesses the key features predicted for an apoptosis-specific enzyme, it is a new candidate for an enzyme(s) that participates in DNA cleavage in apoptotic T cells. C1 NCI,LAB IMMUNE CELL BIOL,BETHESDA,MD 20892. NR 78 TC 49 Z9 52 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 FEB 1 PY 1996 VL 156 IS 3 BP 922 EP 931 PG 10 WC Immunology SC Immunology GA TR327 UT WOS:A1996TR32700006 PM 8558018 ER PT J AU Lloyd, AR Oppenheim, JJ Kelvin, DJ Taub, DD AF Lloyd, AR Oppenheim, JJ Kelvin, DJ Taub, DD TI Chemokines regulate T cell adherence to recombinant adhesion molecules and extracellular matrix proteins SO JOURNAL OF IMMUNOLOGY LA English DT Article ID TUMOR-NECROSIS-FACTOR; ENDOTHELIAL-CELLS; LYMPHOCYTE INTERACTIONS; CYTOKINE FAMILY; BINDING; MIP-1-BETA; EXPRESSION; RECEPTORS; GAMMA; MIP-1-ALPHA AB Chemokines are a family of structurally related, low m.w. proteins that regulate leukocyte migration both in vitro and in vivo, By virtue of their target cell specificity, chemokines have the potential to selectively recruit leukocyte subpopulations into sites of inflammation during the genesis of an immune response. Chemokines have been shown to induce leukocyte adhesion to endothelium, to facilitate trans-endothelial passage, and to direct cell migration along a protein gradient (chemotaxis), The chemokines (macrophage inflammatory protein-1 alpha, macrophage inflammatory protein-1 beta, RANTES, and IFN-inducible protein-10) have recently been reported to be chemotactic for T cells, We have investigated the potential activity of these proteins in regulation of T cell adhesion. These chemokines induce T cell adhesion to purified, recombinant human adhesion molecules (rhlCAM-1, rhVCAM-1) and to ECM proteins: fibronectin, collagen, and laminin, The chemokine-induced adhesion process occurs rapidly, is dose-dependent, and appears to be mediated via beta(1) and beta(2) integrins, The enhanced T cell adhesion is not associated with an increased surface expression of adhesion proteins, suggesting that chemokines stimulate the development of a high affinity state in the integrin molecules, Our findings provide in vitro evidence of a critical role for chemokines in T cell adhesion to endothelial adhesion molecules and ECM proteins, thereby promoting haptotactic migration of T cells to sites of inflammation in vivo. C1 NCI,BIOL RESPONSE MODIFIERS PROGRAM,MOLEC IMMUNOREGULAT LAB,FREDERICK,MD 21702. NR 25 TC 171 Z9 172 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 FEB 1 PY 1996 VL 156 IS 3 BP 932 EP 938 PG 7 WC Immunology SC Immunology GA TR327 UT WOS:A1996TR32700007 PM 8558019 ER PT J AU Denkers, EY Caspar, P Hieny, S Sher, A AF Denkers, EY Caspar, P Hieny, S Sher, A TI Toxoplasma gondii infection induces specific nonresponsiveness in lymphocytes bearing the V beta 5 chain of the mouse T cell receptor SO JOURNAL OF IMMUNOLOGY LA English DT Article ID STAPHYLOCOCCAL ENTEROTOXIN-B; TUMOR-NECROSIS-FACTOR; NATURAL-KILLER-CELLS; INTERFERON-GAMMA; FACTOR-ALPHA; IMMUNE-RESPONSES; IN-VIVO; MICE; SUPERANTIGEN; RESISTANCE AB We recently reported a superantigen activity associated with Toxoplasma gondii tachyzoites that in vitro induces preferential expansion of V beta 5(+) T lymphocytes following parasite stimulation of nonimmune cells. In the experiments presented in this work, V beta 5(+) lymphocyte function was examined ex vivo using mice undergoing chronic and acute infection with the avirulent parasite strain ME49 or acutely infected with the attenuated mutant ts-4, Cells bearing the TCR V beta 5 chain were found to be increased by 1.5- to twofold during acute infection, whereas during the chronic phase, modest decreases (similar to 20%) in cells of the latter subset were observed. When splenocytes from chronically infected animals were stimulated in vitro with tachyzoites, the preferential expansion of V beta 5(+) lymphocytes seen using cells from normal mice was not observed. Furthermore, when purified T lymphocytes were cultured with plate-bound V beta 5-specific mAb, we found that in contrast to normal and acutely infected animals, cells from chronically infected and ts-4-vaccinated mice were nonresponsive to TCR-induced stimulation (70 to 90% reduction relative to normal cells). In control experiments, mAb to CD3 and V beta 8 elicited normal responses in the same animals. Similarly, in contrast to normal splenocytes, cells from chronically infected mice failed to produce IFN-gamma in response to anti-V beta 5 mAb. These data indicate that V beta 5(+) tells are rendered nonresponsive as a result of in vivo encounter with T. gondii, and as such they provide the first demonstration of V beta-specific anergy induced by a protozoan parasite. C1 NIAID, PARASIT DIS LAB, IMMUNOBIOL SECT, BETHESDA, MD 20892 USA. NR 52 TC 24 Z9 24 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD FEB 1 PY 1996 VL 156 IS 3 BP 1089 EP 1094 PG 6 WC Immunology SC Immunology GA TR327 UT WOS:A1996TR32700026 PM 8557983 ER PT J AU StefanovicRacic, M Morales, TI Taskiran, D McIntyre, LA Evans, CH AF StefanovicRacic, M Morales, TI Taskiran, D McIntyre, LA Evans, CH TI The role of nitric oxide in proteoglycan turnover by bovine articular cartilage organ cultures SO JOURNAL OF IMMUNOLOGY LA English DT Article ID CHONDROCYTES; ARTHRITIS; METABOLISM; CYTOKINES; SYNTHASE; NITRATE; ACID; BETA AB Monolayer cultures of articular chondrocytes synthesize large amounts of nitric oxide (NO) following exposure to IL-1. The latter has antianabolic and procatabolic activities on these cells, but little is known about the role, if any, of NO in the integrated metabolic pathways of the chondrocyte. In the present study, the role of endogenously produced NO in both the synthesis and degradation of proteoglycans was investigated for the first time. Bovine articular cartilage slices exposed to 20 U/ml human rIL-1 beta (hrIL-1 beta) synthesized large amounts of NO for 1 to 2 days, after which production fell to a steady state level similar to 20% of the peak value for the remainder of the 14-day incubation. The NO synthase inhibitor, N-monomethyl L-arginine (L-NMA, 1 mM), blocked NO production and enhanced the acute catabolic effects of hrIL-1 beta in cartilage derived from both calves and adult animals. However, in late cultures, release of proteoglycans was reduced in the presence of L-NMA. The proteolytic activity in conditioned medium of these cultures (measured as caseinolytic activity) was enhanced by L-NMA; however, this inhibitor did not affect the rates of synthesis of proteoglycans. Although NO is widely assumed to be a mediator of cartilage catabolism, our data suggest that it may instead have an acute protective effect. Whether this effect is maintained chronically is less clear. C1 UNIV PITTSBURGH,SCH MED,FERGUSON LAB,DEPT ORTHOPED SURG,PITTSBURGH,PA 15261. NIDR,BETHESDA,MD 20892. OI Taskiran, Dilek/0000-0002-4505-0939 FU NIAMS NIH HHS [R01 AR42025] NR 35 TC 98 Z9 99 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 FEB 1 PY 1996 VL 156 IS 3 BP 1213 EP 1220 PG 8 WC Immunology SC Immunology GA TR327 UT WOS:A1996TR32700043 PM 8558000 ER PT J AU Gorse, GJ Keefer, MC Belshe, RB Matthews, TJ Forrest, BD Hsieh, RH Koff, WC Hanson, CV Dolin, R Weinhold, KJ Frey, SE Ketter, N Fast, PE AF Gorse, GJ Keefer, MC Belshe, RB Matthews, TJ Forrest, BD Hsieh, RH Koff, WC Hanson, CV Dolin, R Weinhold, KJ Frey, SE Ketter, N Fast, PE TI A dose-ranging study of a prototype synthetic HIV-1(MN) V3 branched peptide vaccine SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article ID IMMUNODEFICIENCY-VIRUS TYPE-1; LYMPHOCYTE PROLIFERATIVE RESPONSES; GP160 RECOMBINANT VACCINIA; NEUTRALIZING ANTIBODIES; MONOCLONAL-ANTIBODY; NAIVE ADULTS; HTLV-III; GP120; INFECTION; ENVELOPE AB A phase I double-blind trial was done to examine the safety and immunogenicity of a prototype synthetic human immunodeficiency virus type 1 MN strain (HIV-1(MN)) third variable region domain (V3) branched peptide vaccine in HIV-1-uninfected healthy adult volunteers, Subjects were randomly assigned to receive 20, 100, or 500 mu g of vaccine or alum adjuvant control on days 0, 28, and 168, The vaccine was well-tolerated and appeared safe, Induction of binding antibody to V3 MN branched peptide was vaccine dose-related and was detectable in 9 of 10 subjects in the highest-vaccine-dose group, HIV-1(MN)-neutralizing antibody was detected after the third 500-mu g dose in 8 of 10 subjects at the 90% neutralization end point, V3 MN peptide stimulated lymphocyte proliferation in 15 (75%) of 20 subjects after vaccination, In conclusion, this prototype vaccine was safe and it induced humoral and cell-mediated immune responses. C1 VET ADM MED CTR,ST LOUIS,MO. UNIV ROCHESTER,SCH MED & DENT,DEPT MED,ROCHESTER,NY 14642. UNITED BIOMED INC,HAUPPAUGE,NY. DUKE UNIV,SCH MED,DEPT SURG,RALEIGH,NC. CALIF DEPT HLTH SERV,VIRAL & RICKETTSIAL DIS LAB,BERKELEY,CA 94704. NIAID,DIV AIDS,BETHESDA,MD 20892. EMMES CORP,POTOMAC,MD. RP Gorse, GJ (reprint author), ST LOUIS UNIV,SCH MED,DEPT INTERNAL MED,DIV INFECT DIS & IMMUNOL,3635 VISTA AVE,FDT-8N,POB 15250,ST LOUIS,MO 63110, USA. FU NIAID NIH HHS [AI-45211, AI-05064, AI-05063] NR 66 TC 49 Z9 51 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 FEB PY 1996 VL 173 IS 2 BP 330 EP 339 PG 10 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA TT665 UT WOS:A1996TT66500008 PM 8568293 ER PT J AU Mascola, JR Snyder, SW Weislow, OS Belay, SM Belshe, RB Schwartz, DH Clements, ML Dolin, R Graham, BS Gorse, GJ Keefer, MC McElrath, MJ Walker, MC Wagner, KF McNeil, JG McCutchan, FE Burke, DS AF Mascola, JR Snyder, SW Weislow, OS Belay, SM Belshe, RB Schwartz, DH Clements, ML Dolin, R Graham, BS Gorse, GJ Keefer, MC McElrath, MJ Walker, MC Wagner, KF McNeil, JG McCutchan, FE Burke, DS TI Immunization with envelope subunit vaccine products elicits neutralizing antibodies against laboratory-adapted but not primary isolates of human immunodeficiency virus type 1 SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article ID FELINE LEUKEMIA-VIRUS; SOLUBLE CD4; RECOMBINANT GP160; MONOCLONAL-ANTIBODY; GLYCOPROTEIN GP120; HIV-1 INFECTION; SCD4 BINDING; CHIMPANZEES; PROTECTION; IMMUNOGENICITY AB Phase I studies of volunteers not infected with human immunodeficiency virus type 1 (HIV-1) have shown that immunization with envelope subunit vaccine products elicits antibodies that neutralize laboratory-adapted (prototype) HIV-1 strains in vitro, Prototype strains are adapted to grow in continuous (neoplastic) cell lines and are more susceptible to neutralization than are primary isolates cultured in human peripheral blood mononuclear cells, In this study, 50 sera from nine phase I vaccine trials and 16 from HIV-1-infected persons were evaluated for neutralizing antibody activity against 3 laboratory-adapted and 5 primary HIV-1 isolates, Of 50 sera, 49 neutralized at least 1 of the prototype strains; however, none displayed neutralizing activity against primary isolates of HIV-1, Serum from most HIV-1-infected persons neutralized both laboratory-adapted and primary HIV-1 isolates, These data demonstrate a qualitative, or large quantitative, difference in the neutralizing antibody response induced by envelope subunit vaccination and natural HIV-1 infection. C1 SRA TECHNOL INC,ROCKVILLE,MD. USN,MED RES INST,DEPT INFECT DIS,BETHESDA,MD. NIAID,BETHESDA,MD 20892. JOHNS HOPKINS UNIV,SCH HYG & PUBL HLTH,BALTIMORE,MD 21205. SCH MED,BALTIMORE,MD. ST LOUIS UNIV,SCH MED,DEPT MED,ST LOUIS,MO. UNIV ROCHESTER,SCH MED & DENT,DEPT MED,NEW YORK,NY. VANDERBILT UNIV,SCH MED,DEPT MED,NASHVILLE,TN 37212. WASHINGTON UNIV,SCH MED,DEPT MED,SEATTLE,WA. RP Mascola, JR (reprint author), WALTER REED ARMY INST RES,DIV RETROVIROL,HENRY M JACKSON FDN ADV MIL MED,13 TAFT CT,ROCKVILLE,MD 20850, USA. OI /0000-0002-5704-8094 FU NIAID NIH HHS [AI-05061, AI-05063, AI-05064] NR 67 TC 370 Z9 373 U1 2 U2 8 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 FEB PY 1996 VL 173 IS 2 BP 340 EP 348 PG 9 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA TT665 UT WOS:A1996TT66500009 PM 8568294 ER PT J AU Beretta, A Weiss, SH Rappocciolo, G Mayur, R DeSantis, C Quirinale, J Cosma, A Robbioni, P Shearer, GM Berzofsky, JA Villa, ML Siccardi, AG Clerici, M AF Beretta, A Weiss, SH Rappocciolo, G Mayur, R DeSantis, C Quirinale, J Cosma, A Robbioni, P Shearer, GM Berzofsky, JA Villa, ML Siccardi, AG Clerici, M TI Human immunodeficiency virus type 1 (HIV-1)-seronegative injection drug users at risk for HIV exposure have antibodies to HLA class I antigens and T cells specific for HIV envelope SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article ID GP120 AB The question of whether persistently seronegative persons at high risk for human immunodeficiency virus type 1 (HIV-1) infection exhibit HIV-1-specific T cell responses and antibodies to HIV-1 envelope epitopes shared with selected HLAs was assessed, These antibodies are not detectable by conventional serologic methods, Envelope-specific helper T (Env-Th) cell responses and antibodies specific for the HIV/HLA epitopes were studied in 21 HIV-1-negative injection drug users (IDUs), HIV/HLA antibodies were detected in 7 (33.3%) of 21 IDUs and 4 (4.3%) of 94 low-risk controls, Env-Th cell responses were detected in 16 (76.2%) of 21 IDUs and in 2 (3.1%) of 65 low-risk controls, All HIV/HLA antibody-positive IDUs also had Env-Th cell responses, These findings confirm the presence of HIV-1-specific immunity in conventionally seronegative individuals, Further characterization of these responses could provide the basis for new preventive strategies. C1 UNIV MILAN,CATTEDRA IMMUNOL,MILAN,ITALY. NCI,EXPTL IMMUNOL & METAB BRANCH,BETHESDA,MD. UNIV MED & DENT NEW JERSEY,DEPT PREVENT MED & COMMUNITY HLTH,DIV INFECT DIS & EPIDEMIOL,NEWARK,NJ 07103. TECHNOMETRICA INC,EMERSON,NJ. RP Beretta, A (reprint author), S RAFFAELE SCI INST,DEPT BIOL & TECHNOL,VIA OLGETTINA 58,I-20132 MILAN,ITALY. OI Rappocciolo, Giovanna/0000-0002-6415-0847; Cosma, Antonio/0000-0002-3686-8034 NR 14 TC 43 Z9 43 U1 0 U2 1 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 S WOODLAWN AVE, CHICAGO, IL 60637 SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD FEB PY 1996 VL 173 IS 2 BP 472 EP 476 PG 5 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA TT665 UT WOS:A1996TT66500030 PM 8568315 ER PT J AU Hertl, M Asada, H Katz, SI AF Hertl, M Asada, H Katz, SI TI Murine epidermal langerhans cells do not express the low-affinity receptor for immunoglobulin E, Fc epsilon RII (CD23) SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Article DE mouse CD23; interleukin-4; interferon-gamma; trypsin ID ATOPIC-DERMATITIS; IA ANTIGENS; B-CELLS; IGE; FC-EPSILON-RII/CD23; IDENTIFICATION; KERATINOCYTES; MACROPHAGES; ANTIBODIES; INDUCTION AB The low-affinity receptor for IgE, Fc epsilon RII (CD23), plays an important role in IgE-mediated disorders such as allergy, atopy, and parasitic infections. In humans, the Fc epsilon RIIb isoform on epidermal Langerhans cells is thought to be an important accessory molecule in the allergen-specific T cell activation in atopic dermatitis, Since considerable knowledge about the accessory function of Langerhans cells for T-cell activation stems from mouse models, and since an IgE-bearing Langerhans cell mouse model would be useful in studying the pathophysiology of atopic dermatitis, we determined whether Fc epsilon RII was also present on murine Langerhans cells, Fc epsilon RIIa, which is the major Fc epsilon RII isoform in mice, was found to be constitutively expressed on spleen cells from normal mice but was not present on epidermal Langerhans cells. When interleukin-4, a known inducer of Fc epsilon RII, was administered in vivo, Fc epsilon RII-specific mRNA and protein was significantly upregulated in spleen cells but not in Langerhans cells, De novo synthesis of Fc epsilon RII was also induced in vitro by interleukin-4 on spleen cells, but not on epidermal cells. The presence of a recently cloned murine counter-part to the human Fc epsilon RIIb isoform on murine Langerhans cells could also be excluded on the protein and mRNA level because of the high degree of homology to mouse Fc epsilon RIIa. Taken together the data indicate that murine epidermal Langerhans cells do not express the low-affinity receptor for IgE. C1 NCI,DERMATOL BRANCH,BETHESDA,MD 20892. NR 35 TC 5 Z9 5 U1 1 U2 1 PU BLACKWELL SCIENCE INC PI CAMBRIDGE PA 238 MAIN ST, CAMBRIDGE, MA 02142 SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD FEB PY 1996 VL 106 IS 2 BP 221 EP 224 DI 10.1111/1523-1747.ep12340546 PG 4 WC Dermatology SC Dermatology GA TZ567 UT WOS:A1996TZ56700005 PM 8601719 ER PT J AU Li, LW Tennenbaum, T Yuspa, SH AF Li, LW Tennenbaum, T Yuspa, SH TI Suspension-induced murine keratinocyte differentiation is mediated by calcium SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Article ID INTRACELLULAR-FREE CALCIUM; CULTURED HUMAN KERATINOCYTES; CORNIFIED ENVELOPE FORMATION; HUMAN EPIDERMAL-CELLS; TERMINAL DIFFERENTIATION; EXTRACELLULAR CALCIUM; EXPRESSION; GENE; IDENTIFICATION; PROTEIN AB Modulating extracellular Ca2+ (Ca-o) and suspension culture are two frequently used methods to induce maturation of cultured human and mouse keratinocytes, To determine if the two methods share a common mechanists, changes in Ca2+ metabolism were studied in suspension cultures of mouse keratinocytes. Spontaneously detached and suspension-cultured keratinocytes in 0.05 mM Ca2+ medium express markers of suprabasal differentiation, while 0.05 mM Ca2+ is not permissive for marker expression by attached keratinocytes. Intracellular free Ca2+ (Ca-i) increased rapidly after placing keratinocytes in suspension in 0.05 mM Ca2+, reaching levels up to 3- to 4-fold higher than Ca-i in attached cells after 4-5 h. In suspended cells, the increase in Ca-i was associated with a 2- to 6-fold increase in Ca2+ transport across plasma membrane as well as depletion of intracellular Ca2+-stores. Diffrentiation marker expression and terminal differentiation were inhibited in suspension-cultured keratinocytes by preventing the rise of Ca-i using either 1,2-bis(o-aminophenoxy)-ethane-N,N,N',N'-tetraacetic acid to chelate intracellular Ca2+ or ethyleneglycol-bis(beta-aminoethyl ether)-N,N,N',N'-tetraacetic acid to reduce Ca-o. Together, these results indicate that a rise in Ca-i is a common mechanism controlling differentiation in cultured mouse keratinocytes, and suspension of keratinocytes enhances Ca2+ transport and alters intracellular Ca2+ sequestration producing a rise in Ca-i. C1 NCI,DIV CANC ETIOL,CELLULAR CARCINOGENESIS & TUMOR PROMOT LAB,BETHESDA,MD 20892. NR 39 TC 26 Z9 28 U1 0 U2 1 PU BLACKWELL SCIENCE INC PI CAMBRIDGE PA 238 MAIN ST, CAMBRIDGE, MA 02142 SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD FEB PY 1996 VL 106 IS 2 BP 254 EP 260 DI 10.1111/1523-1747.ep12340654 PG 7 WC Dermatology SC Dermatology GA TZ567 UT WOS:A1996TZ56700011 PM 8601725 ER PT J AU Memar, OM Rajaraman, S Thotakura, R Tyring, SK Fan, JL Seetharamaiah, GS Lopez, A Jordon, RE Prabhakar, BS AF Memar, OM Rajaraman, S Thotakura, R Tyring, SK Fan, JL Seetharamaiah, GS Lopez, A Jordon, RE Prabhakar, BS TI Recombinant desmoglein 3 has the necessary epitopes to adsorb and induce blister-causing antibodies SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Article DE autoimmunity; acantholysis; baculovirus; pemphigus vulgaris ID PEMPHIGUS-VULGARIS ANTIGEN; CADHERIN; DISEASE; BINDING; AUTOANTIBODIES; RECEPTOR; DOMAIN; MICE AB The development of an animal model for studying the pathogenesis of pemphigus vulgaris (PV) has been hampered by the unavailability of the purified full-length autoantigen desmoglein 3 (Dsg 3). Therefore, we expressed Dsg 3 using a baculovirus expression system, The expressed protein was identified as Dsg 3 by its reactivity with a pan-cadherin anti-serum, an anti-serum to a Dsg 3 synthetic peptide, or patient serum, and by amino-terminal sequencing. Carbohydrate analysis showed that recombinant Dsg 3 was glycosylated. While a majority of the recombinant protein was cell associated, by immunoprecipitation, some Dsg 3 was demonstrated in the medium. The Dsg 3 could adsorb out blister-causing antibodies from patient sera. Rabbit anti-Dsg 3 antibodies induced by the recombinant Dsg 3 showed specific binding to intercellular spaces of monkey esophagus by indirect immunofluorescence. Moreover, these antibodies induced PV-like blisters in neonatal mice and weakly bound perilesional epidermis. Availability of large quantities of relatively pure Dsg 3 should now facilitate studies aimed at understanding Dsg 3 structure and pathogenesis of PV, with implications for developing specific immunotherapies. C1 UNIV TEXAS,MED BRANCH,DEPT MICROBIOL & IMMUNOL,GALVESTON,TX 77555. UNIV TEXAS,MED BRANCH,DEPT PATHOL,GALVESTON,TX 77555. UNIV TEXAS,MED BRANCH,DEPT DERMATOL,GALVESTON,TX 77555. UNIV TEXAS,MED BRANCH,DEPT INTERNAL MED,GALVESTON,TX 77555. NIH,MOLEC & CELLULAR ENDOCRINOL BRANCH,BETHESDA,MD 20892. UNIV TEXAS,SCH MED,DEPT DERMATOL,HOUSTON,TX. NR 16 TC 25 Z9 25 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI CAMBRIDGE PA 238 MAIN ST, CAMBRIDGE, MA 02142 SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD FEB PY 1996 VL 106 IS 2 BP 261 EP 268 DI 10.1111/1523-1747.ep12340663 PG 8 WC Dermatology SC Dermatology GA TZ567 UT WOS:A1996TZ56700012 PM 8601726 ER PT J AU Hengge, UR Chan, EF Hampshire, V Foster, RA Vogel, JC AF Hengge, UR Chan, EF Hampshire, V Foster, RA Vogel, JC TI The derivation and characterization of pig keratinocyte cell lines that retain the ability to differentiate SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Article DE collagen; differentiation; gene transfer; beta-galactosidase ID HUMAN EPIDERMAL-KERATINOCYTES; GROWTH-FACTOR; SKIN; EXPRESSION; COLONIES; CULTURE; WOUNDS; MODEL AB Pig skin may be a very useful model for studying human skin biology, since its morphology closely resembles that of human skin. To manipulate pig keratinocytes in vitro, we have analyzed different culture conditions for optimal pig keratinocyte growth and describe here a simple method for culture and extended passage of primary pig keratinocytes on collagen substrates, The colony-forming efficiency and proliferative capacity of primary pig keratinocytes were readily supported by Type I collagen and a final calcium concentration of 0.075 mM, These culture conditions permitted efficient gene transfer into keratinocytes using various cationic lipids at a 4:1 ratio (lipid:DNA). In addition, immortalized pig keratinocyte cell lines, which maintained a normal phenotype, were derived using these optimized culture conditions, By karyotype analysis, two independently derived cell lines had the same chromosomal abnormalities, suggesting a causal role in their immortalization. The keratinocyte cell lines exhibited a differentiated phenotype in response to elevated calcium concentration and were nontumorigenic in in vivo tumor assays, Immortalized pig keratinocyte cell lines that maintain the ability to differentiate may become a valuable tool in the study of epidermal differentiation both in vitro and in vivo. In addition, methods using keratinocytes to deliver genes to pigs in vivo could also be enhanced with these pig keratinocyte cell lines. C1 NCI,DERMATOL BRANCH,NIH,BETHESDA,MD 20892. NIH,NATL CTR RES RESOURCES,VET RESOURCES PROGRAM,BETHESDA,MD 20892. NR 30 TC 19 Z9 19 U1 0 U2 1 PU BLACKWELL SCIENCE INC PI CAMBRIDGE PA 238 MAIN ST, CAMBRIDGE, MA 02142 SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD FEB PY 1996 VL 106 IS 2 BP 287 EP 293 DI 10.1111/1523-1747.ep12340722 PG 7 WC Dermatology SC Dermatology GA TZ567 UT WOS:A1996TZ56700016 PM 8601730 ER PT J AU Kartasova, T Darwiche, N Kohno, Y Koizumi, H Osada, S Huh, N Lichti, U Steinert, PM Kuroki, T AF Kartasova, T Darwiche, N Kohno, Y Koizumi, H Osada, S Huh, N Lichti, U Steinert, PM Kuroki, T TI Sequence and expression patterns of mouse SPR1: Correlation of expression with epithelial function SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Article DE small proline rich; cDNA; epithelium ID HUMAN EPIDERMAL-KERATINOCYTES; CROSS-LINKED ENVELOPE; CORNIFIED ENVELOPE; HUMAN LORICRIN; PHORBOL ESTER; RETINOIC ACID; GENE; DIFFERENTIATION; PROTEINS; INVOLUCRIN AB A final event in the terminal differentiation of stratified squamous epithelia is the formation of a cornified cell envelope, which is a complex of several proteins cross-linked together by transglutaminases. One set of proteins is the family of small proline rich (SPR) proteins. In human foreskin epidermal cell envelopes, SPRs serve as cross-bridging proteins among the more abundant loricrin, In order to study further their evolution and expression, we have isolated and sequenced cDNAs encoding two mouse SPR1 proteins, SPR1a and SPR1b. Comparative sequence analyses showed the preservation of the overall structure of mammalian SPR1 proteins with highly conserved termini and a central peptide domain repeated 13 (SPR1a) or seven (SPR1b) times, Tissues obtained from mouse fetal, newborn, and adult skin were tested by Northern blot analyses, ill situ hybridization, and immunohistochemistry using an antibody raised to a synthetic peptide corresponding to the C terminus of the SPR1a protein, Skin expression was first detected in fetal periderm, in anagen hair follicles of newborn and older mice, and in the thickened epidermis of the lip and footpad, but no signal was detected in interfollicular trunk epidermis. High levels of SPR1a expression were found in epithelia from the forestomach and penis, and in benign squamous papillomas. Other epithelia expressing SPR1a include the tongue, esophagus, and vagina, Whenever detected, SPR1a positive staining was present in the spinous and granular layers. In the forestomach and papillomas, the periphery of cells in the cornified layer was also stained. Our results suggest that SPR1a participates widely in the construction of cell envelopes in cornifying epithelia characterized by either increased thickness or a requirement for extreme flexibility. Based on its likely function as a cross-bridging protein in cell envelopes, we conclude that the mechanical attributes of cell envelopes may be determined in part by the SPR1 content, in accordance with the specific function of the epithelium. C1 UNIV TOKYO,INST MED SCI,DEPT CANC CELL RES,TOKYO,JAPAN. HOKKAIDO UNIV,SCH MED,DEPT DERMATOL,SAPPORO,HOKKAIDO 060,JAPAN. SHOWA UNIV,SCH DENT,DEPT ORAL PATHOL,TOKYO 142,JAPAN. YOKOHAMA CITY UNIV,SCH MED,DEPT MOLEC BIOL,YOKOHAMA,KANAGAWA 232,JAPAN. NCI,CELLULAR CARCINOGENESIS & TUMOR PROMOT LAB,BETHESDA,MD 20892. RP Kartasova, T (reprint author), NIAMSD,NIH,SKIN BIOL LAB,BLDG 6,ROOM 425,BETHESDA,MD 20892, USA. RI Kuroki, Toshio/A-9500-2011; OI Kuroki, Toshio/0000-0001-6369-4351; Darwiche, Nadine/0000-0002-1862-5426 NR 59 TC 58 Z9 60 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI CAMBRIDGE PA 238 MAIN ST, CAMBRIDGE, MA 02142 SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD FEB PY 1996 VL 106 IS 2 BP 294 EP 304 DI 10.1111/1523-1747.ep12340741 PG 11 WC Dermatology SC Dermatology GA TZ567 UT WOS:A1996TZ56700017 PM 8601731 ER PT J AU Ryschon, TW Rosenstein, DL Rubinow, DR Niemela, JE Elin, RJ Balaban, RS AF Ryschon, TW Rosenstein, DL Rubinow, DR Niemela, JE Elin, RJ Balaban, RS TI Relationship between skeletal muscle intracellular ionized magnesium and measurements of blood magnesium SO JOURNAL OF LABORATORY AND CLINICAL MEDICINE LA English DT Article ID NUCLEAR MAGNETIC-RESONANCE; SERUM MAGNESIUM; PARATHYROID-HORMONE; CELL MAGNESIUM; HEART-FAILURE; DEFICIENCY; NMR; SPECTROSCOPY; MYOCARDIUM; POTASSIUM AB The current laboratory approach to assessing magnesium status is based on determining the concentration of total Mg ((Mg)) in serum or plasma. This strategy is problematic in that the amount of Mg in blood is less than 1% of total body Mg and does not accurately reflect (Mg) in other tissues, Furthermore, the (Mg) of blood does not distinguish biologically active, ionized Mg from the bound fraction, The goal of this study was to determine intracellular ionized Mg ((MS(++))(i)) of skeletal muscle in vivo and to compare results with the (Mg) of blood constituents, (Mg++)(i) was determined in resting skeletal muscle by using phosphorus 31 magnetic resonance (P-31-MR) spectroscopy. (Mg) was measured in serum (S(Mg)), serum ultrafiltrate (UF(Mg)), mononuclear blood cells (MBC(Mg)), and red blood cells (RBC(Mg)) by using atomic absorption spectroscopy or a colorimetric assay, In a sample of 60 healthy adult subjects, skeletal muscle (Mg++), = 557 +/- 97 mu mol/L (mean a SD); S(Mg) = 0.78 +/- 0.09 mmol/L; UF(Mg) = 0.60 +/- 0.12 mmol/L; MBC(Mg) = 13.8 +/- 2.3 mmol/L; and, RBC(Mg) = 1.92 +/- 0.33 mmol/L, A significant negative correlation was found between (Mg++)(i) and S(Mg) (r = -0.43, p < 0.05). S(Mg) was significantly lower (p < 0.05) and (Mg++)(i) significantly higher (p < 0.05) in women than in men, but neither was related to age. These findings provide new insight into the relationship between blood Mg measures and (Mg++)(i) of the largest soft tissue mass of the human body. C1 NIMH,BIOL PSYCHIAT BRANCH,BETHESDA,MD 20892. WARREN GRANT MAGNUSON CLIN CTR,DEPT CLIN PATHOL,BETHESDA,MD. RP Ryschon, TW (reprint author), NHLBI,CARDIAC ENERGET LAB,NIH,BLDG 1,ROOM B3-07,BETHESDA,MD 20892, USA. RI Balaban, Robert/A-7459-2009; OI Balaban, Robert/0000-0003-4086-0948; Niemela, Julie/0000-0003-4197-3792 NR 44 TC 27 Z9 27 U1 0 U2 1 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 FEB PY 1996 VL 127 IS 2 BP 207 EP 213 DI 10.1016/S0022-2143(96)90080-3 PG 7 WC Medical Laboratory Technology; Medicine, General & Internal; Medicine, Research & Experimental SC Medical Laboratory Technology; General & Internal Medicine; Research & Experimental Medicine GA TU677 UT WOS:A1996TU67700009 PM 8636650 ER PT J AU Ikewaki, K Zech, LA Brewer, HB Rader, DJ AF Ikewaki, K Zech, LA Brewer, HB Rader, DJ TI ApoA-II kinetics in humans using endogenous labeling with stable isotopes: Slower turnover of apoA-II compared with the exogenous radiotracer method SO JOURNAL OF LIPID RESEARCH LA English DT Article DE high density lipoproteins; atherosclerosis ID HIGH-DENSITY-LIPOPROTEIN; APOLIPOPROTEIN-A-I; CORONARY-ARTERY DISEASE; ISCHEMIC-HEART-DISEASE; AMINO-ACID-SEQUENCE; TRANSGENIC MICE; INVIVO METABOLISM; CHOLESTEROL; ATHEROSCLEROSIS; HDL AB ApoA-II is a major apolipoprotein constituent of high density lipoproteins (HDL) and may play an important role in lipoprotein metabolism and predisposition to atherosclerosis. Previous radiotracer kinetic studies have suggested thar the metabolism of apoA-II in humans may be different than the metabolism of apoA-I, the major HDL apolipoprotein. In the present study, we have used an endogenous labeling technique using stable isotopically labeled amino acids to study apoA-II metabolism and compared the results to those obtained by a simultaneous exogenous radiotracer labeling method. Seven subjects with HDL cholesterol levels ranging from 9 to 93 mg/dl and apoA-II levels from 13 to 60 mg/dl were investigated in this study. [C-13(6)]phenylalanine and I-131-labeled apoA-II were simultaneously administered as a primed-constant infusion and a bolus injection, respectively. In the endogenous labeling study, plateau tracer/tracee ratios of VLDL apoB-100 were used as estimates for the precursor pool tracer/tracee ratios for apoA-II synthesis. Residence times of apoA-II using these two independent methods were found to be highly correlated (r = 0.973, P < 0.0002). These results indicate that the endogenous labeling of apoA-II using stable isotopically labeled amino acids is a reasonable alternative to the conventional exogenous radiotracer labeling method for the investigation of apoA-II turnover. However, under the conditions of our experimental design and modeling strategy, the apoA-II residence times as determined by endogenous labeling were significantly longer (mean 5.33 days) than by exogenous radiotracer (mean 4.65 days). This suggests that apoA-II turnover may be even slower than believed based on radiotracer studies, and further supports the concept that HDL containing apoA-II are metabolized differently than HDL without apoA-II. C1 NHLBI,NIH,MOLEC DIS BRANCH,BETHESDA,MD 20892. NR 42 TC 25 Z9 25 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 FEB PY 1996 VL 37 IS 2 BP 399 EP 407 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA TZ910 UT WOS:A1996TZ91000017 PM 9026537 ER PT J AU Wen, H Jaffer, FA Denison, TJ Duewell, S Chesnick, AS Balaban, RS AF Wen, H Jaffer, FA Denison, TJ Duewell, S Chesnick, AS Balaban, RS TI The evaluation of dielectric resonators containing H2O or D2O as RF coils for high-field MR imaging and spectroscopy SO JOURNAL OF MAGNETIC RESONANCE SERIES B LA English DT Article AB Electromagnetic resonators consisting of low-loss dielectric material and/or metallic boundaries are widely used in microwave technologies. These dielectric resonators usually have high Q factors and well-defined field distributions. Magnetic resonance imaging was shown as a way of visualizing the magnetic field distribution of the resonant modes of these resonators, if the dielectric body contains NR;IR sensitive nuclei. Dielectric resonators have also been proposed as RF coils for magnetic resonance experiments. The feasibility of this idea in high-field MR is discussed here. Specifically, the dielectric resonances of cylindrical water columns were characterized at 170.7 MHz (4 T H-1 Larmor frequency), and evaluated as NMR transmit and receive coils. The dielectric resonance of a cylindrical volume of D2O was used to image a hand at 170.7 MHz. This study demonstrated that MRI is an effective way of visualizing the magnetic field in dielectric structures such as a water cylinder, and can potentially be generalized to solid-state dielectric devices. The possible applications of dielectric resonators other than simple cylindrical volumes in MRI and MR solution spectroscopy at high field strengths are also discussed. (C) 1996 Academic Press, Inc. RP Wen, H (reprint author), NHLBI,CARDIAC ENERGET LAB,9000 ROCKVILLE PIKE,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 9 TC 32 Z9 32 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 1064-1866 J9 J MAGN RESON SER B JI J. Magn. Reson. Ser. B PD FEB PY 1996 VL 110 IS 2 BP 117 EP 123 DI 10.1006/jmrb.1996.0019 PG 7 WC Physics, Atomic, Molecular & Chemical SC Physics GA TY737 UT WOS:A1996TY73700001 PM 8819760 ER PT J AU Sidransky, E Tayebi, N Stubblefield, BK Eliason, W Klineburgess, A Pizzolato, GP Cox, JN Porta, J Bottani, A DeLozierBlanchet, CD AF Sidransky, E Tayebi, N Stubblefield, BK Eliason, W Klineburgess, A Pizzolato, GP Cox, JN Porta, J Bottani, A DeLozierBlanchet, CD TI The clinical, molecular, and pathological characterisation of a family with two cases of lethal perinatal type 2 Gaucher disease SO JOURNAL OF MEDICAL GENETICS LA English DT Article DE Gaucher disease; hydrops fetalis; glucocerebrosidase ID ACID BETA-GLUCOSIDASE; HUMAN GLUCOCEREBROSIDASE; TARGETED DISRUPTION; GENE; ALLELES; MODEL AB It has recently been emphasised that a subset of patients with type 2 Gaucher disease die in the neonatal period. This report describes an Afghani family with two conceptuses having severe, prenatally detected Gaucher disease. Mutational analysis showed that the family carried a known complex allele which included mutations at amino acids L444P, A456P, and V460V. Although glucocerebrosidase RNA was present, an affected fetus had virtually no glucocerebrosidase cross reactive material on western analyses. The severe clinical course and pathology observed in these patients resemble that of the null allele Gaucher mouse, and suggest that the absence of glucocerebrosidase activity results in early death. C1 UNIV HOSP GENEVA,DIV MED GENET,GENEVA,SWITZERLAND. UNIV HOSP GENEVA,DEPT PATHOL,GENEVA,SWITZERLAND. RP Sidransky, E (reprint author), NIMH,CLIN NEUROSCI BRANCH,NIH,BLDG 49,ROOM B1EE16,49 CONVENT DR,MSC 4405,BETHESDA,MD 20892, USA. NR 25 TC 30 Z9 31 U1 0 U2 0 PU BRITISH MED JOURNAL PUBL GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON, ENGLAND WC1H 9JR SN 0022-2593 J9 J MED GENET JI J. Med. Genet. PD FEB PY 1996 VL 33 IS 2 BP 132 EP 136 DI 10.1136/jmg.33.2.132 PG 5 WC Genetics & Heredity SC Genetics & Heredity GA TT847 UT WOS:A1996TT84700010 PM 8929950 ER PT J AU Dodane, V Kachar, B AF Dodane, V Kachar, B TI Identification of isoforms of G proteins and PKC that colocalize with tight junctions SO JOURNAL OF MEMBRANE BIOLOGY LA English DT Article DE tight junctions; PKC; G proteins; MDCK; Caco-2 ID KINASE-C-ZETA; PHORBOL ESTER; ADENYLYL CYCLASE; TUMOR PROMOTERS; HUMAN PLATELETS; ALPHA-SUBUNITS; CELLS; DIACYLGLYCEROL; ANTIBODIES; RECEPTOR AB Recent evidence suggests that the formation and permeability of tight junctions are actively regulated by second-messenger-generating systems involving G proteins and protein kinase C (PKC). A possible specific target for these regulatory proteins is the tight junction protein ZO-1. An extensive immunocytochemical study was performed in cultured epithelial monolayers of MDCK and Caco-2 cells to identify which isoforms of G proteins and PKC are present at or near the zonula occludens complex. Antibodies against a-subunits of each one of the four major subfamilies were used for the localization of the G proteins. For the PKC localization, antibodies against eight different isoforms were used. In confluent monolayers, G alpha(12) and PKC xi were the only isoforms of these proteins present at the cell borders. In subconfluent monolayers, G alpha(12) and PKC xi were found at the plasma membrane only along the areas of lateral cell-cell contact. These isoforms formed a pattern of distribution very similar to the ZO-1 protein. The present findings indicate that G alpha(12) and PKC xi may be part of the zonula occludens complex and may locally regulate formation and permeability of tight junctions. C1 NIDOCM,LAB CELLULAR BIOL,NIH,ROCKVILLE,MD 20850. NR 51 TC 98 Z9 98 U1 1 U2 3 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0022-2631 J9 J MEMBRANE BIOL JI J. Membr. Biol. PD FEB PY 1996 VL 149 IS 3 BP 199 EP 209 DI 10.1007/s002329900020 PG 11 WC Biochemistry & Molecular Biology; Cell Biology; Physiology SC Biochemistry & Molecular Biology; Cell Biology; Physiology GA TV534 UT WOS:A1996TV53400005 PM 8801352 ER PT J AU Sellers, JR Goodson, HV Wang, F AF Sellers, JR Goodson, HV Wang, F TI A myosin family reunion SO JOURNAL OF MUSCLE RESEARCH AND CELL MOTILITY LA English DT Review ID HEAVY-CHAIN GENE; DROSOPHILA-NINAC KINASE; ACANTHAMOEBA MYOSIN; UNCONVENTIONAL MYOSIN; NONMUSCLE MYOSIN; MUSCLE MYOSIN; DICTYOSTELIUM-DISCOIDEUM; MOLECULAR-CLONING; MULTIGENE FAMILY; AMINO-ACID C1 UNIV GENEVA, DEPT CELL BIOL, CH-1211 GENEVA 4, SWITZERLAND. RP NHLBI, NIH, BLDG 10, BETHESDA, MD 20892 USA. NR 112 TC 56 Z9 61 U1 1 U2 4 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0142-4319 EI 1573-2657 J9 J MUSCLE RES CELL M JI J. Muscle Res. Cell Motil. PD FEB PY 1996 VL 17 IS 1 BP 7 EP 22 DI 10.1007/BF00140320 PG 16 WC Cell Biology SC Cell Biology GA UJ188 UT WOS:A1996UJ18800002 PM 8740428 ER PT J AU Choi, OH Park, CS Itoh, K Adelstein, RS Beaven, MA AF Choi, OH Park, CS Itoh, K Adelstein, RS Beaven, MA TI Cloning of the cDNA encoding rat myosin heavy chain-A and evidence for the absence of myosin heavy chain-B in cultured rat mast (RBL-2H3) cells SO JOURNAL OF MUSCLE RESEARCH AND CELL MOTILITY LA English DT Article ID PROTEIN-KINASE-C; VERTEBRATE NONMUSCLE MYOSIN; BASOPHILIC LEUKEMIA-CELLS; HIGH-AFFINITY; TYROSINE PHOSPHORYLATION; CELLULAR MYOSIN; MESSENGER-RNAS; RECEPTOR; IGE; ANTIGEN AB The complete amino acid sequence (1961 amino acids) of a vertebrate cellular myosin heavy chain-A was deduced from cDNA clones of a secretory rat mast cell line, the RBL-2H3 cell. The rat, human and chicken cellular myosin heavy chain-A exhibited high similarity in domains that allow binding of ATP and actin. The amino acid sequence of non-muscle myosin heavy chain-A from rat was 96% identical to that in human and 92% identical to that in chicken. Northern blot analysis of mRNA indicated the presence of single message of 7.4 kilobases. Northern blot, reverse-transcriptase polymerase chain reaction, and Western blot with isoform-specific antibodies indicated that RBL-2H3 cells expressed exclusively myosin heavy chain-A. Unlike rat PCl2 cells, as well as a wide variety of other cultured cells and tissues, myosin heavy chain-B mRNA and protein were not detectable in RBL-2H3 cells. Because RBL-2H3 cells can be stimulated to release secretory granules as well as newly generated arachidonic acid and cytokines but lack myosin heavy chain-B, this cell line may provide a unique model to study the role of myosin heavy chain-A in cellular responses to antigen and other stimulants. C1 NHLBI,NIH,LAB MOL IMMUNOL,BETHESDA,MD 20892. NHLBI,NIH,MOLEC CARDIOL LAB,BETHESDA,MD 20892. OI Adelstein, Robert/0000-0002-8683-2144 NR 35 TC 20 Z9 21 U1 0 U2 1 PU CHAPMAN HALL LTD PI LONDON PA 2-6 BOUNDARY ROW, LONDON, ENGLAND SE1 8HN SN 0142-4319 J9 J MUSCLE RES CELL M JI J. Muscle Res. Cell Motil. PD FEB PY 1996 VL 17 IS 1 BP 69 EP 77 DI 10.1007/BF00140325 PG 9 WC Cell Biology SC Cell Biology GA UJ188 UT WOS:A1996UJ18800007 PM 8740433 ER PT J AU Levine, RJC Lankford, E Sweeney, HL Epstein, N Fananapazir, L AF Levine, RJC Lankford, E Sweeney, HL Epstein, N Fananapazir, L TI Thick filament structure in beta-MHC mutation: Arg403Gln, associated with familial hypertrophic cardiomyopathy SO JOURNAL OF MUSCLE RESEARCH AND CELL MOTILITY LA English DT Meeting Abstract C1 MED COLL PENN & HAHNEMANN UNIV, PHILADELPHIA, PA USA. MED COLL PENN & HAHNEMANN UNIV, PHILADELPHIA, PA USA. UNIV PENN, PHILADELPHIA, PA 19104 USA. NHLBI, BETHESDA, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0142-4319 J9 J MUSCLE RES CELL M JI J. Muscle Res. Cell Motil. PD FEB PY 1996 VL 17 IS 1 BP 103 EP 103 PG 1 WC Cell Biology SC Cell Biology GA UJ188 UT WOS:A1996UJ18800032 ER PT J AU Sellers, JR Harvey, EV Preston, YP Wang, F Pato, MD Adelstein, RS AF Sellers, JR Harvey, EV Preston, YP Wang, F Pato, MD Adelstein, RS TI Expression of active nonmuscle myosins using the baculovirus/SF9 system SO JOURNAL OF MUSCLE RESEARCH AND CELL MOTILITY LA English DT Meeting Abstract C1 NHLBI,NIH,MOLEC CARDIOL LAB,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU CHAPMAN HALL LTD PI LONDON PA 2-6 BOUNDARY ROW, LONDON, ENGLAND SE1 8HN SN 0142-4319 J9 J MUSCLE RES CELL M JI J. Muscle Res. Cell Motil. PD FEB PY 1996 VL 17 IS 1 BP 107 EP 107 PG 1 WC Cell Biology SC Cell Biology GA UJ188 UT WOS:A1996UJ18800045 ER PT J AU Chaussepied, P Heureux, KL Bonafe, N AF Chaussepied, P Heureux, KL Bonafe, N TI Functional importance of the degree of saturation of F-actin myosin heads SO JOURNAL OF MUSCLE RESEARCH AND CELL MOTILITY LA English DT Meeting Abstract C1 CNRS,CRBM,F-34033 MONTPELLIER,FRANCE. NCI,MOLEC CARDIOL LAB,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU CHAPMAN HALL LTD PI LONDON PA 2-6 BOUNDARY ROW, LONDON, ENGLAND SE1 8HN SN 0142-4319 J9 J MUSCLE RES CELL M JI J. Muscle Res. Cell Motil. PD FEB PY 1996 VL 17 IS 1 BP 121 EP 122 PG 2 WC Cell Biology SC Cell Biology GA UJ188 UT WOS:A1996UJ18800091 ER PT J AU Vorotnikov, AV Silver, DL Sellers, JR Waterson, DM Shirinsky, VP AF Vorotnikov, AV Silver, DL Sellers, JR Waterson, DM Shirinsky, VP TI Kinase-related protein is phosphorylated both in vitro and in smooth muscle by mitogen-activated and cyclic AMP-dependent protein kinases SO JOURNAL OF MUSCLE RESEARCH AND CELL MOTILITY LA English DT Meeting Abstract C1 CARDIOL RES CTR, INST EXPTL CARDIOL, MOLEC ENDOCRINOL LAB, MOSCOW 121552, RUSSIA. NHLBI, MOLEC CARDIOL LAB, NIH, BETHESDA, MD 20892 USA. NORTHWESTERN UNIV, DEPT BIOL CHEM & MOLEC PHARMACOL, CHICAGO, IL 60611 USA. RI Vorotnikov, Alexander/A-8392-2014 OI Vorotnikov, Alexander/0000-0002-1460-971X NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0142-4319 J9 J MUSCLE RES CELL M JI J. Muscle Res. Cell Motil. PD FEB PY 1996 VL 17 IS 1 BP 153 EP 153 PG 1 WC Cell Biology SC Cell Biology GA UJ188 UT WOS:A1996UJ18800184 ER PT J AU Unsicker, K Meier, C Krieglstein, K Sartor, BM Flanders, KC AF Unsicker, K Meier, C Krieglstein, K Sartor, BM Flanders, KC TI Expression, localization, and function of transforming growth factor-beta s in embryonic chick spinal cord, hindbrain, and dorsal root ganglia SO JOURNAL OF NEUROBIOLOGY LA English DT Article DE in situ hybridization; immunocytochemistry; TGF-beta; nervous system; neurite growth ID CELL-ADHESION MOLECULE; NERVOUS-SYSTEM; GENE-EXPRESSION; MESSENGER-RNA; RAT-BRAIN; OSTEOGENIC PROTEIN-1; NEURITE OUTGROWTH; FLOOR PLATE; TGF BETA-1; DIFFERENTIATION AB We have studied the localizations of transforming growth factor-beta (TGF-beta)2 and 3 immunohistochemically using isoform-specific antibodies and TGF-beta 3 mRNA by in situ hybridization in the nervous system of the 3- to 15-day-old chick embryo with special reference to spinal cord, hindbrain, and dorsal root ganglia (DRG). At embryonic day (E) 3, TGF-beta 3 mRNA as well as TGF-beta 2 and 3 immunoreactivities (IRs) were most prominent in the notochord, wall of the aorta, and dermomyotome. At E5 and E7, strong TGF-beta 2 and 3 IR were seen in or on radial glia of spinal cord and hindbrain. Radial glia in the floor plate region and ventral commissure gave the most intense signal. In the DRG, fiber strands of intense IRs representing extracellular matrix or satellite cells were seen, Neuronal perikarya did not become IR for TGF-beta 2 and 3 until E11, but even then the moderate signals for TGF-beta 3 mRNA could not be specifically localized to the neuronal cell bodies. In E11 and older embryos, spinal cord glial or glial progenitor cells, but not neuronal cell bodies were labeled for TGF-beta 3 mRNA. Immunocytochemistry and western blot analysis indicated that E8 DRG neurons have the TGF-beta receptor type II, and treatment of these cells with NGF induces expression of TGF-beta 3 mRNA. The TGF-beta isoforms 1, 2, and 3 did not promote survival of E8 DRG neurons in dissociated cell cultures. All three TGF-beta isoforms, however, promoted neurite growth from E8 DRG explants, but were less potent than nerve growth factor. Our data suggest identical localizations of TGF-beta 2 and -beta 3 IR in the developing chick and mammalian nervous systems, underscoring the general importance of TGF-beta s in fundamental events of neural, development. (C) 1996 John Wiley & Sons, Inc. C1 NCI,CHEMOPREVENT LAB,BETHESDA,MD 20892. RP Unsicker, K (reprint author), UNIV HEIDELBERG,DEPT ANAT & CELL BIOL,KIRSCHNERSTR 1,D-69120 HEIDELBERG,GERMANY. NR 58 TC 52 Z9 52 U1 1 U2 3 PU JOHN WILEY & SONS INC PI NEW YORK PA 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0022-3034 J9 J NEUROBIOL JI J. Neurobiol. PD FEB PY 1996 VL 29 IS 2 BP 262 EP 276 DI 10.1002/(SICI)1097-4695(199602)29:2<262::AID-NEU10>3.0.CO;2-D PG 15 WC Neurosciences SC Neurosciences & Neurology GA TR362 UT WOS:A1996TR36200010 PM 8821181 ER PT J AU Zhou, LM Szendrei, GI Fossom, LH Maccecchini, ML Skolnick, P Otvos, L AF Zhou, LM Szendrei, GI Fossom, LH Maccecchini, ML Skolnick, P Otvos, L TI Synthetic analogues of conantokin-G: NMDA antagonists acting through a novel polyamine-coupled site SO JOURNAL OF NEUROCHEMISTRY LA English DT Article DE conantokin-G; Ala(7)-conantokin-G; polyamines; spermine; N-methyl; D-aspartate; MK-801 ID METHYL-D-ASPARTATE; RECEPTOR COMPLEX; GAMMA-CARBOXYGLUTAMATE; SECONDARY-STRUCTURE; MK-801 BINDING; RAT-BRAIN; GLYCINE; ACID; IFENPRODIL; PEPTIDES AB Conantokin-G (con-G) is a 17-amino-acid polypeptide that acts as an N-methyl-D-aspartate (NMDA) antagonist. This action has been attributed to a specific but noncompetitive inhibition of the positive modulatory effects of polyamines at NMDA receptors. Con-G possesses several unusual structural features, including five gamma-carboxyglutamate (Cia) residues and a high degree of helicity in aqueous media. Previous structure-activity studies indicated that one or more Gla residues are necessary for NMDA antagonist activity, Con-G analogues were synthesized with alanine (Ala), serine (Ser), and phosphoserine substituted for Gla to assess the contribution of individual Gla residues to biological activity and secondary structure. Replacement of Gla in positions 3 and 4 resulted in polypeptides with markedly reduced and no NMDA antagonist actions, respectively. In contrast, Gla residues in positions 7, 10, and 14 are not required for NMDA antagonist actions because the potencies of con-G analogues containing Ser(7), Ser(10) Ala(14) and Ser(14) to inhibit spermine-stimulated [H-3]MK-801 binding are similar to the parent peptide. Moreover, the Ala(7) derivative of con-G was about fourfold more potent than the parent peptide both as an inhibitor of spermine-stimulated increases in [H-3]MK-801 binding (IC50 of similar to 45 nM) and in reducing NMDA-stimulated increases in cyclic GMP levels (IC50 of similar to 77 nM) in cerebellar granule cell cultures. Although con-G and its analogues assumed mixtures of 3(10) and alpha-helices, no clearcut relationship was evinced between the NMDA antagonist properties of these peptides and the degree of helicity they assumed in aqueous solutions. Together with the inability of con-G to affect 5,7-dichloro[H-3] kynurenic acid, [H-3]CGP-39653, and [H-3]ifenprodil binding, these data are consistent with the hypothesis that this polypeptide acts at a unique, polyamine-associated site on NMDA receptors. C1 NIH,NIDDK LN,BETHESDA,MD 20892. WISTAR INST ANAT & BIOL,PHILADELPHIA,PA 19104. SYMPHONY PHARMACEUT,MALVERN,PA. NR 44 TC 57 Z9 58 U1 1 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 FEB PY 1996 VL 66 IS 2 BP 620 EP 628 PG 9 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA TR131 UT WOS:A1996TR13100021 PM 8592132 ER PT J AU Prasanna, P Thibault, A Liu, L Samid, D AF Prasanna, P Thibault, A Liu, L Samid, D TI Lipid metabolism as a target for brain cancer therapy: Synergistic activity of lovastatin and sodium phenylacetate against human glioma cells SO JOURNAL OF NEUROCHEMISTRY LA English DT Article DE lovastatin; phenylacetic acid, sodium salt; mevalonate pathway; nuclear receptor; phenotypic reversion; glioblastoma ID NEURO-BLASTOMA CELLS; GROWTH-FACTOR; MEVALONIC ACID; CHOLESTEROL-BIOSYNTHESIS; COMPETITIVE INHIBITOR; CULTURED-CELLS; DIFFERENTIATION; REDUCTASE; PROTEINS; BETA AB Malignant gliomas, the most common form of primary brain tumors, are highly dependent on the mevalonate (MVA) pathway for the synthesis of lipid moieties critical to cell replication. Human glioblastoma cells were found to be uniquely vulnerable to growth arrest by lovastatin, a competitive inhibitor of the enzyme regulating MVA synthesis, 3-hydroxy-3-methylglutaryl coenzyme A reductase. The sodium salt of phenylacetic acid (NaPA), an inhibitor of MVA-pyrophosphate decarboxylase, the enzyme that controls MVA use, acted synergistically with lovastatin to suppress malignant growth, When used at pharmacologically attainable concentrations, the two compounds induced profound cytostasis and loss of malignant properties such as invasiveness and expression of the transforming growth factor-beta 2 gene, coding for a potent immunosuppressive cytokine. Supplementation with exogenous ubiquinone, an end product of the MVA pathway, failed to rescue the cells, suggesting that decreased synthesis of intermediary products are responsible for the antitumor effects observed. In addition to blocking the MVA pathway, lovastatin alone and in combination with NaPA increased the expression of the peroxisome proliferator-activated receptor, a transcription factor implicated in the control of lipid metabolism, cell growth, and differentiation. Our results indicate that targeting lipid metabolism with lovastatin, used alone or in combination with the aromatic fatty acid NaPA, may offer a novel approach to the treatment of malignant gliomas. C1 UNIV VIRGINIA,HLTH SCI CTR,CHARLOTTESVILLE,VA 22908. NCI,DIV CANC TREATMENT,CLIN PHARMACOL BRANCH,BETHESDA,MD 20892. NR 49 TC 87 Z9 89 U1 1 U2 8 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PD FEB PY 1996 VL 66 IS 2 BP 710 EP 716 PG 7 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA TR131 UT WOS:A1996TR13100032 PM 8592143 ER PT J AU Winsky, L Kuznicki, J AF Winsky, L Kuznicki, J TI Antibody recognition of calcium-binding proteins depends on their calcium-binding status SO JOURNAL OF NEUROCHEMISTRY LA English DT Article DE calretinin; calbindin D28k; parvalbumin; immunoreactivity ID RAT-BRAIN; IMMUNOHISTOCHEMICAL LOCALIZATION; PARVALBUMIN IMMUNOREACTIVITY; MONOCLONAL-ANTIBODY; GENE-EXPRESSION; CALBINDIN-D; CALRETININ; ISCHEMIA; HIPPOCAMPUS; CELLS AB Previous studies have revealed changes in immunohistochemical stains for calcium-binding proteins after manipulations that influence intracellular calcium. Cases have been revealed in which these changes in immunoreactivity were not correlated with changes in protein amounts. The present experiments examined whether these effects might be explained by changes in antiserum recognition due to calcium-induced changes in protein conformation. Calretinin, calbindin D28k, and parvalbumin incubated in high calcium were recognized by antisera better than when they were incubated in low calcium. Using a calbindin D28k antibody, it was shown that this effect occurs within physiological calcium concentrations. Formalin fixation of the proteins in the presence of calcium resulted in greater antibody recognition than did fixation of proteins in calcium-free states. The calretinin antiserum appeared to recognize a portion of the molecule previously shown to undergo calcium-dependent conformational changes, A calcium-insensitive antiserum was made to a different fragment of calretinin. These results indicate that some antibodies to calcium-binding proteins preferentially recognize particular calcium-induced protein conformations. Given the potential for wide fluctuations in neuronal calcium, the present results indicate that quantitative estimates of intracellular calcium-binding proteins obtained from immunohistochemical studies of neurons must be interpreted with caution. RP Winsky, L (reprint author), NIMH,CLIN SCI LAB,ROOM 3D-48,10 CTR DR,MSC 1266,BETHESDA,MD 20892, USA. NR 45 TC 61 Z9 61 U1 0 U2 1 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PD FEB PY 1996 VL 66 IS 2 BP 764 EP 771 PG 8 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA TR131 UT WOS:A1996TR13100039 PM 8592150 ER PT J AU Kiss, A Palkovits, M Aguilera, G AF Kiss, A Palkovits, M Aguilera, G TI Neural regulation of corticotropin releasing hormone (CRH) and CRH receptor mRNA in the hypothalamic paraventricular nucleus in the rat SO JOURNAL OF NEUROENDOCRINOLOGY LA English DT Article DE CRH mRNA; CRH receptor; paraventricular hypothalamic nucleus (PVN); stress; PVN deafferentation ID CENTRAL AMYGDALOID NUCLEUS; AVP MESSENGER-RNA; ADRENOCORTICOTROPIN RELEASE; ENDOCRINE NEURONS; SPINAL-CORD; STRESS; SECRETION; PROJECTIONS; VASOPRESSIN; EXPRESSION AB The role of afferent innervation to the hypothalamic paraventricular nucleus (PVN) on CRH mRNA and CRH receptor mRNA levels was studied in control and stressed rats. Groups of rats were subjected to unilateral transection of the stria terminalis (ST), the medial forebrain bundle at the rostral hypothalamic level (RMFB), or the lower brainstem through the medulla oblongata between the obex and the locus coeruleus (CBs). Twelve days after surgery, each group of rats was further divided into controls (basal conditions) and stressed (1 h immobilization), before collecting brains for mRNA analysis by in situ hybridization histochemistry. While ST and RMFB cuts had no effect on basal CRH mRNA levels in the PVN, CBs cut decreased CRH mRNA in the PVN ipsilaterally to the knife cut but it was without effect on the contralateral side (-40% and -37% vs contralateral and sham-operated, respectively, P<0.01). Acute stress (rats were killed 3 h after immobilization)increased CRH mRNA levels by about 30% bilaterally, an effect which was unchanged by any of the three hemisections. Under basal conditions, CRH receptor mRNA levels in the PVN were indistinguishable from the surrounding areas in sham-operated controls, ST and RMFB operated rats. However, brainstem hemisection resulted in clear expression of CRH receptor mRNA in areas consistent with the dorsal, medial-ventral and lateral parvicellular subdivisions of the PVN, ipsilateral to the transection. CRH neurons in these subdivisions project to the lower brainstem and the spinal cord. Expression of CRH receptor mRNA in the medial-dorsal and anterior parvicellular divisions (CRH neurons with median eminence projections) was not affected by CBs cut. In these subdivisions, immobilization stress markedly increased CRH receptor mRNA levels but it did not influence CBs cut-induced CRH receptor expression, ST and RMFB hemisections were without effect on PVN CRH receptor mRNA levels under basal or stress conditions. Oxytocin (OT) and vasopressin (VP) mRNA levels in the magnocellular subdivision of the PVN were unchanged after immobilization, or following ST, RMFB or CBs cuts, whereas OT mRNA in the medial-ventral and caudal parvicellular subdivisions was decreased by 52% after CBs cut. The data demonstrate that: 1) basal CRH mRNA levels in the PVN are under tonic stimulatory influence of the lower brainstem (and/or spinal cord) afferents; 2) CRH receptor mRNA expression in PVN subdivisions (pituitary vs lower brainstem/spinal cord projecting neurons) is under different control mechanisms, and 3) immobilization-induced changes in CRH mRNA and CRH receptor mRNA levels are mediated either by neural inputs from brain areas other than those investigated here, or by humoral factors. C1 NICHHD, NIH, DEV ENDOCRINOL BRANCH, SECT ENDOCRINE PHYSIOL, BETHESDA, MD 20892 USA. NIMH, CELL BIOL LAB, NIH, BETHESDA, MD 20892 USA. RI Palkovits, Miklos/F-2707-2013; OI Palkovits, Miklos/0000-0003-0578-0387 NR 54 TC 39 Z9 40 U1 1 U2 3 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0953-8194 J9 J NEUROENDOCRINOL JI J. Neuroendocrinol. PD FEB PY 1996 VL 8 IS 2 BP 103 EP 112 DI 10.1111/j.1365-2826.1996.tb00830.x PG 10 WC Endocrinology & Metabolism; Neurosciences SC Endocrinology & Metabolism; Neurosciences & Neurology GA TZ278 UT WOS:A1996TZ27800004 PM 8868257 ER PT J AU daCunha, A Jackson, RW Vitkovic, L AF daCunha, A Jackson, RW Vitkovic, L TI HIV-1 non-specifically stimulates production of transforming growth factor-beta in primary astrocytes (vol 60, pg 125, 1995) SO JOURNAL OF NEUROIMMUNOLOGY LA English DT Correction, Addition C1 NIAID,IMMUNOREGULAT LAB,NIH,BETHESDA,MD 20892. NIMH,DIV NEUROSCI & BEHAV SCI,NIH,ROCKVILLE,MD 20857. RP daCunha, A (reprint author), NIMH,MOLEC NEUROSCI SECT,CELL BIOL LAB,BETHESDA,MD 20892, USA. NR 1 TC 0 Z9 0 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 FEB PY 1996 VL 64 IS 2 BP 219 EP 219 DI 10.1016/0165-5728(95)00177-8 PG 1 WC Immunology; Neurosciences SC Immunology; Neurosciences & Neurology GA UE051 UT WOS:A1996UE05100014 ER PT J AU DeCarli, C Grady, CL Clark, CM Katz, DA Brady, DR Murphy, DGM Haxby, JV Salerno, JA Gillette, JA GonzalezAviles, A Rapoport, SI AF DeCarli, C Grady, CL Clark, CM Katz, DA Brady, DR Murphy, DGM Haxby, JV Salerno, JA Gillette, JA GonzalezAviles, A Rapoport, SI TI Comparison of positron emission tomography, cognition, and brain volume in Alzheimer's disease with and without severe abnormalities of white matter SO JOURNAL OF NEUROLOGY NEUROSURGERY AND PSYCHIATRY LA English DT Article DE dementia of the Alzheimer type; leukoaraiosis; magnetic resonance imaging; positron emission tomography ID CEREBRAL BLOOD-FLOW; CEREBROVASCULAR RISK-FACTORS; LEUKO-ARAIOSIS; OXYGEN-METABOLISM; VASCULAR DEMENTIA; SENILE DEMENTIA; BINSWANGER TYPE; HEALTHY-MEN; RESONANCE; LEUKOARAIOSIS AB Objectives-To examine cerebral metabolism, cognitive performance, and brain healthy patients Alzheimer's disease, one group with severe abnormalities of white matter (DAT+) and the other group with none, or minimal abnormalities (DAT-). Methods-Neuropsychological tests, CT, MRI, quantitative MRI, and PET studies were carried out to allow comparison between the DAT+ and DAT- groups and the healthy controls. Results-Compared with the healthy controls, both demented groups had significantly reduced global and regional cerebral metabolism, significant brain atrophy, and significantly lower scores on neuropsychological testing. The DAT- patient group showed a pattern of parietal-temporal cerebral metabolic reductions and neuropsychological performance deficits typical of Alzheimer's disease. In addition, metabolism in the association neocortex (AD ratio) and measures of neuropsychological task performance were significantly correlated in the DAT- patient group. Comparison of DAT+ with DAT- patients showed a significantly higher ratio of parietal to whole brain glucose utilisation for the DAT+ group. Moreover, when comparing group z score differences from the healthy controls, the DAT+ group had, on average, smaller differences from controls in the frontal, parietal, and temporal regions than did the DAT- group. Discriminant analysis using metabolic ratios of the frontal, parietal, and temporal regions showed cerebral metabolic patterns to be significantly different among the DAT+, the DAT-, and the healthy controls. These differences were due primarily to relatively higher frontal, parietal, and temporal metabolic ratios in the DAT+ group which resulted in discriminant scores for the DAT+ group between the healthy controls and the DAT- group. Group mean scores on tests of neuropsychological performance were not significantly different between the DAT- and DAT+ patients. By contrast with the DAT- group, however, no significant correlations between the AD ratio and any neuropsychological task were seen in the DAT+ group. Multiple regression analysis showed significant between group differences in the relation between the AD ratio and neuropsychological scores on three tasks. The slopes of the relations between the AD ratio and memory scores (memory and freedom from distractability deviation quotient of the Wechsler adult intelligence scale (WMDQ)) also were significantly different for the two groups. Conclusions-Although multiple causes for abnormalities of white matter exist in patients with Alzheimer's disease, these data suggest that the presence of severe abnormalities of white matter indicate a second pathological process in the DAT+ patients. The DAT- patients showed the parietal-temporal metabolic deficits and correlations between association neocortical metabolism and neuropsychological task performance typical of patients with Alzheimer's disease. By contrast, the DAT+ group had a pattern of cerebral metabolism significantly different from healthy controls and DAT+ patients, as well as no significant correlations between metabolism in the association neocortex and neuropsychological performance. These differences probably reflect the superimposed pathology of the abnormalities of white matter which may exert their affect through disruption of long corticocortical pathways. C1 NIA,NEUROSCI LAB,BETHESDA,MD 20892. NINCDS,EPILEPSY RES BRANCH,BETHESDA,MD 20892. UNIV PENN,DEPT NEUROL,PHILADELPHIA,PA 19104. NCI,PATHOL LAB,BETHESDA,MD 20892. RI DeCarli, Charles/B-5541-2009 NR 63 TC 63 Z9 63 U1 0 U2 3 PU BRITISH MED JOURNAL PUBL GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON, ENGLAND WC1H 9JR SN 0022-3050 J9 J NEUROL NEUROSUR PS JI J. Neurol. Neurosurg. Psychiatry PD FEB PY 1996 VL 60 IS 2 BP 158 EP 167 DI 10.1136/jnnp.60.2.158 PG 10 WC Clinical Neurology; Psychiatry; Surgery SC Neurosciences & Neurology; Psychiatry; Surgery GA TU932 UT WOS:A1996TU93200008 PM 8708645 ER PT J AU Azzam, NA Zalewski, AA Azzam, RN AF Azzam, NA Zalewski, AA Azzam, RN TI Host nerve fibers that regenerate and reside long-term in a rejected nerve allograft are not protected by permeability barriers SO JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY LA English DT Article DE axon; basement membrane; endoneurium; horseradish peroxidase; intercellular cleft; intercellular junction; vascular endothelium ID RAT PERIPHERAL-NERVE; DIFFUSION BARRIER; SCHWANN-CELLS; IMMUNOSUPPRESSED RATS; PROTEIN TRACERS; CYCLOSPORINE-A; GRAFTS; PERINEURIUM; TEMPORARY; MODEL AB We investigated whether permeability barriers develop and protect host nerve fibers that regenerate and reside long-term in a rejected nerve allograft. In order for barriers to form, host cells have to enter the rejected allograft and differentiate into new endothelial and perineurial cells that respectively form the impermeable endoneurial blood-nerve and the perineurium-nerve barriers that are present in normal nerve. A 2-cm long graft of peroneal nerve was taken from American Cancer Institute (ACI) or Fischer (FR) rats and transplanted to bridge a 2-cm gap between the cut ends of the peroneal nerve of other FR rats. Six months postoperatively, histology revealed that regenerated host nerve fibers in ACI allografts were compartmentalized into numerous minifascicles by perineurial cells and that blood vessels were located outside rather than inside the perineurial compartments among the nerve fibers. Administration of the permeability indicator horseradish peroxidase to allograft recipients (intravenously or topically to the graft in situ) revealed that it entered the endoneurium of microcompartments and spread around the nerve fibers. In contrast, none of the indicator reached nerve fibers in FR syngrafts or normal ACI or FR nerves which were not microcompartmentalized. We concluded that host nerve fibers that regenerate and reside long-term in a rejected nerve allograft are not protected by permeability barriers. RP Azzam, NA (reprint author), NINCDS,NIH,LAB NEUROL CONTROL,BLDG 36,ROOM 4A-14,BETHESDA,MD 20892, USA. NR 31 TC 2 Z9 2 U1 0 U2 0 PU AMER ASSN NEUROPATHOLOGISTS INC PI LAWRENCE PA 1041 NEW HAMPSHIRE ST, LAWRENCE, KS 66044 SN 0022-3069 J9 J NEUROPATH EXP NEUR JI J. Neuropathol. Exp. Neurol. PD FEB PY 1996 VL 55 IS 2 BP 150 EP 158 DI 10.1097/00005072-199602000-00003 PG 9 WC Clinical Neurology; Neurosciences; Pathology SC Neurosciences & Neurology; Pathology GA TW031 UT WOS:A1996TW03100003 PM 8786373 ER PT J AU Golomb, D Wang, XJ Rinzel, J AF Golomb, D Wang, XJ Rinzel, J TI Propagation of spindle waves in a thalamic slice model SO JOURNAL OF NEUROPHYSIOLOGY LA English DT Article ID LATERAL GENICULATE-NUCLEUS; ELECTROPHYSIOLOGICAL PROPERTIES; PERIGENICULATE NUCLEUS; RETICULARIS-THALAMI; GUINEA-PIG; INHIBITORY NEURONS; GABAERGIC NEURONS; NEURAL-NETWORK; RELAY NEURONS; CAT AB 1. We study the propagation and dynamics of spindle waves in thalamic slices by developing and analyzing a model of reciprocally coupled populations of excitatory thalamocortical (TC) neurons and inhibitory thalamic reticular (RE) neurons. 2. Each TC neuron has three intrinsic ionic currents: a low-threshold T-type Ca+2 current (I-Ca-T), a hyperpolarization-activated cation (''sag'') current (I-h), and a leak current. Each RE cell also has three currents: I((Ca-T)), a leak current, and a calcium-activated potassium current (I-AHP). Isolated TC cells are at rest. can burst when released or depolarized from a hyperpolarized level, and burst rhythmically under moderate constant hyperpolarizing current. Isolated RE cells are at a hyperpolarized resting membrane potential and can burst when depolarized. 3. TC cells excite RE cells with fast alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) synapses, and RE cells inhibit TC cells with fast gamma-aminobutyric acid-A (GABA(A)) and slow GABA(B) synapses and inhibit each other with GABA(A) synapses only. GABA(B) postsynaptic conductances operate far from saturation, and the slow inhibitory postsynaptic potentials (IPSPs) increase with the width of the presynaptic burst. The model network is a one-dimensional cellular array with localized coupling. The synaptic coupling strength decays with the distance between the pre- and postsynaptic cells, either exponentially or as a step function. 4. The ''intact'' network can oscillate with partial synchrony and a population frequency of similar to 10 Hz. RE cells emit bursts almost at every oscillation cycle, whereas TC cells do so almost at every other cycle. Block of GABA(B) receptors hardly changes the network behavior. Block of GABA(A) receptors leads the network to a slowed oscillatory state, where the population frequency is similar to 4 Hz and both RE and TC cells fire unusually long bursts at every cycle and in full synchrony. These results are consistent with the experimental observations of von Krosigk, Bal, and McCormick. We obtain such consistency only when the above assumptions regarding the synaptic dynamics, particularly nonsaturating GABA(B) synapses, are fulfilled. 5. The slice model has a stable rest state with no neural activity. By initially depolarizing a few neurons at one end of the slice while all the other cells are at rest, a recruitment process may be initiated, and a wavefront of oscillatory activity propagates across the slice. Ahead of the wavefront, neurons are quiescent; neurons behind it oscillate. We find that the wave progresses forward in a lurching manner. TC cells that have just become inhibited must be hyperpolarized for a long enough time before they can fire rebound bursts and recruit RE cells. This step limits the wavefront velocity and may involve a substantial part of the cycle when no cells at the front are depolarized. 6. The wavefront velocity increases linearly with the characteristic spatial length of the connectivity (the footprint length). It increases only gradually with the synaptic strength, logarithmically in the case of an exponential connection function and only slightly for a step connection function. It also decreases gradually with a potassium leak conductance that hyperpolarizes RE cells. 7. To reproduce the experimentally measured wavefront velocity of similar to 1 mm/s, together with other in vitro observations, both the RE-to-TC and the TC-to-RE projections in the model should be spatially localized. The sum of the RE-to-TC and the TC-to-RE synaptic footprint lengths should be on the order of 100 mu m. 8. Neurons at different positions along the slice model oscillate with different phases. in the case of GABA(A) blockade, the phase shifts increase linearly with the distance between neurons and decay only slowly with time. Depending on parameter values, the phase shift can be positive or negative, because in a given bursting cycle a neuron fires before or after those on its right side, respectively. With GABA(A) intact, the phase shift's dependence on interneuronal distance can fluctuate and be more complex. 9. In addition to a propagating wavefront, the network can display various other types of spatiotemporal behaviors as parameter values and initial conditions are varied. Even a few endogenously oscillating cells, as expected in a heterogeneous population, can lead to several initiation points for waves propagating in both directions. The isolated RE network can oscillate with partial synchrony if the RE cells are less hyperpolarized, similar to in vivo results on the isolated RE nucleus by Steriade and colleagues. C1 NIDDK,MATH RES BRANCH,NATL INST HLTH,BETHESDA,MD 20814. UNIV PITTSBURGH,DEPT MATH,PITTSBURGH,PA 15260. RI Wang, Xiao-Jing/D-2722-2009 NR 73 TC 106 Z9 106 U1 1 U2 2 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-3077 J9 J NEUROPHYSIOL JI J. Neurophysiol. PD FEB PY 1996 VL 75 IS 2 BP 750 EP 769 PG 20 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA TV525 UT WOS:A1996TV52500021 PM 8714650 ER PT J AU Brooks, PJ Marietta, C Goldman, D AF Brooks, PJ Marietta, C Goldman, D TI DNA mismatch repair and DNA methylation in adult brain neurons SO JOURNAL OF NEUROSCIENCE LA English DT Article DE DNA repair; DNA methylation; neurons; mutation; cancer; cell nucleus; 5-methyl cytosine; DNA glycosylase; mismatch repair ID NUCLEAR EXTRACTS; HUMAN-CELLS; CYTOSINE METHYLATION; MAMMALIAN-CELLS; POLYMERASE-BETA; G.T MISPAIRS; GLYCOSYLASE; EXCISION; ENZYME; METHYLTRANSFERASE AB DNA repair is essential for maintaining the integrity of the nucleotide sequence of cellular DNA over time. Although much information has accumulated recently on the mechanisms of DNA repair in cultured cells, little is known about the DNA repair capabilities of cells in the adult brain. In the present study, we have investigated the capacity of nuclear extracts from adult rodent brain neurons to carry out DNA mismatch repair. We focused on the repair of G . T and G . U mismatches, which are caused by deamination of 5-methyl cytosine to thymine, or cytosine to uracil, respectively, because these are the only types of mismatches that can arise in nondividing cells. We found that nuclear extracts from adult brain neurons can correct G . T and G . U mismatches, restoring them to G:C base pairs. Several other types of DNA mismatches could not be processed. These data provide the first direct demonstration that neurons in the adult mammalian brain have the capability to carry out DNA mismatch repair. We also we report that adult brain contains high levels of DNA methyltransferase (MTase) activity. We propose that one function of DNA MTase in the adult brain is to remethylate newly incorporated cytosine residues from G . T mismatch repair after deamination of 5-methyl cytosine, thereby maintaining the original pattern of DNA methylation. The high levels of brain DNA MTase suggest further that this enzyme has additional functions in the brain. RP Brooks, PJ (reprint author), NIAAA, NEUROGENET LAB, MOLEC NEUROBIOL SECT, 12501 WASHINGTON AVE, ROCKVILLE, MD 20852 USA. RI Goldman, David/F-9772-2010 OI Goldman, David/0000-0002-1724-5405 NR 38 TC 113 Z9 116 U1 0 U2 2 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD FEB 1 PY 1996 VL 16 IS 3 BP 939 EP 945 PG 7 WC Neurosciences SC Neurosciences & Neurology GA TQ573 UT WOS:A1996TQ57300008 PM 8558262 ER PT J AU McCutcheon, IE Doppman, JL Oldfield, EH AF McCutcheon, IE Doppman, JL Oldfield, EH TI Microvascular anatomy of dural arteriovenous abnormalities of the spine: A microangiographic study SO JOURNAL OF NEUROSURGERY LA English DT Article DE dural arteriovenous fistula; microangiography; dural arteriovenous malformation; spinal arteriovenous malformation; spine ID VASCULAR MALFORMATIONS; CLINICAL-FEATURES; MEDULLARY VEINS; FISTULAS; CORD; EMBOLIZATION; MYELOPATHY; DRAINAGE; SURGERY AB Although most vascular abnormalities of the spinal cord are now ascribed to an abnormal communication between a dural artery and a medullary vein on the dura near a sensory nerve root, these lesions are too small for their anatomy to be demonstrated directly by spinal arteriography. Thus, it is unknown whether the site of dural arteriovenous shunting is an arteriovenous malformation (AVM), implying a congenital origin, or is a direct arteriovenous fistula (AVF), implying an acquired etiology. The authors treated six patients by en bloc resection of the involved dural root sleeve, proximal nerve root, and adjacent spinal dura. All of the patients presented with myelopathy and their arteriograms were consistent with a spinal dural vascular malformation. The lesions occurred between T-6 and T-12, levels al which clinical deficits from such resection are minimal. The dural artery or medullary vein associated with the vascular malformation was cannulated and a dilute solution of barium sulfate was injected during sequential fine-grain radiography. In all of the lesions the artery split into daughter vessels that coalesced one to three times to form a skein of arterial loops in the dura that invariably emptied into a medullary vein without an intervening capillary plexus. Several medium-to-small collateral vessels arising from adjacent intercostal or lumbar arteries were commonly present in the dura and converged at the site of the AVF to join a single medullary vein. These results show that spinal dural AVMs are direct AVFs that link the dural branch of the radiculo-medullary-dural artery with the intradural medullary vein. They also provide an anatomical explanation for the presence of a multiple segmental arterial supply and a single draining medullary vein of spinal dural AVFs, and the propensity for reestablishment of flow through the arteriovenous shunt after embolic occlusion. C1 NINCDS,SURG NEUROL BRANCH,BETHESDA,MD 20892. NIH,CTR CLIN,DEPT DIAGNOST RADIOL,BETHESDA,MD 20892. NR 31 TC 68 Z9 74 U1 1 U2 1 PU AMER ASSOC NEUROLOGICAL SURGEONS PI CHARLOTTESVILLE PA UNIV VIRGINIA, 1224 WEST MAIN ST, STE 450, CHARLOTTESVILLE, VA 22903 SN 0022-3085 J9 J NEUROSURG JI J. Neurosurg. PD FEB PY 1996 VL 84 IS 2 BP 215 EP 220 DI 10.3171/jns.1996.84.2.0215 PG 6 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA TR895 UT WOS:A1996TR89500009 PM 8592223 ER PT J AU Schmidt, KC Lucignani, G Sokoloff, L AF Schmidt, KC Lucignani, G Sokoloff, L TI Fluorine-18-fluorodeoxyglucose PET to determine regional cerebral glucose utilization: A re-examination SO JOURNAL OF NUCLEAR MEDICINE LA English DT Article ID DEOXYGLUCOSE-6-PHOSPHATE STABILITY INVIVO; BRAIN TRANSFER CONSTANTS; TIME UPTAKE DATA; LUMPED CONSTANT; GLUCOSE-6-PHOSPHATASE ACTIVITY; METABOLIC-RATE; F-18 FLUORODEOXYGLUCOSE; HETEROGENEOUS TISSUES; GRAPHICAL EVALUATION; PLASMA C1 UNIV MILAN,INST H SAN RAFFAELE,DEPT NUCL MED,INB,CNR,MILAN,ITALY. RP Schmidt, KC (reprint author), NIMH,CEREBRAL METAB LAB,BETHESDA,MD 20892, USA. RI Lucignani, Giovanni/C-6773-2008 NR 42 TC 37 Z9 38 U1 0 U2 3 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 22090-5316 SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD FEB PY 1996 VL 37 IS 2 BP 394 EP 399 PG 6 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA TU763 UT WOS:A1996TU76300044 PM 8667082 ER PT J AU Shippenberg, TS LeFevour, A Heidbreder, C AF Shippenberg, TS LeFevour, A Heidbreder, C TI kappa-Opioid receptor agonists prevent sensitization to the conditioned rewarding effects of cocaine SO JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS LA English DT Article ID MESSENGER-RNA; EXTRACELLULAR DOPAMINE; NUCLEUS-ACCUMBENS; PLACE PREFERENCE; RAT; MU; REINSTATEMENT; INVOLVEMENT; ANTAGONISTS; WITHDRAWAL AB A place preference conditioning procedure was used to examine the influence of kappa-opioid receptor ligands upon the development of sensitization to the conditioned rewarding effects of cocaine. Previous exposure to cocaine (10-20 mg/kg; i.p.; days 1-5) resulted in an enhancement of the conditioned rewarding effects of this agent, e.g., sensitization, Thus, doses of cocaine (5.0-10.0 mg/kg; i.p.) that failed to produce place preferences in control rats produced significant place preferences in cocaine-experienced animals. In animals that had received the kappa-agonist U50,488H (5.0 mg/kg; s.c.) in combination with the repeated cocaine treatment regimen, no enhancement of cocaine-induced place conditioning was seen. Similarly, the kappa-agonist C169593 administered on days 1 to 5 or only on days 3 to 5 of the cocaine treatment regimen prevented the enhanced response to cocaine. This effect occurred after either systemic (0.04-0.16 mg/kg; s.c.) or intracerebroventricular (1.0 mg) treatment and was abolished by the kappa-opioid receptor antagonist, nor-binaltorphimine. In contrast to its effects when administered in combination with cocaine, prior administration of U69593, alone, failed to modify the conditioned response to cocaine. Microdialysis studies revealed a marked elevation of extracellular dopamine levels within the ventral striatum after repeated cocaine administration. In animals that had received U69593 in combination with cocaine, no elevation of dopamine was seen. These data demonstrate that sensitization develops to the conditioned rewarding effects of cocaine and that the activation of central nervous system kappa-opioid receptors prevents the development of this phenomenon, An involvement of the mesolimbic dopamine system in mediating the interaction of kappa-agonists with cocaine is suggested. RP Shippenberg, TS (reprint author), NIDA, INTRAMURAL RES PROGRAM, BEHAV PHARMACOL & GENET SECT, POB 5180, BALTIMORE, MD 21224 USA. NR 56 TC 119 Z9 122 U1 0 U2 4 PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3995 USA SN 0022-3565 J9 J PHARMACOL EXP THER JI J. Pharmacol. Exp. Ther. PD FEB PY 1996 VL 276 IS 2 BP 545 EP 554 PG 10 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA TV378 UT WOS:A1996TV37800025 PM 8632320 ER PT J AU Ali, H Choi, OH Fraundorfer, PF Yamada, K Gonzaga, HMS Beaven, MA AF Ali, H Choi, OH Fraundorfer, PF Yamada, K Gonzaga, HMS Beaven, MA TI Sustained activation of phospholipase D via adenosine A(3) receptors is associated with enhancement of antigen- and Ca2+-ionophore-induced secretion in a rat mast cell line SO JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS LA English DT Article ID PROTEIN-KINASE-C; BASOPHILIC LEUKEMIA-CELLS; GTP-BINDING PROTEIN; RBL-2H3 CELLS; TYROSINE PHOSPHORYLATION; HISTAMINE-RELEASE; MOLECULAR-CLONING; MEDIATOR RELEASE; HIGH-AFFINITY; 2H3 CELLS AB The adenosine analog, N-ethylcarboxamidoadenosine (NECA), causes transient activation of phospholipase C and an enhancement of antigen-induced secretion in a rat mast cell (RBL-2H3) line via adenosine A(3)-receptors (Ramkumar et al., J. Biol. Chem. 268:16887, 1993) by a mechanism that is inhibited by bacterial toxins and potentiated by dexamethasone (Ali et al., J. Biol. Chem. 265:745-753, 1990). Here we show that NECA synergizes the secretory response to Ca2+-ionophore as well as to antigen. The ability of NECA to synergize the secretory responses persisted for 10 to 20 min, long after the early phospholipase C-mediated reactions to NECA had subsided. NECA caused, however, a dose-dependent sustained activation of phospholipase D, as indicated by the formation of [H-3]phosphatidic acid, or in the presence of 0.3% ethanol, [H-3]phosphatidylethanol. This activation was associated with a sustained increase in diglycerides, in protein kinase C activity and in the phosphorylation of myosin light chains by protein kinase C. The generation of diglycerides was enhanced in dexamethasone-treated cells and suppressed in cells that had been treated with cholera toxin or pertussis toxin. Collectively, the studies suggested that the generation of diglycerides via phospholipase D and the associated activation of protein kinase C were, by themselves, insufficient signals for secretion in RBL-2H3 cells, but that these reactions synergized responses to stimulants such as antigen or A23187 that caused substantial increases in [Ca2+](i). C1 NHLBI,NIH,LAB MOLEC IMMUNOL,BETHESDA,MD 20892. NR 65 TC 75 Z9 75 U1 0 U2 3 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 FEB PY 1996 VL 276 IS 2 BP 837 EP 845 PG 9 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA TV378 UT WOS:A1996TV37800062 PM 8632357 ER PT J AU Dawisha, SM Yarboro, CH Vaughan, EM Austin, HA Balow, JE Klippel, JH AF Dawisha, SM Yarboro, CH Vaughan, EM Austin, HA Balow, JE Klippel, JH TI Outpatient monthly oral bolus cyclophosphamide therapy in systemic lupus erythematosus SO JOURNAL OF RHEUMATOLOGY LA English DT Article DE systemic lupus erythematosus; cyclophosphamide; nephritis; thrombocytopenia ID DOSE INTRAVENOUS CYCLOPHOSPHAMIDE; PULSE METHYLPREDNISOLONE; CONTROLLED TRIAL; MESNA; THROMBOCYTOPENIA; NEPHRITIS AB Objective. An open label study to determine the feasibility and acute toxicity of a 6 month course of outpatient intermittent bolus high dose oral cyclophosphamide in patients with active systemic lupus erythematosus (SLE). Methods. Oral cyclophosphamide in a single dose of 0.5 to 1.0 g/m(2) was given monthly for 6 consecutive months. Disease activity was monitored by quantitative assessments of urine sediment, 24h urine protein excretion, and the Systemic Lupus Activity Measure (SLAM). Results. Twelve patients (11 with glomerulonephritis and one with thrombocytopenia) were studied. Improvements in SLAM scores, proteinuria, and urinary cellular casts were observed in the majority of the 9 patients with nephritis who completed the study. Adverse effects included mild nausea in most patients and intercurrent infections in 2 patients (herpes tester, cellulitis, urinary tract infection). Three patients failed to complete the 6 month course of therapy because of treatment failure in the patient with thrombocytopenia, pregnancy, and severe vomiting, respectively. Conclusion. High dose pulse oral cyclophosphamide is an acceptable alternative for the aggressive outpatient management of selected patients with lupus nephritis. C1 NIAMS,ARTHRITIS & RHEUMATISM BRANCH,BETHESDA,MD. NIH,CTR CLIN,DEPT NURSING,BETHESDA,MD 20892. NIDDKD,CLIN NEPHROL SERV,KIDNEY DIS SECT,BETHESDA,MD. NR 22 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 FEB PY 1996 VL 23 IS 2 BP 273 EP 278 PG 6 WC Rheumatology SC Rheumatology GA TU765 UT WOS:A1996TU76500015 PM 8882031 ER PT J AU Finnegan, EM Luschei, ES Barkmeier, JM Hoffman, HT AF Finnegan, EM Luschei, ES Barkmeier, JM Hoffman, HT TI Sources of error in estimation of laryngeal airway resistance in persons with spasmodic dysphonia SO JOURNAL OF SPEECH AND HEARING RESEARCH LA English DT Article DE laryngeal airway resistance; spasmodic dysphonia; airflow; subglottal pressure; voice disorders ID VOWEL PRODUCTION; INTRAORAL PRESSURE; VOICE; WOMEN; ADDUCTOR; ADULTS; FLOW; AGE AB Estimation of laryngeal airway resistance is a noninvasive method that has proven useful in the study of people with normal and some types of disordered voices. We were interested in examining more closely the application of this method to persons with spasmodic dysphonia (SD), a voice disorder sometimes associated with fluctuating airflow. We speculated unstable airflow could affect the estimation of subglottal pressure and laryngeal airway resistance. Oral pressure and airflow were collected from 10 subjects with SD and 10 control subjects during repetition of /pi/. The coefficient of variation (COV) of airflow during vowel production was calculated to quantify stability of airflow. The results indicated that although some SD subjects produced steady flows during the syllable repetition task, others exhibited substantially varying flows. Inability on the part of the subject to attain steady flows could compromise the usefulness of a midpoint measure of airflow and/or estimation of subglottal pressure, resulting in sources of error in estimation of laryngeal airway resistance. As a result, of the 10 subjects with SD in this study, laryngeal airway resistance could not be estimated in 6 subjects with unsteady flows. Laryngeal airway resistance was estimated in 4 SD subjects who produced steady airflow. Two of these subjects exhibited high laryngeal airway resistance, the others exhibited normal laryngeal airway resistance. C1 UNIV IOWA,WENDELL JOHNSON SPEECH & HEARING CTR,DEPT SPEECH PATHOL & AUDIOL,IOWA CITY,IA. NIDOCD,VOICE & SPEECH SECT,BETHESDA,MD. RP Finnegan, EM (reprint author), UNIV IOWA HOSP & CLIN,DEPT OTOLARYNGOL,200 HAWKINS DR,E 230 GH,IOWA CITY,IA 52242, USA. FU NIDCD NIH HHS [P60 DC00976] NR 33 TC 9 Z9 9 U1 1 U2 4 PU AMER SPEECH-LANG-HEARING ASSN PI ROCKVILLE PA 10801 ROCKVILLE PIKE RD, ROCKVILLE, MD 20852-3279 SN 0022-4685 J9 J SPEECH HEAR RES JI J. Speech Hear. Res. PD FEB PY 1996 VL 39 IS 1 BP 105 EP 113 PG 9 WC Language & Linguistics; Rehabilitation SC Linguistics; Rehabilitation GA TV629 UT WOS:A1996TV62900008 PM 8820702 ER PT J AU Shotland, LI AF Shotland, LI TI Dosimetry measurements using a probe tube microphone in the ear canal SO JOURNAL OF THE ACOUSTICAL SOCIETY OF AMERICA LA English DT Article ID TEMPORARY THRESHOLD SHIFT; PRESSURE; TRANSFORMATION; EARDRUM; FIELD AB Federal and international standards recommend use of microphone placement either on or in the vicinity of the shoulder for dosimetry to minimize deviations from the undisturbed sound field. Probe microphone measurements from the ear canal were compared to shoulder and chest measures in order to investigate the validity of current dosimetry methodologies. Six subjects were monitored in an industrial setting. As expected, ear-canal levels exceeded other measures for all subjects. Shoulder and chest measures showed very low intersubject variability whereas ear-canal measures resulted in large intersubject variability. The ear-canal methodology has the potential to identify individuals whose external ear gain exceed the mean, putting them at increased risk of noise-induced permanent threshold shift (NIPTS). It is proposed that overall external ear pressure gain be used as an index to adjust exposure levels when predicting NIPTS using ISO 1999. A normative database of external ear pressure gain was constructed from 30 ears for this purpose. RP Shotland, LI (reprint author), NIDOCD,NIH,BLDG 10,ROOM 5C306,BETHESDA,MD 20892, USA. NR 33 TC 1 Z9 1 U1 0 U2 0 PU AMER INST PHYSICS PI WOODBURY PA CIRCULATION FULFILLMENT DIV, 500 SUNNYSIDE BLVD, WOODBURY, NY 11797-2999 SN 0001-4966 J9 J ACOUST SOC AM JI J. Acoust. Soc. Am. PD FEB PY 1996 VL 99 IS 2 BP 979 EP 984 DI 10.1121/1.414626 PG 6 WC Acoustics; Audiology & Speech-Language Pathology SC Acoustics; Audiology & Speech-Language Pathology GA TU680 UT WOS:A1996TU68000037 PM 8609306 ER PT J AU Bernstein, EF Chen, YQ Kopp, JB Fisher, L Brown, DB Hahn, PJ Robey, FA Lakkakorpi, J Uitto, J AF Bernstein, EF Chen, YQ Kopp, JB Fisher, L Brown, DB Hahn, PJ Robey, FA Lakkakorpi, J Uitto, J TI Long-term sun exposure alters the collagen of the papillary dermis - Comparison of sun-protected and photoaged skin by Northern analysis, immunohistochemical staining, and confocal laser scanning microscopy SO JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY LA English DT Article ID CULTURED HUMAN FIBROBLASTS; GENE-EXPRESSION; ELASTIC FIBERS; DAMAGED SKIN; PHOTODAMAGE; PROTEIN; MOUSE; CHAIN; ACID; CDNA AB Background: Long-term solar irradiation produces both morphologic and functional changes in affected skin. Because collagen is the major structural component of skin, any alteration in its production or degradation could have profound effects on cutaneous functional integrity. Objective: Our purpose was to investigate alterations in the production and morphology of collagen fibers brought about by long-term sun exposure. Methods: We compared collagen and collagenase gene expression and collagen immunohistochemical staining and used confocal laser scanning microscopy for morphologic examination of dermal collagen fibers in photodamaged compared with sun-protected skin from the same persons. Results: Despite a large increase in elastin messenger RNA in sun-damaged skin, collagen and collagenase gene expression remained essentially unchanged. However, striking alterations in the papillary dermis of photoaged skin were found, which revealed large, abnormally clumped elastic fibers and deformed collagen fibers of various diameters, replacing the normal architecture of the papillary dermis. Conclusion: Our data provide evidence for normal collagen gene expression in sun-damaged skin and suggest that degradation and remodeling of collagen take place in the papillary der mis accompanied by deposition of other matrix components, predominantly abnormal elastic fibers. C1 THOMAS JEFFERSON UNIV,JEFFERSON MED COLL,DEPT BIOCHEM & MOLEC BIOL,PHILADELPHIA,PA 19107. THOMAS JEFFERSON UNIV,JEFFERSON INST MOLEC MED,MOLEC DERMATOL SECT,PHILADELPHIA,PA 19107. NIDR,NIH,BONE RES BRANCH,BETHESDA,MD 20892. RP Bernstein, EF (reprint author), THOMAS JEFFERSON UNIV,JEFFERSON MED COLL,DEPT DERMATOL,233 S 10TH ST,RM 450,PHILADELPHIA,PA 19107, USA. FU NIAMS NIH HHS [R01-AR28450, T32-AR7561] NR 40 TC 107 Z9 112 U1 1 U2 8 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 FEB PY 1996 VL 34 IS 2 BP 209 EP 218 DI 10.1016/S0190-9622(96)80114-9 PN 1 PG 10 WC Dermatology SC Dermatology GA TV697 UT WOS:A1996TV69700005 PM 8642084 ER PT J AU Tomar, SL Husten, CG Manley, MW AF Tomar, SL Husten, CG Manley, MW TI Do dentists and physicians advise tobacco users to quit? SO JOURNAL OF THE AMERICAN DENTAL ASSOCIATION LA English DT Article ID CIGARETTE-SMOKING; SMOKELESS TOBACCO; RANDOMIZED TRIAL; HELPING SMOKERS; UNITED-STATES; INTERVENTION AB To examine dentists' and physicians' effectiveness in advising patients who use tobacco to quit, the authors estimated the percentages of smokers in the United States who visited a dentist or physician in the preceding year, the percentages of those who were advised by their health care provider to quit and the percentages of those who planned to quit smoking. They also estimated the percentage of smokeless tobacco users who were ever advised by their dentist or physician to quit. The results of the study indicate that dentists and physicians may not be maximizing their opportunities to advise their patients who use tobacco to quit, or they are not adequately communicating to their patients the importance of quitting. C1 NCI,DIV CANC PREVENT & CONTROL,PUBL HLTH APPLICAT RES BRANCH,BETHESDA,MD 20892. RP Tomar, SL (reprint author), CTR DIS CONTROL & PREVENT,NATL CTR CHRON DIS PREVENT & HLTH PROMOT,OFF SMOKING & HLTH,ATLANTA,GA 30341, USA. NR 29 TC 102 Z9 105 U1 0 U2 1 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 FEB PY 1996 VL 127 IS 2 BP 259 EP 265 PG 7 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA TU522 UT WOS:A1996TU52200018 PM 8682997 ER PT J AU Slavkin, HG AF Slavkin, HG TI Understanding human genetics SO JOURNAL OF THE AMERICAN DENTAL ASSOCIATION LA English DT Article RP Slavkin, HG (reprint author), NIDR,31 CTR DR,MSC 2290,BLDG 31,ROOM 2C39,BETHESDA,MD 20892, USA. NR 0 TC 4 Z9 4 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 FEB PY 1996 VL 127 IS 2 BP 266 EP 267 PG 2 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA TU522 UT WOS:A1996TU52200019 PM 8682998 ER PT J AU Hodes, RJ Cahan, V Pruzan, M AF Hodes, RJ Cahan, V Pruzan, M TI The national institute on aging at its twentieth anniversary: Achievements and promise of research on aging SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Article RP Hodes, RJ (reprint author), NIA,BLDG 31,RM 5C35,CTR DR MSC2292,BETHESDA,MD 20892, USA. NR 0 TC 9 Z9 9 U1 0 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 FEB PY 1996 VL 44 IS 2 BP 204 EP 206 PG 3 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA TU674 UT WOS:A1996TU67400017 PM 8576514 ER PT J AU Welch, PG Fattom, A Moore, J Schneerson, R Shiloach, J Bryla, DA Li, XR Robbins, JB AF Welch, PG Fattom, A Moore, J Schneerson, R Shiloach, J Bryla, DA Li, XR Robbins, JB TI Safety and immunogenicity of Staphylococcus aureus type 5 capsular polysaccharide-Pseudomonas aeruginosa recombinant exoprotein A conjugate vaccine in patients on hemodialysis SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Article DE end-stage renal disease; Staphylococcus aureus vaccine; antibody response; conjugate vaccine ID INFLUENZAE TYPE-B; AMBULATORY PERITONEAL-DIALYSIS; SERUM ANTIBODY-RESPONSE; EXOTOXIN-A; NASAL CARRIAGE; BACTEREMIA; INFECTION; PREDOMINANCE; PHAGOCYTOSIS; SEPTICEMIA AB Seventeen volunteers with ESRD on hemodialysis, negative for infection with HIV or hepatitis B and C and not receiving immunosuppressive therapy, were injected two times 6 wk apart with 25 mu g of Staphylococcus aureus Type 5 capsular polysaccharide-Pseudomonos aeruginosa exoprotein A (rEPA) conjugate, Controls were healthy adults, 18 to 44 yr old, injected previously with the same vaccine. None of the patients had fever or significant elevations in their SGOT or SGPT attributable to the vaccine, Two vaccinees had transient induration >1 cm in diameter at the injection site, The preimmunization geometric mean (GM) Type 5 antibody levels of the ESRD patients and controls were similar, Type 5 antibody levels of the three major immunoglobulin (Ig) classes rose at 2 and 6 wk after immunization (P < 0.001 for IgG, P < 0.005 for IgM, and P = 0.0001 for IgA), Reimmunization at 6 wk did not elicit a booster response, At 6 months, the GM IgG level of the patients was approximately 50% of that of the healthy volunteers and 14 of 17 had a more than fourfold higher antibody level than the preimmune value, The GM IgM level, in contrast, declined to the preimmunization value. Vaccine-induced Type 5 antibodies had opsonophagocytic activity, There was a slight increase of IgG antibodies to the heterologous S. aureus Type 8 polysaccharide (P < 0.01) that was sustained at 6 months. The S. aureus Type 5-rEPA vaccine is safe and immunogenic in ESRD patients, and evaluation of its effectiveness against S. aureus bacteremia in this at-risk group is planned. C1 NICHHD,PUBL HLTH SERV,NIH,BETHESDA,MD 20892. WALTER REED ARMY MED CTR,SERV NEPHROL,WASHINGTON,DC 20307. UNIVAX BIOL INC,ROCKVILLE,MD. NIDDKD,NIH,BETHESDA,MD 20892. NR 52 TC 38 Z9 40 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD FEB PY 1996 VL 7 IS 2 BP 247 EP 253 PG 7 WC Urology & Nephrology SC Urology & Nephrology GA TZ306 UT WOS:A1996TZ30600010 PM 8785394 ER PT J AU Kersting, U Spring, KR AF Kersting, U Spring, KR TI Ketoconazole activates chloride and fluid secretion by Necturus gallbladder at low pH SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Article DE conductance; secretion; pH; arachidonic acid; epoxides; prostaglandins ID ARACHIDONIC-ACID METABOLISM; APICAL MEMBRANE; CYCLIC-AMP; EPITHELIAL-CELL; ION-TRANSPORT; PERMEABILITY; CONDUCTANCE AB Necturus gallbladder epithelium, normally a reabsorptive epithelium, was stimulated to secrete chloride and fluid by the combined effects of ketoconazole and a reduction in perfusate pH to 7.0, The reversal in the direction of net fluid transport was accompanied by inhibition of the conductance of the apical cell membrane to sodium, potassium, and a striking stimulation of the conductance to chloride. The results are consistent with a previously unidentified mechanism for regulation of the apical cell membrane transport properties of reabsorptive epithelia. C1 NHLBI,KIDNEY & ELECTROLYTE METAB LAB,NIH,BETHESDA,MD 20892. UNIV WURZBURG,DEPT CLIN BIOCHEM,W-8700 WURZBURG,GERMANY. NR 34 TC 2 Z9 2 U1 0 U2 1 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD FEB PY 1996 VL 7 IS 2 BP 254 EP 259 PG 6 WC Urology & Nephrology SC Urology & Nephrology GA TZ306 UT WOS:A1996TZ30600011 PM 8785395 ER PT J AU Richardson, TM Stryjewski, BL Broder, CC Hoxie, JA Mascola, JR Earl, PL Doms, RW AF Richardson, TM Stryjewski, BL Broder, CC Hoxie, JA Mascola, JR Earl, PL Doms, RW TI Humoral response to oligomeric human immunodeficiency virus type 1 envelope protein SO JOURNAL OF VIROLOGY LA English DT Article ID HUMAN MONOCLONAL-ANTIBODY; CD4 BINDING-SITE; GLYCOPROTEIN GP120; HTLV-III; TRANSMEMBRANE GLYCOPROTEIN; SURFACE GLYCOPROTEIN; CD4-BINDING SITE; HIV-1; NEUTRALIZATION; GP41 AB The humoral immune response to human immunodeficiency virus type 1 (HIV-1) is often studied by using monomeric or denatured envelope proteins (Env), However, native HIV-1 Env complexes that maintain quaternary structure elicit immune responses that are qualitatively distinct from those seen with monomeric or denatured Env, To more accurately assess the levels and types of antibodies elicited by HIV-1 infection, we developed an antigen capture enzyme-linked immunosorbent assay using a soluble, oligomeric form of HIV-1(IIIB) Env (gp140) that contains gp120 and the gp41 ectodomain. The gp140, captured by various monoclonal antibodies (MAbs), retained its native oligomeric structure: it bound CD4 and was recognized by MAbs to conformational epitopes in gp120 and gp41, including oligomer-specific epitopes in gp41, We compared the reactivities of clade B and clade E serum samples to captured Env preparations and found that while both reacted equally well with oligomeric gp140, clade B seras reacted more strongly with monomeric gp120 than did clade E samples, However, these differences were minimized when gp120 was captured by a V3 loop MAb, which may lead to increased exposure of the CD4 binding site, We also measured the ability of serum samples to block binding of MAbs to epitopes in gp120 and gp41, Clade B serum samples consistently blocked binding of oligomer-dependent MAbs to gp41 and, to a slightly lesser extent, MAbs to the CD4 binding site in gp120, Clade E serum samples showed equivalent or greater blocking of oligomer-dependent gp41 antibodies and considerably less blocking of CD4-binding-site MAbs, Finally, we found that <5% of the antibodies in clade B sera bound to epitopes present only in monomeric gp120, 30% bound to epitopes present in both monomeric gp120 and oligomeric gp140, and 70% bound to epitopes present in oligomeric gp140, which includes gp41. Thus, captured oligomeric Env closely reflects the antigenic characteristics of Env protein on the surface of virions and infected cells, retains highly conserved epitopes that are recognized by antibodies raised against different clades, and makes it possible to detect a much greater fraction of total anti-HIV-1 Env activity in sera than does native monomeric gp120. C1 UNIV PENN,DEPT PATHOL & LAB MED,PHILADELPHIA,PA 19104. UNIV PENN,DEPT MED HEMATOL ONCOL,PHILADELPHIA,PA 19104. NIAID,VIRAL DIS LAB,BETHESDA,MD 20892. WALTER REED ARMY INST RES,DIV RETROVIROL,ROCKVILLE,MD 20850. FU NIAID NIH HHS [R01 AI35383] NR 60 TC 72 Z9 72 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0022-538X J9 J VIROL JI J. Virol. PD FEB PY 1996 VL 70 IS 2 BP 753 EP 762 PG 10 WC Virology SC Virology GA TP526 UT WOS:A1996TP52600010 PM 8551612 ER PT J AU Schubert, U Bour, S FerrerMontiel, AV Montal, M Maldarelli, F Strebel, K AF Schubert, U Bour, S FerrerMontiel, AV Montal, M Maldarelli, F Strebel, K TI The two biological activities of human immunodeficiency virus type 1 Vpu protein involve two separable structural domains SO JOURNAL OF VIROLOGY LA English DT Article ID ENDOPLASMIC-RETICULUM; CYTOPLASMIC DOMAIN; INDUCED DEGRADATION; CD4; CELLS; HIV-1; GENE; GLYCOPROTEIN; INFECTIVITY; MATURATION AB The human immunodeficiency virus type 1 (HIV-1) Vpu protein is an integral membrane phosphoprotein that induces CD4 degradation in the endoplasmic reticulum and enhances virus release from the cell surface, CD4 degradation is specific, requires phosphorylation of Vpu, and involves the interaction between Vpu and the CD4 cytoplasmic domain, In contrast, regulation of virus release is less specific and not restricted to HIV-1 and may be mechanistically distinct from CD4 degradation, We show here that a mutant of Vpu, Vpu(35), lacking most of its cytoplasmic domain has residual biological activity for virus release but is unable to induce CD4 degradation, This finding suggests that the N terminus of Vpu encoding the transmembrane (TM) anchor represents an active domain important for the regulation of virus release but not CD4 degradation, To better define the functions of Vpu's TM anchor and cytoplasmic domain, we designed a mutant, Vpu(RD), containing a scrambled TM sequence with a conserved amino acid composition and alpha-helical structure. The resulting protein was integrated normally into membranes, was able to form homo-oligomers, and exhibited expression levels, protein stability, and subcellular localization similar to those of wild-type Vpu. Moreover, Vpu(RD) was capable of binding to CD4 and to induce CD4 degradation with wild-type efficiency, confirming proper membrane topology and indicating that the alteration of the Vpu TM domain did not interfere with this function of Vpu, However, Vpu(RD) was unable to enhance the release of virus particles from infected or transfected cells, and virus encoding Vpu(RD) had replication characteristics in T cells indistinguishable from those of a Vpu-deficient HIV-1 isolate, Mutation of the phosphorylation sites in Vpu(RD) resulted in a protein which was unable to perform either function of Vpu, The results of our experiments suggest that the two biological activities of Vpu operate via two distinct molecular mechanisms and involve two different structural domains of the Vpu protein. C1 UNIV CALIF SAN DIEGO,DEPT BIOL,LA JOLLA,CA 92093. RP Schubert, U (reprint author), NIAID,MOLEC MICROBIOL LAB,4-314,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. RI Ferrer-Montiel, Antonio/C-3072-2015 OI Ferrer-Montiel, Antonio/0000-0002-2973-6607 FU NIGMS NIH HHS [GM-49711] NR 43 TC 235 Z9 238 U1 0 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0022-538X J9 J VIROL JI J. Virol. PD FEB PY 1996 VL 70 IS 2 BP 809 EP 819 PG 11 WC Virology SC Virology GA TP526 UT WOS:A1996TP52600017 PM 8551619 ER PT J AU Bour, S Schubert, U Peden, K Strebel, K AF Bour, S Schubert, U Peden, K Strebel, K TI The envelope glycoprotein of human immunodeficiency virus type 2 enhances viral particle release: A Vpu-like factor? SO JOURNAL OF VIROLOGY LA English DT Article ID PROTEIN INDUCES DEGRADATION; CYTOPLASMIC DOMAIN; CELL-LINES; HIV-1 GAG; CD4; EXPRESSION; GENE; ENV; MORPHOGENESIS; INFECTIVITY AB The Vpu protein is a human immunodeficiency virus type 1 (HIV-1)-specific accessory protein that is required for the efficient release of viral particles from infected cells, Even though HIV-2 does not encode Vpu, we found that this virus is nevertheless capable of efficiently releasing virus particles. In fact, the rate of virus release from HeLa cells transfected with a full-length molecular clone of HIV-2, ROD10, was comparable to that observed for the vpr(+) HIV-1 NL4-3 isolate and was not further enhanced by expression of Vpu in trans. However, consistent with previous observations showing that HIV-2 particle release is Vpu responsive in the context of HIV-1/HIV-2 chimeric constructs, exchanging the gag-pol region of NL4-3 with the corresponding region from pROD10 rendered the resulting chimeric virus Vpu responsive, Our finding that the responsiveness of HIV-2 particle release to Vpu is context dependent suggested the presence of a Vpu-like factor(s) encoded by HIV-2. Using chimeric proviruses encoding HIV-2 gag and pol in the context of the HIV-1 provirus that were coexpressed with subgenomic HIV-2 constructs, we found that the HIV-2 envelope glycoprotein had the ability to enhance HIV-2 particle release with an efficiency comparable to that of the HIV-I Vpu protein, Conversely, inactivation of the HIV-2 env gene in the original ROD10 clone resulted in a decrease in the rate of viral particle release to a level that was comparable to that of Vpu-deficient HIV-1 isolates. Providing the wild-type envelope in trans rescued the particle release defect of the ROD10 envelope mutant, Thus, unlike HIV-1, which encodes two separate proteins to regulate virus release or to mediate viral entry, the HIV-2 Env protein has evolved to perform both functions. C1 US FDA,CTR BIOL EVALUAT & RES,LAB RETROVIRUS RES,BETHESDA,MD 20892. RP Bour, S (reprint author), NIAID,MOLEC MICROBIOL LAB,BETHESDA,MD 20892, USA. NR 58 TC 86 Z9 87 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 FEB PY 1996 VL 70 IS 2 BP 820 EP 829 PG 10 WC Virology SC Virology GA TP526 UT WOS:A1996TP52600018 PM 8551620 ER PT J AU Lyu, MS Kozak, CA AF Lyu, MS Kozak, CA TI Genetic basis for resistance to polytropic murine leukemia viruses in the wild mouse species Mus castaneus SO JOURNAL OF VIROLOGY LA English DT Article ID INFECTION; LOCUS; MICE; RETROVIRUSES; CHROMOSOME-1; INDUCTION; RECEPTOR; CELLS; FV-4 AB Cultured cells derived from the wild mouse species Mus castaneus were found to be uniquely resistant to exogenous infection by polytropic mink cell focus-forming (MCF) murine leukemia viruses (MuLVs). This MCF MuLV resistance is inherited as a genetically recessive trait in the progeny of F-1 crosses between M. castaneus and MCF MuLV-susceptible laboratory mice, Examination of the progeny of backcrosses demonstrated that susceptibility is inherited as a single gene which maps to chromosome 1. The map location of this gene places it at or near the locus RmcI, the gene encoding the receptor for MCF/xenotropic MuLVs, suggesting that resistance is mediated by the M. castaneus allele of this receptor. C1 NIAID,MOLEC MICROBIOL LAB,BETHESDA,MD 20892. NR 22 TC 22 Z9 22 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 FEB PY 1996 VL 70 IS 2 BP 830 EP 833 PG 4 WC Virology SC Virology GA TP526 UT WOS:A1996TP52600019 PM 8551621 ER PT J AU Oie, KL Durrant, G Wolfinbarger, JB Martin, D Costello, F Perryman, S Hogan, D Hadlow, WJ Bloom, ME AF Oie, KL Durrant, G Wolfinbarger, JB Martin, D Costello, F Perryman, S Hogan, D Hadlow, WJ Bloom, ME TI Relationship between capsid protein (VP2) sequence and pathogenicity of Aleutian mink disease parvovirus (ADV): A possible role for raccoons in the transmission of ADV infections SO JOURNAL OF VIROLOGY LA English DT Article ID FELINE PANLEUKOPENIA VIRUS; POLYMERASE CHAIN-REACTION; AMINO-ACID SUBSTITUTIONS; CANINE PARVOVIRUS; NUCLEOTIDE-SEQUENCE; ENTERITIS VIRUS; MINUTE VIRUS; HOST RANGE; INTERSTITIAL PNEUMONIA; 5'-TERMINAL PALINDROME AB Aleutian mink disease parvovirus (ADV) DNA was identified by PCR in samples from mink and raccoons on commercial ranches during an outbreak of Aleutian disease (AD). Comparison of DNA sequences of the hypervariable portion of VP2, the major capsid protein of ADV, indicated that both mink and raccoons were infected by a new isolate of ADV, designated ADV-TR. Because the capsid proteins of other parvoviruses play a prominent role in the determination of viral pathogenicity and host range, we decided to examine the relationship between the capsid protein sequences and pathogenicity of ADV. Comparison of the ADV-TR hypervariable region sequence with sequences of other isolates of ADV revealed that ADV-TR was 94 to 100% related to the nonpathogenic type 1 ADV-G at both the DNA and amino acid levels but less than 90% related to other pathogenic ADVs like the type 2 ADV-Utah, the type 3 ADV-ZK8, or ADV-Pullman. This finding indicated that a virus with a type 1 hypervariable region could be pathogenic. To perform a more comprehensive analysis, the complete VP2 sequence of ADV-TR was obtained and compared with that of the 647-amino-acid VP2 of ADV-G and the corresponding VP2 sequences of the pathogenic ADV-Utah, ADV-Pullman, and ADV-ZK8, Although the hypervariable region amino acid sequence of ADV-TR was identical to that of ADV-G, there were 12 amino acid differences between ADV-G and ADV-TR. Each of these differences was at a position where other pathogenic isolates also differed from ADV-G. Thus, although ADV-TR had the hypervariable sequence of the nonpathogenic type 1 ADV-G, the remainder of the VP2 sequence resembled sequences of other pathogenic ADVs. Under experimental conditions, ADV-TR and ADV-Utah were highly pathogenic and induced typical AD in trios of both Aleutian and non-Aleutian mink, whereas ADV-Pullman was pathogenic only for Aleutian mink and ADV-G was noninfectious. Trios of raccoons experimentally inoculated with ADV-TR and ADV-Utah all became infected with ADV, but only a single ADV-Pullman-inoculated raccoon showed evidence of infection. Furthermore, none of the ADV isolates induced pathological findings of AD in raccoons. Finally, when a preparation of ADV-TR prepared from infected raccoon lymph nodes was inoculated into mink and raccoons, typical AD was induced in Aleutian and non-Aleutian mink, but raccoons failed to show serological or pathological evidence of infection. These results indicated that raccoons can become infected with ADV and may have a role in the transmission of virus to mink but that raccoon-to-raccoon transmission of ADV is unlikely. C1 NIAID,ROCKY MT LABS,PERSISTENT VIRAL DIS LAB,HAMILTON,MT 59840. NIAID,ROCKY MT LABS,MICROBIAL STRUCT & FUNCT LAB,HAMILTON,MT 59840. UTAH FUR BREEDERS AGR COOPERAT,SANDY,UT 84070. NR 74 TC 51 Z9 58 U1 1 U2 14 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 FEB PY 1996 VL 70 IS 2 BP 852 EP 861 PG 10 WC Virology SC Virology GA TP526 UT WOS:A1996TP52600022 PM 8551624 ER PT J AU Purcell, DFJ Broscius, CM Vanin, EF Buckler, CE Nienhuis, AW Martin, MA AF Purcell, DFJ Broscius, CM Vanin, EF Buckler, CE Nienhuis, AW Martin, MA TI An array of murine leukemia virus-related elements is transmitted and expressed in a primate recipient of retroviral gene transfer SO JOURNAL OF VIROLOGY LA English DT Article ID LONG TERMINAL REPEAT; FOCUS-INDUCING VIRUSES; AMPHOTROPIC RETROVIRUS; CELL-LINE; DNA; RECOMBINATION; VECTORS; REPLICATION; ENHANCER; IDENTIFICATION AB Direct RNA-PCR analyses of T-cell lymphomas that developed in rhesus macaques during a gene transfer experiment revealed the presence of several different recombinant murine leukemia viruses (MuLV). Most prominent was the expected MuLV recombinant, designated Mo(LTR)Ampho(env), in which the amphotropic env of the helper packaging virus was joined to the long terminal repeat (LTR) of the Moloney MuLV-derived vector, This retrovirus does not exist in nature, An additional copy of the core enhancer acquired from the vector LTR may have augmented the replicative properties of Mo(LTR)mpho(env) MuLV in several different rhesus cell types compared with the prototype amphotropic MuLV(4070A). Unexpectedly, at least two types of mink cell focus-forming MuLV elements, arising from endogenous retroviral sequences expressed in the murine packaging cell line, were also transmitted and highly expressed in one of the macaques, Furthermore, murine virus-like VL-30 sequences were detected in the rhesus lymphomas, but these were not transcribed into RNA. The unanticipated presence of an array of MuLV-related structures in a primate gene transfer recipient demands ever-vigilant scrutiny for the existence of transmissible retroviral elements and replication-competent viruses possessing altered tropic or growth properties in packaging cells producing retroviral vectors. C1 NIAID, MOLEC MICROBIOL LAB, BETHESDA, MD 20892 USA. GENET THERAPY INC, GAITHERSBURG, MD 20878 USA. ST JUDE CHILDRENS RES HOSP, DEPT HEMATOL & ONCOL, DIV EXPTL HEMATOL, MEMPHIS, TN 38101 USA. RI Purcell, Damian/G-5068-2011 NR 58 TC 73 Z9 74 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD FEB PY 1996 VL 70 IS 2 BP 887 EP 897 PG 11 WC Virology SC Virology GA TP526 UT WOS:A1996TP52600026 PM 8551628 ER PT J AU Levin, MC Fox, RJ Lehky, T Walter, M Fox, CH Flerlage, N Bamford, R Jacobson, S AF Levin, MC Fox, RJ Lehky, T Walter, M Fox, CH Flerlage, N Bamford, R Jacobson, S TI PCR-in situ hybridization detection of human T-cell lymphotropic virus type 1 (HTLV-1) tax proviral DNA in peripheral blood lymphocytes of patients with HTLV-1-associated neurologic disease SO JOURNAL OF VIROLOGY LA English DT Article ID TROPICAL SPASTIC PARAPARESIS; POLYMERASE CHAIN-REACTION; MONONUCLEAR-CELLS; INSITU HYBRIDIZATION; LEUKEMIA-VIRUS; MYELOPATHY; ANTIBODIES; INFECTION; AMPLIFICATION; RETROVIRUSES AB PCR-in situ hybridization (PCR-ISH) was developed and utilized to determine the distribution of human T-cell lymphotropic virus type 1 (HTLV-1) tax proviral DNA in peripheral blood lymphocytes (PBL) from patients with HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). PCR-ISH of HTLV-1 tax DNA in PBL from patients with HAM/TSP revealed that 1 in 5,000 to 1 in 10,000 PBL contained virus. PCR-ISH was sensitive, because a positive signal was consistently demonstrated from the HTLV-l-infected cell lines HUT-102 (which contains four to six copies of HTLV-1 proviral DNA per cell) and MT-1 (which contains one to three copies of HTLV-1 proviral DNA per cell). Also, intracellular amplification by PCR-ISH significantly increased sensitivity compared with conventional ISH and was shown to be specific for HTLV-1 tax DNA. These results are in contrast to solution-phase PCR amplification in which greater than 1% of cells were estimated to be infected. The discordance between these results is discussed and may indicate that more than one copy of HTLV-1 tax proviral DNA is present in an individual PBL. C1 NCI,BETHESDA,MD 20892. MOLEC HISTOL LABS,GAITHERSBURG,MD 20879. RP Levin, MC (reprint author), NINCDS,NEUROIMMUNOL BRANCH,BLDG 10,ROOM 5B-16,9000 ROCKVILLE PIKE,BETHESDA,MD 20852, USA. NR 46 TC 26 Z9 26 U1 1 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0022-538X J9 J VIROL JI J. Virol. PD FEB PY 1996 VL 70 IS 2 BP 924 EP 933 PG 10 WC Virology SC Virology GA TP526 UT WOS:A1996TP52600030 PM 8551632 ER PT J AU Eiden, MV Farrell, KB Wilson, CA AF Eiden, MV Farrell, KB Wilson, CA TI Substitution of a single amino acid residue is sufficient to allow the human amphotropic murine leukemia virus receptor to also function as a gibbon ape leukemia virus receptor SO JOURNAL OF VIROLOGY LA English DT Article ID SUBGROUP-B; INFECTION; CELLS AB We have previously reported the unique properties of a receptor for amphotropic murine leukemia viruses (A-MuLVs) expressed on Chinese hamster E36 cells (C. A. Wilson, K. B. Farrell, and M. V. Eiden, J. Virol. 68:7697-7703, 1994). This receptor, HaPiT2 (formerly designated EAR), in contrast to the human form of the A-MuLV receptor (PiT2), functions as a receptor not only for A-MuLVs but also for gibbon ape leukemia virus (GALV). Comparison of the deduced amino acid sequences of the HaPiT2 and PiT2 proteins suggested that differences in the amino acid composition of the extracellular region(s) of the hamster and human proteins account for their functional differences, We substituted extracellular regions of HaPiT2 for those of PiT2 to map the region of the HaPiT2 protein required for GALV receptor function, Only those PiT2-HaPiT2 chimeric receptors containing the fourth and fifth extracellular regions of HaPiT2 functioned as GALV receptors, We have now determined that the substitution of a single amino acid residue, glutamic acid, for the lysine residue at position 522 in the fourth extracellular region of the PiT2 protein is sufficient to render PiT2 functional as a GALV receptor. C1 NIMH,CELL BIOL LAB,BETHESDA,MD 20892. US FDA,DIV CELLULAR & GENE THERAPIES,LAB MOLEC TUMOR BIOL,CTR BIOL EVALUAT & RES,ROCKVILLE,MD 20892. NR 22 TC 43 Z9 43 U1 0 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0022-538X J9 J VIROL JI J. Virol. PD FEB PY 1996 VL 70 IS 2 BP 1080 EP 1085 PG 6 WC Virology SC Virology GA TP526 UT WOS:A1996TP52600048 PM 8551566 ER PT J AU Iversen, AKN Shafer, RW Wehrly, K Winters, MA Mullins, JI Chesebro, B Merigan, TC AF Iversen, AKN Shafer, RW Wehrly, K Winters, MA Mullins, JI Chesebro, B Merigan, TC TI Multidrug-resistant human immunodeficiency virus type 1 strains resulting from combination antiretroviral therapy SO JOURNAL OF VIROLOGY LA English DT Article ID HIV-1 REVERSE-TRANSCRIPTASE; ANGSTROM RESOLUTION; CRYSTAL-STRUCTURE; ZIDOVUDINE AZT; SENSITIVITY; MUTATION; QUANTITATION; INFECTIVITY; INHIBITORS; ASSAY AB Multidrug-resistant human immunodeficiency virus type 1 (HIV-1) strains with reverse transcriptase (RT) mutations at codons A62-->V, V75-->I, F77-->L, F116-->Y, and Q151-->M have been reported in patients receiving combination therapy with zidovudine (AZT) and didanosine (ddI). Infectious clones with each mutation alone, all five mutations together, and various combinations of mutations were created by site-directed mutagenesis, Mutation Q151-->I conferred partial resistance to AZT, ddI, zalcitibine, and stavudine, whereas a combination of four mutations conferred increased resistance to AZT, ddI, zalcitibine, and stavudine, The positions of residues 75, 77, and 151 in the three-dimensional crystal structure of HIV-1 RT suggest that these residues may affect the ability of the enzyme to discriminate between deoxynucleoside triphosphates and nucleoside analog RT inhibitors, Replication experiments showed that clones with mutation F77-->L but without V75-->I (HIV-1(77), HIV-1(77,151), and HIV-1(77,116,151)) had attenuated growth compared with that of the original HIV-1(NL4-3) strain and strains containing mutations at both positions 75 and 77 (HIV-1(75,77,151) and HIV-1(75,77,116,151)). Sequence analysis of viral RNA and proviral DNA from several patients indicated that RT mutations developed in a sequential and cumulative pattern over the course of a 2- to 4-year observation period, The present results suggest that drug resistance and viral replicative capacity both may play a role in selection of HIV-1 RT mutations. C1 STANFORD UNIV,CTR AIDS RES,DIV INFECT DIS & GEOG MED,STANFORD,CA 94305. STANFORD UNIV,DEPT MICROBIOL & IMMUNOL,STANFORD,CA 94305. NIAID,ROCKY MT LABS,PERSISTENT VIRAL DIS LAB,HAMILTON,MT 59840. FU NIAID NIH HHS [AI27666, AI32885] NR 29 TC 208 Z9 212 U1 0 U2 4 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 FEB PY 1996 VL 70 IS 2 BP 1086 EP 1090 PG 5 WC Virology SC Virology GA TP526 UT WOS:A1996TP52600049 PM 8551567 ER PT J AU Skiadopoulos, MH McBride, AA AF Skiadopoulos, MH McBride, AA TI The bovine papillomavirus type 1 E2 transactivator and repressor proteins use different nuclear localization signals SO JOURNAL OF VIROLOGY LA English DT Article ID DNA-BINDING ACTIVITY; CARBOXY-TERMINAL DOMAIN; TRANSCRIPTIONAL REPRESSOR; REGULATORY PROTEINS; REPLICATION INVITRO; TARGETING SEQUENCE; REDOX REGULATION; ORIGIN; VIRUS; IDENTIFICATION AB The E2 gene of bovine papillomavirus type 1 encodes at least three nuclear phosphoproteins that regulate viral transcription and DNA replication, All three proteins have a common C-terminal domain that has DNA-binding and dimerization activities. A basic region in this domain forms an alpha helix which makes direct contact with the DNA target, In this study, it is shown that in addition to its role in DNA binding, this basic region functions as a nuclear localization signal both in the E2 DNA-binding domain and in a heterologous protein, Deletion of this signal sequence resulted in increased accumulation of the E2 transactivator and repressor proteins in the cytoplasm, but nuclear localization was not eliminated, In the full-length transactivator protein, another signal, present in the N-terminal transactivation domain, is used for transport to the nucleus, and the C-terminal nuclear localization signal(s) are masked. The use of different nuclear localization signals could potentially allow differential regulation of the subcellular localization of the E2 transactivator and repressor proteins at some stage in the viral life cycle. C1 NIAID,VIRAL DIS LAB,BETHESDA,MD 20892. OI McBride, Alison/0000-0001-5607-5157 NR 47 TC 30 Z9 30 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 FEB PY 1996 VL 70 IS 2 BP 1117 EP 1124 PG 8 WC Virology SC Virology GA TP526 UT WOS:A1996TP52600053 PM 8551571 ER PT J AU Robbins, DC Knowler, WC Lee, ET Yeh, JL Go, OT Welty, T Fabsitz, R Howard, BV AF Robbins, DC Knowler, WC Lee, ET Yeh, JL Go, OT Welty, T Fabsitz, R Howard, BV TI Regional differences in albuminuria among American Indians: An epidemic of renal disease SO KIDNEY INTERNATIONAL LA English DT Article ID DEPENDENT DIABETES-MELLITUS; PIMA-INDIANS; KIDNEY-DISEASE; BLOOD-PRESSURE; PROTEINURIA; NEPHROPATHY; MORTALITY; MICROALBUMINURIA; SUSCEPTIBILITY; PREDICTOR AB Albuminuria is a risk factor for renal and cardiovascular disease. We conducted a cross sectional survey of 4549 older American Indians in Arizona, Oklahoma and North and South Dakota of (micro)albuminuria. A range of 20.1 to 48.3% of all participants had either micro- (greater than or equal to 30 to < 300 mg albumin/g creatinine) or macroalbuminuria (greater than or equal to 300 mg albumin/g creatinine). A total of 53% of the participants were diabetic, and the prevalence in Arizona (65 to 70%) was significantly greater than the other two sites. Prevalence of micro- and macroalbuminuria were significantly higher among those who were older, diabetic or hypertensive, and participants from Arizona. Even normotensive, nondiabetic Arizona Indians had higher prevalence rates than similar participants elsewhere. Higher prevalence rates of micro- and macroalbuminuria were also found among Arizona participants than participants with similar degrees of glucose intolerance from the other two sites. Indians reporting the greatest degree of Indian blood were more likely to have abnormal albuminuria (P < 0.0001). The duration of diabetes, fasting plasma glucose, systolic blood pressure, fibrinogen and Indian heritage were independently associated with micro- or macroalbuminuria. The association of albuminuria with subsequent ESRD, cardiovascular morbidity and overall mortality suggests that these American Indians will face a large disease burden. The correlation with reported Indian blood implies a strong component of genetic susceptibility, possibly independent of diabetes. C1 NIDDKD,PHOENIX EPIDEMIOL & CLIN RES BRANCH,ARTHRIT EPIDEMIOL SECT,PHOENIX,AZ. UNIV OKLAHOMA,HLTH SCI CTR,CTR EPIDEMIOL RES,OKLAHOMA CITY,OK 73190. ABERDEEN AREA INDIAN HLTH SERV,RAPID CITY,SD. NHLBI,DIV EPIDEMIOL,BETHESDA,MD 20892. RP Robbins, DC (reprint author), MEDLANT RES INST,108 IRVING ST NW,WASHINGTON,DC 20010, USA. FU NHLBI NIH HHS [HL41642] NR 37 TC 46 Z9 47 U1 0 U2 1 PU BLACKWELL SCIENCE INC PI CAMBRIDGE PA 238 MAIN ST, CAMBRIDGE, MA 02142 SN 0085-2538 J9 KIDNEY INT JI Kidney Int. PD FEB PY 1996 VL 49 IS 2 BP 557 EP 563 DI 10.1038/ki.1996.79 PG 7 WC Urology & Nephrology SC Urology & Nephrology GA TR103 UT WOS:A1996TR10300034 PM 8821844 ER PT J AU Ward, JM Anver, MR Haines, DC Melhorn, JM Gorelick, P Yan, L Fox, JG AF Ward, JM Anver, MR Haines, DC Melhorn, JM Gorelick, P Yan, L Fox, JG TI Inflammatory large bowel disease in immunodeficient mice naturally infected with Helicobacter hepaticus SO LABORATORY ANIMAL SCIENCE LA English DT Article ID HOMOSEXUAL MEN; SP-NOV; PYLORI AB Large bowel disease detected clinically by rectal prolapse was studied in 64 immunodeficient mice (37 athymic NCr-nu/nu, 12 BALB/c AnNCr-nu/nu, 9 C57BL/6NCr-nu/nu, and 6 C.B17/Icr-scid/NCr) naturally infected with Helicobacter hepaticus, Rectal prolapse was found in approximately 5% of immunodeficient mice maintained in a research facility over a period of 3.5 years. All mice had various degrees of chronic proliferative typhlitis, colitis, and proctitis, usually without concomitant hepatitis, Some mice had severe proliferative proctitis with cystic hyperplasia, Histologic study of the large bowel of 48 athymic NCr-nu/nu mice without H. hepaticus infection and housed in another clean facility revealed only 12% of the mice with minimal-to-mild large bowel inflammation, Helicobacter hepaticus infection is associated with large bowel disease in immunodeficient mice but is not seen in H. hepaticus-infected immunocompetent mice, This new pathogenic bacterial infection should be considered as another potential cause or co-factor for rectal prolapse and large bowel disease in mice. C1 NCI,FCRDC,INC DYNCORP,OFF LAB ANIM SCI,PATHOL HISTOTECHNOL LAB,FREDERICK,MD 21702. NCI,FCRDC,INC DYNCORP,LAB ANIM SCI PROGRAM,PROGRAM RESOURCES,FREDERICK,MD 21702. MIT,DIV COMPARAT MED,CAMBRIDGE,MA 02139. RP Ward, JM (reprint author), NCI,FCRDC,INC DYNCORP,VET TUMOR PATHOL SECT,FREDERICK,MD 21702, USA. FU NCI NIH HHS [R01CA67529]; NCRR NIH HHS [RR01046, RR07036] NR 27 TC 152 Z9 154 U1 0 U2 1 PU AMER ASSOC LABORATORY ANIMAL SCIENCE PI CORDOVA PA 70 TIMBERCREEK DR, SUITE 5, CORDOVA, TN 38018 SN 0023-6764 J9 LAB ANIM SCI JI Lab. Anim. Sci. PD FEB PY 1996 VL 46 IS 1 BP 15 EP 20 PG 6 WC Veterinary Sciences; Zoology SC Veterinary Sciences; Zoology GA TW872 UT WOS:A1996TW87200005 PM 8699813 ER PT J AU Otsuki, T Jaffe, ES Wellmann, A Kumar, S Condron, KS Raffeld, M AF Otsuki, T Jaffe, ES Wellmann, A Kumar, S Condron, KS Raffeld, M TI Absence of p18 mutations or deletions in lymphoid malignancies SO LEUKEMIA LA English DT Article DE p18; cyclin-dependent kinase inhibitors; tumor suppressor genes; lymphoid malignancies; molecular pathogenesis ID CYCLIN-DEPENDENT KINASES; CELL-CYCLE; INHIBITOR; P21 AB p18 is a recently described cyclin-dependent kinase inhibitor (CDK-l) with homology to p16 and p15. The latter two CDK-ls have been implicated as possible tumor suppressor genes in a wide variety of human tumors, including hematological malignancies. Because of p18's structural and functional homology to p16 and p15, we hypothesized that it may also function as a tumor suppressor gene in some lymphoid malignancies. To explore this possibility we examined 81 primary lymphoid tumors for deletion and mutation of p18. The primary tumors included 40 T cell malignancies and 41 B cell malignancies. None of the lymphoid tumors studied possessed deletions of p18, including a group of lymphoblastic lymphomas which we previously reported to have deletions of p16 and p15. PCR-SSCP analysis of the p18 gene identified a single polymorphism of codon 114, but failed to demonstrate mutations in any of the lymphoid tumors. These results do not support a role for p18 in the pathogenesis of the lymphoid neoplasms studied. C1 NATL CANC INST,NIH,PATHOL LAB,HEMATOPATHOL SECT,BETHESDA,MD 20892. NR 35 TC 13 Z9 13 U1 0 U2 0 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE, HAMPSHIRE, ENGLAND RG21 6XS SN 0887-6924 J9 LEUKEMIA JI Leukemia PD FEB PY 1996 VL 10 IS 2 BP 356 EP 360 PG 5 WC Oncology; Hematology SC Oncology; Hematology GA UA772 UT WOS:A1996UA77200024 PM 8637248 ER PT J AU Blagosklonny, MV Alvarez, M Fojo, A Neckers, LM AF Blagosklonny, MV Alvarez, M Fojo, A Neckers, LM TI bcl-2 protein downregulation is not required for differentiation of multidrug resistant HL60 leukemia cells SO LEUKEMIA RESEARCH LA English DT Article DE leukemia; drug resistance; differentiation; phorbol ester; bcl-2; bax; p21/Waf1 ID GENE-EXPRESSION; HL-60 CELLS; DEATH; ADRIAMYCIN; KINASE AB Parental and multidrug resistant HL60 leukemia cell lines were used to study coupling of expression of apoptotic/cytostatic (bcl-2, bax, bclxL, p21/Waf1, and c-myc) genes during differentiation. The multidrug resistant HL60 cell line, HL60/ADR, was less sensitive than parental cells to cytostatic activity of low (0.4-2 ng/ml) doses of PMA. However, during treatment with standard differentiating doses of PMA (10 ng/ml), no difference between the two cell lines in cytostasis and differentiation was found, Downregulation of c-myc and upregulation of p21/Waf1 proteins showed the same time-course in both cell lines. The bcl-2 mRNA was rapidly downregulated while bax and bclxL gene expression was not altered in both differentiating HL60 and HL60/ADR cells. Significant downregulation of bcl-2 protein occurred only in parental HL60 cells. In HL60/ADR, despite rapid cessation of bcl-2 protein synthesis, almost no change in steady-state bcl-2 protein level was found. The lack of bcl-2 protein downregulation was a result of the prolonged half-life of this protein in HL60/ADR cells. Thus, although downregulation of bcl-2 mRNA is coupled to differentiation, actual loss of bcl-2 protein is not required for accomplishment of the differentiation program. C1 NCI, MED BRANCH, NIH, BETHESDA, MD 20892 USA. RP Blagosklonny, MV (reprint author), NCI, CLIN PHARMACOL BRANCH, NIH, BLDG 10, ROOM 12N226, BETHESDA, MD 20892 USA. NR 26 TC 39 Z9 41 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0145-2126 J9 LEUKEMIA RES JI Leuk. Res. PD FEB PY 1996 VL 20 IS 2 BP 101 EP 107 DI 10.1016/0145-2126(95)00103-4 PG 7 WC Oncology; Hematology SC Oncology; Hematology GA UD585 UT WOS:A1996UD58500001 PM 8628007 ER PT J AU Zhou, J Jensen, SM Steinberg, SM Mulshine, JL Linnoila, RI AF Zhou, J Jensen, SM Steinberg, SM Mulshine, JL Linnoila, RI TI Expression of early lung cancer detection marker p31 in neoplastic and non-neoplastic respiratory epithelium SO LUNG CANCER LA English DT Article DE early detection; histologic abnormalities; immunohistochemistry; human lung; lung cancer ID SENSITIVITY; CELLS AB In an immunocytochemical study of sputum, two antibodies, including a mouse monoclonal antibody (703D4) to a 31 kDa protein (p31) antigen, have been previously shown to detect lung cancer earlier than routine cytomorphology or chest X-ray. To understand the basis of p31 expression, the distribution of this antigen in the respiratory epithelium of individuals known to have lung cancer was mapped. These individuals are likely to demonstrate extensive changes throughout the epithelium due to field cancerization, p31 immunoreactivity was examined in primary tumors and surrounding non-neoplastic lungs containing both histologically normal and abnormal areas obtained from 28 Stage I non-small cell lung cancer (NSCLC) patients. Distribution and intensity of p31 expression was scored in three lung compartments (bronchi, bronchioli, alveoli). While p31 was present in histologically unremarkable bronchial and bronchiolar epithelium, no expression was detected in bronchi or bronchioli containing histologic abnormalities. Furthermore, in the peripheral lung p31 staining was frequently observed in alveolar type II cells and was most commonly detected in reactive, hyperplastic type II cells, When p31 immunoreactivity was correlated with clinicopathological features, a statistically significant increase in p31 expression was found both in bronchioli and alveoli of older individuals as well as in bronchioli of patients with most extensive smoking exposure. We conclude that p31 expression occurs in both non-neoplastic and neoplastic epithelium of the human respiratory tract. The increased expression of p31 in the peripheral lung may be potentially informative as to what critical cell populations are involved in the development of invasive cancers. Moreover, this study provides a model approach for analysis of the nature of early epithelial changes leading to the development of lung cancer. C1 NCI,NIH,BIOMARKERS & PREVENT RES BRANCH,ROCKVILLE,MD 20850. NCI,CLIN ONCOL PROGRAM,NIH,BIOSTAT & DATA MANAGEMENT SECT,BETHESDA,MD 20892. NR 23 TC 19 Z9 23 U1 1 U2 1 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0169-5002 J9 LUNG CANCER-J IASLC JI Lung Cancer PD FEB PY 1996 VL 14 IS 1 BP 85 EP 97 DI 10.1016/0169-5002(95)00514-5 PG 13 WC Oncology; Respiratory System SC Oncology; Respiratory System GA TZ048 UT WOS:A1996TZ04800008 PM 8696723 ER PT J AU Crosby, AH Lyu, MS Lin, K McBride, OW Kerr, JM Aplin, HM Fisher, LW Young, MF Kozak, CA Dixon, MJ AF Crosby, AH Lyu, MS Lin, K McBride, OW Kerr, JM Aplin, HM Fisher, LW Young, MF Kozak, CA Dixon, MJ TI Mapping of the human and mouse bone sialoprotein and osteopontin loci SO MAMMALIAN GENOME LA English DT Article ID LOCALIZATION; GENE; SEQUENCE; CHROMOSOME-5; EXPRESSION; TISSUES; CLONING 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. NIAID,MOLEC MICROBIOL LAB,BETHESDA,MD 20892. NCI,BIOCHEM LAB,BETHESDA,MD 20892. NIDR,BONE RES BRANCH,BETHESDA,MD 20892. RI Crosby, Andrew/E-2218-2015 FU Wellcome Trust NR 25 TC 29 Z9 31 U1 0 U2 1 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0938-8990 J9 MAMM GENOME JI Mamm. Genome PD FEB PY 1996 VL 7 IS 2 BP 149 EP 151 DI 10.1007/s003359900037 PG 3 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity GA TV274 UT WOS:A1996TV27400012 PM 8835534 ER PT J AU Kozak, CA Adamson, MC Weinberger, C AF Kozak, CA Adamson, MC Weinberger, C TI Genetic mapping of gene encoding the farnesoid receptor, Fxr, to mouse Chromosome 10 SO MAMMALIAN GENOME LA English DT Article C1 NIEHS,REPROD & DEV TOXICOL LAB,ORPHAN RECEPTOR GRP,RES TRIANGLE PK,NC 27709. RP Kozak, CA (reprint author), NIAID,BLDG 4,ROOM 329,BETHESDA,MD 20892, USA. NR 8 TC 2 Z9 2 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0938-8990 J9 MAMM GENOME JI Mamm. Genome PD FEB PY 1996 VL 7 IS 2 BP 164 EP 165 DI 10.1007/s003359900042 PG 2 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity GA TV274 UT WOS:A1996TV27400019 PM 8835541 ER PT J AU OMarcaigh, AS Johnson, CM Smithson, WA Patterson, MC Widemann, BC Adamson, PC McManus, MJ AF OMarcaigh, AS Johnson, CM Smithson, WA Patterson, MC Widemann, BC Adamson, PC McManus, MJ TI Successful treatment of intrathecal methotrexate overdose by using ventriculolumbar perfusion and intrathecal instillation of carboxypeptidase G(2) SO MAYO CLINIC PROCEEDINGS LA English DT Article ID CEREBROSPINAL-FLUID AB Prompt and appropriate management measures are critical in order to achieve a favorable outcome after a major overdose of intrathecally (IT) administered methotrexate (MTX). Published information available to guide clinicians in the immediate management of this medical emergency is scant. Herein we describe a 6-year-old boy with acute lymphoblastic leukemia who received an inadvertent overdose of 600 mg of IT administered MTX instead of the intended dose of 12 mg. Severe acute neurotoxicity developed rapidly. Lumbar puncture and drainage of 15 mt of cerebrospinal fluid 2 hours after administration resulted in removal of 32% of the administered drug. Ventriculolumbar perfusion with 240 mt of warmed isotonic saline through ventricular and lumbar catheters for 3 hours resulted in removal of a total of 90% of the drug within 81/2 hours after administration. IT administration of 2,000 U of carboxypeptidase G(2) (CPDG(2)), an enzyme that inactivates MTX, resulted in a further 150-fold reduction in cerebrospinal fluid MTX concentration. The patient experienced complete recovery. To our knowledge, this is the first reported case of the use of IT instillation of CPDG(2) for the treatment of an overdose of IT administered MTX in a human, and it is only the second reported favorable outcome after an IT overdose of more than 500 mg of MTX. Minor IT overdoses of MTX can be managed by immediate lumbar drainage alone. Major overdoses may also necessitate prompt ventriculolumbar perfusion, IT instillation of CPDG(2), and further supportive measures for a successful outcome after this infrequent but potentially catastrophic event. C1 MAYO CLIN,SECT PEDIAT HEMATOL ONCOL,ROCHESTER,MN 55905. MAYO CLIN,PEDIAT CRIT CARE SERV,ROCHESTER,MN 55905. MAYO CLIN,SECT CHILD & ADOLOSCENT NEUROL,ROCHESTER,MN. NCI,PEDIAT BRANCH,BETHESDA,MD 20892. OI Patterson, Marc/0000-0002-1116-126X NR 13 TC 30 Z9 30 U1 0 U2 0 PU MAYO CLINIC PROCEEDINGS PI ROCHESTER PA 660 SIEBENS BLDG MAYO CLINIC, ROCHESTER, MN 55905 SN 0025-6196 J9 MAYO CLIN PROC JI Mayo Clin. Proc. PD FEB PY 1996 VL 71 IS 2 BP 161 EP 165 PG 5 WC Medicine, General & Internal SC General & Internal Medicine GA TU539 UT WOS:A1996TU53900007 PM 8577190 ER PT J AU Bradbury, AJ Gruer, MJ Rudd, KE Guest, JR AF Bradbury, AJ Gruer, MJ Rudd, KE Guest, JR TI The second aconitase (AcnB) of Escherichia coli SO MICROBIOLOGY-SGM LA English DT Article DE aconitase; Escherichia coli; citric acid cycle; iron-sulphur proteins; protein domains ID ELEMENT-BINDING PROTEIN; NUCLEOTIDE-SEQUENCE; IRON; GENE; ACID; MAP AB The second aconitase (AcnB) of Escherichia coli was partially purified from an acnA::kan(R) mutant lacking AcnA, and the corresponding polypeptide identified by activity staining and weak cross-reactivity with AcnA antiserum. The acnB gene was located at 2.85 min (131.6 kb) in a region of the chromosome previously assigned to two unidentified ORFs. Aconitase specific activities were amplified up to fivefold by infection with lambda acnB phages from the Kohara lambda-E. coli gene library, and up to 120-fold (50% of soluble protein) by inducing transformants containing a plasmid (pGS783) in which the acnB coding region is expressed from a regulated T7 promoter. The AcnB protein was purified to greater than or equal to 98% homogeneity from a genetically enriched source (JRG3171) and shown to be a monomeric protein of M(r) 100000 (SDS-PAGE) and 105000 (gel filtration analysis) compared with M(r) 93 500 predicted from the nucleotide sequence, The sequence identity between AcnA and AcnB is only 17% and the domain organization of AcnA and related proteins (1-2-3-linker-4) is rearranged in AcnB (4-1-2-3). C1 UNIV SHEFFIELD, KREBS INST BIOMOLEC RES, DEPT MOLEC BIOL & BIOTECHNOL, SHEFFIELD S10 2UH, S YORKSHIRE, ENGLAND. NIH, NATL LIB MED, NATL CTR BIOTECHNOL INFORMAT, BETHESDA, MD 20894 USA. FU Wellcome Trust NR 30 TC 27 Z9 28 U1 0 U2 4 PU SOC GENERAL MICROBIOLOGY PI READING PA MARLBOROUGH HOUSE, BASINGSTOKE RD, SPENCERS WOODS, READING RG7 1AG, BERKS, ENGLAND SN 1350-0872 J9 MICROBIOL-SGM JI Microbiology-(UK) PD FEB PY 1996 VL 142 BP 389 EP 400 PN 2 PG 12 WC Microbiology SC Microbiology GA TW477 UT WOS:A1996TW47700019 PM 8932712 ER PT J AU Deitsch, KW Wellems, TE AF Deitsch, KW Wellems, TE TI Membrane modifications in erythrocytes parasitized by Plasmodium falciparum SO MOLECULAR AND BIOCHEMICAL PARASITOLOGY LA English DT Review DE malaria; host-parasite relations; red blood cell; membrane transport; protein trafficking; cytoadherence; antigenic variation; immune evasion ID HISTIDINE-RICH PROTEIN; MALARIA-INFECTED ERYTHROCYTES; MONOCLONAL-ANTIBODY; ANTIGENIC VARIATION; SURFACE-MEMBRANE; KNOBLESS CLONE; MELANOMA-CELLS; DIRECT ACCESS; CYTOADHERENCE; SEQUESTRATION AB Plasmodium falciparum malaria parasites invade human red blood cells and immediately begin making significant alterations to the structure of the erythrocyte. These alterations facilitate the movement of nutrients into, and waste products and parasite-derived proteins out of the cell to meet the needs of the growing parasite. A tubovesicular membrane network extending from the parasite vacuole membrane probably has a central role in the transport processes. The parasite also modifies the erythrocyte membrane itself in a way that not only changes its permeablilty but also places parasite-derived proteins in knob-like protrusions at the cell surface. These proteins enable the parasite to adhere to endothelial cells and thereby avoid clearance from the blood stream by the spleen. Antigenic variation of these proteins allows parasitized erythrocytes to vary their phenotype and produce a sustained and chronic malaria infection. Study of the molecular processes that underlie these parasite-induced modifications of the host red blood cell will lead to improved understanding of malaria pathogenesis and, perhaps, suggest new approaches against the disease. C1 NIAID,PARASIT DIS LAB,NIH,BETHESDA,MD 20892. NR 87 TC 103 Z9 104 U1 1 U2 7 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 FEB-MAR PY 1996 VL 76 IS 1-2 BP 1 EP 10 DI 10.1016/0166-6851(95)02575-8 PG 10 WC Biochemistry & Molecular Biology; Parasitology SC Biochemistry & Molecular Biology; Parasitology GA UF093 UT WOS:A1996UF09300001 PM 8919990 ER PT J AU Silberman, JD Clark, CG Sogin, ML AF Silberman, JD Clark, CG Sogin, ML TI Dientamoeba fragilis shares a recent common evolutionary history with the trichomonads SO MOLECULAR AND BIOCHEMICAL PARASITOLOGY LA English DT Article DE Dientamoeba fragilis; rRNA; 16S-like rRNA; evolution; protist C1 NIH,PARASIT DIS LAB,BETHESDA,MD 20892. RP Silberman, JD (reprint author), MARINE BIOL LAB,CTR MOLEC EVOLUT,WOODS HOLE,MA 02543, USA. RI Clark, C Graham/H-3683-2011 OI Clark, C Graham/0000-0002-0521-0977 FU NIGMS NIH HHS [GM 32964] NR 15 TC 50 Z9 52 U1 0 U2 4 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 FEB-MAR PY 1996 VL 76 IS 1-2 BP 311 EP 314 DI 10.1016/0166-6851(95)02516-2 PG 4 WC Biochemistry & Molecular Biology; Parasitology SC Biochemistry & Molecular Biology; Parasitology GA UF093 UT WOS:A1996UF09300029 PM 8920018 ER PT J AU Ellison, JS AF Ellison, JS TI Fluorescence-based mutation detection SO MOLECULAR BIOTECHNOLOGY LA English DT Article DE DNA mutational analysis; point mutation; suppressor mutation; DNA, single-stranded; single-strand conformation polymorphism; nucleic acid conformation; heterozygote detection genetic screening; nonradioisotope detection; polymerase chain reaction methods ID STRAND CONFORMATION POLYMORPHISM; PCR-SSCP ANALYSIS; POINT MUTATIONS; P53 GENE; HUMAN DNA; SINGLE; IDENTIFICATION; PROTOCOLS; CANCER; TUMORS AB Conventional SSCP analysis of DNA amplified by polymerase chain reaction (PCR-SSCP) is one of the simplest and most reliable tools for identifying point mutations, and small insertions or deletions. The sensitivity of the technique is increased by using the Applied Biosystems (ABI) semiautomated DNA sequencer equipped with GENESCAN 672 software for F-SSCP. The four-dye ABI system permits a red dye-labeled internal lane standard to be run in the same lanes as the DNA being examined, leaving three dye colors for labeling DNA of interest. The internal lane standard is used to normalize gels or correct for minor differences in apparent electrophoretic mobility between lanes. Correction for these lane-dependent differences in migration and the capability to stack data from two different lanes on the computer screen makes it possible to detect sequence variants that produce very small mobility shifts. Coelectrophoresis of control and unknown DNA in the same lane, using different dye labels for each, is also helpful for detecting sequence variants that produce small mobility changes. Multiplexing multiple F-SSCP targets in the sme lane increases sample throughput. C1 NIH,NATL CTR HUMAN GENOME RES,BETHESDA,MD 20892. NR 46 TC 4 Z9 4 U1 0 U2 0 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 SN 1073-6085 J9 MOL BIOTECHNOL JI Mol. Biotechnol. PD FEB PY 1996 VL 5 IS 1 BP 17 EP 31 DI 10.1007/BF02762409 PG 15 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology GA TZ829 UT WOS:A1996TZ82900003 PM 8853013 ER PT J AU Nagasawa, M Sakimura, K Mori, KJ Bedell, MA Copeland, NG Jenkins, NA Mishina, M AF Nagasawa, M Sakimura, K Mori, KJ Bedell, MA Copeland, NG Jenkins, NA Mishina, M TI Gene structure and chromosomal localization of the mouse NMDA receptor channel subunits SO MOLECULAR BRAIN RESEARCH LA English DT Article DE NMDA receptor channel; epsilon 3 subunit; gene structure; chromosomal localization ID D-ASPARTATE RECEPTOR; MOLECULAR-CLONING; PURKINJE-CELLS; MESSENGER-RNAS; DNA-SEQUENCES; CLONED CDNAS; AMINO-ACIDS; EXPRESSION; ORGANIZATION; CONSERVATION AB Multiple epsilon subunits are major determinants of the diversity of the N-methyl-D-aspartate (NMDA) receptor channel. The four epsilon subunit mRNAs exhibit distinct expression patterns in the brain. In an attempt to elucidate the molecular basis of selective and characteristic expression of the NMDA receptor channel subunits, we have isolated the gene encoding the mouse NMDA receptor epsilon 3 subunit and have determined its structural organization. The epsilon 3 subunit gene spans 17.5 kb and consists of 14 exons. The major transcription start site is 439 bp upstream of the ATG initiation codon as determined by primer extension and S1 nuclease protection analyses. Two polyadenylation sites are 397 (or 398) and 402 bp downstream of the termination codon. The 5'-flanking region of the epsilon 3 subunit gene contains GC-rich segments including consensus sequences for binding of the transcription factors Sp1 and EGR-1. The murine chromosomal locations of the five NMDA receptor channel subunits, the epsilon 1 (Grin2a), epsilon 2 (Grin2b), epsilon 3 (Grin2c), epsilon 4 (Grin2d) and zeta 1 (Grin1) subunits, were determined using an interspecific backcross mapping panel derived from crosses of [(C57BL/6JXM. spretus)F-1 X C57BL/6J] mice. Each of these genes mapped to a single chromosome location. The mapping results assigned the five loci to five different mouse autosomes, indicating that they have become well dispersed among mouse chromosomes. C1 NIIGATA UNIV,BRAIN RES INST,DEPT NEUROPHARMACOL,NIIGATA 951,JAPAN. NIIGATA UNIV,FAC SCI,DEPT BIOL,NIIGATA 95121,JAPAN. NCI,FREDERICK CANC RES & DEV CTR,MAMMALIAN GENET LAB,ABL BASIC RES PROGRAM,FREDERICK,MD 21702. UNIV TOKYO,FAC MED,DEPT PHARMACOL,BUNKYO KU,TOKYO 113,JAPAN. FU NCI NIH HHS [N01-CO-46001] NR 60 TC 30 Z9 33 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0169-328X J9 MOL BRAIN RES JI Mol. Brain Res. PD FEB PY 1996 VL 36 IS 1 BP 1 EP 11 DI 10.1016/0169-328X(95)00225-H PG 11 WC Neurosciences SC Neurosciences & Neurology GA TW869 UT WOS:A1996TW86900001 PM 9011744 ER PT J AU Isaacs, KR deErausquin, G Strauss, KI Jacobowitz, DM Hanbauer, I AF Isaacs, KR deErausquin, G Strauss, KI Jacobowitz, DM Hanbauer, I TI Differential effects of excitatory amino acids on mesencephalic neurons expressing either calretinin or tyrosine hydroxylase in primary SO MOLECULAR BRAIN RESEARCH LA English DT Article DE calcium-binding protein; dopamine; kainic acid; N-methyl-D-aspartic acid (+/-)-alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid; cytotoxicity; phosphorylated cAMP/Ca2+ response element-binding protein ID CALCIUM-BINDING PROTEIN; RAT-BRAIN; IMMUNOHISTOCHEMICAL LOCALIZATION; IMMUNOCYTOCHEMICAL LOCALIZATION; DOPAMINERGIC-NEURONS; PARKINSONS-DISEASE; CALBINDIN-D28K; GLUTAMATE; RECEPTORS; BACTERIA AB In mesencephalic primary cultures derived from E14 rat embryos, calretinin- and tyrosine hydroxylase-immunoreactive neurons comprised 2% and 5% of the total cell population, respectively, at 6-7 days in vitro. The number of calretinin-immunoreactive neurons was unchanged after a 12- or 24-h exposure to 500 mu M kainic acid (KA), but a 50% cell loss was detected after a 48-h exposure to KA. Tyrosine hydroxylase-immunore active neurons demonstrated a 50% and 67% cell loss at 24- and 48-h exposures to 500 mu M KA. A 500 mu M N-methyl-D-aspartic acid (NMDA) incubation for 24 h had no effect on calretinin-immunoreactive cell number, but did significantly reduce tyrosine hydroxylase-immunoreactive cell numbers by 26%. In tyrosine hydroxylase-immunoreactive cells, exposure to KA appeared to stimulate the retraction of the neuritic tree and to cause somatic swelling. In contrast, calretinin-immunoreactive neurons developed larger and more complex neuritic trees after a 24-h exposure to 500 mu M KA but not NMDA. Immunohistochemical colocalization studies revealed that all tyrosine hydroxylase-immunoreactive and the majority of calretinin-immunoreactive neurons expressed the glutamate receptor subunits GluR2-R3. Very low levels of NMDAR1 receptor subunits were detected on cells in this culture and GluR4 receptor subunits were not detectable. Our experiments showed that glutamate receptors present in both calretinin- and tyrosine hydroxylase-immunoreactive cells were functional, since phosphorylated cAMP/Ca2+ response element-binding protein levels were increased in both cell types after 10 or 30 min exposures to 500 mu M KA. The present results indicate that in the mesencephalic cultures tyrosine hydroxylase-immunoreactive cells are more vulnerable to KA excitotoxicity than calretinin-immunoreactive neurons. C1 YALE UNIV,SCH MED,DEPT PSYCHIAT,W HAVEN,CT 06516. NHLBI,LAB MOLEC IMMUNOL,BETHESDA,MD 20892. RP Isaacs, KR (reprint author), NIMH,CLIN SCI LAB,BLDG 10,ROOM 3D-48,10 CTR DR,BETHESDA,MD 20892, USA. RI de Erausquin, Gabriel/G-5840-2010 OI de Erausquin, Gabriel/0000-0001-6423-4461 NR 56 TC 28 Z9 28 U1 2 U2 2 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 FEB PY 1996 VL 36 IS 1 BP 114 EP 126 DI 10.1016/0169-328X(95)00252-N PG 13 WC Neurosciences SC Neurosciences & Neurology GA TW869 UT WOS:A1996TW86900013 PM 9011746 ER PT J AU Bjoras, M Gjesdal, O Erickson, JD Torp, R Levy, LM Ottersen, OP Degree, M StormMathisen, J Seeberg, E Danbolt, NC AF Bjoras, M Gjesdal, O Erickson, JD Torp, R Levy, LM Ottersen, OP Degree, M StormMathisen, J Seeberg, E Danbolt, NC TI Cloning and expression of a neuronal rat brain glutamate transporter SO MOLECULAR BRAIN RESEARCH LA English DT Article DE glutamate; cotransport; in situ hybridization; vaccinia virus; sequence; Expression ID RNA-POLYMERASE; SYSTEM; ASPARTATE; BIOLOGY; FAMILY; GENES; 3.0.CO;2-1 PG 12 WC Biochemistry & Molecular Biology; Cell Biology; Developmental Biology; Reproductive Biology SC Biochemistry & Molecular Biology; Cell Biology; Developmental Biology; Reproductive Biology GA TT627 UT WOS:A1996TT62700013 PM 8824922 ER PT J AU RoelkeParker, ME Munson, L Packer, C Kock, R Cleaveland, S Carpenter, M OBrien, SJ Pospischil, A HofmannLehmann, R Lutz, H Mwamengele, GLM Mgasa, MN Machange, GA Summers, BA Appel, MJG AF RoelkeParker, ME Munson, L Packer, C Kock, R Cleaveland, S Carpenter, M OBrien, SJ Pospischil, A HofmannLehmann, R Lutz, H Mwamengele, GLM Mgasa, MN Machange, GA Summers, BA Appel, MJG TI A canine distemper virus epidemic in Serengeti lions (Panthera leo) SO NATURE LA English DT Article AB CANINE distemper virus (CDV) is thought to have caused several fatal epidemics in canids within the Serengeti-Mara ecosystem of East Africa, affecting silver-backedjackals (Canis mesomelas) and bat-cared foxes (Otocyon megalotis) in 1978 (ref. 1), and African wild dogs (Lycaon pictus) in 1991 (refs 2, 3). The large, closely monitored Serengeti lion population(4,5) was not affected in these epidemics. However, an epidemic caused by a morbillivirus closely related to CDV emerged abruptly in the lion population of the Serengeti National Pack, Tanzania, in early 1994, resulting in fatal neurological disease characterized by grand mal seizures and myoclonus; the lions that died had encephalitis and pneumonia. Here we report the identification of CDV from these lions, and the close phylogenetic relationship between CDV isolates from lions and domestic dogs. By August 1994, 85% of the Serengeti lion population had anti-CDV antibodies, and the epidemic spread north to lions in the Maasai Mara National reserve, Kenya, and uncounted hyaenas, bat-eared foxes, and leopards were also affected. C1 UNIV TENNESSEE,COLL VET MED,DEPT PATHOL,KNOXVILLE,TN 37901. SERENGETI WILDLIFE RES INST,TANZANIA NATL PARKS,ARUSHA,TANZANIA. MESSERLI FDN,ZURICH,SWITZERLAND. UNIV MINNESOTA,DEPT ECOL EVOLUT & BEHAV,ST PAUL,MN 55108. KENYA WILDLIFE SERV,NAIROBI,KENYA. INST ZOOL,LONDON NW1 4RY,ENGLAND. UNIV LONDON LONDON SCH HYG & TROP MED,LONDON WC1E 7HT,ENGLAND. NCI,VIRAL CARCINOGENESIS LAB,FREDERICK,MD 21702. UNIV ZURICH,INST VET PATHOL,CH-8057 ZURICH,SWITZERLAND. UNIV ZURICH,DEPT VET INTERNAL MED,CH-8057 ZURICH,SWITZERLAND. SOKOINE UNIV AGR,DEPT VET PATHOL,MOROGORO,TANZANIA. VET INVEST CTR,ARUSHA,TANZANIA. CORNELL UNIV,COLL VET MED,DEPT PATHOL,ITHACA,NY 14853. CORNELL UNIV,COLL VET MED,JAMES A BAKER INST ANIM HLTH,ITHACA,NY 14853. RI Hofmann-Lehmann, Regina/C-6528-2009; OI Carpenter, Margaret/0000-0003-1606-1986 NR 20 TC 379 Z9 395 U1 16 U2 99 PU MACMILLAN MAGAZINES LTD PI LONDON PA 4 LITTLE ESSEX STREET, LONDON, ENGLAND WC2R 3LF SN 0028-0836 J9 NATURE JI Nature PD FEB 1 PY 1996 VL 379 IS 6564 BP 441 EP 445 DI 10.1038/379441a0 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA TT304 UT WOS:A1996TT30400057 PM 8559247 ER PT J AU Largaespada, DA Brannan, CI Jenkins, NA Copeland, NG AF Largaespada, DA Brannan, CI Jenkins, NA Copeland, NG TI Nf1 deficiency causes Ras-mediated granulocyte macrophage colony stimulating factor hypersensitivity and chronic myeloid leukaemia SO NATURE GENETICS LA English DT Article ID NEUROFIBROMATOSIS TYPE-1 GENE; BONE-MARROW CELLS; LEUKEMIA; MICE; PROTEIN; GROWTH; NEUROBLASTOMA; INTERLEUKIN-3; ONCOGENES; MUTATIONS AB The Ras signal transduction pathway is often deregulated in human myeloid leukaemia. For example, activating point mutations in RAS genes are found in some patients with juvenile chronic myelogenous leukaemia (JCML), while other patients with JCML show loss of the neurofibromatosis type 1 (NF1) gene, a Ras GTPase activating protein. By generating mice whose haematopoietic system is reconsituted with Nf1 deficient haematopoietic stem cells we show that Nf1 gene loss, by itself, is sufficient to produce the myeloproliferative symptoms associated with human JCML. We also provide evidence to indicate that Nf1 gene loss induces myeloproliferative disease through a Ras-mediated hypersensitivity to granulocyte/macrophage-colony stimulating factor (GM-CSF). Finally, we describe a genetic screen for identifying genes that cooperate with Nf1 gene loss during progression to acute myeloid leukaemia. C1 NCI,FREDERICK CANC RES & DEV CTR,MAMMALIAN GENET LAB,ABL BASIC RES PROGRAM,FREDERICK,MD 21702. RI Largaespada, David/C-9832-2014 NR 35 TC 235 Z9 238 U1 0 U2 1 PU NATURE PUBLISHING CO PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 SN 1061-4036 J9 NAT GENET JI Nature Genet. PD FEB PY 1996 VL 12 IS 2 BP 137 EP 143 DI 10.1038/ng0296-137 PG 11 WC Genetics & Heredity SC Genetics & Heredity GA TU079 UT WOS:A1996TU07900012 PM 8563750 ER PT J AU Nakamura, T Largaespada, DA Shaughnessy, JD Jenkins, NA Copeland, NG AF Nakamura, T Largaespada, DA Shaughnessy, JD Jenkins, NA Copeland, NG TI Cooperative activation of Hoxa and Pbx1-related genes in murine myeloid leukaemias SO NATURE GENETICS LA English DT Article ID LEUKEMIA-VIRUS DNA; T-CELL LEUKEMIA; HOMEOBOX GENE; CHROMOSOMAL TRANSLOCATION; LINKAGE MAP; PRE-B; MICE; TRANSCRIPTION; PROTEIN; MOUSE AB Retroviruses induce myeloid leukaemia in BXH-2 mice by the insertional mutation of cellular proto-oncogenes or tumour suppressor genes. Disease genes can thus be identified by proviral tagging through the identification of common viral integration sites in BXH-2 leukaemia. Here, we describe a new approach for proviral tagging that greatly facilitates the identification of BXH-2 leukaemia genes. Using this approach, we identify three genes whose expression is activated by proviral integration in BXH-2 leukaemias; Hoxa7, Hoxa9, and a Pbx1-related homeobox gene, Meis1. Proviral activation of Hoxa7 or Hoxa9 is strongly correlated with proviral activation of Meis1 implying that Hoxa7 and Hoxa9 cooperate with Meis1 in leukaemia formation. These studies provide the first genetic evidence that Pbx1-related genes cooperate with Hox genes in leukaemia formation and identify a number of new murine myeloid leukaemia genes. C1 NCI,FREDERICK CANC RES & DEV CTR,ABL BASIC RES PROGRAM,MAMMALIAN GENET LAB,FREDERICK,MD 21702. RI Largaespada, David/C-9832-2014 NR 42 TC 259 Z9 260 U1 0 U2 1 PU NATURE PUBLISHING CO PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 SN 1061-4036 J9 NAT GENET JI Nature Genet. PD FEB PY 1996 VL 12 IS 2 BP 149 EP 153 DI 10.1038/ng0296-149 PG 5 WC Genetics & Heredity SC Genetics & Heredity GA TU079 UT WOS:A1996TU07900014 PM 8563752 ER PT J AU Nakamura, T Largaespada, DA Lee, MP Johnson, LA Ohyashiki, K Toyama, K Chen, SJ Willman, CL Chen, IM Feinberg, AP Jenkins, NA Copeland, NG Shaughnessy, JD AF Nakamura, T Largaespada, DA Lee, MP Johnson, LA Ohyashiki, K Toyama, K Chen, SJ Willman, CL Chen, IM Feinberg, AP Jenkins, NA Copeland, NG Shaughnessy, JD TI Fusion of the nucleoporin gene NUP98 to HOXA9 by the chromosome translocation t(7;11)(p15;p15) in human myeloid leukaemia SO NATURE GENETICS LA English DT Article ID LEUKEMIA; IDENTIFICATION; EXPRESSION; CLONING; FAMILY; SET AB Expression of Hoxa7 and Hoxa9 is activated by proviral integration in BXH2 murine myeloid leukaemias. This result, combined with the mapping of the HOXA, locus to human chromosome 7p15, suggested that one of the HOXA genes might be involved in the t(7;11)(p15;p15) translocation found in some human myeloid leukaemia patients. Here we show that in three patients with t(7;11), the chromosome rearrangement creates a genomic fusion between the HOXA9 gene and the nucleoporin gene NUP98 on chromosome 11p15. The translocation produces an invariant chimaeric NUP98/HOXA9 transcript containing the amino terminal half of NUP98 fused in frame to HOXA9. These studies identify HOXA9 as an important human myeloid leukaemia gene and suggest an important role for nucleoporins in human myeloid leukaemia given that a second nucleoporin, NUP214, has also been implicated in human myeloid leukaemia. C1 NCI,FREDERICK CANC RES & DEV CTR,ABL BASIC RES PROGRAM,MAMMALIAN GENET LAB,FREDERICK,MD 21702. JOHNS HOPKINS UNIV,SCH MED,DEPT MED,BALTIMORE,MD 21205. JOHNS HOPKINS UNIV,SCH MED,DEPT ONCOL,BALTIMORE,MD 21205. JOHNS HOPKINS UNIV,SCH MED,DEPT MOLEC BIOL,BALTIMORE,MD 21205. TOKYO MED COLL,DEPT INTERNAL MED 1,TOKYO 160,JAPAN. SHANGHAI MED UNIV 2,RUI JIN HOSP,INST HEMATOL,SHANGHAI,PEOPLES R CHINA. UNIV NEW MEXICO,CTR CANC,DEPT CELL BIOL,ALBUQUERQUE,NM 87131. RI Largaespada, David/C-9832-2014 FU NCI NIH HHS [CA54358] NR 35 TC 374 Z9 379 U1 2 U2 13 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 FEB PY 1996 VL 12 IS 2 BP 154 EP 158 DI 10.1038/ng0296-154 PG 5 WC Genetics & Heredity SC Genetics & Heredity GA TU079 UT WOS:A1996TU07900015 PM 8563753 ER PT J AU Sood, S Eldadah, ZA Krause, WL McIntosh, I Dietz, HC AF Sood, S Eldadah, ZA Krause, WL McIntosh, I Dietz, HC TI Mutation in fibrillin-1 and the Marfanoid-craniosynostosis (Shprintzen-Goldberg) syndrome SO NATURE GENETICS LA English DT Letter ID MISSENSE MUTATION; GENE C1 JOHNS HOPKINS UNIV,SCH MED,CTR GENET MED,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 MOLEC BIOL & GENET,BALTIMORE,MD 21205. SCOTTISH RITE CHILDRENS MED CTR,DEPT MED GENET,ATLANTA,GA 30342. NIH,NATL CTR HUMAN GENOME RES,MED GENET BRANCH,BETHESDA,MD 20892. FU NCRR NIH HHS [RR-00722]; NHLBI NIH HHS [HL-02815]; NIAMS NIH HHS [AR-41135] NR 14 TC 114 Z9 118 U1 0 U2 2 PU NATURE PUBLISHING CO PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 SN 1061-4036 J9 NAT GENET JI Nature Genet. PD FEB PY 1996 VL 12 IS 2 BP 209 EP 211 DI 10.1038/ng0296-209 PG 3 WC Genetics & Heredity SC Genetics & Heredity GA TU079 UT WOS:A1996TU07900025 PM 8563763 ER PT J AU Spergel, DJ Catt, KJ Rojas, E AF Spergel, DJ Catt, KJ Rojas, E TI Immortalized GnRH neurons express large-conductance calcium-activated potassium channels SO NEUROENDOCRINOLOGY LA English DT Article DE calcium; cadmium; gonadotropin-releasing hormone; charybdotoxin; GT1 cells; potassium channels; thapsigargin ID GONADOTROPIN-RELEASING-HORMONE; HYPOTHALAMIC NEURONS; RAT-BRAIN; TRANSMITTER RELEASE; HIPPOCAMPAL-NEURONS; OUTWARD CURRENT; IONIC CURRENTS; K+ CHANNELS; CELLS; DIVERSITY AB The expression and function of large-conductance Ca2+-activated K+ (BK) channels in the GT1-7 line of immortalized gonadotropin-releasing hormone (GnRH) neurons was investigated. Ionic currents were recorded using the patch-clamp technique, cytoplasmic free Ca2+ concentration ([Ca2+](i)) was monitored using the fluorescent indicator, fura-2, and GnRH secretion was measured by radioimmunoassay. In cell-attached and inside-out patch-clamp recordings, K+ channels with a single-channel conductance of similar to 200 pS were detected. Depolarizing the patch increased the unitary current size and the open probability. In perforated-patch recordings, depolarizing pulses (50 ms) to potentials of -10 to +60 mV from a holding potential of -90 mV elicited outward current with early transient and sustained components. The transient current peaked 2-10 ms after the beginning of each pulse and increased in a voltage-dependent manner. This current was: (1) unaffected by the small-conductance Ca2+-activated K+ channel blocker, apamin (100 nM); (2) reduced by the BK channel blocker, charybdotoxin (5 nM); (3) abolished by the Ca2+ channel blocker, CdCl2 (25 mu M), and (4) prolonged by the endoplasmic reticulum Ca2+-ATPase inhibitor, thapsigargin(1 mu M). Based on the single-channel and whole-cell conductances, the number of channels per patch, the patch area, and the surface area of the cell, each GT1-7 cell contains 30-60 BK channels. The functional role of BK channels in GT1-7 cells was evaluated by measuring the effect of charybdotoxin (100 nM) on basal [Ca2+](i) and GnRH secretion, as well as on the [Ca2+](i) and GnRH secretory responses to gamma-aminobutyric acid (GABA, 100 mu M), an excitatory neurotransmitter in this system. Charybdotoxin had no effect on basal [Ca2+](i) or GnRH secretion, or on the GABA-evoked [Ca2(+)]i and GnRH secretory responses. These results indicate that GT1-7 cells express BK channels; however, the physiological role of BK channels in GT1-7 cells remains elusive. C1 NICHHD,ENDOCRINOL & REPROD RES BRANCH,NIH,BETHESDA,MD 20892. NIDDKD,CELL BIOL & GENET LAB,NIH,BETHESDA,MD 20892. RI Spergel, David/A-4410-2011 NR 45 TC 28 Z9 29 U1 0 U2 1 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0028-3835 J9 NEUROENDOCRINOLOGY JI Neuroendocrinology PD FEB PY 1996 VL 63 IS 2 BP 101 EP 111 DI 10.1159/000126946 PG 11 WC Endocrinology & Metabolism; Neurosciences SC Endocrinology & Metabolism; Neurosciences & Neurology GA TW290 UT WOS:A1996TW29000001 PM 9053774 ER PT J AU Wassermann, EM Wang, BS Zeffiro, TA Sadato, N PascualLeone, A Toro, C Hallett, M AF Wassermann, EM Wang, BS Zeffiro, TA Sadato, N PascualLeone, A Toro, C Hallett, M TI Locating the motor cortex on the MRI with transcranial magnetic stimulation and PET SO NEUROIMAGE LA English DT Article ID CEREBRAL BLOOD-FLOW; POSITRON EMISSION TOMOGRAPHY; ELECTRICAL-STIMULATION; INTRAVENOUS (H2O)-O-15; HAND MOVEMENTS; HUMAN-BRAIN; RESPONSES; REPRESENTATIONS; FORELIMB; MUSCLES AB Transcranial magnetic stimulation with a focal coil was used to map the cortical representation of a hand muscle in four healthy subjects, In each subject, the three-dimensional locations of the magnetic stimulation positions and about 400 positions on the surface of the head were digitized, The amplitude-weighted center of gravity of each subject's map was found, and a line perpendicular to the local head surface was projected inward, The digitized heads were registered with the subjects' MRIs using the scalp contours, The coordinate transformations yielded by this process were used to map the stimulation positions and the perpendicular line into the MRIs, Brain areas imaged with positron emission tomography (PET) and O-15-labeled water, activated by movement of the same muscle, were registered with the MRIs using the brain contours, In all cases, the magnetic stimulation lines encountered the surface of the brain at the anterior lip of the central sulcus and ran along the precentral gyrus a few millimeters anterior to the central sulcus, coming within 5-22 mm of all the PET activation maxima, This technique demonstrates the accuracy of transcranial magnetic stimulation for locating the primary motor area. (C) 1996 Academic Press, Inc. C1 NIH,NATL CTR RES RESOURCES,BIOMED ENGN & INSTRUMENTAT PROGRAM,BETHESDA,MD 20892. RP Wassermann, EM (reprint author), NINCDS,NIH,MED NEUROL BRANCH,HUMAN MOTOR CONTROL SECT,BLDG 10,ROOM 5N226,10 CTR DR MSC 1428,BETHESDA,MD 20892, USA. NR 40 TC 140 Z9 141 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 1053-8119 J9 NEUROIMAGE JI Neuroimage PD FEB PY 1996 VL 3 IS 1 BP 1 EP 9 DI 10.1006/nimg.1996.0001 PG 9 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA TY638 UT WOS:A1996TY63800001 PM 9345470 ER PT J AU Goldberg, TE Berman, KF Randolph, C Gold, JM Weinberger, DR AF Goldberg, TE Berman, KF Randolph, C Gold, JM Weinberger, DR TI Isolating the mnemonic component in spatial delayed response: A controlled PET O-15-labeled water regional cerebral blood flow study in normal humans SO NEUROIMAGE LA English DT Article ID PREFRONTAL CORTEX; WORKING-MEMORY; DISSOCIATION; PERFORMANCE; TOMOGRAPHY; MOVEMENT; DEFICITS; AREAS AB In this study we attempted to elucidate the neural network involved in maintaining spatial information over short delays by means of the PET O-15-labeled water method for measuring regional cerebral blood flow. To isolate the mnemonic component of delayed response processing we designed a control task isomorphic to the experimental task (in which the subject remembered the location of four targets in an array over a 7 s delay) and controlled for spatial encoding. Fourteen normal subjects participated in the study. Regional cerebral blood flow (rCBF) data were analyzed using statistical parametric mapping, a data-driven approach which canvasses the whole brain for significantly activated pixels in the experimental vis-a-vis the control task, and a hypothesis driven region of interest approach involving comparisons of control and experimental conditions using normalized rCBF data. We found convergent evidence for a spatially distinct but functionally related network in which dorsolateral prefrontal cortex and extrastriate occipital cortex were activated by the experimental task vis-a-vis the control task, as well as evidence for superior parietal and supplementary motor area cortical activation. These findings suggest that anterior components of the network may be involved in mnemonic rehearsal functions, while posterior components may store critical perceptual attributes of the memoranda. (C) 1996 Academic Press, Inc. RP Goldberg, TE (reprint author), NIMH,NEUROSCI CTR ST ELIZABETHS,NIH,INTRAMURAL RES PROGRAM,CLIN BRAIN DISORDERS BRANCH,WASHINGTON,DC 20032, USA. NR 45 TC 52 Z9 52 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 1053-8119 J9 NEUROIMAGE JI Neuroimage PD FEB PY 1996 VL 3 IS 1 BP 69 EP 78 DI 10.1006/nimg.1996.0008 PG 10 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA TY638 UT WOS:A1996TY63800008 PM 9345477 ER PT J AU Lippa, CF Saunders, AM Smith, TW Swearer, JM Drachman, DA Ghetti, B Nee, L PulaskiSalo, D Dickson, D Robitaille, Y Bergeron, C Crain, B Benson, MD Farlow, M Hyman, BT StGeorgeHyslop, P Roses, AD Pollen, DA AF Lippa, CF Saunders, AM Smith, TW Swearer, JM Drachman, DA Ghetti, B Nee, L PulaskiSalo, D Dickson, D Robitaille, Y Bergeron, C Crain, B Benson, MD Farlow, M Hyman, BT StGeorgeHyslop, P Roses, AD Pollen, DA TI Familial and sporadic Alzheimer's disease: Neuropathology cannot exclude a final common pathway SO NEUROLOGY LA English DT Article ID PRECURSOR PROTEIN GENE; MIS-SENSE MUTATION; APOLIPOPROTEIN-E; SENILE DEMENTIA; MISSENSE MUTATION; CEREBRAL-CORTEX; TYPE-4 ALLELE; APP GENE; LOCUS; CHROMOSOME-14 AB Whether all etiologic forms of Alzheimer's disease (AD) share a final common pathway is a major issue, We determined the severity and regional distribution of neuronal loss, amyloid plaques, neuritic plaques (NPs), and neurofibrillary tangles (NFTs), and calculated the ratio of neuronal loss to NPs and NFTs in brains of 19 familial AD (FAD) patients with linkage to chromosome 14, six AD patients with mutations of chromosome 21 (codon 717 of the beta-amyloid precursor protein gene), and 11 sporadic AD (SAD) patients, There was no difference in the pattern of distribution of the various pathologic features or in the ratio of neuronal loss to NPs or NFTs in any AD group, However, FAD groups could be distinguished from SAD by the greater severity and the lack of influence of apolipoprotein E genotype on pathology, These differences may reflect differences in age at onset rather than different etiopathologic mechanisms, The similarity of pathologic findings in the different AD groups provides evidence for a final common pathophysiologic pathway in AD. C1 UNIV MASSACHUSETTS,MED CTR,DEPT NEUROL,WORCESTER,MA 01655. UNIV MASSACHUSETTS,MED CTR,DEPT PATHOL,WORCESTER,MA. INDIANA UNIV,MED CTR,DEPT PATHOL,INDIANAPOLIS,IN. INDIANA UNIV,MED CTR,DEPT MED & MOLEC GENET,INDIANAPOLIS,IN. INDIANA UNIV,MED CTR,DEPT MED,INDIANAPOLIS,IN. INDIANA UNIV,MED CTR,DEPT NEUROL,INDIANAPOLIS,IN. RICHARD L ROUDEBUSH VET AFFAIRS MED CTR,INDIANAPOLIS,IN 46202. NIH,DEPT NEUROL,BETHESDA,MD 20892. MASSACHUSETTS GEN HOSP,DEPT NEUROL,BOSTON,MA 02114. UNIV MONTREAL,DEPT PATHOL,MONTREAL,PQ H3C 3J7,CANADA. UNIV TORONTO,TORONTO,ON,CANADA. DUKE UNIV,DEPT NEUROL,DURHAM,NC. ALBERT EINSTEIN COLL MED,DEPT PATHOL,BRONX,NY 10467. JOHNS HOPKINS UNIV,DEPT PATHOL,BALTIMORE,MD 21205. OI Dickson, Dennis W/0000-0001-7189-7917 FU NIA NIH HHS [AG-10133, AG-05134, AG-70922] NR 70 TC 75 Z9 77 U1 1 U2 3 PU LITTLE BROWN CO PI BOSTON PA 34 BEACON STREET, BOSTON, MA 02108-1493 SN 0028-3878 J9 NEUROLOGY JI Neurology PD FEB PY 1996 VL 46 IS 2 BP 406 EP 412 PG 7 WC Clinical Neurology SC Neurosciences & Neurology GA TZ712 UT WOS:A1996TZ71200019 PM 8614503 ER PT J AU Small, JA Sheridan, PH AF Small, JA Sheridan, PH TI Research priorities for syringomyelia: A National Institute of Neurological Disorders and Stroke Workshop summary SO NEUROLOGY LA English DT Editorial Material RP Small, JA (reprint author), NINCDS,NIH,DEV NEUROL BRANCH,DIV CONVULS DEV & NEUROMUSCULAR DISORDERS,FED BLDG,ROOM 8C04,BETHESDA,MD 20892, USA. NR 0 TC 11 Z9 11 U1 0 U2 0 PU LITTLE BROWN CO PI BOSTON PA 34 BEACON STREET, BOSTON, MA 02108-1493 SN 0028-3878 J9 NEUROLOGY JI Neurology PD FEB PY 1996 VL 46 IS 2 BP 577 EP 582 PG 6 WC Clinical Neurology SC Neurosciences & Neurology GA TZ712 UT WOS:A1996TZ71200057 PM 8614541 ER PT J AU Isaacs, E Christie, D VarghaKhadem, F Mishkin, M AF Isaacs, E Christie, D VarghaKhadem, F Mishkin, M TI Effects of hemispheric side of injury, age at injury, and presence of seizure disorder on functional ear and hand asymmetries in hemiplegic children SO NEUROPSYCHOLOGIA LA English DT Article DE dichotic listening; hemiplegic children; manual asymmetry; language reorganization; seizure disorder ID CEREBRAL-LESIONS; CHILDHOOD; INTELLIGENCE; PREFERENCE; HANDEDNESS; APHASIA; SPEECH AB Dichotic listening, manual functions, and IQ were measured in a large group of hemiplegic children with unilateral hemispheric damage. In the children without a history of seizure disorder, only manual functions were impaired, but in those with such a history (and hence a regime of anticonvulsant medication), all measures were affected. Some children with congenital left hemisphere lesions (with and without seizure disorder) showed a left ear advantage for dichotic digits as well as greater impairment in right hand function than those who showed the usual right ear advantage. The latter result suggests that the hemipheric damage in the subgroup with altered ear asymmetry was greater than in the others and extensive enough to encroach on language areas, shifting language representation to the right. C1 NIMH,BETHESDA,MD 20892. RP Isaacs, E (reprint author), INST CHILD HLTH,WOLFSON CTR,NEUROSCI UNIT,MECKLENBURGH SQ,LONDON WC1N 2AP,ENGLAND. RI Vargha-Khadem, Faraneh/C-2558-2008 NR 44 TC 43 Z9 43 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0028-3932 J9 NEUROPSYCHOLOGIA JI Neuropsychologia PD FEB PY 1996 VL 34 IS 2 BP 127 EP 137 DI 10.1016/0028-3932(95)00089-5 PG 11 WC Behavioral Sciences; Neurosciences; Psychology, Experimental SC Behavioral Sciences; Neurosciences & Neurology; Psychology GA TY637 UT WOS:A1996TY63700005 PM 8852875 ER PT J AU Castellanos, FX Elia, J Kruesi, MJP Marsh, WL Gulotta, CS Potter, WZ Ritchie, GF Hamburger, SD Rapoport, JL AF Castellanos, FX Elia, J Kruesi, MJP Marsh, WL Gulotta, CS Potter, WZ Ritchie, GF Hamburger, SD Rapoport, JL TI Cerebrospinal fluid homovanillic acid predicts behavioral response to stimulants in 45 boys with attention deficit hyperactivity disorder SO NEUROPSYCHOPHARMACOLOGY LA English DT Article DE attention deficit disorder with hyperactivity; cerebrospinal fluid; homovanillic acid; analeptics; psychostimulants; drug effects ID CSF MONOAMINE METABOLITES; 5-HYDROXYINDOLEACETIC ACID; CHILDHOOD HYPERACTIVITY; MOTOR-ACTIVITY; CONCENTRATION GRADIENTS; DOPAMINE METABOLITES; METHYLPHENIDATE; CHILDREN; DRUG; DEXTROAMPHETAMINE AB Central dopaminergic activity hits been assumed to play a role in the efficacy of stimulant drugs in attention deficit/hyperactivity disorder (ADHD), although supporting evidence has been scant. This study examined baseline cerebrospinal fluid (CSF) of boys with ADHD in relation to response to three different stimulant drugs. Forty five boys with DSM-III-R-diagnosed ADHD had a lumbar puncture before double-blind trials of methylphenidate, dextroamphetamine, and placebo. Sixteen also received pemoline as part of a subsequent open trial. Stepwise linear regressions determined significant predictors of drug response. Our prior report of a positive significant correlation between CSF homovanillic acid (HVA) and ratings of hyperactivity on placebo was replicated in a new sample of 20 boys. After baseline symptom severity, CSF HVA teas the best predictor of stimulant drug response, with significant independent contribution to four of the ten measures of hyperactivity that changed significantly with medication. Higher HVA predicted better drug response, and lower HVA was associated with worsening on some measures. This supports the mediating role of central dopaminergic activity in stimulant drug efficacy in childhood hyperactivity. C1 NIMH,DIV INTRAMURAL RES PROGRAMS,CLIN PHARMACOL SECT,EXPTL THERAPEUT BRANCH,BETHESDA,MD 20892. UNIV ILLINOIS,INST JUVENILE RES,CHICAGO,IL. MED COLL PENN,DEPT PSYCHIAT,PHILADELPHIA,PA 19129. VIRGINIA POLYTECH INST & STATE UNIV,DEPT PSYCHOL,BLACKSBURG,VA 24061. RP Castellanos, FX (reprint author), NIMH,CHILD PSYCHIAT BRANCH,BLDG 10,ROOM 6N240,BETHESDA,MD 20892, USA. OI Castellanos, Francisco/0000-0001-9192-9437 NR 97 TC 89 Z9 92 U1 3 U2 8 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 FEB PY 1996 VL 14 IS 2 BP 125 EP 137 DI 10.1016/0893-133X(95)00077-Q PG 13 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA TR544 UT WOS:A1996TR54400007 PM 8822535 ER PT J AU Thai, L Hong, JS Wiley, RG Gallagher, M AF Thai, L Hong, JS Wiley, RG Gallagher, M TI The regulation of hippocampal dynorphin by neural neuroendocrine pathways: Models for effects of aging on an opioid peptide system SO NEUROSCIENCE LA English DT Article DE dynorphin; enkephalin; corticosterone; acetylcholine; dentate gyrus; rats ID PRODYNORPHIN MESSENGER-RNA; AGED RATS; SPATIAL MEMORY; GRANULE CELLS; DEGENERATIVE CHANGES; OPIATE ANTAGONISTS; BASAL FOREBRAIN; DENTATE GYRUS; STIMULATION; IMPAIRMENT AB Previous research has demonstrated increased messenger RNA expression and peptide content in an opioid system localized to hippocampal dentate granule cells in aged rats. This altered regulation of dynorphin was correlated with the emergence of an age-related impairment in spatial learning. Considerable evidence exists for additional effects of aging on systems that provide input to the dynorphin-containing dentate granule cells. Such changes have been well documented for loss of perforant path innervation from entorhinal cortex, deterioration in septohippocampal cholinergic neurons, and high amounts of glucocorticoids that have, among their targets, receptors located in the dentate gyrus. Similar to the effects of aging on hippocampal dynorphin, age-related changes in each of these systems correlate with the severity of spatial learning impairment in aged rats. This raises the possibility that dysregulation of dynorphin in the aged brain is a reactive response to antecedant change(s) in this circuitry, a hypothesis that was examined by separately manipulating in young rats the three neural/neuroendocrine systems identified above. Of the three models examined only removal of the perforant path reproduced the effect of aging on dynorphin in the hippocampal formation. An immunotoxin was used in Experiment 1 to selectively remove septo-hippocampal cholinergic neurons in young rats. No alteration in hippocampal opioid peptides was produced by this treatment. Experiment 2 examined effects of exposure to excess corticosterone. Adrenalectomized rats exhibited a significant decrease in hippocampal dynorphin-A (1-8) content, which was reversed by corticosterone replacement at a concentration approximating normal basal levels. Dynorphin-A (1-8) content, however, was not reliably increased by exposure to excess corticosterone. In contrast, perforant path removal was found to reproduce the effect of aging on dynorphin content; either aspiration of the entorhinal cortex or knife-cut transections of the perforant path reliably increased hippocampal dynorphin content. These results support the conclusion that age-related deterioration in the septohippocampal cholinergic system and evaluated exposure to corticosterone are not sufficient to induce an elevation in hippocampal dynorphin content. Only removal of the perforant path innervation was found to reproduce the elevation in hippocampal dynorphin content observed in aged rats with hippocampal-dependent learning impairment. C1 UNIV N CAROLINA,CURRICULUM NEUROBIOL,CHAPEL HILL,NC 27599. NIEHS,MOLEC & INTEGRAT NEUROSCI LAB,RES TRIANGLE PK,NC 27709. VET ADM MED CTR,LAB EXPTL NEUROL,NASHVILLE,TN 37212. FU NIA NIH HHS [P01-AG09973] NR 47 TC 6 Z9 6 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 FEB PY 1996 VL 70 IS 3 BP 661 EP 671 DI 10.1016/S0306-4522(96)83005-3 PG 11 WC Neurosciences SC Neurosciences & Neurology GA TN528 UT WOS:A1996TN52800005 PM 9045079 ER PT J AU Schechter, AN Rodgers, GP AF Schechter, AN Rodgers, GP TI Hydroxyurea in sickle cell disease SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Letter RP Schechter, AN (reprint author), NIH,BLDG 10,BETHESDA,MD 20892, USA. NR 7 TC 7 Z9 7 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 FEB 1 PY 1996 VL 334 IS 5 BP 333 EP 333 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA TV695 UT WOS:A1996TV69500024 PM 8532042 ER PT J AU Jones, SB Tiffany, LJ Garmestani, K Gansow, OA Kozak, RW AF Jones, SB Tiffany, LJ Garmestani, K Gansow, OA Kozak, RW TI Evaluation of dithiol chelating agents as potential adjuvants for anti-IL-2 receptor lead or bismuth alpha radioimmunotherapy SO NUCLEAR MEDICINE AND BIOLOGY LA English DT Article DE dithiol chelating; radiotoxicity; DMPS ID TAC MONOCLONAL-ANTIBODY; SODIUM 2,3-DIMERCAPTOPROPANE-1-SULFONATE; ACID; RAT; METABOLISM; STABILITY; EXCRETION; THERAPY AB The dithiol chelating agents 2,3-dimercapto-1-propanesulfonic acid (DMPS) and meso-2,3-dimercaptosuccinic acid (DMSA) were evaluated for use as potential adjuvants to reduce or prevent radiotoxicity in anti interleukin 2 receptor (IL-2R) Lead-212 or Bismuth-212 alpha-radioimmunotherapy. DMPS was less toxic than DMSA to tumor cell lines in culture. No adverse effects on the ability of an anti-IL-2R monoclonal antibody (MAb) to bind to its specific antigen were detected using DMPS or DMSA at concentrations up to 600 ug/mL in 10% or 100% mouse serum. After a 5-day oral administration of chelating agent, neither acute nor chronic toxicities on blood hematology, blood chemistry or organ weights were observed for treated mice. DMPS and DMSA were effective in accelerating whole body clearance of the gamma-emitting tracer Bismuth-206. Both chelates significantly reduced femur uptake of tracer when compared to nontreated control mice. However, only DMPS prevented early (2 h postinjection) renal accumulation. These studies support the use of DMPS as a potential adjuvant chelation therapy in Lead-212 or Bismuth-212 radioimmunotherapy protocols. C1 NATL NAVAL MED CTR, DEPT OTOLARYNGOL HEAD & NECK SURG, BETHESDA, MD 20889 USA. US FDA, CTR BIOL EVALUAT & RES, DIV MONOCLONAL ANTIBODIES, BETHESDA, MD 20892 USA. NCI, NIH, RADIAT ONCOL BRANCH, BETHESDA, MD 20892 USA. NR 27 TC 11 Z9 12 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0883-2897 J9 NUCL MED BIOL JI Nucl. Med. Biol. PD FEB PY 1996 VL 23 IS 2 BP 105 EP 113 DI 10.1016/0969-8051(95)02006-3 PG 9 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA TW682 UT WOS:A1996TW68200001 PM 8868281 ER PT J AU De Luca, LM Ross, SA AF De Luca, LM Ross, SA TI Retinoic acid response elements as positive and negative regulators of the expression of the homeobox b-1 gene SO NUTRITION REVIEWS LA English DT Review ID MOUSE HINDBRAIN AB Retinoic acid-dependent homeobox Hoxb-1 gene expression offers an unanticipated example of both a positive and a negative transcriptional activity of RA, as exerted at different times during embryogenesis. A paradigm for the transduction of positive and negative signaling is the discovery that retinoic acid response elements (RAREs), positioned in the 3' enhancer and 5' promoter of the Hoxb-1 gene, may function respectively as positive and negative regulators, thereby permitting a diffused (early positive) as well as a segmentally specified and limited (late negative) expression of the gene. This molecular action of retinoic acid may provide a mechanism for our understanding of normal embryogenesis and of the interference with this process by ectopic retinoic acid, thereby leading to teratogenesis. RP De Luca, LM (reprint author), NCI, CELLULAR CARCINOGENESIS & TUMOR PROMOT LAB, DIFFERENTIAT CONTROL SECT, BLDG 37, BETHESDA, MD 20892 USA. NR 17 TC 3 Z9 3 U1 0 U2 0 PU INT LIFE SCIENCES INST NORTH AMERICA PI WASHINGTON PA ONE THOMAS CIRCLE, N W, 9TH FLOOR, WASHINGTON, DC 20005 USA SN 0029-6643 J9 NUTR REV JI Nutr. Rev. PD FEB PY 1996 VL 54 IS 2 BP 61 EP 63 PN 1 PG 3 WC Nutrition & Dietetics SC Nutrition & Dietetics GA UJ759 UT WOS:A1996UJ75900004 PM 9053826 ER PT J AU Smith, JA Espeland, M Bellevue, R Bonds, D Brown, AK Koshy, M AF Smith, JA Espeland, M Bellevue, R Bonds, D Brown, AK Koshy, M TI Pregnancy in sickle cell disease: Experience of the cooperative study of sickle cell disease SO OBSTETRICS AND GYNECOLOGY LA English DT Article ID PLACENTAL WEIGHT; FETAL AB Objective: To determine the maternal and fetal outcomes of pregnancy in women with sickle cell disease. Methods: The subjects were part of a cohort recruited from 19 centers for a prospective study of the clinical course of sickle cell disease. Each participant was evaluated using a structured protocol in which steady-state data and information on both sickle- and non-sickle-related events were collected. The rates of antepartum and intrapartum complications were tallied for pregnancies carried to delivery. Fetal outcome was assessed according to gestational age, birth weight, and Apgar score. Differences among genotypes in event rates were assessed using Fisher exact test. Differences in gestational age and birth weight, and predictors of these outcomes, were assessed using analyses of covariance. Results: Two hundred eighty-six of the 445 reported pregnancies proceeded to delivery. Non-sickle-related antepartum and intrapartum complication rates were comparable with those of African-American women who did not have sickle cell disease. One of the two deaths observed during this study was directly related to the presence of sickle cell disease. Rates of maternal morbidity from sickle cell disease were the same during pregnancy as during the nonpregnant state. Ninety-nine percent of those pregnancies carried to delivery resulted in a live birth. Twenty-one percent of the infants born to women of the SS genotype were small for gestational age (SGA). Preeclampsia and acute anemic events were identified as risk factors for SGA infants. Conclusion: Those caring for women with sickle cell disease should support them if they desire to have children. C1 WAKE FOREST UNIV,BOWMAN GRAY SCH MED,DEPT PUBL HLTH SCI,BIOSTAT SECT,WINSTON SALEM,NC 27103. SUNY HLTH SCI CTR,DEPT PUBL HLTH SCI,BIOSTAT SECT,BROOKLYN,NY 11203. METHODIST HOSP,DEPT MED,BROOKLYN,NY 11215. SUNY HLTH SCI CTR,CHILDRENS MED CTR BROOKLYN,DEPT PEDIAT,BROOKLYN,NY. NHLBI,DIV BLOOD DIS & RESOURCES,SICKLE CELL DIS BRANCH,BETHESDA,MD 20892. UNIV ILLINOIS,DIV HEMATOL,CHICAGO,IL. RP Smith, JA (reprint author), COLUMBIA UNIV,HARLEM HOSP CTR,DEPT MED,CTR COMPREHENS SICKLE CELL,506 LENOX AVE,NEW YORK,NY 10037, USA. FU NHLBI NIH HHS [N01 HB 97051-72, N01 HB 97051-85] NR 22 TC 84 Z9 88 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0029-7844 J9 OBSTET GYNECOL JI Obstet. Gynecol. PD FEB PY 1996 VL 87 IS 2 BP 199 EP 204 DI 10.1016/0029-7844(95)00367-3 PG 6 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA TR530 UT WOS:A1996TR53000008 PM 8559523 ER PT J AU Yoon, BH Yang, SH Jun, JK Park, KH Kim, CJ Romero, R AF Yoon, BH Yang, SH Jun, JK Park, KH Kim, CJ Romero, R TI Maternal blood C-reactive protein, white blood cell count, and temperature in preterm labor: A comparison with amniotic fluid white blood cell count SO OBSTETRICS AND GYNECOLOGY LA English DT Article ID INTRAAMNIOTIC INFECTION; INTACT MEMBRANES; HISTOLOGIC CHORIOAMNIONITIS; MICROBIAL INVASION; PREMATURE LABOR; GRAM STAIN; WOMEN; INTERLEUKIN-6; PATHOGENESIS; GLUCOSE AB Objective: To compare the diagnostic and prognostic performance of maternal blood C-reactive protein, white blood cell count (WBC), and temperature with that of amniotic fluid (AF) WBC in preterm labor. Methods: One hundred two women with preterm labor and intact membranes were studied. Maternal blood was collected to measure C-reactive protein concentration and WBC, and maternal temperature was also measured. Amniotic fluid obtained by amniocentesis was cultured and WBC determined. Receiver operating characteristic curve, logistic regression, and survival techniques were used for analysis. Results: Patients with acute histologic chorioamnionitis had significantly higher median C-reactive protein concentration, WBC, temperature, and AF WBC than patients without this lesion (P <.05). Receiver operating characteristic curve and survival analysis demonstrated that an elevated C-reactive protein, WBC, or AF WBC was strongly associated with the likelihood of histologic chorioamnionitis, shorter interval to delivery, clinical chorioamnionitis, and neonatal morbidity (P <.05 for each). Of all the tests, AF WBC was the best independent predictor of a positive AF culture (odds ratio [OR] 16.8), interval to delivery (hazard ratio 5.7), clinical chorioamnionitis (OR 15.2), neonatal sepsis (OR 16.8), and significant neonatal complications (OR 7.4), after other confounding variables were adjusted (P <.05 for each). Conclusion: An elevated C-reactive protein, WBC, or AF WBC identified patients with intrauterine infection and adverse perinatal outcomes. Amniotic fluid WBC was a better independent predictor of these outcomes than C-reactive protein, WBC, or temperature. C1 SEOUL NATL UNIV,DEPT OBSTET & GYNECOL,SEOUL,SOUTH KOREA. SEOUL NATL UNIV,COLL MED,DEPT PATHOL,SEOUL,SOUTH KOREA. NICHHD,PERINATAL RES BRANCH,BETHESDA,MD 20892. RI Seoul National University, Pathology/B-6702-2012; Yoon, Bo Hyun/H-6344-2011; Jun, Jong Kwan/D-5776-2012 OI Jun, Jong Kwan/0000-0002-0242-1736 NR 22 TC 69 Z9 70 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0029-7844 J9 OBSTET GYNECOL JI Obstet. Gynecol. PD FEB PY 1996 VL 87 IS 2 BP 231 EP 237 DI 10.1016/0029-7844(95)00380-0 PG 7 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA TR530 UT WOS:A1996TR53000015 PM 8559530 ER PT J AU Lancaster, JM Wiseman, RW Berchuck, A AF Lancaster, JM Wiseman, RW Berchuck, A TI An inevitable dilemma: Prenatal testing for mutations in the BRCA1 breast ovarian cancer susceptibility gene SO OBSTETRICS AND GYNECOLOGY LA English DT Article ID HUNTINGTON DISEASE; ATTITUDES; DIAGNOSIS; FAMILIES; RISK AB The BRCA1 breast-ovarian cancer susceptibility gene was identified recently. Germline mutations in BRCA1 may be responsible for as many as 5% of breast and ovarian cancers. Inherited alterations confer up to a 94% risk of developing breast and/or ovarian cancer by age 70. With the discovery of BRCA1, there will be a heavy demand for genetic testing. Because of the large size of the gene and the distribution of reported mutations, scientists face considerable technical problems in developing widely available screening tests; clinicians will face even greater ethical problems in applying them. In the context of research programs, women with BRCA1 mutations are already being identified, and their physicians are confronted with a number of complex medical, ethical, legal, and social issues. Obstetricians will be faced with counseling parents regarding prenatal testing for specific BRCA1 mutations. Although it is difficult to formulate straightforward guidelines regarding prenatal BRCA1 testing, clinicians and health care providers must be familiar with the nuances of the debate so that these issues can be discussed wisely with patients. As with many ethically challenging problems in medicine, individual clinicians and their patients will have to work together to determine the course of action with which they are most comfortable. Although elective termination of a pregnancy with a germline mutation in BRCA1 is an option, experience with other adult-onset diseases suggests that only a minority of parents will choose this option. C1 DUKE UNIV,MED CTR,DEPT OBSTET & GYNECOL,DIV GYNECOL ONCOL,DURHAM,NC 27710. RP Lancaster, JM (reprint author), NIEHS,MOLEC CARCINOGENESIS LAB,MD C4-06,POB 12233,111 ALEXANDER DR,RES TRIANGLE PK,NC 27709, USA. FU NCI NIH HHS [CA55640] NR 19 TC 30 Z9 30 U1 1 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0029-7844 J9 OBSTET GYNECOL JI Obstet. Gynecol. PD FEB PY 1996 VL 87 IS 2 BP 306 EP 309 DI 10.1016/0029-7844(95)00405-X PG 4 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA TR530 UT WOS:A1996TR53000029 PM 8559544 ER PT J AU Davis, JL Winward, KR Lonardo, EC Nussenblatt, RB Meisler, DM Lee, TD AF Davis, JL Winward, KR Lonardo, EC Nussenblatt, RB Meisler, DM Lee, TD TI Association of propionibacterium acnes endophthalmitis with HLA-DQw5 SO OCULAR IMMUNOLOGY AND INFLAMMATION LA English DT Article DE Propionibacterium acnes; endophthalmitis; HLA-DQw5; cataract surgery ID PHACOANAPHYLACTIC ENDOPHTHALMITIS; LENS IMPLANTATION; INFLAMMATION; ALLELES AB Background: An HLA-DQ1 association has been suspected in patients who develop Propionibacterium acnes endophthalmitis following cataract surgery. New techniques exist which may help to define this association. Materials and Methods. Patients with culture-proven P. acnes endophthalmitis following cataract surgery were HLA-typed with new sera able to detect fine specificities in the HLA-DQ1 region and compared to a large number of racially-matched controls. Sequence-specific oligonucleotide typing with probes and primers designed to amplify and define the HLA-DQ1 region was then performed. P. acnes patients were compared to HLA-DQ1-matched controls who had undergone cataract surgery but had no evidence of chronic post-operative inflammation. Results: Thirteen of 15 P. acnes patients (87%) were serologically defined as carrying a split of DQW1 (DQW5 or DQW6). HLA DQW5 was increased to a statistically significant degree (p less than or equal to 0.014) with an odds ratio of 3.72 (95% confidence interval 1.34 to 10.31) Sequence-specific oligonucleotide typing confirmed the DQW5 predominance: Seventy-three percent of P. acnes patients had DQB1*0501 or DQB1*0503 vs. 33% of DQW1-matched cataract patients without inflammation (not significant). Conclusion: HLA-DQW5 is associated with the development of P. acnes endophthalmitis following cataract surgery. The molecular mechanism of this association is unknown. C1 EXXON BIOMED SCI INC, E MILLSTONE, NJ USA. NEI, BETHESDA, MD 20892 USA. CLEVELAND CLIN FDN, DEPT OPHTHALMOL, CLEVELAND, OH 44195 USA. NEW YORK IMMUNOGENET CTR INC, NEW YORK, NY USA. RP UNIV MIAMI, SCH MED, BASCOM PALMER EYE INST, DEPT OPHTHALMOL, 900 NW 17TH AVE, MIAMI, FL 33136 USA. NR 19 TC 9 Z9 9 U1 1 U2 2 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 530 WALNUT STREET, STE 850, PHILADELPHIA, PA 19106 USA SN 0927-3948 EI 1744-5078 J9 OCUL IMMUNOL INFLAMM JI Ocul. Immunol. Inflamm. PD FEB PY 1996 VL 4 IS 1 BP 25 EP 32 DI 10.3109/09273949609069124 PG 8 WC Ophthalmology SC Ophthalmology GA VV671 UT WOS:A1996VV67100003 PM 22827330 ER PT J AU Cheung, MK Martin, DG Nussenblatt, RB Chan, CC AF Cheung, MK Martin, DG Nussenblatt, RB Chan, CC TI Clinical pathologic findings of Propionibacterium acnes endophthalmitis SO OCULAR IMMUNOLOGY AND INFLAMMATION LA English DT Article DE Propioni bacterium acnes; endophthalmitis; cataract extraction; lens implantation ID EXTRACAPSULAR CATARACT-EXTRACTION AB The autors presented two typical cases of patients who were infected with Propionibacterium acnes (P. acnes) after intraocular lens implantation. The patients were treated successfully by the removal of the intraocular lens and the residual lens capsule, and the administration of intravitreal vacomycin. The histopathology illustrated numerous prokaryote bacilli surrounding the lens material without inflammatory reaction. The thickened bacterial cell wall structure may relate to the resistance of P. acnes killing and degradation by the host neutrophils and macrophages. Complete removal of the lens material which may sequester the bacterial growth in the eye is important to eradicate P. acnes endophthalmitis. C1 NEI,IMMUNOL LAB,NIH,BETHESDA,MD 20892. NR 12 TC 1 Z9 1 U1 0 U2 1 PU AEOLUS PRESS PI BUREN PA PO BOX 740, 4116 ZJ BUREN, NETHERLANDS SN 0927-3948 J9 OCUL IMMUNOL INFLAMM JI Ocul. Immunol. Inflamm. PD FEB PY 1996 VL 4 IS 1 BP 69 EP 73 DI 10.3109/09273949609069129 PG 5 WC Ophthalmology SC Ophthalmology GA VV671 UT WOS:A1996VV67100008 PM 22827335 ER PT J AU Chen, IT Akamatsu, M Smith, ML Lung, FDT Duba, D Roller, PP Fornace, AJ OConnor, PM AF Chen, IT Akamatsu, M Smith, ML Lung, FDT Duba, D Roller, PP Fornace, AJ OConnor, PM TI Characterization of p21(Cip1/Waf1) peptide domains required for cyclin E/Cdk2 and PCNA interaction SO ONCOGENE LA English DT Article DE Cip1; cyclin E/Cdk2; GADD45; PCNA; peptide; p53; Waf1 ID REPLICATION; INHIBITOR; KINASES AB The cyclin-dependent kinase inhibitor p21(Cip1/Waf1) is responsible for the p53-dependent growth arrest of cells in G1 phase following DNA damage, In the present study we investigated regions of p21 involved in inhibition of the G(1)/S phase cyclin-dependent kinase, cyclin E/Cdk2, as well as regions of p21 important for binding to this kinase and recombinant PCNA, To perform these studies we synthesized a series of overlapping peptides spanning the entire p21 sequence and used them in in vitro assays with cyclin E/Cdk2-immune complexes and with recombinant p21 and PCNA proteins, One amino-terminal p21 peptide spanning amino acids 15-40, antagonized p21 binding and inhibition of cyclin E/Cdk2 kinase, Antagonism of p21 binding was, however, lost in a similar peptide lacking amino acids 15-20, or in a peptide in which cysteine-18 was substituted for a serine, These results suggest that this peptide region is important for p21 interaction with cyclin E/Cdk2, A second peptide (amino acids 58-77) also antagonized p21-activity, but this peptide did not affect the ability of p21 to interact with cyclin E/Cdk2, A region in p21 larger than 26 amino acids is presumably required for Cdk-inhibition because none of the peptides we tested inhibited cyclin E/Cdk2, We also found that a peptide spanning amino acids 21-45 bound recombinant p21 in ELISA assays, and additional studies revealed a requirement for amino acids 26 through 45 for this interaction, A p21 peptide spanning amino acids 139-164 was found to bind PCNA in a filter binding assay and this peptide suppressed recombinant p21-PCNA interaction, Conformational analysis revealed that peptides spanning amino acids 21-45 and 139-164 tended towards an alpha-helical conformation in trifluoroethanol buffer, indicating that these regions are probably in a coiled conformation in the native protein, Taken together, our results provide an insight into domains of p21 that are involved in cyclin E/Cdk2 and PCNA interaction, Our results also suggest that a potential p21 dimerization domain may lie in the amino-terminus of p21, Continued exploration of these domains could prove useful in assessing p21-mimetic strategies for cancer treatment. C1 NCI,MOLEC PHARMACOL LAB,NIH,BETHESDA,MD 20892. NCI,MED CHEM LAB,DIV BASIC SCI,NIH,BETHESDA,MD 20892. RI Fornace, Albert/A-7407-2008 OI Fornace, Albert/0000-0001-9695-085X NR 53 TC 78 Z9 82 U1 0 U2 1 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE, HAMPSHIRE, ENGLAND RG21 6XS SN 0950-9232 J9 ONCOGENE JI Oncogene PD FEB 1 PY 1996 VL 12 IS 3 BP 595 EP 607 PG 13 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA TV597 UT WOS:A1996TV59700017 PM 8637717 ER PT J AU Evans, MK Chin, KV Gottesman, MM Bohr, VA AF Evans, MK Chin, KV Gottesman, MM Bohr, VA TI Gene-specific DNA repair and steady state transcription of the MDR1 gene in human tumor cell lines SO ONCOGENE LA English DT Article DE DNA repair; drug resistance; tumor cells ID COMPLEMENTATION GROUP-C; STRAND-SPECIFIC REPAIR; KB CARCINOMA-CELLS; PYRIMIDINE DIMERS; DEFECTIVE REPAIR; COUPLING FACTOR; ACTIVE GENE; RESISTANT; AMPLIFICATION; FIBROBLASTS AB We have explored the relationship between DNA repair and transcription in vivo, A gene-specific repair assay has been employed to study removal of ultraviolet light-induced cyclobutane pyrimidine diners in the MDR1 gene at different levels of MDR1 mRNA expression, The parental human adenocarcinoma cell line, KB-3-1, has very low levels of MDR1 mRNA expression, but its multidrug resistant derivatives KB-8-5 and KB-C1 have 42-fold and 3800-fold increases in MDR1 mRNA expression, respectively, In the KB-3-1 cell line that has a low level of MDR1 mRNA expression, we find a low level of MDR1 gene-specific repair and inefficient repair of the transcribed strand of the gene, In the KB-8-5 cell line that has a modest increase in MDR1 mRNA expression, we find only a minor increase in dimer repair in the MDR1 gene, Here, the repair in the transcribed strand is not significantly higher than that in the KB-3-1 cell line, However, in the KB-C1 derivative, where there is a 3800-fold increase in the level of MDR1 mRNA expression, we find a substantial increase in the level of dimer repair in the MDR1 gene, In addition, the MDR1 transcribed strand repair is markedly more efficient than the repair in the nontranscribed strand, Our data suggest that the rate of transcription in the MDR1 gene must be substantially increased before there is any measurable effect on DNA repair, Repair in the housekeeping gene, dihydrofolate reductase (DHFR), was similar in all three tumor cell lines, Repair in its transcribed strand was markedly lower than previously reported in normal human fibroblasts, We suspect that these human HeLa-derived tumor cell lines have deficient gene-specific DNA repair, This may be an important aspect of their malignant phenotype. C1 NIA,MOLEC GENET LAB,NIH,BALTIMORE,MD 21224. UNIV MED & DENT NEW JERSEY,ROBERT WOOD JOHNSON MED SCH,CANC INST NEW JERSEY,PISCATAWAY,NJ 08854. NCI,CELL BIOL LAB,NIH,BETHESDA,MD 20892. RI Chin, Khew-Voon/F-2670-2013 NR 42 TC 10 Z9 10 U1 0 U2 0 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE, HAMPSHIRE, ENGLAND RG21 6XS SN 0950-9232 J9 ONCOGENE JI Oncogene PD FEB 1 PY 1996 VL 12 IS 3 BP 651 EP 658 PG 8 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA TV597 UT WOS:A1996TV59700022 PM 8637722 ER PT J AU Weintraub, M Lin, AY Franklin, J Tucker, MA Magrath, IT Bhatia, KG AF Weintraub, M Lin, AY Franklin, J Tucker, MA Magrath, IT Bhatia, KG TI Absence of germline p53 mutations in familial lymphoma SO ONCOGENE LA English DT Article DE p53; germline mutations; familial lymphoma ID TUMOR-SUPPRESSOR GENE; ABNORMAL EXPRESSION; MALIGNANT-LYMPHOMAS; HODGKINS-DISEASE; BREAST-CANCER; LEUKEMIA; RELATIVES; NEOPLASMS; PROTEIN; CELLS AB p53, a tumor suppressor gene, is frequently mutated in sporadic human cancer, and inherited mutations in p53 predispose to the early onset of cancer, p53 mutations occur frequently in sporadic lymphoma, and, in mice deficient for p53, lymphoma is the most common type of malignancy, Families with an increased incidence of lymphoma have been described, suggesting an inherited predisposition to lymphoma in these circumstances, To determine whether the predisposition to lymphoma in these families results from germline mutations in p53, we analysed exons 4-11 of the p53 gene in 35 individuals from 19 lymphoma-prone kindreds, We found no germline p53 mutations in any of the individuals tested, However, p53 expression assessed by immunohistochemistry, which suggests mutation, was observed in 35% of the tumor samples from the familial Hodgkin's disease cases and in 13% of the familial non-Hodgkin's lymphoma cases, These results suggest that p53 mutations do not play a critical role in heritable susceptibility to lymphoma, p53 may act by different, non-mutation related mechanisms in this setting, or be involved in late events in the pathogenesis of these tumors. C1 NCI,PEDIAT BRANCH,NIH,BETHESDA,MD 20892. NCI,GENET EPIDEMIOL BRANCH,NIH,BETHESDA,MD 20892. RI Tucker, Margaret/B-4297-2015 NR 39 TC 10 Z9 10 U1 0 U2 0 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE, HAMPSHIRE, ENGLAND RG21 6XS SN 0950-9232 J9 ONCOGENE JI Oncogene PD FEB 1 PY 1996 VL 12 IS 3 BP 687 EP 691 PG 5 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA TV597 UT WOS:A1996TV59700026 PM 8637726 ER PT J AU Smyth, MS Burke, TR AF Smyth, MS Burke, TR TI Enantioselective synthesis of N-Boc and N-Fmoc protected diethyl 4-phosphono(difluoroniethyl)-1-phenylalanine (F(2)Pmp) SO ORGANIC PREPARATIONS AND PROCEDURES INTERNATIONAL LA English DT Article ID DERIVATIVES; SERINE; ACIDS RP Smyth, MS (reprint author), NCI, DIV CANC TREATMENT,DEV THERAPEUT PROGRAM, MED CHEM LAB,BLDG 37, RM 5C06, BETHESDA, MD 20892 USA. RI Burke, Terrence/N-2601-2014 NR 12 TC 10 Z9 10 U1 0 U2 1 PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXFORDSHIRE, ENGLAND SN 0030-4948 J9 ORG PREP PROCED INT JI Org. Prep. Proced. Int. PD FEB PY 1996 VL 28 IS 1 BP 77 EP 81 PG 5 WC Chemistry, Organic SC Chemistry GA TW433 UT WOS:A1996TW43300003 ER PT J AU Badman, DG Jaffe, ER AF Badman, DG Jaffe, ER TI Blood and air pollution: State of knowledge and research needs SO OTOLARYNGOLOGY-HEAD AND NECK SURGERY LA English DT Article; Proceedings Paper CT Conference on Air Pollution Impacts on Body Organs and Systems CY NOV 18, 1994 CL WASHINGTON, DC SP Natl Assoc Physicians Environm, Natl Press Club ID CHILDHOOD LEUKEMIA; LEAD TOXICITY; TOXICOLOGY; EXPOSURE; VICINITY AB The ready access to blood (plasma and formed cellular elements) makes it unusually susceptible to the deleterious effects of pollutants whose origins may be in the air. The red blood cells' hemoglobin may be rendered useless for oxygen transport by combination with carbon monoxide or conversion to methemoglobin or sulfhemoglobin. Lead and arsine can damage the erythrocytes' membranes, resulting in anemia. Metabolites of benzene and other volatile polycyclic hydrocarbons are implicated in the causation of leukemias. The extensive use of pesticides and herbicides may be associated with the development of Hodgkin's disease, non-Hodgkin's lymphoma, and aplastic anemia. The carcinogenic risks from ionizing radiation, especially for leukemia, are well known. More information is needed concerning the epidemiology of environmental factors responsible for damage to blood. Enhanced knowledge about the molecular biology of toxins' effects on the hematopoietic system and improved detection and prevention technologies are needed to answer environmentally related health questions. C1 NIDDKD,BETHESDA,MD 20892. ALBERT EINSTEIN COLL MED,BRONX,NY 10467. NR 16 TC 10 Z9 10 U1 1 U2 6 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 SN 0194-5998 J9 OTOLARYNG HEAD NECK JI Otolaryngol. Head Neck Surg. PD FEB PY 1996 VL 114 IS 2 BP 205 EP 208 DI 10.1016/S0194-5998(96)70166-3 PG 4 WC Otorhinolaryngology; Surgery SC Otorhinolaryngology; Surgery GA TX013 UT WOS:A1996TX01300005 PM 8637733 ER PT J AU McGowan, JA AF McGowan, JA TI Bone: Target and source of environmental pollutant exposure SO OTOLARYNGOLOGY-HEAD AND NECK SURGERY LA English DT Article; Proceedings Paper CT Conference on Air Pollution Impacts on Body Organs and Systems CY NOV 18, 1994 CL WASHINGTON, DC SP Natl Assoc Physicians Environm, Natl Press Club ID LEAD AB The skeleton can play a unique role in modulating and responding to environmental air pollutants, Bone and its metabolic activities may be immediate targets for particular agents, leading to skeletal disease, However, bone is also an important storage site in the body, Chemical pollutants may be actively absorbed into bone mineral and released later during the normal process of bone remodeling. Critical periods when bone remodeling is enhanced, such as pregnancy, lactation, menopause, immobilization, and exposure to microgravity, may be important to recognize because of the potential for enhanced release of previously stored chemical agents, Lead has been identified as a ''criteria air pollutant'' by the 1970 Clean Air Act because of its ubiquity in the environment and its effect on a multiplicity of health outcomes, It is used in this article as an example of a substance that can have both a direct effect on bone and a latent effect on other organ systems through release from bone long after the initial exposure. RP McGowan, JA (reprint author), NIAMSD,MUSCULOSKELETAL DIS BRANCH,NIH,NATCHER BLDG,ROOM 5AS-43E,BETHESDA,MD 20892, USA. NR 14 TC 8 Z9 8 U1 1 U2 1 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 SN 0194-5998 J9 OTOLARYNG HEAD NECK JI Otolaryngol. Head Neck Surg. PD FEB PY 1996 VL 114 IS 2 BP 220 EP 223 DI 10.1016/S0194-5998(96)70170-5 PG 4 WC Otorhinolaryngology; Surgery SC Otorhinolaryngology; Surgery GA TX013 UT WOS:A1996TX01300009 PM 8637737 ER PT J AU Albright, JF Goldstein, RA AF Albright, JF Goldstein, RA TI Airborne pollutants and the immune system SO OTOLARYNGOLOGY-HEAD AND NECK SURGERY LA English DT Article; Proceedings Paper CT Conference on Air Pollution Impacts on Body Organs and Systems CY NOV 18, 1994 CL WASHINGTON, DC SP Natl Assoc Physicians Environm, Natl Press Club ID MERCURIC-CHLORIDE; INDUCED AUTOIMMUNITY; OZONE; CELLS; HOST; RAT; LYMPHOCYTES; RESPONSES; INDUCTION; EXPOSURE AB The effects of airborne pollutants on the immune system have been most widely studied in the respiratory tract, Entry may occur as a volatile gas (ozone, benzene), as liquid droplets (sulfuric acid, nitrogen dioxide), or as particulate matter (diesel exhaust, aromatic hydrocarbons), The subsequent interaction with the immune system may result in local and systemic responses, and studies have shown examples of disease occurring from both overactive immune responses and immunosuppression. For the most part, airborne pollutants (small molecular weight chemicals) have to be coupled with other substances (proteins or conjugates) before they can be recognized by the immune system and exert their effects. Fortunately, this encounter rarely causes immunologically mediated human disorders, The following briefly reviews some of the disorders that may occur, Immunologically nonspecific inflammation of the lung can occur after inhalation of ozone in anyone given sufficient dose and time of exposure, Immunologically specific cell-mediated (T lymphocyte) reactions appear to predominate in chronic beryllium disease, which results in a granulomatous form of lung disease, Beryllium alone does not appear to be antigenic but requires chemical linkage with a larger molecule, Mercury-induced autoimmune disease (immune system attacks self-antigens) affecting kidneys and lungs has been demonstrated in animal models (changes similar to those seen in people with Goodpasture's syndrome), Immunosuppression can be demonstrated after exposure to polycyclic aromatic hydrocarbons (2,3,7,8-tetrachlorodibenzo-p-dioxin). Hypersensitivity (or allergic) reactions can occur after exposure to toluene diisocyanate (occupational asthma). In summary, airborne pollutants may cause a wide spectrum of immunologically mediated disorders, There is clearly an underlying genetic basis for the susceptibility to immunologic disease resulting from exposure to pollutants, but knowledge in this area is rudimentary at present. Studies have been impeded by lack of appropriate in vitro models, as well as difficulties in identifying the biologically active substance. RP Albright, JF (reprint author), NIAID,DIV ALLERGY IMMUNOL & TRANSPLANTAT,NIH,4A18 SOLAR BLDG,6003 EXECUT BLVD,BETHESDA,MD 20892, USA. NR 35 TC 20 Z9 22 U1 0 U2 6 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 SN 0194-5998 J9 OTOLARYNG HEAD NECK JI Otolaryngol. Head Neck Surg. PD FEB PY 1996 VL 114 IS 2 BP 232 EP 238 DI 10.1016/S0194-5998(96)70173-0 PG 7 WC Otorhinolaryngology; Surgery SC Otorhinolaryngology; Surgery GA TX013 UT WOS:A1996TX01300012 PM 8637740 ER PT J AU Olden, K AF Olden, K TI Effects of air pollution on African-American and other minority populations SO OTOLARYNGOLOGY-HEAD AND NECK SURGERY LA English DT Article; Proceedings Paper CT Conference on Air Pollution Impacts on Body Organs and Systems CY NOV 18, 1994 CL WASHINGTON, DC SP Natl Assoc Physicians Environm, Natl Press Club RP Olden, K (reprint author), NIEHS,POB 12233,RES TRIANGLE PK,NC 27709, USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 SN 0194-5998 J9 OTOLARYNG HEAD NECK JI Otolaryngol. Head Neck Surg. PD FEB PY 1996 VL 114 IS 2 BP 255 EP 255 DI 10.1016/S0194-5998(96)70178-X PG 1 WC Otorhinolaryngology; Surgery SC Otorhinolaryngology; Surgery GA TX013 UT WOS:A1996TX01300017 PM 8637745 ER PT J AU Izraeli, S Mueller, BU Ling, A Temeck, BK Lewis, LL Chang, R Shad, AT Pass, HI Pizzo, PA AF Izraeli, S Mueller, BU Ling, A Temeck, BK Lewis, LL Chang, R Shad, AT Pass, HI Pizzo, PA TI Role of tissue diagnosis in pulmonary involvement in pediatric human immunodeficiency virus infection SO PEDIATRIC INFECTIOUS DISEASE JOURNAL LA English DT Article DE human immunodeficiency virus; acquired immunodeficiency syndrome; lung biopsy; pulmonary infections; pulmonary lymphoma; lymphocytic interstitial pneumonitis; child infant ID IMMUNE-DEFICIENCY SYNDROME; HIV-INFECTION; LUNG-BIOPSY; CHILDREN; AIDS AB Background. Pulmonary complications occur commonly during HIV infection, The aim of this study was to evaluate the clinical value of lung tissue examination in the diagnosis and treatment of pulmonary disorders in children with HIV infection, Methods, The medical records of 347 children enrolled between January, 1990, and April, 1994, into various antiretroviral therapy protocols were reviewed to identify patients who underwent a lung biopsy, Results. Fourteen patients underwent diagnostic lung biopsies on 16 separate occasions, The most common radiologic findings were nodular infiltrates which were localized in 7 patients and diffuse in 6, Eight patients presented with fever and progressive respiratory distress unresponsive to empiric therapy, whereas the rest had progressive nodular infiltrates. The pathologic diagnoses included opportunistic infection in 7 patients, lymphocytic interstitial pneumonitis in 5, non-Hodgkin's lymphoma in 3 and interstitial fibrosis in 1, The biopsy led to a major change in the treatment of 7 patients which resulted in a significant improvement of the pulmonary process in all of them, In an additional patient the excisional biopsy proved curative. Conclusions. When patients are selected appropriately, lung biopsy might have a significant impact on therapy and outcome in HIV-infected children with pulmonary infiltrates. C1 NCI,PEDIAT BRANCH,BETHESDA,MD 20892. NCI,THORAC SURG SECT,BETHESDA,MD 20892. NIH,CTR CLIN,DEPT DIAGNOST RADIOL,BETHESDA,MD 20892. NR 16 TC 13 Z9 14 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0891-3668 J9 PEDIATR INFECT DIS J JI Pediatr. Infect. Dis. J. PD FEB PY 1996 VL 15 IS 2 BP 112 EP 116 DI 10.1097/00006454-199602000-00005 PG 5 WC Immunology; Infectious Diseases; Pediatrics SC Immunology; Infectious Diseases; Pediatrics GA TV344 UT WOS:A1996TV34400003 PM 8822282 ER PT J AU Claesson, BA Trollfors, B Anderson, PW Johansson, J Taranger, J Schneerson, R Robbins, JB AF Claesson, BA Trollfors, B Anderson, PW Johansson, J Taranger, J Schneerson, R Robbins, JB TI Serum antibodies in six-year-old children vaccinated in infancy with a Haemophilus influenzae type b-tetanus toxoid conjugate vaccine SO PEDIATRIC INFECTIOUS DISEASE JOURNAL LA English DT Article DE Haemophilus influenzae type b; conjugate vaccine; antibodies; persistence ID CAPSULAR POLYSACCHARIDE; IMMUNIZATION; INFECTIONS C1 GOTHENBURG UNIV,DEPT INFECT DIS,GOTHENBURG,SWEDEN. GOTHENBURG UNIV,DEPT PEDIAT,GOTHENBURG,SWEDEN. BORAS HOSP,DEPT PEDIAT,BORAS,SWEDEN. UNIV ROCHESTER,DEPT PEDIAT,ROCHESTER,NY. NICHHD,DEV & MOLEC IMMUN LAB,NIH,BETHESDA,MD 20892. FU NIAID NIH HHS [N0I AI 45196] NR 13 TC 20 Z9 20 U1 0 U2 1 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0891-3668 J9 PEDIATR INFECT DIS J JI Pediatr. Infect. Dis. J. PD FEB PY 1996 VL 15 IS 2 BP 170 EP 172 DI 10.1097/00006454-199602000-00016 PG 3 WC Immunology; Infectious Diseases; Pediatrics SC Immunology; Infectious Diseases; Pediatrics GA TV344 UT WOS:A1996TV34400016 PM 8822293 ER PT J AU Halsey, NA Chesney, PJ Gerber, MA Gromisch, DS Kohl, S Marcy, SM Marks, MI Murray, DL Overall, JC Pickering, LK Whitley, RJ Yogev, R Peter, G Berkelman, RL Breiman, R Hardegree, MC Jacobs, RF MacDonald, NE Orenstein, WA Rabinovich, NR AF Halsey, NA Chesney, PJ Gerber, MA Gromisch, DS Kohl, S Marcy, SM Marks, MI Murray, DL Overall, JC Pickering, LK Whitley, RJ Yogev, R Peter, G Berkelman, RL Breiman, R Hardegree, MC Jacobs, RF MacDonald, NE Orenstein, WA Rabinovich, NR TI The relationship between pertussis vaccine and central nervous system sequelae: Continuing assessment SO PEDIATRICS LA English DT Article ID IMMUNIZATION AB Reassessment of the role of whole-cell pertussis vaccine as a cause of permanent neurologic damage is necessitated by the 10-year follow-up of the National Childhood Encephalopathy Study (NCES) in Great Britain. The findings of this study demonstrate that infants and young children with serious acute neurologic disorders are at an increased risk of later neurologic impairment or death, irrespective of the initial precipitating event. The results, however, do not establish a causal relationship between pertussis vaccination and chronic neurologic abnormalities. The Academy reaffirms its earlier conclusion that whole-cell pertussis vaccine has not been proven to be a cause of brain damage and continues to recommend pertussis vaccination in accordance with the guidelines in the 1994 Red Book.(1) C1 US FDA,ROCKVILLE,MD 20857. AMER THORAC SOC,NEW YORK,NY. NIH,BETHESDA,MD 20892. RP Halsey, NA (reprint author), CTR DIS CONTROL & PREVENT,WASHINGTON,DC, USA. NR 13 TC 13 Z9 13 U1 0 U2 2 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 FEB PY 1996 VL 97 IS 2 BP 279 EP 281 PG 3 WC Pediatrics SC Pediatrics GA TU284 UT WOS:A1996TU28400027 ER PT J AU Halsey, NA Chesney, PJ Gerber, MA Gromisch, DS Kohl, S Marcy, SM Marks, MI Murray, DL Overall, JC Pickering, LK Whitley, RJ Yogev, R Peter, G Berkelman, RL Breiman, R Hardegree, MC Jacobs, RF MacDonald, NE Orenstein, WA Rabinovich, NR AF Halsey, NA Chesney, PJ Gerber, MA Gromisch, DS Kohl, S Marcy, SM Marks, MI Murray, DL Overall, JC Pickering, LK Whitley, RJ Yogev, R Peter, G Berkelman, RL Breiman, R Hardegree, MC Jacobs, RF MacDonald, NE Orenstein, WA Rabinovich, NR TI Update on tuberculosis skin testing of children SO PEDIATRICS LA English DT Article C1 US FDA, ROCKVILLE, MD 20857 USA. AMER THORAC SOC, NEW YORK, NY USA. NIH, BETHESDA, MD USA. RP CTR DIS CONTROL & PREVENT, WASHINGTON, DC USA. NR 11 TC 37 Z9 37 U1 0 U2 0 PU AMER ACAD PEDIATRICS PI ELK GROVE VILLAGE PA 141 NORTH-WEST POINT BLVD,, ELK GROVE VILLAGE, IL 60007-1098 USA SN 0031-4005 EI 1098-4275 J9 PEDIATRICS JI Pediatrics PD FEB PY 1996 VL 97 IS 2 BP 282 EP 284 PG 3 WC Pediatrics SC Pediatrics GA TU284 UT WOS:A1996TU28400028 ER PT J AU Long, RM AF Long, RM TI What are the differences between a request for application (RFA) and a program announcement (PA)? What are the advantages and disadvantages of each? SO PHARMACEUTICAL RESEARCH LA English DT News Item RP Long, RM (reprint author), NIGMS,NIH,PHARMACOL PHYSIOL & BIOL CHEM DIV,PHARMACOL & PHYSIOL SCI BRANCH,BETHESDA,MD, USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU PLENUM PUBL CORP PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 SN 0724-8741 J9 PHARMACEUT RES JI Pharm. Res. PD FEB PY 1996 VL 13 IS 2 BP 185 EP 185 PG 1 WC Chemistry, Multidisciplinary; Pharmacology & Pharmacy SC Chemistry; Pharmacology & Pharmacy GA TW198 UT WOS:A1996TW19800001 ER PT J AU Egan, MF Ferguson, J Hyde, TM AF Egan, MF Ferguson, J Hyde, TM TI Effects of rating parameters on assessment of neuroleptic-induced vacuous chewing movements SO PHARMACOLOGY BIOCHEMISTRY AND BEHAVIOR LA English DT Article DE vacuous chewing movements; habituation; haloperidol ID GLUTAMIC-ACID DECARBOXYLASE; INDUCED ORAL DYSKINESIAS; TARDIVE-DYSKINESIA; CHRONIC HALOPERIDOL; ATYPICAL NEUROLEPTICS; MOUTH MOVEMENTS; ANIMAL-MODEL; RATS; INTERMITTENT; RECEPTORS AB Long-term administration of neuroleptics to rats produces a syndrome of vacuous chewing movements (VCMs). The validity of the VCM syndrome as a model for tardive dyskinesia (TD) in humans is unclear. This is due, in part, to inconsistencies between studies. Methods for rating VCMs have varied markedly and could account for the inconsistencies. The purpose of this study was to evaluate the importance of the different methods on VCM scores. The effects of habituation and length of rating sessions were examined in rats habituated for 2 min, 1 h, or several hours over 4 days, compared to unhabituated rats. Ratings with and without habituation were highly correlated, as were ratings from 2- and 5-min observation periods. Ratings from neuroleptic-treated rats in restraining tubes, however, were significantly correlated with unrestrained ratings only following several hours of habituation. Locomotor activity was not correlated with VCM scores. These results suggest that habituation to open cages is not an important factor in assessing VCMs. Use of restraining tubes, however, may alter scores. The lack of an habituation effect or of a relationship between activity and VCMs suggests that locomotor and oral behaviors are not necessarily in competition. Restraining rats to rate VCMs does not appear to be necessary and could alter the neurobiology of VCMs. C1 NIMH,NEUROSCI CTR ST ELIZABETHS,CLIN BRAIN DISORDERS BRANCH,WASHINGTON,DC 20032. RP Egan, MF (reprint author), NIMH,NEUROSCI CTR ST ELIZABETHS,NEUROPSYCHIAT BRANCH,2700 ML KING JR AVE SE,WASHINGTON,DC 20032, USA. NR 34 TC 17 Z9 17 U1 1 U2 2 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0091-3057 J9 PHARMACOL BIOCHEM BE JI Pharmacol. Biochem. Behav. PD FEB PY 1996 VL 53 IS 2 BP 401 EP 410 DI 10.1016/0091-3057(95)02041-1 PG 10 WC Behavioral Sciences; Neurosciences; Pharmacology & Pharmacy SC Behavioral Sciences; Neurosciences & Neurology; Pharmacology & Pharmacy GA TT772 UT WOS:A1996TT77200025 PM 8808150 ER PT J AU Dimmock, JR Puthucode, RN Lo, MS Quail, JW Yang, J Stables, JP AF Dimmock, JR Puthucode, RN Lo, MS Quail, JW Yang, J Stables, JP TI Structural modifications of the primary amino group of anticonvulsant aryl semicarbazones SO PHARMAZIE LA English DT Article ID ANTIEPILEPTIC DRUG DEVELOPMENT; PROGRAM AB A number of aryl semicarbazones had been shown previously to possess significant anticonvulsant properties. The principal objective of the present investigation was to determine the importance of the primary amino group in this series of compounds by replacing it with other substituents. The results indicate that the amino group was not essential for anticonvulsant activity. However its replacement by an aryl ring generally abolished activity while a terminal phenylamino function was better tolerated. Thus both the size of the group and its hydrogen bonding capabilities appear to influence bioactivity. Alteration of the oxygen atom of the semicarbazones by isosteres did not enhance anticonvulsant properties. C1 UNIV SASKATCHEWAN,DEPT CHEM,SASKATOON,SK,CANADA. NINCDS,NIH,BETHESDA,MD 20892. RP Dimmock, JR (reprint author), UNIV SASKATCHEWAN,COLL PHARM & NUTR,SASKATOON,SK,CANADA. NR 13 TC 9 Z9 9 U1 0 U2 1 PU GOVI-VERLAG GMBH PI ESCHBORN PA PHARMAZEUTISCHER VERLAG GINNHEIMER STRASSE 26, D-65760 ESCHBORN, GERMANY SN 0031-7144 J9 PHARMAZIE JI Pharmazie PD FEB PY 1996 VL 51 IS 2 BP 83 EP 88 PG 6 WC Chemistry, Medicinal; Chemistry, Multidisciplinary; Pharmacology & Pharmacy SC Pharmacology & Pharmacy; Chemistry GA TY071 UT WOS:A1996TY07100004 PM 8720804 ER PT J AU Kirov, SA Talan, MI Engel, BT AF Kirov, SA Talan, MI Engel, BT TI Sympathetic outflow to interscapular brown adipose tissue in cold acclimated mice SO PHYSIOLOGY & BEHAVIOR LA English DT Article DE adaptation; nervous activity; nonshivering thermogenesis; rodents; temperature regulation ID METABOLIC HEAT-PRODUCTION; MALE C57BL/6J MICE; NERVOUS ACTIVITY; THERMOGENESIS; STRESS; STIMULATION; EXPRESSION; TOLERANCE; NERVES; ADULT AB C57BL/6J male mice were subjected to a cold acclimation procedure which consisted of three consecutive cold stress tests: 3-h partial restraint at 6 degrees C at 2-wk intervals. During the week following the last cold stress test, each animal previously subjected to the cold acclimation procedure, and an additional group of naive mice (animals that never had been exposed to an environment below room temperature) were anesthetized with urethane, paralyzed with vecuronium bromide, artificially ventilated, and subjected to cold stimulation for approximately 16 min. Electrical impulse activity from one of the fine sympathetic nerves entering the interscapular brown adipose tissue was recorded before and during cold stimulation, until body temperature dropped 8 degrees C below control level. Sympathetic outflow increased significantly during cold stimulation in all mice. Animals that did not achieve cold acclimation in three repeated cold stress tests (they demonstrated less cold tolerance in the last test) had lower sympathetic nervous outflow to brown adipose tissue at room temperature and during cold stimulation than mice that had achieved cold acclimation. In fact, sympathetic nervous outflow to brown adipose tissue in mice that had failed to show cold acclimation was similar to that of naive mice. These findings indicate that the sympathetic nervous system plays a primary role in cold acclimation. C1 NIA,GERONTOL RES CTR,BEHAV SCI LAB,BALTIMORE,MD 21224. NR 27 TC 5 Z9 5 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0031-9384 J9 PHYSIOL BEHAV JI Physiol. Behav. PD FEB PY 1996 VL 59 IS 2 BP 231 EP 235 DI 10.1016/0031-9384(95)02129-9 PG 5 WC Psychology, Biological; Behavioral Sciences SC Psychology; Behavioral Sciences GA VG962 UT WOS:A1996VG96200003 PM 8838599 ER PT J AU Brinton, LA Malone, KE Coates, RJ Schoenberg, JB Swanson, CA Daling, JR Stanford, JL AF Brinton, LA Malone, KE Coates, RJ Schoenberg, JB Swanson, CA Daling, JR Stanford, JL TI Breast enlargement and reduction. Results from a breast cancer case-control study SO PLASTIC AND RECONSTRUCTIVE SURGERY LA English DT Article ID GEL-FILLED IMPLANTS; AUGMENTATION MAMMAPLASTY; WOMEN; RISK; MAMMOPLASTY; MAMMOGRAPHY; CARCINOMA; DIAGNOSIS AB In a population-based case-control study of breast cancer that included 2174 cases and 2009 population controls under 55 years of age, prior breast implants were reported by 36 cases Versus 44 controls. After adjustment for the matching factors as well as variables associated with both breast cancer risk and breast enlargement (race, family history of breast cancer, body size, screening history), the relative risk of breast cancer associated with a prior implant was 0.6 (95% CI 0.4-1.0). The reduced risk persisted with increasing interval since surgery, arguing against selection bias as an explanation. Further, although a deficit of in situ tumors was seen among women with implants (RR = 0.2), the risk associated with implants remained reduced for both localized and distant tumors (RR = 0.8 for both stages). In a smaller group of women who had prior breast reduction surgery (10 cases, 13 controls), a reduced risk of breast cancer also was observed (RR = 0.7, 95% CI 0.3-1.6). The results of this study must be interpreted cautiously because of the small number of women involved and reliance on patient reports of prior operations. In not showing any elevation in breast cancer risk following a breast implant, our results confirm several record linkage studies but contradict some clinical studies that suggest an adverse effect. Additional investigations are needed in relation to specific types of breast implants, including the polyurethane-coated implants, which have been linked to high cancer rates in laboratory animals. RP Brinton, LA (reprint author), NCI, ENVIRONM EPIDEMIOL BRANCH, EXECUT PLAZA N, ROOM 443, BETHESDA, MD 20892 USA. RI Brinton, Louise/G-7486-2015 OI Brinton, Louise/0000-0003-3853-8562 NR 38 TC 66 Z9 67 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0032-1052 EI 1529-4242 J9 PLAST RECONSTR SURG JI Plast. Reconstr. Surg. PD FEB PY 1996 VL 97 IS 2 BP 269 EP 275 DI 10.1097/00006534-199602000-00001 PG 7 WC Surgery SC Surgery GA TT028 UT WOS:A1996TT02800001 PM 8559808 ER PT J AU Chen, RD Grobler, JA Hurley, JH Dean, AM AF Chen, RD Grobler, JA Hurley, JH Dean, AM TI Second-site suppression of regulatory phosphorylation in Escherichia coli isocitrate dehydrogenase SO PROTEIN SCIENCE LA English DT Article DE intragenic suppression; isocitrate dehydrogenase; regulatory phosphorylation ID ACTIVE-SITE; RANDOM MUTAGENESIS; ENZYME; RESOLUTION; MECHANISM; PHOSPHATE; PROGRAM; MUTANT; CHAIN AB Inactivation of Escherichia coli isocitrate dehydrogenase upon phosphorylation at S113 depends upon the direct electrostatic repulsion of the negatively charged gamma-carboxylate of isocitrate by the negatively charged phosphoserine. The effect is mimicked by replacing S113 with aspartate or glutamate, which reduce performance (k(cat)/Ki . isocitrat/Km . NADP) by a factor of 10(7). Here, we demonstrate that the inactivating effects of the electrostatic repulsion are completely eliminated by a second-site mutation, and provide the structural basis for this striking example of intragenic suppression. N115 is adjacent to S113 on one face of the D-helix, interacts with isocitrate and NADP(+), and has been postulated to serve in both substrate binding and in catalysis. The single N115L substitution reduces affinity for isocitrate by a factor of 50 and performance by a factor of 500. However, the N115L substitution completely suppresses the inactivating electrostatic effects of S113D or S113E: the performance of the double mutants is 10(5) higher than the S113D and S113E single mutants. These mutations have little effect on the kinetics of alternative substrates, which lack the charged gamma-carboxylate of isocitrate. Both glutamate and aspartate at site 113 remain fully ionized in the presence of leucine. In the crystal structure of the N115L mutant, the leucine adopts a different conformer from the wild-type asparagine. Repacking around the leucine forces the amino-terminus of the D-helix away from the rest of the active site. The hydrogen bond between E113 and N115 in the S113E single mutant is broken in the S113E/N115L mutant, allowing the glutamate side chain to move away from the gamma-carboxylate of isocitrate. These movements increase the distance between the carboxylates, diminish the electrostatic repulsion, and lead to the remarkably high activity of the S113E/N115L mutant. C1 CHICAGO MED SCH,DEPT BIOL CHEM,N CHICAGO,IL 60064. NIDDKD,NIH,MOLEC BIOL LAB,BETHESDA,MD 20892. FU NIGMS NIH HHS [GM-48735] NR 36 TC 20 Z9 20 U1 0 U2 1 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 40 WEST 20TH STREET, NEW YORK, NY 10011-4211 SN 0961-8368 J9 PROTEIN SCI JI Protein Sci. PD FEB PY 1996 VL 5 IS 2 BP 287 EP 295 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA TU724 UT WOS:A1996TU72400013 PM 8745407 ER PT J AU MazzolaPomietto, P Aulakh, CS Wozniak, KM Murphy, DL AF MazzolaPomietto, P Aulakh, CS Wozniak, KM Murphy, DL TI Evidence that m-chlorophenylpiperazine-induced: Hyperthermia in rats is mediated by stimulation of 5-HT2C receptors SO PSYCHOPHARMACOLOGY LA English DT Article DE ketanserin; metergoline; mesulergine; ondansetron; propranolol; ritanserin; spiperone ID FAWN-HOODED RAT; HEAT-ADAPTED RATS; ANTIDEPRESSANT TREATMENTS; SEROTONIN AGONIST; M-CPP; RESPONSES; NEUROENDOCRINE; ANTAGONISTS; TEMPERATURE; BRAIN AB Intraperitoneal administration of m-chlorophenylpiperazine (m-CPP) to Wistar rats produced hyperthermia with a peak effect at 30 min. Pretreatment with low doses of metergoline (5-HT1/5-HT2 antagonist), mesulergine and mianserin (5-HT2C/5-HT2A antagonists) blocked m-CPP-induced hyperthermia. Pretreatment with propranolol (beta-adrenergic receptor antagonist that also has binding affinity for 5-HT1A, 5-HT1B and 5-HT2B sites), yohimbine (alpha(2)-noradrenergic antagonist that also has binding affinity for 5-HT2B sites), MDL-72222 or ondansetron (5-HT3 antagonists) did not attenuate m-CPP-induced hyperthermia. Only high doses of ketanserin, LY-53857 and ritanserin (5-HT2A/5-HT2C antagonists) as well as spiperone (5-HT1A/5-HT2A/D-2 antagonist) attenuated m-CPP-induced hyperthermia. Daily administration of m-CPP produced complete tolerance to its hyperthermic effect by day 5. However, there was no cross-tolerance to 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI, a 5-HT2A agonist that also has high affinity for 5-HT2C receptors)-induced hyperthermia. m-CPP-induced increases in temperature were found to be significantly less in the Fawn-Hooded (FH) rat strain as compared to the Wistar rat strain; in prior studies, FH rats have been found to be subsensitive to other 5-HT2C-mediated pharmacologic responses. Altogether, these findings suggest that m-CPP-induced hyperthermia in rats is mediated by selective stimulation of 5-HT2C receptors. C1 NIMH,NATL INST HLTH,CLIN SCI LAB,BETHESDA,MD 20892. NR 45 TC 33 Z9 33 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 FEB PY 1996 VL 123 IS 4 BP 333 EP 339 DI 10.1007/BF02246643 PG 7 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA TZ331 UT WOS:A1996TZ33100006 PM 8867872 ER PT J AU Doppman, JL Gill, JR AF Doppman, JL Gill, JR TI Hyperaldosteronism: Sampling the adrenal veins SO RADIOLOGY LA English DT Article DE adrenal gland, hyperplasia; adrenal gland, neoplasms; radiology and radiologists, how I do it ID PRIMARY HYPER-ALDOSTERONISM; UNILATERAL ALDOSTERONOMA; CLINICAL-SIGNIFICANCE; LOCALIZATION; HYPERPLASIA; DIAGNOSIS; CT; FREQUENCY; ADENOMA; LESIONS C1 NHLBI,DIV INTRAMURAL RES,BETHESDA,MD 20892. RP Doppman, JL (reprint author), NHLBI,WARREN GRANT MAGNUSON CLIN CTR,HENRY M JACKSON FDN,DEPT DIAGNOST RADIOL,BLDG 10,BETHESDA,MD 20892, USA. NR 22 TC 123 Z9 131 U1 0 U2 0 PU RADIOLOGICAL SOC NORTH AMER PI EASTON PA 20TH AND NORTHAMPTON STS, EASTON, PA 18042 SN 0033-8419 J9 RADIOLOGY JI Radiology PD FEB PY 1996 VL 198 IS 2 BP 309 EP 312 PG 4 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA TR363 UT WOS:A1996TR36300002 PM 8596821 ER PT J AU Rogers, MJ Gutell, RR Damberger, SH Li, J McConkey, GA Waters, AP McCutchan, TF AF Rogers, MJ Gutell, RR Damberger, SH Li, J McConkey, GA Waters, AP McCutchan, TF TI Structural features of the large subunit rRNA expressed in Plasmodium falciparum sporozoites that distinguish it from the asexually expressed large subunit rRNA SO RNA-A PUBLICATION OF THE RNA SOCIETY LA English DT Article DE malaria; mosquito stage; ribosome; RNA secondary structure ID RIBOSOMAL-RNA GENES; DNA; IDENTIFICATION; CROSS AB The developmentally regulated transcription of at least two distinct sets of nuclear-encoded ribosomal RNAs is detected in Plasmodium species, The identification of functional differences between the two sets of rRNAs is of interest, To facilitate the search for such differences, we have identified the 5,8S and 285 rRNAs from Plasmodium falciparum that are expressed in the sporozoite stage (5 gene) of the parasites' life cycle in the mosquito host and compare them to transcripts expressed in the red blood cells (A gene) of the vertebrate host, This completes the first set of A- and S-type nuclear-encoded rRNA genes for a Plasmodium species, Analysis of the predicted secondary structures of the two units reveals the majority of differences between the A- and S-type genes occur in regions previously known to be variable, However, the predicted secondary structure of both 285 rRNAs indicates 11 positions within conserved areas that are not typical of eucaryotic rRNAs, Although the A-type gene resembles almost all eucaryotes, being atypical in only 4 of the 11 positions, the S gene is variant in 8 of the 11 positions, In three of these positions, the S-type gene resembles the consensus nucleotides for the 235 rRNA from Eubacteria and/or Archaea, A few differences occur in regions associated with ribosome function, in particular the GTPase site where the S-type differs in a base pair and loop from all known sequences. Further, the identification of compensatory changes at conserved points of interactions between the 5,8S-28S rRNAs indicates that transcripts from A- and S-units should not be interchangeable. C1 NIAID,NIH,GROWTH & DEV SECT,PARASIT DIS LAB,BETHESDA,MD 20892. UNIV COLORADO,DEPT MCD BIOL,BOULDER,CO 80309. UNIV COLORADO,DEPT CHEM & BIOCHEM,BOULDER,CO 80309. LEIDEN UNIV,PARASITOL LAB,LEIDEN,NETHERLANDS. RI Waters, Andy/C-9377-2009 OI Waters, Andy/0000-0001-8900-2982 FU NIGMS NIH HHS [GM48207, R01 GM048207] NR 47 TC 33 Z9 35 U1 1 U2 2 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 40 WEST 20TH STREET, NEW YORK, NY 10011-4211 SN 1355-8382 J9 RNA JI RNA-Publ. RNA Soc. PD FEB PY 1996 VL 2 IS 2 BP 134 EP 145 PG 12 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA UD294 UT WOS:A1996UD29400004 PM 8601280 ER PT J AU Ma, SL Thompson, J Hu, HZ Neville, DM AF Ma, SL Thompson, J Hu, HZ Neville, DM TI Expression and characterization of a divalent chimeric anti-human CD3 single chain antibody SO SCANDINAVIAN JOURNAL OF IMMUNOLOGY LA English DT Article ID OKT3 MONOCLONAL-ANTIBODY; T-CELL PROLIFERATION; FC-RECEPTORS; IGM; IMMUNOGLOBULIN; SECRETION; MOUSE; SPECIFICITY; REJECTION; RESPONSES AB Murine anti-CD3 monoclonal antibodies (MoAbs) are used in clinical practice for immunosuppression. However, there are two major drawbacks to this treatment: the associated cytokine release syndrome and human anti-mouse antibody response. To overcome these side-effects, the authors generated a chimeric anti-human CD3 single chain antibody, scUCHT1. It is an IgM variant of UCHT1, a mouse IgG1 MoAb directed against human CD3. scUCHT1 consists of the light and heavy variable chain binding domains of UCHT1 and a human IgM Fc region (CH2 to CH4), scUCHT1 was produced by COS-7 and SP2/0 transfectants, and mainly assembled in a dimeric form. It retained the binding specificity and affinity of the parental MoAb UCHT1. In contrast to UCHT1, scUCHT1 did not induce T-cell proliferation and cytokine release (TNF-alpha and IFN-gamma) in in vitro assays. These results suggest that the engineered chimeric anti-CD3 single chain antibody (scUCHT1) may be useful in clinical immunosuppressive treatment. C1 NIMH,MOLEC BIOL LAB,NIH,SECT BIOPHYS CHEM,BETHESDA,MD 20892. NR 30 TC 7 Z9 7 U1 0 U2 1 PU BLACKWELL SCIENCE LTD PI OXFORD PA OSNEY MEAD, OXFORD, OXON, ENGLAND OX2 0EL SN 0300-9475 J9 SCAND J IMMUNOL JI Scand. J. Immunol. PD FEB PY 1996 VL 43 IS 2 BP 134 EP 139 DI 10.1046/j.1365-3083.1996.d01-22.x PG 6 WC Immunology SC Immunology GA TU126 UT WOS:A1996TU12600002 PM 8633192 ER PT J AU Murphy, DGM Mentis, MJ Xenetidis, K Henry, J Rapoport, SI AF Murphy, DGM Mentis, MJ Xenetidis, K Henry, J Rapoport, SI TI A pet study of glucose metabolism in brain areas implicated in schizophrenia: Effects of X chromosome triplet repeats SO SCHIZOPHRENIA RESEARCH LA English DT Meeting Abstract C1 INST PSYCHIAT,SECT MENTAL IMPAIRMENT,LONDON SE5 8AF,ENGLAND. NIA,NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0920-9964 J9 SCHIZOPHR RES JI Schizophr. Res. PD FEB PY 1996 VL 18 IS 2-3 BP IXD2 EP IXD2 PG 1 WC Psychiatry SC Psychiatry GA UE365 UT WOS:A1996UE36500202 ER PT J AU Torrey, EF Waldman, IN Clark, K AF Torrey, EF Waldman, IN Clark, K TI Urban residence as a risk factor for psychosis in the 1880 United States census SO SCHIZOPHRENIA RESEARCH LA English DT Meeting Abstract C1 ST ELIZABETH HOSP,NIMH,CTR NEUROSCI,WASHINGTON,DC 20032. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0920-9964 J9 SCHIZOPHR RES JI Schizophr. Res. PD FEB PY 1996 VL 18 IS 2-3 BP IIIB2 EP IIIB2 PG 1 WC Psychiatry SC Psychiatry GA UE365 UT WOS:A1996UE36500039 ER PT J AU Roth, BL Hamblin, MW Sibley, DR Meltzer, HY AF Roth, BL Hamblin, MW Sibley, DR Meltzer, HY TI Binding of atypical antipsychotic drugs to novel neurotransmitter receptors SO SCHIZOPHRENIA RESEARCH LA English DT Meeting Abstract C1 CASE WESTERN RESERVE UNIV,SCH MED,DEPT PSYCHIAT,CLEVELAND,OH 44106. CASE WESTERN RESERVE UNIV,SCH MED,DEPT BIOCHEM,CLEVELAND,OH 44106. UNIV WASHINGTON,SCH MED,DEPT PSYCHIAT,SEATTLE,WA. NINCDS,NIH,BETHESDA,MD 20892. RI Roth, Bryan/F-3928-2010; Meltzer, Herbert/E-8131-2013 NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0920-9964 J9 SCHIZOPHR RES JI Schizophr. Res. PD FEB PY 1996 VL 18 IS 2-3 BP VIA10 EP VIA10 PG 1 WC Psychiatry SC Psychiatry GA UE365 UT WOS:A1996UE36500134 ER PT J AU Wyatt, RJ Masserano, J Kulaga, H Karoum, F Hitri, A Elkashef, A AF Wyatt, RJ Masserano, J Kulaga, H Karoum, F Hitri, A Elkashef, A TI The anterior cingulate cortex in schizophrenia: Decreased dopamine and possible mechanism for its occurrence SO SCHIZOPHRENIA RESEARCH LA English DT Meeting Abstract C1 NIMH,NEUROSCI CTR ST ELIZABETHS,NEUROPSYCHIAT BRANCH,WASHINGTON,DC 20032. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0920-9964 J9 SCHIZOPHR RES JI Schizophr. Res. PD FEB PY 1996 VL 18 IS 2-3 BP VIII1 EP VIII1 PG 1 WC Psychiatry SC Psychiatry GA UE365 UT WOS:A1996UE36500167 ER PT J AU Torrey, EF Johnston, NL Cervenak, J Paltan, JD Yolken, RH AF Torrey, EF Johnston, NL Cervenak, J Paltan, JD Yolken, RH TI Selecting postmortem brain tissue for research: How important is the postmortem interval? SO SCHIZOPHRENIA RESEARCH LA English DT Meeting Abstract C1 ST ELIZABETH HOSP,NIMH,CTR NEUROSCI,WASHINGTON,DC 20032. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0920-9964 J9 SCHIZOPHR RES JI Schizophr. Res. PD FEB PY 1996 VL 18 IS 2-3 BP XH2 EP XH2 PG 1 WC Psychiatry SC Psychiatry GA UE365 UT WOS:A1996UE36500239 ER PT J AU Pommier, Y AF Pommier, Y TI Eukaryotic DNA topoisomerase I: Genome gatekeeper and its intruders, camptothecins SO SEMINARS IN ONCOLOGY LA English DT Article; Proceedings Paper CT Satellite Symposium on CPT-11 - From DNA Topology to Clinical Activity, at the 5th International Congress on Anticancer Therapy CY JAN-FEB -, 1995 CL PARIS, FRANCE SP Rhone Poulenc Rorer ID PROTEIN-KINASE-C; P-GLYCOPROTEIN EXPRESSION; PLANT ANTITUMOR AGENTS; TUMOR-CELL LINES; CYTO-TOXICITY; BIOLOGICAL-ACTIVITY; REPLICATION FORKS; MAMMALIAN-CELLS; STRAND BREAKS; L1210 CELLS RP Pommier, Y (reprint author), NCI,MOLEC PHARMACOL LAB,NIH,DNA TOPOL SECT,BLDG 37,ROOM 5C25,BETHESDA,MD 20892, USA. NR 87 TC 83 Z9 85 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0093-7754 J9 SEMIN ONCOL JI Semin. Oncol. PD FEB PY 1996 VL 23 IS 1 SU 3 BP 3 EP 10 PG 8 WC Oncology SC Oncology GA UG032 UT WOS:A1996UG03200002 PM 8633251 ER PT J AU Abrams, SI Hand, PH Tsang, KY Schlom, J AF Abrams, SI Hand, PH Tsang, KY Schlom, J TI Mutant ras epitopes as targets for cancer vaccines SO SEMINARS IN ONCOLOGY LA English DT Article ID T-CELL CLONES; ACUTE MYELOID-LEUKEMIA; POLYMERASE CHAIN-REACTION; CLASS-II MOLECULES; POINT MUTATIONS; TUMOR-CELLS; OLIGONUCLEOTIDE HYBRIDIZATION; LYMPHOCYTES-T; FUNCTIONAL-PROPERTIES; LYMPHOKINE SECRETION C1 NCI,NIH,TUMOR IMMUNOL & BIOL LAB,BETHESDA,MD 20892. NR 79 TC 71 Z9 71 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0093-7754 J9 SEMIN ONCOL JI Semin. Oncol. PD FEB PY 1996 VL 23 IS 1 BP 118 EP 134 PG 17 WC Oncology SC Oncology GA TY194 UT WOS:A1996TY19400015 PM 8607022 ER PT J AU Murray, E AF Murray, E TI Memory systems in the primate brain - Introduction SO SEMINARS IN THE NEUROSCIENCES LA English DT Editorial Material RP Murray, E (reprint author), NIMH,NEUROPSYCHOL LAB,BETHESDA,MD 20892, USA. NR 0 TC 8 Z9 8 U1 0 U2 0 PU ACADEMIC PRESS LTD PI LONDON PA 24-28 OVAL RD, LONDON, ENGLAND NW1 7DX SN 1044-5765 J9 SEMIN NEUROSCI JI Semin. Neurosci. PD FEB PY 1996 VL 8 IS 1 BP 1 EP 2 DI 10.1006/smns.1996.0001 PG 2 WC Neurosciences SC Neurosciences & Neurology GA TW444 UT WOS:A1996TW44400001 ER PT J AU Suzuki, WA AF Suzuki, WA TI Neuroanatomy of the monkey entorhinal, perirhinal and parahippocampal cortices: Organization of cortical inputs and interconnections with amygdala and striatum SO SEMINARS IN THE NEUROSCIENCES LA English DT Article DE connections; hippocampal formation; medial temporal lobe; memory ID AREA 35 CORTICES; RHESUS-MONKEY; HIPPOCAMPAL-FORMATION; MEMORY IMPAIRMENT; CORTICOCORTICAL CONNECTIONS; MACACA-FASCICULARIS; LOBE AFFERENTS; CORTEX; LESIONS; SUBDIVISIONS AB Experimental lesion studies in monkeys have demonstrated that the cortical areas surrounding the hippocampus, including the entorhinal perihinal and parahippocampal cortices play an important role in declarative memory (i.e. memory for facts and events). A series of neuroanatomical studies, motivated in part by the lesion studies, have shown that the macaque monkey entorhinal, perirhinal and parahippocampal cortices are poly modal association areas that each receive distinctive complements of cortical Inputs. These areas also have extensive interconnections with other brain areas implicated in non-declarative forms of memory including the amygdala and striatum. This pattern cf connections is consistent with the idea that the entorhinal, perirhinal and parahippocampal cortices may participate in a larger network of structures that integrates information across memory systems. RP Suzuki, WA (reprint author), NIMH,NEUROPSYCHOL LAB,BETHESDA,MD 20892, USA. NR 53 TC 119 Z9 119 U1 0 U2 3 PU ACADEMIC PRESS LTD PI LONDON PA 24-28 OVAL RD, LONDON, ENGLAND NW1 7DX SN 1044-5765 J9 SEMIN NEUROSCI JI Semin. Neurosci. PD FEB PY 1996 VL 8 IS 1 BP 3 EP 12 DI 10.1006/smns.1996.0002 PG 10 WC Neurosciences SC Neurosciences & Neurology GA TW444 UT WOS:A1996TW44400002 ER PT J AU Murray, EA AF Murray, EA TI What have ablation studies told us about the neural substrates of stimulus memory? SO SEMINARS IN THE NEUROSCIENCES LA English DT Article DE amygdala; entorhinal cortex; hippocampus; perirhinal cortex; recognition ID IMPAIRMENT FOLLOWING LESIONS; INFERIOR TEMPORAL CORTEX; LONG-TERM-MEMORY; HIPPOCAMPAL-FORMATION; RECOGNITION MEMORY; VISUAL RECOGNITION; ENTORHINAL CORTEX; HUMAN AMNESIA; MONKEYS; AMYGDALA AB Recent studies examining the neural substrates of stimulus memory in monkeys have found that the 'rhinal' cortex (i.e. the entorhinal and perirhinal cortex) makes a pivotal contribution to memory. Indeed, the rhinal cortex appears to be the only critical medial temporal lobe structure for stimulus recognition and certain kinds of associative memory as well. Thus, the mnemonic contributions of certain medial temporal structures, especially the amygdala and hippocampus, appear to have been overemphasized, and should be reconsidered. RP Murray, EA (reprint author), NIMH, NEUROPSYCHOL LAB, BETHESDA, MD 20892 USA. OI Murray, Elisabeth/0000-0003-1450-1642 NR 77 TC 148 Z9 149 U1 0 U2 4 PU ACADEMIC PRESS LTD PI LONDON PA 24-28 OVAL RD, LONDON, ENGLAND NW1 7DX SN 1044-5765 J9 SEMIN NEUROSCI JI Semin. Neurosci. PD FEB PY 1996 VL 8 IS 1 BP 13 EP 22 DI 10.1006/smns.1996.0003 PG 10 WC Neurosciences SC Neurosciences & Neurology GA TW444 UT WOS:A1996TW44400003 ER PT J AU Wise, SP AF Wise, SP TI The role of the basal ganglia in procedural memory SO SEMINARS IN THE NEUROSCIENCES LA English DT Article DE striatum; habit; procedure; skill; motor system ID PARKINSONS-DISEASE; HUNTINGTONS-DISEASE; VERBAL RECOGNITION; MONKEYS; MOTOR; LESIONS; AMNESIA; TASK; ORGANIZATION; NEUROANATOMY AB A common conjecture about the basal ganglia holds that these nuclei and their cortical inputs subserve relatively automatic stimulus-response behavior (habits) and other procedural memories. This speculative hypothesis warrants critical reassessment. No unequivocal evidence supports the assignment of this Information processing specialization do the basal ganglia or its cortical afferents. RP Wise, SP (reprint author), NIMH,NEUROPHYSIOL LAB,POB 608,POOLESVILLE,MD 20837, USA. NR 59 TC 26 Z9 27 U1 1 U2 2 PU ACADEMIC PRESS LTD PI LONDON PA 24-28 OVAL RD, LONDON, ENGLAND NW1 7DX SN 1044-5765 J9 SEMIN NEUROSCI JI Semin. Neurosci. PD FEB PY 1996 VL 8 IS 1 BP 39 EP 46 DI 10.1006/smns.1996.0006 PG 8 WC Neurosciences SC Neurosciences & Neurology GA TW444 UT WOS:A1996TW44400006 ER PT J AU Johnson, EO Brady, L Gold, PW Chrousos, GP AF Johnson, EO Brady, L Gold, PW Chrousos, GP TI Distribution of hippocampal mineralocorticoid and glucocorticoid receptor mRNA in a glucocorticoid resistant nonhuman primate SO STEROIDS LA English DT Article DE adrenal; glucocorticoid receptors; hippocampus; HPA axis; primate ID CORTICOSTEROID RECEPTORS; RAT-BRAIN; CORTISOL; STRESS AB Glucocorticoids regulate the activity of the hypothalamic-pituitary-adrenal, axis through both mineralocorticoid (MR) and glucocorticoid (GR) receptors in the hippocampus. In addition, glucocorticoids down-regulate hippocampal expression of MR and GR mRNA and protein, presumably decreasing their own effect. Marmosets are a New World primate characterized by extraordinarily high levels of circulating ACTH and cortisol. The relative glucocorticoid insensitivity of these animals to their massive levels of glucocorticoids was attributed to a decreased affinity of their GR for glucocorticoids, as well as a compromised ability of this receptor to transactivate glucocorticoid-responsive genes. The lack of mineralocorticoid excess, on the other hand was attributed to a renal MR which responded poorly to cortisol, but normally to aldosterone. The purpose of this study was to examine MR and GR mRNA expression in the marmoset (Callithrix jacchus jacchus) hippocampus. Overall, steady state levels of both MR and GR mRNA were elevated in all of the hippocampal subfields of the marmoset, and this was obvious in rough comparisons with those of a typical glucocorticoid-sensitive Old World primate, the rhesus monkey (Macaca mulata). Notable were the extremely high levels of GR mRNA in the dentate gyrus and field CA3 of the marmoset. The GR mRNA density distribution of the marmoset also appeared to differ from that in the rhesus and from those previously reported in rats and humans. These findings suggest that there is a compensatory elevation of MR and GR mRNAs in the marmoset hippocampus, which appears to be the result of target tissue resistance to glucocorticoids and inappropriate down-regulation by the elevated but ineffective, circulating cortisol. C1 NICHHD,DEV ENDOCRINOL BRANCH,SECT PEDIAT ENDOCRINOL,BETHESDA,MD 20892. NIMH,CLIN NEUROENDOCRINOL BRANCH,FUNCT NEUROANAT SECT,BETHESDA,MD. NR 26 TC 13 Z9 14 U1 0 U2 1 PU BUTTERWORTH-HEINEMANN PI WOBURN PA 225 WILDWOOD AVE #UNITB PO BOX 4500, WOBURN, MA 01801-2084 SN 0039-128X J9 STEROIDS JI Steroids PD FEB PY 1996 VL 61 IS 2 BP 69 EP 73 DI 10.1016/0039-128X(95)00195-V PG 5 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA TU869 UT WOS:A1996TU86900005 PM 8750435 ER PT J AU OLeary, DH Polak, JF Kronmal, RA Savage, PJ Borhani, NO Kittner, SJ Tracy, R Gardin, JM Price, TR Furberg, CD AF OLeary, DH Polak, JF Kronmal, RA Savage, PJ Borhani, NO Kittner, SJ Tracy, R Gardin, JM Price, TR Furberg, CD TI Thickening of the carotid wall - A marker for atherosclerosis in the elderly? SO STROKE LA English DT Article DE carotid arteries; diagnostic imaging; elderly; atherosclerosis ID B-MODE ULTRASOUND; INTIMA-MEDIA THICKNESS; DENSITY-LIPOPROTEIN CHOLESTEROL; COLESTIPOL-NIACIN THERAPY; CARDIOVASCULAR HEALTH; PATHOLOGIC FINDINGS; CEREBRAL-ISCHEMIA; ARTERY DISEASE; PULSATILE FLOW; SHEAR-STRESS AB Background and Purpose We investigated the relationships between prevalent coronary heart disease (CHD), clinically manifest atherosclerotic disease (ASD), and major established risk factors for atherosclerosis and intima-media thickness (IMT) in the common carotid arteries (CCA) and internal carotid arteries (ICA) separately and in combination in older adults. We wished to determine whether a noninvasive measurement can serve as an indicator of clinically manifest atherosclerotic disease and to determine which of the two variables, CCA IMT or ICA IMT, is a better correlate. Methods IMT of the CCA and ICA was measured with duplex ultrasound in 5117 of 5201 individuals enrolled in the Cardiovascular Health Study, a study of the risk factors and the natural history of cardiovascular disease in adults aged 65 years or more. Histories of CHD, peripheral arterial disease, and cerebrovascular disease were obtained during baseline examination. Risk factors included cholesterol levels. cigarette smoking, elevated blood pressure, diabetes? age, and sex. Relationships between risk factors and IMT were studied by multiple regression analysis and canonical variate analysis. Prediction of prevalent CHD and ASD by IMT measurements in CCAs and ICAs were made by logistic regression, adjusting for age and sex. Results IMT measurements of the CCAs and ICAs were greater in persons with CHD and ASD than those without, even after controlling for sex (P<.001). IMT measurements in the ICA were greater than those in the CCA. Risk factors for ASD accounted for 17% and 18% of the variability in IMT in the CCA and ICA, respectively. These same risk factors accounted for 25% of the variability of a composite measurement consisting of the sum of the ICA IMT and CCA IMT. The ability to predict CHD and ASD was greater for ICA IMT (odds ratio [confidence interval]: 1.36 [1.31 to 1.41] and 1.35 [1.25 to 1.44], respectively) than for CCA IMT (1.09 [1.05 to 1.13] and 1.17 [1.09 to 1.25]). Conclusions Whereas CCA IMT is associated with major risk factors for atherosclerosis and existing CI-ID and ASD in older adults, this association is not as strong as that for ICA IMT. The combination of these measures relates more strongly to existing CHD and ASD and cerebrovascular disease risk factors than either taken alone. C1 TUFTS UNIV,NEW ENGLAND MED CTR,DEPT RADIOL,BOSTON,MA 02111. BRIGHAM & WOMENS HOSP,DEPT RADIOL,BOSTON,MA 02115. WASHINGTON UNIV,DEPT BIOSTAT,SEATTLE,WA. NHLBI,DIV EPIDEMIOL & CLIN APPLICAT,BETHESDA,MD 20892. UNIV PITTSBURGH,DEPT NEUROSURG,PITTSBURGH,PA. UNIV MARYLAND,DEPT NEUROL,BALTIMORE,MD 21201. UNIV VERMONT,DEPT PATHOL,COLCHESTER,ESSEX,ENGLAND. UNIV CALIF IRVINE,IRVINE,CA 92717. WAKE FOREST UNIV,BOWMAN GRAY SCH MED,DEPT PUBL HLTH SCI,WINSTON SALEM,NC 27103. FU NHLBI NIH HHS [N01-HC85079, N01-HC85086] NR 53 TC 266 Z9 271 U1 0 U2 4 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0039-2499 J9 STROKE JI Stroke PD FEB PY 1996 VL 27 IS 2 BP 224 EP 231 PG 8 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA TU275 UT WOS:A1996TU27500007 PM 8571414 ER PT J AU Revay, R Vaughan, R Grant, S Kuhar, MJ AF Revay, R Vaughan, R Grant, S Kuhar, MJ TI Dopamine transporter immunohistochemistry in median eminence, amygdala, and other areas of the rat brain SO SYNAPSE LA English DT Article DE dopamine transporter; median eminence; dopamine; dopaminergic neuron; dopamine transporter antibody; immunohistochemistry ID NUCLEUS-ACCUMBENS; MIDBRAIN NEURONS; MESSENGER-RNA; COCAINE; EXPRESSION; CLONING; STRIATUM; LOCALIZATION; HYPOTHALAMUS; RECEPTORS AB In an extension of our previous work, an antibody directed against a peptide from the N-terminal region of DAT was used to localize specific dopamine transporter immunoreactivity (DAT-IR) in several regions of rat brain. Apparent axons and varicosities were found in the zona incerta, external layer of the median eminence, various nuclei of the amygdala, the cortex-amygdala transition zone, and in periglomerular regions in the olfactory bulb. Apparent stained neuronal perikarya and dendrites were observed in the arcuate nucleus and olfactory bulb. These regions are known to have dopaminergic neurons and innervations, although there was not a perfect correspondence between DAT-IR and the known distribution of dopaminergic neurons. A possible explanation is that different dopamine containing cell groups express different levels of DAT mRNA and protein, as we have previously shown. Also in the tuberoinfundibular neurons, for example, DAT-IR was preferentially localized to distal axons in the median eminence, suggesting intracellular compartmentation. (C) 1996 wiley-Liss, Inc.* RP Revay, R (reprint author), NIDA,DIV INTRAMURAL RES,NEUROSCI BRANCH,BALTIMORE,MD 21224, USA. NR 34 TC 48 Z9 48 U1 0 U2 2 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0887-4476 J9 SYNAPSE JI Synapse PD FEB PY 1996 VL 22 IS 2 BP 93 EP 99 DI 10.1002/(SICI)1098-2396(199602)22:2<93::AID-SYN1>3.3.CO;2-U PG 7 WC Neurosciences SC Neurosciences & Neurology GA TQ469 UT WOS:A1996TQ46900001 PM 8787132 ER PT J AU Moats, LC Lyon, GR AF Moats, LC Lyon, GR TI Wanted: Teachers with knowledge of language SO TOPICS IN LANGUAGE DISORDERS LA English DT Article ID LEARNING-DISABILITIES; CERTIFICATION; AWARENESS; EDUCATION; DEFICITS AB Research on the nature of reading and spelling disability (dyslexia) indicates unequivocally that most dyslexic individuals do not process language accurately or fluency at the level of phonology and that they may experience disorders in syntax and semantics as well. Simultaneously, intervention research clearly demonstrates that individuals who are taught language structure explicitly progress more readily than those who are not. Given the consistency of research findings, the paucity of teachers skilled in teaching language explicitly to dyslexic children is of more concern than ever. Surveys of teacher knowledge, reviews of the literature on teacher education, and policy statements indicate that many teachers are underprepared to teach language content and processes to children whose learning problems are language based. Even motivated and experienced teachers typically understand too little about spoken and written language structure to be able to provide sufficient instruction in these areas. A new approach to teacher education is needed that emphasizes the importance of language knowledge for literacy instruction, as well as its skilled application to instructional planning. C1 NICHHD,EXTRAMURAL RES PROGRAMS LEARNING DISABIL LANGUAG,BETHESDA,MD 20892. RP Moats, LC (reprint author), GREENWOOD INST,PUTNEY,VT, USA. NR 49 TC 49 Z9 49 U1 2 U2 9 PU ASPEN PUBL INC PI FREDERICK PA 7201 MCKINNEY CIRCLE, FREDERICK, MD 21701 SN 0271-8294 J9 TOP LANG DISORD JI Top. Lang. Disord. PD FEB PY 1996 VL 16 IS 2 BP 73 EP 86 PG 14 WC Linguistics; Rehabilitation SC Linguistics; Rehabilitation GA TQ430 UT WOS:A1996TQ43000007 ER PT J AU Hengen, PN AF Hengen, PN TI Methods and reagents - Preparing ultra-competent Escherichia coli SO TRENDS IN BIOCHEMICAL SCIENCES LA English DT Article ID TRANSFORMATION; CELLS; PLASMIDS; DNA RP Hengen, PN (reprint author), NCI,FREDERICK CANC RES & DEV CTR,FREDERICK,MD 21702, USA. NR 10 TC 11 Z9 11 U1 4 U2 10 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, OXON, ENGLAND OX5 1GB SN 0968-0004 J9 TRENDS BIOCHEM SCI JI Trends Biochem.Sci. PD FEB PY 1996 VL 21 IS 2 BP 75 EP 76 DI 10.1016/S0968-0004(96)80187-3 PG 2 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA TW639 UT WOS:A1996TW63900011 PM 8851666 ER PT J AU Howard, OMZ BenBaruch, A Oppenheim, JJ AF Howard, OMZ BenBaruch, A Oppenheim, JJ TI Chemokines: Progress toward identifying molecular targets for therapeutic agents SO TRENDS IN BIOTECHNOLOGY LA English DT Review ID RECEPTOR; IP-10 AB Leukocyte migration towards injury sites is directed by the interaction of chemokines with their receptors. The stages of migration are closely regulated events that involve chemokine-induced leukocyte adhesion, diapedesis and homing. Current research suggests a pathophysiological role for chemokines in diverse inflammatory states arising from viral, bacterial and parasitic infection, allergic and asthmatic reactions, atherosclerosis and arthritis. A role for chemokines in tumor immunity and angiogenesis has recently been demonstrated. A basis for the rational design of chemokine antagonists is emerging from a knowledge of tertiary structures and mutational analysis of chemokine ligands and receptors. Here, we discuss advances in knowledge about chemokine structure and function, with emphasis on potential therapeutic agents. C1 NCI,FREDERICK CANC RES & DEV CTR,MOLEC IMMUNOREGULAT LAB,FREDERICK,MD 21702. RP Howard, OMZ (reprint author), NCI,FREDERICK CANC RES & DEV CTR,SAIC FREDERICK,POB B,FREDERICK,MD 21702, USA. RI Howard, O M Zack/B-6117-2012 OI Howard, O M Zack/0000-0002-0505-7052 NR 49 TC 111 Z9 113 U1 0 U2 0 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, OXON, ENGLAND OX5 1GB SN 0167-7799 J9 TRENDS BIOTECHNOL JI Trends Biotechnol. PD FEB PY 1996 VL 14 IS 2 BP 46 EP 51 DI 10.1016/0167-7799(96)80920-6 PG 6 WC Biotechnology & Applied Microbiology SC Biotechnology & Applied Microbiology GA TV895 UT WOS:A1996TV89500007 PM 8746116 ER PT J AU Wolffe, AP Pruss, D AF Wolffe, AP Pruss, D TI Deviant nucleosomes: The functional specialization of chromatin SO TRENDS IN GENETICS LA English DT Review ID CRYSTAL-STRUCTURE; HISTONE OCTAMER; SATELLITE DNA; TRANSCRIPTION; DYNAMICS; BINDING AB Regulatory proteins exist with strong sequence and structural similarities to the histone Proteins. Molecular genetic and cell biological analyses suggest that these proteins are localized at particular sites within the chromosome. Their assembly into nucleosomal structures confers specialized functions to individual chromosomal domains. RP Wolffe, AP (reprint author), NICHHD,MOLEC EMBRYOL LAB,BLDG 6,RM B1A-13,BETHESDA,MD 20892, USA. NR 31 TC 72 Z9 73 U1 0 U2 3 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, OXON, ENGLAND OX5 1GB SN 0168-9525 J9 TRENDS GENET JI Trends Genet. PD FEB PY 1996 VL 12 IS 2 BP 58 EP 62 DI 10.1016/0168-9525(96)81401-6 PG 5 WC Genetics & Heredity SC Genetics & Heredity GA TV158 UT WOS:A1996TV15800006 PM 8851972 ER PT J AU Misik, V Riesz, P AF Misik, V Riesz, P TI EPR study of free radicals induced by ultrasound in organic liquids .2. Probing the temperatures of cavitation regions SO ULTRASONICS SONOCHEMISTRY LA English DT Article DE ultrasound; organic liquids; spin trapping; EPR; nitrosodurene ID ISOTOPE-EXCHANGE-REACTIONS; SPIN-TRAPPING EVIDENCE; THERMAL-DECOMPOSITION; HYDROGEN ABSTRACTION; AQUEOUS-SOLUTION; WATER MIXTURES; SONOCHEMISTRY; PHOTOLYSIS; SONOLYSIS; PYROLYSIS AB The spin trap nitrosodurene was used for the detection of radical intermediates formed by 50 kHz ultrasound in argon-saturated n-alcohols, n-alkanes, cyclic ethers, toluene, N,N-dimethylformamide (DMF) and dimethylacetamide (DMA). Radicals, produced by pyrolysis in collapsing cavitation bubbles, such as 'CH(2)R in n-alkanes, 'CH(2)R and 'CH2OH in n-alcohols, 'CH2-phenyl in toluene, 'CH(2)OR and 'CH(2)R in cyclic ethers and 'CH3 and 'N(CH3)R in DMF and DMA were spin trapped. Secondary radicals formed by hydrogen abstraction from organic liquids (such as 'CHRR' radicals in n-alcohols and n-alkanes and 'CH2N-type radicals in DMF and DMA) by the primary pyrolysis radicals were also spin trapped. For a series of n-alcohols, the logarithm of the rate of radical formation decreases linearly with the vapour pressures of the n-alcohols. The kinetic isotope effect, k(H)/k(D) for the ultrasound-induced production of 'CHRR' and 'CDRR' radicals in mixtures of n-dodecane and n-dodecane-d(26) was found to be 2.6. For the 'CH2-phenyl and 'CD2-phenyl-d(5) radicals from toluene-toluene-d(8), the ratio k(H)/k(D) = 1.09 was obtained. From the temperature dependence of the kinetic isotope effect, the temperature region of hydrogen abstraction radical formation ('CHRR') in n-dodecane was estimated to be 750 +/- 150 K; the effective temperature of the region where benzyl radicals are formed from toluene by sonochemical pyrolysis was estimated to be about 6000 K. This method appears to be a promising tool for probing the temperatures of different sonochemical regions. C1 NCI, RADIAT BIOL BRANCH, NIH, BETHESDA, MD 20892 USA. NR 45 TC 27 Z9 27 U1 3 U2 14 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1350-4177 J9 ULTRASON SONOCHEM JI Ultrason. Sonochem. PD FEB PY 1996 VL 3 IS 1 BP 25 EP 37 DI 10.1016/1350-4177(95)00036-4 PG 13 WC Acoustics; Chemistry, Multidisciplinary SC Acoustics; Chemistry GA UD175 UT WOS:A1996UD17500005 ER PT J AU vanLoon, FPL Clemens, JD Chakraborty, J Rao, MR Kay, BA Sack, DA Yunus, M Ali, M Svennerholm, AM Holmgren, J AF vanLoon, FPL Clemens, JD Chakraborty, J Rao, MR Kay, BA Sack, DA Yunus, M Ali, M Svennerholm, AM Holmgren, J TI Field trial of inactivated oral cholera vaccines in Bangladesh: Results from 5 years of follow-up SO VACCINE LA English DT Article DE cholera; oral vaccination; Bangladesh ID RURAL BANGLADESH AB To determine the protective efficacy (PE) of three noses of oral B subunit-killed whole cell (BS-WC) or killed whole cell-only (WC) vaccines against cholera, a clinical trial was conducted among 62285 children over 2 years and adult women in rural Bangladesh. During 5 years of follow-up, there were 144 cases of cholera in the BS-WC group (PE=49%; P<0.001), 150 in the WC group (PE=47%; P<0.001), and 283 in the K12 group. Protection by each vaccine was evident only during the first three years of follow-up; long-term protection of young children was observed only against classical but not El Tor cholera; 3-year protection against both cholera biotypes occurred among older persons, but at a higher level against classical cholera. C1 CTR DIS CONTROL & PREVENT,ATLANTA,GA 30341. NICHHD,BETHESDA,MD 20892. UNIV MARYLAND,CTR BIOTECHNOL,BALTIMORE,MD. JOHNS HOPKINS UNIV,SCH HYG & PUBL HLTH,BALTIMORE,MD. GOTHENBURG UNIV,GOTHENBURG,SWEDEN. RP vanLoon, FPL (reprint author), INT CTR DIARRHOEAL DIS RES,GPO BOX 128,DHAKA 1000,BANGLADESH. RI Ali, Mohammad/E-2365-2017 OI Ali, Mohammad/0000-0003-1410-388X NR 14 TC 67 Z9 68 U1 1 U2 3 PU BUTTERWORTH-HEINEMANN LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, OXON, ENGLAND OX5 1GB SN 0264-410X J9 VACCINE JI Vaccine PD FEB PY 1996 VL 14 IS 2 BP 162 EP 166 DI 10.1016/0264-410X(95)00122-H PG 5 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA TY662 UT WOS:A1996TY66200013 PM 8852414 ER PT J AU Lanata, CF Black, RE Flores, J Lazo, F Butron, B Linares, A Huapaya, A Ventura, G Gil, A Kapikian, AZ AF Lanata, CF Black, RE Flores, J Lazo, F Butron, B Linares, A Huapaya, A Ventura, G Gil, A Kapikian, AZ TI Immunogenicity, safety and protective efficacy of one dose of the rhesus rotavirus vaccine and serotype 1 and 2 human-rhesus rotavirus reassortants in children from Lima, Peru SO VACCINE LA English DT Article DE rotavirus vaccines; rhesus rotavirus; reassortants; diarrhea; vaccine; efficacy; Peru ID DIARRHEAL DISEASES; VENEZUELAN INFANTS; ESCHERICHIA-COLI; FIELD TRIAL; RIT-4237; NEUTRALIZATION; IDENTIFICATION; ANTIBODIES; CANDIDATES; VP7 AB In a four cell trial, a single 10(4) plaque-forming unit dose of rhesus rotavirus (RRV) vaccine (serotype G3), a human rotavirus-rhesus reassortant vaccine with serotype G1 specificity, a similar vaccine with serotype G2 specificity, or a placebo was administered with buffer orally at 2 months of age to 800 Peruvian infants. Only the RRV vaccine was associated with a febrile response (<38 degrees C) that occurred in 9% of the infants on day 4 after vaccination. Diarrhea or other side-effects were not associated with administration of vaccine. Vaccine strains were shed by only 12-18% of the infants as determined by examination of a single stool specimen obtained on days 4 or 5 after vaccination. Fifty per cent of vaccines developed an IgA ELISA seroresponse; however, a serotype-specific seroresponse by plaque reduction neutralization was demonstrated in <20% of the participant against each of the three candidate vaccine strains. Vaccine efficacy was evaluated by twice-weekly home surveillance for diarrheal diseases during 24 months post-immunization. Rotavirus diarrheal episodes were identified by ELISA. Only the RRV vaccine had a significant protective efficacy (29%, p=0.03, chi-square test) against rotavirus diarrhea. Analysis of vaccine efficacy against rotavirus episodes of any severity in which there was some degree of dehydration or when health services were utilized. Serotype G1 or G2 rotavirus strains were most prevalent during surveillance. Neither serotype G1 or serotype G2 vaccine were protective against serotype 1 or 2 rotavirus diarrhea, respectively. The serotype G2 vaccine was 84% protective against serotype 1 and 2 dehydrating rotavirus diarrhea in the small numbers of individuals evaluated. We conclude that one dose of 10(4) p.f.u of the RRV, serotype G1, or serotype G2 rotavirus vaccine failed to induce either an adequate serotype-specific seroresponse or serotype-specific protection in children against rotavirus diarrhea mainly of serotype G1 specificity. Future studies need to explore whether higher vaccine dose and/or more than one dose would increase the immunogenicity and efficacy of the rotavirus vaccine, especially in developing countries with a high level of baseline rotavirus antibodies. C1 JOHNS HOPKINS UNIV,SCH HYG & PUBL HLTH,DEPT INT HLTH,BALTIMORE,MD. NIAID,NIH,INFECT DIS LAB,BETHESDA,MD. RP Lanata, CF (reprint author), INST INVEST NUTR,AP 18-0191,LIMA 18,PERU. OI Black, Robert/0000-0001-9926-7984 NR 30 TC 19 Z9 20 U1 0 U2 1 PU BUTTERWORTH-HEINEMANN LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, OXON, ENGLAND OX5 1GB SN 0264-410X J9 VACCINE JI Vaccine PD FEB PY 1996 VL 14 IS 3 BP 237 EP 243 DI 10.1016/0264-410X(95)00132-K PG 7 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA UD336 UT WOS:A1996UD33600010 PM 8920706 ER PT J AU Biggar, RJ Taylor, ME Neel, JV Hjelle, B Levine, PH Black, FL Shaw, GM Sharp, PM Hahn, BH AF Biggar, RJ Taylor, ME Neel, JV Hjelle, B Levine, PH Black, FL Shaw, GM Sharp, PM Hahn, BH TI Genetic variants of human T-lymphotropic virus type II in American Indian groups SO VIROLOGY LA English DT Article ID COMPLETE NUCLEOTIDE-SEQUENCE; HTLV-II; UNITED-STATES; INFECTION; ISOLATE AB The human T-lymphotropic virus type II (HTLV-II) is found in many New World Indian groups in North and South America and may have entered the New World from Asia with the earliest migration of ancestral Amerindians over 15,000 years ago. To characterize the phylogenetic relationships of HTLV-II strains infecting geographically diverse Indian populations, we used polymerase chain reaction to amplify HTLV-II sequences from lymphocytes of seropositive Amerindians from Brazil (Kraho, Kayapo, and Kaxuyana), Panama (Guaymi), and the United States (the Navajo and Pueblo tribes of the southwestern states and the Seminoles of Florida). Sequence analysis of a 780-base pair fragment (located between the env gene and the second exons of tax/rex) revealed that Amerindian viruses clustered in the same two genetic subtypes (IIa and IIb) previously identified for viruses from intravenous drug users. Most infected North and Central American Indians had subtype Ilb, while HTLV-II infected members of three remote Amazonian tribes clustered as a distinct group within subtype IIa. These findings suggest that the ancestral Amerindians migrating to the New World brought at least two genetic subtypes, IIa and IIb. Because HTLV-II strains from Amazonian Indians form a distinct group within subtype HTLV-IIa, these Brazilian tribes are unlikely to be the source of IIa viruses in North American drug users. Finally, the near identity of viral sequences from geographically diverse populations indicate that HTLV-II is a very ancient virus of man. (C) 1996 Academic Press. Inc C1 NCI, VIRAL EPIDEMIOL BRANCH, BETHESDA, MD 20892 USA. UNIV ALABAMA, DEPT MED, BIRMINGHAM, AL 35294 USA. UNIV ALABAMA, DEPT MICROBIOL, BIRMINGHAM, AL 35294 USA. UNIV MICHIGAN, DEPT HUMAN GENET, ANN ARBOR, MI 48109 USA. UNIV NEW MEXICO, DEPT PATHOL, ALBUQUERQUE, NM 87131 USA. YALE UNIV, SCH MED, DEPT EPIDEMIOL, NEW HAVEN, CT 06510 USA. UNIV NOTTINGHAM, QUEENS MED CTR, DEPT GENET, NOTTINGHAM NG7 2RD, ENGLAND. RI Sharp, Paul/F-5783-2010 OI Sharp, Paul/0000-0001-9771-543X FU NIAID NIH HHS [P30-AI-27767] NR 33 TC 31 Z9 34 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0042-6822 J9 VIROLOGY JI Virology PD FEB 1 PY 1996 VL 216 IS 1 BP 165 EP 173 DI 10.1006/viro.1996.0043 PG 9 WC Virology SC Virology GA TU782 UT WOS:A1996TU78200016 PM 8614983 ER PT J AU Keller, SL Gruner, SM Gawrisch, K AF Keller, SL Gruner, SM Gawrisch, K TI Small concentrations of alamethicin induce a cubic phase in bulk phosphatidylethanolamine mixtures SO BIOCHIMICA ET BIOPHYSICA ACTA-BIOMEMBRANES LA English DT Article DE alamethicin; cubic phase; lipid-protein interaction ID N-METHYLATED DIOLEOYLPHOSPHATIDYLETHANOLAMINE; HEXAGONAL-HII PHASE; MODEL ION CHANNELS; MEMBRANES; GRAMICIDIN; TRANSITION; BEHAVIOR AB Under normal conditions, excess water dispersions of liquid crystalline 1,2-dielaidoyl-sn-glycero-3-phosphoethanolamine (DEPE) are known to convert from a liquid crystalline lamellar (L(alpha)) to inverse hexagonal (H-II) phase at about 60 degrees C. The nonlamellar phase behavior of lipid systems is also known to depend on the monolayer spontaneous curvature. The single-channel activity of alamethicin in black lipid bilayer membranes has been shown to be dependent upon the lipid composition of the membrane. Since the monolayer spontaneous curvature properties (e.g., the monolayer spontaneous curvature, curvature coefficients and bilayer thickness) vary with lipid composition, the single-channel activity of alamethicin presumably also correlates with the monolayer spontaneous curvature properties, Accordingly, we reasoned that if alamethicin couples to the curvature properties of a lipid film, then the curvature properties must, in turn, be perturbed by the presence of alamethicin and that this perturbation should be observable in the lipid phase behavior. Here X-ray diffraction and NMR are used to show that the presence of as little as 1% alamethicin introduces a large region of cubic phase into the thermal phase diagram. This suggests that perturbation of the nonlamellar phase behavior of a lipid system may be a method to survey different channel-forming molecules for possible behavior that indicates that the ion channel is sensitive to the monolayer spontaneous curvature properties. C1 PRINCETON UNIV,DEPT PHYS,PRINCETON,NJ 08544. NIAAA,NIH,BETHESDA,MD 20892. RI Gruner, Sol/G-2924-2010 OI Gruner, Sol/0000-0002-1171-4426 FU NIGMS NIH HHS [GM32614] NR 31 TC 83 Z9 84 U1 0 U2 7 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0005-2736 J9 BBA-BIOMEMBRANES JI Biochim. Biophys. Acta-Biomembr. PD JAN 31 PY 1996 VL 1278 IS 2 BP 241 EP 246 DI 10.1016/0005-2736(95)00229-4 PG 6 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA TW348 UT WOS:A1996TW34800013 PM 8593282 ER PT J AU Matsuoka, N Aigner, TG AF Matsuoka, N Aigner, TG TI Cholinergic-glutamatergic interactions in visual recognition memory of rhesus monkeys SO NEUROREPORT LA English DT Article DE acetylcholine; NMDA receptors; glutamate; recognition memory; monkeys; scopolamine; MK-801 ID LONG-TERM POTENTIATION; IBOTENIC-ACID LESIONS; RAT HIPPOCAMPUS; ACETYLCHOLINE; PHYSOSTIGMINE; SCOPOLAMINE; IMPAIRMENT; FOREBRAIN; RECEPTORS; RELEASE AB ADMINISTRATION Of either a non-competitive N-methyl-D-aspartate (NMDA) receptor antagonist, MK-801 (dizocilpine), or a muscarinic antagonist, scopolamine, produces dose-related impairments in performance of a visual recognition memory task, delayed non-matching to sample (DNMS) with lists of 20 symbols, in rhesus monkeys. In the present study, low doses of these two drugs, which were ineffective when given alone, significantly impaired performance when given in combination. Moreover, the effect was greater than additive, indicating a synergistic interaction. These results suggest that interactions between cholinergic and glutamatergic systems play an important role in regulation of visual recognition memory. C1 NIMH, NEUROPSYCHOL LAB, BETHESDA, MD 20892 USA. FUJISAWA PHARMACEUT CO LTD, EXPLORATORY RES LABS, TSUKUBA, IBARAKI 30026, JAPAN. NR 24 TC 23 Z9 23 U1 3 U2 3 PU RAPID SCIENCE PUBLISHERS PI LONDON PA 2-6 BOUNDARY ROW, LONDON, ENGLAND SE1 8NH SN 0959-4965 J9 NEUROREPORT JI Neuroreport PD JAN 31 PY 1996 VL 7 IS 2 BP 565 EP 568 DI 10.1097/00001756-199601310-00045 PG 4 WC Neurosciences SC Neurosciences & Neurology GA UC299 UT WOS:A1996UC29900045 PM 8730830 ER PT J AU Hamel, E Lin, CM Flynn, E DAmato, RJ AF Hamel, E Lin, CM Flynn, E DAmato, RJ TI Interactions of 2-methoxyestradiol, an endogenous mammalian metabolite, with unpolymerized tubulin and with tubulin polymers SO BIOCHEMISTRY LA English DT Article ID COLCEMID-BINDING; COLCHICINE SITE; BRAIN; INHIBITION; POLYMERIZATION; MICROTUBULES; MECHANISM; INVITRO; LIGAND; PROBE AB 2-Methoxyestradiol (2ME) is an endogenous mammalian catabolite of estradiol with antimitotic activity. Although it is a competitive inhibitor of the binding of colchicine to tubulin, it has unusual effects on glutamate-induced tubulin polymerization. Polymer that was little changed in morphology assembled at a reduced rate and was relatively cold stable. We have now examined interactions of [4-H-3]2ME with unpolymerized tubulin and polymer. The [H-3]2ME binds avidly to tubulin even on ice, and it is readily displaced by other colchicine site drugs. An association rate constant on ice of 1.9 x 10(2) M(-1)s(-1) was obtained. Scatchard analysis indicated a single class of binding site and an association equilibrium constant of 5.7 x 10(5) M(-1). These values lead to a calculated dissociation rate constant of 3.3 x 10(-4) s(-1). In glutamate-induced tubulin assembly, a reaction that requires GTP and leads to the formation of sheets of parallel protofilaments, increasing amounts of [H-3]2ME were incorporated into polymer, reaching near-stoichiometry with tubulin at 100 mu M 2ME. Equivalent binding of [H-3]2ME occurred when the drug was added to preformed polymer, but binding of [H-3]2ME to polymer was not readily inhibited by colchicine site drugs. Significant amounts of [3H]2ME were also incorporated into microtubule polymer formed with microtubule-associated proteins, glycerol, or 4-morpholineethanesulfonate buffer, but the stoichiometry was substantially lower than that in the sheet polymer induced by either glutamate or 1,4-piperazineethanesulfonate buffer. The structural differences between the microtubule and sheet polymers leading to these differences in apparent affinity for 2ME are unknown, but presumably interaction of the estrogen metabolite with cellular microtubules has functional significance related to the antimitotic properties of the compound. C1 HARVARD UNIV,SCH MED,CHILDRENS HOSP,DEPT SURG RES,BOSTON,MA 02115. RP Hamel, E (reprint author), NATL CANC INST,DIV CANC TREATMENT,DEV THERAPEUT PROGRAM,MOLEC PHARMACOL LAB,BLDG 37,ROOM 5C25,BETHESDA,MD 20892, USA. NR 35 TC 81 Z9 84 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 JAN 30 PY 1996 VL 35 IS 4 BP 1304 EP 1310 DI 10.1021/bi951559s PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA TT375 UT WOS:A1996TT37500025 PM 8573587 ER PT J AU Podgor, MJ Hiller, R AF Podgor, MJ Hiller, R TI Associations of types of lens opacities between and within eyes of individuals: An application of second-order generalized estimating equations SO STATISTICS IN MEDICINE LA English DT Article ID CORRELATED BINARY REGRESSION; ODDS-RATIO; MODELS; CATARACTS; DISEASE AB The lens opacity characteristics of individuals constitute multivariate data. Our goal was to estimate the associations between the three main types of age-related lens opacities (nuclear, cortical, posterior subcapsular) both between and within eyes of individuals using cross-sectional data from the Framingham (Massachusetts) Eye Studies. We describe use of a recently proposed extension of the generalized estimating equations approach to marginal logistic models (GEE2), and we demonstrate that a variety of research problems can be investigated with this methodology. For example, in our data, there were strong associations of the same opacity types between the two eyes of individuals and weak associations between different types of opacities. We also note that estimation of such associations may be limited in other epidemiologic settings. C1 BOSTON UNIV,BOSTON,MA 02215. JOSLIN DIABET CTR,BOSTON,MA 02215. NHLBI,FRAMINGHAM,MA. RP Podgor, MJ (reprint author), NEI,DIV BIOMETRY & EPIDEMIOL,BLDG 31,ROOM 6A52,31 CTR DR,MSC 2510,BETHESDA,MD 20892, USA. FU NEI NIH HHS [N01-EY-9-2109, N01-EY-6-2105] NR 27 TC 9 Z9 9 U1 0 U2 0 PU JOHN WILEY & SONS LTD PI W SUSSEX PA BAFFINS LANE CHICHESTER, W SUSSEX, ENGLAND PO19 1UD SN 0277-6715 J9 STAT MED JI Stat. Med. PD JAN 30 PY 1996 VL 15 IS 2 BP 145 EP 156 DI 10.1002/(SICI)1097-0258(19960130)15:2<145::AID-SIM150>3.0.CO;2-1 PG 12 WC Mathematical & Computational Biology; Public, Environmental & Occupational Health; Medical Informatics; Medicine, Research & Experimental; Statistics & Probability SC Mathematical & Computational Biology; Public, Environmental & Occupational Health; Medical Informatics; Research & Experimental Medicine; Mathematics GA TP247 UT WOS:A1996TP24700003 PM 8614751 ER PT J AU Savory, J Huang, Y Herman, MM Wills, MR AF Savory, J Huang, Y Herman, MM Wills, MR TI Quantitative image analysis of temporal changes in tau and neurofilament proteins during the course of acute experimental neurofibrillary degeneration; Non-phosphorylated epitopes precede phosphorylation SO BRAIN RESEARCH LA English DT Article DE neurofibrillary degeneration and phosphorylation sequence; quantitative image analysis; Al maltolate; rabbit ID ALZHEIMERS-DISEASE; ALUMINUM MALTOL; RABBITS; ANTIBODIES AB Perturbation of the neuronal cytoskeleton represents an integral feature of neurofibrillary tangles which are characteristic neuropathological findings seen in Alzheimer's disease. Microtubule associated protein tau (tau) is considered to be the major component of these lesions although neurofilament proteins also are present. The present study explores the formation of intraneuronal tan and neurofilament protein aggregates using intracisternal administration of aluminum maltolate to rabbits. The time course of the formation of these aggregates and subsequent phosphorylation have been investigated by immunohistochemical methods using a panel of monoclonal antibodies, with quantitation of the staining by image analysis. Neurofilament proteins begin to aggregate by day 1 following aluminum maltolate injection on day 0. Increases in non-phosphorylated neurofilament proteins are observed first, with phosphorylated epitopes being recognized by day 3. Tau follows a similar pattern in that non-phosphorylated epitopes appear to precede phosphorylation. The monoclonal antibody Alz-50 which recognizes a phosphorylation-independent epitope of tau in Alzheimer's disease paired helical filaments, demonstrates positivity in the aluminum maltolate-treated rabbits by day 3. Other tau monoclonal antibodies which recognize phosphorylated tau in paired helical filaments (AT8 and PHF-1) show positive immunostaining on days 6-8. These results indicate that intraneuronal aggregation of cytoskeletal proteins can be initiated by factors other than phosphorylation. However, phosphorylation occurring as a secondary event probably contributes to stabilization of the aggregates. C1 UNIV VIRGINIA,HLTH SCI CTR,DEPT INTERNAL MED,CHARLOTTESVILLE,VA 22903. UNIV VIRGINIA,HLTH SCI CTR,DEPT BIOCHEM,CHARLOTTESVILLE,VA 22903. NIMH,NIH,NEUROSCI CTR ST ELIZABETHS,CLIN BRAIN DISORDERS BRANCH,NEUROPATHOL SECT,WASHINGTON,DC. RP Savory, J (reprint author), UNIV VIRGINIA,HLTH SCI CTR,DEPT PATHOL,CHARLOTTESVILLE,VA 22903, USA. NR 24 TC 32 Z9 32 U1 0 U2 4 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0006-8993 J9 BRAIN RES JI Brain Res. PD JAN 29 PY 1996 VL 707 IS 2 BP 272 EP 281 DI 10.1016/0006-8993(95)01264-8 PG 10 WC Neurosciences SC Neurosciences & Neurology GA TV823 UT WOS:A1996TV82300016 PM 8919305 ER PT J AU Lanczycki, CJ DasSarma, S AF Lanczycki, CJ DasSarma, S TI Dynamical scaling and phase separation in growth models with a diffusion bias SO PHYSICAL REVIEW LETTERS LA English DT Article ID SURFACE-DIFFUSION; KINETIC GROWTH; CONTINUUM AB We study stochastic Monte Carlo solid-on-solid growth on one-dimensional substrates in the presence of two types of diffusion barriers near a step edge, termed reflection and edge barriers. In both cases we observe two-exponent dynamical scaling over three decades in time. Growth including a strong (vanishing) reflection barrier exhibits a globally faceted (Rat) phase, while at intermediate barrier values the two phases coexist in the saturated morphology. With an edge barrier, coarsening stops after some time, and the morphologies exhibit wavelength selection. C1 NIH,DIV COMP RES & TECHNOL,BETHESDA,MD 20892. RP Lanczycki, CJ (reprint author), UNIV MARYLAND,DEPT PHYS,COLLEGE PK,MD 20742, USA. RI Das Sarma, Sankar/B-2400-2009 OI Das Sarma, Sankar/0000-0002-0439-986X NR 18 TC 17 Z9 17 U1 0 U2 2 PU AMERICAN PHYSICAL SOC PI COLLEGE PK PA ONE PHYSICS ELLIPSE, COLLEGE PK, MD 20740-3844 USA SN 0031-9007 J9 PHYS REV LETT JI Phys. Rev. Lett. PD JAN 29 PY 1996 VL 76 IS 5 BP 780 EP 783 DI 10.1103/PhysRevLett.76.780 PG 4 WC Physics, Multidisciplinary SC Physics GA TR740 UT WOS:A1996TR74000016 ER PT J AU Lee, HY Murata, J Clair, T Polymeropoulos, MH Torres, R Manrow, RE Liotta, LA Stracke, ML AF Lee, HY Murata, J Clair, T Polymeropoulos, MH Torres, R Manrow, RE Liotta, LA Stracke, ML TI Cloning, chromosomal localization, and tissue expression of autotaxin from human teratocarcinoma cells SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article ID AMINO-ACID-SEQUENCE; NUCLEOTIDE PYROPHOSPHATASE; LINE; DIFFERENTIATION; IDENTIFICATION; PURIFICATION; INVITRO; SURFACE; PC-1 AB Autotaxin. a potent human tumor cell motility-stimulating exophosphodiesterase, was isolated and cloned from the human teratocarcinoma cell line NTera2D1. The deduced amino acid sequence for the teratocarcinoma autotaxin has 94% identity to the melanoma-derived protein, 90% identity to rat brain phosphodiesterase I/nucleotide pyrophosphatase (PD-I alpha), and 44% identity to the plasma cell membrane marker PC-1. Utilizing polymerase chain reaction screening of the CEPH YAC library, we localized the autotaxin gene to human chromosome 8q23-24. Northern blot analysis of relative mRNA from multiple human tissues revealed that autoraxin mRNA steady state expression is most abundant in brain, placenta, ovary, and small intestine. (C) 1996 Academic Press, Inc. C1 NIH,NATL CTR HUMAN GENOME RES,BETHESDA,MD 20892. RP Lee, HY (reprint author), NCI,PATHOL LAB,BLDG 10,BETHESDA,MD 20892, USA. NR 16 TC 79 Z9 84 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 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD JAN 26 PY 1996 VL 218 IS 3 BP 714 EP 719 DI 10.1006/bbrc.1996.0127 PG 6 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA TT598 UT WOS:A1996TT59800013 PM 8579579 ER PT J AU Hwang, M Ahn, CH Pine, PS Yin, JJ Hrycyna, CA Licht, T Aszalos, A AF Hwang, M Ahn, CH Pine, PS Yin, JJ Hrycyna, CA Licht, T Aszalos, A TI Effect of combination of suboptimal, concentrations of p-glycoprotein blockers on the proliferation of MDR1 gene expressing cells SO INTERNATIONAL JOURNAL OF CANCER LA English DT Article ID EHRLICH ASCITES TUMOR; MULTIDRUG-RESISTANCE; CREMOPHOR-EL; DAUNORUBICIN; VERAPAMIL; REVERSAL; DRUGS; CONFORMATION; TRANSPORTER; MEMBRANES AB Pharmacologically active in vivo doses of P-glycoprotein (Pgp) blockers, specifically verapamil, Cremophor EL and PSC833 cause toxicity in addition to that from the concomitantly used cancer chemotherapeutic drugs. It was shown before that these blockers cause different types of toxicities in vivo. We found that these 3 chemically distinct Pgp blockers exert different biophysical effects on the membranes of L1210 MDR cells. They also affect the general metabolism of these cells differently, but all block affinity labeling of Pgp. We could also show that the combination of suboptimal doses of these blockers can restore the uptake of the Pgp substrate rhodamine 123 into L1210MDR, 3T3MDR and KB-VI cells and can reduce the survival rate of these cells when treated in combination with daunorubicin. Our results suggest that the combination of suboptimal doses of these Pgp blockers may be advantageous in clinical practice. (C) 1996 Wiley-Liss, Inc.* C1 US FDA,CTR DRUG EVALUAT & RES,WASHINGTON,DC 20204. US FDA,CTR FOOD SAFETY & NUTR,WASHINGTON,DC 20204. NCI,MOLEC BIOL LAB,BETHESDA,MD 20892. NCI,CELL BIOL LAB,BETHESDA,MD 20892. RI Yin, Jun Jie /E-5619-2014 NR 31 TC 26 Z9 26 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0020-7136 J9 INT J CANCER JI Int. J. Cancer PD JAN 26 PY 1996 VL 65 IS 3 BP 389 EP 397 DI 10.1002/(SICI)1097-0215(19960126)65:3<389::AID-IJC19>3.0.CO;2-5 PG 9 WC Oncology SC Oncology GA TT513 UT WOS:A1996TT51300019 PM 8575863 ER PT J AU Muller, M Bakos, E Welker, E Varadi, A Germann, UA Gottesman, MM Morse, BS Roninson, IB Sarkadi, B AF Muller, M Bakos, E Welker, E Varadi, A Germann, UA Gottesman, MM Morse, BS Roninson, IB Sarkadi, B TI Altered drug-stimulated ATPase activity in mutants of the human multidrug resistance protein SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID NUCLEOTIDE-BINDING DOMAIN; PURIFIED P-GLYCOPROTEIN; ESCHERICHIA-COLI; INSECT CELLS; MDR1; TRANSPORTER; EXPRESSION; MUTATIONS; GENE; RECONSTITUTION AB The characteristics of P-glycoprotein (MDR1), an ATP-dependent drug extrusion pump responsible for the multidrug resistance of human cancer, were investigated in an in vitro expression system. The wild-type and several mutants of the human MDR1 cDNA were engineered into recombinant baculoviruses and the mutant proteins were expressed in Sf9 insect cells. In isolated cell membrane preparations of the virus-infected cells the MDR1-dependent drug-stimulated ATPase activity, and 8-azido-ATP binding to the MDR1 protein were studied. We found that when lysines 433 and/or 1076 were replaced by methionines in the ATP-binding domains, all these mutations abolished drug-stimulated ATPase activity independent of the MgATP concentrations applied. Photoaffinity labeling with 8-azido-ATP showed that the double lysine mutant had a decreased ATP-binding affinity. In the MDR1 mutant containing a Gly(185) to Val replacement we found no significant alteration in the maximum activity of the MDR1-ATPase or in its activation by verapamil and vinblastine, and this mutation did not modify the MgATP affinity or the 8-azido-ATP binding of the transporter either. However, the Gly(185) to Val mutation significantly increased the stimulation of the MDR1-ATPase by colchicine and etoposide, while slightly decreasing its stimulation by vincristine. These shifts closely correspond to the effects of this mutation on the drug-resistance profile, as observed in tumor cells. These data indicate that the Sf9-baculovirus expression system for MDR1 provides an efficient tool for examining structure-function relationships and molecular characteristics of this clinically important enzyme. C1 NATL INST HAEMATOL BLOOD TRANSFUS & IMMUNOL,H-1113 BUDAPEST,HUNGARY. HUNGARIAN ACAD SCI,BIOL RES CTR,INST ENZYMOL,H-1113 BUDAPEST,HUNGARY. NCI,BETHESDA,MD 20892. UNIV ILLINOIS,CHICAGO,IL 60612. RI Varadi, Andras/A-2055-2012; Sarkadi, Balazs/I-5024-2013 NR 40 TC 131 Z9 131 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 JAN 26 PY 1996 VL 271 IS 4 BP 1877 EP 1883 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA TR320 UT WOS:A1996TR32000015 PM 8567633 ER PT J AU Olive, M Williams, SC Dezan, C Johnson, PF Vinson, C AF Olive, M Williams, SC Dezan, C Johnson, PF Vinson, C TI Design of a C/EBP-specific, dominant-negative bZIP protein with both inhibitory and gain-of-function properties SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID DNA-BINDING PROTEINS; LEUCINE ZIPPER PROTEINS; TRANSCRIPTION FACTOR; ALBUMIN GENE; ACTIVATOR PROTEIN; MAMMALIAN-CELLS; NUCLEAR-PROTEIN; MESSENGER-RNA; EXPRESSION; FAMILY AB We have developed a bZIP protein, GBF-F, with both dominant-negative (DN) and gain-of-function properties, GBF-F is a chimera consisting of two components: the DNA binding (basic) region from the plant bZIP protein GBF-1 (GBF) and a leucine zipper (F) designed to preferentially heterodimerize with the C/EBP alpha leucine zipper. Biochemical studies show that GBF-F preferentially forms heterodimers with C/EBP alpha and thus binds a chimeric DNA sequence composed of the half-sites recognized by the C/EBP and GBF basic regions. Transient transfections in HepG2 hepatoma cells show that both components of GBF-F are necessary for inhibition of C/EBP alpha transactivation. When the C/EBP alpha leucine zipper is replaced with that of either GCN4 or VBP, the resulting protein can transactivate a C/EBP cis-element but is not inhibited by GBF-F, indicating that the specificity of dominant-negative action is determined by the leucine zipper. All known members of the C/EBP family contain similar leucine zipper regions and are inhibited by GBF-F, GBF-F also exhibits gain-of-function properties, since, with the essential cooperation of a C/EBP family member, it can transactivate a promoter containing the chimeric C/EBP\GBF site. This protein therefore has potential utility both as a dominant-negative inhibitor of C/EBP function and as an activator protein with novel DNA sequence specificity. C1 NCI,BIOCHEM LAB,BETHESDA,MD 20892. NCI,FREDERICK CANC RES & DEV CTR,ABL BASIC RES PROGRAM,FREDERICK,MD 21702. RI Johnson, Peter/A-1940-2012 OI Johnson, Peter/0000-0002-4145-4725 NR 62 TC 46 Z9 46 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 JAN 26 PY 1996 VL 271 IS 4 BP 2040 EP 2047 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA TR320 UT WOS:A1996TR32000039 PM 8567657 ER PT J AU Levy, DD Magee, AD Namiki, C Seidman, MM AF Levy, DD Magee, AD Namiki, C Seidman, MM TI The influence of single base changes on UV mutational activity at two translocated hotspots SO JOURNAL OF MOLECULAR BIOLOGY LA English DT Article DE mutation hotspots; sequence context ID SHUTTLE VECTOR PLASMID; ESCHERICHIA-COLI; SEQUENCE SPECIFICITY; MAMMALIAN-CELLS; POINT MUTATIONS; EXCISION REPAIR; STRAND BIAS; HOT-SPOTS; LACI GENE; DNA AB Mutation hotspots have been a staple of mutation spectra since the introduction of fine structure mutation mapping almost 40 years ago. It has been well established that sequence context is an important determinant of mutational activity at mutagen induced hotspots and coldspots. However, our understanding of the sequence effecters of base substitution hotspots is quite limited. This is because manipulation of the sequence about a hotspot site in a marker gene is restricted by the need to maintain a functional marker. In this work, we describe a generalizable system for studying sequence context effects on mutagenesis. We have prepared a variant of the supF tRNA gene (a marker used by us in previous studies) in which an eight-base palindrome, the site of two UV hotspots in the interior of the gene, was copied into the acceptor stem and pre-tRNA region. The variant tRNA was active. The UV mutation spectrum of this variant showed that the new copy of the palindrome generated two hotspots which were as intense as the original sites in the interior of the gene. Variant genes were constructed with all possible bases at the first position in the palindrome in the pre-tRNA sequence, which does not affect tRNA function. The mutation analysis showed that activity at one of the hotspots could be reduced or enhanced by the changes, while activity at the other site was not significantly affected. The base changes did not influence the frequency of cyclobutane dimer or (6-4) photoproduct formation at the two hotspot sites. Thus, the changes in mutational activity were due to the influence of sequence context on the efficiency of mutation formation at the sites of UV lesions. (C) 1996 Academic Press Limited C1 ONCOR PHARMACEUT,GAITHERSBURG,MD 20877. NCI,MOLEC CARCINOGENESIS LAB,BETHESDA,MD 20892. NR 51 TC 19 Z9 19 U1 0 U2 0 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 JAN 26 PY 1996 VL 255 IS 3 BP 435 EP 445 DI 10.1006/jmbi.1996.0036 PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA TQ242 UT WOS:A1996TQ24200010 PM 8568888 ER PT J AU Linnen, J Wages, J ZhangKeck, ZY Fry, KE Krawczynski, KZ Alter, H Koonin, E Gallagher, M Alter, M Hadziyannis, S Karayiannis, P Fung, K Nakatsuji, Y Shih, JWK Young, L Piatak, M Hoover, C Fernandez, J Chen, S Zou, JC Morris, T Hyams, KC Ismay, S Lifson, JD Hess, G Foung, SKH Thomas, H Bradley, D Margolis, H Kim, JP AF Linnen, J Wages, J ZhangKeck, ZY Fry, KE Krawczynski, KZ Alter, H Koonin, E Gallagher, M Alter, M Hadziyannis, S Karayiannis, P Fung, K Nakatsuji, Y Shih, JWK Young, L Piatak, M Hoover, C Fernandez, J Chen, S Zou, JC Morris, T Hyams, KC Ismay, S Lifson, JD Hess, G Foung, SKH Thomas, H Bradley, D Margolis, H Kim, JP TI Molecular cloning and disease association of hepatitis G virus: A transfusion-transmissible agent SO SCIENCE LA English DT Article ID NON-B-HEPATITIS; C VIRUS; NON-A; CDNA LIBRARIES; ANTIBODY; RNA; IDENTIFICATION; CONSTRUCTION; PROTEINASE; SEQUENCES AB An RNA virus, designated hepatitis G virus (HGV), was identified from the plasma of a patient with chronic hepatitis. Extension from an immunoreactive complementary DNA clone yielded the entire genome (9392 nucleotides) encoding a polyprotein of 2873 amino acids. The virus is closely related to GB virus C (GBV-C) and distantly related to hepatitis C virus, GBV-A, and GBV-B. HGV was associated with acute and chronic hepatitis. Persistent viremia was detected for up to 9 years in patients with hepatitis. The virus is transfusion-transmissible. It has a global distribution and is present within the volunteer blood donor population in the United States. C1 GENELABS TECHNOL,REDWOOD CITY,CA 94063. CTR DIS CONTROL & PREVENT,HEPATITIS BRANCH,ATLANTA,GA 30333. NIH,DEPT TRANSFUS MED,BETHESDA,MD 20205. NATL LIB MED,NATL CTR BIOTECHNOL INFORMAT,BETHESDA,MD 20894. HIPPOKRATEION HOSP,ACAD DEPT MED,ATHENS,GREECE. ST MARYS HOSP,SCH MED,DEPT MED,LONDON,ENGLAND. USN,MED RES INST,ROCKVILLE,MD 20852. NEW S WALES RED CROSS BLOOD TRANSFUS SERV,SYDNEY,NSW,AUSTRALIA. BOEHRINGER MANNHEIM GMBH,D-68305 MANNHEIM,GERMANY. RI Thomas, Howard/A-3152-2009 NR 31 TC 1249 Z9 1330 U1 0 U2 15 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 SN 0036-8075 J9 SCIENCE JI Science PD JAN 26 PY 1996 VL 271 IS 5248 BP 505 EP 508 DI 10.1126/science.271.5248.505 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA TR322 UT WOS:A1996TR32200042 PM 8560265 ER PT J AU Vito, P Lacana, E DAdamio, L AF Vito, P Lacana, E DAdamio, L TI Interfering with apoptosis: Ca2+-binding protein ALG-2 and Alzheimer's disease gene ALG-3 SO SCIENCE LA English DT Article ID FIBROBLAST GROWTH-FACTOR; T-CELL HYBRIDOMAS; DNA FRAGMENTATION; ENDONUCLEASE ACTIVATION; THYMOCYTE APOPTOSIS; IMMATURE THYMOCYTES; SUICIDE PROCESS; MESSENGER-RNA; DEATH; INITIATION AB Two apoptosis-linked genes, named ALG-2 and ALG-3, were identified by means of a functional selection strategy. ALG-2 codes for a Ca2+-binding protein required for T cell receptor-, Fas-, and glucocorticoid-induced cell death. ALG-3, a partial complementary DNA that is homologous to the familial Alzheimer's disease gene STM2, rescues a T cell hybridoma from T cell receptor- and Fas-induced apoptosis. These findings suggest that ALG-2 may mediate Ca2+-regulated signals along the death pathway and that cell death may play a role in Alzheimer's disease. C1 NIAID,CELLULAR & MOLEC IMMUNOL LAB,T CELL MOLEC BIOL UNIT,BETHESDA,MD 20892. NR 55 TC 416 Z9 421 U1 2 U2 12 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 SN 0036-8075 J9 SCIENCE JI Science PD JAN 26 PY 1996 VL 271 IS 5248 BP 521 EP 525 DI 10.1126/science.271.5248.521 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA TR322 UT WOS:A1996TR32200047 PM 8560270 ER PT J AU Gatley, SJ Volkow, ND Chen, RY Fowler, JS Carroll, FI Kuhar, MJ AF Gatley, SJ Volkow, ND Chen, RY Fowler, JS Carroll, FI Kuhar, MJ TI Displacement of RTI-55 from the dopamine transporter by cocaine SO EUROPEAN JOURNAL OF PHARMACOLOGY LA English DT Article DE [I-123]RTI-55; cocaine analog; psychostimulant abuse; (mouse) ID I-125 RTI-55; SEROTONIN TRANSPORTERS; UPTAKE SITES; BETA-CIT; AFFINITY; BINDING; BRAIN; INVIVO; AUTORADIOGRAPHY; PHARMACOLOGY AB The cocaine analog 3 beta-(4-iodophenyl)tropane-2 beta-carboxylic acid methyl ester (RTI-55 or beta CIT) has a higher affinity for the dopamine transporter and may be potentially useful in interfering with cocaine's actions in brain. However, imaging studies have demonstrated displacement of tracer doses of [I-123]RTI-55 by a subsequent dose of cocaine. Similar displacement of pharmacological doses of RTI-55 might compromize therapy with RTI-55 in cocaine abuse. The reduction in dopamine transporter availability, assessed in vivo in mouse striatum using [H-3]cocaine, caused by pretreatment with RTI-55 was significantly mitigated by subsequent administration of cocaine. In a similar experiment using a tracer dose of [I-123]RTI-55 significant reductions of striatal radioligand binding by pretreatment with cocaine or RTI-55 were not observed. These results suggest that: (1) cocaine can displace pharmacological doses of RTI-55 from striatum, and (2) radioligands used to assess binding site occupancy should have a lower affinity than the occupying drug. C1 BROOKHAVEN NATL LAB,DEPT CHEM,UPTON,NY 11973. RES TRIANGLE INST,RES TRIANGLE PK,NC 27709. NIDA,ADDICT RES CTR,NEUROSCI BRANCH,BALTIMORE,MD 21224. RP Gatley, SJ (reprint author), BROOKHAVEN NATL LAB,DEPT MED,490 BELL AVE,UPTON,NY 11973, USA. FU NIDA NIH HHS [R01DA06278] NR 34 TC 8 Z9 8 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0014-2999 J9 EUR J PHARMACOL JI Eur. J. Pharmacol. PD JAN 25 PY 1996 VL 296 IS 2 BP 145 EP 151 DI 10.1016/0014-2999(95)00698-2 PG 7 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA TU210 UT WOS:A1996TU21000004 PM 8838450 ER PT J AU Kroutil, LC Register, K Bebenek, K Kunkel, TA AF Kroutil, LC Register, K Bebenek, K Kunkel, TA TI Exonucleolytic proofreading during replication of repetitive DNA SO BIOCHEMISTRY LA English DT Article ID EXONUCLEASE ACTIVITY; FRAMESHIFT; FIDELITY; MUTAGENESIS; BACTERIOPHAGE-T4; MISALIGNMENT; POLYMERASES; MECHANISM; DEFICIENT; INVITRO AB We are attempting to understand the processes required to accurately replicate the repetitive DNA sequences whose instability is associated with several human diseases. Here we test the hypothesis that the contribution of exonucleolytic proofreading to frameshift fidelity during replication of repetitive DNA sequences diminishes as the number of repeats in the sequence increases. The error rates of proofreading-proficient T7, T4, and Pyrococcus furiosis DNA polymerases are compared to their exonuclease-deficient derivatives, for +1 and -1 base errors in homopolymeric repeat sequences of three to eight base pairs. All three exonuclease-deficient polymerases produce frameshift errors during synthesis at rates that increase as a function of run length, suggesting the involvement of misaligned intermediates. Their wild-type counterparts are all much more accurate, suggesting that the majority of the intermediates are corrected by proofreading. However, the contribution of the exonuclease to fidelity decreases substantially as the length of the homopolymeric run increases. For example, the exonuclease enhances the frameshift fidelity of T7 DNA polymerase in a run of three A . T base pairs by 160-fold, similar to its contribution to base substitution fidelity. However, in a run of eight consecutive A . T base pairs, the exonuclease only enhances frameshift fidelity by 7-fold. A similar pattern was observed with T4 and Pfu DNA polymerases. Thus, both polymerase selectivity and exonucleolytic proofreading efficiency are diminished during replication of repetitive sequences. This may place an increased relative burden on post-replication repair processes to reduce rates of addition and deletion mutations in organisms whose genome contains abundant simple repeat DNA sequences. C1 NIEHS, MOLEC GENET LAB, RES TRIANGLE PK, NC 27709 USA. NR 31 TC 95 Z9 95 U1 2 U2 5 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD JAN 23 PY 1996 VL 35 IS 3 BP 1046 EP 1053 DI 10.1021/bi952178h PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA TR178 UT WOS:A1996TR17800044 PM 8547240 ER PT J AU Scremin, CL Boal, JH Wilk, A Phillips, LR Beaucage, SL AF Scremin, CL Boal, JH Wilk, A Phillips, LR Beaucage, SL TI [(2-deoxy-alpha- and beta-D-erythro-pentofuranosyl)thymin-1-yl] methane derivatives as potential conformational probes for altDNA oligonucleotides SO BIOORGANIC & MEDICINAL CHEMISTRY LETTERS LA English DT Article AB The previously unknown deoxyribonucleoside analogues 2a,b have been efficiently synthesized from commercial 1-O-methyl-2-deoxy-3,5-di-O-p-toluoyl-D-erythro-pentofuranose. The conversion of these nucleosides to the phosphoramidite derivatives 13a,b and 14a,b for subsequent incorporation into oligodeoxyribonucleotide analogues is also described. C1 US FDA,CTR BIOL EVALUAT & RES,DIV HEMATOL PROD,BETHESDA,MD 20892. US FDA,CTR BIOL EVALUAT & RES,DIV ALLERGEN PROD & PARASITOL,BETHESDA,MD 20892. NCI,DEV THERAPEUT PROGRAM,LAB PHARMACEUT CHEM,FREDERICK,MD 21701. NR 11 TC 11 Z9 11 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0960-894X J9 BIOORG MED CHEM LETT JI Bioorg. Med. Chem. Lett. PD JAN 23 PY 1996 VL 6 IS 2 BP 207 EP 212 DI 10.1016/0960-894X(95)00589-L PG 6 WC Chemistry, Medicinal; Chemistry, Organic SC Pharmacology & Pharmacy; Chemistry GA TU582 UT WOS:A1996TU58200019 ER PT J AU Xu, RH Dong, ZG Maeno, M Kim, J Suzuki, A Ueno, N Sredni, D Colburn, NH Kung, HF AF Xu, RH Dong, ZG Maeno, M Kim, J Suzuki, A Ueno, N Sredni, D Colburn, NH Kung, HF TI Involvement of Ras/Raf/AP-1 in BMP-4 signaling during Xenopus embryonic development SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE activator protein 1; bone morphogenetic protein 4 ID BONE MORPHOGENETIC PROTEIN-4; MESODERM INDUCTION; VENTRALIZING FACTOR; C-JUN; CELLS; TRANSCRIPTION; EXPRESSION; ONCOGENE; FAMILY; LAEVIS AB Previously, we elucidated the role of bone morphogenetic protein 4 (BMP-4) in the dorsal-ventral patterning of the Xenopus embryo by using a dominant negative mutant of the BMP-4 receptor (DN-BR). The present paper describes the involvement of Pas, Raf, and activator protein 1 (AP-1) in BMP-4 signaling during Xenopus embryonic development, The AP-1 activity was determined by injecting an AP-1-dependent luciferase reporter gene into two-cell-stage Xenopus embryos and measuring the luciferase activity at various developmental stages. We found that injection of BMP-4 mRNA increased AP-1 activity, whereas injection of DN-BR mRNA inhibited AP-1 activity, Similar inhibitory effects were seen with injection of mRNAs encoding dominant negative mutants of c-Ha-Ras, c-Raf, or c-Jun, These results suggest that the endogenous AP-1 activity is regulated by BMP-4/Ras/Raf/Jun signals, We next investigated the effects of Ras/Raf/AP-1 signals on the biological functions of BMP-4. DN-BR-induced dorsalization of the embryo, revealed by the formation of a secondary body axis or dorsalization of the ventral mesoderm explant analyzed by histological and molecular criteria, was significantly reversed by coinjection of [Val(12)]Ha-Ras, c-Raf, or c-Jun mRNA, Furthermore, the BMP-4-stimulated erythroid differentiation in the ventral mesoderm was substantially inhibited by coinjection with the dominant negative c-Ha-Ras, c-Raf, or c-Jun mutant. Our results suggest the involvement of Ras/Raf/AP-1 in the BMP 4 signaling pathway. C1 NCI,FREDERICK CANC RES & DEV CTR,DIV BASIC SCI,LAB BIOCHEM PHYSIOL,FREDERICK,MD 21702. NCI,FREDERICK CANC RES & DEV CTR,SAIC FREDERICK,BIOL CARCINOGENESIS & DEV PROGRAM,FREDERICK,MD 21702. NCI,FREDERICK CANC RES & DEV CTR,VIRAL CARCINOGENESIS LAB,CELL BIOL SECT,FREDERICK,MD 21702. NIIGATA UNIV,FAC SCI,DEPT BIOL,NIIGATA 95021,JAPAN. HOKKAIDO UNIV,FAC PHARMACEUT SCI,SAPPORO,HOKKAIDO 060,JAPAN. BAR ILAN UNIV,INTERDISCIPLINARY DEPT,IL-52900 RAMAT GAN,ISRAEL. RI Xu, Ren-He/M-3125-2016 NR 37 TC 62 Z9 64 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 JAN 23 PY 1996 VL 93 IS 2 BP 834 EP 838 DI 10.1073/pnas.93.2.834 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA TR326 UT WOS:A1996TR32600058 PM 8570644 ER PT J AU Sullivan, SL Adamson, MC Ressler, KJ Kozak, CA Buck, LB AF Sullivan, SL Adamson, MC Ressler, KJ Kozak, CA Buck, LB TI The chromosomal distribution of mouse odorant receptor genes SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID OLFACTORY EPITHELIUM; EXPRESSION; FAMILY; MAPS AB Odorant receptors (ORs) on nasal olfactory sensory neurons are encoded by a large multigene family. Each member of the family is expressed in a small percentage of neurons that are confined to one of several spatial zones in the nose but are randomly distributed throughout that zone. This pattern of expression suggests that when the sensory neuron selects which OR gene to express it may be confined to a particular zonal gene set of several hundred OR genes but select from among the members of that set via a stochastic mechanism. Both locus-dependent and locus-independent models of OR gene choice have been proposed. To investigate the feasibility of these models, we determined the chromosomal locations of 21 OR genes expressed in four different spatial zones. We found that OR genes are clustered within multiple loci that are broadly distributed in the genome. These loci lie within paralogous chromosomal regions that appear to have arisen by duplications of large chromosomal domains followed by extensive gene duplication and divergence. Our studies show that OR genes expressed in the same zone map to numerous loci; moreover, a single locus can contain genes expressed in different zones. These findings raise the possibility that OR gene choice may be locus-independent or involve consecutive stochastic choices. C1 HARVARD UNIV,SCH MED,DEPT NEUROBIOL,BOSTON,MA 02115. NIAID,MOLEC MICROBIOL LAB,BETHESDA,MD 20892. RP Sullivan, SL (reprint author), HARVARD UNIV,SCH MED,HOWARD HUGHES MED INST,220 LONGWOOD AVE,BOSTON,MA 02115, USA. OI Ressler, Kerry/0000-0002-5158-1103 FU NIDCD NIH HHS [P01 DC000347-10, 5-F32-DC00188-01, 1-R01-DC01662-01] NR 39 TC 160 Z9 180 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 JAN 23 PY 1996 VL 93 IS 2 BP 884 EP 888 DI 10.1073/pnas.93.2.884 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA TR326 UT WOS:A1996TR32600067 PM 8570653 ER PT J AU Haxby, JV Ungerleider, LG Horwitz, B Maisog, JM Rapoport, SI Grady, CL AF Haxby, JV Ungerleider, LG Horwitz, B Maisog, JM Rapoport, SI Grady, CL TI Face encoding and recognition in the human brain SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE positron emission tomography; cerebral blood flow ID FRONTAL-LOBE LESIONS; HIPPOCAMPAL-FORMATION; MEMORY IMPAIRMENT; PET IMAGES; NEUROANATOMY; LOCALIZATION; ACTIVATION; AMNESIA; OBJECT AB A dissociation between human neural systems that participate in the encoding and later recognition of new memories for faces was demonstrated by measuring memory task-related changes in regional cerebral blood flow with positron emission tomography. There was almost no overlap between the brain structures associated with these memory functions. A region in the right hippocampus and adjacent cortex was activated during memory encoding but not during recognition, The most striking finding in neocortex was the lateralization of prefrontal participation. Encoding activated left prefrontal cortex, whereas recognition activated right prefrontal cortex. These results indicate that the hippocampus and adjacent cortex participate in memory function primarily at the time of new memory encoding. Moreover, face recognition is not mediated simply by recapitulation of operations performed at the time of encoding but, rather, involves anatomically dissociable operations. C1 NIMH,SECT NEURAL CIRCUITRY,PSYCHOL & PSYCHOPATHOL LAB,BETHESDA,MD 20892. NIA,NEUROSCI LAB,BETHESDA,MD 20892. RP Haxby, JV (reprint author), NIMH,SECT FUNCT BRAIN IMAGING,10-4C110,BETHESDA,MD 20892, USA. NR 36 TC 410 Z9 412 U1 0 U2 13 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 JAN 23 PY 1996 VL 93 IS 2 BP 922 EP 927 DI 10.1073/pnas.93.2.922 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA TR326 UT WOS:A1996TR32600075 PM 8570661 ER PT J AU Vasan, RS Benjamin, EJ Levy, D AF Vasan, RS Benjamin, EJ Levy, D TI Congestive heart failure with normal left ventricular systolic function clinical approaches to the diagnosis and treatment of diastolic heart failure SO ARCHIVES OF INTERNAL MEDICINE LA English DT Review ID CORONARY-ARTERY DISEASE; TWO-DIMENSIONAL ECHOCARDIOGRAPHY; LONG-TERM FOLLOW; PULSED DOPPLER ECHOCARDIOGRAPHY; ACUTE MYOCARDIAL-INFARCTION; NORMAL EJECTION FRACTION; ACUTE PULMONARY-EDEMA; HYPERTROPHIC CARDIOMYOPATHY; RESTRICTIVE CARDIOMYOPATHY; CONSTRICTIVE PERICARDITIS AB The syndrome of congestive heart failure with preserved left ventricular systolic function is common in clinical practice. The signs and symptoms of the disorder are similar to those of congestive heart failure with left ventricular systolic dysfunction, underscoring a need for routine evaluation of left and right ventricular systolic function in patients with congestive heart failure. The syndrome may be related to anatomic abnormalities that increase the resistance to ventricular filling, or to physiologic abnormalities of myocardial relaxation or compliance, Advancing age, often in association with hypertension, coronary artery disease, tachycardia, and atrial fibrillation, is commonly associated with the disorder. Randomized controlled clinical trials are needed to evaluate the efficacy of various therapeutic agents in reducing the risks associated with diastolic heart failure. C1 FRAMINGHAM HEART DIS EPIDEMIOL STUDY, FRAMINGHAM, MA 01701 USA. BETH ISRAEL HOSP, DIV CARDIOL, BOSTON, MA 02215 USA. BETH ISRAEL HOSP, DIV CLIN EPIDEMIOL, BOSTON, MA 02215 USA. BOSTON UNIV, SCH MED, BOSTON, MA 02118 USA. BOSTON CITY HOSP, CARDIOL SECT, BOSTON, MA USA. NHLBI, BETHESDA, MD 20892 USA. OI Ramachandran, Vasan/0000-0001-7357-5970; Benjamin, Emelia/0000-0003-4076-2336 FU NHLBI NIH HHS [N0I-HC-38038]; NINDS NIH HHS [2-ROI-NS-17950-11] NR 184 TC 106 Z9 118 U1 0 U2 1 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 0003-9926 EI 1538-3679 J9 ARCH INTERN MED JI Arch. Intern. Med. PD JAN 22 PY 1996 VL 156 IS 2 BP 146 EP 157 DI 10.1001/archinte.156.2.146 PG 12 WC Medicine, General & Internal SC General & Internal Medicine GA TP958 UT WOS:A1996TP95800006 PM 8546548 ER PT J AU Gustchina, E Rumsh, L Ginodman, L Majer, P Andreeva, N AF Gustchina, E Rumsh, L Ginodman, L Majer, P Andreeva, N TI Post X-ray crystallographic studies of chymosin: The existence of two structural forms and the regulation of activity by the interaction with the histidine-proline cluster of kappa-casein SO FEBS LETTERS LA English DT Article DE chymosin; aspartic proteinase; three-dimensional structure; chymosin specificity; chymosin activation; allosteric activator ID BOVINE CHYMOSIN; RESOLUTION; PROTEINASES; SPECIFICITY; SEQUENCES AB Calf chymosin molecules exist in the two alternative structural forms: the first one has S-1 and S-3 binding pockets occluded by its own Tyr(77) residue (the seif-inhibited form); the second has these pockets free for a substrate binding (the active form), The preliminary incubation of the enzyme with a pentapeptide corresponding to the histidine-proline duster of the specific substrate K-casein results in a 200-fold increase of the hydrolysis rate for the enzyme 'slow substrate', The result suggests that the cluster is an allosteric effector that promotes the conversion of the enzyme into the active form, These data provide the experimental ground for the explanation of chymosin specificity towards kappa-casein. C1 RUSSIAN ACAD SCI,VA ENGELHARDT MOLEC BIOL INST,MOSCOW 117984,RUSSIA. RUSSIAN ACAD SCI,SHEMYAKIN OVCHINNIKOV INST BIOORGAN CHEM,MOSCOW,RUSSIA. NCI,STRUCT BIOCHEM PROGRAM,FREDERICK,MD 21702. NR 16 TC 21 Z9 21 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0014-5793 J9 FEBS LETT JI FEBS Lett. PD JAN 22 PY 1996 VL 379 IS 1 BP 60 EP 62 DI 10.1016/0014-5793(95)01488-8 PG 3 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA TR094 UT WOS:A1996TR09400013 PM 8566230 ER PT J AU Travlos, GS Morris, RW Elwell, MR Duke, A Rosenblum, S Thompson, MB AF Travlos, GS Morris, RW Elwell, MR Duke, A Rosenblum, S Thompson, MB TI Frequency and relationships of clinical chemistry and liver and kidney histopathology findings in 13-week toxicity studies in rats SO TOXICOLOGY LA English DT Article DE liver lesions; kidney lesions; histopathological changes; morphological change; treatment-related alterations ID NATIONAL-TOXICOLOGY-PROGRAM; SAFETY EVALUATION; PATHOLOGY; ENZYMES; NEPHROTOXICITY; DIAGNOSIS AB The relative sensitivities of eight commonly used clinical chemistry end points and histopathology to detect potential toxic effects in liver and kidney were evaluated for a series of 61 13-week rat toxicity studies conducted for the National Toxicology Program. The data consisted of 1-, 2- to 3-, and 13-week clinical chemistry measurements and 13-week histopathological assessments of liver and kidney. Except for serum alkaline phosphatase, treatment-related alterations of individual clinical chemistry variables occurred in 20-48% of the studies, depending on the analyte, sampling time, and sex. Liver and kidney lesions were reported for 31% and 41% of the studies respectively. There was an association between treatment-related increases in alanine aminotransferase (ALT) and sorbitol dehydrogenase (SDH) activities and histopathological changes in the liver. SDH activity had greater positive and negative predictive values than similar changes in ALT; by week 1 in females and weeks 2-3 in both sexes, SDH predicted morphological hepatic change at study termination with 75% or better accuracy. If increases in activities of both enzymes occurred simultaneously, however, terminal histopathological changes could be predicted, in both sexes, with 75% accuracy by week 1, increasing to 100% by weeks 2-3. There also was an association between treatment-related increases in urea nitrogen (UN) and creatinine (Cre) concentrations and morphological kidney change. Cre concentration had greater positive predictive values than similar changes in UN; by weeks 2-3 in males and week 13 in both sexes, Cre predicted morphological renal change at study termination with 56% or better accuracy. UN concentration was associated and predictive of morphological kidney change only in females at week 13. Depending on time point and sex, serum alkaline phosphatase activity increased in only 5-22% of the studies, Increases in total bile acid concentration occurred in 33-48% of the studies. Because both tests are used as markers of cholestasis, this marked discrepancy was unexpected. Treatment-related decreases in alkaline phosphatase activity occurred, however, in 39-56% of the studies; serum alkaline phosphatase may be more useful as an indicator of decreased food intake (decreased activity) than of cholestasis (increased activity). In summary, treatment-related alterations of clinical chemistry and histopathology occurred frequently in this series of toxicity studies in rats. Changes in the chemistry end points also occurred frequently at interim time points, indicating that clinical chemistry evaluations can be useful for detecting potential treatment effects throughout a study. This observation is important, since histopathological evaluations are limited to animal termination and not useful for detecting transient responses or the onset of treatment-related effects. C1 ANALYT SCI INC,DURHAM,NC 27713. EXPTL PATHOL LABS INC,RES TRIANGLE PK,NC 27709. RP Travlos, GS (reprint author), NIEHS,LAB EXPTL PATHOL,POB 12233,RES TRIANGLE PK,NC 27709, USA. NR 43 TC 65 Z9 74 U1 0 U2 4 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0300-483X J9 TOXICOLOGY JI Toxicology PD JAN 22 PY 1996 VL 107 IS 1 BP 17 EP 29 DI 10.1016/0300-483X(95)03197-N PG 13 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA TV578 UT WOS:A1996TV57800003 PM 8597028 ER PT J AU Bhattacharyya, D Brooks, BR Callahan, L AF Bhattacharyya, D Brooks, BR Callahan, L TI Positioning of positively charged residues in the V3 loop correlates with HIV type 1 syncytium-inducing phenotype SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; PRINCIPAL NEUTRALIZING DETERMINANT; HEPARAN-SULFATE PROTEOGLYCANS; BIOLOGICAL PHENOTYPE; DEXTRAN SULFATE; INFECTION; DOMAIN; GP120; PROGRESSION; CAPACITY AB Although the V3 loop of the envelope glycoprotein (gp120) plays a role in determining the phenotype, pathogenesis, and tropism of human immunodeficiency virus-1 (HIV-1), there has not been any consistent correlation between structure and phenotype, Theoretically determined structures of the V3 loop of gp120, from 20 different viral strains, 10 syncytium-inducing (SI) and 10 non-syncytium-inducing (NSI) phenotype, revealed that all V3 loops from SI phenotypic strains had at least two positively charged residues in close proximity, on the same face of the loop, All of the SI phenotypic V3 loop structures were capable of forming strong divalent electrostatic interactions with disulfated sugars. The ability to form this interaction may be a determinant of the phenotype, tropism, and pathogenicity of HIV-1 viral strains, This structural motif was absent in all V3 loops from viral strains with the NSI phenotype. C1 NIH, DIV COMP RES & TECHNOL, STRUCT BIOL LAB, BETHESDA, MD 20892 USA. US PHARMACOPEIAL CONVENT INC, ROCKVILLE, MD 20852 USA. NR 47 TC 31 Z9 34 U1 0 U2 0 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 0889-2229 EI 1931-8405 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD JAN 20 PY 1996 VL 12 IS 2 BP 83 EP 90 DI 10.1089/aid.1996.12.83 PG 8 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA TV295 UT WOS:A1996TV29500001 PM 8834457 ER PT J AU Hagiwara, E Sacks, T LeitmanKlinman, SF Klinman, DM AF Hagiwara, E Sacks, T LeitmanKlinman, SF Klinman, DM TI Effect of HIV infection on the frequency of cytokine-secreting cells in human peripheral blood SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Article ID ACQUIRED IMMUNE-DEFICIENCY; HOMOSEXUAL MEN; IMMUNODEFICIENCY SYNDROME; ACTIVATION; EXPRESSION; ABNORMALITIES; INTERLEUKIN-2; RESPONSES; RECEPTOR; HELPER AB A selective decrease in type 1 cytokine secretion by in vitro stimulated peripheral blood cells is reportedly associated with disease progression in HIV-infected individuals, To examine whether a similar change in cytokine secretion occurs under physiologic conditions in vivo, sensitive and specific ELIspot assays were used to compare the phenotype and frequency of PBMC spontaneously producing interleukin (IL)-2, IL-4, IL-10, and interferon-gamma (IFN-gamma) in 83 HIV-infected subjects and 60 normal controls, Phenotypic analysis of freshly isolated cytokine-secreting cells showed that T cells were the primary source of IL-2, IL-4, and IFN-gamma while CD14(+) macrophages/monocytes were the dominant source of IL-10 in vivo, The number of peripheral blood mononuclear cells (PBMC) spontaneously secreting both type 1 and type 2 cytokines was significantly reduced in HIV-infected patients versus controls, The magnitude of this decrease did not correlate with disease severity, Changes in IL-2-secreting cell number correlated with CD4 count, while changes in the frequency of IFN-gamma-secreting cells correlated with disease duration, These findings do not support the contention that a selective reduction in type 1 cytokine production correlates with disease progression. C1 US FDA,CTR BIOL EVALUAT & RES,DIV VIRAL PROD,LAB RETROVIRAL RES,BETHESDA,MD 20892. NIH,CTR CLIN,DEPT TRANSFUS MED,BETHESDA,MD 20892. NR 44 TC 26 Z9 26 U1 0 U2 0 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 SN 0889-2229 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD JAN 20 PY 1996 VL 12 IS 2 BP 127 EP 133 DI 10.1089/aid.1996.12.127 PG 7 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA TV295 UT WOS:A1996TV29500006 PM 8834462 ER PT J AU Dunbar, C Kohn, D Karlsson, S Barton, N Brady, R CottlerFox, M Crooks, G Emmons, R Esplin, J Leitman, S Lenarsky, C Nolta, J Parkman, R Pensiero, M Schifmann, R Tolstoshev, P Weinberg, K AF Dunbar, C Kohn, D Karlsson, S Barton, N Brady, R CottlerFox, M Crooks, G Emmons, R Esplin, J Leitman, S Lenarsky, C Nolta, J Parkman, R Pensiero, M Schifmann, R Tolstoshev, P Weinberg, K TI Retroviral mediated transfer of the cDNA for human glucocerebrosidase into hematopoietic stem cells of patients with gaucher disease. A phase I study SO HUMAN GENE THERAPY LA English DT Article ID BONE-MARROW TRANSPLANTATION; LONG-TERM HEMATOPOIESIS; GENE-TRANSFER; PROGENITOR CELLS; REPLACEMENT THERAPY; ADENOSINE-DEAMINASE; GROWTH-FACTOR; EXPRESSION; MICE; CULTURE AB Patients with Gaucher disease suffer from a lack of functional glucocerebrosidase enzyme (Gc). Disease symptoms are a result of macrophage engorgement secondary to this enzyme deficiency. This study is designed to determine if cDNA encoding normal Gc can be introduced into macrophage precursors using a retroviral vector. CD34(+) cells obtained from G-CSF mobilized peripheral blood stem cells or from bone marrow will be transduced ex vivo using one of the following three methods of transduction: 1) (G)lGc retroviral supernatant in the presence of autologous stroma over a period of 72 hours, 2) GlGc retroviral supernatant in the presence of interleukin-3 interleukin-6, stem cell factor and autologous stroma over a 72 hour period, 3) GlGc retroviral supernatant in the presence of interleukin-3, interleukin-6, and stem cell factor over a 72 hour period. These transduced cells will be reinfused into the patient and the patient monitored for toxicities as well as evidence of successful gene transfer and expression. A total of twenty-four patients will be enrolled on the protocol. Patients will be assigned in equal numbers to each of six groups. The two sites participating are the National Institutes of Health and Childrens Hospital of Los Angeles. C1 CHILDRENS HOSP LOS ANGELES,LOS ANGELES,CA 90027. NINCDS,BETHESDA,MD 20892. NIH,DTM,BETHESDA,MD 20892. UNIV SO CALIF,LOS ANGELES,CA. GENET THERAPY INC,GAITHERSBURG,MD. RP Dunbar, C (reprint author), NHLBI,BLDG 10,BETHESDA,MD 20892, USA. RI Kohn, Donald/N-5085-2016; OI Kohn, Donald/0000-0003-1840-6087; Nolta, Jan/0000-0003-4576-8542 NR 49 TC 35 Z9 35 U1 0 U2 1 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 SN 1043-0342 J9 HUM GENE THER JI Hum. Gene Ther. PD JAN 20 PY 1996 VL 7 IS 2 BP 231 EP 253 DI 10.1089/hum.1996.7.2-231 PG 23 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA UG135 UT WOS:A1996UG13500011 PM 8788174 ER PT J AU Zhu, JM Yin, JL Law, PY Claude, PA Rice, KC Evans, CJ Chen, CG Yu, L LiuChen, LY AF Zhu, JM Yin, JL Law, PY Claude, PA Rice, KC Evans, CJ Chen, CG Yu, L LiuChen, LY TI Irreversible binding of cis-(+)-3-methylfentanyl isothiocyanate to the delta opioid receptor and determination of its binding domain SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID FUNCTIONAL EXPRESSION; MOLECULAR-CLONING; OPIATE RECEPTOR; LOCALIZATION; SITE; CDNA AB Binding of cis-(+)-3-methylfentanyl isothiocyanate (SUPERFIT) to cloned opioid receptors stably expressed in Chinese hamster ovary cells was characterized, SUPERFIT inhibited [H-3]diprenorphine binding with much higher affinity for the delta than the mu or kappa receptor, Pretreatment with SUPERFIT followed by extensive washing reduced delta binding with an IC50 value of 7.1 nM, yet it did not affect mu and kappa binding up to 0.1 mu M. The reduction in delta binding by SUPERFIT pretreatment was due to a decrease in B-max with no change in K-d. These results indicate that SUPERFIT is a highly selective delta irreversible ligand, We then determined the region in the delta receptor that confered binding selectivity for SUPERFIT by examining its binding to six mu/delta chimeric receptors, SUPERFIT bound to delta, mu/delta 1 (amino acids mu 1-94/delta 76-372), delta/mu 3 (delta 1-134/mu 154-398), and delta/mu 4 (delta 1-187/mu 207-398) receptors with high affinity but to mu, delta/mu 1 (delta 1-75/mu 95-398), delta/mu 3 (delta 1-153/delta 135-372), and mu/delta 4 (mu 1-206/delta 188-372) receptors with low affinity, Pretreatment with SUPERFIT potently inhibited [3H]diprenorphine binding to delta, mu/delta 3, delta/mu 3, and delta/delta 4 but affected binding to mu, delta/mu 1, delta/mu 3, and mu/delta 4 only at much higher concentrations, Thus, the segment from the beginning of the first intracellular loop to the middle of the third transmembrane helix of the delta receptor is important for selective binding of SUPERFIT. C1 TEMPLE UNIV,SCH MED,DEPT PHARMACOL,PHILADELPHIA,PA 19140. UNIV MINNESOTA,SCH MED,DEPT PHARMACOL,MINNEAPOLIS,MN 55455. NIDDK,MED CHEM LAB,BETHESDA,MD 20892. UNIV CALIF LOS ANGELES,INST NEUROPSYCHIAT,LOS ANGELES,CA 90024. INDIANA UNIV,SCH MED,DEPT MED & MOLEC GENET,INDIANAPOLIS,IN 46202. OI Law, Ping-Yee/0000-0002-5364-1093 FU NIDA NIH HHS [DA04745, T32 DA07237, P50 DA005010] NR 31 TC 28 Z9 33 U1 0 U2 1 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JAN 19 PY 1996 VL 271 IS 3 BP 1430 EP 1434 PG 5 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA TQ525 UT WOS:A1996TQ52500030 PM 8576134 ER PT J AU Lewin, I JacobHirsch, J Zang, ZC Kupershtein, V Szallasi, Z Rivera, J Razin, E AF Lewin, I JacobHirsch, J Zang, ZC Kupershtein, V Szallasi, Z Rivera, J Razin, E TI Aggregation of the Fc epsilon RI in mast cells induces the synthesis of Fos-interacting protein and increases its DNA binding activity: The dependence on protein kinase C-beta SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID LEUCINE ZIPPER; RBL-2H3 CELLS; EXPRESSION; JUN; TRANSCRIPTION; PROLIFERATION; FIBROBLASTS; ACTIVATION; EXOCYTOSIS; ISOZYMES AB The ability of c-Fos to dimerize with various proteins creates transcription complexes which can exert their regulatory function on a variety of genes. One of the transcription factors that binds to c-Fos is the newly discovered Fos-interacting protein (FIP). In this report we present evidence for the regulation of the synthesis of FIP by a physiological stimulus. We found that the aggregation of the mast cell high affinity receptor for IgE (Fc epsilon RI) induced the synthesis of FIP and increased its DNA binding activity. Moreover, down-regulation of the isoenzyme protein kinase C-beta (PKC-beta) by a specific antisense phosphorothioate oligonucleotide resulted in profound inhibition of FIP Fos DNA binding activity. Thus, aggregation of the Fc epsilon RI on mast cells elicits a PKC-beta dependent signaling pathway which regulates FIP-Fos DNA binding activity. C1 HEBREW UNIV JERUSALEM,HADASSAH MED SCH,DEPT BIOCHEM,IL-91120 JERUSALEM,ISRAEL. NCI,CELLULAR CARCINOGENESIS & TUMOR PROMOT LAB,BETHESDA,MD 20892. NIAMS,SECT CHEM IMMUNOL,BETHESDA,MD 20892. NR 25 TC 22 Z9 23 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JAN 19 PY 1996 VL 271 IS 3 BP 1514 EP 1519 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA TQ525 UT WOS:A1996TQ52500042 PM 8576146 ER PT J AU Yoo, SH AF Yoo, SH TI pH- and Ca2+-dependent aggregation property of secretory vesicle matrix proteins and the potential role of chromogranins A and B in secretory vesicle biogenesis SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID ISOLATED CHROMAFFIN VESICLES; CONFORMATIONAL CHANGE; SECRETOGRANIN-II; NERVOUS-TISSUE; MESSENGER-RNA; SEQUENCE; MEMBRANE; CALCIUM; BINDING; CELLS AB Chromogranins A and B (CGA and CGB), the major proteins of the secretory vesicles of the regulated secretory pathway, have been shown to aggregate in a low pH and high calcium environment, the condition found in the trans-Golgi network where secretory vesicles are formed. Moreover, CGA and CGB, as well as several other secretory vesicle matrix proteins, have recently been shown to bind to the vesicle membrane at the intravesicular pH of 5.5 and to be released from it at a near physiological pH of 7.5. The pH- and Ca2(+)-dependent aggregation and interaction of chromogranins, as well as several other matrix proteins, with the vesicle membrane are considered essential in vesicle biogenesis. Therefore, to gain further insight into how vesicle matrix proteins find their way into the secretory vesicles, the pH- and Ca2+-dependent aggregation and vesicle membrane binding properties of the vesicle matrix proteins were studied, and it was found that most of the vesicle matrix proteins aggregated in the presence of Ca2+ at the intravesicular pH of 5.5. Furthermore, most of the vesicle matrix proteins bound not only to the vesicle membrane but also to CGA at pH 5.5, with the exception of a few matrix proteins that appeared to bind only to CGA or to vesicle membrane. Purified CGB was also shown to interact with CGA at pH 5.5. The extent and Ca2+-sensitivity of the aggregation of vesicle matrix proteins lay between those of purified CGB and CGA, CGE aggregation showing the highest degree of aggregation and being the most Ca2+ sensitive at a given protein concentration. Hence, in view of the abundance of chromogranins in secretory vesicles and their low pH and high calcium-dependent aggregation property, combined with their ability to interact with both the vesicle matrix proteins and the vesicle membrane, CGA and CGB are proposed to play essential roles in the selective aggregation and sorting of potential vesicle matrix proteins to the immature secretory vesicles of the regulated secretory pathway. RP Yoo, SH (reprint author), NIDCD, NEUROCHEM LAB, 5 RES COURT, 2A37, BETHESDA, MD 20892 USA. NR 36 TC 79 Z9 80 U1 0 U2 2 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JAN 19 PY 1996 VL 271 IS 3 BP 1558 EP 1565 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA TQ525 UT WOS:A1996TQ52500049 PM 8576153 ER PT J AU Germann, UA Chambers, TC Ambudkar, SV Licht, T Cardarelli, CO Pastan, I Gottesman, MM AF Germann, UA Chambers, TC Ambudkar, SV Licht, T Cardarelli, CO Pastan, I Gottesman, MM TI Characterization of phosphorylation-defective mutants of human P-glycoprotein expressed in mammalian cells SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID PROTEIN-KINASE-C; BACTERIAL TRANSPORT PROTEINS; MULTIDRUG RESISTANCE GENE; HUMAN-KB CELLS; DRUG ACCUMULATION; MDR1 CDNA; VINBLASTINE RESISTANCE; PHORBOL ESTERS; LEUKEMIA-CELLS; INSECT CELLS AB To assess the role of phosphorylation of the human multidrug resistance MDR1 gene product P-glycoprotein for its drug transport activity, phosphorylation sites within its linker region were subjected to mutational analysis. We constructed a 5A mutant, in which serines at positions 661, 667, 671, 675, and 683 were replaced by nonphosphorylatable alanine residues, and a 5D mutant carrying aspartic acid residues at the respective positions to mimic permanently phosphorylated serine residues. Transfection studies revealed that both mutants were targeted properly to the cell surface and conferred multidrug resistance by diminishing drug accumulation. In contrast to wild-type P-glycoprotein, the overexpressed 5A and the 5D mutants exhibited no detectable levels of phosphorylation, either in vivo following metabolic labeling of cells with [P-32] orthophosphate or in vitro in phosphorylation assays with protein kinase C, cAMP-dependent protein kinase, or a P-glycoprotein-specific protein kinase purified from multidrug-resistant KB-V1 cells. These results reconfirm that the major P-glycoprotein phosphorylation sites are located within the linker region. Furthermore, the first direct evidence is provided that phosphorylation/dephosphorylation mechanisms do not play an essential role in the establishment of the multidrug resistance phenotype mediated by human P-glycoprotein. C1 NCI,CELL BIOL LAB,BETHESDA,MD 20892. VERTEX PHARMACEUT INC,CAMBRIDGE,MA 02139. UNIV ARKANSAS MED SCI HOSP,DEPT BIOCHEM & MOLEC BIOL,LITTLE ROCK,AR 72205. JOHNS HOPKINS UNIV,SCH MED,DEPT MED,DIV NEPHROL,BALTIMORE,MD 21205. JOHNS HOPKINS UNIV,SCH MED,DEPT PHYSIOL,BALTIMORE,MD 21205. NCI,MOLEC BIOL LAB,BETHESDA,MD 20892. RI Ambudkar, Suresh/B-5964-2008 NR 52 TC 141 Z9 142 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JAN 19 PY 1996 VL 271 IS 3 BP 1708 EP 1716 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA TQ525 UT WOS:A1996TQ52500069 PM 8576173 ER PT J AU vanRhee, AM Siddiqi, SM Melman, N Shi, D Padgett, WL Daly, JW Jacobson, KA AF vanRhee, AM Siddiqi, SM Melman, N Shi, D Padgett, WL Daly, JW Jacobson, KA TI Tetrahydrobenzothiophenone derivatives as a novel class of adenosine receptor antagonists SO JOURNAL OF MEDICINAL CHEMISTRY LA English DT Article ID ADENYLATE-CYCLASE; RAT-BRAIN; BINDING; ADENOSINE-A1-RECEPTOR; CELLS AB A novel class of non-nitrogen-containing heterocycles, the tetrahydrobenzothiophenones, was found to bind to adenosine receptors as antagonists in the micromolar range. Affinity was determined in radioligand-binding assays at rat brain A(1) and A(2a) receptors. A structure-activity analysis indicated that a 3-thioether group is favored and affinity at A(2a), but not at AL, receptors is highly dependent on this thioether substituent. A carboxylic acid-derived substituent is required at the 1-position of the thiophene ring, with esters being more potent in binding at A(1) receptors than the corresponding carboxyl hydrazide or carboxylic acid derivatives. The methyl (15) and ethyl (16) esters are about equipotent at A(1) but not at A(2a) receptors. A 4-keto group on the saturated ring is favored for receptor affinity. Dimethyl substitution at the B-position of the saturated ring is allowed. One of the most potent derivatives was the nonselective compound ethyl 3-(benzylthio)-4-oxo-4,5,6,7-tetrahydrobenzo[c]thiophene-1-carboxylate (BTH4, 7; Figure 1), which antagonized adenosine agonist-induced inhibition of adenylyl cyclase in rat adipocyte membranes with a K-B value of 1.62 +/- 0.73 mu M and adenosine agonist-induced stimulation of adenylyl cyclase in pheochromocytoma cell membranes with a K-B value of 9.19 +/- 0.98 mu M. Displacement of radioligand binding by BTH4 (7) at cloned human A(3) receptors was negligible, but one slightly A(3) selective compound (11, 3.9-fold over A(1) and >7.5-fold over A(2a)) was found. A 1-methylpropyl thioether (17) was 29-fold selective for A(1) vs A(2a) receptors. BTH4 (7) alone, at 10 mg/kg, stimulated locomotor activity in mice but paradoxically acted, under certain circumstances, synergistically with an A(1) selective agonist to depress locomotor activity. A pharmacophore model relating structural features of xanthine and non-xanthine adenosine antagonists to BTH4 (7) suggests a high degree of similarity in electrostatic surfaces, assuming that the thiophene ring superimposes the region of the uracil ring of xanthines. C1 NIDDK,BIOORGAN CHEM LAB,MOLEC RECOGNIT SECT,BETHESDA,MD 20892. NIDDK,BIOORGAN CHEM LAB,PHARMACODYNAM SECT,BETHESDA,MD 20892. RI Jacobson, Kenneth/A-1530-2009 OI Jacobson, Kenneth/0000-0001-8104-1493 FU Intramural NIH HHS [Z01 DK031117-20, Z99 DK999999] NR 39 TC 20 Z9 20 U1 0 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0022-2623 J9 J MED CHEM JI J. Med. Chem. PD JAN 19 PY 1996 VL 39 IS 2 BP 398 EP 406 DI 10.1021/jm9504823 PG 9 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA TR125 UT WOS:A1996TR12500010 PM 8558508 ER PT J AU Silva, AM Cachau, RE Sham, HL Erickson, JW AF Silva, AM Cachau, RE Sham, HL Erickson, JW TI Inhibition and catalytic mechanism of HIV-1 aspartic protease SO JOURNAL OF MOLECULAR BIOLOGY LA English DT Article DE HIV-1 protease; catalytic mechanism; difuoroketone inhibitor; transition states; reaction path ID IMMUNODEFICIENCY VIRUS-1 PROTEASE; CRYSTALLOGRAPHIC ANALYSIS; SYSTEMATIC PREPARATION; CHEMICAL MECHANISM; ELUCIDATE DETAILS; ORBITAL SETS; BINDING; PROTEINASES; INVITRO AB The structure of the HIV-1 protease in complex with a pseudo-C2 symmetric inhibitor, which contains a central difluoroketone motif, has been determined with X-ray diffraction data extending to 1.7 Angstrom resolution. The electron density map clearly indicates that the inhibitor is bound in a symmetric fashion as the hydrated, or gemdiol, form of the difluoroketone. Refinement of the complex reveals a unique, and almost symmetric, set of interactions between the geminal hydroxyl groups, the geminal fluorine atoms, and the active-site aspartate residues. Several hydrogen bonding patterns are consistent with that conformation. The lowest energy hydrogen disposition, as determined by semiempirical energy calculations, shows only one active site aspartate protonated. A comparison between the corresponding dihedral angles of the difluorodiol core and those of a hydrated peptide bond analog, calculated nb-initio, shows that the inhibitor core is a mimic of a hydrated peptide bond in a gauche conformation. The feasibility of an anti-gauche transition for a peptide bond after hydration is verified by extensive molecular dynamics simulations. The simulations suggest that rotation about the C-N scissile bond would readily occur after hydration and would be driven by the optimization of the interactions of peptide side-chains with the enzyme. These results, together with the characterization of a transition state leading to bond breakage via a concerted exchange of two protons, suggest a proteolysis mechanism whereby only one active site aspartate is initially protonated. The steps of this mechanism are: asymmetric binding of the substrate; hydration of the peptidic carbonyl by an active site water; proton translocation between the active site aspartate residues simultaneously with carbonyl hydration; optimization of the binding of the entire substrate facilitated by the flexible structure of the hydrated peptide bond, which, in turn, forces the hydrated peptide bond to assume a gauche conformation; simultaneous proton exchange whereby one hydroxyl donates a proton to the charged aspartate, and, at the same time, the nitrogen lone pair accepts a proton from the other aspartate; and, bond breakage and regeneration of the initial protonation state of the aspartate residues. (C) 1996 Academic Press Limited C1 ABBOTT LABS,NATL CANC INST,ABBOTT PK,IL 60064. RP Silva, AM (reprint author), NCI,STRUCT BIOCHEM PROGRAM,FREDERICK,MD 21702, USA. NR 44 TC 126 Z9 128 U1 1 U2 7 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 JAN 19 PY 1996 VL 255 IS 2 BP 321 EP 340 DI 10.1006/jmbi.1996.0026 PG 20 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA TP682 UT WOS:A1996TP68200005 PM 8551523 ER PT J AU Cachau, RE GarciaMoreno, B AF Cachau, RE GarciaMoreno, B TI A method for estimating the effective dielectric constant at an enzyme reaction center SO JOURNAL OF MOLECULAR BIOLOGY LA English DT Article ID MNDO C1 JOHNS HOPKINS UNIV,DEPT BIOPHYS,3400 N CHARLES ST,BALTIMORE,MD 21218. RP Cachau, RE (reprint author), NCI,STRUCT BIOCHEM PROGRAM,FREDERICK,MD 21702, USA. NR 9 TC 6 Z9 6 U1 0 U2 1 PU ACADEMIC PRESS LTD PI LONDON PA 24-28 OVAL RD, LONDON, ENGLAND NW1 7DX SN 0022-2836 J9 J MOL BIOL JI J. Mol. Biol. PD JAN 19 PY 1996 VL 255 IS 2 BP 340 EP 343 DI 10.1016/S0022-2836(05)80051-8 PG 4 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA TP682 UT WOS:A1996TP68200006 ER PT J AU Cachau, RE AF Cachau, RE TI Validation of quantum chemistry calculations SO JOURNAL OF MOLECULAR BIOLOGY LA English DT Article ID SYSTEMATIC PREPARATION; ORBITAL SETS RP Cachau, RE (reprint author), NCI,STRUCT BIOCHEM PROGRAM,FREDERICK,MD 21702, USA. NR 12 TC 0 Z9 0 U1 0 U2 0 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 JAN 19 PY 1996 VL 255 IS 2 BP 343 EP 346 DI 10.1016/S0022-2836(05)80052-X PG 4 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA TP682 UT WOS:A1996TP68200007 ER PT J AU Haynes, BF Pantaleo, G Fauci, AS AF Haynes, BF Pantaleo, G Fauci, AS TI Toward an understanding of the correlates of protective immunity to HIV infection SO SCIENCE LA English DT Review ID IMMUNODEFICIENCY-VIRUS TYPE-1; PERSISTENT GENERALIZED LYMPHADENOPATHY; FOLLICULAR DENDRITIC CELLS; LYMPH-NODES; DEFICIENCY-SYNDROME; PROGNOSTIC VALUE; KAPOSIS SARCOMA; HOMOSEXUAL MEN; T-CELLS; HLA-DR AB Considerable progress has been made recently in understanding the genetic, immunologic, and virologic factors in human immunodeficiency virus (HIV)-infected individuals who either rapidly progress or do not progress to acquired immunodeficiency syndrome (AIDS). In addition, detection of HIV-specific immune responses in HIV-negative individuals who have been exposed to the virus multiple times suggests that natural immune responses to HIV may be protective in rare individuals. Understanding the correlates of protective immunity to HIV infection is critical to efforts to develop preventive HIV vaccines as well as to determine the feasibility of treating HIV infection by boosting immunity to HIV. C1 DUKE UNIV,MED CTR,DEPT MED,DIV RHEUMATOL ALLERGY & IMMUNOL,DUKE CTR AIDS RES,DURHAM,NC 27710. NIAID,IMMUNOREGULAT LAB,BETHESDA,MD 20892. RI Pantaleo, Giuseppe/K-6163-2016 FU NCI NIH HHS [CA-28936, CA-43447]; NIAID NIH HHS [AI-28662] NR 194 TC 341 Z9 352 U1 2 U2 10 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 SN 0036-8075 J9 SCIENCE JI Science PD JAN 19 PY 1996 VL 271 IS 5247 BP 324 EP 328 DI 10.1126/science.271.5247.324 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA TQ528 UT WOS:A1996TQ52800032 PM 8553066 ER PT J AU Collins, FS AF Collins, FS TI BRCA1 - Lots of mutations, lots of dilemmas SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material ID BREAST; CANCER RP Collins, FS (reprint author), NIH,NATL CTR HUMAN GENOME RES,BETHESDA,MD 20892, USA. NR 16 TC 145 Z9 147 U1 0 U2 6 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 JAN 18 PY 1996 VL 334 IS 3 BP 186 EP 188 DI 10.1056/NEJM199601183340311 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA TQ017 UT WOS:A1996TQ01700011 PM 8531977 ER PT J AU Cohen, JI AF Cohen, JI TI Bacterial pneumonia in HIV SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Letter RP Cohen, JI (reprint author), NIAID,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 3 TC 0 Z9 0 U1 0 U2 0 PU MASS MEDICAL SOC PI BOSTON PA 10 SHATTUCK, BOSTON, MA 02115 SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD JAN 18 PY 1996 VL 334 IS 3 BP 195 EP 195 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA TQ017 UT WOS:A1996TQ01700025 PM 8531989 ER PT J AU Athanasiou, M Mavrothalassitis, GJ Yuan, CC Blair, DG AF Athanasiou, M Mavrothalassitis, GJ Yuan, CC Blair, DG TI The Gag-Myb-Ets fusion oncogene alters the apoptotic response and growth factor dependence of interleukin-3 dependent murine cells SO ONCOGENE LA English DT Article DE v-ets; ETS oncogene; apoptosis; IT-3 dependent; erythropoietin; erythroid differentiation ID TRANSCRIPTION FACTOR GATA-1; AVIAN LEUKEMIA-VIRUS; HEMATOPOIETIC-CELLS; ERYTHROPOIETIN RECEPTOR; NEURORETINA CELLS; GENE-EXPRESSION; LINE; E26; TRANSACTIVATION; DIFFERENTIATION AB Expression of the avian E26-derived Gag-Myb-Ets fusion oncogene in interleukin-3(IL3)-dependent murine hematopoietic cell lines results in a pattern of cell line dependent changes in growth factor-induced proliferation and apoptosis. A drug-selectable retrovirus expressing p135(Gag-Myb-Ets) induced an erythropoietin(Epo)-responsive phenotype in the cell lines FDC-P2, BaF3 and 32Dc123. Gag-Myb-Ets expression alone did not increase expression of GATA-1 or the Epo receptor(EpoR) in the presence of IL3, and infected cell lines express increased GATA-1 and EpoR only when IL3 was replaced by Epo in the culture media. Indicative of Epo-induced erythroid differentiation, these cells also began to express beta-globin after 3-5 days growth in Epo. Unlike control cells, infected FDC-P2 cells failed to undergo programmed cell death (apoptosis) when transferred from IL3- to Epo-containing media, although a fraction of the cells failed to proliferate following the media shift. Three other IL3-dependent cell Lines showed no changes in growth behavior when induced to express the fusion oncogene. Our data shows that Gag-Myb-Ets can have different affects on growth factor pathways depending on the cell background, suggesting a model in which the p135(gag-myb-ets) fusion oncogene promotes these different responses through its affect on apoptosis. C1 SAIC,LAB CELLULAR BIOCHEM,FREDERICK,MD 21702. NCI,MOLEC ONCOL LAB,FREDERICK,MD. NR 51 TC 14 Z9 14 U1 0 U2 0 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE, HAMPSHIRE, ENGLAND RG21 6XS SN 0950-9232 J9 ONCOGENE JI Oncogene PD JAN 18 PY 1996 VL 12 IS 2 BP 337 EP 344 PG 8 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA TR538 UT WOS:A1996TR53800012 PM 8570210 ER PT J AU Bies, J Hoffman, B Amanullah, A Giese, T Wolff, L AF Bies, J Hoffman, B Amanullah, A Giese, T Wolff, L TI B-Myb prevents growth arrest associated with terminal differentiation of monocytic cells SO ONCOGENE LA English DT Article DE B-myb; differentiation; monocytic cells; growth arrest; apoptosis ID MYELOID-LEUKEMIA CELLS; C-MYB; V-MYB; TRANSCRIPTIONAL ACTIVATION; REGULATED EXPRESSION; HEMATOPOIETIC-CELLS; MESSENGER-RNA; MIM-1 GENE; A-MYB; PROLIFERATION AB B-Myb is a transcriptional regulator of gene expression and is highly homologous to c-Myb in its N-terminal DNA binding domain. However, unlike c-myb, whose expression is restricted largely to immature hematopoietic cells, B-myb mRNA has been found to be expressed in all proliferating mammalian cell lines and is clearly regulated in a cell cycle dependent manner. That c-Myb and B-Myb proteins perform different roles in proliferation and/or differentiation is suggested by the redundancy of their expression. It was previously shown that deregulated c-Myb expression can inhibit IL-6 induced terminal differentiation of the leukemia cell line M1. We found that, unlike the downregulation of c-Myb protein which is an early response of progenitor M1 cells to IL-6 treatment, the downregulation of B-Myb occurs late, just prior to terminal differentiation and growth arrest. It was, therefore, of interest to examine the role of the murine B-Myb protein in the proliferation and differentiation of the M1 cells and to compare these effects to those of c-Myb in the same system. Clones ectopically producing B-Myb, like those ectopically expressing c-Myb, proliferated in the presence of the differentiation-inducing agent and did not undergo the programmed cell death which normally follows terminal macrophage differentiation. In addition, the cell-cycle distribution of M1/B-Myb cells was comparable to untreated cells. Although M1/B-Myb and M1/c-Myb clones treated with IL-6 appeared quite immature, differentiation markers were demonstrated to be maintained at near normal levels (e.g. MyD88, Mac-2), or be partially reduced in expression (C3, Fc and Mac-1 receptors) suggesting that the cells had undergone commitment to maturation, but were unable to terminally differentiate. C1 NCI,GENET LAB,BETHESDA,MD 20892. TEMPLE UNIV,SCH MED,FELS INST CANC RES & MOLEC BIOL,PHILADELPHIA,PA 19140. FU NCI NIH HHS [1RO1CA51162] NR 48 TC 53 Z9 53 U1 0 U2 2 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE, HAMPSHIRE, ENGLAND RG21 6XS SN 0950-9232 J9 ONCOGENE JI Oncogene PD JAN 18 PY 1996 VL 12 IS 2 BP 355 EP 363 PG 9 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA TR538 UT WOS:A1996TR53800014 PM 8570212 ER PT J AU Byeon, MK Westerman, MA Maroulakou, IG Henderson, KW Suster, S Zhang, XK Papas, TS Vesely, J Willingham, MC Green, JE Schweinfest, CW AF Byeon, MK Westerman, MA Maroulakou, IG Henderson, KW Suster, S Zhang, XK Papas, TS Vesely, J Willingham, MC Green, JE Schweinfest, CW TI The down-regulated in adenoma (DRA) gene encodes an intestine-specific membrane glycoprotein SO ONCOGENE LA English DT Article DE colon; tumorigenesis; sulfate transporter; mucosa; differentiation ID HUMAN COLORECTAL-CANCER; HUMAN-COLON CARCINOMA; HEPARAN-SULFATE; P-GLYCOPROTEIN; APC GENE; GASTRIC-CANCER; FREQUENT LOSS; EXPRESSION; MUTATIONS; IDENTIFICATION AB The protein product of the DRA gene, a gene whose expression is down-regulated in colon adenomas and adenocarcinomas, is a membrane glycoprotein and a member of a family of sulfate transporters. It is expressed in the intestinal tract (duodenum, ileum, cecum, distal colon), but not in the esophagus or stomach, DRA mRNA expression is restricted to the mucosal epithelium, and DRA protein expression is further limited to the columnar epithelial cells, particularly to the brush border, Consistent with its expression in the differentiated columnar epithelium of the adult human colon, DRA is first expressed in the midgut of developing mouse embryos at day 16.5, corresponding with the time of differentiation of the epithelium of the small intestine, A model for the structure of the DRA protein is proposed and its possible role in colon tumorigenesis is discussed. C1 MED UNIV S CAROLINA,CTR MOLEC & STRUCT BIOL,HOLLINGS CANC CTR,CHARLESTON,SC 29425. NCI,MOLEC ONCOL LAB,FREDERICK,MD 21702. MT SINAI MED CTR,DEPT PATHOL & LAB MED,MIAMI BEACH,FL 33140. UNIV MIAMI,SCH MED,MIAMI,FL 33140. MED UNIV S CAROLINA,DEPT PATHOL & LAB MED,CHARLESTON,SC 29425. NR 50 TC 70 Z9 70 U1 0 U2 4 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE, HAMPSHIRE, ENGLAND RG21 6XS SN 0950-9232 J9 ONCOGENE JI Oncogene PD JAN 18 PY 1996 VL 12 IS 2 BP 387 EP 396 PG 10 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA TR538 UT WOS:A1996TR53800018 PM 8570216 ER PT J AU Muramatsu, T Kincaid, RL AF Muramatsu, T Kincaid, RL TI Inhibition of NF-AT signal transduction events by a dominant-negative form of calcineurin SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article ID DEPENDENT PROTEIN PHOSPHATASE; CATALYTIC SUBUNIT; GENE-EXPRESSION; BINDING DOMAIN; CALMODULIN; IDENTIFICATION; ACTIVATION; CLONING; ISOFORMS; PROMOTER AB An inhibitory, ''dominant-negative,'' form of the calcineurin catalytic (A) subunit was prepared, which lacks the calmodulin-binding domain. autoinhibitory domain and most of its catalytic core but possesses the regulatory (B) subunit binding domain. When tested for its ability to block calcineurin-dependent signaling in Jurkat cells, expression of this ''B-subunit knock-out'' (BKO) construct suppressed reporter gene activity driven by NF-AT, the pivotal promoter element for interleukin (IL)-2 gene induction. Immunoprecipitation of epitope-labeled BKO demonstrated for the formation of a tight complex with endogenous B subunit in Jurkat cells, consistent with an inhibitory mechanism that involves the sequestration of the B subunit. Furthermore, the sharply reduced NF-AT activity produced by co-transfecting BKO could be ''rescued'' by overexpression of transfected B subunit, suggesting that depletion of this subunit was responsible for the inhibition. These data suggest the potential utility of agents that disrupt calcineurin-mediated signal transduction pathways by blocking formation of the catalytically active dimer of calcineurin A and B subunits. (C) 1996 Academic Press, Inc. C1 NIAAA,MOLEC & CELLULAR NEUROBIOL LAB,IMMUNOL SECT,ROCKVILLE,MD 20852. NR 26 TC 13 Z9 13 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD JAN 17 PY 1996 VL 218 IS 2 BP 466 EP 472 DI 10.1006/bbrc.1996.0083 PG 7 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA TQ565 UT WOS:A1996TQ56500009 PM 8561779 ER PT J AU Rojanasakul, Y Shi, XG Deshpande, D Liang, WW Wang, LY AF Rojanasakul, Y Shi, XG Deshpande, D Liang, WW Wang, LY TI Protection against oxidative injury and permeability alteration in cultured alveolar epithelium by transferrin-catalase conjugate SO BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE LA English DT Article DE oxidant; alveolar damage; catalase; endocytosis; transferrin ID PULMONARY OXYGEN-TOXICITY; INDUCED CELLULAR INJURY; SUPEROXIDE-DISMUTASE; HYDROGEN-PEROXIDE; ANTIOXIDANT ENZYMES; CELLS; LUNG; RATS; MONOLAYERS; MECHANISMS AB The successful prevention of hydrogen peroxide-induced alveolar permeability alterations and cell injury by transferrin-catalase conjugate is described in this study. Permeability alterations and cell injury were induced in cultured alveolar epithelial monolayers by hydrogen peroxide. Transepithelial transport of a permeability marker, [C-14]mannitol, and cellular nuclear fluorescence of a membrane integrity indicator, propidium iodide, were used to quantitate epithelial permeability and damage respectively. Hydrogen peroxide (0.1-10 mM) induced a dose-dependent increase in both alveolar permeability and cellular damage; however, the oxidant effect on monolayer permeability did not require prior cell damage, Electron spin resonance measurements using the spin trap 5,5-dimethyl-1-pyrroline-N-oxide indicated the formation of hydroxyl radicals in hydrogen peroxide-treated cells. Chelation of the cellular pool of iron by deferoxamine inhibited radical formation and helped protect the cells from oxidative changes. Prior treatment of the cells with catalase (0.1 U-10 U/ml) had minimal protective effects on cell injury and permeability alterations. In contrast, transferrin-catalase conjugate, at the same concentration range, exhibited much improved protective effects on the cells in response to oxidant stress. This enhanced protection was found to correlate well with an increase in cellular uptake of the enzyme conjugate via the transferrin receptor endocytosis pathway. Effective protection by the enzyme conjugate was shown to require both the antioxidant enzyme moiety and the cognate moiety for the cell surface receptor. These findings indicate the potential therapeutic merit of transferrin-catalase conjugate for the treatment of pathological processes in the lung, whenever oxidative stress is involved. C1 NCI,LAB EXPTL PATHOL,BETHESDA,MD 20892. RP Rojanasakul, Y (reprint author), W VIRGINIA UNIV,DEPT BASIC PHARMACEUT SCI,MORGANTOWN,WV 26506, USA. RI Shi, Xianglin/B-8588-2012; OI Rojanasakul, Yon/0000-0002-8839-6462 NR 36 TC 8 Z9 8 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0925-4439 J9 BBA-MOL BASIS DIS JI Biochim. Biophys. Acta-Mol. Basis Dis. PD JAN 17 PY 1996 VL 1315 IS 1 BP 21 EP 28 DI 10.1016/0925-4439(95)00090-9 PG 8 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA TU298 UT WOS:A1996TU29800005 PM 8611642 ER PT J AU Izquierdo, MA Shoemaker, RH Flens, MJ Scheffer, GL Wu, L Prather, TR Scheper, RJ AF Izquierdo, MA Shoemaker, RH Flens, MJ Scheffer, GL Wu, L Prather, TR Scheper, RJ TI Overlapping phenotypes of multidrug resistance among panels of human cancer-cell lines SO INTERNATIONAL JOURNAL OF CANCER LA English DT Article ID P-GLYCOPROTEIN; TOPOISOMERASE-II; OVEREXPRESSION; EXPRESSION AB In addition to P-glycoprotein (Pgp), 2 proteins related to multidrug resistance (MDR) have recently been described. The Multidrug-Resistance-associated protein (MRP) is one of the ATP-binding-cassette (ABC) transporters. The Lung-Resistance Protein (LRP) is the major component of human vaults, which are newly described cellular organelles and thought to mediate intracellular transport processes. Using immunocytochemical methods, we have examined the expression of MRP and LRP among panels of human cancer-cell lines not selected for drug resistance which have been previously characterized for expression of Pgp, and in vitro response to a variety of anti-cancer drugs. Expression of MRP and LRP was observed in 47/55 (87%) and 46/59 (78%) cell lines, respectively. Statistically significant correlations were observed between expression of each of these 3 proteins and in vitro sensitivity to at least one drug classically associated with MDR. LRP showed the greatest individual predictive value, which also applied to several nonclassical MDR drugs. Co expression of 2-3 MDR-related proteins was observed in 64% of the lines and was, in general, associated with high relative levels of drug resistance. Previously identified ''classic'' MDR lines as well as ''pan-resistant'' lines concurrently expressed all 3 MDR-related proteins. Some highly drug-resistant cell lines without detectable MDRI/Pgp were found to express relatively high levels of MRP and LRP. The high prevalence of MRP and LRP expression observed in this large set of cell lines, which have not been subjected to laboratory drug selection, suggests that MDR mechanisms associated with these proteins may be widespread in human malignancies. Moreover, the overlapping of these more recently recognized MDR phenotypes with Pgp-type MDR results in a complex phenotype, the understanding of which may be of importance in the development of new drugs and design of clinical treatment protocols, particularly those seeking to employ strategies to reverse the MDR phenotype. (C) 1996 Wiley-Liss, Inc. C1 FREE UNIV AMSTERDAM HOSP, DEPT PATHOL, 1081 HV AMSTERDAM, NETHERLANDS. NCI, DIV CANC TREATMENT, DEV THERAPEUT PROGRAM, LAB DRUG DISCOVERY RES & DEV, FREDERICK, MD USA. NR 26 TC 183 Z9 191 U1 3 U2 9 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0020-7136 J9 INT J CANCER JI Int. J. Cancer PD JAN 17 PY 1996 VL 65 IS 2 BP 230 EP 237 PG 8 WC Oncology SC Oncology GA TR245 UT WOS:A1996TR24500017 PM 8567122 ER PT J AU Pickar, D AF Pickar, D TI Clozapine for treatment of schizophrenia - Reply SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Letter RP Pickar, D (reprint author), NIH,BLDG 10,BETHESDA,MD 20892, USA. NR 3 TC 0 Z9 0 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD JAN 17 PY 1996 VL 275 IS 3 BP 187 EP 187 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA TP282 UT WOS:A1996TP28200022 ER PT J AU Restifo, NP Marincola, FM Kawakami, Y Taubenberger, J Yannelli, JR Rosenberg, SA AF Restifo, NP Marincola, FM Kawakami, Y Taubenberger, J Yannelli, JR Rosenberg, SA TI Loss of functional beta(2)-microglobulin in metastatic melanomas from five patients receiving immunotherapy SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID CD8+ T-CELLS; I ANTIGEN EXPRESSION; BETA-2-MICROGLOBULIN MESSENGER-RNA; COMPLEX CLASS-I; HISTOCOMPATIBILITY ANTIGEN; DEFECTIVE PRESENTATION; IMMUNE-RESPONSE; SELECTIVE LOSS; LYMPHOCYTES-T; B2M GENE AB Background: In a subset of patients with metastatic melanoma, T lymphocytes bearing the cell-surface marker CD8 (CD8(+) T cells) can cause the regression of even large tumors, These antitumor CD8(+) T cells recognize peptide antigens presented on the surface of tumor cells by major histocompatibility complex (MHC) class I molecules. The MHC class I molecule is a heterodimer composed of an integral membrane glycoprotein designated the a chain and a noncovalently associated, soluble protein called beta(2)-microglobulin (beta(2)m). Loss of beta(2)m generally eliminates antigen recognition by antitumor CD8(+) T cells, Purpose: We studied the loss of beta(2)m as a potential means of tumor escape from immune recognition in a cohort of patients receiving immunotherapy. Methods: We successfully grew 13 independent tumor cell cultures from tumor specimens obtained from 13 patients in a cohort of 40 consecutive patients undergoing immunotherapy for metastatic melanoma and for whom tumor specimens were available. These cell lines, as well as another melanoma cell line (called 1074mel) that had been derived from tumor obtained from a patient in a cytokine-gene therapy study, were characterized in vitro cytofluorometrically for MHC class I expression and by northern and western blot analyses for messenger RNA (mRNA) and protein expression, respectively, and ex vivo by immunohistochemistry. Results: After one melanoma cell line (1074mel) was found not to express functional beta(2)m by cytofluorometric analysis, four (31%) of the 13 newly established melanoma cell lines were found to have an absolute lack of functional MHC class I expression, Northern blot analysis of RNA extracted from the five cell Lines exhibiting no functional MHC class I expression showed that these cells contained normal levels of a-chain mRNA but variable levels of beta(2)m mRNA, In addition, no immunoreactive Pam protein was detected by western blot analysis. When human beta(2)m was transiently expressed with the use of a recombinant vaccinia virus, cell-surface MHC class I expression was reconstituted and the ability of these five cell lines to present endogenous antigens was restored, Immunohistochemical staining of tumor sections revealed a lack of immunoreactive MHC class I in vivo, supporting the notion that the in vitro observations were not artifactual. Furthermore, archival tumor sections obtained from patients prior to immunotherapy were available from three patients and were found to be beta(2)m positive, This result was consistent with the hypothesis that loss of beta(2)m resulted from immunotherapy. Conclusions: These data suggest that the loss of beta(2)m may be a mechanism whereby tumor cells can acquire immunoresistance. This study represents the first characterization of a molecular route of escape of tumors from immune recognition in a cohort of patients being treated with immunotherapy. C1 NCI,DIV CANC BIOL DIAG & CTR,DEPT PATHOL,BETHESDA,MD 20892. RP Restifo, NP (reprint author), NCI,DIV CANC TREATMENT,CLIN ONCOL PROGRAM,SURG BRANCH,BLDG 10,RM 2B42,BETHESDA,MD 20892, USA. RI Restifo, Nicholas/A-5713-2008; Kawakami, Yutaka /E-7429-2013; OI Kawakami, Yutaka /0000-0003-4836-2855; Restifo, Nicholas P./0000-0003-4229-4580 FU Intramural NIH HHS [Z01 BC010763-01, Z99 CA999999] NR 57 TC 236 Z9 239 U1 1 U2 7 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 JAN 17 PY 1996 VL 88 IS 2 BP 100 EP 108 DI 10.1093/jnci/88.2.100 PG 9 WC Oncology SC Oncology GA TP359 UT WOS:A1996TP35900010 PM 8537970 ER PT J AU Anzano, MA Peer, CW Smith, JM Mullen, LT Shrader, MW Logsdon, DL Driver, CL Brown, CC Roberts, AB Sporn, MB AF Anzano, MA Peer, CW Smith, JM Mullen, LT Shrader, MW Logsdon, DL Driver, CL Brown, CC Roberts, AB Sporn, MB TI Chemoprevention of mammary carcinogenesis in the rat: Combined use of raloxifene and 9-cis-retinoic acid SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID BREAST-CANCER; TAMOXIFEN; TUMORIGENESIS; PREVENTION; ESTROGEN C1 NCI,DIV CANC ETIOL,CHEMOPREVENT LAB,BETHESDA,MD 20892. NCI,DIV CANC PREVENT & CONTROL,BIOMETRY BRANCH,BETHESDA,MD 20892. SCI APPLICAT INT CORP,IN VIVO CARCINOGENESIS PROGRAM,FREDERICK,MD. NCI,FREDERICK CANC RES & DEV CTR,FREDERICK,MD. DARTMOUTH COLL SCH MED,HANOVER,NH. NR 23 TC 130 Z9 132 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 JAN 17 PY 1996 VL 88 IS 2 BP 123 EP 125 DI 10.1093/jnci/88.2.123 PG 3 WC Oncology SC Oncology GA TP359 UT WOS:A1996TP35900013 PM 8537973 ER PT J AU Newton, DL Xue, Y Olson, KA Fett, JW Rybak, SM AF Newton, DL Xue, Y Olson, KA Fett, JW Rybak, SM TI Angiogenin single-chain immunofusions: Influence of peptide linkers and spacers between fusion protein domains SO BIOCHEMISTRY LA English DT Article ID RIBONUCLEOLYTIC ACTIVITY; MONOCLONAL-ANTIBODIES; PSEUDOMONAS EXOTOXIN; ESCHERICHIA-COLI; GROWTH-FACTOR; TRANSFER-RNA; BINDING; FV; IMMUNOTOXINS; INVIVO AB The gene for human angiogenin (Ang), a member of the ribonuclease superfamily, was fused to a gene encoding a single-chain antibody (sFv) against the human transferrin receptor. Three Ang single-chain immunofusion proteins (AngsFvs) were constructed with variations in the type of linker connecting the V-L and V-H chain [EGKSSGSGSESKEF, L1 or (GGGGS)(3), L2] as well as with or without a spacer (FB) connecting the Ang and sFv (AngFBsFvL1 or L2; AngsFv(L2)]. Although the nature of the linker did not affect the enzymatic activity of the FB-containing fusion proteins, the fusion protein containing the L2 linker was 2.3-fold more effective than the L1 linker in competing with the labeled monoclonal IgG1 antibody for binding to the transferrin receptor. The fusion protein containing the L2 linker without the FB spacer exhibited a 13-fold decrease in binding to the transferrin receptor as well as a decrease in its capacity to degrade tRNA and to inhibit translation in the rabbit reticulocyte lysate compared to its counterpart containing the FB spacer. Binding of placental ribonuclease inhibitor (PRI) to Ang also was affected by the nature of the linker and by the presence or absence of a spacer. PRI bound to Ang and AngFBsFv(L2) and inhibited their ribonuclease activity. A 3-fold greater concentration of PRI, however, did not affect the activity of AngFBsFv(L1) or AngsFv(L2), suggesting that the conformation of these fusion proteins was altered. Binding of monoclonal and polyclonal anti-Ang antibodies to AngsFvs was also used to investigate conformational alterations of the fusion proteins. AngFBsFv(L2) was the least altered while AngFBsFv(L1) exhibited the greatest change in structure. Yet maximal concentrations of all AngsFvs elicited angiogenesis in the chick chorioallantoic membrane assay, demonstrating that Ang in all three fusion proteins remained functionally active, Consistent with all the activities, the fusion protein containing the FB spacer and L2 linker was the most cytotoxic to three different human tumor cell lines. The fusion protein lacking the FB spacer exhibited the least cytotoxicity. These data demonstrate that the linker connecting the V-H-V-L chains can affect the binding and cellular cytotoxicity of Ang immunofusions and that placement of a spacer between the antibody binding domains and Ang is necessary for optimal activity. Thus, a new class of targeted therapeutic agents containing Ang as the toxic moiety can be designed that potentially will be less immunogenic and less toxic than immunotoxins available currently. C1 NCI, FREDERICK CANC RES & DEV CTR, BIOCHEM PHYSIOL LAB, BRMP, FREDERICK, MD 21702 USA. SAIC FREDERICK, BCDP, FREDERICK, MD 21702 USA. HARVARD UNIV, SCH MED, CTR BIOCHEM & BIOPHYS SCI & MED, BOSTON, MA 02115 USA. HARVARD UNIV, SCH MED, DEPT PATHOL, BOSTON, MA 02115 USA. NR 48 TC 68 Z9 79 U1 0 U2 14 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD JAN 16 PY 1996 VL 35 IS 2 BP 545 EP 553 DI 10.1021/bi951650w PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA TQ225 UT WOS:A1996TQ22500022 PM 8555226 ER PT J AU Grahame, DA Khangulov, S DeMoll, E AF Grahame, DA Khangulov, S DeMoll, E TI Reactivity of a paramagnetic enzyme-CO adduct in acetyl-CoA synthesis and cleavage SO BIOCHEMISTRY LA English DT Article ID CARBON-MONOXIDE DEHYDROGENASE; GROWN METHANOSARCINA-THERMOPHILA; CLOSTRIDIUM-THERMOACETICUM; IRON-SULFUR; COENZYME-A; COMPLEX; SUBSTRATE; NICKEL; RES; METHANOPTERIN AB Partial reactions of acetyl-CoA cleavage by the Methanosarcina barkeri acetyl-CoA decarbonylase synthase enzyme complex were investigated by UV-visible and electron paramagnetic resonance (EPR) spectroscopy. Reaction of the enzyme complex with carbon monoxide generated an EPR-detectable adduct with principal g values of 2.089, 2.076, and 2.028, and line widths of 13.76, 16.65, and 5.41 G, respectively. The EPR signal intensity was dependent upon both enzyme and carbon monoxide concentration. A second signal with g(av) = 2.050 was generated by storage of the GO-exposed enzyme for 17 months at -70 degrees C. Reaction of the enzyme complex with low levels of CO caused reduction of the enzyme complex, but did not result in immediate formation of the NiFeC signal (designated NiFeC based on isotopic substitution studies carried out by others in analogous systems from Clostridium thermoaceticum and Methanosarcina thermophila). Further addition of CO generated the NiFeC signal, and the signal amplitude then increased progressively with increasing CO concentration. UV-visible spectra showed that enzyme Fe-S and corrinoid centers were already fully reduced at levels of CO significantly lower than needed for maximal EPR signal intensity, This result indicated that the EPR signal is formed by reaction of the reduced enzyme with CO (or a reduced one-carbon species), rather than with a one-carbon unit at the oxidation level of CO2, Addition of coenzyme A, acetyl-CoA, or tetrahydrosarcinapterin had no effect on the EPR signal, In contrast, addition of N-5-methyltetrahydrosarcinapterin (CH3-H4SPt) abolished the EPR signal, EPR spectra recorded at 20-21 K revealed that reaction with CH3-H4SPt affects only the enzyme NiFeC signal, and does not influence other EPR-detectable Fe-S center(s). The results suggest that the enzyme-CO adduct reacts with CH3-H4SPt to form an EPR-silent enzyme-acetyl species. Preincubation of the enzyme complex with CO and CH3-H4SPt, both of which were required, produced an approximately 44-fold increase in the turnover rate of acetyl-CoA synthesis. The relevance of these findings to mechanisms involving possible reductive methylation of the enzyme and/or acetyl-enzyme formation is discussed. C1 UNIFORMED SERV UNIV HLTH SCI,DEPT BIOCHEM,BETHESDA,MD 20814. NCI,BIOCHEM LAB,BETHESDA,MD 20892. RP Grahame, DA (reprint author), UNIV KENTUCKY,DEPT MICROBIOL & IMMUNOL,CHANDLER MED CTR,LEXINGTON,KY 40536, USA. NR 28 TC 31 Z9 31 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 JAN 16 PY 1996 VL 35 IS 2 BP 593 EP 600 DI 10.1021/bi9511494 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA TQ225 UT WOS:A1996TQ22500028 PM 8555232 ER PT J AU Camaioni, A Salustri, A Yanagishita, M Hascall, VC AF Camaioni, A Salustri, A Yanagishita, M Hascall, VC TI Proteoglycans and proteins in the extracellular matrix of mouse cumulus cell-oocyte complexes SO ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS LA English DT Article ID HYALURONIC-ACID SYNTHESIS; ALPHA-TRYPSIN INHIBITOR; OVARIAN GRANULOSA-CELLS; CARTILAGE PROTEOGLYCANS; ACROSOME REACTION; ZONA PELLUCIDA; GOLDEN-HAMSTER; LINK PROTEIN; INVITRO; SERUM AB In the preovulatory follicle, the oocyte is surrounded by similar to 1000 closely associated cumulus cells forming the compact form of the cumulus cell-oocyte complex (COC). In response to the gonadotropin surge, the COC in a follicle destined for ovulation undergoes expansion when the cumulus cells synthesize and organize an extensive extracellular matrix enriched in hyaluronan, Successful expansion of the COC appears to be essential for ovulation and ultimately for fertilization, We studied this process in vitro by isolating compact COCs from preovulatory mouse follicles and incubating them under conditions which promote COC expansion by retention of newly synthesized hyaluronan (HA) in the extracellular matrix around the cells. [H-3]-Leucine and [S-35]sulfate were used as precursors to label macromolecules synthesized by the cells that may be necessary for organizing the HA in this matrix. After labeling, expanded COCs were washed to remove medium and any labeled molecules that were not associated with the matrix. Macromolecules selectively associated with the matrix were then solubilized by digesting the expanded COCs briefly with Streptomyces hyaluronidase, an enzyme that specifically cleaves HA. Cells were removed by centrifugation, and the digest supernate was analyzed by molecular sieve chromatography and SDS-PAGE. A dermatan sulfate proteoglycan of large hydrodynamic size (> 1 million Da) and a similar to 46-kDa protein were the predominant labeled species identified. The proteoglycan has properties similar to proteoglycans such as aggrecan and versican which interact specifically with HA. The similar to 46-kDa protein has the same molecular size as the link protein which interacts with HA and HA-binding proteoglycans to form stable ternary complexes in a variety of extracellular matrices. We propose that the dermatan sulfate proteoglycan and the similar to 46-kDa protein synthesized by the cumulus cells form similar ternary complexes that are necessary for retaining HA in the COC matrix and hence are required for successful COC expansion. (C) 1996 Academic Press, Inc. C1 NIDR, BONE RES BRANCH, BETHESDA, MD 20892 USA. CLEVELAND CLIN FDN, DEPT BIOMED ENGN, CLEVELAND, OH 44195 USA. RP Camaioni, A (reprint author), UNIV ROMA TOR VERGATA, FAC MED, DEPT SANITA PUBBL & BIOL CELLULARE, I-00173 ROME, ITALY. OI SALUSTRI, ANTONIETTA/0000-0002-8731-1041; CAMAIONI, ANTONELLA/0000-0002-7059-2617 NR 35 TC 57 Z9 57 U1 0 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0003-9861 EI 1096-0384 J9 ARCH BIOCHEM BIOPHYS JI Arch. Biochem. Biophys. PD JAN 15 PY 1996 VL 325 IS 2 BP 190 EP 198 DI 10.1006/abbi.1996.0024 PG 9 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA TQ783 UT WOS:A1996TQ78300007 PM 8561497 ER PT J AU Davis, MD Parniak, MA Kaufman, S Kempner, E AF Davis, MD Parniak, MA Kaufman, S Kempner, E TI Structure-function relationships of phenylalanine hydroxylase revealed by radiation target analysis SO ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS LA English DT Article DE phenylalanine hydroxylase; protein oligomer; tetrahydrobiopterin; radiation damage ID RAT-LIVER; INACTIVATION; STIMULATION; INVIVO; PHOSPHORYLATION; LYSOLECITHIN; ACTIVATION AB Phenylalanine hydroxylase (PAH) purified from rat Liver is an oligomeric protein (predominantly tetramers) composed of 52-kDa subunits that are identical in primary structure, We have used radiation target analysis to probe the subunit organization of the enzyme, When 6-methyltetrahydropterin was used as the cofactor, the loss of hydroxylase activity as a function of radiation dose was defined by a single exponential decay, yielding a target size of about 120 kDa. However, when the enzyme was assayed with the natural cofactor tetrahydrobiopterin (BH4), the inactivation curves were much more complex, In these cases, the activity first increased, then decreased, as a function of radiation dose, The inactivation profile at higher radiation doses implied a target size of approximately 100 kDa. Kinetic analysis of the enzyme irradiated at 12 Mrads indicated that this enzyme was significantly activated relative to the nonirradiated sample. In addition, the irradiated enzyme was desensitized to substrate-level activation by phenylalanine, The initial increase in activity at low radiation doses is due to the destruction of a large inhibitor, Analysis of the irradiated samples by high-performance size-exclusion chromatography indicated that the hydroxylase tetramer was lost with a target size of 110 kDa. Our data indicate that the tetrameric form of purified PAH consists of two enzymatically active dimers and that BH4, interacts with a tetramer to inhibit or deactivate the enzymatic activity. C1 NIMH,BETHESDA,MD 20892. NIAMSD,BETHESDA,MD 20892. SIR MORTIMER B DAVIS JEWISH HOSP,LADY DAVIS INST MED RES,MONTREAL,PQ H3T 1E2,CANADA. MCGILL UNIV,DEPT MED,MONTREAL,PQ H3T 1E2,CANADA. NR 30 TC 15 Z9 15 U1 0 U2 1 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0003-9861 J9 ARCH BIOCHEM BIOPHYS JI Arch. Biochem. Biophys. PD JAN 15 PY 1996 VL 325 IS 2 BP 235 EP 241 DI 10.1006/abbi.1996.0029 PG 7 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA TQ783 UT WOS:A1996TQ78300012 PM 8561502 ER PT J AU Gosiewska, A Mahmoodian, F Peterkofsky, B AF Gosiewska, A Mahmoodian, F Peterkofsky, B TI Gene expression of iron-related proteins during iron deficiency caused by scurvy in guinea pigs SO ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS LA English DT Article DE vitamin C; iron; transferrin; ferritin; transferrin receptor; iron regulatory protein; iron-responsive element ID ELEMENT-BINDING-PROTEIN; TRANSFERRIN RECEPTOR; MOLECULAR-CLONING; SUBUNIT SYNTHESIS; RNA; PURIFICATION; METABOLISM; ASCORBATE; LIVER; CHAIN AB The regulation of expression of hepatic iron-related proteins was examined during iron deficiency caused by scurvy in guinea pigs. Previous studies showed that some effects of scurvy, such as suppression of collagen gene expression, result from events associated with weight loss. During the initial phase of scurvy when vitamin C is depleted but animals grow normally, serum iron levels decreased to 50% of normal. During the second phase of scurvy when animals lose weight, there was a further decrease in iron levels to 10-15% of normal. Serum transferrin levels increased during scurvy, but this increase was related neither to the rate of weight loss nor to hepatic transferrin mRNA expression, which decreased. Serum ferritin levels diminished early in scurvy with a preferential loss of the L subunit. In liver, however, both ferritin subunits were almost undetectable even in scorbutic animals gaining weight. Ferritin gene expression during vitamin C deficiency was correlated with serum ferritin levels in that the level of mRNA for the H subunit remained relatively constant while that of the L subunit decreased early. Transferrin receptor mRNA expression in liver was induced as soon as iron levels decreased early in scurvy, which is similar to results reported for iron-depleted cultured cells. In contrast to results in cell culture, expression of iron regulatory protein 1 mRNA was decreased to approximately 50% of normal early in scurvy with a concomitant decrease in hepatic cytosolic aconitase activity. Our data indicate that iron deficiency occurs early during vitamin C deficiency and leads to changes in expression of iron-related proteins that differ in some aspects from regulation by iron in cell culture. Other events associated with weight loss in late scurvy may play a further role in this regulation. (C) 1996 Academic Press, Inc. C1 NCI,BIOCHEM LAB,BETHESDA,MD 20892. NR 33 TC 12 Z9 13 U1 1 U2 3 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0003-9861 J9 ARCH BIOCHEM BIOPHYS JI Arch. Biochem. Biophys. PD JAN 15 PY 1996 VL 325 IS 2 BP 295 EP 303 DI 10.1006/abbi.1996.0037 PG 9 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA TQ783 UT WOS:A1996TQ78300020 PM 8561510 ER PT J AU Khurana, S Kreydiyyeh, S Aronzon, A Hoogerwerf, WA Rhee, SG Donowitz, M Cohen, ME AF Khurana, S Kreydiyyeh, S Aronzon, A Hoogerwerf, WA Rhee, SG Donowitz, M Cohen, ME TI Asymmetric signal transduction in polarized ileal Na+-absorbing cells: Carbachol activates brush-border but not basolateral-membrane PIP2-PLC and translocates PLC-gamma(1) only to the brush border SO BIOCHEMICAL JOURNAL LA English DT Article ID PROTEIN-KINASE-C; EPIDERMAL GROWTH-FACTOR; TYROSINE PHOSPHORYLATION; PHOSPHOLIPASE C-GAMMA-1; MUSCARINIC RECEPTOR; EXOCRINE PANCREAS; CA-2+; OSCILLATIONS; STIMULATION; INHIBITION AB In ileal Na+ absorptive cells, carbachol inhibits NaCl absorption and its component brush-border Na+/H+ exchanger, acting via basolateral membrane (BLM) receptors. This carbachol effect involves brush-border but not BLM protein kinase C. In the present work we describe another asymmetric aspect of signal transduction in these epithelial cells, this time involving phosphatidylinositol 4,5-bisphosphate (PIP2)-specific phospholipase C (PLC). Thirty seconds and 1 min after carbachol treatment, brush-border PIP2-specific PLC activity increased, returning to control levels by 2.5 min. Involvement of brush-border tyrosine kinase(s) in this effect was suggested by inhibition of the carbachol effect on NaCl absorption by the tyrosine kinase inhibitor genistein, added to the mucosal but not the serosal surface. Luminal genistein pretreatment also prevented the carbachol-induced increase in brush-border PLC activity. In contrast, carbachol exposure did not change the BLM PIP2- specific PLC activity. Western analysis and immunoprecipitation demonstrated that PLC-gamma(1) is present in the brush border and that carbachol increases the PLC-gamma(1) amount in the brush border. Both the brush border and BLM contain PLC-beta(3) and a small amount of PLC-delta(1) but no PLC-beta(1), whereas BLM lacks detectable PLC-gamma(1). No change in PLC-beta(3) or PLC-delta(1) amount in the brush border occurred with carbachol exposure. No change in tyrosine phosphorylation of brush-border PLC-gamma(1) occurred with carbachol treatment. The Ca2+ ionophore A23187 did not alter PIP2-specific PLC activity in either the brush border or the BLM. These studies demonstrate that carbachol but not Ca2+ ionophore effects on brush-border NaCl absorption are associated with increases in brush-border but not BLM PIP2-specific PLC activity and in the amount of brush-border PLC-gamma(1), and involve tyrosine phosphorylation. This asymmetric aspect of epithelial signal transduction, together with the previous demonstration of localization of high-sensitivity IP3 stores to the apical membrane area in intestinal epithelial cells, shows that different aspects of signal transduction occur at the apical and basolateral membranes in epithelia and requires studies in both domains to define mechanisms of intracellular signalling. C1 JOHNS HOPKINS UNIV,SCH MED,DEPT MED,BALTIMORE,MD 21205. JOHNS HOPKINS UNIV,SCH MED,DEPT PHYSIOL,DIV GI,BALTIMORE,MD 21205. NHLBI,BIOCHEM LAB,BETHESDA,MD 20892. FU NIDDK NIH HHS [R01 DK 26523] NR 36 TC 23 Z9 24 U1 0 U2 0 PU PORTLAND PRESS PI LONDON PA 59 PORTLAND PLACE, LONDON, ENGLAND W1N 3AJ SN 0264-6021 J9 BIOCHEM J JI Biochem. J. PD JAN 15 PY 1996 VL 313 BP 509 EP 518 PN 2 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA TR393 UT WOS:A1996TR39300021 PM 8573085 ER PT J AU Arango, V Underwood, MD Mann, JJ AF Arango, V Underwood, MD Mann, JJ TI Fewer pigmented locus coeruleus neurons in suicide victims: Preliminary results SO BIOLOGICAL PSYCHIATRY LA English DT Article DE noradrenaline; human; brain; 3-D reconstruction; suicide ID ADRENERGIC-RECEPTOR BINDING; MONOAMINE METABOLITES; SENILE DEMENTIA; FRONTAL-CORTEX; CATECHOLAMINE NEURONS; PARKINSONS-DISEASE; SYMPTOM PATTERNS; CEREBRAL-CORTEX; MOOD DISORDERS; ALZHEIMER TYPE AB Studies of the noradrenergic system in suicide victims have found evidence of alterations in cortical beta- and alpha-adrenergic receptor binding, Since these receptor changes may be secondary to altered noradrenergic input, we sought to determine whether the pigmented neurons of the locus coeruleus (LC), which provide the noradrenergic innervation to the cerebral cortex, are altered in suicide victims. We studied 11 controls without known psychiatric or neurologic disorders and six suicide victims. LC neuron number, LC volume, and neuron density were determined by computer-assisted mapping. The suicide group had 23% fewer LC neurons and a 38% lower density of LC neurons than controls. The reduction in neuron number,vas localized to the rostral two thirds of the LC. Neither the LC length nor the LC volume in suicide victims differed from controls. Altered brain noradrenergic neurotransmission in suicide victims may be due to fewer noradrenergic neurons in the LC. Further studies are needed to determine whether this noradrenergic neuron loss is associated with an underlying major depression or specifically with suicidal behavior. C1 COLUMBIA UNIV COLL PHYS & SURG, NEW YORK STATE PSYCHIAT INST, NIMH, NEW YORK, NY 10032 USA. RP Arango, V (reprint author), COLUMBIA UNIV COLL PHYS & SURG, NEW YORK STATE PSYCHIAT INST, DEPT NEUROSCI, 722 W 168TH ST, BOX 28, NEW YORK, NY 10032 USA. RI Arango, Victoria/K-9377-2015; Underwood, Mark/N-1412-2015 OI Arango, Victoria/0000-0001-8811-400X; Underwood, Mark/0000-0003-0595-8712 FU NIAAA NIH HHS [AA09004]; NIMH NIH HHS [MH40210, MH46745] NR 49 TC 83 Z9 85 U1 3 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 EI 1873-2402 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD JAN 15 PY 1996 VL 39 IS 2 BP 112 EP 120 DI 10.1016/0006-3223(95)00107-7 PG 9 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA TQ330 UT WOS:A1996TQ33000006 PM 8717609 ER PT J AU Eckardt, MJ Rohrbaugh, JW Stapleton, JM Davis, EZ Martin, PR Weingartner, HJ AF Eckardt, MJ Rohrbaugh, JW Stapleton, JM Davis, EZ Martin, PR Weingartner, HJ TI Attention-related brain potential and cognition in alcoholism-associated organic brain disorders SO BIOLOGICAL PSYCHIATRY LA English DT Article DE attention; Korsakoff; brain potentials; alcoholism; cognition ID MEMORY; SCALE C1 NIAAA,CLIN STUDIES LAB,BETHESDA,MD 20892. RI Martin, Peter/A-7738-2008 NR 21 TC 2 Z9 2 U1 1 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD JAN 15 PY 1996 VL 39 IS 2 BP 143 EP 146 DI 10.1016/0006-3223(95)00368-1 PG 4 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA TQ330 UT WOS:A1996TQ33000011 PM 8717614 ER PT J AU Schwarzenberger, P Spence, SE Gooya, JM Michiel, D Curiel, DT Ruscetti, FW Keller, JR AF Schwarzenberger, P Spence, SE Gooya, JM Michiel, D Curiel, DT Ruscetti, FW Keller, JR TI Targeted gene transfer to human hematopoietic progenitor cell lines through the c-kit receptor SO BLOOD LA English DT Article ID POLYLYSINE DNA COMPLEXES; CD34+ MARROW-CELLS; STEM-CELLS; MEDIATED ENDOCYTOSIS; ADENOVIRUS; DELIVERY; THERAPY; EXPRESSION; INFUSION; CANCER AB In this report, we describe a novel gene therapy approach for hematopoietic stem/progenitor cells using a specific receptor-mediated gene transfection procedure to target c-kit(+) cell lines. The vector consists of plasmid DNA containing a luciferase reporter gene that is condensed by electrostatic forces with polylysine (PL) covalently linked to streptavidin (binds biotinylated ligand) and PL covalently linked to adenovirus (AD; to achieve endosomal lysis) with the final addition of biotinylated steel factor (SLF-biotin). Targeted transfection of growth factor-dependent hematopoietic progenitor cell lines that express c-kit showed specific luciferase gene expression over cell lines that did not express c-kit. This effect was dependent on the dose of SLF-biotin and was competed by excess SLF or with monoclonal antibodies that recognize c-kit and block the binding of SLF to its receptor. Maximum transfection efficiency (>90%) requires a 2-hour incubation period of the vector with the cells, and maximum gene expression occurred 30 hours later. Removal of the endosomalytic agent, AD, from the vector resulted in the loss of gene expression. Vector targeting was versatile and could be changed by the addition of other biotinylated ligands. In principle, this vector should be broadly applicable to deliver genes to hematopoietic stem/progenitor cells in vitro and in vivo. (C) 1996 by The American Society of Hematology. C1 NCI,FREDERICK CANC RES & DEV CTR,BIOL RESPONSE MODIFIERS PROGRAM,LAB LEUKOCYTE BIOL,FREDERICK,MD 21702. NCI,FREDERICK CANC RES & DEV CTR,SAIC FREDERICK,BIOL CARCINOGENESIS & DEV PROGRAM,FREDERICK,MD 21702. UNIV ALABAMA,GENE THERAPY PROGRAM,BIRMINGHAM,AL. FU NCI NIH HHS [N01-CO-56000] NR 29 TC 56 Z9 56 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD JAN 15 PY 1996 VL 87 IS 2 BP 472 EP 478 PG 7 WC Hematology SC Hematology GA TR114 UT WOS:A1996TR11400006 PM 8555468 ER PT J AU Tumas, DB Spangrude, GJ Brooks, DM Williams, CD Chesebro, B AF Tumas, DB Spangrude, GJ Brooks, DM Williams, CD Chesebro, B TI High-frequency cell surface expression of a foreign protein in murine hematopoietic stem cells using a new retroviral vector SO BLOOD LA English DT Article ID FOCUS-FORMING VIRUS; LEUKEMIA-VIRUS; GENE-THERAPY; ERYTHROPOIETIN RECEPTOR; BONE-MARROW; FRIEND; MICE; HELPER; ERYTHROLEUKEMIA; 5-FLUOROURACIL AB A retroviral vector (pSFF) derived from murine Friend spleen focus forming virus was used to transduce murine hematopoietic stem cells and express a cell surface marker protein, mutated murine prion protein, in vitro and in vivo after transplantation. To enhance retroviral vector integration in bone marrow cells, mice were treated with 5-fluorouracil (5-FU) to increase stem cell mitotic activity, which peaked on day 8 post-5-FU. The infectivity titer of the vector, pSFF-mPrP-3F4, was determined by a novel assay in which antigen-positive foci of infected cells were detected after replication and spread of the vector in cultures of mixed packaging cell lines. Infection of Sca-1+/Lineage(neg-low) cells with pSFF-mPrP-3F4 resulted in marker protein expression in 40% of the progeny cells after 7 days of culture. Transplantation of marrow cells or sorted Sca-1(+)/Lineage(neg-low) cells transduced with vector resulted in 3F4-positive mPrP expression in 11% to 37% of donor-derived peripheral blood leukocytes at 2 weeks. Though the percentage of 3F4-positive blood cells gradually declined, at 28 weeks 23% of recipient mice still maintained expression of the marker gene. Expression was observed in lymphoid, myeloid, and erythroid lineages and was detected in Sca-1+/Lineage(neg-low) marrow cells. The multilineage, high-frequency expression observed suggests that pSFF may be useful in gene therapy directed at hematopoietic stem cells and their differentiated progeny. (C) 1996 by The American Society of Hematology. C1 NIAID,ROCKY MT LABS,PERSISTENT VIRAL DIS LABS,HAMILTON,MT 59840. UNIV UTAH,SCH MED,DEPT PATHOL,SALT LAKE CITY,UT. NR 52 TC 19 Z9 20 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD JAN 15 PY 1996 VL 87 IS 2 BP 509 EP 517 PG 9 WC Hematology SC Hematology GA TR114 UT WOS:A1996TR11400010 PM 8555472 ER PT J AU Ma, C Staudt, LM AF Ma, C Staudt, LM TI LAF-4 encodes a lymphoid nuclear protein with transactivation potential that is homologous to AF-4, the gene fused to MLL in t(4;11) leukemias SO BLOOD LA English DT Article ID DROSOPHILA-TRITHORAX; BINDING PROTEIN; T(4-11)(Q21-Q23); EXPRESSION; TRANSLOCATION; LYMPHOCYTES; INITIATION; SEQUENCES; TISSUES; FUSIONS AB A novel human gene, LAF-4, was isolated from a subtracted cDNA library that showed strong sequence similarity to AF-4, a gene that is translocated in t(4;11)(q21;q23) acute lymphoblastic leukemias (ALLs). In t(4;11) ALL, the AF-4 gene at 4q21 is translocated into the WILL locus at 11q23, resulting in the expression of an MLL/AF-4 fusion protein that is the presumptive oncoprotein. AF-4 and LAF-4 are homologous throughout their coding regions, yet neither protein is related to previously cloned genes. Human LAF-4 readily hybridized with genes in mouse and chicken, thus showing that this gene family has been highly conserved during vertebrate evolution. In mouse tissues, LAF-4 mRNA was found to be present at highest levels in lymphoid tissues, present at lower levels in brain and lung, and absent from other tissues. In human and mouse lymphoid cell lines, LAF-4 expression was highest in pre-B cells, intermediate in mature B cells, and absent in plasma cells, thus pointing to a potential regulatory role for LAF-4 in lymphoid development. Antibodies to LAF-4 showed it to be a nuclear protein that showed an uneven, granular immunofluorescence pattern. In vitro-translated LAF-4 was able to bind strongly to double-stranded DNA cellulose. Furthermore, both LAF-4 and AF-4 had domains that activated transcription strongly when fused to the GAL4 DNA-binding domain. Interestingly, the AF-4 transactivation domain is retained in the MLL/AF-4 fusion protein; thus, it may contribute to the transforming potential of the oncoprotein. Therefore, the cloning of LAF-4 has defined a new family of potential regulatory proteins that may function in lymphoid development and oncogenesis. (C) 1996 by The American Society of Hematology. C1 NCI,METAB BRANCH,BETHESDA,MD 20892. NR 33 TC 76 Z9 78 U1 2 U2 3 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 JAN 15 PY 1996 VL 87 IS 2 BP 734 EP 745 PG 12 WC Hematology SC Hematology GA TR114 UT WOS:A1996TR11400036 PM 8555498 ER PT J AU Karlsson, C Stenman, G Vojta, PJ BongcamRudloff, E Barrett, JC Westermark, B Paulsson, Y AF Karlsson, C Stenman, G Vojta, PJ BongcamRudloff, E Barrett, JC Westermark, B Paulsson, Y TI Escape from senescence in hybrid cell clones involves deletions of two regions located on human chromosome 1q SO CANCER RESEARCH LA English DT Article ID INDEFINITE DIVISION; GENETIC-ANALYSIS; HETEROZYGOSITY; INVITRO; FIBROBLASTS; CARCINOMAS; INVIVO AB Human normal cells have been shown to undergo a limited number of cell doublings, a phenomenon termed cellular senescence. Human chromosome 1 has been implicated in this process, and several lines of evidence indicate that there is a senescence-inducing gene or genes on human chromosome 1q. Our approach to analyze the senescence-inducing effect of chromosome 1 includes the use of somatic cell hybrid revertants. We show here that fusion of a hypoxanthine phosphoribosyl transferase-negative mouse cell line (A9) containing a human neo-tagged chromosome 1 with an immortal hamster cell line (10W-2) results in cell hybrids that senesce after a few population doublings. Rare revertants that had escaped senescence were obtained after one large fusion experiment. Thirty-five nonsenescent hybrids were obtained from a total of approximately 1 million hybrids, and 25 of these were subjected to further analysis. The presence of a single copy of human chromosome 1 in the revertant hybrids was confirmed by fluorescence in situ hybridization analysis using a chromosome 1-specific painting probe, No visible translocations or deletions of chromosome 1 were observed in any of the hybrids. Deletion mapping revealed that 11 (56%) of the hybrids analyzed had lost one or more markers on chromosome 1q. Two regions with deletions were detected, one of which has been shown to be implicated in the senescence-inducing effect exerted by chromosome 1 following monochromosome transfer (P. J. Vojta et al., manuscript submitted for publication). The present study suggests that two separate loci on human chromosome 1q may be of importance for the induction of senescence. Moreover, this set of nonsenescent revertants could be useful for future detailed analyses of the senescence-inducing loci. C1 LINKOPING UNIV,FAC HLTH SCI,DEPT CELL BIOL,S-54185 LINKOPING,SWEDEN. NIEHS,MOLEC CARCINOGENESIS LAB,RES TRIANGLE PK,NC 27709. UNIV N CAROLINA,CURRICULUM GENET & MOLEC BIOL,CHAPEL HILL,NC 27599. RP Karlsson, C (reprint author), UNIV UPPSALA HOSP,DEPT PATHOL,DAG HAMMARSKJOLDS V 20,S-75185 UPPSALA,SWEDEN. NR 26 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 0008-5472 J9 CANCER RES JI Cancer Res. PD JAN 15 PY 1996 VL 56 IS 2 BP 241 EP 245 PG 5 WC Oncology SC Oncology GA TP888 UT WOS:A1996TP88800003 PM 8542573 ER PT J AU Taylor, JA Li, Y He, M Mason, T Mettlin, C Vogler, WJ Maygarden, S Liu, E AF Taylor, JA Li, Y He, M Mason, T Mettlin, C Vogler, WJ Maygarden, S Liu, E TI p53 mutations in bladder tumors from arylamine-exposed workers SO CANCER RESEARCH LA English DT Article ID GENE MUTATION; CANCER; CARCINOMA; OVEREXPRESSION; ASSOCIATION; HOTSPOTS; SMOKING; PROTEIN AB In this study rye compared the frequency and pattern of p53 mutations in 34 bladder tumors from people with high-level occupational exposure to arylamines to those in 30 bladder tumors from people without such exposure, No differences were observed for p53 mutations between the two groups, The frequency of mutation was similar at 47% for arylamine-exposed individuals and 53% for unexposed individuals and showed a similar pattern of mutation, with GC to AT transitions accounting for the majority of the mutations in both groups. This finding suggests that arylamine exposure does not leave a mutational ''footprint'' in the p53 gene, However, compared to other tumors, bladder tumors from both exposed and unexposed individuals had a high frequency of multiple mutations and it is interesting that these mutations were highly concordant. ant, We suggest that one explanation of this pattern of mutations could be from decreased DNA repair fidelity within tumor cells, The frequency of mutation in p53 is closely linked to tumor grade and stage and so may be a late event in the development of bladder tumors. C1 UNIV N CAROLINA,CHAPEL HILL,NC 27599. UNIV S FLORIDA,TAMPA,FL 33612. NEW YORK STATE DEPT HLTH,ROSWELL PK MEM INST,BUFFALO,NY 14263. DUPONT SPECIALTY CHEM,DEEP WATER,NJ 08023. RP Taylor, JA (reprint author), NIEHS,MD A3-05,POB 12233,RES TRIANGLE PK,NC 27709, USA. RI Liu, Edison/C-4141-2008 NR 30 TC 40 Z9 41 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA PUBLIC LEDGER BLDG, SUITE 816, 150 S. INDEPENDENCE MALL W., PHILADELPHIA, PA 19106 SN 0008-5472 J9 CANCER RES JI Cancer Res. PD JAN 15 PY 1996 VL 56 IS 2 BP 294 EP 298 PG 5 WC Oncology SC Oncology GA TP888 UT WOS:A1996TP88800013 PM 8542583 ER PT J AU Szabo, E Riffe, ME Steinberg, SM Birrer, MJ Linnoila, RI AF Szabo, E Riffe, ME Steinberg, SM Birrer, MJ Linnoila, RI TI Altered cJUN expression: An early event in human lung carcinogenesis SO CANCER RESEARCH LA English DT Article ID EMBRYONAL CARCINOMA-CELLS; TRANSCRIPTION FACTOR AP-1; JUN PROTO-ONCOGENE; C-JUN; GROWTH-FACTORS; FOS; DIFFERENTIATION; OVEREXPRESSION; INDUCTION; CANCER AB Although the c-jun oncogene is an integral part of the AP-1 transcriptional complex implicated in the process of tumor promotion, its role in the pathogenesis of human tumors is unknown. We analyzed the expression and function of cJun in 110 non-small cell lung cancer (NSCLC) primary and metastatic tumors, histologically atypical areas from the surrounding lung, and 10 NSCLC cell lines to examine the role Of cJun in lung carcinogenesis, cJun was expressed in primary and metastatic lung tumors in 31% of cases, with no association with survival. Whereas normal conducting airway and alveolar epithelia in general did not express cjun by immunohistochemistry, histologically atypical areas were frequently positive for cJun, regardless of the status of the corresponding tumor. Multiple members of the jun and fos gene families were frequently expressed at the mRNA level in vitro, with detectable functional activity (as defined by AP-1-specific DNA binding and/or transactivation of an AP-1-driven reporter construct) present in all 10 NSCLC cell lines examined. Although tumor-promoting phorbol esters had little effect on c-jun expression, serum stimulation generally resulted in significant c-jun induction in NSCLC cell lines. These data show that cJun expression is altered early during human lung carcinogenesis and that dun may function as a mediator of growth factor signals in NSCLC. C1 NCI,BIOSTAT & DATA MANAGEMENT SECT,ROCKVILLE,MD 20850. RP Szabo, E (reprint author), NCI,DIV CANC PREVENT & CONTROL,BIOMARKERS & PREVENT RES BRANCH,9610 MED CTR DR,ROOM 300,ROCKVILLE,MD 20850, USA. NR 51 TC 67 Z9 69 U1 0 U2 3 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA PUBLIC LEDGER BLDG, SUITE 816, 150 S. INDEPENDENCE MALL W., PHILADELPHIA, PA 19106 SN 0008-5472 J9 CANCER RES JI Cancer Res. PD JAN 15 PY 1996 VL 56 IS 2 BP 305 EP 315 PG 11 WC Oncology SC Oncology GA TP888 UT WOS:A1996TP88800015 PM 8542585 ER PT J AU Yamamoto, M Mohanam, S Sawaya, R Fuller, GN Seiki, M Sato, H Gokaslan, ZL Liotta, LA Nicolson, GL Rao, JS AF Yamamoto, M Mohanam, S Sawaya, R Fuller, GN Seiki, M Sato, H Gokaslan, ZL Liotta, LA Nicolson, GL Rao, JS TI Differential expression of membrane-type matrix metalloproteinase and its correlation with gelatinase A activation in human malignant brain tumors in vivo and in vitro SO CANCER RESEARCH LA English DT Article ID TISSUE INHIBITOR; IV COLLAGENASE; HUMAN-FIBROBLASTS; CONCANAVALIN-A; CELL-LINES; TIMP-2; PROGELATINASE; ASSOCIATION; METASTASIS; INVASION AB In this study, we investigated the expression of activated gelatinase A and membrane-type metalloproteinase (MT-MMP) induced by concanavalin A (ConA) in four highly invasive glioma cell lines (UWR2, UWR3, U251MG, and SNB-19). We also examined gelatinase A and MT-MMP expression in human brain tumor tissues in vivo. Gelatin zymography showed that all four cen lines expressed latent progelatinase A (M(r) 66,000). Activated gelatinase A (M(r) 62,000) was induced by ConA in only UWR2 or UWR3 cells. MT-MMP mRNA was present in all four cell lines prior to ConA treatment, and the relative hybridization signals were 1, 0.80, 0.25, and 0.15 in UWR2, UWR3, U251MG, and SNB-19 cells, respectively. These mRNA signals were dramatically increased (2.8-, 5.4-, and 2.2-fold in UWR2, UWR3, and U251MG cells, respectively) following ConA treatment; however, MT-MMP mRNA expression was unchanged in SNB-19 cells. MT-MMP protein was detected in various amounts in the four cell lines, but only after ConA pretreatment. The amount of MT-MMP mRNA was unchanged in SNB-19 after ConA treatment, and the MT-MMP mRNA level in ConA-treated U251MG was lower than in UWR2 and UWR3 without ConA treatment. MT-MMP protein was detected in SNB-19 and U251 cell lines only after Con4 treatment. Gelatin zymography of human brain tumor tissues revealed that almost all samples examined contained a latent form of gelatinase A, whereas the activated form of gelatinase A was only seen in metastatic lung adenocarcinomas and malignant astrocytomas, and especially in glioblastomas. MT-MMP mRNA levels were significantly higher in malignant astrocytomas than in low-grade gliomas and normal brain tissues. These results were confirmed by PCR analysis, which shelved that MT-MMP mRNA was absent or barely detectable in normal brain white matter but was easily detectable in malignant astrocytomas. Immunohistochemistry of MT-MMP in frozen sections showed that MT-MMP was localized in neoplastic astrocytes of malignant astrocytomas but was undetectable in normal white brain matter. The data indicate that MT-MMP is present in malignant human glial tumors and that MT-MMP expression correlates with expression and activation of gelatinase A during malignant progression in vivo. A direct correlation between the levels of MT-MMP protein and its transcripts was not found in vitro, suggesting that MT-MMP expression in glioma cell lines might be regulated either at the level of transcription message stability or at posttranscription. Altered MT-MMP expression might contribute, in part, to gelatinase A activation, which in turn facilitates invasion of these tumors. C1 UNIV TEXAS, MD ANDERSON CANC CTR, DEPT NEUROSURG, HOUSTON, TX 77030 USA. UNIV TEXAS, MD ANDERSON CANC CTR, DEPT PATHOL, HOUSTON, TX 77030 USA. UNIV TEXAS, MD ANDERSON CANC CTR, DEPT TUMOR BIOL, HOUSTON, TX 77030 USA. KANAZAWA UNIV, CANC RES INST, DEPT MOLEC VIROL & ONCOL, KANAZAWA, ISHIKAWA 920, JAPAN. NCI, PATHOL LAB, BETHESDA, MD 20892 USA. RI Seiki, Motoharu/K-9443-2015; SATO, Hiroshi/D-8454-2015; OI Fuller, Gregory/0000-0001-9447-2647 FU NCI NIH HHS [CA 56792] NR 46 TC 251 Z9 262 U1 0 U2 6 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 JAN 15 PY 1996 VL 56 IS 2 BP 384 EP 392 PG 9 WC Oncology SC Oncology GA TP888 UT WOS:A1996TP88800026 PM 8542596 ER PT J AU Muller, JR Jones, GM Potter, M Janz, S AF Muller, JR Jones, GM Potter, M Janz, S TI Detection of immunoglobulin c-myc recombinations in mice that are resistant to plasmacytoma induction SO CANCER RESEARCH LA English DT Article ID POLYMERASE CHAIN-REACTION; MESSENGER-RNA; TUMORS AB Interchromosomal recombinations between c-myc and immunoglobulin sequences can be found in preneoplastic lesions (oil granulomata) during pristane-induced plasmacytoma development in susceptible BALB/cAn mice. In this study we used a more sensitive approach, hybridization-enriched templates with nested PCR, to detect microclones with Ig alpha/c-myc recombinations in oil granulomata of susceptible and resistant mice. Recombinations were detected in as many as 73% (32/44) of plasmacytoma-susceptible BALB/cAn mice 30 days after an injection of pristane. Mice that are resistant to plasmacytoma induction can also harbor recombination-positive cells, but these are less frequent [2/20 DBA/2N, 8/20 (BALB/cAn x DBA/2N)F-1, hereafter called CD2F(1)]. The clones in DBA/2N mice were small (<400 cells), whereas in BALB/cAn, the oil granuloma harbored up to several thousand of these cells. We conclude that the molecular machinery for generating characteristic interchromosomal recombinations can be found in all strains of mice. Both the frequency of generating Ig alpha/c-myc recombinations and the expansion of recombination-positive cells are greater in susceptible mice than in resistant strains. RP Muller, JR (reprint author), NCI,GENET LAB,BLDG 37,ROOM 2B-09,37 CONVENT DR,BETHESDA,MD 20892, USA. NR 12 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 0008-5472 J9 CANCER RES JI Cancer Res. PD JAN 15 PY 1996 VL 56 IS 2 BP 419 EP 423 PG 5 WC Oncology SC Oncology GA TP888 UT WOS:A1996TP88800031 PM 8542601 ER PT J AU Cannon, RO Lesch, M AF Cannon, RO Lesch, M TI The search for a better exercise test - A self-fulfilling prophecy? SO CIRCULATION LA English DT Editorial Material DE editorials; coronary disease; exercise; electrocardiography; ischemia ID CORONARY-ARTERY DISEASE; SLOPE; DEPRESSION; SEVERITY C1 HENRY FORD HOSP,DEPT INTERNAL MED,DETROIT,MI 48202. RP Cannon, RO (reprint author), NHLBI,CARDIOL BRANCH,BLDG 10,ROOM 7B15,10 CTR DR,MSC 1650,BETHESDA,MD 20892, USA. NR 12 TC 0 Z9 0 U1 0 U2 0 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD JAN 15 PY 1996 VL 93 IS 2 BP 205 EP 207 PG 3 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA TP779 UT WOS:A1996TP77900002 PM 8548888 ER PT J AU Dichek, DA Anderson, J Kelly, AB Hanson, SR Harker, LA AF Dichek, DA Anderson, J Kelly, AB Hanson, SR Harker, LA TI Enhanced in vivo antithrombotic effects of endothelial cells expressing recombinant plasminogen activators transduced with retroviral vectors SO CIRCULATION LA English DT Article DE plasminogen activators; thrombosis; endothelium ID PLATELET-DEPENDENT THROMBOSIS; NITRIC-OXIDE; GENE-EXPRESSION; VASCULAR GRAFTS; RELAXING FACTOR; CULTURED HUMAN; ARTERIAL-WALL; BABOONS; INTERRUPTION; INHIBITOR-1 AB Background The effects of regulating endothelial cell (EC) plasminogen activator production on thrombus accumulation in vivo are incompletely understood. By overexpressing plasminogen activators in ECs via gene transfer, the hypothesis was tested that increased levels of plasminogen activators inhibit the accumulation of thrombus in vivo. Methods and Results Cultured baboon ECs transduced with human cDNAs for wild-type tissue plasminogen activator (TPA) or for glycosylphosphatidylinositol-anchored urokinase-type plasminogen activator (a-UPA) were seeded onto collagen-coated segments of vascular graft (collagen segments) and exposed overnight to flow using an in vitro perfusion circuit. The antigenic levels of TPA and UPA each increased 10-fold in the media perfusing the corresponding transduced ECs compared with untransduced ECs (P less than or equal to.05 in both cases). In baboons the antithrombotic effects of TPA-transduced or a-UPA-transduced ECs were measured as In-111-platelet deposition and I-125-fibrin accumulation on collagen segments bearing sparsely attached ECs (transduced versus untransduced) inter posed in exteriorized arteriovenous femoral shunts. Platelet-rich thrombus formed on the collagen segments with fibrin-rich thrombus propagated distally. The presence of TPA-transduced or a-UPA-transduced ECs on collagen segments at a density of 25 000 ECs/cm(2) decreased In-111-platelet deposition and I-125-fibrin accumulation on collagen surfaces compared with untransduced ECs present at equivalent density (P<.05 for platelet deposition with TPA-transduced ECs and P<.05 for platelet deposition on the propagated tail, as well as fibrin accumulation on the graft with a-UPA-transduced ECs). The systemic levels of fibrinopeptide A, thrombin-antithrombin complex, D-dimer, and both local and systemic levels of TPA and UPA were not increased by transduced ECs compared with untransduced ECs. The focal antithrombotic effects of transduced ECs appear to be due to local enhancement of thrombolysis. Conclusions ECs transduced with recombinant TPA and a-UPA enhance local antithrombotic activity in vivo. This strategy of attaching transduced ECs overexpressing plasminogen activators may be therapeutically useful by preventing thrombo-occlusive failure of implanted cardiovascular devices or mechanically denuded vessels. C1 EMORY UNIV,SCH MED,DIV HEMATOL & ONCOL,DEPT MED,ATLANTA,GA 30322. EMORY UNIV,SCH MED,YERKES REG PRIMATE RES CTR,ATLANTA,GA 30322. NHLBI,MOLEC HEMATOL BRANCH,BETHESDA,MD 20892. FU NCRR NIH HHS [RR-00165]; NHLBI NIH HHS [HL-41619, HL-48667] NR 49 TC 72 Z9 76 U1 0 U2 0 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD JAN 15 PY 1996 VL 93 IS 2 BP 301 EP 309 PG 9 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA TP779 UT WOS:A1996TP77900017 PM 8548903 ER PT J AU RodriguezGarcia, MI Kozak, CA Morgan, RO Fernandez, MP AF RodriguezGarcia, MI Kozak, CA Morgan, RO Fernandez, MP TI Mouse annexin V chromosomal localization, cDNA sequence conservation, and molecular evolution SO GENOMICS LA English DT Article ID AMINO-ACID-SEQUENCE; MEMBRANE-BINDING PROTEIN; PHOSPHOLIPID-BINDING; HOMOLOGY; FAMILY; VIRUS; GENE AB A full-length cDNA encoding mouse annexcin V (ANX5) was cloned, sequenced, and utilized for chromosomal mapping. The gene Lies on mouse chromosome 3 in close Linkage with the fibroblast growth factor 2 (basic) gene and is syntenic with other genes known to have orthologous counterparts on human chromosome 4q. The open reading frame encoded a protein of 319 amino acids (aa), with 92-96% identity to ANX5 in other species. Internal repeat 3 of mouse ANX5 exhibited the highest level of nonconservative aa replacements with respect to other annexin subfamilies, but the greatest sequence conservation among ANX5 species members. This region may thus contain features that distinguish ANX5 from other annexins in properties or function. Phylogenetic analysis and homology testing of AMX5 members indicated that the 34-kDa annexin from Torpedo marmorata may also belong to this subfamily. Comparison of nine species of ANX5 led to an estimation of the unit evolutionary mutation rate at 1% aa replacements every 8 million years, comparable to other annexins. (C) 1996 Academic Press, Inc. C1 UNIV OVIEDO,FAC MED,DEPT BIOCHEM & MOLEC BIOL,E-33006 OVIEDO,SPAIN. NIAID,BETHESDA,MD 20892. RI Rodriguez, Isabel/L-9327-2013; OI Fernandez-Fernandez, Maria Pilar/0000-0001-6552-409X NR 47 TC 12 Z9 13 U1 0 U2 5 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0888-7543 J9 GENOMICS JI Genomics PD JAN 15 PY 1996 VL 31 IS 2 BP 151 EP 157 DI 10.1006/geno.1996.0026 PG 7 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA TT138 UT WOS:A1996TT13800002 PM 8824796 ER PT J AU Maemura, K Kurihara, H Kurihara, Y Oda, H Ishikawa, T Copeland, NG Gilbert, DJ Jenkins, NA Yazaki, Y AF Maemura, K Kurihara, H Kurihara, Y Oda, H Ishikawa, T Copeland, NG Gilbert, DJ Jenkins, NA Yazaki, Y TI Sequence analysis, chromosomal location, and developmental expression of the mouse preproendothelin-1 gene SO GENOMICS LA English DT Article ID VASOCONSTRICTOR PEPTIDE; ENDOTHELIN RECEPTOR; NUCLEOTIDE-SEQUENCE; BIOLOGICAL-ACTIVITY; CLONING; CDNA; ORGANIZATION; FAMILY; LINKAGE; GENOME AB Recent studies have designated endothelins (ETs) as morphogenetic factors in embryonic development. In the present study, we cloned and characterized the mouse preproendothelin-1 (preproET-1) gene (Edn1) and examined its expression in reference to development. Edn1 comprises five exons, and the open reading frame encodes the 202-amino-acid preproET-1. The sequences and structural organization of Edn1 are highly homologous to those of other species, especially in the terminal 200-bp sequence of the 3'-noncoding region. Interspecific backcross mapping located Edn1 in the central region of chromosomal 13, where a mouse mutation, congenital hydrocephalus (ch), is also mapped. The highest expression of Edn1 mRNA is detected in the lung in adult mice, whereas Edn1 is predominantly expressed in the epithelium and mes enchyme of the pharyngeal arches and in the endothelium of the large arteries. Edn1 expression and ET-1 peptide levels in the lung progressively increase during the perinatal stage, whereas the expression of Edn3, a gene encoding ET-3, reciprocally decreases. These results suggest that Edn1 expression is developmentally regulated in different tissues and organs in mice in a spatial- and temporal-specific manner. (C) 1996 Academic Press, Inc. C1 UNIV TOKYO,FAC MED,DEPT INTERNAL MED 3,BUNKYO KU,TOKYO 113,JAPAN. UNIV TOKYO,FAC MED,DEPT PATHOL,BUNKYO KU,TOKYO 113,JAPAN. NCI,FREDERICK CANC RES & DEV CTR,BASIC RES PROGRAM,ABL,MAMMALIAN GENET LAB,FREDERICK,MD 21702. FU NCI NIH HHS [N01-CO-46000] NR 36 TC 40 Z9 41 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 JAN 15 PY 1996 VL 31 IS 2 BP 177 EP 184 DI 10.1006/geno.1996.0029 PG 8 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA TT138 UT WOS:A1996TT13800005 PM 8824799 ER PT J AU Bram, RJ Valentine, V Shapiro, DN Jenkins, NA Gilbert, DJ Copeland, NG AF Bram, RJ Valentine, V Shapiro, DN Jenkins, NA Gilbert, DJ Copeland, NG TI The gene for calcium-modulating cyclophilin ligand (CAMLG) is located on human chromosome 5q23 and a syntenic region of mouse chromosome 13 SO GENOMICS LA English DT Article ID LINKAGE; PROTEIN AB The CAMLG gene encodes a novel cyclophilin B-binding protein called calcium-modulating cyclo-philin ligand, which appears to be involved in the regulation of calcium signaling in T lymphocytes and other cells. The murine homolog, Caml, was localized by interspecific backcross analysis to the middle of chromosome 13. Ey fluorescence in situ hybridization, this gene was localized to human chromosome 5 in a region (q23) known to be syntenic to mouse chromosome 13. These results provide further evidence supporting the extensive homology between human chromosome 5q and mouse chromosome 13. In addition, the results will provide a basis for further evaluation of cytogenetic anomalies that may contribute to inherited defects in calcium signaling or immune system function. (C) 1996 Academic Press, Inc. C1 ST JUDE CHILDRENS RES HOSP, DEPT HEMATOL ONCOL, MEMPHIS, TN 38105 USA. UNIV TENNESSEE, DEPT PEDIAT, MEMPHIS, TN 38105 USA. NCI, FREDERICK CANC RES & DEV CTR, ABL BASIC RES PROGRAM, MAMMALIAN GENET LAB, FREDERICK, MD 21702 USA. RP Bram, RJ (reprint author), ST JUDE CHILDRENS RES HOSP, DEPT EXPTL ONCOL, 332 N LAUDERDALE, MEMPHIS, TN 38105 USA. FU NCI NIH HHS [CA-21765, N01-CO46000] NR 15 TC 4 Z9 5 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0888-7543 J9 GENOMICS JI Genomics PD JAN 15 PY 1996 VL 31 IS 2 BP 257 EP 260 DI 10.1006/geno.1996.0044 PG 4 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA TT138 UT WOS:A1996TT13800020 PM 8824814 ER PT J AU Pathak, BG Shull, GE Jenkins, NA Copeland, NG AF Pathak, BG Shull, GE Jenkins, NA Copeland, NG TI Mouse chromosomal location of four Na/H exchanger isoform genes SO GENOMICS LA English DT Article ID LOCALIZATION; EXPRESSION AB The Na/H exchanger genes Slc9a1, Slc9a2, Slc9a3, and Slc9a4 have been mapped in the mouse using an interspecific backcross panel. These loci map to previously defined homologous regions between human and mouse chromosomes and provide additional information regarding human/mouse comparative map ping. (C) 1996 Academic Press, Inc. C1 NCI,FREDERICK CANC RES & DEV CTR,ABL BASIC RES PROGRAM,MAMMALIAN GENET LAB,FREDERICK,MD 21702. UNIV CINCINNATI,COLL MED,DEPT MOLEC GENET BIOCHEM & MICROBIOL,CINCINNATI,OH 45267. FU NCI NIH HHS [N01-CO46000]; NHLBI NIH HHS [HL 41496] NR 13 TC 10 Z9 10 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 JAN 15 PY 1996 VL 31 IS 2 BP 261 EP 263 DI 10.1006/geno.1996.0045 PG 3 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA TT138 UT WOS:A1996TT13800021 PM 8824815 ER PT J AU Liotta, LA AF Liotta, LA TI Probing the depths of degradation: Matrix metalloproteinase-2 and endometrial menstrual breakdown SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Editorial Material RP Liotta, LA (reprint author), NCI,PATHOL LAB,BLDG 10,BETHESDA,MD 20892, USA. NR 9 TC 8 Z9 8 U1 0 U2 0 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 222 E 70TH STREET, NEW YORK, NY 10021 SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD JAN 15 PY 1996 VL 97 IS 2 BP 273 EP 274 DI 10.1172/JCI118412 PG 2 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA TR380 UT WOS:A1996TR38000001 PM 8567944 ER PT J AU Yoo, YD Ueda, H Park, K Flanders, KC Lee, YI Jay, G Kim, SJ AF Yoo, YD Ueda, H Park, K Flanders, KC Lee, YI Jay, G Kim, SJ TI Regulation of transforming growth factor-beta 1 expression by the hepatitis B virus (HBV) X transactivator SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article DE hepatitis B virus; TGF-beta 1; transcription; immunohistochemistry; hepatocellular carcinoma ID HUMAN-IMMUNODEFICIENCY-VIRUS; BETA MESSENGER-RNA; TRANSCRIPTION FACTOR; GENE-PRODUCT; HEPATOCELLULAR-CARCINOMA; TRANS-ACTIVATION; LIVER-CANCER; FACTOR-ALPHA; 3T3 CELLS; C-JUN AB TGF-beta 1 has been implicated in the pathogenesis of liver disease. The high frequency of detection of the hepatitis B virus X (HBx) antigen in liver cells from patients with chronic hepatitis, cirrhosis, and liver cancer suggested that expression of HBx and TGF-beta 1 may be associated. To test this possibility, we examined the expression of TGF-beta 1 in the liver of transgenic mice expressing the HBx gene. We show that the patterns of expression of TGF-beta 1 and Hbx protein are similar in these mice and that HBx activates transcription of the TGF-beta 1 gene in transfected hepatoma cells. The cis-acting element within the TGF-beta 1 gene that is responsive to regulation by Hbx is the binding site for the Egr family of transcription factors. We further show that the Egr-1 protein associates with the HBx protein, allowing HBx to participate in the transcriptional regulation of immediate-early genes. Our results suggest that expression of Hbx might induce expression of TGF-beta 1 in the early stages of infection and raise the possibility that TGF-beta 1 may play a role in hepatitis B virus pathogenesis. C1 NCI,CHEMOPREVENT LAB,BETHESDA,MD 20892. AMER RED CROSS,JEROME H HOLLAND LAB,DEPT VIROL,ROCKVILLE,MD 20855. KOREA INST SCI & TECHNOL,GENET ENGN RES INST,GENET MOLEC LAB,TAEJON 305606,SOUTH KOREA. RI Jay, Gregory/C-6346-2013 FU NCI NIH HHS [CA-51886] NR 67 TC 133 Z9 140 U1 0 U2 0 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 222 E 70TH STREET, NEW YORK, NY 10021 SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD JAN 15 PY 1996 VL 97 IS 2 BP 388 EP 395 DI 10.1172/JCI118427 PG 8 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA TR380 UT WOS:A1996TR38000016 PM 8567959 ER PT J AU Wang, Q Marini, JC AF Wang, Q Marini, JC TI Antisense oligodeoxynucleotides selectively suppress expression of the mutant alpha 2(I) collagen allele in type IV osteogenesis imperfecta fibroblasts - A molecular approach to therapeutics of dominant negative disorders SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article DE connective tissue; gene therapy; bone disease; connective tissue diseases; collagen diseases ID 3T3 CELLS; RNA; GENE; OLIGONUCLEOTIDES; PROCOLLAGEN; MUTATION; INVIVO; HETEROGENEITY; TRANSLATION; INHIBITION AB We are investigating the use of antisense oligodeoxynucleotides to selectively suppress expression of the mutant type I collagen allele in osteogenesis imperfecta (OI). In this report, we target a human collagen mutation in its natural cellular context. We used cultured fibroblasts from a case of type IV OI, in which the mutant alpha 2(I) allele produces mRNA with exon 16 deleted due to a point mutation in the splice donor site. Lipid-mediated transfection was used to deliver antisense, sense and missense phosphorothioates targeted to both the abnormal mRNA exon 15/17 junction and the nuclear level point mutation. Significant suppression of the mutant protein chain and mRNA was achieved with antisense oligonucleotide to both mRNA and nuclear levels, Mutant protein was suppressed to 44-47% and mutant alpha 2(I) mRNA to 37-43% of their levels in control cells, indicating decreased mRNA as the basis for suppression. Selectivity of mutant allele suppression was better with an mRNA target: suppression was sequence specific and normal mRNA was expressed at 79% of its level in untreated cells. With a nuclear target, significant suppression of mutant mRNA occurred not only with antisense and sense, but also with missense oligonucleotide, which suppressed mutant mRNA to 60% of its level in untreated cells. We also investigated the time course of suppression of protein and mRNA in response to a 4 h transfection of antisense oligonucleotide. From 24-72 h after transfection, mutant protein was suppressed to similar to 50% of its untreated level and suppression of mutant message was significantly greater than that of normal message. The suppression achieved in these studies is insufficient for clinical intervention, but our results provide support for further development of antisense therapy as an approach to the treatment of dominant negative disorders. C1 NICHHD,HERITABLE DISORDERS BRANCH,SECT CONNECT TISSUE DISORDERS,BETHESDA,MD 20892. NR 22 TC 35 Z9 35 U1 0 U2 0 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 222 E 70TH STREET, NEW YORK, NY 10021 SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD JAN 15 PY 1996 VL 97 IS 2 BP 448 EP 454 DI 10.1172/JCI118434 PG 7 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA TR380 UT WOS:A1996TR38000023 PM 8567966 ER PT J AU Xu, QB Liu, YS Gorospe, M Udelsman, R Holbrook, NJ AF Xu, QB Liu, YS Gorospe, M Udelsman, R Holbrook, NJ TI Acute hypertension activates mitogen-activated protein kinases arterial wall SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article DE hypertension; MAP kinases; ERK/JNK; transcription factors; artery remodeling ID SMOOTH-MUSCLE CELLS; CARDIAC GENE-EXPRESSION; AGE-DEPENDENT RESPONSE; C-JUN; GROWTH; FOS; INDUCTION; MYOCYTES; COMPLEX; STRESS AB Mitogen-activated protein (MAP) kinases are rapidly activated in cells stimulated with various extracellular signals by dual phosphorylation of tyrosine and threonine residues. They are thought to play a pivotal role in transmitting transmembrane signals required for cell growth and differentiation, Herein we provide evidence that two distinct classes of MAP kinases, the extracellular signal-regulated kinases (ERK) and the c-Jun NH2-terminal kinases (JNK), are transiently activated in rat arteries (aorta, carotid and femoral arteries) in response to an acute elevation in blood pressure induced by either restraint or administration of hypertensive agents (i.e., phenylephrine and angiotensin II). Kinase activation is followed by an increase in c-fos and c-jun gene expression and enhanced activating protein 1 (AP-1) DNA-binding activity. Activation of ERK and JNK could contribute to smooth muscle cell hypertrophy/hyperplasia during arterial remodeling due to frequent and/or persistent elevations in blood pressure. C1 NIA,SECT GENE EXPRESS & AGING,BALTIMORE,MD 21224. JOHNS HOPKINS UNIV HOSP,DIV ENDOCRINE SURG,BALTIMORE,MD 21287. RI Liu, Yusen/E-3527-2011 FU NIDDK NIH HHS [DK02064-04] NR 51 TC 158 Z9 167 U1 0 U2 1 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 222 E 70TH STREET, NEW YORK, NY 10021 SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD JAN 15 PY 1996 VL 97 IS 2 BP 508 EP 514 DI 10.1172/JCI118442 PG 7 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA TR380 UT WOS:A1996TR38000031 PM 8567974 ER PT J AU Molnar, A Wu, P Largespada, DA Vortkamp, A Scherer, S Copeland, NG Jenkins, NA Bruns, G Georgopoulos, K AF Molnar, A Wu, P Largespada, DA Vortkamp, A Scherer, S Copeland, NG Jenkins, NA Bruns, G Georgopoulos, K TI The Ikaros gene encodes a family of lymphocyte-restricted zinc finger DNA binding proteins, highly conserved in human and mouse SO JOURNAL OF IMMUNOLOGY LA English DT Article ID RECEPTOR-ALPHA-GENE; T-CELL DEVELOPMENT; FUNCTIONAL-CHARACTERIZATION; TRANSCRIPTION FACTORS; KAPPA-B; EXPRESSION; IDENTIFICATION; REGULATOR; SEQUENCES; MEDIATOR AB The Ikaros gene is an essential regulator in the development and homeostasis of the mouse lymphopoietic system, To study the role of the Ikaros gene in the human lymphopoietic system, we cloned and characterized human Ikaros cDNAs. In the human, as in the mouse, differential splicing of Ikaros primary transcripts generates a family of lymphoid-restricted zinc finger DNA binding proteins, highly conserved in sequence composition and relative expression to the mouse homologues, Expression of Ikaros isoforms is highly restricted to the lymphopoietic system and is particularly enriched in maturing thymocytes, The Ikaros gene maps at a syntenic locus located on the short arm of human chromosome 7 and on mouse chromosome 11 next to the epidermal growth factor receptor (Egfr), The high degree of conservation of the Ikaros gene at the genetic and expression levels strongly suggests that it plays a fundamental role in the ontogeny of the lymphopoietic system across species. C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,CUTANEOUS BIOL RES CTR,BOSTON,MA 02129. HARVARD UNIV,MASSACHUSETTS GEN HOSP,CHILDRENS HOSP,SCH MED,BOSTON,MA 02129. NCI,FREDERICK CANC RES & DEV CTR,ABL BASIC RES PROGRAM,MAMMALIAN GENET LAB,FREDERICK,MD 21702. HOSP SICK CHILDREN,DEPT GENET,TORONTO,ON M5G 1X8,CANADA. KLINIKUM PHILIPPS UNIV,MARBURG,GERMANY. RI Howe, Jennifer/I-9013-2012; Scherer, Stephen /B-3785-2013 OI Scherer, Stephen /0000-0002-8326-1999 FU NIAID NIH HHS [R01AI33062] NR 22 TC 107 Z9 113 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 JAN 15 PY 1996 VL 156 IS 2 BP 585 EP 592 PG 8 WC Immunology SC Immunology GA TP366 UT WOS:A1996TP36600022 PM 8543809 ER PT J AU Zhai, YF Yang, JC Kawakami, Y Spiess, P Wadsworth, SC Cardoza, LM Couture, LA Smith, AE Rosenberg, SA AF Zhai, YF Yang, JC Kawakami, Y Spiess, P Wadsworth, SC Cardoza, LM Couture, LA Smith, AE Rosenberg, SA TI Antigen-specific tumor vaccines - Development and characterization of recombinant adenoviruses encoding MART1 or gp100 for cancer therapy SO JOURNAL OF IMMUNOLOGY LA English DT Article ID CYSTIC-FIBROSIS; GENE-THERAPY; VIRUS; GLYCOPROTEIN; LYMPHOCYTES; EXPRESSION AB The human melanoma tumor Ags, MART1 and gp100, are specifically recognized by HLA-A2-restricted CD8(+) CTLs derived from melanoma patients and appear to be involved in tumor regression, In order to develop immunizing vectors for the treatment of patients with metastatic melanoma, replication-defective recombinant adenoviruses, Ad2CMV-MART1 and Ad2CMV-gp100, which encode these tumor Ags, have been generated, Infection of non-ag expressing HLA-A2(+) cell lines A375 and MDA-231 with the vectors resulted in recognition by Ag-specific CTLs as demonstrated by specific target cell lysis and release of cytokines, including IFN-gamma, TNF-alpha, and granulocyte-macrophage-CSF. Sodium butyrate and TNF-alpha can further augment adenovirus-mediated transgene expression and increase recognition by specific CTLs, Although adenovirus-infected cells expressed the E3/19K protein at detectable levels, significant reduction of surface MHC class I expression was observed in only 3 of 10 tumor cell lines infected with either Ad2CMV-MART1 or Ad2CMV-gp100, Because of the suspected homology between the human MART1 and gp100 genes and their murine counterparts, we immunized C57BL/6 mice with these recombinant adenoviruses and demonstrated that immunization with Ad2CMV-gp100 could protect mice from murine melanoma B16 challenge administered intradermally, Depletion of CD8(+) but not CD4+ T cells in vivo from Ad2CMV-gp100-vaccinated mice eliminated the protective effect, The anti-gp100 T cells induced by Ad2CMV-gp100 vaccination appeared to be responsible for the protection, Thus, these recombinant adenoviruses encoding tumor Ags may be useful as vaccines to induce specific T cell immunity for cancer therapy. C1 GENZYME CORP,FRAMINGHAM,MA 01701. RP Zhai, YF (reprint author), NCI,SURG BRANCH,BLDG 10,ROOM 2B4G,BETHESDA,MD 20892, USA. RI Kawakami, Yutaka /E-7429-2013 OI Kawakami, Yutaka /0000-0003-4836-2855 NR 33 TC 154 Z9 155 U1 0 U2 4 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD JAN 15 PY 1996 VL 156 IS 2 BP 700 EP 710 PG 11 WC Immunology SC Immunology GA TP366 UT WOS:A1996TP36600036 PM 8543823 ER PT J AU Doherty, TM Seder, RA Sher, A AF Doherty, TM Seder, RA Sher, A TI Induction and regulation of IL-15 expression in murine macrophages SO JOURNAL OF IMMUNOLOGY LA English DT Article ID IFN-GAMMA; T-CELLS; PROLIFERATION; INTERLEUKIN-2 AB IL-15 is a recently described cytokine which resembles IL-2 in its biologic activities, stimulating T cell and NK cell proliferation and activation as well as enhancing B cell expansion and Ab production, Unlike IL-2, IL-15 is not produced by lymphocytes, but instead (at least among cells of the immune system) appears to be synthesized primarily by monocyte/macrophages. We have examined the induction of IL-15 in murine macrophages (by semiquantitative reverse transcriptase-PCR and bioassay) in response to a variety of different macrophage-activating stimuli and compared the regulation of IL-15 production to that of IL-12 and TNF-alpha, Optimal induction of IL-15, in each of the macrophage populations tested, was found to require both priming (IFN-gamma) and triggering (LPS, mycobacteria, or Toxoplasma gondii) stimuli. When compared with IL-12 mRNA synthesis by the same macrophages, IL-15 mRNA production was more resistant to inhibition by the down-regulatory cytokines IL-4, IL-13, and TGF-beta. Moreover, IL-10, which is inhibitory for most other monokines, increased levels of IL-15 mRNA found after stimulation. These data establish IL-15 as a product of the macrophage/monocyte lineage, which is up-regulated on activation. IL-15 could thus play an important role in the initiation of immune responses by microbial agents. C1 NIAID,CLIN INVEST LAB,LYMPHOKINE REGULAT UNIT,BETHESDA,MD 20892. RP Doherty, TM (reprint author), NIAID,PARASIT DIS LAB,IMMUNOBIOL SECT,BLDG 4,BETHESDA,MD 20892, USA. NR 28 TC 270 Z9 277 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 JAN 15 PY 1996 VL 156 IS 2 BP 735 EP 741 PG 7 WC Immunology SC Immunology GA TP366 UT WOS:A1996TP36600040 PM 8543827 ER PT J AU Lemasson, I Briant, L Hague, B Coudronniere, N Heron, L David, C Rebouissou, C Kindt, T Devaux, C AF Lemasson, I Briant, L Hague, B Coudronniere, N Heron, L David, C Rebouissou, C Kindt, T Devaux, C TI An antibody that binds domain 1 of CD4 inhibits replication of HIV-1, but not HTLV-I in a CD4-positive/p56/(lck)-negative HTLV-I-transformed cell line SO JOURNAL OF IMMUNOLOGY LA English DT Article ID IMMUNODEFICIENCY-VIRUS TYPE-1; PROTEIN-TYROSINE KINASE; LONG TERMINAL REPEAT; T-CELLS; MONOCLONAL-ANTIBODIES; SIGNAL TRANSDUCTION; CDR3-LIKE REGION; MOLECULE; RECEPTOR; IDENTIFICATION AB mAbs that bind to the lg CDR3-like region in D1 domain of the CD4 molecule can inhibit the HIV-1 life cycle in CD4-positive T cells and lymphoblastoid cell lines at the stage of transcription, This antiviral effect requires the integrity of the cytoplasmic tail of CD4, which acts as a signal transduction region through its association with protein tyrosine kinases such as p56(lck), Here we investigated the role of p56(lck) in the cascade of molecular events that control HIV-1 transcription in cells treated with anti-CD4 mAb directed against the lg CDR3-like region, The lg CDR3-like region-specific mAb, 13B8-2, blocked HIV-1 production in CD4-positive/p56(lck)-negative HTLV-l-producing MT2 cells superinfected by HIV-1(Lai), but had no effect on HTLV-l production, although it did inhibit Tax-induced NF-kappa B translocation, These results raise the possibility that an as yet unidentified tyrosine kinase may be capable of associating with CD4 and mediating intracellular signaling. C1 INST BIOL,LAB IMMUNOL INFECT RETROVIRALES,CNRS UPR9008,INSERM U249,F-34060 MONTPELLIER,FRANCE. NIAID,IMMUNOGENET LAB,TWINBROOK FACIL,ROCKVILLE,MD 20852. RI Lemasson, Isabelle/N-1355-2013 NR 33 TC 24 Z9 24 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 JAN 15 PY 1996 VL 156 IS 2 BP 859 EP 865 PG 7 WC Immunology SC Immunology GA TP366 UT WOS:A1996TP36600056 PM 8543843 ER PT J AU Nirenberg, MJ Vaughan, RA Uhl, GR Kuhar, MJ Pickel, VM AF Nirenberg, MJ Vaughan, RA Uhl, GR Kuhar, MJ Pickel, VM TI The dopamine transporter is localized to dendritic and axonal plasma membranes of nigrostriatal dopaminergic neurons SO JOURNAL OF NEUROSCIENCE LA English DT Article DE dopamine transporter; dopamine reuptake; immunogold; substantia nigra; striatum; caudate-putamen; neurotoxicity; Parkinson's disease; dendritic release; reverse transport; amphetamine; cocaine ID PARKINSONISM-INDUCING NEUROTOXIN; VENTRAL MIDBRAIN NEURONS; SUBSTANTIA-NIGRA; MESSENGER-RNA; RELEASE; EXPRESSION; COCAINE; AMPHETAMINE; STRIATUM; CLONING AB Nigrostriatal dopaminergic neurons play an essential role in the central regulation of motor functions. These functions are initiated through the release of dopamine from axon terminals in the striatum or from dendrites in the substantia nigra (SN) and are terminated by the reuptake of dopamine by the sodium- and chloride-dependent dopamine transporter (DAT). DAT also can transport dopamine neurotoxins and has been implicated in the selective vulnerability of nigrostriatal dopaminergic neurons in major models of Parkinson's disease. We have used electron microscopic immunocytochemistry with an N-terminal domain anti-peptide antibody to examine the subcellular distribution of DAT in the rat SN and dorsolateral striatum. In the SN, immunogold labeling for DAT was localized to cytoplasmic surfaces of plasma membranes and smooth endoplasmic reticulum of dendrites and dendritic spines, few of which contained synaptic vesicles. Neuronal perikarya in the SN contained immunogold-labeled pleomorphic electron-lucent tubulovesicles but showed immunolabeling of plasma membranes only rarely. Axon terminals in the striatum contained extensive immunogold labeling of cytoplasmic surfaces of plasma membranes near aggregates of synaptic vesicles and less frequent labeling of intervaricose segments of plasma membrane or small electron-lucent vesicles. In sections dually labeled for DAT and the catecholamine-synthesizing enzyme tyrosine hydroxylase, both markers were colocalized in most profiles in the SN and striatum. These findings support the proposed topological model for DAT and suggest that this transporter is strategically located to facilitate uptake of dopamine and neurotoxins into distal dendritic and axonal processes of nigrostriatal dopaminergic neurons. C1 NIDA, NEUROSCI BRANCH, BALTIMORE, MD 21224 USA. NIDA, MOLEC NEUROBIOL BRANCH, BALTIMORE, MD 21224 USA. JOHNS HOPKINS UNIV, SCH MED, DEPT NEUROL, BALTIMORE, MD 21224 USA. JOHNS HOPKINS UNIV, SCH MED, DEPT PHARMACOL, BALTIMORE, MD 21224 USA. JOHNS HOPKINS UNIV, SCH MED, DEPT PSYCHIAT, BALTIMORE, MD 21224 USA. JOHNS HOPKINS UNIV, SCH MED, DEPT NEUROSCI, BALTIMORE, MD 21224 USA. RP Nirenberg, MJ (reprint author), CORNELL UNIV MED COLL, DEPT NEUROL & NEUROSCI, 411 E 69TH ST, ROOM KB 410, NEW YORK, NY 10021 USA. FU NIGMS NIH HHS [GM07739]; NIMH NIH HHS [MH00078, MH40342] NR 57 TC 315 Z9 322 U1 1 U2 7 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD JAN 15 PY 1996 VL 16 IS 2 BP 436 EP 447 PG 12 WC Neurosciences SC Neurosciences & Neurology GA TP519 UT WOS:A1996TP51900002 PM 8551328 ER PT J AU Du, J Zhang, L Weiser, M Rudy, B McBain, CJ AF Du, J Zhang, L Weiser, M Rudy, B McBain, CJ TI Developmental expression and functional characterization of the potassium-channel subunit Kv3.1b in parvalbumin-containing interneurons of the rat hippocampus SO JOURNAL OF NEUROSCIENCE LA English DT Article DE hippocampal interneurons; K+-channel subunits; Kv3.1; GABA; parvalbumin; immunohistochemistry ID BINDING PROTEIN PARVALBUMIN; CENTRAL-NERVOUS-SYSTEM; A K+ CHANNEL; GABAERGIC NEURONS; NONPYRAMIDAL NEURONS; DENTATE GYRUS; IMMUNOREACTIVE NEURONS; CEREBRAL-CORTEX; MESSENGER-RNAS; CELLS AB The expression of the voltage-gated K+-channel subunit Kv3.1b in the developing hippocampus was determined by immunoblot and immunohistochemical techniques. Kv3.1b protein was detected first at postnatal day (P) 8. The Kv3.1b-immunopositive cell number per tissue section reached a maximum at P14 and was maintained through P40, In contrast, the Kv3.1b protein content of isolated membrane vesicles in immunoblots progressively increased through P40, suggesting an increase in Kv3.1b content per cell throughout this time period. Kv3.1b protein was expressed selectively in the somata, proximal dendrites, and axons of cells lying within or near the pyramidal cell layer, consistent with their being GABAergic inhibitory interneurons. Kv3.1b was present in similar to 80% of parvalbumin-positive interneurons. The developmental onset of Kv3.1b and parvalbumin immunoreactivity was identical. In contrast, Kv3.1b was mostly absent from the subset of somatostatin-positive inhibitory interneurons. Electrophysiological recordings were made from stratum pyramidale interneurons in which morphology and Kv3.1b-positive immunoreactivity were confirmed post hoc. Outward currents had voltage-dependent and biophysical properties resembling those of channels formed by Kv3.1b, The current blocked by low concentrations of 4-aminopyridine (4-AP) showed marked inactivation, suggesting that Kv3.1b may coassemble with other members of the Kv3 subfamily, In current-clamp recordings, concentrations of 4-AP that blocked the current through Kv3.1b channels allowed us tentatively to assign a role to Kv3.1b-containing channels in action-potential repolarization. These data demonstrate that Kv3.1b is regulated developmentally in a specific subpopulation of hippocampal interneurons and that channels containing this subunit may be a major determinant in imparting ''fast-spiking'' characteristics to these and other cells throughout the central nervous system containing the Kv3.1b subunit. C1 NICHHD,LCMN,UNIT CELLULAR & SYNAPT PHYSIOL,BETHESDA,MD 20892. NYU,MED CTR,DEPT PHYSIOL & NEUROSCI,NEW YORK,NY 10016. RI Du, Jing/A-9023-2012 FU NINDS NIH HHS [NS30989] NR 59 TC 160 Z9 160 U1 1 U2 4 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD JAN 15 PY 1996 VL 16 IS 2 BP 506 EP 518 PG 13 WC Neurosciences SC Neurosciences & Neurology GA TP519 UT WOS:A1996TP51900009 PM 8551335 ER PT J AU Wang, YH MontroseRafizadeh, C Adams, L Raygada, M Nadiv, O Egan, JM AF Wang, YH MontroseRafizadeh, C Adams, L Raygada, M Nadiv, O Egan, JM TI GIP regulates glucose transporters, hexokinases, and glucose-induced insulin secretion in RIN 1046-38 cells SO MOLECULAR AND CELLULAR ENDOCRINOLOGY LA English DT Article DE RIN 1046-38 cells; GIP; glucose sensitivity; insulin; gene expression ID DEPENDENT DIABETES-MELLITUS; BETA-CELLS; RIBONUCLEIC-ACID; RELEASE; LINE; GLUCOKINASE; GENE; POLYPEPTIDE; EXPRESSION; RESPONSES AB Acute studies of glucose-dependent insulinotropic peptide (GIP) have shown that GIP can synergize with glucose in stimulating insulin secretion both in vivo and in vitro. Here we studied the effects of extended exposure of RIN 1046-38 cells, an insulin-secreting cell line, to GIP and the mechanisms by which GIP synergizes with glucose in stimulating insulin secretion. Incubation of the cells with 100 nM GIP in the presence of glucose for 12 h significantly increased insulin release (287 +/- 31.7 vs. 102 +/- 9.7 ng/mg protein; n = 3), intracellular insulin content (12.8 +/- 0.83 vs. 8.2 +/- 0.52 ng/mg protein; n = 3), and insulin mRNA (approximately 2.7-fold; 24 h incubation) when compared to cells cultured with glucose alone. The insulinotropic effects of GIP on RIN 1046-38 cells were accompanied by an up-regulation of GLUT-I and hexokinase I mRNA (1.75-fold) compared to non-GIP-treated cells; mRNA levels of GLUT-2 and glucokinase were unchanged by GIP, in the presence or absence of glucose. Our study suggests that the mechanism by which extended exposure of RIN 1046-38 cells to GIP increases glucose-stimulated insulin secretion includes up-regulation of glucose sensing elements. C1 NIA,GERONTOL RES CTR 2B02,LAB CLIN PHYSIOL,DIABET UNIT,BALTIMORE,MD 21224. NR 30 TC 46 Z9 49 U1 1 U2 2 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 JAN 15 PY 1996 VL 116 IS 1 BP 81 EP 87 DI 10.1016/0303-7207(95)03701-2 PG 7 WC Cell Biology; Endocrinology & Metabolism SC Cell Biology; Endocrinology & Metabolism GA TQ759 UT WOS:A1996TQ75900008 PM 8822268 ER PT J AU Friedman, TC Cool, DR Jayasvasti, V Louie, D Loh, YP AF Friedman, TC Cool, DR Jayasvasti, V Louie, D Loh, YP TI Processing of pro-opiomelanocortin in GH3 cells: Inhibition by prohormone convertase 2 (PC2) antisense mRNA SO MOLECULAR AND CELLULAR ENDOCRINOLOGY LA English DT Article DE post-translational processing; peptide biosynthesis; antisense; prohormone convertases; adrenocorticotropin; gamma-MSH; beta-endorphin ID PITUITARY INTERMEDIATE LOBE; MESSENGER-RNA; PROPROTEIN CONVERTASE; FUNCTIONAL EXPRESSION; ENDOPROTEASE FAMILY; MAMMALIAN-CELLS; CDNA STRUCTURE; RAT PITUITARY; GENE-PRODUCT; YEAST KEX2 AB The processing of pro-opiomelanocortin (POMC) was examined in GH3 cells, a rat sommatomammotrope cell line, by transiently-transfecting the cells with mouse POMC cDNA. The peptide products were extracted, chromatographed on HPLC and identified by specific radioimmunoassay. POMC was processed to generate ACTH-related peptides, beta-endorphin and Lys-gamma(3)-MSH, with complete disappearance of the POMC precursor. The ACTH-related molecules were identified as ACTH(1-14), ACTH(1-15), ACTH(1-17), as well as ACTH(1-39). GH3 cells which were not transfected with POMC cDNA did not contain endogenous POMC-related peptides. RT-PCR demonstrated that GH3 cells contain prohormone convertase 2 (PC2) mRNA but no PC1 mRNA. To determine if PC2 was the enzyme responsible for POMC processing in this cell line, GH3 cells were stably-transfected with PC2 antisense cDNA. A cell line was obtained which showed an absence of fC2 protein compared to control untransfected GH3 cells, indicating successful hybridization of PC2 antisense mRNA to the endogenous PC2 mRNA. When this cell line was then transiently-transfected with POMC cDNA, POMC was not processed. The results from these experiments suggest that PC2 alone can correctly process POMC to biologically active smaller peptides in vivo. Additionally, the GH3 cell line with and without incorporation of PC2 antisense cDNA can be used as a model system to study the role of PC2 in the post-translational processing of other prohormones and proproteins in vivo. C1 NICHHD,DEV NEUROBIOL LAB,BETHESDA,MD 20892. NR 46 TC 22 Z9 22 U1 0 U2 0 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0303-7207 J9 MOL CELL ENDOCRINOL JI Mol. Cell. Endocrinol. PD JAN 15 PY 1996 VL 116 IS 1 BP 89 EP 96 DI 10.1016/0303-7207(95)03702-0 PG 8 WC Cell Biology; Endocrinology & Metabolism SC Cell Biology; Endocrinology & Metabolism GA TQ759 UT WOS:A1996TQ75900009 PM 8822269 ER PT J AU Bamberger, AM Pu, LP Cool, DR Loh, YP AF Bamberger, AM Pu, LP Cool, DR Loh, YP TI The neuro-2a neuroblastoma cell line expresses [MET]-enkephalin and vasopressin mRNA and peptide (vol 113, pg 155, 1995) SO MOLECULAR AND CELLULAR ENDOCRINOLOGY LA English DT Correction, Addition RP Bamberger, AM (reprint author), NICHHD,DEV NEUROBIOL LAB,CELLULAR NEUROBIOL SECT,BETHESDA,MD 20892, USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0303-7207 J9 MOL CELL ENDOCRINOL JI Mol. Cell. Endocrinol. PD JAN 15 PY 1996 VL 116 IS 1 BP 121 EP 121 PG 1 WC Cell Biology; Endocrinology & Metabolism SC Cell Biology; Endocrinology & Metabolism GA TQ759 UT WOS:A1996TQ75900013 ER PT J AU Morawetz, R Lendenfeld, T Mischak, H Muhlbauer, M Gruber, F Goodnight, J deGraaff, LH Visser, J Mushinski, JF Kubicek, CP AF Morawetz, R Lendenfeld, T Mischak, H Muhlbauer, M Gruber, F Goodnight, J deGraaff, LH Visser, J Mushinski, JF Kubicek, CP TI Cloning and characterisation of genes (pkc1 and pkcA) encoding protein kinase C homologues from Trichoderma reesei and Aspergillus niger SO MOLECULAR AND GENERAL GENETICS LA English DT Article DE Trichoderma reesei; Aspergillus niger; protein kinase C gene; signal transduction ID SACCHAROMYCES-CEREVISIAE; TRANSFORMATION SYSTEM; FISSION YEAST; FAMILY; EXPRESSION; SEQUENCE; DOMAINS; MEMBER; CELLS; NPKC AB Oligonucleotides, designed on the basis of conserved flanking amino acid sequence segments within the catalytic domain of eukaryotic protein kinase C (PKC) proteins, were used as primers for polymerase chain reactions to amplify a 427-bp chromosomal DNA fragment from the filamentous fungus Trichoderma reesei. This fragment was then used to isolate genes encoding PKC homologues of T. reesei and Aspergillus niger (pkc1 and pkcA, respectively). The genes contain six (T. reesei) and eight (A. niger) introns, which exhibit notable conservation in position with those found in the corresponding Schizosaccharomyces pombe pkc1(+) and Drosophila melanogaster dPKC53Ebr genes. A single 4.2-kb transcript was detected in Northern analyses. The deduced PKC1 (T. reesei, 126 kDa) and PKCA (A. niger, 122 kDa) amino acid sequences reveal domains homologous to the C1 and C3/C4 domains of PKC-related proteins, but lack typical Ca2+-binding (C2) domains. Both contain a large, extended N-terminus, which shares a high degree of similarity with the corresponding regions of Saccharomyces cerevisiae PKC1 and S. pombe pkc1(+) and pkc2(+) proteins, but which is not present in PKCs of Dictyostelium or higher eukaryotes. This extended region can be divided into three subdomains; the N-terminal one contains a hydrophobic helix-turn-helix motif, whereas the C-terminal one contains potential targets for proteolytic processing. A polyclonal antiserum raised against the pseudosubstrate-binding domain of PKC1 recognizes in T. reesei a 115-120 kDa protein in Western blots. Expression of pkc1 cDNA in insect cells directs the synthesis of a PKC1 protein of similar size. The T. reesei PKC1 protein was partially purified and some of its properties examined: it is stimulated about twofold by phospholipids or phorbol esters but is not stimulated by Ca2+ We conclude that these PKC proteins from filamentous fungi represent the Ca2+ insensitive fungal homologues of the nPKC family. C1 VIENNA TECH UNIV, INST BIOCHEM TECHNOL & MIKROBIOL, MIKROBIELLE BIOCHEM ABT, A-1060 VIENNA, AUSTRIA. NCI, GENET LAB, MOLEC GENET SECT, BETHESDA, MD 20892 USA. WAGENINGEN UNIV AGR, SECT MOLEC GENET IND MICROORGANISMS, 6703 HA WAGENINGEN, NETHERLANDS. RI Mischak, Harald/E-8685-2011 NR 46 TC 30 Z9 34 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0026-8925 J9 MOL GEN GENET JI Mol. Gen. Genet. PD JAN 15 PY 1996 VL 250 IS 1 BP 17 EP 28 DI 10.1007/BF02191821 PG 12 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA TR720 UT WOS:A1996TR72000003 PM 8569684 ER PT J AU Wisniewski, J Orosz, A Allada, R Wu, C AF Wisniewski, J Orosz, A Allada, R Wu, C TI The C-terminal region of Drosophila heat shock factor (HSF) contains a constitutively functional transactivation domain SO NUCLEIC ACIDS RESEARCH LA English DT Article ID DNA-BINDING ACTIVITY; TRANSCRIPTION FACTOR; SACCHAROMYCES-CEREVISIAE; NUCLEAR-LOCALIZATION; MOLECULAR-CLONING; COILED-COIL; HELA-CELLS; YEAST; ACTIVATION; PROTEIN AB The heat shock transcription factor (HSF) is constitutively expressed in Drosophila cells as an inactive monomer. Upon heat shock HSF undergoes trimerization and acquires high affinity DNA binding ability, leading to specific interaction with its cognate elements in heat shock promoters. Here we show that the transactivation function of HSF is conferred by the extreme C-terminal region of the protein. Deletion analysis of HSF fragments fused to the GAL4 DNA-binding domain demonstrates that transactivation is dependent on HSF residues 610-691. This domain is located beyond the C-terminal heptad repeat (leucine zipper 4) whose presence or integrity is dispensable for transactivation. The transactivation domain is functional in the absence of heat shock and can be replaced by the extreme C-terminal region of human HSF1. The Drosophila and human HSF transactivation domains are both rich in hydrophobic and acidic residues and may be structurally conserved, despite limited sequence identity. C1 NCI,BIOCHEM LAB,BETHESDA,MD 20892. NR 58 TC 45 Z9 46 U1 0 U2 4 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0305-1048 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD JAN 15 PY 1996 VL 24 IS 2 BP 367 EP 374 DI 10.1093/nar/24.2.367 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA TU101 UT WOS:A1996TU10100018 PM 8628664 ER PT J AU Bryngelson, JD Thirumalai, D AF Bryngelson, JD Thirumalai, D TI Internal constraints induce localization in an isolated polymer molecule SO PHYSICAL REVIEW LETTERS LA English DT Article ID NUCLEAR-MAGNETIC-RESONANCE; SPECTROSCOPY AB We investigate a model of an isolated polymer molecule with the constraint that certain pairs of monomers are in close proximity. A combination of a variational theory and scaling arguments shows that the polymer becomes localized in space, i.e., collapsed, when the product of the density of constraints and the logarithm of the geometric mean of the separation between constraints exceeds a critical value. Applications to the understanding of vulcanization, of protein structure determination, and of protein folding are noted. C1 UNIV MARYLAND, INST PHYS SCI & TECHNOL, COLLEGE PK, MD 20742 USA. UNIV MARYLAND, DEPT CHEM, COLLEGE PK, MD 20742 USA. RP NIH, DIV COMP RES & TECHNOL, PHYS SCI LAB, BETHESDA, MD 20892 USA. NR 22 TC 21 Z9 21 U1 0 U2 0 PU AMER PHYSICAL SOC PI COLLEGE PK PA ONE PHYSICS ELLIPSE, COLLEGE PK, MD 20740-3844 USA SN 0031-9007 EI 1079-7114 J9 PHYS REV LETT JI Phys. Rev. Lett. PD JAN 15 PY 1996 VL 76 IS 3 BP 542 EP 545 DI 10.1103/PhysRevLett.76.542 PG 4 WC Physics, Multidisciplinary SC Physics GA TP362 UT WOS:A1996TP36200053 ER PT J AU Bujacz, G Jaskolski, M Alexandratos, J Wlodawer, A Merkel, G Katz, RA Skalka, AM AF Bujacz, G Jaskolski, M Alexandratos, J Wlodawer, A Merkel, G Katz, RA Skalka, AM TI The catalytic domain of avian sarcoma virus integrase: Conformation of the active-site residues in the presence of divalent cations SO STRUCTURE LA English DT Article DE AIDS; ASV; HIV; integration; recombination ID ESCHERICHIA-COLI; CRYSTAL-STRUCTURE; RIBONUCLEASE-H; VIRAL-DNA; RETROVIRAL INTEGRATION; PROTEIN; INVITRO; HIV-1; IDENTIFICATION; BINDING AB Background: Members of the structurally-related superfamily of enzymes that includes RNase H, RuvC resolvase, MuA transposase, and retroviral integrase require divalent cations for enzymatic activity. So far, cation positions are reported in the X-ray crystal structures of only two of these proteins, E. coli and human immunodeficiency virus 1 (HIV-1) RNase H. Details of the placement of metal ions in the active site of retroviral integrases are necessary for the understanding of the catalytic mechanism of these enzymes. Results: The structure of the enzymatically active catalytic domain (residues 52-207) of avian sarcoma virus integrase (ASV IN) has been solved in the presence of divalent cations (Mn2+ or Mg2+) at 1.7-2.2 Angstrom resolution. A single ion of either type interacts with the carboxylate groups of the active site aspartates and uses four water molecules to complete its octahedral coordination. The placement of the aspartate side chains and metal ions is very similar to that observed in the RNase H members of this superfamily; however, the conformation of the catalytic aspartates in the active site of ASV IN differs significantly from that reported for the analogous residues in HIV-1 IN. Conclusions: Binding of the required metal ions does not lead to significant structural modifications in the active site of the catalytic domain of ASV IN. This indicates that at least one metal-binding site is preformed in the structure, and suggests that the observed constellation of the acidic residues represents a catalytically competent active site, Only a single divalent cation was observed even at extremely high concentrations of the metals. We conclude that either only one metal ion is needed for catalysis, or that a second metal-binding site can only exist in the presence of substrate and/or other domains of the protein. The unexpected differences between the active sites of ASV IN and HIV-1 IN remain unexplained; they may reflect the effects of crystal contacts on the active site of HIV-1 IN, or a tendency for structural polymorphism. C1 NCI,FREDERICK CANC RES & DEV CTR,ABL BASIC RES PROGRAM,MACROMOLEC STRUCT LAB,FREDERICK,MD 21702. POLISH ACAD SCI,INST BIOORGAN CHEM,CTR BIOCRYSTALLOG RES,POZNAN,POLAND. FOX CHASE CANC CTR,INST CANC RES,PHILADELPHIA,PA 19111. FU NCI NIH HHS [CA06927, CA47486, N01-CO-46000] NR 35 TC 160 Z9 161 U1 1 U2 4 PU CURRENT BIOLOGY LTD PI LONDON PA 34-42 CLEVELAND STREET, LONDON, ENGLAND W1P 6LB SN 0969-2126 J9 STRUCTURE JI Structure PD JAN 15 PY 1996 VL 4 IS 1 BP 89 EP 96 DI 10.1016/S0969-2126(96)00012-3 PG 8 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA TR313 UT WOS:A1996TR31300012 PM 8805516 ER PT J AU Booy, FP Trus, BL Davison, AJ Steven, AC AF Booy, FP Trus, BL Davison, AJ Steven, AC TI The capsid architecture of channel catfish virus, an evolutionarily distant herpesvirus, is largely conserved in the absence of discernible sequence homology with herpes simplex virus SO VIROLOGY LA English DT Article ID CRYO-ELECTRON-MICROSCOPY; 3-DIMENSIONAL STRUCTURE; EQUINE HERPESVIRUS-1; SIMIAN VIRUS-40; TYPE-1; DNA; RECONSTRUCTION; IDENTIFICATION; PENTONS AB Although herpesviruses have a wide host range and their genomes vary substantially in size, the nucleocapsid appears to be a conservative element of viral design. The capsid shell is icosahedrally symmetric (T = 16), and 125 nm in diameter and 15nm thick in the case of herpes simplex virus 1 (HSV-1). Channel catfish virus (CCV) has the gross morphology of a herpesvirus, although no relationship to other herpesviruses is evident from the sequences of its proteins. To examine CCV capsid architecture more closely, we have determined its structure by cryoelectron microscopy and three-dimensional image reconstruction. The CCV capsid is smaller than that of HSV-1, but its 12% smaller genome is packed to essentially the same average density; its icosahedral facets are flatter, and its shell is about 20% thinner, consistent with the smaller size of its major capsid protein. Otherwise, their major features are remarkably similar: CCV has the same triangulation number; its herons and pentons also have chimney-like protrusions with an axial channel through each capsomer; and there are ''triplexes'' on the outer surface at the sites of local threefold symmetry. The basic herpesvirus capsid architecture is, therefore, remarkably well conserved in CCV and implies a utilitarian basis to this design. The protein composition of CCV mirrors that of HSV-I, except for the absence of the 12-kDa protein, VP26, which is dispensable for assembly in the HSV-I system and, apparently, wholly dispensable for CCV. (C) 1996 Academic Press, Inc. C1 NIAMSD,STRUCT BIOL LAB,BETHESDA,MD 20892. NIH,DIV COMP RES & TECHNOL,LAB COMPUTAT BIOSCI & ENGN,BETHESDA,MD 20892. UNIV GLASGOW,INST VIROL,MRC,GLASGOW G11 5JR,LANARK,SCOTLAND. NR 42 TC 41 Z9 42 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0042-6822 J9 VIROLOGY JI Virology PD JAN 15 PY 1996 VL 215 IS 2 BP 134 EP 141 DI 10.1006/viro.1996.0016 PG 8 WC Virology SC Virology GA TQ893 UT WOS:A1996TQ89300003 PM 8560760 ER PT J AU Masuda, M Hanson, CA Alvord, WG Hoffman, PM Ruscetti, SK Masuda, M AF Masuda, M Hanson, CA Alvord, WG Hoffman, PM Ruscetti, SK Masuda, M TI Effects of subtle changes in the SU protein of ecotropic murine leukemia virus on its brain capillary endothelial cell tropism and interference properties SO VIROLOGY LA English DT Article ID NEUROPATHOGENIC VARIANT; PVC-211; DNA; TRANSFECTION; LOCALIZATION; FRAGMENT; ASSAY AB PVC-211 murine leukemia virus (MuLV) is a neuropathogenic variant of Friend MuLV (F-MuLV) that causes a rapidly progressive neurodegenerative disease in susceptible rodents. PVC-211 MuLV, but not the parental F-MuLV, can infect rat brain capillary endothelial cells (BCEC) efficiently, and the major determinant for BCEC tropism of PVC-211 MuLV is localized within the Xbal-BamHI fragment of the viral genome containing the 5' half of the env gene. To further dissect the Xbal-BamHI region for its effects on BCEC tropism, we constructed recombinant viruses between PVC-211 MuLV and F-MuLV and tested their infectivity on a cell line established from rat BCEC. Our results indicated that Glu(116)-to-Gly and Glu(129)-to-Lys substitutions in the background of the F-MuLV envelope SU protein were sufficient for conferring BCEC tropism on the virus. Interference studies of these viruses on Rat-1 fibroblastic cells showed that the structure of the SU protein encoded by the Xbal-BamHI region also has significant effects on their affinity for the rat ecotropic MuLV receptor. These results support the possibility that structural elements I and II of the SU protein are important determinants for virus-receptor interaction. (C) 1996 Academic Press, Inc. C1 SAIC,LAB CELLULAR BIOCHEM,FREDERICK,MD 21702. DATA MANAGEMENT SERV INC,FREDERICK,MD 21702. DEPT VET AFFAIRS MED CTR,RES SERV,BALTIMORE,MD 21201. UNIV MARYLAND,DEPT PATHOL & NEUROL,BALTIMORE,MD 21201. RP Masuda, M (reprint author), NCI,MOLEC ONCOL LAB,FREDERICK,MD 21702, USA. NR 26 TC 29 Z9 29 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 0042-6822 J9 VIROLOGY JI Virology PD JAN 15 PY 1996 VL 215 IS 2 BP 142 EP 151 DI 10.1006/viro.1996.0017 PG 10 WC Virology SC Virology GA TQ893 UT WOS:A1996TQ89300004 PM 8560761 ER PT J AU Hamel, E Lin, CM Plowman, J Wang, HK Lee, KH Paull, KD AF Hamel, E Lin, CM Plowman, J Wang, HK Lee, KH Paull, KD TI Antitumor 2,3-dihydro-2-(aryl)-4(1H)-quinazolinone derivatives - Interactions with tubulin SO BIOCHEMICAL PHARMACOLOGY LA English DT Article DE antimitotic agents; colchicine analogs; tubulin polymerization; styrylquinazolinone derivatives; phenylquinolone derivative; flavonols ID TUMOR-CELL-LINES; ANTIMITOTIC AGENTS; ANALOGS; POLYMERIZATION; COLCHICINE; IDENTIFICATION; CYTOTOXICITY AB A series of derivatives of 2,3-dihydro-2-(aryl)-4(1H)-quinazolinone (DHQZ) with known anti-tumor activity was re-evaluated in the National Cancer Institute cancer cell line screen. Analysis by the COMPARE algorithm suggested that their cytotoxicity derived from interactions with tubulin. Significant inhibition of tubulin assembly and of the binding of radiolabeled colchicine to tubulin was demonstrated with several of the compounds, particularly NSC 145669, 175635, and 175636. The DHQZ derivatives are structurally analogous to a number of antimitotic agents, flavonols and derivatives of 2-styrylquinazolin-4(3H)-one and of 2-phenyl-4-quinolone. Structure-activity analogies between these agents, the combretastatins, and the colchicinoids were analyzed and summarized. C1 NCI,DIV CANC TREATMENT,DEV THERAPEUT PROGRAM,INFORMAT TECHNOL BRANCH,BETHESDA,MD 20892. NCI,FREDERICK CANC RES & DEV CTR,DIV CANC TREATMENT,DEV THERAPEUT PROGRAM,BIOL TESTING BRANCH,FREDERICK,MD 21701. UNIV N CAROLINA,SCH PHARM,DIV MED CHEM & NAT PROD,NAT PROD LAB,CHAPEL HILL,NC 27599. RP Hamel, E (reprint author), NCI,DIV CANC TREATMENT,DEV THERAPEUT PROGRAM,MOLEC PHARMACOL LAB,BLDG 37,ROOM 5C25,BETHESDA,MD 20892, USA. NR 24 TC 111 Z9 112 U1 1 U2 5 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 JAN 12 PY 1996 VL 51 IS 1 BP 53 EP 59 DI 10.1016/0006-2952(95)02156-6 PG 7 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA TL817 UT WOS:A1996TL81700008 PM 8534268 ER PT J AU Pak, CC Blumenthal, R AF Pak, CC Blumenthal, R TI Effect of X31 influenza virus fusion on phosphatidylserine asymmetry in erythrocytes SO BIOCHIMICA ET BIOPHYSICA ACTA-BIOMEMBRANES LA English DT Article DE influenza; fusion; phosphatidylserine; asymmetry; hemagglutinin; hemolysis; erythrocyte ID INDUCED MEMBRANE-FUSION; RED-BLOOD-CELLS; INDUCED CONFORMATIONAL CHANGE; TRANSBILAYER MOVEMENT; SICKLED ERYTHROCYTES; LIPID ASYMMETRY; HEMAGGLUTININ; PHOSPHOLIPIDS; PROTEIN; ECTODOMAIN AB Influenza virus fusion is mediated by its fusion protein, hemagglutinin (HA). HA undergoes a low pH dependent conformational change that results in insertion into the cell membrane bilayer, formation of a fusion pore, and merging of membrane lipids and establishment of cytoplasmic continuity. Erythrocytes, which can serve as targets for influenza virus fusion, display an asymmetric transbilayer arrangement of their phospholipids. The effect of influenza virus fusion on erythrocyte phosphatidylserine asymmetry was determined. Influenza virus were bound to erythrocytes containing the fluorescent membrane probe NBD-PS in the inner leaflet. Induction of fusion by exposure to a low pH environment resulted in movement of PS to the outer leaflet of the cell as well as hemolysis, Insertion of the fusion protein into erythrocytes and subsequent fusion can be distinguished from hemolysis by examining the interaction of a soluble form of HA (BHA) with cells and by monitoring viral fusion at low temperatures. No hemolysis was observed under either condition. BHA binding and insertion into cells did not affect the asymmetry of PS, Incubation of influenza virus fusion at pH 5, 0 degrees C resulted in complete fusion but no outward movement of PS was observed. These findings suggest the viral fusion pore does not involve a rearrangement of the transbilayer phospholipid organization of the target membrane. C1 NCI,SECT MEMBRANE STRUCT & FUNCT,NIH,BETHESDA,MD 20892. NR 47 TC 4 Z9 4 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0005-2736 J9 BBA-BIOMEMBRANES JI Biochim. Biophys. Acta-Biomembr. PD JAN 12 PY 1996 VL 1278 IS 1 BP 98 EP 104 DI 10.1016/0005-2736(95)00193-X PG 7 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA TU299 UT WOS:A1996TU29900014 PM 8611613 ER PT J AU Uversky, VN Ptitsyn, OB AF Uversky, VN Ptitsyn, OB TI Further evidence on the equilibrium ''pre-molten globule state'': Four-state guanidinium chloride-induced unfolding of carbonic anhydrase B at low temperature SO JOURNAL OF MOLECULAR BIOLOGY LA English DT Article DE protein folding; molten globule; carbonic anhydrase; size-exclusion chromatography ID BOVINE ALPHA-LACTALBUMIN; CIRCULAR-DICHROISM; SECONDARY STRUCTURE; CYTOCHROME-C; FOLDING PATHWAY; 3-STATE DENATURATION; PROTEIN MOLECULES; COMPACT STATE; SIDE-CHAINS; INTERMEDIATE AB Equilibrium guanidinium chloride-induced unfolding of bovine carbonic anhydrase NE has been investigated by a combination of optical methods with size-exclusion chromatography. It has been shown that, as in the case of staphylococcal beta-lactamase, bovine carbonic anhydrase B unfolds at low temperature through two equilibrium intermediates; the molten globule and the pre-molten globule states. This pre-molten globule state has a hydrodynamic volume no more than twofold larger than that of the native state, i.e. is relatively compact. It has a pronounced far UV CD spectrum, suggesting the presence of a substantial secondary structure. It binds 8-anilinonaphthalene-1-sulphonate (though weaker than the molten globule state), which suggests the formation of solvent-exposed clusters of non-polar groups. Thus, this novel state of protein molecules shares a number of properties with the ''burst'' kinetic intermediate of protein folding and can be considered as its equilibrium counterpart. (C) 1996 Academic Press Limited C1 NCI,MATH BIOL LAB,BETHESDA,MD 20892. RP Uversky, VN (reprint author), RUSSIAN ACAD SCI,INST PROT RES,PUSHCHINO 142292,RUSSIA. RI Uversky, Vladimir/F-4515-2011 OI Uversky, Vladimir/0000-0002-4037-5857 NR 93 TC 176 Z9 181 U1 0 U2 5 PU ACADEMIC PRESS LTD PI LONDON PA 24-28 OVAL RD, LONDON, ENGLAND NW1 7DX SN 0022-2836 J9 J MOL BIOL JI J. Mol. Biol. PD JAN 12 PY 1996 VL 255 IS 1 BP 215 EP 228 DI 10.1006/jmbi.1996.0018 PG 14 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA TQ686 UT WOS:A1996TQ68600018 PM 8568868 ER PT J AU ZsnFernandezSalguero, P Gonzalez, FJ Ward, JM AF ZsnFernandezSalguero, P Gonzalez, FJ Ward, JM TI Hepatic fibrosis in Ahr(-/-) mice - Response SO SCIENCE LA English DT Article C1 NATL CANC INST,OFF LAB ANIM SCI,VET & TUMOR PATHOL SECT,FREDERICK,MD 21702. RP ZsnFernandezSalguero, P (reprint author), NCI,MOLEC CARCINOGENESIS LAB,BLDG 37,BETHESDA,MD 20892, USA. NR 0 TC 0 Z9 0 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 JAN 12 PY 1996 VL 271 IS 5246 BP 224 EP 224 DI 10.1126/science.271.5246.224 PG 1 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA TP364 UT WOS:A1996TP36400051 PM 17793400 ER PT J AU Johnson, KA Prindiville, SA AF Johnson, KA Prindiville, SA TI Aspirin and the risk of colorectal cancer in women SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Letter RP Johnson, KA (reprint author), NCI,BETHESDA,MD 20892, USA. NR 5 TC 0 Z9 0 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 JAN 11 PY 1996 VL 334 IS 2 BP 119 EP 119 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA TP363 UT WOS:A1996TP36300012 PM 8531946 ER PT J AU Fukushima, A Shiloach, J Whitcup, SM Nussenblatt, RB Gery, I AF Fukushima, A Shiloach, J Whitcup, SM Nussenblatt, RB Gery, I TI Human lymphocyte responses against epitopes of a self antigen: A follow-up at different time points SO CELLULAR IMMUNOLOGY LA English DT Article ID MYELIN BASIC-PROTEIN; RETINAL S-ANTIGEN; UVEITIS; RECOGNITION; DISEASE; CELLS; SITE; RATS AB This study was aimed at examining the changes that may occur with time in the lymphocyte responses of an individual against peptide determinants of self antigens. Peripheral blood lymphocytes were collected from the same donor at seven different time points during a 10-month period and tested for their proliferative responses against whole human S-antigen and 40 overlapping peptides derived from the sequence of this uveitogenic retinal protein. Lymphocytes collected at different dates varied in their responsiveness to all tested antigens, as well as in the pattern of their response against individual peptides. The latter variability was expressed by differences in the hierarchical order of the most stimulatory peptides for lymphocytes collected at the seven time points. Despite the variability in their stimulatory capacity, six of the peptides exhibited their immunodominance by eliciting proliferation in lymphocytes collected at all time points. Our results thus indicate that data collected from a single sample of blood may be insufficient to accurately assess the level of cellular response to autologous antigens. (C) 1996 Academic Press, Inc. C1 NEI, IMMUNOL LAB, BETHESDA, MD 20892 USA. NIDDKD, CELLULAR & DEV BIOL LAB, BETHESDA, MD 20892 USA. NR 19 TC 2 Z9 2 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0008-8749 J9 CELL IMMUNOL JI Cell. Immunol. PD JAN 10 PY 1996 VL 167 IS 1 BP 150 EP 153 DI 10.1006/cimm.1996.0019 PG 4 WC Cell Biology; Immunology SC Cell Biology; Immunology GA TQ809 UT WOS:A1996TQ80900019 PM 8548839 ER PT J AU Patterton, D Wolffe, AP AF Patterton, D Wolffe, AP TI Developmental roles for chromatin and chromosomal structure SO DEVELOPMENTAL BIOLOGY LA English DT Review ID POSITION-EFFECT VARIEGATION; DOSAGE-DEPENDENT MODIFIERS; DROSOPHILA HOMEOTIC GENES; EARLY XENOPUS-EMBRYOS; CPG BINDING-PROTEIN; RIBOSOMAL-RNA GENES; SOMATIC HISTONE H1; SEA-URCHIN; BITHORAX COMPLEX; SACCHAROMYCES-CEREVISIAE AB Chromosomal architecture is emerging as a key controlling influence in the developmental regulation of gene expression. Recent genetic experiments using Caenorhabditis elegans, Drosophila melanogaster, and the mouse have provided clear evidence for the functional differentiation of chromosomal structures during development. Chromosomes are visualized as highly specialized entities, within which the activity of particular domains is largely determined by defined structural proteins. At a more local level, the mechanisms regulating gene transcription during early embryogenesis in Xenopus and the mouse have been found to be dependent on the biochemical composition of individual nucleosomes. Thus, variation in the type and modification of chromosomal and chromatin structural proteins provides a dominant means of controlling the transcriptional activity of individual genes, individual chromosomal domains, and of entire chromosomes. (C) 1996 Academic Press, Inc. RP Patterton, D (reprint author), NICHHD,MOLEC EMBRYOL LAB,NIH,BLDG 6,ROOM B1A-13,BETHESDA,MD 20892, USA. NR 142 TC 48 Z9 50 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 0012-1606 J9 DEV BIOL JI Dev. Biol. PD JAN 10 PY 1996 VL 173 IS 1 BP 2 EP 13 DI 10.1006/dbio.1996.0002 PG 12 WC Developmental Biology SC Developmental Biology GA TU033 UT WOS:A1996TU03300002 PM 8575621 ER PT J AU Yamamoto, H Crow, M Cheng, L Lakatta, E Kinsella, J AF Yamamoto, H Crow, M Cheng, L Lakatta, E Kinsella, J TI PDGF receptor-to-nucleus signaling of p91 (STAT1 alpha) transcription factor in rat smooth muscle cells SO EXPERIMENTAL CELL RESEARCH LA English DT Article ID PROTEIN-TYROSINE KINASE; GROWTH-FACTOR RECEPTORS; DNA-BINDING PROTEINS; INTERFERON-GAMMA; ACTIVATION; GENE; ALPHA; ISGF3; PHOSPHORYLATION; TRANSDUCTION AB Vascular smooth muscle cells (VSMC) are the predominant cell type in the media of a normal artery. Injury to the vessel wall leads to platelet deposition and the release of numerous factors, including PDGF, which exerts its biological effects by binding to specific surface receptors on the smooth muscle cell membrane. We demonstrate that PDGF-stimulated smooth muscle cells activate the STAT (signal transducers and activators of transcription) family of proteins in addition to other signaling pathways (e.g., RAS-RAF-MAP Kinase). We show that the transcription factor p91 (STAT1 alpha) is rapidly activated by PDGF in VSMC and specifically binds to the regulatory elements SIE or GAS, We hypothesize that signal transduction by p91 plays an important role in VSMC, especially after injury with the release of growth factors such as PDGF. (C) 1996 Academic Press, Inc. C1 NIA, GERONTOL RES CTR, CARDIOVASC SCI LAB, BALTIMORE, MD 21224 USA. NR 44 TC 30 Z9 30 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0014-4827 J9 EXP CELL RES JI Exp. Cell Res. PD JAN 10 PY 1996 VL 222 IS 1 BP 125 EP 130 DI 10.1006/excr.1996.0016 PG 6 WC Oncology; Cell Biology SC Oncology; Cell Biology GA TQ829 UT WOS:A1996TQ82900016 PM 8549654 ER PT J AU Zhuo, SQ Fan, SJ Kaufman, S AF Zhuo, SQ Fan, SJ Kaufman, S TI Effects of depletion of intracellular tetrahydrobiopterin in murine erythroleukemia cells SO EXPERIMENTAL CELL RESEARCH LA English DT Article ID SEPIAPTERIN REDUCTASE; PROLIFERATION; DIFFERENTIATION; BIOPTERIN; COFACTOR AB The biosynthesis of 6(R)-5,6,7,8-tetrahydrobiopterin (BH4) in murine erythroleukemia (MEL) cells is almost completely inhibited by 10 mM 2,4-diamino-6-hydroxypyrimidine (DAHP), which targets GTP cyclohydrolase. The inhibition results in 'dephosphorylation of the retinoblastoma gene product, prolongation of the G(1)-phase in the cell cycle, and subsequent commitment to terminal differentiation of MEL cells, Reversal of the processes by repletion of cellular BH4 with biopterin-related compounds including BH4, 7,8-dihydrobiopterin (7,8-BH2), sepiapterin, and 7,8-dihydroneopterin has generated complicated results. Low micromolar exogenous pterin compounds had little or no effect, At 300 mu M or higher, the synthesis of hemoglobin by DAHP-induced MEL cells is significantly inhibited by 7,8-dihydrobiopterin and sepiapterin. However, further cell cycle analysis shows that the inhibition of cell differentiation by 7,8-BH2 and sepiapterin may not be due to the reversal of cell proliferation. Inhibition of BH4 biosynthesis in MEL cells by inhibitors of sepiapterin reductase has also been studied. None of the inhibitors that were tested, including N-chloroacetyldopamine and N-acetylserotonin, which are specific for sepiapterin reductase, can block MEL cells in G(1)-phase or induce the cells to commit to terminal differentiation. Furthermore, inhibitors of sepiapterin reductase are found to reduce or to abolish hemoglobin synthesis in differentiating MEL cells induced by hexamethylene bisacetamide, The mechanism for this is not clear. Not all of the effects caused by the depletion of BH4 synthesis can be rescued by repletion of BH4. These results suggest that BH4 may not regulate proliferation or differentiation of MEL cells as previously thought, Its function in MEL cells is still not clear. (C) 1996 Academic Press, Inc. C1 NIMH,NEUROCHEM LAB,BETHESDA,MD 20892. NCI,DIV CANC TREATMENT,DEV THERAPEUT PROGRAM,MOLEC PHARMACOL LAB,BETHESDA,MD 20892. NR 19 TC 1 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 0014-4827 J9 EXP CELL RES JI Exp. Cell Res. PD JAN 10 PY 1996 VL 222 IS 1 BP 163 EP 170 DI 10.1006/excr.1996.0021 PG 8 WC Oncology; Cell Biology SC Oncology; Cell Biology GA TQ829 UT WOS:A1996TQ82900021 PM 8549660 ER PT J AU Ferguson, JH AF Ferguson, JH TI On-line medicine @nih.gov SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article RP Ferguson, JH (reprint author), NIH,OFF MED APPLICAT RES,BETHESDA,MD 20892, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD JAN 10 PY 1996 VL 275 IS 2 BP 94 EP 94 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA TN280 UT WOS:A1996TN28000004 PM 8531318 ER PT J AU Whitcup, SM AF Whitcup, SM TI Grand rounds at the Clinical Center of the National Institutes of Health - Ocular manifestations of AIDS SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Discussion ID ACQUIRED-IMMUNODEFICIENCY-SYNDROME; CYTOMEGALO-VIRUS RETINITIS; RETINAL VASCULOPATHY; GANCICLOVIR; FOSCARNET; INFECTION; THERAPY; PATIENT RP Whitcup, SM (reprint author), NEI,CLIN BRANCH,10 CTR DR,BLDG 10,ROOM 10N 202,BETHESDA,MD 20892, USA. NR 26 TC 10 Z9 10 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 JAN 10 PY 1996 VL 275 IS 2 BP 142 EP 144 DI 10.1001/jama.275.2.142 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA TN280 UT WOS:A1996TN28000031 PM 8531310 ER PT J AU Qin, J Clore, GM Gronenborn, AM AF Qin, J Clore, GM Gronenborn, AM TI Ionization equilibria for side-chain carboxyl groups in oxidized and reduced human thioredoxin and in the complex with its target peptide from the transcription factor NF kappa B SO BIOCHEMISTRY LA English DT Article ID ESCHERICHIA-COLI THIOREDOXIN; DNA-BINDING ACTIVITY; IONIZABLE GROUPS; STABILITY; TITRATION; PROTEINS; REDUCTION; INVITRO; PKA AB The pH dependence of the C-13 chemical shifts of the side-chain carboxyl carbons of all Asp and Glu residues in the reduced and oxidized states of human thioredoxin and in a mixed disulfide complex of human thioredoxin with a target peptide from the transcription factor NF kappa B has been investigated by multidimensional triple-resonance NMR spectroscopy. While the titration curves for most of the side-chain carboxyl resonances exhibit simple Henderson-Hasselbalch behavior with pK(a) values not far from those found for model compounds, several side chains give rise to two- or three-step titration curves, indicative of the influence of multiple ionizations, In particular, the triad formed by Asp58, Asp60, and Asp61, forms such a complex network of titrating groups. The ionization behavior of Asp26 shows an abnormally high pK(a) value for an aspartate residue in all states of human thioredoxin, with pK(a) values of 9.9 in the reduced state, 8.1 in the oxidized state, 8.9 in the mixed disulfide complex, and 8.6 in an active site mutant in which Cys35 was replaced by Ala. The unambiguous determination of the pK(a) values of Asp26 for a variety of states of human thioredoxin presented in this paper is highly significant in view of two recent reports on Escherichia coli thioredoxin which presented contradicting pK(a) values for Asp26 and Cys35 [Wilson et al, (1995) Biochemistry 34, 8931-8939; Jeng et al, (1995) Biochemistry 34, 10101-10105]. The stabilization of the protonated side chain of Asp26 in human thioredoxin is achieved via a hydrogen-bonding network involving the hydroxyl group of the neighboring Ser28 which is then connected to the active site region (comprising Cys32 and Cys35) via bound water molecules. The coupling of the buried Asp26 to the active site is responsible for the influence of the Asp26 ionization behavior on the titration shifts of active site residues. C1 NIDDKD,CHEM PHYS LAB,BETHESDA,MD 20892. RI Clore, G. Marius/A-3511-2008 OI Clore, G. Marius/0000-0003-3809-1027 NR 41 TC 75 Z9 76 U1 0 U2 9 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD JAN 9 PY 1996 VL 35 IS 1 BP 7 EP 13 DI 10.1021/bi952299h PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA TP482 UT WOS:A1996TP48200002 PM 8555200 ER PT J AU Gladyshev, VN Khangulov, SV Stadtman, TC AF Gladyshev, VN Khangulov, SV Stadtman, TC TI Properties of the selenium- and molybdenum-containing nicotinic acid hydroxylase from Clostridium barkeri SO BIOCHEMISTRY LA English DT Article ID HYDROPEROXIDE GLUTATHIONE-PEROXIDASE; FORMATE DEHYDROGENASE; AMINO-ACID; XANTHINE-OXIDASE; METHANOCOCCUS-VANNIELII; GLYCINE REDUCTASE; ESCHERICHIA-COLI; GENE-PRODUCT; SELENOCYSTEINE; PURIFICATION AB NADP(+)-coupled nicotinic acid hydroxylase (NAH) has been purified to near-homogeneity from Clostridium barkeri by an improved purification scheme that allowed the isolation of milligram amounts of enzyme of higher specific activity then previously reported. NAH is most stable at alkaline pH in the presence of glycerol. The protein which consists of four dissimilar subunits occurs in forms of different molecular masses. There are 5-7 Fe, 1 FAD, and 1 Mo per 160 kDa protein protomer. Mo in the enzyme is bound to a dinucleotide form of molybdopterin and is coordinated with selenium. Mo(V), flavin radical, and two Fe2S2 clusters could be observed with EPR spectroscopy. The Se cofactor which is essential for nicotinic acid hydroxylase activity could be released from NAH as a reactive low molecular weight compound by a number of denaturing procedures. Parallel losses of Se and catalytic activity were observed during purification and storage of the enzyme. Addition of sodium selenide or selenophosphate did not restore the catalytic activity of the enzyme. Instead, NAH is reversibly inactivated by these compounds and also by sulfide. Cyanide, a common inhibitor of Mo-containing hydroxylases, does not affect NAH catalytic activity. The ''as isolated'' enzyme exhibits a Mo(V) EPR signal (2.067 signal) that was detected at early stages of purification. NAH exhibits a high substrate specificity toward electron donor substrates. The ability of a nicotinate analog to reduce NAH (disappearance of 2.067 signal) correlates with the rate of oxidation of the analog in the standard assay mixture. The properties of NAH differentiate the enzyme from known Mo-containing hydroxylases. C1 NHLBI,BIOCHEM LAB,BETHESDA,MD 20892. NR 45 TC 41 Z9 48 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 JAN 9 PY 1996 VL 35 IS 1 BP 212 EP 223 DI 10.1021/bi951793i PG 12 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA TP482 UT WOS:A1996TP48200027 PM 8555176 ER PT J AU Seok, YJ Lee, BR Gazdar, C Svenson, I Yadla, N Peterkofsky, A AF Seok, YJ Lee, BR Gazdar, C Svenson, I Yadla, N Peterkofsky, A TI Importance of the region around glycine-338 for the activity of enzyme I of the Escherichia coli Phosphoenolpyruvate:sugar phosphotransferase system SO BIOCHEMISTRY LA English DT Article ID BACTERIAL PHOSPHOENOLPYRUVATE; SEQUENCE; TRANSPORT; CLONING; GENE AB The gene encoding enzyme I of the phosphoenolpyruvate:sugar phosphotransferase system from an Escherichia call enzyme I mutant was cloned and sequenced. The mutation was shown to be a guanine to adenine transition resulting in an altered protein in which glycine-338 was replaced by aspartic acid. The enzyme I structural gene was mutated to change glycine-338 to a variety of other amino acid residues. Fermentation tests indicated that glycine-338 could be mutated to alanine with no gross loss in phosphotransferase activity, while mutation to valine, glutamic acid, aspartic acid, arginine, histidine, or asparagine led to significant loss of activity. an expression vector for enzyme I was mutated to change glycine-338 to a variety of other amino acid residues and highly purified mutant proteins were prepared. analysis of phosphorylation of the proteins by PEP indicated that mutation of glycine-338 to alanine had little effect on phosphorylation, mutation to valine substantially decreased phosphorylation, change to histidine or arginine drastically diminished phosphorylation, and mutation to aspartic or glutamic acids abolished phosphorylation activity. Mutation at glycine-338 influences the autophosphorylation rather than the phosphoryl transfer activity of enzyme I. C1 NHLBI,BIOCHIM GENET LAB,BETHESDA,MD 20892. NR 23 TC 17 Z9 18 U1 1 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 JAN 9 PY 1996 VL 35 IS 1 BP 236 EP 242 DI 10.1021/bi952052k PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA TP482 UT WOS:A1996TP48200030 PM 8555180 ER PT J AU terHaar, E Kowalski, RJ Hamel, E Lin, CM Longley, RE Gunasekera, SP Rosenkranz, HS Day, BW AF terHaar, E Kowalski, RJ Hamel, E Lin, CM Longley, RE Gunasekera, SP Rosenkranz, HS Day, BW TI Discodermolide, a cytotoxic marine agent that stabilizes microtubules more potently than taxol SO BIOCHEMISTRY LA English DT Article ID IMMUNOSUPPRESSIVE COMPOUND; TUBULIN AB Computer-assisted structure analysis indicated (+)-discodermolide, a polyhydroxylated alkatetraene lactone marine natural product, was an antimitotic compound, and we confirmed this prediction. Previous work had shown an accumulation of discodermolide-treated cells in the G(2)/M portion of the cell cycle, and we have now found that discodermolide arrests Burkitt lymphoma cells in mitosis. Discodermolide-treated breast carcinoma cells displayed spectacular rearrangement of the microtubule cytoskeleton, including extensive microtubule bundling. Microtubule rearrangement that occurred with 10 nM discodermolide required 1 mu M taxol. Discodermolide had equally impressive effects on tubulin assembly in vitro. Near-total polymerization occurred at 0 degrees C with tubulin plus microtubule-associated proteins (MAPs) under conditions in which taxol at an identical concentration was inactive. Without MAPs and/or without GTP, tubulin assembly was also more vigorous with discodermolide than with taxol under every reaction condition examined. Discodermolide-induced polymer differed from taxol-induced polymer in that it was completely stable at 0 degrees C in the presence of high concentrations of Ca2+. In a quantitative assay designed to select for agents more effective than taxol in inducing assembly, discodermolide had an EC(50) value of 3.2 mu M versus 23 mu M for taxol. C1 UNIV PITTSBURGH,DEPT ENVIRONM & OCCUPAT HLTH,PITTSBURGH,PA 15238. UNIV PITTSBURGH,DEPT PHARMACEUT SCI,PITTSBURGH,PA 15238. UNIV PITTSBURGH,PITTSBURGH CANC INST,PITTSBURGH,PA 15238. NCI,DIV CANC TREATMENT,DEV THERAPEUT PROGRAM,MOLEC PHARMACOL LAB,BETHESDA,MD 20892. HARBOR BRANCH OCEANOG INST INC,DIV BIOMED MARINE RES,FT PIERCE,FL 34946. NR 31 TC 331 Z9 341 U1 2 U2 14 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD JAN 9 PY 1996 VL 35 IS 1 BP 243 EP 250 DI 10.1021/bi9515127 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA TP482 UT WOS:A1996TP48200031 PM 8555181 ER PT J AU Davies, DR Cohen, GH AF Davies, DR Cohen, GH TI Interactions of protein antigens with antibodies SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Review ID HISTIDINE-CONTAINING PROTEIN; 3-DIMENSIONAL STRUCTURE; CRYSTAL-STRUCTURES; TERTIARY STRUCTURE; ESCHERICHIA-COLI; COMBINING SITES; FAB COMPLEX; NEURAMINIDASE; BINDING; RESOLUTION AB There are now several crystal structures of antibody Fab fragments complexed to their protein antigens. These include Fab complexes with lysozyme, two Fab complexes with influenza virus neuraminidase, and three Fab complexes with their anti-idiotype Fabs. The pattern of binding that emerges is similar to that found with other protein-protein interactions, with good shape complementarity between the interacting surfaces and reasonable juxtapositions of polar residues so as to permit hydrogen-bond formation. Water molecules have been observed in cavities within the interface and on the periphery, where they often form bridging hydrogen bonds between antibody and antigen. For the most part the antigen is bound in the middle of the antibody combining site with most of the six complementarity-determining residues involved in binding, For the most studied antigen, lysozyme, the epitopes for four antibodies occupy approximate to 45% of the accessible surface area. Some conformational changes have been observed to accompany binding in both the antibody and the antigen, although most of the information on conformational change in the latter comes from studies of complexes with small antigens. RP Davies, DR (reprint author), NATL INST HLTH,NIDDK,MOLEC BIOL LAB,BETHESDA,MD 20892, USA. NR 68 TC 414 Z9 418 U1 3 U2 38 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 JAN 9 PY 1996 VL 93 IS 1 BP 7 EP 12 DI 10.1073/pnas.93.1.7 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA TP367 UT WOS:A1996TP36700003 PM 8552677 ER PT J AU Salem, N Wegher, B Mena, P Uauy, R AF Salem, N Wegher, B Mena, P Uauy, R TI Arachidonic and docosahexaenoic acids are biosynthesized from their 18-carbon precursors in human infants SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE polyunsaturated fatty acids; elongation; desaturation; fatty acid metabolism; infant nutrition; gas chromatography; mass spectrometry ID ESSENTIAL FATTY-ACIDS; ALPHA-LINOLENIC ACID; BRAIN; DIET; SENSITIVITY; DEFICIENCY; METABOLISM; PRETERM; RETINA; GROWTH AB It is becoming clear that an adequate level of long-chain highly unsaturated fatty acids in the nervous system is required for optimal function and development; however, the ability of infants to biosynthesize long-chain fatty acids is unknown. This study explores the capacity of human infants to convert 18-carbon essential fatty acids to their elongated and desaturated forms, in vivo, A newly developed gas chromatography/negative chemical ionization/mass spectrometry method employing H-2-labeled essential fatty acids allowed assessment of this in vivo conversion with very high sensitivity and selectivity, Our results demonstrate that human infants have the capacity to convert dietary essential fatty acids administered enterally as 2H-labeled ethyl esters to their longer-chain derivatives, transport them to plasma, and incorporate them into membrane lipids, The in vivo conversion of linoleic acid (18:2n6) to arachidonic acid (20:4n6) is demonstrated in human beings. All elongases/desaturases necessary for the conversion of linolenic acid (18:3n3) to docosahexaenoic acid (22:6n3) are also active in the first week after birth, Although the absolute amounts of n-3 fatty acid metabolites accumulated in plasma are greater than those of the n-6 family, estimates of the endogenous pools of 18:2n6 and 18:3n3 indicate that n-6 fatty acid conversion rates are greater than those of the n-3 family. While these data clearly demonstrate the capability of infants to biosynthesize 22:6n3, a lipid that is required for optimal neural development, the amounts produced in vivo from 18:3n3 may be inadequate to support the 22:6n3 level observed in breast-fed infants. C1 UNIV CHILE, INST NUTR & TECNOL ALIMENTOS, CLIN NUTR UNIT, SANTIAGO 11, CHILE. RP Salem, N (reprint author), NATL INST HLTH, NIAAA, LMBB, 12501 WASHINGTON AVE, ROCKVILLE, MD 20852 USA. FU NICHD NIH HHS [HD22380] NR 33 TC 333 Z9 348 U1 1 U2 15 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 JAN 9 PY 1996 VL 93 IS 1 BP 49 EP 54 DI 10.1073/pnas.93.1.49 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA TP367 UT WOS:A1996TP36700010 PM 8552667 ER PT J AU Steinbach, PJ Brooks, BR AF Steinbach, PJ Brooks, BR TI Hydrated myoglobin's anharmonic fluctuations are not primarily due to dihedral transitions SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE protein dynamics; protein hydration; conformational substates; dynamical transition; molecular dynamics simulation ID INELASTIC NEUTRON-SCATTERING; RAYLEIGH-SCATTERING; MOSSBAUER RADIATION; PROTEIN DYNAMICS; TEMPERATURE; WATER; SIMULATION; MOTIONS AB To characterize the functionally important anharmonic motions of proteins, simulations of carboxymyoglobin (MbCO) dynamics have been performed during which dihedral transitions were prohibited, Comparison of torsionally restrained and unrestrained protein dynamics simulated at three levels of hydration and at temperatures ranging from 100 to 400 K suggests that hydration ''catalyzes'' protein mobility by facilitating collective anharmonic motions that do not require dihedral transitions. When dihedral transitions were prohibited, dehydrated MbCO, to a good approximation, exhibited only harmonic fluctuations, whereas hydrated MbCO exhibited both harmonic and anharmonic motions, The fluctuation of helix centers of mass also remained highly anharmonic in the torsionally restrained hydrated system, Atomic mean-square fluctuation at 300 K was reduced upon prohibition of dihedral transitions by only 28% and 10% for MbCO hydrated by 350 and 3830 water molecules, respectively. RP Steinbach, PJ (reprint author), NATL INST HLTH,DIV COMP RES & TECHNOL,STRUCT BIOL LAB,BETHESDA,MD 20892, USA. NR 25 TC 44 Z9 44 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 JAN 9 PY 1996 VL 93 IS 1 BP 55 EP 59 DI 10.1073/pnas.93.1.55 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA TP367 UT WOS:A1996TP36700011 PM 8552674 ER PT J AU VanHove, JLK Yang, HW Wu, JY Brady, RO Chen, YT AF VanHove, JLK Yang, HW Wu, JY Brady, RO Chen, YT TI High-level production of recombinant human lysosomal acid alpha-glucosidase in Chinese hamster ovary cells which targets to heart muscle and corrects glycogen accumulation in fibroblasts from patients with Pompe disease SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID MAMMALIAN-CELLS; SKELETAL-MUSCLE; ENZYME; EXPRESSION; MATURATION AB Infantile Pompe disease is a fatal genetic muscle disorder caused by a deficiency of acid alpha-glucosidase, a glycogen-degrading lysosomal enzyme. We constructed a plasmid containing a 5'-shortened human acid alpha-glucosidase cDNA driven by the cytomegalovirus promoter, as well as the aminoglycoside phosphotransferase and dihydrofolate reductase genes. Following transfection in dihydrofolate reductase-deficient Chinese hamster ovary cells, selection with Geneticin, and amplification with methotrexate, a cell line producing high levels of the alpha-glucosidase was established. In 48 hr, the cells cultured in Iscove's medium with 5 mM butyrate secreted 110-kDa precursor enzyme that accumulated to 91 mu g . ml(-1) in the medium (activity, >22.6 mu mol . hr(-1). ml(-1)). This enzyme has a pH optimum similar to that of the mature form, but a lower V-max and K-m for 4-methylumbelliferyl-alpha-D-glucoside. It is efficiently taken up by fibroblasts from Pompe patients, restoring normal levels of acid alpha-glucosidase and glycogen, The uptake is blocked by mannose 6-phosphate. Following intravenous injection, high enzyme levels are seen in heart and liver. An efficient production system now exists for recombinant human acid alpha-glucosidase targeted to heart and capable of correcting fibroblasts from patients with Pompe disease. C1 NATL INST HLTH,NINDS,BETHESDA,MD 20892. RP VanHove, JLK (reprint author), DUKE UNIV,MED CTR,DEPT PEDIAT,DURHAM,NC 27710, USA. NR 28 TC 76 Z9 79 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 JAN 9 PY 1996 VL 93 IS 1 BP 65 EP 70 DI 10.1073/pnas.93.1.65 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA TP367 UT WOS:A1996TP36700013 PM 8552676 ER PT J AU Collins, PL Hill, MG Cristina, J Grosfeld, H AF Collins, PL Hill, MG Cristina, J Grosfeld, H TI Transcription elongation factor of respiratory syncytial virus, a nonsegmented negative-strand RNA virus SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE paramyxovirus; reverse genetics; replication; polymerase ID EXPRESSION; GENE; SEQUENCE; ATTENUATION; REPLICATION; POLYMERASE; INVITRO AB RNA synthesis by the paramyxovirus respiratory syncytial virus, a ubiquitous human pathogen, was found to be more complex than previously appreciated for the nonsegmented negative-strand RNA viruses. Intracellular RNA replication of a plasmid-encoded ''minigenome'' analog of viral genomic RNA was directed by coexpression of the N, P, and L proteins. But, under these conditions, the greater part of mRNA synthesis terminated prematurely. This difference in processivity between the replicase and the transcriptase was unanticipated because the two enzymes ostensively shared the same protein subunits and template. Coexpression of the M2 gene at a low level of input plasmid resulted in the efficient production of full-length mRNA and, in the case of a dicistronic minigenome, sequential transcription. At a higher Level, coexpression of the M2 gene inhibited transcription and RNA replication. The M2 mRNA contains two overlapping translational open reading frames (ORFs), which were segregated for further analysis. Expression of the upstream ORF1, which encoded the previously described 22-kDa M2 protein, was associated with transcription elongation, A model involving this protein in the balance between transcription and replication is proposed. ORF2, which lacks an assigned protein, was associated with inhibition of RNA synthesis, We propose that this activity renders nucleocapsids synthetically quiescent prior to incorporation into virions. RP Collins, PL (reprint author), NIAID,INFECT DIS LAB,7 CTR DR,MSC 0720,BETHESDA,MD 20892, USA. NR 21 TC 175 Z9 181 U1 1 U2 5 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD JAN 9 PY 1996 VL 93 IS 1 BP 81 EP 85 DI 10.1073/pnas.93.1.81 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA TP367 UT WOS:A1996TP36700016 PM 8552680 ER PT J AU Krah, R Kozyavkin, SA Slesarev, AI Gellert, M AF Krah, R Kozyavkin, SA Slesarev, AI Gellert, M TI A two-subunit type I DNA topoisomerase (reverse gyrase) from an extreme hyperthermophile SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID ESCHERICHIA-COLI; ATPASE ACTIVITY; PROTEIN; ARCHAEBACTERIA; RECOMBINATION; SULFOLOBUS; HELICASES; SEQUENCE; INVITRO; ENZYME AB A recently described reverse gyrase from the hyperthermophilic methanogen Methanopyrus kandleri is the only known example of a heterodimeric type I topoisomerase. The enzyme is made up of a 42-kDa subunit which covalently interacts with DNA (RgyA) and a 138-kDa subunit which binds ATP (RgyB). We have now cloned and sequenced the genes for both subunits of this enzyme, Surprisingly, the universally conserved type I topoisomerase domain [Lima, C. D., Wang, J. C. & Mondragon, A. (1994) Nature (London) 367, 138-146] which has been found as a contiguous polypeptide in the prokaryotes and eukaryotes is shared between the protomers. The subdomain with the active-site tyrosine is entirely within RgyA, whereas the subdomain implicated in noncovalent binding of the cleaved DNA strand is contained entirely in RgyB, The appearance of this unique structure in a highly conserved enzyme family supports the hypothesis that the methanogens branched from other prokaryotes and eukaryotes very early in evolution. C1 NATL INST HLTH,NIDDK,MOLEC BIOL LAB,BETHESDA,MD 20892. UNIV CALIF LOS ANGELES,INST MOLEC BIOL,LOS ANGELES,CA 90024. UNIV CALIF LOS ANGELES,DEPT BIOL,LOS ANGELES,CA 90024. NR 38 TC 41 Z9 42 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 JAN 9 PY 1996 VL 93 IS 1 BP 106 EP 110 DI 10.1073/pnas.93.1.106 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA TP367 UT WOS:A1996TP36700021 PM 8552584 ER PT J AU Chang, K Pastan, I AF Chang, K Pastan, I TI Molecular cloning of mesothelin, a differentiation antigen present on mesothelium, mesotheliomas, and ovarian cancers SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE glycosylphosphatidylinositol anchor; plasma membrane; antibody; cell adhesion ID MONOCLONAL-ANTIBODY; K1; PROTEIN; SURFACE; CAK1; DNA AB Monoclonal antibody MAb K1 recognizes a 40-kDa glycoprotein present on the surface of mesothelial cells, mesotheliomas, and ovarian cancers, We have used MAb K1 to isolate a 2138-bp cDNA that encodes this antigen. The cDNA has an 1884-bp open reading frame encoding a 69-kDa protein. When the cDNA was transfected into COS and NIH 3T3 cells, the antigen was found on the cell surface and could be released by treatment with phosphatidylinositol-specific phospholipase C. The 69-kDa precursor is processed to the 40-kDa form. The protein has been named mesothelin because it is made by mesothelial cells, Mesothelin may play a role in cellular adhesion. RP Chang, K (reprint author), NCI,DIV CANC BIOL DIAG & CTR,MOLEC BIOL LAB,BLDG 37,ROOM 4E16,37 CONVENT DR MSC 4255,BETHESDA,MD 20892, USA. NR 18 TC 361 Z9 379 U1 4 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 JAN 9 PY 1996 VL 93 IS 1 BP 136 EP 140 DI 10.1073/pnas.93.1.136 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA TP367 UT WOS:A1996TP36700027 PM 8552591 ER PT J AU Tsai, SC Adamik, R Moss, J Vaughan, M AF Tsai, SC Adamik, R Moss, J Vaughan, M TI Purification and characterization of a guanine nucleotide exchange protein for ADP-ribosylation factor from spleen cytosol SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID BREFELDIN-A; ADENYLATE-CYCLASE; CHOLERA-TOXIN; BOVINE BRAIN; FACTOR ARF; GOLGI; GTP; MEMBRANES; BINDING; ASSOCIATION AB ADP-ribosylation factors (ARFs) are 20-kDa guanine nucleotide-binding proteins and are active in the GTP-bound state and inactive with GDP bound. ARF GTP has a critical role in vesicular transport in several cellular compartments. Conversion of ARF GDP to ARF GTP is promoted by a guanine nucleotide-exchange protein (GEP). We earlier reported the isolation from bovine brain cytosol of a 700-kDa protein complex containing GEP activity that was inhibited by brefeldin A (BFA). Partial purification yielded an approximate to 60-kDa BFA-insensitive GEP that enhanced binding of ARF1 and ARF3 to Golgi membranes. GEP has now been purified extensively from rat spleen cytosol in a BFA-insensitive, approximate to 55-kDa form. It activated class I ARFs (ARFs 1 and 3) that were N-terminally myristoylated, but not nonmyristoylated ARFs from class I, II, or III. GEP activity required MgCl2. In the presence of 0.6-0.8 mM MgCl2 and 1 mM EDTA, binding of guanosine 5'-[gamma-[S-35]thio]triphosphate ([S-35]GTP gamma S) by ARF1 and ARF3 was equally high without and with GEP. At higher Mg2+ concentrations', binding without GEP was much Lower; with 2-5 mM MgCl2, GEP-stimulated binding was maximal. The rate of GDP binding was much less than that of GTP gamma S with and without GEP. Phospholipids were necessary for GEP activity; phosphatidylinositol was more effective than phosphatidylserine, and phosphatidic acid was less so. Other phospholipids tested were ineffective. Maximal effects required approximate to 200 mu M phospholipid, with half-maximal activation at 15-20 mu M. Release of bound [S-35]GTP gamma S from ARF3 required the presence of both GEP and unlabeled GTP or GTP gamma S; GDP was much less effective. This characterization of the striking effects of Mg2+ concentration and specific phospholipids on the purified BFA-insensitive ARF GEP should facilitate experiments to define its function in vesicular transport. RP Tsai, SC (reprint author), NHLBI,PULM CRIT CARE MED BRANCH,ROOM 5N-307,BLDG 10,BETHESDA,MD 20892, USA. NR 28 TC 31 Z9 31 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 JAN 9 PY 1996 VL 93 IS 1 BP 305 EP 309 DI 10.1073/pnas.93.1.305 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA TP367 UT WOS:A1996TP36700061 PM 8552627 ER PT J AU Unson, CG Cypess, AM Wu, CR Goldsmith, PK Merrifield, RB Sakmar, TP AF Unson, CG Cypess, AM Wu, CR Goldsmith, PK Merrifield, RB Sakmar, TP TI Antibodies against specific extracellular epitopes of the glucagon receptor block glucagon binding SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE peptide; antigen; hormone receptor; G protein; signal transduction ID ANTIGENIC DETERMINANTS; EXPRESSION CLONING; MOLECULAR-CLONING; HORMONE AB Polyclonal antibodies were prepared against synthetic peptides corresponding to four different extramembrane segments of the rat glucagon receptor. The antibodies bound specifically to native glucagon receptor as judged by immunofluorescence microscopy of cultured cells expressing a synthetic gene for the receptor, Antibodies to peptides designated PR-15 and DK-12 were directed against amino acid residues 103-117 and 126-137, respectively, of the extracellular N-terminal tail. Antibody to peptide KD-14 was directed against residues 206-219 of the first extracellular loop, and antibody to peptide ST-18, against the intracellular C-terminal tail, residues 468-485. The DK-12 and KD-14 antibodies, but not the PR-15 and ST-18 antibodies, could effectively block binding of I-125-labeled glucagon to its receptor in liver membranes, Incubation of these antibodies with rat liver membranes resulted in both a decrease in the maximal hormonal binding capacity and an apparent decrease in glucagon affinity for its receptor, These effects were abolished in the presence of excess specific peptide antigen. In addition, DK-12 and KD-14 antibodies, but not PR-15 and ST-18 antibodies, interfered with glucagon-induced adenylyl cyclase activation in rat liver membranes and behaved as functional glucagon antagonists, These results demonstrate that DK-12 and KD-14 antibodies are pharmacologically active glucagon antagonists and strongly suggest that residues 125-137 of the N-terminal tail and residues 206-219 of the first extracellular loop contain determinants of ligand binding and may comprise the primary ligand-binding site on the glucagon receptor. C1 HOWARD HUGHES MED INST,NEW YORK,NY 10021. NIDDKD,MOLEC PATHOPHYSIOL BRANCH,BETHESDA,MD 20814. RP Unson, CG (reprint author), ROCKEFELLER UNIV,BOX 294,1230 YORK AVE,NEW YORK,NY 10021, USA. RI Sakmar, Thomas/D-1833-2015 OI Sakmar, Thomas/0000-0002-2836-8953 FU NIDDK NIH HHS [DK24039] NR 29 TC 47 Z9 47 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 JAN 9 PY 1996 VL 93 IS 1 BP 310 EP 315 DI 10.1073/pnas.93.1.310 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA TP367 UT WOS:A1996TP36700062 PM 8552628 ER PT J AU Seok, YJ Lee, BR Zhu, PP Peterkofsky, A AF Seok, YJ Lee, BR Zhu, PP Peterkofsky, A TI Importance of the carboxyl-terminal domain of enzyme I of the Escherichia coli phosphoenolpyruvate: Sugar phosphotransferase system for phosphoryl donor specificity SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID EXPRESSION; GENE; TRANSPORT; PROTEINS AB The first protein component of the Escherichia coli phosphoanolpyruvate:sugar phosphotransferase system (PTS) is the 64-kDa protein enzyme I (EI), which can be phosphorylated by phosphoenolpyruvate (PEP) and carry out phosphotransfer to the acceptor heat-stable protein (HPr). The isolated amino-terminal domain (EIN) of E. coli EI is no longer phosphorylated by PEP but retains the ability to participate in reversible phosphotransfer to HPr. An expression vector was constructed for the production of large amounts of EIN, and conditions were developed for maximal expression of the protein. A three-column procedure is described for purification to homogeneity of EIN; a 500-ml culture fields approximately 80 mg of pure protein in about a 75% yield. Intact E. coli EI is effective in phosphotransfer from PEP to HPr from E. coli but not to the HPrs from Bacillus subtilis or Mycoplasma capricolum, Phosphotransfer from EI to enzyme IIA(glc) (EIIA(glc)) from E. coli or M. capricolum requires the intermediacy of HPr. The phosphorylated form of EIN is capable of more general phosphotransfer; it will effect phosphotransfer to HPrs from E. coli, B. subtilis, and M. capricolum as well as to EIIA(glc) from E. coli. These studies demonstrate that the carboxyl-terminal domain of EI confers on the protein the capability to accept a phosphoryl group from PEP as well as a discriminator function that allows the intact protein to promote effective phosphoryl transfer only to E. coli HPr. C1 NHLBI,BIOCHEM GENET LAB,BETHESDA,MD 20892. NR 16 TC 47 Z9 47 U1 3 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 JAN 9 PY 1996 VL 93 IS 1 BP 347 EP 351 DI 10.1073/pnas.93.1.347 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA TP367 UT WOS:A1996TP36700069 PM 8552636 ER PT J AU Thornton, AM Buller, RML DeVico, AL Wang, IM Ozato, K AF Thornton, AM Buller, RML DeVico, AL Wang, IM Ozato, K TI Inhibition of human immunodeficiency virus type 1 and vaccinia virus infection by a dominant negative factor of the interferon regulatory factor family expressed in monocytic cells SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE antiviral activity; interferon-simulated response element; transcription factor ICSBP; DNA-binding domain; monocyte ID PROTEIN-KINASE; INDUCIBLE GENES; TRANSCRIPTION; ALPHA; RNA; REPLICATION; ACTIVATION; RETROVIRUS; ELEMENTS; SEQUENCE AB ICSBP is a member of the interferon (IFN) regulatory factor (IRF) family that regulates expression of type I interferon (IFN) and IFN-regulated genes, To study the role of the IRF family in viral infection, a cDNA for the DNA-binding domain (DBD) of ICSBP was stably transfected into U937 human monocytic cells,Clones that expressed DBD exhibited a dominant negative phenotype and did not elicit antiviral activity against vesicular stomatitis virus (VSV) infection upon IFN treatment. Most notably, cells expressing DBD were refractory to infection by vaccinia virus (VV) and human immunodeficiency virus type 1 (HIV-1). The inhibition of VV infection was attributed to defective virion assembly, and that of HIV-1 to low CD4 expression and inhibition of viral transcription in DBD clones. HIV-1 and VV were found to have sequences in their regulatory regions similar to the IFN-stimulated response element (ISRE) to which IRF family proteins bind. Accordingly, these viral sequences and a cellular ISRE bound a shared factor(s) expressed in U937 cells. These observations suggest a novel host-virus relationship in which the productive infection of some viruses is regulated by the IRF-dependent transcription pathway through the ISRE. C1 NICHHD,MOLEC GROWTH REGULAT LAB,BETHESDA,MD 20892. GEORGE WASHINGTON UNIV,DEPT MICROBIOL & IMMUNOL,WASHINGTON,DC 20052. ST LOUIS UNIV,SCH MED,DEPT MOLEC MICROBIOL & IMMUNOL,ST LOUIS,MO 63104. ADV BIOSCI LABS,KENSINGTON,MD 20852. NR 36 TC 21 Z9 24 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 JAN 9 PY 1996 VL 93 IS 1 BP 383 EP 387 DI 10.1073/pnas.93.1.383 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA TP367 UT WOS:A1996TP36700076 PM 8552643 ER PT J AU Gozes, I Bardea, A Reshef, A Zamostiano, R Zhukovsky, S Rubinraut, S Fridkin, M Brenneman, DE AF Gozes, I Bardea, A Reshef, A Zamostiano, R Zhukovsky, S Rubinraut, S Fridkin, M Brenneman, DE TI Neuroprotective strategy for Alzheimer disease: Intranasal administration of a fatty neuropeptide SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID VASOACTIVE-INTESTINAL-PEPTIDE; HIPPOCAMPAL-LESIONS; ENVELOPE PROTEIN; MESSENGER-RNA; REM-SLEEP; VIP; POLYPEPTIDE; RECEPTORS; IMPAIRMENT; ANTAGONIST AB Neurodegenerative diseases, in which neuronal cells disintegrate, bring about deteriorations in cognitive functions as is evidenced in millions of Alzheimer patients. A major neuropeptide, vasoactive intestinal peptide (VIP), has been shown to be neuroprotective and to play an important role in the acquisition of learning and memory. A potent lipophilic analogue to VIP now has been synthesized, [stearylnorleucine(17)]VIP ([St-Nle(17)]VIP), that exhibited neuroprotection in model systems related to Alzheimer disease. The beta-amyloid peptide is a major component of the cerebral amyloid plaque in Alzheimer disease and has been shown to be neurotoxic. We have found a 70% loss in the number of neurons in rat cerebral cortical cultures treated with the beta-amyloid peptide (amino acids 25-35) in comparison to controls. This cell death was completely prevented by cotreatment with 0.1 pM [St-Nle(17)]VIP. Furthermore, characteristic deficiencies in Alzheimer disease result from death of cholinergic neurons, Rats treated with a cholinergic blocker (ethylcholine aziridium) have been used as a model for cholinergic deficits. St-Nle-VIP injected intracerebroventricularly or delivered intranasally prevented impairments in spatial learning and memory associated with cholinergic blockade, These studies suggest both an unusual therapeutic strategy for treatment of Alzheimer deficiencies and a means for noninvasive peptide administration to the brain. C1 WEIZMANN INST SCI,DEPT ORGAN CHEM,IL-76100 REHOVOT,ISRAEL. NICHHD,DEV NEUROBIOL LAB,SECT DEV & MOLEC PHARMACOL,BETHESDA,MD 20892. RP Gozes, I (reprint author), TEL AVIV UNIV,SACKLER SCH MED,DEPT CLIN BIOCHEM,IL-69978 TEL AVIV,ISRAEL. NR 49 TC 137 Z9 145 U1 2 U2 13 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 JAN 9 PY 1996 VL 93 IS 1 BP 427 EP 432 DI 10.1073/pnas.93.1.427 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA TP367 UT WOS:A1996TP36700085 PM 8552653 ER PT J AU Heselmeyer, K Schrock, E duManoir, S Blegen, H Shah, K Steinbeck, R Auer, G Ried, T AF Heselmeyer, K Schrock, E duManoir, S Blegen, H Shah, K Steinbeck, R Auer, G Ried, T TI Gain of chromosome 3q defines the transition from severe dysplasia to invasive carcinoma of the uterine cervix SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID COMPARATIVE GENOMIC HYBRIDIZATION; MOLECULAR CYTOGENETIC ANALYSIS; SOLID TUMORS; HETEROZYGOSITY; EVOLUTION AB We have chosen tumors of the uterine cervix as a model system to identify chromosomal aberrations that occur during carcinogenesis, A phenotype/genotype correlation was established in defined regions of archived, formalin-fixed, and hematoxylin/eosin-stained tissue sections that were dissected from normal cervical epithelium (n = 3), from mild (n = 4), moderate (n = 6), and severe dysplasias/carcinomas irt situ (CIS) (n = 13), and from invasive carcinomas (n = 10) and investigated by comparative genomic hybridization, The same tissues were analyzed for DNA ploidy, proliferative activity, and the presence of human papillomavirus (HPV) sequences. The results show that an increase in proliferative activity and tetraploidization had occurred already in mildly dysplastic lesions. No recurrent chromosomal aberrations were observed in DNA extracted from normal epithelium or from mild and moderate dysplasias, indicating that the tetraploidization precedes the loss or gain of specific chromosomes, A gain of chromosome 3q became visible in one of the severe dysplasias/CIS, Notably, chromosome 3q was overrepresented in 90% of the carcinomas and was also found to have undergone a high-level copy-number increase (amplification). We therefore conclude that the gain of chromosome 30 that occurs in HPV16-infected, aneuploid cells represents a pivotal genetic aberration at the transition from severe dysplasia/CIS to invasive cervical carcinoma. C1 JOHNS HOPKINS UNIV,SCH HYG & PUBL HLTH,BALTIMORE,MD. KAROLINSKA INST & HOSP,DEPT PATHOL,STOCKHOLM,SWEDEN. INST PATHOL,FLENSBURG,GERMANY. RP Heselmeyer, K (reprint author), NIH,NATL CTR HUMAN GENOME RES,DIAGNOST DEV BRANCH,BLDG 49,ROOM 4A28,49 CONVENT DR,MSC 4470,BETHESDA,MD 20892, USA. NR 31 TC 364 Z9 374 U1 1 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 JAN 9 PY 1996 VL 93 IS 1 BP 479 EP 484 DI 10.1073/pnas.93.1.479 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA TP367 UT WOS:A1996TP36700096 PM 8552665 ER PT J AU Sell, DR Lane, MA Johnson, WA Masoro, EJ Mock, OB Reiser, KM Fogarty, JF Cutler, RG Ingram, DK Roth, GS Monnier, VM AF Sell, DR Lane, MA Johnson, WA Masoro, EJ Mock, OB Reiser, KM Fogarty, JF Cutler, RG Ingram, DK Roth, GS Monnier, VM TI Longevity and the genetic determination of collagen glycoxidation kinetics in mammalian senescence SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE life-span; oxidation; glycation; Maillard reaction; skin ID DIETARY RESTRICTION; DIABETES-MELLITUS; OXIDATIVE STRESS; CROSS-LINKING; AGE; GLUCOSE; HYPOTHESIS; DISEASE AB A fundamental question in the basic biology of aging is whether there is a universal aging process. If indeed such a process exists, one would expect that it develops at a higher rate in short- versus long-lived species, We have quantitated pentosidine, a marker of glycoxidative stress in skin collagen from eight mammalian species as a function of age. A curvilinear increase was modeled for all species, and the rate of increase correlated inversely with maximum life-span. Dietary restriction, a potent intervention associated with increased life-span, markedly inhibited glycoxidation rate in the rodent. On the assumption that collagen turnover rate is primarily influenced by the crosslinking due to glycoxidation, these results suggest that there is a progressive age-related deterioration of the process that controls the collagen glycoxidation rate, Thus, the ability to withstand damage due to glycoxidation and the Maillard reaction may be under genetic control. C1 NIA, GERONTOL RES CTR, BALTIMORE, MD 21224 USA. US FDA, DEPT HLTH & HUMAN SERV, LAUREL, MD 20708 USA. UNIV TEXAS, HLTH SCI CTR, DEPT PHYSIOL, SAN ANTONIO, TX 78284 USA. KIRKSVILLE COLL OSTEOPATH MED, DEPT ANAT, KIRKSVILLE, MO 63501 USA. UNIV CALIF DAVIS, CALIF REG PRIMATE RES CTR, DAVIS, CA 95616 USA. RP Sell, DR (reprint author), CASE WESTERN RESERVE UNIV, INST PATHOL, 2085 ADELBERT RD, CLEVELAND, OH 44106 USA. RI Monnier, Vincent/B-1371-2009 FU NIA NIH HHS [AG05601, AG11080]; NIAMS NIH HHS [P30 AR39750] NR 46 TC 140 Z9 144 U1 1 U2 5 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 JAN 9 PY 1996 VL 93 IS 1 BP 485 EP 490 DI 10.1073/pnas.93.1.485 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA TP367 UT WOS:A1996TP36700097 PM 8552666 ER PT J AU Larionov, V Kouprina, N Graves, J Chen, XN Korenberg, JR Resnick, MA AF Larionov, V Kouprina, N Graves, J Chen, XN Korenberg, JR Resnick, MA TI Specific cloning of human DNA as yeast artificial chromosomes by transformation-associated recombination SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID SACCHAROMYCES-CEREVISIAE; SEQUENCES; VECTORS; MANIPULATION; SEGMENTS; CLONES; CELLS; ALU AB DNA molecules undergoing transformation into yeast are highly recombinogenic, even when diverged, We reasoned that transformation-associated recombination (TAR) could be employed to clone large DNAs containing repeat sequences, thereby eliminating the need for in vitro enzymatic reactions such as restriction and Ligation and reducing the amount of DNA handling, Gently isolated human DNA was transformed directly into yeast spheroplasts along with two genetically marked (M1 and M2) linearized vectors that contained a human Alu sequence at one end and a telomere sequence at the other end (Alu-CEN-M1-TEL and Alu-M2-TEL), Nearly all the M1-selected transformants had yeast artificial chromosomes (YACs) containing human DNA inserts that varied in size from 70 kb to >600 kb, Approximately half of these had also acquired the unselected M2 marker. The mitotic segregational stability of YACs generated from one (M1) or two (M1 and M2) vector(s) was comparable, suggesting de novo generation of telomeric ends, Since no YACs were isolated when rodent DNAs or a vector lacking an Alu sequence was used, the YACs were most likely the consequence of TAR between the repeat elements on the vector(s) and the human DNA, Using the BLUR13 Alu-containing vector, we demonstrated that human DNA could be efficiently cloned from mouse cells that contained a single human chromosome 16, The distribution of cloned DNAs on chromosome 16 was determined by fluorescence in situ hybridization, We propose that TAR cloning can provide an efficient means for generating YACs from specific chromosomes and subchromosome fragments and that TAR cloning may be useful for isolating families of genes and specific genes from total genome DNA. C1 UNIV CALIF LOS ANGELES,CEDARS SINAI MED CTR,AHMANSON DEPT PEDIAT,DIV GENET,LOS ANGELES,CA 90048. RP Larionov, V (reprint author), NIEHS,GENET MOLEC LAB,BOX 12233,RES TRIANGLE PK,NC 27709, USA. FU NHGRI NIH HHS [1-YO2-HG-60021-01] NR 29 TC 84 Z9 89 U1 0 U2 15 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 JAN 9 PY 1996 VL 93 IS 1 BP 491 EP 496 DI 10.1073/pnas.93.1.491 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA TP367 UT WOS:A1996TP36700098 PM 8552668 ER PT J AU Crespo, CJ Keteyian, SJ Heath, GW Sempos, CT AF Crespo, CJ Keteyian, SJ Heath, GW Sempos, CT TI Leisure-time physical activity among US adults - Results from the third national health and nutrition examination survey SO ARCHIVES OF INTERNAL MEDICINE LA English DT Article ID UNITED-STATES ADULTS; CHOLESTEROL; PREVALENCE AB Background: The prevalence of no leisure-time physical activity (LTPA) among US adults is estimated to be between 24% and 30%. Such information, however, usually does not include prevalence estimates for non-Hispanic blacks, Mexican Americans, and the elderly. Objective: To assess the prevalence of participation in leisure-time physical activity among US adults. Methods: Between 1988 and 1991, 9488 adults aged 20 years and older were interviewed in their home as part of the third National Health and Nutrition Examination Survey. A clinic examination in a mobile center was also included. Mexican Americans, non-Hispanic blacks, and the elderly were oversampled to produce reliable estimates for these groups. Questions were asked about the type and frequency of physically active hobbies, sports, and exercises. Results: The prevalence of no LTPA for US adults aged 20 years or older from 1988 through 1991 was 22%. The rate was higher in women (27%) than in men (17%). Mexican-American men (33%) and women (46%) and non-Hispanic black women (40%) had the highest rates of no LTPA. Participation in moderate to vigorous LTPA five or more times per week decreased with age, with the largest decreases observed among non-Hispanic black men and women. In almost all subpopulations, gardening and/or yard work and walking were stated as the two top LTPAs of choice. Conclusions: Many Americans are inactive or irregularly active during their leisure time. Rates of inactivity are greater for women, older persons, non-Hispanic blacks, and Mexican Americans. Intervention strategies meant to promote lifetime physical activities among all Americans represents a major health priority. C1 NATL CTR HLTH STAT,DIV HLTH EXAMINAT STAT,HYATTSVILLE,MD. NATL CTR CHRON DIS PREVENT & HLTH PROMOT,CTR DIS CONTROL & PREVENT,ATLANTA,GA. RP Crespo, CJ (reprint author), NHLBI,NIH,OFF PREVENT EDUC & CONTROL,31 CTR DR,MSC 2480,ROOM 4A18,BETHESDA,MD 20892, USA. NR 35 TC 378 Z9 379 U1 2 U2 33 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0003-9926 J9 ARCH INTERN MED JI Arch. Intern. Med. PD JAN 8 PY 1996 VL 156 IS 1 BP 93 EP 98 DI 10.1001/archinte.156.1.93 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA TN398 UT WOS:A1996TN39800013 PM 8526703 ER PT J AU Gnabre, JN Ito, Y Ma, Y Huang, RC AF Gnabre, JN Ito, Y Ma, Y Huang, RC TI Isolation of anti-HIV-1 lignans from Larrea tridentata by counter-current chromatography SO JOURNAL OF CHROMATOGRAPHY A LA English DT Article DE human immunodeficiency virus; Larrea tridentata; secreted alkaline phosphatase assay; lignans; 3'-O-methylnordihydroguaiaretic acid ID GENE AB Several lignans, mostly new, were isolated from Larrea tridentata by assay-guided counter-current chromatography (CCC). Using the secreted alkaline phosphatase bioassay of HIV Tat transactivation and the two-phase hexane-ethyl acetate-methanol-water solvent system, two major components (Gr and Lo) were identified as anti-HIV active principles. The chemical structures of the constituents of Gr (G(1)-G(4)) and Lo (L(1)-L(4)) were determined by GC-MS and NMR. After optimization of isolation conditions, a large-scale isolation with the chloroform-methanol-water system yielded five constituents (FB1-FB5). The most predominant anti-HIV compound FB2 (denoted Malachi 4:5-6 or mal.4), which occurs in 0.23% yield, was separated from its FB1 isomer (0.13% yield). Compound FB4 and two tricyclic lignans (FB3 and FB5) were also isolated in a substantial amount for further testing of their anti-HIV activities. These compounds may represent a new class of anti-HIV agents with important clinical relevance. C1 JOHNS HOPKINS UNIV,DEPT BIOL,BALTIMORE,MD 21218. NHLBI,BIOPHYS CHEM LAB,BETHESDA,MD 20892. FU NIAID NIH HHS [AI 32301] NR 26 TC 36 Z9 42 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0021-9673 J9 J CHROMATOGR A JI J. Chromatogr. A PD JAN 8 PY 1996 VL 719 IS 2 BP 353 EP 364 DI 10.1016/0021-9673(95)00727-X PG 12 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA TR005 UT WOS:A1996TR00500011 PM 8581122 ER PT J AU Shi, XL Jiang, HG Mao, Y Ye, JP Saffiotti, U AF Shi, XL Jiang, HG Mao, Y Ye, JP Saffiotti, U TI Vanadium(IV)-mediated free radical generation and related 2'-deoxyguanosine hydroxylation and DNA damage SO TOXICOLOGY LA English DT Article DE vanadium(IV); free radical; 8-hydroxyl-2'-deoxyguanosine; DNA damage ID LIPID-PEROXIDATION PRODUCTS; CHELATING-AGENTS; HUMAN-ERYTHROCYTES; HYDROGEN-PEROXIDE; ESR EVIDENCE; VANADATE; VANADIUM; MICE; IONS; COOXYGENATION AB Free radical generation, 2'-deoxyguanosine (dG) hydroxylation and DNA damage by vanadium(IV) reactions were investigated. Vanadium(IV) caused molecular oxygen dependent dG hydroxylation to form 8-hydroxyl-2'deoxyguanosine (8-OHdG). During a 15 min incubation of 1.0 mM dG and 1.0 mM VOSO4 in phosphate buffer solution (pH 7.4) at room temperature under ambient air, dG was converted to 8-OHdG with a yield of about 0.31%. Catalase and formate inhibited the 8-OHdG formation while superoxide dismutase enhanced it. Metal ion chelators, DTPA and deferoxamine, blocked the 8-OHdG formation. Incubation of vanadium(IV) with dG in argon did not generate any significant amount of 8-OHdG, indicating the role of molecular oxygen in the mechanism of vanadium(IV)induced dG hydroxylation. Vanadium(IV) also caused molecular oxygen-dependent DNA strand breaks in a pattern similar to that observed for dG hydroxylation. ESR spin trapping measurements demonstrated that the reaction of vanadium(IV) with H2O2 generated (OH)-O-. radicals, which were inhibited by DTPA and deferoxamine. Incubation of vanadium(IV) with dG or with DNA in the presence of H2O2 resulted in an enhanced 8-OHdG formation and substantial DNA double strand breaks. Sodium formate inhibited 8-OHdG formation while DTPA had no significant effect. Deferoxamine enhanced the 8-OHdG generation by 2.5-fold. ESR and UV measurements provided evidence for the complex formation between vanadium(IV) and deferoxamine. UV-visible measurements indicate that dG, vanadium(IV) and deferoxamine are able to form a complex, thereby, facilitating site-specific 8-OHdG formation. Reaction of vanadium(IV) with t-butyl hydroperoxide generated hydroperoxide-derived free radicals, which caused 8-OHdG formation from dG and DNA strand breaks. DTPA and deferoxamine attenuated vanadium(IV)/t-butyl-OOH-induced DNA strand breaks. C1 FREDERICK CANC RES & DEV CTR,PROGRAM RESOURCES INC,FREDERICK,MD 21702. NCI,LAB EXPTL IMMUNOL,FREDERICK,MD 21702. RP Shi, XL (reprint author), NCI,LAB EXPTL PATHOL,NIH,BLDG 41,ROOM C301,BETHESDA,MD 20892, USA. RI Shi, Xianglin/B-8588-2012 NR 50 TC 67 Z9 69 U1 0 U2 2 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0300-483X J9 TOXICOLOGY JI Toxicology PD JAN 8 PY 1996 VL 106 IS 1-3 BP 27 EP 38 DI 10.1016/0300-483X(95)03151-5 PG 12 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA TR224 UT WOS:A1996TR22400004 PM 8571399 ER PT J AU Ing, BL Chen, H Robinson, KA Buse, MG Quon, MJ AF Ing, BL Chen, H Robinson, KA Buse, MG Quon, MJ TI Characterization of a mutant GLUT4 lacking the N-glycosylation site: Studies in transfected rat adipose cells SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article ID GLUCOSE-TRANSPORT ACTIVITY; HEXOSE-TRANSPORT; INSULIN; TRANSLOCATION; TUNICAMYCIN; FIBROBLASTS; ISOFORMS AB GLUT4, the insulin-responsive glucose transporter expressed primarily in muscle and adipose tissue, contains a single N-glycosylation sire. We characterized a mutant GLUT4 lacking the N-glycosylation site (Asn(57) --> Gin) in primary cultures of rat adipose cells, We transiently transfected cells with expression vectors for epitope-tagged GLUT4 containing either wild-type (GLUT4-HA) or mutant (GLN57-HA) cDNA sequences, Expression of GLN57-HA in adipose cells was similar to 10-fold lower than for GLUT4-HA even though mRNA levels for bath recombinant transporters were comparable, Biosynthetic labeling studies showed markedly decreased incorporation of [S-35]-methionine/cysteine into GLN57-HA relative to GLUT4-HA consistent with either a decreased synthetic rate or accelerated degradation of GLN57-HA. Interestingly, transient transfection of GLUT4-HA and GLN57-HA in COS-7 cells (which do not express endogenous GLUT4) resulted in comparable levels of protein expression for both transporters. Thus, in the physiologically relevant adipose cell, glycosylation of GLUT4 appears to play an important functional role. (C) 1996 Academic Press, Inc. C1 NIDDKD,DIABET BRANCH,BETHESDA,MD 20892. NHLBI,HYPERTENS ENDOCRINE BRANCH,BETHESDA,MD 20892. MED UNIV S CAROLINA,DEPT MED,DIV ENDOCRINOL,CHARLESTON,SC 29425. RI Quon, Michael/B-1970-2008; OI Quon, Michael/0000-0002-9601-9915; Quon , Michael /0000-0002-5289-3707 FU NIDDK NIH HHS [DK-02001] NR 30 TC 16 Z9 16 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD JAN 5 PY 1996 VL 218 IS 1 BP 76 EP 82 DI 10.1006/bbrc.1996.0015 PG 7 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA TP754 UT WOS:A1996TP75400015 PM 8573180 ER PT J AU Tasaki, I AF Tasaki, I TI Rapid changes in light-scattering in the prism of Torpedo electric organ slice associated with the production of postsynaptic potentials SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article ID IONIC GELS; ACETYLCHOLINE AB Using a bifurcated lightguide placed on the surface of a prism of the electric organ slice of Torpedo, the generation of postsynaptic potentials by direct stimulation was found to be associated with readily detectable, disphasic optical changes. The changes consisted of a decrease in light-scattering during the rising phase of the electric potential, followed by a prolonged increase in scattering. The effects of varying the calcium-ion concentration in the medium strongly support the view that replacement of transmitter molecules for bound Ca-ions in the receptor proteins is at the base of these changes. The effects of synaptically active reagents on these optical signals were demonstrated. (C) 1996 Academic Press, Inc. RP Tasaki, I (reprint author), NIMH,CELL BIOL LAB,BETHESDA,MD 20892, USA. NR 12 TC 3 Z9 3 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD JAN 5 PY 1996 VL 218 IS 1 BP 298 EP 301 DI 10.1006/bbrc.1996.0052 PG 4 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA TP754 UT WOS:A1996TP75400052 PM 8573149 ER PT J AU Blake, BL Philpot, RM Levi, PE Hodgson, E AF Blake, BL Philpot, RM Levi, PE Hodgson, E TI Xenobiotic biotransforming enzymes in the central nervous system: An isoform of flavin-containing monooxygenase (FMO4) is expressed in rabbit brain SO CHEMICO-BIOLOGICAL INTERACTIONS LA English DT Article DE flavin-containing monooxygenase; brain; metabolism; xenobiotic ID LUNG; RAT; CLONING; LIVER; RNA AB The flavin-containing monooxygenase (FMO, EC 1.14.13.8) is involved in the metabolism of a number of important xenobiotics including many which affect the central nervous system (CNS). Recently, reports in the literature concerning the amount, activity, location, and isozyme characteristics of this enzyme in the brain have presented conflicting evidence. In order to resolve some of the controversy surrounding FMO in the brain, a highly sensitive method for the detection of flavin-containing monooxygenase (FMO) mRNA in whole brain was employed. A poorly conserved region of FMO transcripts was used to design five sets of oligonucleotide primers. Each primer set was specific for one of the five currently known isoforms of FMO. Four and five isoforms, respectively, are expressed in rabbit liver and kidney, as determined by reverse transcription-polymerase chain reaction. However, only one set of primers amplified a specific rabbit brain cDNA fragment. The sequence of the amplification product affirmed its identity as a segment of FMO4 cDNA. Thus, the FMO of rabbit brain may consist of a single, as yet uncharacterized isozyme and, contrary to several recent reports, is likely to be expressed at low levels. C1 N CAROLINA STATE UNIV,DEPT TOXICOL,RALEIGH,NC 27695. NIEHS,CELLULAR & MOLEC PHARMACOL LAB,RES TRIANGLE PK,NC 27709. FU NIEHS NIH HHS [ES07046, ES00044] NR 18 TC 13 Z9 13 U1 0 U2 0 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0009-2797 J9 CHEM-BIOL INTERACT JI Chem.-Biol. Interact. PD JAN 5 PY 1996 VL 99 IS 1-3 BP 253 EP 261 DI 10.1016/0009-2797(95)03679-2 PG 9 WC Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Toxicology SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Toxicology GA TR908 UT WOS:A1996TR90800019 PM 8620573 ER PT J AU Lee, SB Rhee, SG AF Lee, SB Rhee, SG TI Molecular cloning, splice variants, expression, and purification of phospholipase C-delta 4 SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID GENE-PRODUCT; DROSOPHILA; SEQUENCE; SYSTEM AB Complementary DNAs encoding a previously unidentified phosphoinositide-specific phospholipase C (PLC) isozyme were cloned from a rat brain cDNA library by the polymerase chain reaction with degenerate oligonucleotide primers based on sequences common to three known delta-type PLC isozymes. The encoded polypeptide contains 772 amino acids (calculated molecular mass, 88,966 daltons) and is similar in primary structure to delta-type PLC isozymes, with overall sequence identities of 45% to PLC-delta 1, 72% to PLC-delta 2, and 47% to PLC-delta 3. Thus, the new PLC isozyme was named PLC-delta 4. Recombinant PLC-delta 4 was purified from extracts of HeLa cells that had been infected with vaccinia virus containing the corresponding cDNA, The purified protein exhibited an apparent molecular mass of 90 kDa on SDS-polyacrylamide gels. The specific activity of PLC-delta 4 and its dependence on Ca2+ were similar to those of PLC-delta 1. The distribution of PLC-delta 4 in 16 different rat tissues was studied by immunoblot analysis with PLC-delta 4-specific antibodies of fractions obtained after an enzyme-enrichment procedure. The 90-kDa immunoreactive protein was detected unambiguously in only eight tissues and was present at concentrations that were low compared to those of other major PLC isozymes. A 93-kDa immunoreactive protein was also prominent in testis but was not detected in the other seven positive tissues. The 93-kDa enzyme appears to be derived from a splice variant of the mRNA that encodes the 90-kDa PLC-delta 4 and contains an additional 32 amino acids between the X and Y catalytic domains. Splice variants have not previously been detected for delta-type PLC isozymes. C1 NHLBI,CELL SIGNALLING LAB,BETHESDA,MD 20892. NR 23 TC 78 Z9 80 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 JAN 5 PY 1996 VL 271 IS 1 BP 25 EP 31 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA TP361 UT WOS:A1996TP36100006 PM 8550568 ER PT J AU Miles, AM Bohle, DS Glassbrenner, PA Hansert, B Wink, DA Grisham, MB AF Miles, AM Bohle, DS Glassbrenner, PA Hansert, B Wink, DA Grisham, MB TI Modulation of superoxide-dependent oxidation and hydroxylation reactions by nitric oxide SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID RADICAL PRODUCTION; PEROXYNITRITE; NO; INHIBITORS; ARTHRITIS; SYNTHASE; RELEASE; INJURY; DAMAGE; AGENTS AB The rapid and spontaneous interaction between superoxide (O-2(radical anion)) and nitric oxide (NO) to yield the potent oxidants peroxynitrite (ONOO-) and peroxynitrous acid (ONOOH), has been suggested to represent an important pathway by which tissue may be injured during inflammation. Although several groups of investigators have demonstrated substantial oxidizing and cytotoxic activities of chemically synthesized ONOO-, there has been little information available quantifying the interaction between O-2(radical anion) and NO in the absence or the presence of redox-active iron. Using the hypoxanthine (HX)/xanthine oxidase system to generate various fluxes of O-2(radical anion) and H2O2 and the spontaneous decomposition of the spermine/NO adduct to produce various fluxes of NO, we found that in the absence of redox-active iron, the simultaneous production of equimolar fluxes of O-2(radical anion) and NO increased the oxidation of dihydrorhodamine (DHR) from normally undetectable levels to approximately 15 mu M, suggesting the formation of a potent oxidant. Superoxide dismutase, but not catalase, inhibited this oxidative reaction, suggesting that O-2(radical anion) and not hydrogen peroxide (H2O2) interacts with NO to generate a potent oxidizing agent. Excess production of either radical virtually eliminated the oxidation of DHR. In the presence of 5 mu M Fe+3-EDTA to insure optimum O-2(radical anion)-driven Fenton chemistry, NO enhanced modestly HX/xanthine oxidase-induced oxidation of DHR. As expected, both superoxide dismutase and catalase inhibited this Fe-catalyzed oxidation reaction. Excess NO production with respect to O-2(radical anion) flux produced only modest inhibition (33%) of DHR oxidation. In a separate series of studies, we found that equimolar fluxes of O-2(radical anion) and NO in the absence of iron only modestly enhanced hydroxylation of benzoic acid from undetectable levels to 0.6 mu M S-hydroxybenzoate. In the presence of 5 mu M Fe+8-EDTA, HX/xanthine oxidase-mediated hydroxylation of benzoic acid increased dramatically from undetectable levels to 4.5 mu M of the hydroxylated product. Superoxide dismutase and catalase were both effective at inhibiting this classic O-2(radical anion)-driven Fenton reaction, Interestingly, NO inhibited this iron-catalyzed hydroxylation reaction in a concentration-dependent manner such that fluxes of NO approximating those of O-2(radical anion) and H2O2 virtually abolished the hydroxylation of benzoic acid. We conclude that in the absence of iron, equimolar fluxes of NO and O-2(radical anion) interact to yield potent oxidants such as ONOO-/ONOOH, which oxidize organic compounds. Excess production of either radical remarkably inhibits these oxidative reactions. In the presence of low molecular weight redox-active iron complexes, NO may enhance or inhibit O-2(radical anion)-dependent oxidation and hydroxylation reactions depending upon their relative fluxes. C1 LOUISIANA STATE UNIV,MED CTR,DEPT PHYSIOL & BIOPHYS,SHREVEPORT,LA 71130. UNIV WYOMING,DEPT CHEM,LARAMIE,WY 82071. NCI,RADIAT BIOL BRANCH,BETHESDA,MD 20892. FU NCI NIH HHS [CA63641]; NIDDK NIH HHS [DK43785] NR 43 TC 297 Z9 304 U1 1 U2 11 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 JAN 5 PY 1996 VL 271 IS 1 BP 40 EP 47 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA TP361 UT WOS:A1996TP36100008 PM 8550595 ER PT J AU Otteken, A Moss, B AF Otteken, A Moss, B TI Calreticulin interacts with newly synthesized human immunodeficiency virus type 1 envelope glycoprotein, suggesting a chaperone function similar to that of calnexin SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID RECOMBINANT VACCINIA VIRUSES; CALCIUM-BINDING PROTEINS; ENDOPLASMIC-RETICULUM; MEMBRANE-PROTEIN; APLYSIA LEADS; CELL; RECOGNIZES; INCREASE; COMPLEX; REGION AB The ubiquitous eukaryotic protein calreticulin has been detected in a wide variety of different cell types. Recently, calreticulin was found to bind in vitro to a number of proteins isolated from the endoplasmic reticulum. In addition, calreticulin has sequence similarities with the molecular chaperone calnexin. These data suggest that calreticulin might also act as a chaperone. We found that calreticulin associated transiently with a large number of newly synthesized cellular proteins. In cells expressing recombinant human immunodeficiency virus (HIV) envelope glycoprotein, gp160 bound transiently to calreticulin with a peak at 10 min after its synthesis. Binding of gp120 to calreticulin was not detected because proteolytic cleavage of gp160 occurs in the trans-Golgi. Nonglycosylated HIV envelope protein was not associated with calreticulin, suggesting a requirement for N-linked oligosaccharides on newly synthesized proteins as has been reported for calnexin. The in vivo binding kinetics of calnexin and calreticulin to gp160 were very similar. Sequential immunoprecipitations provided evidence for the existence of ternary complexes of gp160, calreticulin, and calnexin. The data suggested that most of the gp160 associated with calreticulin was also bound to calnexin but that only a portion of the gp160 associated with calnexin was also bound to calreticulin. C1 NIAID,VIRAL DIS LAB,BETHESDA,MD 20892. NR 32 TC 106 Z9 107 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 JAN 5 PY 1996 VL 271 IS 1 BP 97 EP 103 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA TP361 UT WOS:A1996TP36100016 PM 8550632 ER PT J AU Ahuja, SK Lee, JC Murphy, PM AF Ahuja, SK Lee, JC Murphy, PM TI CXC chemokines bind to unique sets of selectivity determinants that can function independently and are broadly distributed on multiple domains of human interleukin-8 receptor B - Determinants of high affinity binding and receptor activitation are distinct SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID AMINO TERMINUS; LIGAND; EXPRESSION AB Human interleukin-8 receptors A (IL-8RA) and B (IL-8RB) are seven-transmembrane domain (TMD) neutrophil chemokine receptors with similar sequences (77% amino acid identity) and similar G protein selectivity, but markedly different selectivity for CXC chemokines, IL-8RB is selective for IL-8, growth-related oncogene alpha (GRO alpha) and neutrophil activating peptide-2 (NAP-2), whereas IL-8RA is selective only for IL-8. To identify selectivity determinants, we made eight chimeric receptors exchanging: 1) the three main regions of sequence divergence between IL-8RA and IL-8RB (the N-terminal segment before TMD1, the region from TMD4 to the end of the second extracellular (e2) loop, and the C-terminal tail), and 2) the N-terminal segment of CC chemokine receptor 1, which does not bind CXC chemokines. Chimeras were tested by direct I-125-IL-8, I-125-GRO alpha, and I-125-NAP-2 binding, heterologous competition binding, and calcium flux assays using human embryonic kidney 293 cells stably transfected with receptor DNAs. The following results were obtained: 1) chimeric receptors had binding sites for IL-8, GRO alpha and NAP-2 distinct from those on IL-8RA and IL-8RB; 2) IL-8, GRO alpha and NAP-2 bound to overlapping but distinct sites that mapped differentially to multiple domains on IL-8RB; 3) high affinity radioligand binding and high agonist potency were separable functions for IL-8, GRO alpha and NAP-2, suggesting that the determinants of high affinity binding may not be critical for receptor activation; and 4) determinants of GRO alpha and NAP-2 selectivity were found in both the N-terminal segment before TMD1 and the region from TMD4 to the end of the e2 loop of IL-8RB, and functioned independently of each other, Stated reciprocally, the N-terminal segment of IL-8RA was not a dominant selectivity determinant. These data suggest that both narrow and broad spectrum chemokine antagonists can be developed to block functions mediated by IL-8RB. RP Ahuja, SK (reprint author), NIAID,HOST DEF LAB,BLDG 10,RM 11N113,BETHESDA,MD 20892, USA. NR 28 TC 116 Z9 117 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 JAN 5 PY 1996 VL 271 IS 1 BP 225 EP 232 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA TP361 UT WOS:A1996TP36100035 PM 8550564 ER PT J AU Baldi, L Brown, K Franzoso, G Siebenlist, U AF Baldi, L Brown, K Franzoso, G Siebenlist, U TI Critical role for lysines 21 and 22 in signal-induced, ubiquitin-mediated proteolysis of I kappa B-alpha SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID ONCOPROTEIN BCL-3; DNA-BINDING; INDUCIBLE EXPRESSION; ACTIVATION; CELLS; GENE; TRANSACTIVATION; INHIBITION; I-KAPPA-B/MAD-3; PHOSPHORYLATION AB The NF-kappa B transcription factor induces rapid transcription of many genes in response to a variety of extracellular signals, NF-kappa B is readily activated from normally inhibited cytoplasmic stores by induced proteolytic degradation of I kappa B-alpha, a principal inhibitor of this transcription factor, Following the inhibitor's degradation, NF-kappa B is free to translocate to the nucleus and induce gene transcription. The I kappa B-alpha inhibitor is targeted for degradation by signal-induced phosphorylation of two closely spaced serines in its NH2 terminus (Ser(32) and Ser(36)). Proteolytic degradation appears to be carried out by proteasomes which can recognize ubiquitinated intermediates of the I kappa B-alpha inhibitor, We provide evidence which supports a ubiquitin-mediated mechanism, Amino acid substitutions of two adjacent potential ubiquitination sites in the NH2 terminus of I kappa B-alpha (Lys(21) and Lys(22)) almost completely block the rapid, signal-induced degradation of the mutant protein, while they do not interfere with induced phosphorylation, The mutant I kappa B-alpha also does not permit signal-induced activation of NF-kappa B bound to it, The data suggest that ubiquitination at either of the two adjacent lysines (21 and 22) is required for degradation following induced phosphorylation at nearby serines 32 and 36, Such dependence on ubiquitination of specific sites for protein degradation is unusual, This mechanism of degradation may also apply to I kappa B-beta, an inhibitor related to and functionally overlapping with I kappa B-alpha, as well as to cactus, an I kappa B homolog of Drosophila. C1 NIAID,IMMUNOREGULAT LAB,BETHESDA,MD 20892. RI Baldi, Lucia/D-9491-2011 OI Baldi, Lucia/0000-0001-5550-9435 NR 49 TC 124 Z9 128 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 JAN 5 PY 1996 VL 271 IS 1 BP 376 EP 379 PG 4 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA TP361 UT WOS:A1996TP36100059 PM 8550590 ER PT J AU Tumminia, SJ Jonak, GJ Focht, RJ Cheng, YSE Russell, P AF Tumminia, SJ Jonak, GJ Focht, RJ Cheng, YSE Russell, P TI Cataractogenesis in transgenic mice containing the HIV-1 protease linked to the lens alpha A-crystallin promoter SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID IMMUNODEFICIENCY-VIRUS PROTEASE; CALPAIN-II; VIRAL INFECTIVITY; BETA-CRYSTALLIN; PROTEOLYSIS; CATARACTS; CALCIUM; MOUSE; HUMOR AB Several lines of transgenic mice were generated with either active or inactive forms of the human immunodeficiency virus type 1 (HIV-1) protease gene under the control of the mouse lens alpha A-crystallin promoter, Mice bearing the inactive protease coding sequence displayed no gross abnormalities in the lens, while mice with the active protease developed time-dependent bilateral cataracts, One line, TG(61), developed cataracts in utero while the second line, TG(72), developed cataracts postnatally. TG(61) mice, homozygous for the transgene, developed severe microphthalmia and were significantly smaller than the control mice at postnatal day 30. two-dimensional-polyacrylamide gel electrophoresis analysis of the protein profiles of TG(72) and TG(61) lenses revealed extensive modifications in the lens crystallins. Proteolysis in the homozygous TG(72) mouse lenses began at postnatal day 20 with the disappearance or partial loss of beta B1-, beta B3-, and beta A3-crystallins and the appearance of crystallin fragments, Protein leakage and the gradual breakdown of cytoskeletal elements also occurred, In contrast, the opacification of the homozygous TG(61) lenses appeared to have been influenced by differentiation and developmental processes. It apppears that HIV-1 protease expression activates other proteases, and these enzymes, in concert with the HIV-1 protease, are responsible for the protein modifications that eventually result in the opacification of the lens. C1 DUPONT MERCK PHARMACEUT CO,WILMINGTON,DE 19880. FUJI IMMUNOPHARMACEUT,LEXINGTON,MA 02173. RP Tumminia, SJ (reprint author), NEI,LAB MECHANISMS OCULAR DIS,BLDG 6,RM 228,6 CTR DR,MSC 2735,BETHESDA,MD 20892, USA. NR 36 TC 22 Z9 23 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 JAN 5 PY 1996 VL 271 IS 1 BP 425 EP 431 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA TP361 UT WOS:A1996TP36100066 PM 8550598 ER PT J AU LopezBayghen, E Vega, A Cadena, A Granados, SE Jave, LF Gariglio, P AlvarezSalas, LM AF LopezBayghen, E Vega, A Cadena, A Granados, SE Jave, LF Gariglio, P AlvarezSalas, LM TI Transcriptional analysis of the 5'-noncoding region of the human involucrin gene SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID CULTURED HUMAN-EPIDERMIS; SERUM RESPONSE FACTOR; KERATINOCYTE TRANSGLUTAMINASE; TRANSGENIC MICE; C-MYC; PROMOTER; DIFFERENTIATION; PROTEIN; YY1; IDENTIFICATION AB Human involucrin whose gene transcription is directed by a 2456-nucleotide (nt) 5'-noncoding region is a structural component of the epithelial cornified layer, Transient transfection assays demonstrated that this region is transcriptionally active in multiplying keratinocytes and is enhanced by 2 mM CaCl2 treatment, Calcium-independent transcriptional activity and the interaction with the AP-1 transcriptional factor was located on the proximal part (nt -159 to -1) of the 5'-noncoding region. However, CaCl2 responsiveness was mapped to a distal 1185-nt fragment (nt -2456 to -1272), Moreover, this fragment potentiated the Herpes simplex thymidine kinase promoter in normal keratinocytes and is responsive to calcium treatment in a cell type-specific manner, Interestingly, the absence of a 491-nt fragment located between the two enhancer domains (nt -651 to -160) resulted in transcriptional activation in multiplying keratinocytes. This fragment interacts with AP-1 and the YY1 transcriptional silencer, It is concluded that human involucrin 5'-noncoding region contains at least three regulatory domains, a distal CaCl2-responsive enhancer, a putative transcriptional silencer (that interacts with AP-1 and YY1), and a proximal enhancer/promoter (that interacts with AP-1), Thus, this study demonstrates the presence of particular transcriptional factors can potentially regulate the human involucrin expression. C1 NCI,BIOL LAB,BETHESDA,MD 20892. INST POLITECN NACL,CTR INVEST & ESTUDIOS AVANZADOS,DEPT GENET & BIOL MOLEC,MEXICO CITY 07000,DF,MEXICO. OI Lopez-Bayghen, Esther/0000-0002-2849-7587; Jave-Suarez, Luis Felipe/0000-0001-6209-5031 NR 54 TC 70 Z9 71 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 JAN 5 PY 1996 VL 271 IS 1 BP 512 EP 520 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA TP361 UT WOS:A1996TP36100078 PM 8550612 ER PT J AU Sharma, R Lee, J Wang, SM Milne, GWA Lewin, NE Blumberg, PM Marquez, VE AF Sharma, R Lee, J Wang, SM Milne, GWA Lewin, NE Blumberg, PM Marquez, VE TI Conformationally constrained analogues of diacylglycerol .10. Ultrapotent protein kinase C ligands based on a racemic 5-disubstituted tetrahydro-2-furanone template SO JOURNAL OF MEDICINAL CHEMISTRY LA English DT Article ID PHORBOL ESTER RECEPTOR; GAMMA-LACTONES; MOUSE-BRAIN; CALCIUM; ACTIVATION; CYTOSOL AB 5,5-Bis(hydroxymethyl)tetrahydro-2-furanone and its isomer 4,4-bis(hydroxymethyl)tetrahydro-2-furanone were investigated as possible templates for the construction of conformationally constrained analogues of the biologically important second messenger, diacylglycerol (DAG). The former lactone contains embedded within its structure an exact glycerol moiety, while in the latter the ring oxygen has been transposed to the other side of the carbonyl group. Al target compounds were synthesized as racemates from 1,3-dihydroxy-2-propanone. The 5,5-bis(hydroxymethyl)tetrahydro-2-furanone proved to be the better template for the construction of DAG surrogates that were demonstrated to have high binding affinities for the biological target, protein kinase C (PK-C). The simplest target compounds derived from this template (3e and 3f) have one of the hydroxyl moieties functionalized either as a myristate or as an oleate ester. The simplest target compound (9e) derived from the ineffective 4,4-bis(hydroxymethyl)tetrahydro-2-furanone template was investigated only with a myristoyl acyl chain. Reducing the long acyl chain to an acetyl moiety and attaching a compensating lipophilic chain to the lactone ring as an alpha-alkylidene moiety produced compounds 10e and 10f(Z-isomers) and 11e and 11f(E-isomers), which were constructed on the more effective 5,5-bis(hydroxymethyl)tetrahydro-2-furanone template. Targets 14c (Z-isomer) and 15c (E-isomer) were derived, in turn, from 4,4-bis(hydroxymethyl)tetrahydro-2-furan. The affinities of these ligands for PK-C were assessed in terms of their ability to displace bound [H-3-20]phorbol 12,13-dibutyrate (PDBU) from the single isozyme PK-C alpha. The biological data support the hypothesis that the increase in binding affinity for PK-C shown by some of these constrained DAG mimetics appears to be entropic in nature. Two of the designed ligands (10e and 10f) showed the highest affinities (34 and 24 nM, respectively) reported so far for a DAG analogue. Assuming that the interaction between these racemic compounds and PK-C is stereospecific, the potency of the active enantiomer is anticipated to double. C1 NCI,MED CHEM LAB,DEV THERAPEUT PROGRAM,DIV CANC TREATMENT,BETHESDA,MD 20892. NCI,CELLULAR CARCINOGENESIS & TUMOR PROMOT LAB,MOLEC MECH TUMOR PROMOT SECT,BETHESDA,MD 20892. RI Wang, Shaomeng/E-9686-2010 NR 23 TC 42 Z9 42 U1 0 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0022-2623 J9 J MED CHEM JI J. Med. Chem. PD JAN 5 PY 1996 VL 39 IS 1 BP 19 EP 28 DI 10.1021/jm950276v PG 10 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA TN771 UT WOS:A1996TN77100004 PM 8568806 ER PT J AU Lee, J Wang, SM Milne, GWA Sharma, R Lewin, NE Blumberg, PM Marquez, VE AF Lee, J Wang, SM Milne, GWA Sharma, R Lewin, NE Blumberg, PM Marquez, VE TI Conformationally constrained analogues of diacylglycerol .11. Ultrapotent protein kinase C ligands based on a chiral 5-disubstituted tetrahydro-2-furanone template SO JOURNAL OF MEDICINAL CHEMISTRY LA English DT Article ID ACTIVATION AB Conformationally constrained analogues of diacylglycerol (DAG) built on a racemic-5-[(acyloxy)methyl]-5-(hydroxymethyl)tetrahydro-2-furanone template template were shown previously to have excellent binding affinities for protein kinase C (PK-C). Since the interaction of PK-C with DAG is stereospecific, it was anticipated that PK-C would bind tightly to only one enantiomeric form of the compounds constructed with this new lactone template. Separation of enantiomers by chiral HPLC was discarded due to the ease with which acyl migration occurs in these class of compounds, and a total chiral synthesis was undertaken. Prior to chemical synthesis, the selection of the ''correct'' enantiomeric template was predicted by a molecular conformational analysis that compared the two enantiomers of DAG in their presumed ''active'' conformation with the two enantiomeric lactone templates. This presumed ''active'' conformation for DAG was derived from a previously developed pharmacophore model that uses the molecule of a potent phorbol diester as the ideal rigid template. The results from this analysis indicated that the ''correct'' lactone template corresponded to the inactive (R)-isomer of DAG. This analysis also predicted that the lactone template corresponding to the active (S)-DAG enantiomer would not fit adequately into the pharmacophore. The chiral syntheses of target compounds 2, 4, and 6, constructed on the selected, and presumably ''correct'' lactone template, were achieved from a common bicyclic intermediate (5R,8R,9R)-8,9-O-isopropylidene-2-keto-1,7-dioxaspiro[4.4]nonane (10) that was synthesized from commercially available 1,2:3,5-di-O-isopropylidene-alpha-D-threo-apiofuranose (7) by a very effective spirolactonization approach. On the basis of their ability to inhibit the binding of [H-3-20]phorbol 12,13-dibutyrate (PDBU) to PK-C alpha, the enantiomeric ligands 2, 4, and 6 were twice as potent as the corresponding racemates. These results confirm that binding of these lactones is stereospecific and consistent with a binding mechanism similar to that of DAG. C1 NCI,MED CHEM LAB,DEV THERAPEUT PROGRAM,DIV CANC TREATMENT,BETHESDA,MD 20892. NCI,CELLULAR CARCINOGENESIS & TUMOR PROMOT LAB,MOLEC MECH TUMOR PROMOT SECT,BETHESDA,MD 20892. RI Wang, Shaomeng/E-9686-2010 NR 14 TC 39 Z9 39 U1 1 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 JAN 5 PY 1996 VL 39 IS 1 BP 29 EP 35 DI 10.1021/jm950277n PG 7 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA TN771 UT WOS:A1996TN77100005 PM 8568819 ER PT J AU Lee, J Sharma, R Wang, SM Milne, GWA Lewin, NE Szallasi, Z Blumberg, PM George, C Marquez, VE AF Lee, J Sharma, R Wang, SM Milne, GWA Lewin, NE Szallasi, Z Blumberg, PM George, C Marquez, VE TI Conformationally constrained analogues of diacylglycerol .12. Ultrapotent protein kinase C ligands based on a chiral 4,4-disubstituted heptono-1,4-lactone template SO JOURNAL OF MEDICINAL CHEMISTRY LA English DT Article ID GAMMA-LACTONES AB Conformationally constrained analogues of diacylglycerol (DAG) built on a 5-[(acyloxy)methyl] 5-(hydroxymethyl)tetrahydro-2-furanon template (1, Chart 1) were shown previously to bind tightly to protein kinase Ca (PK-C alpha) in a stereospecific manner. These compounds, however, racemized readily through rapid acyl migration and lost biological potency. In order to circumvent this problem, the ''reversed ester'' analogues were designed as a new set of PK-C ligands. This reversal of the ester function produced some new DAG mimetics that are embedded in a C4 doubly-branched heptono-1,4-lactone template. The reversed ester analogues were impervious to racemization, and their chemically distinct branches facilitated the enantiospecific syntheses of all targets. Compound 2, the simplest; reversed ester analogue of 1 (Chart 1), exhibited a 3.5-fold reduction in binding sanity toward PK-C alpha which we attributed to the loss of a stabilizing gauche interaction that caused the ester branch in 2 to be more disordered than in the normal ester 1. However, conversion of the propanoyl branch of 2 into a propenoyl branch restored binding affinity (3 versus 5). As expected, the compounds bound to the enzyme with strict enantioselectivity (3 and 5 versus 4 and 6). Functionalization of the propenoyl-branched compounds as alpha-alkylidene lactones, in a manner which proved successful with the 5-[(acyloxy)methyl]-5-(hydroxymethyl)tetrahydro-2-furanone template (9 and 10), produced stable compounds with equivalent ultrapotent binding affinities for PK-C alpha (7 and 8). The additional incorporation of the propenoyl-branched carbonyl into a gamma-lactone ring was performed (11-14) not only to derive a possible additional entropic advantage but also to confirm the spatial disposition of this carbonyl function in the ligand-enzyme complex. Although no additional entropic advantage was derived, the high binding affinities displayed by compounds 11 and 12 helped to establish the correct orientation of the equivalent carbonyl group in PKC-bound DAG, As expected, these DAG analogues activated PK-C alpha. The most potent agonist, compound 8, stimulated phosphorylation of the a-pseudosubstrate peptide, and in primary mouse keratinocytes it caused inhibition of binding of epidermal growth factor with an ED(50) of approximately 1 mu M. In contrast to the phorbol esters, compound 8 did not induce acute edema or hyperplasia in skin of CD-1 mice, and its pattern of downregulation with several PK-C isozymes was different from that of phorbol 12-myristate 13-acetate (PMA). C1 NCI, MED CHEM LAB, DEV THERAPEUT PROGRAM, DIV CANC TREATMENT, BETHESDA, MD 20892 USA. NCI, CELLULAR CARCINOGENESIS & TUMOR PROMOT LAB, MOLEC MECH TUMOR PROMOT SECT, BETHESDA, MD 20892 USA. USN, RES LAB, STRUCT MATTER LAB, WASHINGTON, DC 20375 USA. RI Wang, Shaomeng/E-9686-2010 NR 14 TC 31 Z9 31 U1 0 U2 0 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 JAN 5 PY 1996 VL 39 IS 1 BP 36 EP 45 DI 10.1021/jm950278f PG 10 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA TN771 UT WOS:A1996TN77100006 PM 8568825 ER PT J AU Eich, E Pertz, H Kaloga, M Schulz, J Fesen, MR Mazumder, A Pommier, Y AF Eich, E Pertz, H Kaloga, M Schulz, J Fesen, MR Mazumder, A Pommier, Y TI (-)-Arctigenin as a lead structure for inhibitors of human immunodeficiency virus type-1 integrase SO JOURNAL OF MEDICINAL CHEMISTRY LA English DT Article ID TOPOISOMERASE-II; PROTEIN; INVITRO; ANALOGS; LIGNANS; FUTURE; ACID AB The natural dibenzylbutyrolactone type lignanolide (-)-arctigenin (2), an inhibitor of human immunodeficiency virus type-1 (HIV-1) replication in infected human cell. systems, was found to suppress the integration of prosiral DNA into the cellular DNA genome.(11b) In the present study 2 was tested with purified HIV-1 integrase and found to be inactive in the cleavage (3'-processing) and integration (strand transfer) assays. However, the semisynthetic 3-O-demethylated congener 9 characterized by a catechol substructure exhibited remarkable activities in both assays. Structure-activity relationship studies with 30 natural (1-6), semisynthetic (7-21), and synthetic (37-43, 45, 46) lignans revealed that (1) the lactone moiety is crucial since compounds with a butane-1,4-diol or tetrahydrofuran substructure and also lignanamide analogues lacked activity and (2) the number and arrangement of phenolic hydroxyl groups is important for the activity of lignanolides. The congener with two catechol sulostructures (7) was found to be the most active compound in this study. 7 was also a potent inhibitor of the ''disintegration'' reaction which models the reversal of the strand transfer reaction. The inhibitory activity of 7 with the core enzyme fragment consisting of amino acids 50-212 suggests that the binding site of 7 resides in the catalytic domain. C1 NCI,MOLEC PHARMACOL LAB,DIV BASIC SCI,BETHESDA,MD 20892. RP Eich, E (reprint author), FREE UNIV BERLIN,INST PHARMAZEUT BIOL,KOENIGIN LUISE STR 2,D-14195 BERLIN,GERMANY. NR 45 TC 144 Z9 156 U1 2 U2 10 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 JAN 5 PY 1996 VL 39 IS 1 BP 86 EP 95 DI 10.1021/jm950387u PG 10 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA TN771 UT WOS:A1996TN77100011 PM 8568830 ER PT J AU Andrews, LB Nelkin, D AF Andrews, LB Nelkin, D TI The Bell Curve: A statement SO SCIENCE LA English DT Letter RP Andrews, LB (reprint author), NIH,DEPT ENERGY JOINT WORKING GRP ETH LEGAL & SOCIAL,ELSI WORKING GRP,31 CTR DR,BETHESDA,MD 20892, USA. NR 1 TC 1 Z9 2 U1 0 U2 0 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 SN 0036-8075 J9 SCIENCE JI Science PD JAN 5 PY 1996 VL 271 IS 5245 BP 13 EP 14 PG 2 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA TP022 UT WOS:A1996TP02200002 PM 8539585 ER PT J AU Nowak, G Li, Y Paul, IA AF Nowak, G Li, Y Paul, IA TI Adaptation of cortical but not hippocampal NMDA receptors after chronic citalopram treatment SO EUROPEAN JOURNAL OF PHARMACOLOGY LA English DT Article DE chronic citalopram; NMDA receptor; excitatory amino acid; adaptation; cortex; hippocampus ID D-ASPARTATE RECEPTOR; FORCED SWIMMING TEST; RAT-BRAIN; ANTIDEPRESSANT DRUGS; D-SERINE; 1-AMINOCYCLOPROPANECARBOXYLIC ACID; ELECTROCONVULSIVE SHOCK; EXHIBIT ANTIDEPRESSANT; NORADRENALINE INVIVO; NEURONAL-ACTIVITY AB Chronic treatment with citalopram produced a 6.2-fold reduction in the proportion of high affinity glycine-displaceable [H-3]CGP-39653 binding sites and a 1.5-fold reduction in the potency of glycine to inhibit [H-3]5,7-dichlorokynurenic acid binding in mouse cortex but not in hippocampus. Chronic citalopram also increased the aspartate concentration by 110% in cortex and 33% in hippocampus, and increased the glycine/threonine concentration by 33% in hippocampus. These results support the hypotheses that: (1) the adaptation of strychnine-insensitive glycine recognition sites and the allosteric coupling of the glycine and glutamate recognition sites are independently regulated by chronic antidepressant treatment; (2) chronic antidepressant administration induces regionally selective adaptation of the NMDA receptor complex; and (3) antidepressant-induced adaptation of the NMDA receptor complex may be mediated by regionally selective changes in excitatory amino acid concentration. C1 UNIV MISSISSIPPI,MED CTR,DEPT PHARMACOL,JACKSON,MS 39216. NIDDK,NEUROSCI LAB,BETHESDA,MD 20892. RP Nowak, G (reprint author), UNIV MISSISSIPPI,MED CTR,DEPT PSYCHIAT & HUMAN BEHAV,2500 N STATE ST,BOX 127,JACKSON,MS 39216, USA. NR 68 TC 57 Z9 59 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0014-2999 J9 EUR J PHARMACOL JI Eur. J. Pharmacol. PD JAN 4 PY 1996 VL 295 IS 1 BP 75 EP 85 DI 10.1016/0014-2999(95)00585-4 PG 11 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA TR081 UT WOS:A1996TR08100010 PM 8925878 ER PT J AU Shakhnovich, E Abkevich, V Ptitsyn, O AF Shakhnovich, E Abkevich, V Ptitsyn, O TI Conserved residues and the mechanism of protein folding SO NATURE LA English DT Article ID CHYMOTRYPSIN INHIBITOR-2; 3-DIMENSIONAL STRUCTURE; TRANSITION; SEQUENCES AB EXPERIMENTAL(1-6) and simulation(7) studies show that small monomeric proteins fold in one kinetic step, which entails overcoming the free-energy barrier between the unfolded and the native protein through a transition state(8,9). Two models of transition state formation have been proposed: a 'nonspecific' one in which it depends on the formation of a sufficient number of native-like contacts regardless of what amino acids are involved(10-12) and a 'specific' one, in which it depends on formation of a specific subset of the native structure (a folding nucleus)(8,13,14). The latter requires that some amino acids form most of their contacts in the transition state, whereas others only do so on reaching the native conformation. If so, mutations affecting the stability of the transition state nucleus should have a greater effect on the folding kinetics than mutations elsewhere, and the residues involved should be evolutionarily conserved. Lattice-model simulations and experiments(8,13-16) suggest that such mutations exist. Here we present a method for determining the folding nucleus of a protein with known structure with two-state folding kinetics. This method is based on the alignment of many sequences designed to fold into the native conformation of a protein to identify the positions where amino acids are most conserved in designed sequences. The method is applied to chymotrypsin inhibitor 2 (CI2), a protein whose transition state has been previously studied by protein engineering(14-16). The involvement of residues in folding nucleus of CI2 is clearly correlated with their conservation in design, and the residues forming the nucleus are highly conserved in 23 natural sequences homologous to CI2. C1 RUSSIAN ACAD SCI,INST PROT RES,PUSHCHINO 142292,RUSSIA. NCI,MOLEC STRUCT SECT,LMMB,BETHESDA,MD. RP Shakhnovich, E (reprint author), HARVARD UNIV,DEPT CHEM,12 OXFORD ST,CAMBRIDGE,MA 02138, USA. NR 31 TC 293 Z9 298 U1 0 U2 9 PU MACMILLAN MAGAZINES LTD PI LONDON PA 4 LITTLE ESSEX STREET, LONDON, ENGLAND WC2R 3LF SN 0028-0836 J9 NATURE JI Nature PD JAN 4 PY 1996 VL 379 IS 6560 BP 96 EP 98 DI 10.1038/379096a0 PG 3 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA TN216 UT WOS:A1996TN21600064 PM 8538750 ER PT J AU Hodge, DR Robinson, L Watson, D Lautenberger, J Zhang, XK Venanzoni, M Seth, A AF Hodge, DR Robinson, L Watson, D Lautenberger, J Zhang, XK Venanzoni, M Seth, A TI Interaction of ETS-1 and ERGB/FLI-1 proteins with DNA is modulated by spacing between multiple binding sites as well as phosphorylation SO ONCOGENE LA English DT Article DE ETS-1,ERGB FL1-1; transcription factors; HIV-1 enhancer; transactivation; EBS palindrome; Cam-KII phosphorylation site ID TRANSCRIPTION; COMPLEX; FAMILY; GENE; IDENTIFICATION; PROTOONCOGENE; ACTIVATION; MECHANISM; SEQUENCES; ONCOGENE AB ETS is a family of transcription factors that contain a highly conserved ETS DNA binding domain. Various members of the ETS family are expressed in cells of hematopoietic lineage. ETS-1, ETS-2 and ERGB/FLI-1 are expressed at high levels in T-lymphocytes. HIV-1 infects T-cells and it has been shown that its LTR contains binding sites for various transcription factors. In this study we show that the HIV-1 core enhancer is directly regulated by ERGB/FLI-1 protein positively, as well as, negatively, depending upon the presence or absence of accessory factors in different cell types. In addition, we show that the ETS-1 transactivation activity is enhanced upon dephosphorylation of the Calmodulin-dependant Protein Kinase II phosphorylation site located in exon VII. Finally, we demonstrate that the spacing two EBS cores in palindromic or direct play a crucial role in binding of ETS proteins to DNA. C1 UNIV TORONTO, DEPT PATHOL, TORONTO, ON M5S 1B2, CANADA. UNIV TORONTO, MRC, PERIODONTAL PHYSIOL GRP, TORONTO, ON M5S 1B2, CANADA. WOMENS COLL HOSP, MOLEC PATHOL LAB, TORONTO, ON M5S 1B2, CANADA. NCI, MOLEC ONCOL LAB, FREDERICK, MD 21702 USA. PROGRAM RESOURCES INC DYNCORP, FREDERICK, MD 21702 USA. MED UNIV S CAROLINA, CTR MOLEC & STRUCT BIOL, CHARLESTON, SC 29425 USA. NR 31 TC 31 Z9 31 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0950-9232 J9 ONCOGENE JI Oncogene PD JAN 4 PY 1996 VL 12 IS 1 BP 11 EP 18 PG 8 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA TQ014 UT WOS:A1996TQ01400002 PM 8552380 ER PT J AU Pettersson, B Coleman, MP Ron, E Adami, HO AF Pettersson, B Coleman, MP Ron, E Adami, HO TI Iodine supplementation in Sweden and regional trends in thyroid cancer incidence by histopathologic type SO INTERNATIONAL JOURNAL OF CANCER LA English DT Article ID TEMPORAL VARIATION; COHORT MODELS; AGE PERIOD; FREQUENCY; PROPHYLAXIS; CARCINOMA; TUMORS; RATES; AREA AB We studied regional patterns of thyroid cancer incidence in relation to iodine intake and iodinization in Sweden using 5,838 incident cases diagnosed in the period 1958-1981. Region was defined either by iodine status, urban-rural status or health-care region (internal controls). Age, period and cohort models were fitted to evaluate trends and regional variation in incidence by histopathologic type. In iodine-deficient areas, the relative risk (RR) of developing thyroid cancer was 0.92 for all histologic types combined, 0.80 for papillary cancer and 0.87 for anaplastic carcinoma. Residence in iodine-deficient regions was associated with a 2-fold increased risk of follicular cancer in men (RR 1.98) and a 17% increase in risk in women (RR 1.17). Regional differences in iodine intake fell after iodinization of the food supply, which was started in 1936 and enhanced in 1966. Nevertheless, incidence of both papillary and follicular carcinoma increased during the study period, with largely similar trends in iodine-deficient and iodine-sufficient areas. Overall, residence in urban or rural areas was not an important determinant of incidence, though trends in the incidence of papillary, follicular and anaplastic cancer did vary between urban and rural areas. The occurrence of thyroid cancer differed only marginally between the 6 health-cave regions in Sweden, suggesting that the observations in regions defined by iodine intake were unlikely to be artifactual. Our data suggest that iodinization of the food supply is not associated with adverse trends in the occurrence of thyroid cancer. (C) 1996 Wiley-Liss, Inc. C1 UNIV LONDON LONDON SCH HYG & TROP MED,DEPT EPIDEMIOL & POPULAT SCI,LONDON WC1E 7HT,ENGLAND. NCI,RADIAT BRANCH,BETHESDA,MD 20892. HARVARD UNIV,SCH PUBL HLTH,DEPT EPIDEMIOL,BOSTON,MA 02115. RP Pettersson, B (reprint author), UNIV UPPSALA HOSP,DEPT CANC EPIDEMIOL,S-75185 UPPSALA,SWEDEN. OI Coleman, Michel/0000-0001-8940-3807 NR 31 TC 59 Z9 60 U1 0 U2 5 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0020-7136 J9 INT J CANCER JI Int. J. Cancer PD JAN 3 PY 1996 VL 65 IS 1 BP 13 EP 19 DI 10.1002/(SICI)1097-0215(19960103)65:1<13::AID-IJC3>3.0.CO;2-4 PG 7 WC Oncology SC Oncology GA TM773 UT WOS:A1996TM77300003 PM 8543389 ER PT J AU Panico, L DAntonio, A Salvatore, G Mezza, E Tortora, G DeLaurentiis, M DePlacido, S Giordano, T Merino, M Salomon, DS Gullick, WJ Pettinato, G Schnitt, SJ Bianco, AR Ciardiello, F AF Panico, L DAntonio, A Salvatore, G Mezza, E Tortora, G DeLaurentiis, M DePlacido, S Giordano, T Merino, M Salomon, DS Gullick, WJ Pettinato, G Schnitt, SJ Bianco, AR Ciardiello, F TI Differential immunohistochemical detection of transforming growth factor alpha, amphiregulin and CRIPTO in human normal and malignant breast tissues SO INTERNATIONAL JOURNAL OF CANCER LA English DT Article ID EPITHELIAL-CELL LINE; COLORECTAL TUMORS; TGF-ALPHA; EXPRESSION; CANCER; ESTROGEN; FAMILY; C-ERBB-2; RECEPTOR; LEADS AB The expression of growth factors, such as transforming growth factor alpha (TGF alpha), amphiregulin (AR) and CRIPTO, a type-1 tyrosine-kinase growth factor receptor (erbB-2), and a tumor-suppressor gene (P53), that have been implicated in the development and/or the progression of breast cancer, was evaluated by immunohistochemistry in 100 human primary infiltrating breast carcinomas (IBC). AR and CRIPTO immunoreactivity was also assessed in 55 human breast ductal carcinomas in site (DCIS). Within the 100 IBC, 80, 50, 73, 17, and 34 tumors expressed moderate to high levels of TGF alpha, AR, CRIPTO, erbB-2, and p53 respectively. In addition, AR and CRIPTO immunoreactivity were found in 11 and in 26 out of 55 DCIS respectively. In contrast, only 4, 3, and 2 out of 10 normal mammary-gland samples were weakly positive for TGF alpha AR, and CRIPTO expression, respectively, whereas none was positive for erbB-2 or p53. Within the 100 IBC, expression of erbB-2 significantly correlated with high histologic and nuclear grading, with high growth fraction, and with estrogen-receptor(ER)- and progesterone-receptor(PgR)-negative tumors. A statistically significant correlation was also observed between p53 expression and high histologic grading, high growth fraction, and PgR-negative tumors. In contrast, no significant correlations were found between TGF alpha, AR, and CRIPTO immunoreactivity and various clinicopathological parameters, with the exception of a positive correlation between TGF alpha and ER expression. These data demonstrate that TGF alpha AR, and CRIPTO expression are significantly increased in malignant mammary epithelium relative to normal epithelium. In particular, the differential expression of CRIPTO may serve as a potential tumor marker for breast carcinogenesis. (C) 1996 Wiley-Liss, Inc. C1 UNIV NAPLES,IST PATOL,NAPLES,ITALY. UNIV NAPLES,FAC MED & CHIRURG,DIPARTIMENTO ENDOCRINOL & ONCOL MOLEC & CLIN,CATTEDRA ONCOL MED,NAPLES,ITALY. NCI,PATHOL LAB,BETHESDA,MD 20892. NCI,TUMOR GROWTH FACTOR SECT,TUMOR IMMUNOL & BIOL LAB,BETHESDA,MD 20892. HAMMERSMITH HOSP,IMPERIAL CANC RES FUND,MOLEC ONCOL LAB,LONDON,ENGLAND. BETH ISRAEL HOSP,DEPT PATHOL,BOSTON,MA 02215. OI PETTINATO, Guido/0000-0003-2599-0357; Ciardiello, Fortunato/0000-0002-3369-4841 NR 25 TC 92 Z9 94 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 0020-7136 J9 INT J CANCER JI Int. J. Cancer PD JAN 3 PY 1996 VL 65 IS 1 BP 51 EP 56 DI 10.1002/(SICI)1097-0215(19960103)65:1<51::AID-IJC9>3.0.CO;2-0 PG 6 WC Oncology SC Oncology GA TM773 UT WOS:A1996TM77300009 PM 8543395 ER PT J AU Wolk, A Gridley, G Niwa, S Lindblad, P McCredie, M Mellemgaard, A Mandel, JS Wahrendorf, J McLaughlin, JK Adami, HO AF Wolk, A Gridley, G Niwa, S Lindblad, P McCredie, M Mellemgaard, A Mandel, JS Wahrendorf, J McLaughlin, JK Adami, HO TI International renal cell cancer study .7. Role of diet SO INTERNATIONAL JOURNAL OF CANCER LA English DT Article ID TOTAL ENERGY-INTAKE; RISK-FACTORS; EPIDEMIOLOGIC ANALYSES; CARCINOMA; CONSUMPTION; PROTEIN; COFFEE AB We investigated the role of diet in the etiology of renal cell cancer (RCC) in a multi-center, population-based case-control study conducted in Australia, Denmark, Sweden and the United States, using a shared protocol. A total of 1,185 incident histopathologically confirmed cases (698 men, 487 women) and 1,526 controls (915 men, 611 women) frequency-matched to cases by sex and age were included in the analyses. The association between RCC and diet was estimated by relative risks (RR) and 95% confidence intervals (CI) adjusted for age, sex, study center, body mass index and smoking. A statistically significant positive association was observed for total energy intake (RR = 1.7, 95% CI = 1.4-2.2 for the highest vs. lowest quartile, p value for trend <0.00001), while the hypothesis that protein and fat are risk factors independent of energy was not supported. Fried meats were associated with increased RCC risk, while vegetables and fruits were protective, with the strongest effect observed for the highest quartile of consumption of orange/dark green vegetables but not vitamin C or beta carotene. Increased risk was associated with low intake (lowest decile) of vitamin E and magnesium. We observed an apparent protective effect of alcohol confined to women and probably due to chance. Our findings indicate an important role of nutrition in the development of RCC. The apparent positive association of energy intake with risk of RCC needs further investigation in a prospective cohort study to exclude the possible impact of differences in recall between cases and controls. (C) 1996 Wiley-Liss, Inc. C1 NCI,EPIDEMIOL & BIOSTAT PROGRAM,ROCKVILLE,MD. WESTAT CORP,ROCKVILLE,MD. SUNDSVALL HOSP,DEPT UROL,SUNDSVALL,SWEDEN. NSW CANC COUNCIL,CANC EPIDEMIOL RES UNIT,SYDNEY,NSW,AUSTRALIA. DANISH CANC SOC,DIV CANC EPIDEMIOL,COPENHAGEN,DENMARK. UNIV MINNESOTA,SCH PUBL HLTH,MINNEAPOLIS,MN 55455. GERMAN CANC RES CTR,DIV EPIDEMIOL,W-6900 HEIDELBERG,GERMANY. INT EPIDEMIOL INST,ROCKVILLE,MD. HARVARD UNIV,SCH PUBL HLTH,DEPT EPIDEMIOL,BOSTON,MA 02115. RP Wolk, A (reprint author), UNIV UPPSALA HOSP,DEPT CANC EPIDEMIOL,S-75185 UPPSALA,SWEDEN. NR 33 TC 135 Z9 136 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0020-7136 J9 INT J CANCER JI Int. J. Cancer PD JAN 3 PY 1996 VL 65 IS 1 BP 67 EP 73 DI 10.1002/(SICI)1097-0215(19960103)65:1<67::AID-IJC12>3.0.CO;2-F PG 7 WC Oncology SC Oncology GA TM773 UT WOS:A1996TM77300012 PM 8543399 ER PT J AU Wigginton, JM Komschlies, KL Back, TC Franco, JL Brunda, MJ Wiltrout, RH AF Wigginton, JM Komschlies, KL Back, TC Franco, JL Brunda, MJ Wiltrout, RH TI Administration of interleukin 12 with pulse interleukin 2 and the rapid and complete eradication of murine renal carcinoma SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID CELL STIMULATORY FACTOR; LYMPHOCYTE MATURATION FACTOR; T RESPONSES INVITRO; RECOMBINANT INTERLEUKIN-2; IMMUNE-RESPONSES; INTERFERON-GAMMA; IL-12; CANCER; PROLIFERATION; INDUCTION AB Background: Interleukin 2 (IL-2) and interleukin 12 (IL-12) are potent immunoregulatory cytokines that exhibit antitumor activity. Preliminary evidence suggests that combined administration of IL-2 and IL-12 may yield greater antitumor activity than that observed with either agent alone. Purpose: We evaluated the ability of combination regimens of IL-2 and IL-12 to induce regression of established primary and metastatic murine renal carcinoma (Renca) tumors. Methods: BALB/c mice were given either subcutaneous or intrarenal injections of 10(5) Renca cells; tumor cell injections were given to 10-12 mice for each treatment group. Mice bearing subcutaneous primary tumors were treated with chronic IL-2 (300 000 IU given on a daily basis) or pulse 1L-2 (300 000 IU given twice daily one day per week) alone, IL-12 alone (0.5 mu g given on a daily basis), or IL-12 in combination with either chronic or pulse IL-2. Mice with metastatic tumors (arising from intrarenal implants; animals were nephrectomized to remove the primary tumors) were treated with IL-12 plus or minus pulse IL-2; in these experiments, IL-12 was given at doses of either 0.5 or 1.0 mu g. In most experiments, treatment was continued for at least 3 weeks. Two-sided statistical tests were used to evaluate the data. Results: Most mice with subcutaneous Renca tumors treated with the combination of IL-12 and chronic IL-2 died of treatment-related toxic effects within 7-14 days. In contrast, treatment with IL-12 plus pulse IL-2 was well tolerated, and six of 10 mice experienced complete tumor regression; none of the mice treated with either IL-12 alone or pulse IL-2 alone experienced a curative response. Seven of eight and nine of nine mice with metastatic tumors experienced complete tumor regression after treatment with 0.5 mu g IL-12 plus pulse IL-2 or 1.0 mu g IL-12 plus pulse IL-2, respectively; two of 12 mice treated with pulse IL-2 alone and 10% or less of mice treated with IL-12 alone were cured of metastatic tumors (with 0.5 mu g IL-12, none of 10 mice; with 1.0 mu g IL-12, one of 10 mice). Five of 10 mice with metastatic tumors treated with a short-course regimen of IL-12 and pulse IL-2 (two pulses of IL-2 flanking 5 days of 0.5 mu g IL-12) experienced complete tumor regression, while only one of the 12 mice treated with IL-2 alone and none of the mice treated with IL-12 alone experienced complete tumor regression. Virtually ail curative response frequencies obtained with IL-12 and pulse IL-2 combination regimens differed significantly (P<.05) from those obtained with corresponding single-agent treatments. Conclusions: IL-12 administered in combination with pulse IL-2 induced rapid and complete regression of primary and metastatic Renca tumors and displayed greater antitumor activity than that observed with either IL-12 or IL-2 alone. C1 NCI,FREDERICK CANC RES & DEV CTR,DIV CANC TREATMENT,BIOL RESPONSE MODIFIERS PROGRAM,FREDERICK,MD 21702. NCI,FREDERICK CANC RES & DEV CTR,SAIC FREDERICK,BIOL CARCINOGENESIS & DEV PROGRAM,FREDERICK,MD 21702. HOFFMANN LA ROCHE INC,DEPT ONCOL,NUTLEY,NJ. NR 38 TC 151 Z9 153 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 JAN 3 PY 1996 VL 88 IS 1 BP 38 EP 43 DI 10.1093/jnci/88.1.38 PG 6 WC Oncology SC Oncology GA TM170 UT WOS:A1996TM17000014 PM 8847724 ER PT J AU Janik, JE Miller, LL Longo, DL Powers, GC Urba, WJ Kopp, WC Gause, BL Curti, BD Fenton, RG Oppenheim, JJ Conlon, KC Holmlund, JT Sznol, M Sharfman, WH Steis, RG Creekmore, SP Alvord, WG Beauchamp, AE Smith, JW AF Janik, JE Miller, LL Longo, DL Powers, GC Urba, WJ Kopp, WC Gause, BL Curti, BD Fenton, RG Oppenheim, JJ Conlon, KC Holmlund, JT Sznol, M Sharfman, WH Steis, RG Creekmore, SP Alvord, WG Beauchamp, AE Smith, JW TI Phase II trial of interleukin 1 alpha and indomethacin in treatment of metastatic melanoma SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID RECOMBINANT HUMAN INTERLEUKIN-1-ALPHA; LEUKOCYTE-A INTERFERON; TUMOR-NECROSIS-FACTOR; MALIGNANT-MELANOMA; CYTO-TOXICITY; SOLID TUMORS; COMBINATION; PROTEIN; ASPIRIN; CANCER AB Background: The rising incidence of malignant melanoma and the lack of curative therapies for metastatic disease represent a therapeutic challenge. New agents effective in treating this disease are needed. Purpose: Because of the additive antitumor effects of interleukin 1 alpha (IL-1 alpha) and indomethacin in vivo, we conducted a phase II trial of this combination in patients with melanoma. We used the recommended dose determined from our phase I trial to ascertain the antitumor activity of the combination. Methods: From August 1, 1990, through July 28, 1992, 49 patients entered the study. They were stratified into two groups based on the presence of visceral (n = 14) and nonvisceral (n = 35) metastases. The patients received 7 days of both IL-1 alpha (0.1 mu g/kg per day by intravenous bolus infusion) and indomethacin (50 mg orally every 8 hours). At least two cycles of therapy, repeated at 21-day intervals, were planned. Additional treatment was given to those patients who had stable or responding lesions. A chi-squared test for homogeneity of proportions was used to compare groups on several measures. All P values resulted from two-sided tests. Results: Fever, chills, and hypotension were among the most common side effects. None of the 14 patients with visceral metastases responded to the treatment. Of the 35 patients with nonvisceral metastases, three showed a partial response for 6 months each and one showed a complete response for more than 34 months; the response rate was 11% (95% confidence interval [CI] = 5%-26%). All responding patients required phenylephrine for treatment of IL-1 alpha-induced hypotension, whereas six (19%) of 31 of the nonresponding patients with nonvisceral metastases required phenylephrine (P = .0008). The response rate in women was higher; three of 10 women (30%; 95% CI = 11%-60%) responded, whereas one of 25 men (4%; 95% CI = 0%-20%) responded (P = .029). All three women were positive for human leukocyte antigen (HLA) B7 expression (P = .011). Conclusions: The combination of IL-1 alpha and indomethacin has minimal antitumor activity in melanoma patients. All responses were confined to patients with nonvisceral metastases, IL-1 alpha-induced hypotension, gender, and HLA B7 expression were positively associated with response. Implications: Administration of higher doses of IL-1 alpha alone has been shown to produce hypotension in a large proportion of patients but can be given safely with phenylephrine support. Because of the association of hypotension with antitumor activity, treatment with higher IL-1 alpha doses alone may be a strategy for attaining better response rates. C1 PROVIDENCE MED CTR,EARLE CHILES RES INST,PORTLAND,OR. FREDERICK MEM HOSP,FREDERICK,MD. NCI,FREDERICK CANC RES & DEV CTR,BIOL RESPONSE MODIFIERS PROGRAM,PROGRAM RESOURCES INC DYNCORP,FREDERICK,MD 21702. RP Janik, JE (reprint author), NCI,FREDERICK CANC RES & DEV CTR,BIOL RESPONSE MODIFIERS PROGRAM,501 W 7TH ST,SUITE 3,FREDERICK,MD 21701, USA. NR 35 TC 17 Z9 19 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 JAN 3 PY 1996 VL 88 IS 1 BP 44 EP 49 DI 10.1093/jnci/88.1.44 PG 6 WC Oncology SC Oncology GA TM170 UT WOS:A1996TM17000015 PM 8847725 ER PT J AU Travis, LB Curtis, RE Bennett, WP Hankey, BF Boice, JD Travis, WD AF Travis, LB Curtis, RE Bennett, WP Hankey, BF Boice, JD Travis, WD TI Re: Lung cancer after Hodgkin's disease - Response SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Letter C1 ARMED FORCES INST PATHOL,WASHINGTON,DC 20306. RP Travis, LB (reprint author), NCI,DIV CANC ETIOL,EPIDEMIOL & BIOSTAT PROGRAM,EXECUT PLAZA N,BETHESDA,MD 20852, USA. NR 12 TC 0 Z9 0 U1 0 U2 0 PU NATL CANCER INSTITUTE PI BETHESDA PA 9030 OLD GEORGETOWN RD, BETHESDA, MD 20814 SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD JAN 3 PY 1996 VL 88 IS 1 BP 52 EP 52 DI 10.1093/jnci/88.1.52 PG 1 WC Oncology SC Oncology GA TM170 UT WOS:A1996TM17000018 ER PT J AU LaGrenade, L Sonoda, S Miller, W Pate, E RodgersJohnson, P Hanchard, B Cranston, B Fujiyoshi, T Yashiki, S Blank, M Gibbs, CJ Manns, A AF LaGrenade, L Sonoda, S Miller, W Pate, E RodgersJohnson, P Hanchard, B Cranston, B Fujiyoshi, T Yashiki, S Blank, M Gibbs, CJ Manns, A TI HLA DRB1(*)DQB1(*) haplotype in HTLV-I-associated familial infective dermatitis may predict development of HTLV-I-associated myelopathy tropical spastic paraparesis SO AMERICAN JOURNAL OF MEDICAL GENETICS LA English DT Article DE HLA; DRB1; DQB1; HTLV-I; infective dermatitis; HTLV-I-associated myelopathy; tropical spastic paraparesis; Jamaica ID T-CELL LEUKEMIA; VIRUS TYPE-I; ANTIBODIES; CARRIERS AB A possible causal association between infective dermatitis and HTLV-I infection was reported in 1990 and confirmed in 1992, We now report familial infective dermatitis (ID) occurring in a 28-year-old mother and her 9-year-old son, The mother was first diagnosed with ID in 1969 at the age of 2 years in the Dermatology Unit at the University Hospital of the West Indies (U.H.W.I.) in Jamaica. The elder of her 2 sons was diagnosed with ID at the age of 3 years, also at U.H.W.I, Both mother and son are HTLV-I-seropositive. A second, younger son, currently age 2 years, is also HTLV-I-seropositive, but without clinical evidence of ID, Major histocompatibility complex (MHC), class II, human leucocyte antigen (HLA) genotyping documented a shared class II haplotype, DRB1*DQB1* (1101-0301), in the mother and her 2 sons, This same haplotype has been described among Japanese patients with HTLV-I-associated myelopathy/tropical spastic paraparesis (HAM/TSP), and has been associated with a possible pathologically heightened immune response to HTLV-I infection, The presence of this haplotype in these familial ID cases with clinical signs of HAM/TSP may have contributed to their risk for development of HAM/TSP, The unaffected, HTLV-I-seropositive, younger son requires close clinical follow-up. (C) 1996 Wiley-Liss, Inc. C1 UNIV W INDIES,DEPT CHILD HLTH,MONA,JAMAICA. UNIV W INDIES,DEPT PATHOL,MONA,JAMAICA. KAGOSHIMA UNIV,DEPT VIROL,KAGOSHIMA 890,JAPAN. NCI,NATL INST NEUROL DISORDERS & STROKE,CENT NERVOUS SYST STUDIES LAB,BETHESDA,MD 20892. NCI,VIRAL EPIDEMIOL BRANCH,BETHESDA,MD. RP LaGrenade, L (reprint author), UNIV W INDIES,DEPT MED,KINGSTON 7,MONA,JAMAICA. FU NCI NIH HHS [N01-CP-31006] NR 20 TC 23 Z9 25 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 0148-7299 J9 AM J MED GENET JI Am. J. Med. Genet. PD JAN 2 PY 1996 VL 61 IS 1 BP 37 EP 41 DI 10.1002/(SICI)1096-8628(19960102)61:1<37::AID-AJMG7>3.0.CO;2-U PG 5 WC Genetics & Heredity SC Genetics & Heredity GA TM206 UT WOS:A1996TM20600008 PM 8741915 ER PT J AU Tritscher, AM Seacat, AM Yager, JD Groopman, JD Miller, BD Bell, D Sutter, TR Lucier, GW AF Tritscher, AM Seacat, AM Yager, JD Groopman, JD Miller, BD Bell, D Sutter, TR Lucier, GW TI Increased oxidative DNA damage in livers of 2,3,7,8-tetrachlorodibenzo-p-dioxin treated intact but not ovariectomized rats SO CANCER LETTERS LA English DT Article DE oxidative damage; 8-oxo-deoxyguanpsine; 2,3,7,8-tetrachlorodibenzo-p-dioxin; estrogens; CYP1B1; RT-PCR ID TUMOR PROMOTION; AH-RECEPTOR; 8-HYDROXYGUANINE; CARCINOGENESIS; ESTROGENS; TOXICITY; EXPOSURE; MODEL; RNA AB 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is a more potent hepatocarcinogen in female than in male or ovariectomized rats. A possible mechanism for this increased sensitivity is through enhanced metabolic activation of estrogens by TCDD-induced enzymes leading to oxidative damage in the cell. As a marker for oxidative DNA damage, 8-oxo-deoxyguanosine (8-oxo-dC) was quantitated in livers of intact and ovariectomized Sprague-Dawley rats chronically treated with TCDD (125 ng/kg per day) with and without diethylnitrosamine as initiator. Elevated levels of 8-oxo-dG were detected in a significantly greater number of the intact compared to ovariectomized TCDD-treated rats. Expression of CYP1B1 mRNA, a newly identified cytochrome P450 with proposed estrogen hydroxylase activity, was highly induced by TCDD, The results are consistent with the hypothesis that increased metabolism of endogenous estrogens to catechols by TCDD-induced enzymes may lead to increased oxidative DNA damage and hence contribute to TCDD-mediated hepatocarcinogenicity in female rats. C1 NIEHS, BIOCHEM RISK ANAL LAB, RES TRIANGLE PK, NC 27709 USA. JOHNS HOPKINS SCH HYG & PUBL HLTH, DEPT ENVIRONM HLTH SCI, DIV TOXICOL SCI, BALTIMORE, MD USA. FU NCI NIH HHS [R01 CA 36701]; NIEHS NIH HHS [ES 03819, ES 06071] NR 31 TC 57 Z9 60 U1 0 U2 1 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0304-3835 EI 1872-7980 J9 CANCER LETT JI Cancer Lett. PD JAN 2 PY 1996 VL 98 IS 2 BP 219 EP 225 PG 7 WC Oncology SC Oncology GA TM803 UT WOS:A1996TM80300014 PM 8556712 ER PT J AU Hammerschmidt, S Hilse, R vanPutten, JPM GerardySchahn, R Unkmeir, A Frosch, M AF Hammerschmidt, S Hilse, R vanPutten, JPM GerardySchahn, R Unkmeir, A Frosch, M TI Modulation of cell surface sialic acid expression in Neisseria meningitidis via a transposable genetic element SO EMBO JOURNAL LA English DT Article DE capsule; insertion sequence element; invasion; Neisseria meningitidis ID ENDOTHELIAL-CELLS; ESCHERICHIA-COLI; GROUP-B; CAPSULE; POLYSACCHARIDE; GONORRHOEAE; LIPOPOLYSACCHARIDE; TRANSPOSITION; SIALYLATION; INFECTION AB Cell surface-located sialic acids of the capsule and the lipooligosaccharide (LOS) are both pivotal virulence factors in Neisseria meningitidis, promoting survival and dissemination of this pathogen which can cause both sepsis and meningitis, With the aid of a unique set of isogenic meningococcal mutants defective in the expression of cell surface-located sialic acids, we have demonstrated that encapsulation hinders the primary event in the development of the disease, but the spontaneous switching of encapsulated wild-type bacteria to a capsule-negative phenotype promotes meningococcal adherence and invasion into mucosal epithelial cells, Genetic analysis of the capsule-negative, invasive bacteria revealed a unique mechanism for modulation of capsule expression based on the reversible inactivation of an essential sialic acid biosynthesis gene, siaA, by insertion/excision of a naturally occurring insertion sequence element, IS1301, Inactivation of siaA regulates both capsule expression and endogenous LOS sialylation, This is the first example of an insertion sequence element-based genetic switch mechanism in the pathogenic bacterium and is an important step in the understanding of bacterial virulence. C1 HANNOVER MED SCH,INST MED MIKROBIOL,D-30623 HANNOVER,GERMANY. NIAID,ROCKY MT LABS,HAMILTON,MT 59840. RI Frosch, Matthias/H-2411-2013; OI Hammerschmidt, Sven/0000-0002-6382-6681; van Putten, Jos/0000-0002-4126-8172 NR 36 TC 157 Z9 159 U1 0 U2 3 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0261-4189 J9 EMBO J JI Embo J. PD JAN 2 PY 1996 VL 15 IS 1 BP 192 EP 198 PG 7 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA TQ160 UT WOS:A1996TQ16000020 PM 8598202 ER PT B AU Sastry, S VanMeter, JW Carson, RE AF Sastry, S VanMeter, JW Carson, RE BE Moonier, PA TI Multimodality Bayesian algorithm for image reconstruction in positron emission tomography SO 1995 IEEE NUCLEAR SCIENCE SYMPOSIUM AND MEDICAL IMAGING CONFERENCE RECORD, VOLS 1-3 LA English DT Proceedings Paper CT 1995 IEEE Nuclear Science Symposium and Medical Imaging Conference CY OCT 21-28, 1995 CL SAN FRANCISCO, CA SP IEEE C1 NIH,LAB PHYS SCI,DIV COMP RES & TECHNOL,BETHESDA,MD 20892. RI Carson, Richard/H-3250-2011 OI Carson, Richard/0000-0002-9338-7966 NR 0 TC 0 Z9 0 U1 0 U2 0 PU I E E E PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 BN 0-7803-3181-8 PY 1996 BP 1694 EP 1698 PG 5 WC Engineering, Electrical & Electronic; Instruments & Instrumentation; Nuclear Science & Technology; Radiology, Nuclear Medicine & Medical Imaging SC Engineering; Instruments & Instrumentation; Nuclear Science & Technology; Radiology, Nuclear Medicine & Medical Imaging GA BF95Z UT WOS:A1996BF95Z00372 ER PT B AU Vrhel, M Lee, C Unser, M AF Vrhel, M Lee, C Unser, M GP IEEE TI Fast computation of the continuous wavelet transform through oblique projections SO 1996 IEEE INTERNATIONAL CONFERENCE ON ACOUSTICS, SPEECH, AND SIGNAL PROCESSING, CONFERENCE PROCEEDINGS, VOLS 1-6 LA English DT Proceedings Paper CT 1996 IEEE International Conference on Acoustics, Speech, and Signal Processing (ICASSP 96) CY MAY 07-10, 1996 CL ATLANTA, GA SP IEEE, Signal Proc Soc C1 NIH,BIOMED ENGN & INSTRUMENTAT PROGRAM,NCRR,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU I E E E PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 BN 0-7803-3192-3 J9 INT CONF ACOUST SPEE PY 1996 BP 1459 EP 1462 PG 4 WC Acoustics; Engineering, Electrical & Electronic SC Acoustics; Engineering GA BG26G UT WOS:A1996BG26G00368 ER PT B AU Lee, C Eden, M Unser, M AF Lee, C Eden, M Unser, M GP IEEE TI Near optimal geometric image scaling using oblique projection operators SO 1996 IEEE INTERNATIONAL CONFERENCE ON ACOUSTICS, SPEECH, AND SIGNAL PROCESSING, CONFERENCE PROCEEDINGS, VOLS 1-6 LA English DT Proceedings Paper CT 1996 IEEE International Conference on Acoustics, Speech, and Signal Processing (ICASSP 96) CY MAY 07-10, 1996 CL ATLANTA, GA SP IEEE, Signal Proc Soc C1 NCRR,NIH,BEIP,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU I E E E PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 BN 0-7803-3192-3 J9 INT CONF ACOUST SPEE PY 1996 BP 2399 EP 2402 PG 4 WC Acoustics; Engineering, Electrical & Electronic SC Acoustics; Engineering GA BG26G UT WOS:A1996BG26G00605 ER PT B AU Unser, M AF Unser, M GP IEEE IEEE IEEE TI Wavelets, statistics, and biomedical applications SO 8TH IEEE SIGNAL PROCESSING WORKSHOP ON STATISTICAL SIGNAL AND ARRAY PROCESSING, PROCEEDINGS LA English DT Proceedings Paper CT 8th IEEE Signal Processing Workshop on Statistical Signal and Array Processing (SSAP) CY JUN 24-26, 1996 CL CORFU, GREECE SP IEEE, Signal Proc Soc, USA, Res Off, USN, Off Naval Res C1 NIH, BIOMED ENGN & INSTRUMENTAT PROGRAM, NCRR, BETHESDA, MD 20892 USA. RI Unser, Michael/A-1550-2008 NR 53 TC 5 Z9 6 U1 0 U2 0 PU IEEE COMPUTER SOC PI LOS ALAMITOS PA 10662 LOS VAQUEROS CIRCLE, PO BOX 3014, LOS ALAMITOS, CA 90720-1264 USA BN 0-8186-7576-4 PY 1996 BP 244 EP 249 DI 10.1109/SSAP.1996.534863 PG 6 WC Computer Science, Information Systems; Engineering, Electrical & Electronic; Telecommunications SC Computer Science; Engineering; Telecommunications GA BF94C UT WOS:A1996BF94C00058 ER EF