FN Thomson Reuters Web of Science™ VR 1.0 PT J AU Ma, YC Kim, HY AF Ma, YC Kim, HY TI Determination of steroids by liquid chromatography mass spectrometry SO JOURNAL OF THE AMERICAN SOCIETY FOR MASS SPECTROMETRY LA English DT Article ID GABA-A RECEPTOR; GAS-CHROMATOGRAPHY; DEHYDROEPIANDROSTERONE-SULFATE; NEUROSTEROIDS; PLASMA; BRAIN; CORTISOL; RAT; IDENTIFICATION; PREGNENOLONE AB On-line atmospheric pressure chemical ionization (APCI) and electrospray ionization (ESI) liquid chromatography/mass spectrometry (LC/MS) were evaluated for the analysis of a variety of steroids. Steroids were classified into three major groups based on the spectra and the sensitivities observed: (I) those containing a 3-one, 4-ene functional group, (LI) those containing at least one ketone group without conjugation, and (III) those containing hydroxy group(s) only. In the APCI mode, the best sensitivity and the lowest detection limit for all three groups were obtained by using a mobile phase consisting of methanal and 1%-2% acetic acid in water. The APCI spectra were characterized by MH+, MH+-H2O, MH+-2H(2)O, etc., with the degree of H2O loss being compound dependent: group I steroids produced stable MH+ and group III steroids showed extensive water loss. In the electrospray mode the best sensitivity and the lowest detection limit for the first two groups were obtained when pure methanal and water were used as the mobile phase. This condition produced abundant stable MNa+ due to ubiquitous sodium. Detection limits in the 5-15 pg range can be easily achieved using ESI LC/MS. Addition of ammonium acetate or use of acetonitrile in the mobile phase, common in the LC/MS analysis of steroids, decreased the sensitivity for the group I and II steroids and thus should be avoided. For group III steroids, the detection limit can be improved by the addition of acetic acid to the mobile phase. (C) 1997 American Society for Mass Spectrometry. C1 NIAAA,SECT MASS SPECTROMETRY,LMBB,NIH,ROCKVILLE,MD 20852. NR 29 TC 112 Z9 114 U1 0 U2 13 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 1044-0305 J9 J AM SOC MASS SPECTR JI J. Am. Soc. Mass Spectrom. PD SEP PY 1997 VL 8 IS 9 BP 1010 EP 1020 DI 10.1016/S1044-0305(97)00122-0 PG 11 WC Chemistry, Analytical; Chemistry, Physical; Spectroscopy SC Chemistry; Spectroscopy GA XT643 UT WOS:A1997XT64300008 ER PT J AU Asico, LD Fuchs, S Accili, D Carey, RM Eisner, GM Jose, PA AF Asico, LD Fuchs, S Accili, D Carey, RM Eisner, GM Jose, PA TI Disruption of the dopamine D3 receptor gene produces renin-dependent hypertension. SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract C1 GEORGETOWN UNIV,MED CTR,WASHINGTON,DC 20007. UNIV VIRGINIA,HLTH SCI CTR,CHARLOTTESVILLE,VA. NIDDK,BETHESDA,MD. NR 0 TC 0 Z9 0 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 SEP PY 1997 VL 8 SU S BP A1353 EP A1353 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA XY103 UT WOS:A1997XY10301353 ER PT J AU Bird, JE Kopp, JB Giancarli, MR Gitlitz, P Durham, SK AF Bird, JE Kopp, JB Giancarli, MR Gitlitz, P Durham, SK TI Captopril (CAP) intervention is of benefit in HIV-transgenic mice. SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract C1 BRISTOL MYERS SQUIBB,PRINCETON,NJ. NIDDK,NIH,BETHESDA,MD. NR 0 TC 0 Z9 0 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 SEP PY 1997 VL 8 SU S BP A2848 EP A2848 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA XY103 UT WOS:A1997XY10302846 ER PT J AU Chang, SH Phelps, PC Coursen, JD Wang, XW Berezesky, IK Harris, CC Trump, BF AF Chang, SH Phelps, PC Coursen, JD Wang, XW Berezesky, IK Harris, CC Trump, BF TI Ultrastructural and cytochemical changes during apoptosis and necrosis induced by microinjection of wild-type p53 genes into NRK-52E cells. SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract C1 UNIV MARYLAND,SCH MED,DEPT PATHOL,BALTIMORE,MD 21201. NCI,HUMAN CARCINOGENESIS LAB,NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 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 SEP PY 1997 VL 8 SU S BP A1948 EP A1948 PG 2 WC Urology & Nephrology SC Urology & Nephrology GA XY103 UT WOS:A1997XY10301948 ER PT J AU Christensen, BM Olsson, B Knepper, MA Maunsbach, AB Nielsen, S AF Christensen, BM Olsson, B Knepper, MA Maunsbach, AB Nielsen, S TI Cellular and subcellular localization of aquaporin-2 and aquaporin-3 in human kidney. SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract C1 UNIV AARHUS,DK-8000 AARHUS C,DENMARK. NHLBI,NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 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 SEP PY 1997 VL 8 SU S BP A0072 EP A0072 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA XY103 UT WOS:A1997XY10300072 ER PT J AU Chumlea, WC Bergen, C Dwyer, J Henry, R McGhee, A McLeroy, S Paranandi, L AF Chumlea, WC Bergen, C Dwyer, J Henry, R McGhee, A McLeroy, S Paranandi, L TI Anthropometric data for hemodialysis patients: An interim report from the HEMO study. SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract C1 NIDDK,HEMO STUDY GRP,BETHESDA,MD. NR 0 TC 0 Z9 0 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 SEP PY 1997 VL 8 SU S BP A0880 EP A0880 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA XY103 UT WOS:A1997XY10300880 ER PT J AU Cohen, HT Zarghamee, S Knebelmann, B Kishida, T Zbar, B Sukhatme, VP AF Cohen, HT Zarghamee, S Knebelmann, B Kishida, T Zbar, B Sukhatme, VP TI A critical domain of the von Hippel-Lindau (VHL) tumor suppressor gene product. SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract C1 BETH ISRAEL MED CTR,BOSTON,MA. NCI,FREDERICK,MD 21701. NR 0 TC 0 Z9 0 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 SEP PY 1997 VL 8 SU S BP A1792 EP A1792 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA XY103 UT WOS:A1997XY10301792 ER PT J AU Coleman, RA Knepper, MA Wade, JB AF Coleman, RA Knepper, MA Wade, JB TI Rat renal connecting cells express AQP2. SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract C1 UNIV MARYLAND,BALTIMORE,MD 21201. NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 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 SEP PY 1997 VL 8 SU S BP A0073 EP A0073 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA XY103 UT WOS:A1997XY10300073 ER PT J AU Coronado, B Beck, GJ Greene, T Kusek, JW Levey, AS AF Coronado, B Beck, GJ Greene, T Kusek, JW Levey, AS TI Cardiovascular disease risk factors and GFR in the MDRD study. SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract C1 TUFTS UNIV NEW ENGLAND MED CTR,BOSTON,MA 02111. CLEVELAND CLIN FDN,CLEVELAND,OH 44195. NIDDK,BETHESDA,MD. NR 0 TC 0 Z9 0 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 SEP PY 1997 VL 8 SU S BP A0643 EP A0643 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA XY103 UT WOS:A1997XY10300643 ER PT J AU Daugirdas, J Depner, T Greene, T Kaufman, A Leypoldt, K Schulman, G AF Daugirdas, J Depner, T Greene, T Kaufman, A Leypoldt, K Schulman, G TI Effect of vascular access type and blood draw method on recirculation and rebound in the HEMO study. SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract C1 NIDDK,BETHESDA,MD. NR 0 TC 0 Z9 0 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 SEP PY 1997 VL 8 SU S BP A1288 EP A1288 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA XY103 UT WOS:A1997XY10301288 ER PT J AU deCaestecker, MP Huff, C Parks, WT Eng, C Wang, TW Roberts, AB Lechleider, RJ AF deCaestecker, MP Huff, C Parks, WT Eng, C Wang, TW Roberts, AB Lechleider, RJ TI Cloning and characterization of a novel SMAD repressor protein (SRP) in the TGF-beta signaling pathway. SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract C1 NCI,CHEMOPREVENT LAB,NIH,BETHESDA,MD 20892. MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. NR 0 TC 0 Z9 0 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 SEP PY 1997 VL 8 SU S BP A2022 EP A2022 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA XY103 UT WOS:A1997XY10302022 ER PT J AU deCaestecker, MP Parks, WT Eng, C Roberts, AB Lechleider, RJ AF deCaestecker, MP Parks, WT Eng, C Roberts, AB Lechleider, RJ TI TGF-beta family signal transduction by SMAD4. SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract C1 NCI,CHEMOPREVENT LAB,NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 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 SEP PY 1997 VL 8 SU S BP A2023 EP A2023 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA XY103 UT WOS:A1997XY10302023 ER PT J AU DiGiovanni, SR Lolait, SJ Knepper, MA AF DiGiovanni, SR Lolait, SJ Knepper, MA TI Expression of oxytocin receptor mRNA in the rat nephron. SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract C1 VIRGINIA COMMONWEALTH UNIV,RICHMOND,VA 23284. NHLBI,NIH,BETHESDA,MD 20892. NIMH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 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 SEP PY 1997 VL 8 SU S BP A0075 EP A0075 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA XY103 UT WOS:A1997XY10300075 ER PT J AU Doi, SO Jacot, TT Donald, C Striker, LJ Hirszel, P AF Doi, SO Jacot, TT Donald, C Striker, LJ Hirszel, P TI The effect of serum on the L-arginine nitric oxide metabolic pathway in mesangial cells. SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract C1 UNIF SERV UNIV, NATL INST HLTH, BETHESDA, MD USA. NATL NAVAL MED CTR, BETHESDA, MD USA. NR 0 TC 0 Z9 0 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 SEP PY 1997 VL 8 SU S BP A0405 EP A0405 PG 2 WC Urology & Nephrology SC Urology & Nephrology GA XY103 UT WOS:A1997XY10300405 ER PT J AU Earm, JH Marples, D Christensen, BM Frokiaer, J Han, JS Knepper, MA Nielsen, S AF Earm, JH Marples, D Christensen, BM Frokiaer, J Han, JS Knepper, MA Nielsen, S TI Decreased aquaporin-2 (AQP2) water channel expression in kidney of hypercalcemic rats. SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract C1 UNIV AARHUS,DK-8000 AARHUS C,DENMARK. UNIV LEEDS,LEEDS LS2 9JT,W YORKSHIRE,ENGLAND. SEOUL NATL UNIV,SEOUL 151,SOUTH KOREA. NHLBI,NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 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 SEP PY 1997 VL 8 SU S BP A0076 EP A0076 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA XY103 UT WOS:A1997XY10300076 ER PT J AU Ecelbarger, CA FernandezLlama, P Lee, AJ Nielsen, S Ware, JA Shen, S Pohl, LR Knepper, MA AF Ecelbarger, CA FernandezLlama, P Lee, AJ Nielsen, S Ware, JA Shen, S Pohl, LR Knepper, MA TI Enhancement of urinary concentrating ability by cyclooxygenase inhibitors is associated with increased expression of Na-K-2Cl cotransporter and increased trafficking of aquaporin-2 water channel. SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract C1 NHLBI,NIH,BETHESDA,MD 20892. UNIV AARHUS,AARHUS,DENMARK. NR 0 TC 0 Z9 0 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 SEP PY 1997 VL 8 SU S BP A1913 EP A1913 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA XY103 UT WOS:A1997XY10301913 ER PT J AU Ecelbarger, CA Yu, S Lee, AJ Chou, CL Weinstein, LS Knepper, MA AF Ecelbarger, CA Yu, S Lee, AJ Chou, CL Weinstein, LS Knepper, MA TI Decreased expression of bumetanide-sensitive Na-K-2Cl cotransporter (BSC1) and aquaporin-2 (AQP2) in mice with heterozygous disruption of the G(s)alpha G-protein subunit gene. SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract C1 NHLBI,BETHESDA,MD 20892. NIDDKD,NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 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 SEP PY 1997 VL 8 SU S BP A0077 EP A0077 PG 2 WC Urology & Nephrology SC Urology & Nephrology GA XY103 UT WOS:A1997XY10300077 ER PT J AU Eknoyan, G Agodoa, L Beck, G Daugirdas, J Greene, T Kusek, J Levin, N AF Eknoyan, G Agodoa, L Beck, G Daugirdas, J Greene, T Kusek, J Levin, N TI Adequacy of delivered dialysis doses in the HEMO study: An interim report. SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract C1 NIDDK,HEMO STUDY GRP,BETHESDA,MD. NR 0 TC 0 Z9 0 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 SEP PY 1997 VL 8 SU S BP A1296 EP A1296 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA XY103 UT WOS:A1997XY10301296 ER PT J AU Elliot, SJ Striker, GE Jacot, TA Striker, L AF Elliot, SJ Striker, GE Jacot, TA Striker, L TI Elmiron(R) (pentosan polysulfate) modifies extracellular matrix production (ECM) in mouse mesangial cells. SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract C1 NIH,RCB,MDB,BETHESDA,MD 20892. NR 0 TC 1 Z9 1 U1 0 U2 2 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 SEP PY 1997 VL 8 SU S BP A2388 EP A2388 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA XY103 UT WOS:A1997XY10302388 ER PT J AU FernandezLlama, P Nielsen, S Ecelbarger, CA Andrews, P Knepper, MA AF FernandezLlama, P Nielsen, S Ecelbarger, CA Andrews, P Knepper, MA TI Global downregulation of collecting duct solute transporter and water channel expression in adriamycin-induced nephrotic syndrome. SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract C1 NHLBI,NIH,BETHESDA,MD 20892. AARHUS UNIV,AARHUS,DENMARK. GEORGETOWN UNIV,WASHINGTON,DC 20057. NR 0 TC 0 Z9 0 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 SEP PY 1997 VL 8 SU S BP A2865 EP A2865 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA XY103 UT WOS:A1997XY10302862 ER PT J AU FernandezLlama, P Andrews, P Ecelbarger, CA Nielsen, S Knepper, MA AF FernandezLlama, P Andrews, P Ecelbarger, CA Nielsen, S Knepper, MA TI Downregulation of bumetanide-sensitive Na-K-2Cl cotransporter (BSC-1) expression in adriamycin-induced nephrotic syndrome. SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract C1 NHLBI,NIH,BETHESDA,MD 20892. GEORGETOWN UNIV,WASHINGTON,DC 20057. AARHUS UNIV,DK-8000 AARHUS C,DENMARK. NR 0 TC 0 Z9 0 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 SEP PY 1997 VL 8 SU S BP A0155 EP A0155 PG 2 WC Urology & Nephrology SC Urology & Nephrology GA XY103 UT WOS:A1997XY10300155 ER PT J AU Frokiaer, J Wen, H Isikay, L Marples, D Knepper, MA Djurhuus, JC Orskov, H Nielsen, S AF Frokiaer, J Wen, H Isikay, L Marples, D Knepper, MA Djurhuus, JC Orskov, H Nielsen, S TI Aquaporin-2 is excreted in urine by a selective apical pathway different from whole-cell shedding. SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract C1 UNIV AARHUS,DK-8000 AARHUS C,DENMARK. UNIV LEEDS,LEEDS LS2 9JT,W YORKSHIRE,ENGLAND. NHLBI,NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 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 SEP PY 1997 VL 8 SU S BP A0080 EP A0080 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA XY103 UT WOS:A1997XY10300080 ER PT J AU Geetha, D Liang, MX Metter, EJ Fozard, JL Spector, DA AF Geetha, D Liang, MX Metter, EJ Fozard, JL Spector, DA TI Age and gender influence urinary solute excretion. SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract C1 NIA,NIH,BALTIMORE,MD 21224. J HOPKINS BAYVIEW MED CTR,BALTIMORE,MD. RI Fozard, James Leonard/B-3660-2009 NR 0 TC 0 Z9 0 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 SEP PY 1997 VL 8 SU S BP A0490 EP A0490 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA XY103 UT WOS:A1997XY10300490 ER PT J AU Hoffman, BB Guo, J Mozes, MM Kopp, JB Ziyadeh, FN AF Hoffman, BB Guo, J Mozes, MM Kopp, JB Ziyadeh, FN TI Characterization of cultured renal epithelial cells from TGF-beta 1 knock-out and wild-type mice and their behavior in high glucose. SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract C1 UNIV PENN,PHILADELPHIA,PA 19104. NIDDK,BETHESDA,MD. RI Mozes, Miklos/E-9003-2011 NR 0 TC 0 Z9 0 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 SEP PY 1997 VL 8 SU S BP A2309 EP A2309 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA XY103 UT WOS:A1997XY10302309 ER PT J AU Inoue, T Mandon, B Nielsen, S Knepper, MA AF Inoue, T Mandon, B Nielsen, S Knepper, MA TI Expression of SNAP23, the ''missing snare'', in rat collecting duct principal cells. SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract C1 NHLBI,NIH,BETHESDA,MD 20892. UNIV AARHUS,AARHUS,DENMARK. NR 0 TC 2 Z9 2 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 SEP PY 1997 VL 8 SU S BP A0296 EP A0296 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA XY103 UT WOS:A1997XY10300296 ER PT J AU Kanno, Y Kimmel, PL Fox, CH Tanawattanacharoen, S Kopp, JB AF Kanno, Y Kimmel, PL Fox, CH Tanawattanacharoen, S Kopp, JB TI HIV-1 infects human kidney in organ culture. SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract C1 GEORGE WASHINGTON UNIV,MED CTR,DEPT MED,WASHINGTON,DC 20037. MOL HISTOL,GAITHERSBURG,MD. NIDDK,NIH,BETHESDA,MD. NR 0 TC 0 Z9 0 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 SEP PY 1997 VL 8 SU S BP A2886 EP A2886 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA XY103 UT WOS:A1997XY10302883 ER PT J AU Kishore, BK Schorr, K Mandon, B Wade, JB Knepper, MA AF Kishore, BK Schorr, K Mandon, B Wade, JB Knepper, MA TI Synaptotagmin-8 localization in rat kidney. SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract C1 NIH,BETHESDA,MD 20892. UNIV MARYLAND,BALTIMORE,MD. NR 0 TC 0 Z9 0 U1 1 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 SEP PY 1997 VL 8 SU S BP A0297 EP A0297 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA XY103 UT WOS:A1997XY10300297 ER PT J AU Krishnamurti, U Rondeau, E Sraer, JD Stevenson, S Michael, A Tsilibary, E AF Krishnamurti, U Rondeau, E Sraer, JD Stevenson, S Michael, A Tsilibary, E TI Alterations in signaling in human glomerular epithelial cells interacting glycated matrix. SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract C1 UNIV MINNESOTA,MINNEAPOLIS,MN 55455. INSERM,F-75654 PARIS 13,FRANCE. NIH,BETHESDA,MD. NR 0 TC 0 Z9 0 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 SEP PY 1997 VL 8 SU S BP A2416 EP A2416 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA XY103 UT WOS:A1997XY10302416 ER PT J AU Lee, AJ Bradford, AD Terris, JM Knepper, MA Ecelbarger, CA AF Lee, AJ Bradford, AD Terris, JM Knepper, MA Ecelbarger, CA TI The type 1 bumetanide-sensitive Na-K-2Cl cotransporter (BSC1) exists in the plasma membrane as a high molecular weight oligomeric complex. SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract C1 NHLBI,BETHESDA,MD 20892. UNIFORMED SERV UNIV HLTH SCI,DEPT PHYSIOL,BETHESDA,MD 20814. NR 0 TC 0 Z9 0 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 SEP PY 1997 VL 8 SU S BP A0180 EP A0180 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA XY103 UT WOS:A1997XY10300180 ER PT J AU Lee, AJ Terris, J Ecelbarger, CA Wade, JB Knepper, MA AF Lee, AJ Terris, J Ecelbarger, CA Wade, JB Knepper, MA TI Expression of a 55 kilodalton urea transporter isoform in mouse outer medulla. SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract C1 NHLBI,NIH,BETHESDA,MD 20892. UNIV MARYLAND,BALTIMORE,MD 21201. NR 0 TC 0 Z9 0 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 SEP PY 1997 VL 8 SU S BP A0096 EP A0096 PG 2 WC Urology & Nephrology SC Urology & Nephrology GA XY103 UT WOS:A1997XY10300096 ER PT J AU Lenz, O Zheng, F Striker, LJ Striker, GE AF Lenz, O Zheng, F Striker, LJ Striker, GE TI A novel model for the inheritance of glomerulosclerosis in mice. SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract C1 NIDDK,RCBS,MDB,NIH,BETHESDA,MD. RI Lenz, Oliver/M-4672-2016 OI Lenz, Oliver/0000-0003-2997-3976 NR 0 TC 0 Z9 0 U1 1 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 SEP PY 1997 VL 8 SU S BP A1816 EP A1816 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA XY103 UT WOS:A1997XY10301816 ER PT J AU Levey, AS Athienites, NV Gassman, JJ Martin, AA Ornt, DB Kusek, JW Meyer, KB AF Levey, AS Athienites, NV Gassman, JJ Martin, AA Ornt, DB Kusek, JW Meyer, KB TI Comorbidity assessment in the hemo study: An interim report. SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract C1 NIDDK,BETHESDA,MD. NR 0 TC 0 Z9 0 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 SEP PY 1997 VL 8 SU S BP A0933 EP A0933 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA XY103 UT WOS:A1997XY10300933 ER PT J AU Levey, AS Bosch, JP Breyer, JA Greene, T Rogers, N Roth, D AF Levey, AS Bosch, JP Breyer, JA Greene, T Rogers, N Roth, D TI Predicting GFR from serum creatinine in the MDRD study. SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract C1 NIDDK,MDRD STUDY GRP,BETHESDA,MD. NR 0 TC 0 Z9 0 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 SEP PY 1997 VL 8 SU S BP A0671 EP A0671 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA XY103 UT WOS:A1997XY10300671 ER PT J AU Ma, T Chou, CL Yang, B Knepper, MA Verkman, AS AF Ma, T Chou, CL Yang, B Knepper, MA Verkman, AS TI Decreased urinary concentrating ability and inner medullary collecting duct water permeability in transgenic mice lacking aquaporin-4. SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract C1 UNIV CALIF SAN FRANCISCO,SAN FRANCISCO,CA 94143. NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 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 SEP PY 1997 VL 8 SU S BP A0098 EP A0098 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA XY103 UT WOS:A1997XY10300098 ER PT J AU Maroni, B Burkhart, J Burrowes, J Dwyer, J Henry, R Kusek, J Paranandi, L Poole, D AF Maroni, B Burkhart, J Burrowes, J Dwyer, J Henry, R Kusek, J Paranandi, L Poole, D TI Relationship between dialysis dose, membrane flux and indices of nutritional status at baseline in the HEMO study: An interim report. SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract C1 NIDDK,HEMO STUDY GRP,BETHESDA,MD. NR 0 TC 0 Z9 0 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 SEP PY 1997 VL 8 SU S BP A1322 EP A1322 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA XY103 UT WOS:A1997XY10301322 ER PT J AU Marples, D Knepper, MA Nielsen, S AF Marples, D Knepper, MA Nielsen, S TI Prostaglandins are involved in the long-term modulation of aquaporin-2 (AQP2) water channel expression in kidney of normal rats and rats with lithium-induced nephrogenic diabetes insipidus. SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract C1 UNIV LEEDS,LEEDS LS2 9JT,W YORKSHIRE,ENGLAND. AARHUS UNIV,AARHUS,DENMARK. NHLBI,NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 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 SEP PY 1997 VL 8 SU S BP A0102 EP A0102 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA XY103 UT WOS:A1997XY10300102 ER PT J AU Mever, K Paranandi, L Hays, R Benz, R Athienites, N Kusek, J Levey, A AF Mever, K Paranandi, L Hays, R Benz, R Athienites, N Kusek, J Levey, A TI Clinical correlates of baseline quality of life in the hemo study: An interim report. SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract C1 NIDDK,HEMO STUDY GRP,BETHESDA,MD. NR 0 TC 0 Z9 0 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 SEP PY 1997 VL 8 SU S BP A0945 EP A0945 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA XY103 UT WOS:A1997XY10300945 ER PT J AU Meyer, K Paranandi, L Hays, R Benz, R Athienites, N Kusek, J Levey, A AF Meyer, K Paranandi, L Hays, R Benz, R Athienites, N Kusek, J Levey, A TI Quality of life in the hemo study: An interim report. SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract C1 NIDDK,HEMO STUDY GRP,BETHESDA,MD. NR 0 TC 0 Z9 0 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 SEP PY 1997 VL 8 SU S BP A0946 EP A0946 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA XY103 UT WOS:A1997XY10300946 ER PT J AU Murase, T Ecelbarger, CA Lee, AJ Nielsen, S Knepper, MA Verbalis, JG AF Murase, T Ecelbarger, CA Lee, AJ Nielsen, S Knepper, MA Verbalis, JG TI Downregulation of kidney aquaporin-2 expression during renal escape from antidiuresis occurs independently of changes in plasma or interstitial osmolality. SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract C1 GEORGETOWN UNIV,DIV ENDOCRINOL,WASHINGTON,DC. NHLBI,KIDNEY & ELECTROLYTE METAB LAB,NIH,BETHESDA,MD 20892. AARHUS UNIV,AARHUS,DENMARK. NR 0 TC 0 Z9 0 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 SEP PY 1997 VL 8 SU S BP A0105 EP A0105 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA XY103 UT WOS:A1997XY10300105 ER PT J AU Nielsen, S Maunsbach, AB Ecelbarger, C Knepper, MA AF Nielsen, S Maunsbach, AB Ecelbarger, C Knepper, MA TI Cellular and subcellular localization of the Na,K,2Cl co-transporter BSC-1 in apical plasma membrane and vesicles of thick ascending limb and macula densa cells. SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract C1 AARHUS UNIV,DK-8000 AARHUS C,DENMARK. NHLBI,NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 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 SEP PY 1997 VL 8 SU S BP A0195 EP A0195 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA XY103 UT WOS:A1997XY10300195 ER PT J AU Poncelet, AC deCaestecker, MP Schnaper, HW AF Poncelet, AC deCaestecker, MP Schnaper, HW TI Regulation of collagen turnover by TGF-beta I in human mesangial cells: Potential role of Smad proteins. SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract C1 NORTHWESTERN UNIV,SCH MED,DEPT PEDIAT,CHICAGO,IL 60611. NCI,CHEMOPREVENT LAB,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 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 SEP PY 1997 VL 8 SU S BP A2440 EP A2440 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA XY103 UT WOS:A1997XY10302440 ER PT J AU Portilla, D Crew, MD Buonanno, A AF Portilla, D Crew, MD Buonanno, A TI cDNA cloning and expression of a novel family of calcium-independent phospholipase A2 (CaIPLA2) enzymes. SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract C1 UNIV ARKANSAS MED SCI,LITTLE ROCK,AR 72205. VAMC,LITTLE ROCK,AR. NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 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 SEP PY 1997 VL 8 SU S BP A1931 EP A1931 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA XY103 UT WOS:A1997XY10301931 ER PT J AU Roberts, ISD Kunne, S DeCaestecker, M Bottinger, EP AF Roberts, ISD Kunne, S DeCaestecker, M Bottinger, EP TI Role of TGF-beta 1 in progressive renal fibrosis induced by acute accelerated hypertension in salt sensitive DALH rats. SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract C1 UNIV MANCHESTER,MANCHESTER,LANCS,ENGLAND. NCI,CHEMOPREVENT LAB,NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 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 SEP PY 1997 VL 8 SU S BP A2351 EP A2351 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA XY103 UT WOS:A1997XY10302351 ER PT J AU Rocco, M Benz, R Burkart, J Cheung, A Heyka, R Irving, S Wright, C AF Rocco, M Benz, R Burkart, J Cheung, A Heyka, R Irving, S Wright, C TI Baseline blood pressure in HEMO study participants: An interim report. SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract C1 NIDDK,HEMO STUDY GRP,BETHESDA,MD. NR 0 TC 4 Z9 4 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD SEP PY 1997 VL 8 SU S BP A1153 EP A1153 PG 2 WC Urology & Nephrology SC Urology & Nephrology GA XY103 UT WOS:A1997XY10301153 ER PT J AU Shrivastav, S Mozes, MM Kopp, JB AF Shrivastav, S Mozes, MM Kopp, JB TI Androgen regulates transgene expression in HIV transgenic mice. SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract C1 NIDDK,KIDNEY DIS SECT,NIH,BETHESDA,MD. RI Mozes, Miklos/E-9003-2011 NR 0 TC 0 Z9 0 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 SEP PY 1997 VL 8 SU S BP A2357 EP A2357 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA XY103 UT WOS:A1997XY10302357 ER PT J AU Sun, D Huang, YG Smart, A Schnermann, J Briggs, JP Yang, TX AF Sun, D Huang, YG Smart, A Schnermann, J Briggs, JP Yang, TX TI Mechanisms of renal COX-2 induction by lipopolysaccharide. SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract C1 UNIV MICHIGAN,ANN ARBOR,MI 48109. NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 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 SEP PY 1997 VL 8 SU S BP A1935 EP A1935 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA XY103 UT WOS:A1997XY10301935 ER PT J AU Sundaram, S Cendoroglo, M Jaber, B Yan, G Levey, A Owen, WF King, AJ Pereira, BJG AF Sundaram, S Cendoroglo, M Jaber, B Yan, G Levey, A Owen, WF King, AJ Pereira, BJG TI Interactions between clinical and nutritional indices with endotoxin (ET) stimulated cytokine production in hemodialysis (HD) patients. SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract C1 HEMO STUDY GRP,BOSTON,MA. TUFTS UNIV NEW ENGLAND MED CTR,BOSTON,MA 02111. BRIGHAM & WOMENS HOSP,BOSTON,MA 02115. NIDDK,BETHESDA,MD. NR 0 TC 0 Z9 0 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 SEP PY 1997 VL 8 SU S BP A1166 EP A1166 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA XY103 UT WOS:A1997XY10301166 ER PT J AU Tanawattanacharoen, S Kopp, JB AF Tanawattanacharoen, S Kopp, JB TI HIV-1 establishes a non-productive infection of renal tubular epithelial cells. SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract C1 NIDDK,KIDNEY DIS SECT,NIH,BETHESDA,MD. NR 0 TC 0 Z9 0 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 SEP PY 1997 VL 8 SU S BP A0471 EP A0471 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA XY103 UT WOS:A1997XY10300471 ER PT J AU Terris, J Inoue, T Chou, CL Lee, AJ Bradford, AD Ecelbarger, CA Nielsen, S Knepper, MA AF Terris, J Inoue, T Chou, CL Lee, AJ Bradford, AD Ecelbarger, CA Nielsen, S Knepper, MA TI Vasopressin regulates aquaporin-2 and the vasopressin-regulated urea transporter (VRUT) by different short-term mechanisms. SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract C1 NHBLI,NIH,BETHESDA,MD. UNIFORMED SERV UNIV HLTH SCI,BETHESDA,MD 20814. AARHUS UNIV,DK-8000 AARHUS C,DENMARK. NR 0 TC 0 Z9 0 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 SEP PY 1997 VL 8 SU S BP A0121 EP A0121 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA XY103 UT WOS:A1997XY10300121 ER PT J AU Uribarri, J Levin, N Delmez, J Depner, T Ornt, D Owen, W Yan, G AF Uribarri, J Levin, N Delmez, J Depner, T Ornt, D Owen, W Yan, G TI Association of acidosis and nutritional parameters in hemodialysis (HD) patients. SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract C1 NIDDK,HEMO STUDY GRP,BETHESDA,MD. NR 0 TC 0 Z9 0 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 SEP PY 1997 VL 8 SU S BP A0513 EP A0513 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA XY103 UT WOS:A1997XY10300513 ER PT J AU Weiss, RA AF Weiss, RA TI Cadmium chloride fails to induce interstitial nephritis in Class II MHC knockout mice. SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract C1 NIAID,LCMI,NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 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 SEP PY 1997 VL 8 SU S BP A2178 EP A2178 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA XY103 UT WOS:A1997XY10302178 ER PT J AU Wolfe, RA Ashby, VB Milford, EL Ojo, AO Ettenger, RE Agodoa, LYC Held, PJ Port, FK AF Wolfe, RA Ashby, VB Milford, EL Ojo, AO Ettenger, RE Agodoa, LYC Held, PJ Port, FK TI Patient survival for wait-listed (WL) dialysis versus cadaveric renal transplant (TX) patients in the US. SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract C1 UNIV MICHIGAN,USRDS,ANN ARBOR,MI 48109. UNIV CALIF LOS ANGELES,LOS ANGELES,CA. NIDDK,BETHESDA,MD. BRIGHAM & WOMENS HOSP,BOSTON,MA 02115. NR 0 TC 0 Z9 0 U1 1 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 SEP PY 1997 VL 8 SU S BP A3289 EP A3289 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA XY103 UT WOS:A1997XY10303286 ER PT J AU Wolfe, RA Ashby, VB Milford, EL Bloembergen, WE Ettenger, RE Agodoa, LYC Held, PJ Port, FK AF Wolfe, RA Ashby, VB Milford, EL Bloembergen, WE Ettenger, RE Agodoa, LYC Held, PJ Port, FK TI Differences in access to cadaveric renal transplantation (TX) in the US: [1] rates of wait-list (WL) and [2] of TX among patients on WL. SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract C1 UNIV MICHIGAN,USRDS,ANN ARBOR,MI 48109. UNIV CALIF LOS ANGELES,LOS ANGELES,CA. NIDDK,BETHESDA,MD. NR 0 TC 0 Z9 0 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 SEP PY 1997 VL 8 SU S BP A3288 EP A3288 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA XY103 UT WOS:A1997XY10303285 ER PT J AU Yang, TX Huang, YG Michele, D Smart, A Schnermann, J Briggs, JP AF Yang, TX Huang, YG Michele, D Smart, A Schnermann, J Briggs, JP TI Renal production of 15-deoxy-Delta(12,14)PGJ2 and localization of expression of its nuclear receptors. SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract C1 NIDDKD,NIH,BETHESDA,MD 20892. UNIV MICHIGAN,ANN ARBOR,MI 48109. NR 0 TC 0 Z9 0 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 SEP PY 1997 VL 8 SU S BP A1939 EP A1939 PG 2 WC Urology & Nephrology SC Urology & Nephrology GA XY103 UT WOS:A1997XY10301939 ER PT J AU Yu, S Yu, D Lee, E Lee, R Corria, Z Accili, D Eckhaus, M Westphal, H Weinstein, LS Knepper, MA AF Yu, S Yu, D Lee, E Lee, R Corria, Z Accili, D Eckhaus, M Westphal, H Weinstein, LS Knepper, MA TI Distinct phenotypes result from maternal versus paternal inheritance of a heterozygous disruption of the G(s)alpha gene. SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract C1 NIDDK,NIH,BETHESDA,MD. NR 0 TC 0 Z9 0 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 SEP PY 1997 VL 8 SU S BP A2090 EP A2090 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA XY103 UT WOS:A1997XY10302090 ER PT J AU Zheng, F Esposito, C Striker, GE Striker, L AF Zheng, F Esposito, C Striker, GE Striker, L TI The severity of diabetic nephropathy in mice is influenced by the susceptibility to sclerosis rather than the glycemic level. SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract C1 NIH,RCB,MDB,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 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 SEP PY 1997 VL 8 SU S BP A3035 EP A3035 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA XY103 UT WOS:A1997XY10303032 ER PT J AU Zheng, F Elliot, SJ Schwedler, S Vilar, J Lupia, E Lenz, O Striker, GE Striker, LJ AF Zheng, F Elliot, SJ Schwedler, S Vilar, J Lupia, E Lenz, O Striker, GE Striker, LJ TI An oral preparation of pentosan polysulfate (PPS) decreases glomerulosclerosis (GS) in ROP OS/+ diabetic mice. SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract C1 NIH,RCB,MDB,BETHESDA,MD 20892. UNIV PARIS 07,INSERM U319,PARIS,FRANCE. RI Lenz, Oliver/M-4672-2016 OI Lenz, Oliver/0000-0003-2997-3976 NR 0 TC 0 Z9 0 U1 1 U2 3 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 SEP PY 1997 VL 8 SU S BP A3034 EP A3034 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA XY103 UT WOS:A1997XY10303031 ER PT J AU Zheng, F Elliot, SJ Schwedler, S Vilar, J Lupia, E Lenz, O Striker, GE Striker, LJ AF Zheng, F Elliot, SJ Schwedler, S Vilar, J Lupia, E Lenz, O Striker, GE Striker, LJ TI An oral preparation of pentosan polysulfate (PPS) decreases established glomerulosclerosis (GS) in mice transgenic for bovine growth hormone (bGH). SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract C1 NIH,RCB,MDB,BETHESDA,MD 20892. UNIV PARIS 07,INSERM,U319,PARIS,FRANCE. RI Lenz, Oliver/M-4672-2016 OI Lenz, Oliver/0000-0003-2997-3976 NR 0 TC 0 Z9 0 U1 1 U2 3 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 SEP PY 1997 VL 8 SU S BP A2376 EP A2376 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA XY103 UT WOS:A1997XY10302376 ER PT J AU Zhong, Z Arteel, GE Connor, HD Frankenberg, MV Stachlewitz, RF Mason, RP Raleigh, JA Thurman, RG AF Zhong, Z Arteel, GE Connor, HD Frankenberg, MV Stachlewitz, RF Mason, RP Raleigh, JA Thurman, RG TI Cyclosporin A (CsA) causes hypoxia and free radical production in the kidney: prevention by dietary glycine. SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract C1 UNIV N CAROLINA,DEPT PHARMACOL,CURR TOXICOL,CHAPEL HILL,NC. UNIV N CAROLINA,DEPT RADIAT ONCOL,CURR TOXICOL,CHAPEL HILL,NC. NIEHS,MOL BIOPHYS LAB,RES TRIANGLE PK,NC 27709. NR 0 TC 0 Z9 0 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 SEP PY 1997 VL 8 SU S BP A2377 EP A2377 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA XY103 UT WOS:A1997XY10302377 ER PT J AU Bergan, RC Walls, RG Figg, WD Dawson, NA Headlee, D Tompkins, A Steinberg, SM Reed, E AF Bergan, RC Walls, RG Figg, WD Dawson, NA Headlee, D Tompkins, A Steinberg, SM Reed, E TI Similar clinical outcomes in African-American and non-African-American males treated with suramin for metastatic prostate cancer SO JOURNAL OF THE NATIONAL MEDICAL ASSOCIATION LA English DT Article DE prostate cancer; suramin; African Americans; ethnic groups; clinical outcome ID ANDROGEN RECEPTOR GENE; FLUTAMIDE WITHDRAWAL; WHITE MEN; GROWTH; BLACK; PROLIFERATION; ANGIOGENESIS; INHIBITION; CARCINOMA; MUTATION AB African-American males have a higher incidence of prostate cancer than non-African-American males and an overall poorer prognosis. Environmental factors such as socioeconomic status and biological factors such as an increased frequency of androgen receptor mutation have been identified as causal. As androgen ablation therapy is ubiquitous in the treatment of metastatic prostate cancer, little information is available on clinical outcome independent of hormone therapy. Our experience at the Warren G. Magnusson Clinical Center, National Institutes of Health with the anticancer agent, suramin, offers the opportunity to study clinical outcome in patients treated with an agent whose tumoricidal activity is not dependent on androgen receptor function. Clinical outcome was examined retrospectively in 43 patients treated on a single suramin-based protocol and evaluated as a Function of ethnic background. No significant difference in time to disease progression or survival was observed between African Americans (n=4) and the other 39 patients. These findings are consistent with the hypothesis that therapies that work through mechanisms independent of the androgen receptor may result in similar outcomes across ethnic groups. RP Bergan, RC (reprint author), NCI,DEPT CELL & CANC BIOL,BLDG 10,ROOM 12N226,BETHESDA,MD 20892, USA. RI Figg Sr, William/M-2411-2016 NR 32 TC 7 Z9 7 U1 0 U2 0 PU SLACK INC PI THOROFARE PA 6900 GROVE RD, THOROFARE, NJ 08086 SN 0027-9684 J9 J NATL MED ASSOC JI J. Natl. Med. Assoc. PD SEP PY 1997 VL 89 IS 9 BP 622 EP 628 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA XW121 UT WOS:A1997XW12100008 PM 9302860 ER PT J AU Walther, MM Patel, B Choyke, PL Lubensky, IA Vocke, CD Harris, C Venzon, D Burtis, WJ Linehan, WM AF Walther, MM Patel, B Choyke, PL Lubensky, IA Vocke, CD Harris, C Venzon, D Burtis, WJ Linehan, WM TI Hypercalcemia in patients with metastatic renal cell carcinoma: Effect of nephrectomy and metabolic evaluation SO JOURNAL OF UROLOGY LA English DT Article DE hypercalcemia; carcinoma, renal cell; parathyroid hormones; surgery; neoplasm metastasis ID HORMONE-RELATED PROTEIN; CYCLASE-STIMULATING ACTIVITY; PARATHYROID-HORMONE; HUMORAL HYPERCALCEMIA; PROGNOSTIC-SIGNIFICANCE; SERUM LEVELS; MALIGNANCY; PEPTIDE; CALCIUM; IDENTIFICATION AB Purpose: The role of nephrectomy in the management of hypercalcemia in metastatic renal carcinoma is not known. Hypercalcemia in patients with renal cell carcinoma frequently mimics primary hyperparathyroidism and has been attributed to tumor secretion of parathyroid hormone related protein. We determined the role of cytoreductive surgery in patients with metastatic renal cell carcinoma and hypercalcemia, identified factors that predict patient benefit from surgery, and evaluated the mechanisms of hypercalcemia in these patients. Materials and Methods: A total of 15 patients with metastatic renal cell carcinoma and hypercalcemia underwent metabolic and laboratory evaluation followed by nephrectomy. Postoperatively they were followed for changes in serum calcium levels. We selected 18 normocalcemic patients with metastatic renal cell carcinoma and 4 normocalcemic patients without renal cancer to serve as control groups for survival and parathyroid hormone related protein expression. Results: A decrease in serum calcium corrected for albumin occurred in 9 of 11 patients at 1 to 4 weeks after nephrectomy and in 7 of 12 patients at 5 to 16 weeks after nephrectomy. Clinical evaluation supported a parathyroid hormone related protein mechanism of hypercalcemia in 5 of 8 patients. Two patients had evidence of local osteolytic hypercalcemia and 1 had prostaglandin mediated hypercalcemia. Conclusions: Nephrectomy temporarily ameliorated hypercalcemia in a subgroup of patients with metastatic renal cancer and hypercalcemia. Parathyroid hormone related protein expression was commonly found to be associated with hypercalcemia. Nonparathyroid hormone related protein mechanisms of hypercalcemia in renal carcinoma may be more common than previously thought. C1 NCI, BIOSTAT & DATA MANAGEMENT SECT, NIH, BETHESDA, MD 20892 USA. W HAVEN VET AFFAIRS MED CTR, DIV ENDOCRINOL, W HAVEN, CT USA. RP Walther, MM (reprint author), NCI, UROL ONCOL SECT,SURG BRANCH,DEPT RADIOL, LAB PATHOL, NIH, BETHESDA, MD 20892 USA. RI Venzon, David/B-3078-2008 NR 49 TC 19 Z9 20 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0022-5347 EI 1527-3792 J9 J UROLOGY JI J. Urol. PD SEP PY 1997 VL 158 IS 3 BP 733 EP 739 DI 10.1016/S0022-5347(01)64303-9 PN 1 PG 7 WC Urology & Nephrology SC Urology & Nephrology GA XP869 UT WOS:A1997XP86900010 PM 9258070 ER PT J AU Maini, A Hillman, G Haas, GP Wang, CY Montecillo, E Hamzavi, F Pontes, JE Leland, P Pastan, I Debinski, W Puri, RK AF Maini, A Hillman, G Haas, GP Wang, CY Montecillo, E Hamzavi, F Pontes, JE Leland, P Pastan, I Debinski, W Puri, RK TI Interleukin-13 receptors on human prostate carcinoma cell lines represent a novel target for a chimeric protein composed of IL-13 and a mutated form of Pseudomonas exotoxin SO JOURNAL OF UROLOGY LA English DT Article DE prostate carcinoma; IL-13 Pseudomonas exotoxin; IL-13 receptors; growth stimulation ID B-CELLS; PROLIFERATION; CYTOKINE; MONOCYTE AB We have discovered a new cell surface protein in the form of interleukin-13 receptor on several solid tumor cells, including human renal cell carcinoma cells (Obiri et al,, 1995; Debinski et al., 1995). This study reports that human prostate cancer cell lines also express high affinity IL-13 receptors (Kd=159 pM). These receptors are functional because IL-13 surprisingly increased proliferation of all three prostate cancer cell lines studied as determined by thymidine uptake and clonogenic assays, IL-13 receptors on prostate cancer cell lines were targeted using a chimeric protein composed of IL-13 and a mutated form of Pseudomonas exotoxin (PE38QQR). This molecule, termed IL13-PE38QQR, has been found cytotoxic to all three prostate cancer cell Lines as determined by the inhibition of protein synthesis, The IC50 ranged between 1 nmol/l. to 15 nmol/l. These data were confirmed by clonogenic assays in which IL13-PE38QQR almost completely inhibited colony formation at 10 nmol/l. IL13-PE38QQR was not cytotoxic to cells that express little or no IL-13R. Heat inactivated IL13-PE38QQR was not cytotoxic to prostate cancer cells indicating specificity. IL13-PE38QQR was also cytotoxic to colonies when they were allowed to form first for several days before the addition of toxins. Our data suggest that additional studies should be performed to target IL-13 receptor bearing prostate cancer. C1 US FDA,LAB MOL TUMOR BIOL,DIV CELLULAR & GENE THERAPIES,CTR BIOL EVALUAT & RES,NIH,BETHESDA,MD 20892. SUNY SYRACUSE,HLTH SCI CTR,DEPT UROL,SYRACUSE,NY 13210. WAYNE STATE UNIV,SCH MED,DEPT UROL,DETROIT,MI 48202. PENN STATE UNIV,MILTON S HERSHEY MED CTR,COLL MED,DEPT SURG,DIV NEUROSURG,HERSHEY,PA 17033. NCI,MOL BIOL LAB,DIV CANC BIOL DIAG & CTR,BETHESDA,MD 20892. NR 25 TC 56 Z9 57 U1 0 U2 1 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0022-5347 J9 J UROLOGY JI J. Urol. PD SEP PY 1997 VL 158 IS 3 BP 948 EP 953 DI 10.1016/S0022-5347(01)64369-6 PN 1 PG 6 WC Urology & Nephrology SC Urology & Nephrology GA XP869 UT WOS:A1997XP86900077 PM 9258124 ER PT J AU Jeang, KT Derse, D Matocha, M Sharma, O AF Jeang, KT Derse, D Matocha, M Sharma, O TI Expression status of tax protein in human T-cell leukemia virus type 1-transformed MT4 cells: Recall of MT4 cells distributed by the NIH AIDS research and reference reagent program SO JOURNAL OF VIROLOGY LA English DT Editorial Material ID PRIMARY HUMAN-LYMPHOCYTES; HTLV-I; TRANSFORMATION; GENE C1 NIAID,AIDS RES & REFERENCE REAGENT PROGRAM,PATHOGENESIS & BASIC RES BRANCH,DIV AIDS,NIH,BETHESDA,MD 20892. NCI,LAB LEUKOCYTE BIOL,FCRDC,NIH,FREDERICK,MD 21701. RP Jeang, KT (reprint author), NIAID,MOL VIROL SECT,MOL MICROBIOL LAB,NIH,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. RI Jeang, Kuan-Teh/A-2424-2008 NR 18 TC 14 Z9 14 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 SEP PY 1997 VL 71 IS 9 BP 6277 EP 6278 PG 2 WC Virology SC Virology GA XQ799 UT WOS:A1997XQ79900001 PM 9261343 ER PT J AU Zhang, YM Imamichi, H Imamichi, T Lane, HC Falloon, J Vasudevachari, MB Salzman, NP AF Zhang, YM Imamichi, H Imamichi, T Lane, HC Falloon, J Vasudevachari, MB Salzman, NP TI Drug resistance during Indinavir therapy is caused by mutations in the protease gene and in its Gag substrate cleavage sites SO JOURNAL OF VIROLOGY LA English DT Article ID HIV PROTEASE; IN-VIVO; INHIBITOR; INFECTION; CELLS; SUSCEPTIBILITY; AIDS AB Two different responses to the therapy were observed in a group of patients receiving the protease inhibitor Indinavir. In one, suppression of virus replication occurred and has persisted for 90 weeks (bDNA, <500 human immunodeficiency virus type 1 [HIV-1] RNA copies/ml), In the second group, a rebound in virus levels in plasma followed the initial sharp decline observed al the start of therapy, This was associated with the emergence of drug-resistant variants, Sequence analysis of the protease gene during the course of therapy revealed that in this second group there was a sequential acquisition of protease mutations at amino acids 46, 82, 54, 71, 89, and 90, In the six patients in this group, there was also an identical mutation in the gag p7/p1 gag protease cleavage site, In three of the patients, this change was seen as early as 6 to 10 weeks after the start of therapy, In one patient, a second mutation occurred at the gag p1/p6 cleavage site, but it appeared 18 weeks after the time of appearance of the p7/p1 mutation, Recombinant HIV-1 variants containing two or three mutations in the protease gene were constructed either with mutations at the p7/p1 cleavage site or with wild-type (WT) gag sequences, When recombinant HIV-1 containing protease mutations at 46 and 82 was grown in MT2 cells, there was a 68% reduction in its rate of replication compared to the WT virus, Introduction of an additional mutation at the gag p7/p1 protease cleavage site compensated for the partially defective protease gene, Similarly, rates of replication of viruses with mutations M46L/I, I54V, and V82A in protease were enhanced both in the presence and in the absence of Indinavir when combined with mutations in the gag p7/p1 and the gag p1/p6 cleavage sites, Optimal rates of virus replication require protease cleavage of precursor polyproteins, A mutation in the cleavage site that enhanced the availability of a protein that was rate limiting for virus maturation would confer on that virus a significant growth advantage and may explain the uniform emergence of viruses with alterations at the p7/p1 cleavage site, This is the first report of the emergence of mutations in the gag p7/p1 protease cleavage sites in patients receiving protease therapy and identifies this change as an important determinant of HIV-1 resistance to protease inhibitors in patient populations. C1 NCI,SAIC FREDERICK,FREDERICK CANC RES & DEV CTR,FREDERICK,MD 21701. NIAID,IMMUNOREGULAT LAB,BETHESDA,MD 20892. NR 36 TC 256 Z9 262 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 SEP PY 1997 VL 71 IS 9 BP 6662 EP 6670 PG 9 WC Virology SC Virology GA XQ799 UT WOS:A1997XQ79900046 PM 9261388 ER PT J AU Valk, PJM Hol, S Vankan, Y Ihle, JN Askew, D Jenkins, NA Gilbert, DJ Copeland, NG deBoth, NJ Lowenberg, B Delwel, R AF Valk, PJM Hol, S Vankan, Y Ihle, JN Askew, D Jenkins, NA Gilbert, DJ Copeland, NG deBoth, NJ Lowenberg, B Delwel, R TI The genes encoding the peripheral cannabinoid receptor and alpha-L-fucosidase are located near a newly identified common virus integration site, Evi11 SO JOURNAL OF VIROLOGY LA English DT Article ID PROTEIN-COUPLED RECEPTOR; CELL-LINES; EXON AMPLIFICATION; RETROVIRAL INTEGRATION; VIRAL INTEGRATION; MYELOID-LEUKEMIA; GENOMIC DNA; LINKAGE MAP; CLONING; NEUROBLASTOMA AB A new common region of virus integration, Evi11, has been identified in two retrovirally induced murine myeloid leukemia cell lines, NFS107 and NFS78, By interspecific backcross analysis, it was shown that Evi11 is located at the distal end of mouse chromosome 4, in a region that shows: homolog with human 1p36, The genes encoding the peripheral cannabinoid receptor (Cnr2) and alpha-L-fucosidase (Fuca1) were identified near the integration site by using a novel exon trapping system, Cnr2 is suggested to be the target gene for viral interference in Evi11, since proviruses are integrated in the first intron of Cnr2 and retroviral integrations alter mRNA expression of Cnr2 in NFS107 and NFS78, In addition, proviral integrations were demonstrated within the 3' untranslated region of Cnr 2 in five independent newly derived CasBrM-MuLV (mouse murine leukemia virus) tumors, CSL13, CSL14 CSL16, CSL27, and CSL97. The Cnr2 gene encodes a seven-transmembrane G-protein-coupled receptor which is normally expressed in hematopoietic tissues, Our data suggest that the peripheral cannabinoid receptor gene might he involved in leukemogenesis as a result of aberrant expression of Cnr2 due to retroviral integration in Evi11. C1 ERASMUS UNIV ROTTERDAM, INST HEMATOL, NL-3000 DR ROTTERDAM, NETHERLANDS. ERASMUS UNIV ROTTERDAM, DEPT PATHOL, NL-3000 DR ROTTERDAM, NETHERLANDS. ST JUDE CHILDRENS RES HOSP, DEPT BIOCHEM, MEMPHIS, TN 38105 USA. UNIV CINCINNATI, DEPT PATHOL & LAB MED, CINCINNATI, OH 45267 USA. NCI, MAMMALIAN GENET LAB, ABL BASIC RES PROGRAM, FREDERICK CANC RES & DEV CTR, FREDERICK, MD 21702 USA. NR 55 TC 33 Z9 38 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 SEP PY 1997 VL 71 IS 9 BP 6796 EP 6804 PG 9 WC Virology SC Virology GA XQ799 UT WOS:A1997XQ79900062 PM 9261404 ER PT J AU Chiorini, JA Yang, L Liu, YJ Safer, B Kotin, RM AF Chiorini, JA Yang, L Liu, YJ Safer, B Kotin, RM TI Cloning of adeno-associated virus type 4 (AAV4) and generation of recombinant AAV4 particles SO JOURNAL OF VIROLOGY LA English DT Article ID TRANSMEMBRANE CONDUCTANCE REGULATOR; SITE-SPECIFIC INTEGRATION; ADENOASSOCIATED VIRUS; REP PROTEINS; BINDING-PROTEIN; GENE-EXPRESSION; ESCHERICHIA-COLI; CAPSID PROTEINS; HUMAN-CELLS; DNA AB We have cloned and characterized the full-length genome of adeno-associated virus type 4 (AAV4). The genome of AAV4 is 4,767 nucleotides in length and contains an expanded p5 promoter region compared to AAV2 and AAV3. Within the inverted terminal repeat (ITR), several base changes were identified with respect to AAV2. However, these changes did not affect the ability of this region to fold into a hairpin structure. Within the ITR, the terminal resolution site and Rep binding sites were conserved; however, the Rep binding site was expanded from three GAGC repeats to four. The Rep gene product of AAV4 shows greater than 90% homology to the Rep products of serotypes 2 and 3, with none of the changes occurring in regions which had previously been shown to affect the known functions of Rep68 or Rep78. Most of the differences in the capsid proteins lie in regions which are thought to be on the exterior surface of the viral capsid. It is these unique regions which are most likely to be responsible for the lack of cross-reacting antibodies and the altered tissue tropism compared to AAV2. The results of our studies, performed with a recombinant version of AAV4 carrying a lacZ reporter gene, suggest that AAV4 can transduce human, monkey, and rat cells. Furthermore, comparison of transduction efficiencies in a number of cell lines, competition cotransduction experiments, and the effect of trypsin on transduction efficiency all suggest that the cellular receptor for AAV4 is distinct from that of AAV2. C1 NHLBI,MOL HEMATOL BRANCH,NIH,BETHESDA,MD 20892. RI kotin, robert/B-8954-2008 NR 70 TC 169 Z9 171 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 SEP PY 1997 VL 71 IS 9 BP 6823 EP 6833 PG 11 WC Virology SC Virology GA XQ799 UT WOS:A1997XQ79900065 PM 9261407 ER PT J AU Cohen, JI Nguyen, H AF Cohen, JI Nguyen, H TI Varicella-Zoster virus glycoprotein I is essential for growth of virus in vero cells SO JOURNAL OF VIROLOGY LA English DT Article ID HERPES-SIMPLEX VIRUS; RAT VISUAL-SYSTEM; MEMBRANE-PROTEINS; GI; SPREAD; GPIV; GE; PHOSPHORYLATION; INFECTION; SEQUENCE AB Varicella-zoster virus (VZV) encodes at least six glycoproteins. Glycoprotein I (gI), the product of open reading frame 67, is a 58- to 62-kDa glycoprotein found in VZV-infected cells, We constructed two VZV gI deletion mutants, Immunoprecipitation of VZV gE from infected cells indicated that cells infected with VZV deleted for gI expressed a gE that was larger (100 kDa) than that expressed in cells infected with the parental virus (98 kDa). Cell-associated or cell-free VZV deleted for gI grew to lower titers in melanoma cells than did parental VZV, While VZV deleted for gI replicated in other human cells, the mutant virus replicated to very low titers in primary guinea pig and monkey cells and did not replicate in Vero cells. When compared with the parental virus, rescued viruses, in which the gI deletion was restored with a and-type allele, showed a similarly sized gE and comparable growth patterns in melanoma and Vero cells, VZV deleted for gI entered Vero cells; however, viral DNA synthesis was impaired in these cells. The VZV gI mutant was slightly impaired for adsorption to human cells. Thus, VZV gI is required for replication of the. virus in Vero cells, for efficient replication of the virus in nonhuman cells, and for normal processing of gE. RP Cohen, JI (reprint author), NIAID, MED VIROL SECT,CLIN INVEST LAB,NIH,BLDG 10, RM 11N214, BETHESDA, MD 20892 USA. NR 34 TC 48 Z9 51 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 SEP PY 1997 VL 71 IS 9 BP 6913 EP 6920 PG 8 WC Virology SC Virology GA XQ799 UT WOS:A1997XQ79900076 PM 9261418 ER PT J AU Fu, W OrtizConde, BA Gorelick, RJ Hughes, SH Rein, A AF Fu, W OrtizConde, BA Gorelick, RJ Hughes, SH Rein, A TI Placement of tRNA primer on the primer-binding site requires pol gene expression in avian but not murine retroviruses SO JOURNAL OF VIROLOGY LA English DT Article ID IMMUNODEFICIENCY-VIRUS TYPE-1; TRYPTOPHAN TRANSFER-RNA; LEUKEMIA-VIRUS; REVERSE-TRANSCRIPTASE; READ-THROUGH; VIRAL-RNA; SEQUENCE; REPLICATION; PARTICLES; GAG AB In an early step in the retroviral infectious process, reverse transcriptase copies the genomic RNA of the virus into complementary minus-strand DNA. The primer for this synthetic event is a molecule of cellular tRNA, which is annealed by its 3' 18 nucleotides to a region of the genomic RNA termed the primer-binding site (PBS); the sequence of the PBS and hence the identity of the tRNA depend upon the retrovirus species. In addition to the primer tRNA, retrovirus particles contain a substantial number of other tRNA molecules, The latter tRNA population is enriched for the tRNA species which serves as primer for the virus, While there is considerable evidence that the enrichment for the primer species can be attributed to the pol gene product, nothing is known regarding mechanisms of annealing the primer to the PBS, We have analyzed pol(-) mutants of avian leukosis virus (ALV) and murine leukemia virus (MuLV) for the presence of primer at the PBS in virion genomic RNA, Remarkably, the results were different for the two viruses: the PBS was substantially occupied by primer in MuLV but not in ALV, Previous data indicates that the Pol-dependent enrichment of the primer within the virion is much greater in ALV than in MuLV, We therefore propose that the absence of primer at the PBS in pol(-) ALV is due to the deficiency of the primer species within the particle, The results suggest that, at least in MuLV, the tRNA is unwound by either the Gag protein or a cellular protein for annealing to the PBS, Further, the C-terminal 17 amino acids of Gag are unnecessary for this function in MuLV. C1 NCI,FREDERICK CANC RES & DEV CTR,ABL BASIC RES PROGRAM,MOL VIROL & CARCINOGENESIS LAB,FREDERICK,MD 21702. NCI,FREDERICK CANC RES & DEV CTR,ABL BASIC RES PROGRAM,MOL BASIS CARCINOGENESIS LAB,FREDERICK,MD 21702. NCI,FREDERICK CANC RES & DEV CTR,ABL BASIC RES PROGRAM,SAIC,AIDS VACCINE PROGRAM,FREDERICK,MD 21702. NR 33 TC 34 Z9 34 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0022-538X J9 J VIROL JI J. Virol. PD SEP PY 1997 VL 71 IS 9 BP 6940 EP 6946 PG 7 WC Virology SC Virology GA XQ799 UT WOS:A1997XQ79900080 PM 9261422 ER PT J AU Cowan, EP Alexander, RK Daniel, S Kashanchi, F Brady, JN AF Cowan, EP Alexander, RK Daniel, S Kashanchi, F Brady, JN TI Induction of tumor necrosis factor alpha in human neuronal cells by extracellular human T-cell lymphotropic virus type 1 Tax(1) SO JOURNAL OF VIROLOGY LA English DT Article ID TROPICAL SPASTIC PARAPARESIS; I-ASSOCIATED MYELOPATHY; CENTRAL-NERVOUS-SYSTEM; CYTOTOXIC LYMPHOCYTES-T; TAX1 PROTEIN; NEUROLOGICAL DISEASE; LYMPHOID-CELLS; NTERA-2 CELLS; MOUSE-BRAIN; SPINAL-CORD AB To examine the role of human T-lymphotropic virus type 1 (HTLV-I) Tax(1) in the development of neurological disease, we studied the effects of extracellular Tax(1) on gene expression in NT2-N cells, postmitotic cells that share morphologic, phenotypic, and functional features with mature human primary neurons, Treatment with soluble HTLV-1 Tax(1) resulted in the induction of tumor necrosis factor alpha (TNF-alpha) gene expression, as detected by reverse-transcribed PCR and by enzyme-linked immunosorbent assay, TNF-alpha induction was completely blocked by clearance,vith anti-Tax(1) monoclonal antibodies, Furthermore, cells treated with either a mock bacterial extract or with lipopolysaccharide produced no detectable TNF-alpha, Synthesis of TNF-alpha in response to soluble Tax(1) occurred in a dose-dependent fashion between 0.25 and 75 nM and peaked within 6 h of treatment, Interestingly, culturing NT2-N cells in the presence of soluble Tax(1) for as little as 5 min was sufficient to result in TNF-alpha production, indicating that the induction of TNF-alpha in NT2-N does not require Tax(1) to be continually present in the culture medium, Treatment of the undifferentiated parental embryonal carcinoma cell line NT2 with soluble Tax(1) did not result in TNF-alpha synthesis, suggesting that differentiation-dependent, neuron-specific factors may be required, These results provide the first experimental evidence that neuronal cells are sensitive to HTLV-1 Tax(1) as an extracellular cytokine, with a potential role in the pathology of HTLV-1-associated/tropical spastic paraparesis. C1 US FDA,DIV TRANSFUS TRANSMITTED DIS,CTR BIOL EVALUAT & RES,ROCKVILLE,MD 20857. NATL CANC INST,MOL VIROL LAB,NATL INST HLTH,BETHESDA,MD. NR 42 TC 51 Z9 51 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 SEP PY 1997 VL 71 IS 9 BP 6982 EP 6989 PG 8 WC Virology SC Virology GA XQ799 UT WOS:A1997XQ79900085 PM 9261427 ER PT J AU Walker, SL Wonderling, RS Owens, RA AF Walker, SL Wonderling, RS Owens, RA TI Mutational analysis of the adeno-associated virus type 2 Rep68 protein helicase motifs SO JOURNAL OF VIROLOGY LA English DT Article ID SITE-SPECIFIC INTEGRATION; ADENOASSOCIATED VIRUS; NUCLEOTIDE-SEQUENCE; DNA-REPLICATION; WILD-TYPE; GENOMIC ORGANIZATION; DIRECT VISUALIZATION; ESCHERICHIA-COLI; TERMINAL REPEATS; BINDING MOTIF AB The adeno-associated virus type 2 (AAV) Rep78 and Rep68 proteins are required for viral replication, These proteins are encoded hv unspliced and spliced transcripts, respectively, from the p(5) promoter of AAV and therefore have overlapping amino acid sequences, The Rep78 and Rep68 proteins share a variety of activities including endonuclease, helicase, and ATPase activities and the ability to hind AAV hairpin DNA. The part of the amino acid sequence which is identical in Rep78 and Rep68 contains consensus helicase motifs that are conserved among the parvovirus replication proteins, In the present study, we mutated highly conserved amino acids within these helicase motifs. The mutant proteins were synthesized as maltose binding protein-Rep68 fusions in Escherichia coli cells and affinity purified on amylose resin, The fusion proteins were assayed in vitro, and their activities were directly compared to those of the fusion protein MDP-ReD68 Delta which contains most of the amino acid sequences common to Rep78 and Rep68 and was demonstrated previously to have all of the in vitro activities of wild-type Rep78 and Rep68. Our analysis showed that almost all mutations in the putative helicase motifs severely reduced or abolished helicase activity in vitro. Most mutants also had ATPase activity less than one-eighth of the wild-type levels and lacked endonuclease activity. C1 NIDDK,CELLULAR & MOL BIOL LAB,NATL INST HLTH,BETHESDA,MD 20892. NR 58 TC 45 Z9 45 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0022-538X J9 J VIROL JI J. Virol. PD SEP PY 1997 VL 71 IS 9 BP 6996 EP 7004 PG 9 WC Virology SC Virology GA XQ799 UT WOS:A1997XQ79900087 PM 9261429 ER PT J AU Lebedeva, I Fujita, K Nihrane, A Silver, J AF Lebedeva, I Fujita, K Nihrane, A Silver, J TI Infectious particles derived from Semliki Forest virus vectors encoding murine leukemia virus envelopes SO JOURNAL OF VIROLOGY LA English DT Article ID EXPRESSION VECTORS; GLYCOPROTEIN; ALPHAVIRUSES; RNA; PROTEINS; GENE AB Semliki Forest virus vectors encoding murine leukemia virus (MLV) envelope protein with a truncated cytoplasmic tail generate submicrometer, cell-associated, membranous particles that transmit replication competent vector RNA specifically to cells bearing the MLV receptor. Such ''minimal'' viruses could have applications as retroviral vaccines or in the study of virus evolution. C1 NIAID,MOL MICROBIOL LAB,NATL INST HLTH,BETHESDA,MD 20892. NR 27 TC 18 Z9 19 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 SEP PY 1997 VL 71 IS 9 BP 7061 EP 7067 PG 7 WC Virology SC Virology GA XQ799 UT WOS:A1997XQ79900094 PM 9261436 ER PT J AU Speck, RF Wehrly, K Platt, EJ Atchison, RE Charo, IF Kabat, D Chesebro, B Goldsmith, MA AF Speck, RF Wehrly, K Platt, EJ Atchison, RE Charo, IF Kabat, D Chesebro, B Goldsmith, MA TI Selective employment of chemokine receptors as human immunodeficiency virus type 1 coreceptors determined by individual amino acids within the envelope V3 loop SO JOURNAL OF VIROLOGY LA English DT Article ID SYNCYTIUM-INDUCING PHENOTYPE; CELL TROPISM; SUBSTITUTION; MACROPHAGES; INFECTIVITY; PROGRESSION; VARIANTS; DISEASE; DOMAIN; GENE AB The chemokine receptor CCR5 acts as an essential cofactor for cell entry by macrophage-tropic human immunodeficiency virus type 1 (HIV-1) strains, whereas CXCR4 acts as an essential cofactor for T-cell-line-adapted strains. We demonstrated that the specific amino acids in the V3 loop of the HIV-1 envelope protein that determine cellular tropism also regulate chemokine coreceptor preference for cell entry by the virus. Further, a strong correlation was found between HIV-1 strains classified as syncytium inducing in standard assays and those using CXCR4 as a coreceptor. These data support the hypothesis that progressive adaptation to additional coreceptors is a key molecular basis for HIV-1 phenotypic evolution in vivo. C1 GLADSTONE INST VIROL & IMMUNOL,SAN FRANCISCO,CA 94110. UNIV CALIF SAN FRANCISCO,GLADSTONE INST CARDIOVASC DIS,SAN FRANCISCO,CA 94141. UNIV CALIF SAN FRANCISCO,DEPT MED,SAN FRANCISCO,CA 94143. OREGON HLTH SCI UNIV,SCH MED,DEPT BIOCHEM & MOL BIOL,PORTLAND,OR 97201. NIAID,ROCKY MT LABS,PERSISTENT VIRAL DIS LAB,HAMILTON,MT 59840. RI Speck, Roberto/O-2433-2016 FU NCI NIH HHS [CA 67358] NR 39 TC 241 Z9 249 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0022-538X J9 J VIROL JI J. Virol. PD SEP PY 1997 VL 71 IS 9 BP 7136 EP 7139 PG 4 WC Virology SC Virology GA XQ799 UT WOS:A1997XQ79900109 PM 9261451 ER PT J AU DeOre, K Greig, NH Holloway, HW Wang, YH Perfetti, R Egan, JM AF DeOre, K Greig, NH Holloway, HW Wang, YH Perfetti, R Egan, JM TI The effects of GLP-1 on insulin release in young and old rats in the fasting state and during an intravenous glucose tolerance test SO JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL SCIENCES LA English DT Article ID GLUCAGON-LIKE PEPTIDE-1(7-37); PANCREATIC BETA-CELLS; DIABETES-MELLITUS; SECRETION; AGE; INCRETIN; POLYPEPTIDE; PHASE; AMIDE; GIP AB Glucose intolerance is a common feature of the aging process, and aging per se is an etiologic factor for Type II diabetes mellitus. To characterize the beta cell abnormalities that occur with aging, we looked at the serum glucose and insulin levels of sh young (3-month) and six old (22-month) Wistar rats at 0, 2, 4, 7, 10, 15, 20, and 30 minutes after an intravenous glucose load (IVGTT; 0.5g/kg glucose). We found that the fasting glucose and insulin levels were not significantly different between young and old rats. However, peak glucose levels were significantly higher in the old (349 + 10 mg/dl) compared to the young (250 +/- 7 mg/dl) animals (p <.0001). Insulin levels in the young animals peaked at 2 minutes (859 +/- 171 pmol/l) with a quick return toward fasting levels by 7 minutes. The old animals had a delayed and blunted insulin response to glucose, achieving lower peak insulin levels (656 +/- 164 pmol/l) 7 minutes after the glucose load. As insulin levels are also positively modulated by incretin hormones, we quantitated the fasting insulin responses of young and old animals to .05, 0.1, 0.2, 0.4, and 0.5 nmol/kg intravenous glucagon-like peptide-1 (GLP-1), the most potent incretin known. Insulin responses were similar in both age groups, with maximum insulin responses seen at 0.4 nmol/kg. GLP-1, in conjunction with the IVGTT restored the acute insulin response to glucose and increased the clearance of glucose in the old animals. It therefore appears that old animals have an impaired glucose-mediated insulin release but maintain their insulin responsivity to GLP-1. This makes it a likely candidate in the treatment of Type II diabetes. C1 NIA, GERONTOL RES CTR, DIABET SECT, BALTIMORE, MD 21224 USA. NIA, GERONTOL RES CTR, DRUG DESIGN & DEV SECT, BALTIMORE, MD 21224 USA. NR 27 TC 17 Z9 18 U1 0 U2 1 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1079-5006 EI 1758-535X J9 J GERONTOL A-BIOL JI J. Gerontol. Ser. A-Biol. Sci. Med. Sci. PD SEP PY 1997 VL 52 IS 5 BP B245 EP B249 PG 5 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA XX364 UT WOS:A1997XX36400004 PM 9310073 ER PT J AU Metter, EJ Conwit, R Tobin, J Fozard, JL AF Metter, EJ Conwit, R Tobin, J Fozard, JL TI Age-associated loss of power and strength in the upper extremities in women and men SO JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL SCIENCES LA English DT Article ID HUMAN SKELETAL-MUSCLES; DIFFERENT FIBER TYPES; HUMAN GROWTH-HORMONE; KNEE EXTENSION; MASS; PERFORMANCE; MORPHOLOGY; OLD; METABOLISM; VALIDITY AB Cross-sectional and longitudinal age-associated reductions in power and isometric strength are described for the upper extremities. Over a 25-year period repeated measures were taken approximately every 2 years from men and women in the Baltimore Longitudinal Study of Aging (BLSA). The longitudinal measures covered an average 9.6 years, range 1-25 years for men and an average 4.6 years, range 1-8 years for women. Strength and power declined beginning by age 40 ill both women and men. Thereafter, power declined about 10% more than strength in men, while Ilo significant differences were found in women. Age had a statistically independent influence on strength and power measures after adjusting for gender, height, weight, calorie expenditure, and muscle mass. Twenty-five-year longitudinal analyses ill men confirmed the declines observed cross-sectionally while Ilo charges were observed in women over the 4-5 years of longitudinal data available. Further longitudinal studies are needed to understand the relationships between strength and power losses whit age in women. The differences between power and strength changes with age in men argue for the importance of factors other than strength affecting power. C1 JOHNS HOPKINS BAYVIEW CTR, DEPT NEUROL, BALTIMORE, MD USA. RP Metter, EJ (reprint author), NIA, GERONTOL RES CTR, 4940 EASTERN AVE, BALTIMORE, MD 21224 USA. RI Fozard, James Leonard/B-3660-2009 NR 50 TC 188 Z9 193 U1 1 U2 11 PU GERONTOLOGICAL SOCIETY AMER PI WASHINGTON PA 1275 K STREET NW SUITE 350, WASHINGTON, DC 20005-4006 SN 1079-5006 J9 J GERONTOL A-BIOL JI J. Gerontol. Ser. A-Biol. Sci. Med. Sci. PD SEP PY 1997 VL 52 IS 5 BP B267 EP B276 PG 10 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA XX364 UT WOS:A1997XX36400008 PM 9310077 ER PT J AU Ferrucci, L Guralnik, JM Buchner, D Kasper, J Lamb, SE Simonsick, EM Corti, MC BandeenRoche, K Fried, LP AF Ferrucci, L Guralnik, JM Buchner, D Kasper, J Lamb, SE Simonsick, EM Corti, MC BandeenRoche, K Fried, LP TI Departures from linearity in the relationship between measures of muscular strength and physical performance of the lower extremities: The Women's Health and Aging Study SO JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL SCIENCES LA English DT Article ID OLDER ADULTS; DISABILITY; EXERCISE; BALANCE; MUSCLE; GAIT; VELOCITY; PEOPLE; CHAIR; AGE AB Background. Sarcopenia, an age-related reduction in muscular mass and strength, may cause a decline in physical functioning and subsequent loss of autonomy. It has been suggested that strength is associated with lower extremity function mainly in the lower portion of the range of strength. Identifying the threshold under which strength is most critical to function may help in targeting groups who may benefit most fi:om exercise interventions. Methods, The study uses data from the Women's Health and Aging Study. The study population, recruited by screening a population-based sample aged 65 years and older, comprised 1,002 women who represent the one-third most disabled women without severe cognitive impairment living in the community. Knee extensor and hip flexor strength were assessed using a hand-held dynamometer. Lower extremity performance was evaluated using rests of walking, standing balance, and rising from a chair. Results. Among women tested for strength (n = 892), those who could walk (97%), do the side-by-side stand (87%), or complete 5 chair stands (74%) had significantly greater strength. Walking speed was linearly associated with knee extensor strength over the entire range of strength, but its association with hip strength was limited to values below 15 kg. Time for five chair stands was associated with knee extensor and hip flexor strength below 10 and 15 kg, respectively, and no significant association was detected above these values. Stronger women were more likely to hold balance for 10 sec in the side-by-side, semi-tandem, and tandem positions. The percentage of the variance in performance explained by strength alone was always lower than 20%. Conclusions, In this population, which does not include the strongest older women, there is a departure from linearity in the relationship between muscular strength and some measures of lower extremity performance. C1 I FRATICINI NATL RES INST,INRCA,DEPT GERIATR,FLORENCE,ITALY. UNIV WASHINGTON,DEPT HLTH SERV,SEATTLE,WA 98195. JOHNS HOPKINS UNIV,SCH HYG & PUBL HLTH,DEPT HLTH POLICY & MANAGEMENT,BALTIMORE,MD. JOHNS HOPKINS UNIV,SCH HYG & PUBL HLTH,DEPT BIOSTAT,BALTIMORE,MD 21205. JOHNS HOPKINS MED INST,SCH MED,DEPT MED & EPIDEMIOL,BALTIMORE,MD 21205. RP Ferrucci, L (reprint author), NIA,EPIDEMIOL DEMOG & BIOMETRY PROGRAM,7201 WISCONSIN AVE,GATEWAY BLDG,SUITE 3C-309,BETHESDA,MD 20892, USA. NR 34 TC 160 Z9 162 U1 2 U2 7 PU GERONTOLOGICAL SOCIETY AMER PI WASHINGTON PA 1275 K STREET NW SUITE 350, WASHINGTON, DC 20005-4006 SN 1079-5006 J9 J GERONTOL A-BIOL JI J. Gerontol. Ser. A-Biol. Sci. Med. Sci. PD SEP PY 1997 VL 52 IS 5 BP M275 EP M285 PG 11 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA XX364 UT WOS:A1997XX36400012 PM 9310081 ER PT J AU Simonsick, EM Maffeo, CE Rogers, SK Skinner, EA Davis, D Guralnik, JM Fried, LP AF Simonsick, EM Maffeo, CE Rogers, SK Skinner, EA Davis, D Guralnik, JM Fried, LP TI Methodology and feasibility of a home-based examination in disabled older women: The Women's Health and Aging Study SO JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL SCIENCES LA English DT Article ID FUNCTIONAL REACH; MARKER; RISK AB Background. To ascertain disease and functional capacity in community-resident disabled older women in the Women's Health and Aging Study (WHAS), a prospective investigation of the causes and course of disability, a home-based standardized physical examination and performance test battery were developed. Thirty-nine tests were administered, 9 by a lay interviewer and 30 by a nurse. This scope and intensity of testing had not been performed previously in a home environment or on such a functionally limited population. Thus, substantial developmental work was required. This report describes the administrative procedures and field experience for each exam component, highlighting innovations pertinent to home administration. Methods. Exclusion criteria, safety issues, administration time, completion rates, and reasons for incomplete data are reported. Administration time is based on 30 exams conducted over a 3-week period 90% of the way through baseline data collection. Completion status was determined using all 1,002 participants and is categorized as follows: complete; partial; not done, health; not done, other; and refused. Results, Seventy-two percent of the screened, eligible respondents completed the 30-min interviewer-administered physical assessment and thr 2-hr, 10-min nurse examination. Classifiable data were obtained for 90% of participants on 36 examination items. Lower completion rates were obtained on the other three tests primarily due to exclusions for health-related conditions; environmental constraints and participant refusal were minimal. Conclusion. Extensive, research-oriented physical evaluation can be successfully and safely performed in a home setting. In future studies, home-based examination may be preferable, as participation in the WHAS examination substantially exceeded rates for clinic-based exams in similar populations. C1 WESTAT CORP,ROCKVILLE,MD. JOHNS HOPKINS UNIV,INST MED,BALTIMORE,MD 21218. RP Simonsick, EM (reprint author), NIA,EPIDEMIOL DEMOG & BIOMETRY PROGRAM,GATEWAY BLDG,SUITE 3C-309,BETHESDA,MD 20892, USA. NR 31 TC 76 Z9 76 U1 11 U2 11 PU GERONTOLOGICAL SOCIETY AMER PI WASHINGTON PA 1275 K STREET NW SUITE 350, WASHINGTON, DC 20005-4006 SN 1079-5006 J9 J GERONTOL A-BIOL JI J. Gerontol. Ser. A-Biol. Sci. Med. Sci. PD SEP PY 1997 VL 52 IS 5 BP M264 EP M274 PG 11 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA XX364 UT WOS:A1997XX36400011 PM 9310080 ER PT J AU Meslin, EM Thomson, EJ Boyer, JT AF Meslin, EM Thomson, EJ Boyer, JT TI The ethical, legal, and social implications research program at the National Human Genome Research Institute SO KENNEDY INSTITUTE OF ETHICS JOURNAL LA English DT Article RP Meslin, EM (reprint author), NIH,ETH LEGAL & SOCIAL IMPLICAT RES PROGRAM,NATL HUMAN GENOME RES INST,BETHESDA,MD 20892, USA. NR 16 TC 32 Z9 33 U1 0 U2 2 PU JOHNS HOPKINS UNIV PRESS PI BALTIMORE PA JOURNALS PUBLISHING DIVISION, 2715 NORTH CHARLES ST, BALTIMORE, MD 21218-4319 SN 1054-6863 J9 KENNEDY INST ETHIC J JI Kennedy Inst. Ethics J. PD SEP PY 1997 VL 7 IS 3 BP 291 EP 298 PG 8 WC Ethics; Philosophy; Social Issues SC Social Sciences - Other Topics; Philosophy; Social Issues GA XV813 UT WOS:A1997XV81300006 PM 11660360 ER PT J AU Kopple, JD Levey, AS Greene, T Chumlea, WC Gassman, JJ Hollinger, DL Maroni, BJ Merrill, D Scherch, LK Schulman, G Wang, SR Zimmer, GS AF Kopple, JD Levey, AS Greene, T Chumlea, WC Gassman, JJ Hollinger, DL Maroni, BJ Merrill, D Scherch, LK Schulman, G Wang, SR Zimmer, GS TI Effect of dietary protein restriction on nutritional status in the Modification of Diet in Renal Disease Study SO KIDNEY INTERNATIONAL LA English DT Article DE dietary protein; MDRD Study; chronic renal failure; malnutrition; anthropometry; serum albumin ID MAINTENANCE HEMODIALYSIS-PATIENTS; CREATININE METABOLISM; DIALYSIS PATIENTS; MUSCLE MASS; AMINO-ACID; FAILURE; PROGRESSION; METAANALYSIS; INTERVENTION; REDUCTION AB The safety of dietary protein and phosphorous restriction was evaluated in the Modification of Diet in Renal Disease (MDRD) Study, In Study A, 585 patients with a glomerular filtration rate (GFR) of 25 to 55 ml/min/1.73 m(2) were randomly assigned to a usual-protein diet (1.3 g/kg/day) or a low-protein diet (0.58 g/kg/day). In Study B, 255 patients with a GFR of 13 to 24 ml/min/1.73 m(2) were randomly assigned to the low-protein diet or a very-low-protein diet (0.28 g/kg/day), supplemented with a ketoacid-amino acid mixture (0.28 g/kg/day). The low-protein and very-low-protein diets were also low in phosphorus. Mean duration of follow-up was 2.2 years in both studies. Protein and energy intakes were lower in the low-protein and very-low-protein diet groups than in the usual-protein group. Two patients in Study B reached a ''stop point'' for malnutrition. There was no difference between randomized groups in the rates of death, first hospitalizations, or other ''stop points'' in either study. Mean values for various indices of nutritional status remained within the normal range during follow-up in each diet group. However, there were small but significant changes from baseline in some nutritional indices, and differences between the randomized groups in some of these changes. In the low-protein and very-low-protein diet groups, serum albumin rose, while serum transferrin, body wt, percent body fat, arm muscle area and urine creatinine excretion declined. Combining patients in both diet groups in each study, a lower achieved protein intake (from food and supplement) was not correlated with a higher rate of death, hospitalization or stop points, or with a progressive decline in any of the indices of nutritional status after controlling for baseline nutritional status and follow-up energy intake. These analyses suggest that the low-protein and very-low-protein diets used in the MDRD Study are safe for periods of two to three years. Nonetheless, both protein and energy intake declined and there were small but significant declines in various indices of nutritional status. These declines are of concern because of the adverse effect of protein calorie malnutrition in patients with end-stage renal disease. Physicians who prescribe low-protein diets must carefully monitor patients' protein and energy intake and nutritional status. C1 NIDDKD,NIH,BETHESDA,MD 20892. NR 55 TC 127 Z9 138 U1 1 U2 3 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 SN 0085-2538 J9 KIDNEY INT JI Kidney Int. PD SEP PY 1997 VL 52 IS 3 BP 778 EP 791 DI 10.1038/ki.1997.395 PG 14 WC Urology & Nephrology SC Urology & Nephrology GA XT549 UT WOS:A1997XT54900025 PM 9291200 ER PT J AU Stokes, WS AF Stokes, WS TI A prickly issue SO LAB ANIMAL LA English DT Editorial Material RP Stokes, WS (reprint author), NATL INST ENVIRONM HLTH SCI,ENVIRONM TOXICOL PROGRAM,RES TRIANGLE PK,NC 27709, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING CO PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 SN 0093-7355 J9 LAB ANIMAL JI Lab Anim. PD SEP PY 1997 VL 26 IS 8 BP 24 EP 25 PG 2 WC Veterinary Sciences SC Veterinary Sciences GA XV353 UT WOS:A1997XV35300004 ER PT J AU Cara, A Reitz, MS AF Cara, A Reitz, MS TI New insight on the role of extrachromosomal retroviral DNA SO LEUKEMIA LA English DT Review DE HIV-1; extrachromosomal DNA; integrase; transcription vaccinia ID HUMAN-IMMUNODEFICIENCY-VIRUS; UNINTEGRATED HIV-1 DNA; MURINE LEUKEMIA-VIRUS; T-CELL ACTIVATION; VIRAL-DNA; TYPE-1 INTEGRASE; ANTIRETROVIRAL THERAPY; PROVIRAL INTEGRATION; NUCLEAR-LOCALIZATION; IN-VIVO AB During infection with different retroviruses, high levels of unintegrated extrachromosomal DNA accumulate in infected cells. While extrachromosomal linear DNA is the immediate precursor of the integrated provirus, the function, if any, of extrachromosomal circular DNA has been unclear. Several groups have attempted to address the possible function, activity, and importance of this unintegrated DNA during the life cycle of retroviruses and the course of retroviral-associated diseases. This review summarizes recent work in this field and tries to analyze some aspects of extrachromosomal forms of retroviral DNA and their possible application as a molecular biological tool. C1 NCI,BASIC RES LABS,NIH,BETHESDA,MD 20892. UNIV MARYLAND,INST BIOTECHNOL,INST HUMAN VIROL,BALTIMORE,MD 21201. SCH MED,BALTIMORE,MD 21201. RI Cara, Andrea/M-4865-2015 OI Cara, Andrea/0000-0003-4967-1895 NR 48 TC 34 Z9 34 U1 0 U2 2 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE, HAMPSHIRE, ENGLAND RG21 6XS SN 0887-6924 J9 LEUKEMIA JI Leukemia PD SEP PY 1997 VL 11 IS 9 BP 1395 EP 1399 DI 10.1038/sj.leu.2400776 PG 5 WC Oncology; Hematology SC Oncology; Hematology GA XU704 UT WOS:A1997XU70400001 PM 9305590 ER PT J AU Murugesan, R Cook, JA Devasahayam, N Afeworki, M Subramanian, S Tschudin, R Larsen, JA Mitchell, JB Russo, A Krishna, MC AF Murugesan, R Cook, JA Devasahayam, N Afeworki, M Subramanian, S Tschudin, R Larsen, JA Mitchell, JB Russo, A Krishna, MC TI In vivo imaging of a stable paramagnetic probe by pulsed-radiofrequency electron paramagnetic resonance spectroscopy SO MAGNETIC RESONANCE IN MEDICINE LA English DT Article DE pulsed EPR; EPR imaging; in vivo EPR; free radical ID NITRIC-OXIDE GENERATION; SPIN-RESONANCE; HEART; SPECTROMETER; MOUSE AB Imaging of free radicals by electron paramagnetic resonance (EPR) spectroscopy using time domain acquisition as in nuclear magnetic resonance (NMR) has not been attempted because of the short spin-spin relaxation times, typically under 1 mu s, of most biologically relevant paramagnetic species. Recent advances in radiofrequency (RF) electronics have enabled the generation of pulses of the order of 10-50 ns. Such short pulses provide adequate spectral coverage for EPR studies at 300 MHz resonant frequency, Acquisition of free induction decays (FID) of paramagnetic species possessing inhomogenously broadened narrow lines after pulsed excitation is feasible with an appropriate digitizer/averager. This report describes the use of time-domain RF EPR spectrometry and imaging for in vivo applications, FID responses were collected from a water-soluble, narrow line width spin probe within phantom samples in solution and also when infused intravenously in an anesthetized mouse. Using static magnetic field gradients and back-projection methods of image reconstruction, two-dimensional images of the spin-probe distribution were obtained in phantom samples as well as in a mouse. The resolution in the images was better than 0.7 mm and devoid of motional artifacts in the in vivo study. Results from this study suggest a potential use for pulsed RF EPR imaging (EPRI) for three-dimensional spatial and spectral-spatial imaging applications. In particular, pulsed EPRI may find use in in vivo studies to minimize motional artifacts from cardiac and lung motion that cause significant problems in frequency-domain spectral acquisition, such as in continuous wave (cw) EPR techniques. C1 NCI,RADIAT BIOL BRANCH,DIV CLIN SCI,NIH,BETHESDA,MD 20892. NYCOMED INNOVAT AB,MALMO,SWEDEN. RI Ardenkjar-Larsen, Jan Henrik/B-5765-2017 OI Ardenkjar-Larsen, Jan Henrik/0000-0001-6167-6926 NR 30 TC 60 Z9 61 U1 0 U2 3 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0740-3194 J9 MAGNET RESON MED JI Magn.Reson.Med. PD SEP PY 1997 VL 38 IS 3 BP 409 EP 414 DI 10.1002/mrm.1910380309 PG 6 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA XW162 UT WOS:A1997XW16200008 PM 9339442 ER PT J AU Jiang, RL Copeland, NG Gilbert, DJ Jenkins, NA Gridley, T AF Jiang, RL Copeland, NG Gilbert, DJ Jenkins, NA Gridley, T TI Genomic organization and chromosomal localization of the mouse snail (Sna) gene SO MAMMALIAN GENOME LA English DT Article ID EXPRESSION; SUGGESTS; HOMOLOG C1 JACKSON LAB,BAR HARBOR,ME 04609. NCI,FREDERICK CANC RES & DEV CTR,ABL BASIC RES PROGRAM,MAMMALIAN GENET LAB,FREDERICK,MD 21702. FU NCI NIH HHS [CA34196]; NHGRI NIH HHS [HG00330] NR 16 TC 9 Z9 10 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 SEP PY 1997 VL 8 IS 9 BP 686 EP 688 DI 10.1007/s003359900537 PG 3 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity GA XR258 UT WOS:A1997XR25800011 PM 9271672 ER PT J AU Morishige, K Takumi, T Takahashi, N Koyama, H Kurachi, H Miyake, A Murata, Y Copeland, NG Gilbert, DJ Jenkins, NA Kurachi, Y AF Morishige, K Takumi, T Takahashi, N Koyama, H Kurachi, H Miyake, A Murata, Y Copeland, NG Gilbert, DJ Jenkins, NA Kurachi, Y TI Assignment of the murine inwardly rectifying potassium channel IRK3 gene (Kcnj4) to the mouse Chromosome 15 SO MAMMALIAN GENOME LA English DT Article ID FUNCTIONAL EXPRESSION; MOLECULAR-CLONING; LINKAGE MAP; BRAIN; DISEASE C1 OSAKA UNIV,FAC MED,DEPT PHARMACOL 2,SUITA,OSAKA 565,JAPAN. OSAKA UNIV,FAC MED,DEPT OBSTET & GYNECOL,SUITA,OSAKA 565,JAPAN. NIPPON VET & ANIM SCI UNIV,DEPT VET INTERNAL MED,MUSASHINO,TOKYO 180,JAPAN. NCI,FREDERICK CANC RES & DEV CTR,ABL BASIC RES PROGRAM,MAMMALIAN GENET LAB,FREDERICK,MD 21702. NR 13 TC 0 Z9 0 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 SEP PY 1997 VL 8 IS 9 BP 699 EP 700 PG 2 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity GA XR258 UT WOS:A1997XR25800017 PM 9271678 ER PT J AU Raimond, J Zimonjic, DB Mignon, C Mattei, MG Popescu, NC Monsigny, M Legrand, A AF Raimond, J Zimonjic, DB Mignon, C Mattei, MG Popescu, NC Monsigny, M Legrand, A TI Mapping of the galectin-3 gene (LGALS3) to human Chromosome 14 at region 14q21-22 SO MAMMALIAN GENOME LA English DT Article ID MOLECULAR-CLONING; BINDING PROTEIN; LOCALIZATION; HYBRIDIZATION; GALACTOSE C1 CNRS,CTR BIOPHYS MOL,F-45071 ORLEANS 2,FRANCE. UNIV ORLEANS,F-45071 ORLEANS 2,FRANCE. NCI,EXPT CARCINOGENESIS LAB,BETHESDA,MD 20892. HOP ENFANTS LA TIMONE,F-13385 MARSEILLE 5,FRANCE. NR 9 TC 32 Z9 33 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 SEP PY 1997 VL 8 IS 9 BP 706 EP 707 DI 10.1007/s003359900548 PG 2 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity GA XR258 UT WOS:A1997XR25800024 PM 9271684 ER PT J AU Favara, BE Feller, AC Pauli, M Jaffe, ES Weiss, LM Arico, M Bucsky, P Egeler, RM Elinder, G Gadner, H Gresik, M Henter, JI Imashuku, S JankaSchaub, G Jaffe, R Ladisch, S Nezelof, C Pritchard, J AF Favara, BE Feller, AC Pauli, M Jaffe, ES Weiss, LM Arico, M Bucsky, P Egeler, RM Elinder, G Gadner, H Gresik, M Henter, JI Imashuku, S JankaSchaub, G Jaffe, R Ladisch, S Nezelof, C Pritchard, J TI Contemporary classification of histiocytic disorders SO MEDICAL AND PEDIATRIC ONCOLOGY LA English DT Article DE histiocytosis; histiocytic neoplasms; Langerhans cell histiocytosis; hemophagocytic syndrome; histiocytes ID LANGERHANS-CELL HISTIOCYTOSIS; ROSAI-DORFMAN-DISEASE; MALIGNANT HISTIOCYTOSIS; HEMOPHAGOCYTIC SYNDROME; SINUS-HISTIOCYTOSIS; HODGKINS-DISEASE; INDETERMINATE CELLS; ACUTE-LEUKEMIA; LYMPHOMA; PHENOTYPE AB Pathologists and pediatric hematologist/oncologists of the World Health Organization's Committee on Histiocytic/Reticulum Cell Proliferations and the Reclassification Working Group of the Histiocyte Society present a classification of the histiocytic disorders that primarily affect children. Nosology, based on the lineage of lesional cells and biological behavior, is related to the ontogeny of histiocytes (macrophages and dendritic cells of the immune system). Dendritic cell-related disorders of varied biological behavior are dominated by Langerhans cell histiocytosis, but separate secondary proliferations of dendritic cells must be differentiated. Juvenile xanthogranuloma represents a disorder of dermal dendrocytes, another dendritic cell of skin. The hemophagocytic syndromes are the most common of the macrophage-related disorders of varied biological behavior. Guidelines for distinguishing the exceedingly rare malignant diseases of histiocytes from large cell lymphomas through the use of a battery of special studies are provided. (C) 1997 Wiley-Liss, Inc. RP Favara, BE (reprint author), NIH,ROCKY MT LABS,PERSISTENT VIRAL DIS LAB,HAMILTON,MT 59840, USA. RI Feller, Alfred/E-3853-2010 NR 66 TC 481 Z9 513 U1 0 U2 13 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0098-1532 J9 MED PEDIATR ONCOL JI Med. Pediatr. Oncol. PD SEP PY 1997 VL 29 IS 3 BP 157 EP 166 DI 10.1002/(SICI)1096-911X(199709)29:3<157::AID-MPO1>3.0.CO;2-C PG 10 WC Oncology; Pediatrics SC Oncology; Pediatrics GA XH257 UT WOS:A1997XH25700001 PM 9212839 ER PT J AU Cheever, AW AF Cheever, AW TI Differential regulation of granuloma size and hepatic fibrosis in schistosome infections SO MEMORIAS DO INSTITUTO OSWALDO CRUZ LA English DT Article; Proceedings Paper CT V International Symposium on Schistosomiasis CY OCT 10, 1995 CL SALVADOR, BRAZIL DE schistosomiasis; granulomatous inflammation; fibrosis ID TH2 CYTOKINES; MANSONI; MICE; ANTIBODIES; JAPONICUM; STRAINS; CELLS; IMMUNOREGULATION; EOSINOPHILIA; PATHOLOGY AB Granuloma size is the variable most frequently used to evaluate the immunopathogenesis of schistosome infections. However, hepatic fibrosis is at the least an equally relevant variable. Hepatic fibrosis and the size of circumoval granulomas are frequently dissociates in experimental murine Schistosoma mansoni and S-japonicum infections. Virtually nothing is known of the immunoregulation of schistosomal hepatic fibrosis. This review notes many of the studies which have found discrepancies in granuloma volume and hepatic fibrosis, attempts to put them in perspective and to evaluate different methods of calculating changes in collagen synthesis or content. C1 NIAID,PARASIT DIS LAB,BETHESDA,MD 20892. RP Cheever, AW (reprint author), BIOMED RES INST,12111 PARKLAWN DR,ROCKVILLE,MD 20852, USA. NR 25 TC 14 Z9 15 U1 0 U2 2 PU FUNDACO OSWALDO CRUZ PI RIO DE JANEIRO, RJ PA AV BRASIL 4365, 21045-900 RIO DE JANEIRO, RJ, BRAZIL SN 0074-0276 J9 MEM I OSWALDO CRUZ JI Mem. Inst. Oswaldo Cruz PD SEP-OCT PY 1997 VL 92 IS 5 BP 689 EP 692 DI 10.1590/S0074-02761997000500024 PG 4 WC Parasitology; Tropical Medicine SC Parasitology; Tropical Medicine GA XU937 UT WOS:A1997XU93700024 PM 9566240 ER PT J AU Deitsch, KW Moxon, ER Wellems, TE AF Deitsch, KW Moxon, ER Wellems, TE TI Shared themes of antigenic variation and virulence in bacterial, protozoal, and fungal infections SO MICROBIOLOGY AND MOLECULAR BIOLOGY REVIEWS LA English DT Review ID VARIANT SURFACE GLYCOPROTEIN; INFLUENZAE TYPE-B; TRANSFERRIN-BINDING PROTEIN; OUTER-MEMBRANE PROTEIN; GENE-EXPRESSION SITE; PLASMODIUM-FALCIPARUM MALARIA; RELAPSING FEVER BORRELIA; WHITE-OPAQUE TRANSITION; HUMAN ENDOTHELIAL-CELLS; HUMAN EPITHELIAL-CELLS AB Pathogenic microbes have evolved highly sophisticated mechanisms for colonizing host tissues and evading ol deflecting assault by the immune response. The ability of these microbes to avoid clearance prolongs infection, thereby promoting their long-term survival within individual hosts and through transmission, between hosts. Many pathogens are capable of extensive antigenic changes in the face of the multiple constitutive and dynamic components of host immune defenses. As a result, highly diverse populations that have widely different virulence properties can arise from a single infecting organism (clone). in this review, we consider the molecular and genetic features of antigenic variation and corresponding host-parasite interactions of different pathogenic bacterial, fungal, and protozoan microorganisms. The host and microbial molecules involved in these interactions often determine the adhesive, invasive, and antigenic properties of the infecting organisms and can dramatically affect the virulence and pathobiology of individual infections. Pathogens capable of such antigenic variation exhibit mechanisms of rapid mutability in confined chromosomal regions containing specialized genes designated contingency genes. The mechanisms of hypermutability of contingency genes are common to a variety of bacterial and eukaryotic pathogens and include promoter alterations reading-frame shifts, gene conversion events, genomic rearrangements, and point mutations. C1 NIAID,PARASIT DIS LAB,NIH,BETHESDA,MD 20892. UNIV OXFORD,JOHN RADCLIFFE HOSP,DEPT PAEDIAT,OXFORD OX3 9DU,ENGLAND. JOHN RADCLIFFE HOSP,INST MOL MED,OXFORD OX3 9DU,ENGLAND. NR 192 TC 176 Z9 178 U1 2 U2 4 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 1092-2172 J9 MICROBIOL MOL BIOL R JI Microbiol. Mol. Biol. Rev. PD SEP PY 1997 VL 61 IS 3 BP 281 EP & PG 14 WC Microbiology SC Microbiology GA XU950 UT WOS:A1997XU95000001 PM 9293182 ER PT J AU Lujan, HD Mowatt, MR Nash, TE AF Lujan, HD Mowatt, MR Nash, TE TI Mechanisms of Giardia lamblia differentiation into cysts SO MICROBIOLOGY AND MOLECULAR BIOLOGY REVIEWS LA English DT Review ID LEUCINE-RICH-REPEAT; STEROL REGULATORY ELEMENT; SECRETORY VESICLE FORMATION; ACETYL-D-GLUCOSAMINE; FIELD-EMISSION SEM; FUNGAL CELL-WALL; BILE-SALT UPTAKE; PRIMITIVE EUKARYOTE; ENDOPLASMIC-RETICULUM; TRANSCRIPTION FACTOR AB Microbiologists have long been intrigued by the ability of parasitic organisms to adapt to changes in the environment. Since most parasites occupy several niches during their journey between vectors and hosts, they have developed adaptive responses which allow them to survive under adverse conditions. Therefore, the life cycles of protozoan and helminthic parasites are excellent models with which to study numerous mechanisms involved in cell differentiation, such as the regulation of gene expression, signal transduction pathways, and organelle biogenesis. Unfortunately, many of these studies ar-e very difficult because the conditions needed to elicit developmental changes in parasites remain undetermined in most cases. Recently, several interesting findings were reported on the process of differentiation of Giardia lamblia trophozoites into cysts. G. lamblia is a flagellated protozoan that inhabits the upper small intestine of its vertebrate host and is a major cause of enteric disease worldwide. It belongs to the earliest identified lineage among eukaryotes and therefore offers a unique insight into the progression from primitive to more complex eukaryotic cells. The discovery of a specific stimulus that induces trophozoites to differentiate into cysts, the identification and characterization of encystation-specific molecules, the elucidation of novel biochemical pathways, and the development of useful reagents and techniques have made this parasite an excellent model with which to study differentiation in eukaryotic cells. In this review, we summarize the most recent findings on several aspects of Giardia differentiation and discuss the significance of these findings within the context of current knowledge in the field. C1 NIAID, PARASIT DIS LAB, NIH, BETHESDA, MD 20892 USA. NATL UNIV CORDOBA, SCH MED, DEPT BIOL CHEM, CORDOBA, ARGENTINA. NR 165 TC 115 Z9 115 U1 2 U2 12 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 1092-2172 J9 MICROBIOL MOL BIOL R JI Microbiol. Mol. Biol. Rev. PD SEP PY 1997 VL 61 IS 3 BP 294 EP + PG 0 WC Microbiology SC Microbiology GA XU950 UT WOS:A1997XU95000002 PM 9293183 ER PT J AU Ren, RF Hawver, DB Kim, RS Flanders, KC AF Ren, RF Hawver, DB Kim, RS Flanders, KC TI Transforming growth factor-beta protects human hNT cells from degeneration induced by beta-amyloid peptide: involvement of the TGF-beta type II receptor SO MOLECULAR BRAIN RESEARCH LA English DT Article DE hNT cell; beta-amyloid peptide; Alzheimer's disease; neuroprotection; Transforming growth factor-beta; TGF-beta type II receptor ID RAT HIPPOCAMPAL-NEURONS; ALZHEIMERS-DISEASE; EXPRESSION CLONING; COMPLEMENTARY-DNA; PRECURSOR PROTEIN; NERVOUS-SYSTEM; MESSENGER-RNA; NTERA-2 CELLS; MOUSE EMBRYO; TGF-BETA-1 AB Post-mitotic, human neurons (hNT cells) which have a phenotype similar to that of terminally differentiated neurons of the central nervous system were generated by treating the NT2/D1 human teratocarcinoma cell line with retinoic acid. Treatment of both hNT and NT2/D1 cells with 10(-5) M beta-amyloid peptide fragment 25-35 (A beta P) for 24 h resulted in a decrease in cell viability as determined by MTT incorporation and Trypan blue exclusion, and also induced an apoptotic morphology in hNT cells. Pre-treatment of cells for 24 h with 10 ng/ml TGF-beta 1 or 2 before addition of A beta P reduced the apoptotic morphology of hNT cells and increased cell viability in hNT cells, but not in NT2/D1 cells. Results of RT-PCR, immunohistochemistry and analysis of receptor cross-linking of [I-125]TGF-beta 1 to the cell membrane, all showed that the TGF-beta type II receptor is expressed by hNT cells, but not NT2/D1 cells. These results suggest that TGF-beta can protect human, terminally differentiated, TGF-beta type II receptor-positive neurons from A beta P toxicity. We propose that the increased expression of TGF-beta in brains of patients with Alzheimer's disease may offer some degree of neuroprotection if neurons also express a functional TGF-beta type II receptor. C1 NCI, CHEMOPREVENT LAB, BETHESDA, MD 20892 USA. NIMH, EXPT THERAPEUT BRANCH, BETHESDA, MD 20892 USA. NR 46 TC 32 Z9 34 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 SEP PY 1997 VL 48 IS 2 BP 315 EP 322 DI 10.1016/S0169-328X(97)00108-3 PG 8 WC Neurosciences SC Neurosciences & Neurology GA XV868 UT WOS:A1997XV86800015 ER PT J AU Trempus, CS Haseman, JK Tennant, RW AF Trempus, CS Haseman, JK Tennant, RW TI Decreases in phorbol ester-induced papilloma development in v-Ha-ras transgenic TG.AC mice during reduced gene dosage of bcl-2 SO MOLECULAR CARCINOGENESIS LA English DT Article; Proceedings Paper CT 2nd International Experimental Skin Carcinogenesis Conference CY OCT 28-31, 1996 CL BASTROP, TX DE apoptosis; multi-stage carcinogenesis; papillomagenesis; skin cancer ID TUMOR-SUPPRESSOR GENES; CELL-DEATH; MOUSE SKIN; INDUCED APOPTOSIS; EXPRESSION; PROTEIN; CANCER; ASSOCIATION; PROMOTION; CARCINOMA AB We have demonstrated that induction of transgene expression in the v-Ha-ras-transgenic TG.AC mouse is a critical event in skin tumorigenesis and that cutaneous papillomas arise from follicular epidermis after treatment with chemical carcinogens. The sensitivity of TG.AC mice to skin tumorigenesis, coupled with their low incidence of spontaneous skin tumors, makes this strain a good model for identifying carcinogens and for investigating the roles that other genes may play in the development of skin neoplasia. To investigate the possible involvement of the bcl-2 gene in skin tumorigenesis in the TG.AC mouse, we crossed heterozygous bcl-2-knockout mice (C57Bl/6, 129 background) with TG.AC mice (FVB/N background). Female mice were genotyped by using a neo cassette to identify bcl-2-deficient mice. In addition, homozygous TG.AC mice were bred with FVB/N mice to generate hemizygous TG.AC mice on an FVB/N background to serve as a gene-dosage control. The F-1 progeny consisted of FVB/Nv-Ha-ras+/-:C57Bl/6, 129(bcl-2+/+), FVB/Nv-Ha-ras+/-:C57Bl/6, 129(bcl-2+/-), and FVB/N-v-Ha-ras+/-,N-bcl-2+/+. Ten-week-old mice were dosed twice weekly for 10 wk with acetone, 1.25 mu g of 7,12-tetradecanoylphorbol-13-acetate (TPA), or 2.5 mu g of TPA, and papillomas were counted weekly. Papillomas were analyzed for ras transgene and bcl-2 expression by reverse transcription-polymerase chain reaction, v-Ha-ras expression by in situ hybridization, and proliferating cell nuclear antigen expression by immunohistochemical analysis. Fewer papillomas (P < 0.05) were observed at the low dose of TPA (1.25 mu g) in mice carrying the bcl-2 knockout allele than in the wild-type mice, suggesting that reduction of the bcl-2 gene product affects the susceptibility of TG.AC mice to TPA-induced papillomas. However, at the high dose of TPA (2.5 Gig), there was no difference in papilloma response between knockout and wild-type mice, regardless of strain background. This suggests that at the higher dose of TPA, the effect of reduction in bcl-2 gene product was obscured. These results support the hypothesis that bcl-2 plays a limited role in skin tumorigenesis in the TG.AC mouse. (C) 1997 Wiley-Liss, Inc.dagger C1 NIEHS,LAB ENVIRONM CARCINOGENESIS & MUTAGENESIS,RES TRIANGLE PK,NC 27709. NIEHS,STAT & BIOMATH BRANCH,RES TRIANGLE PK,NC 27709. NR 59 TC 12 Z9 12 U1 0 U2 3 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0899-1987 J9 MOL CARCINOGEN JI Mol. Carcinog. PD SEP PY 1997 VL 20 IS 1 BP 68 EP 77 DI 10.1002/(SICI)1098-2744(199709)20:1<68::AID-MC8>3.0.CO;2-E PG 10 WC Biochemistry & Molecular Biology; Oncology SC Biochemistry & Molecular Biology; Oncology GA XZ343 UT WOS:A1997XZ34300008 PM 9328437 ER PT J AU Rutberg, SE Lee, EJ Hansen, LH Glick, AB Yuspa, SH AF Rutberg, SE Lee, EJ Hansen, LH Glick, AB Yuspa, SH TI Identification of differentially expressed genes in chemically induced skin tumors SO MOLECULAR CARCINOGENESIS LA English DT Article; Proceedings Paper CT 2nd International Experimental Skin Carcinogenesis Conference CY OCT 28-31, 1996 CL BASTROP, TX DE differential display; skin carcinogenesis; AP-1 regulation; bcl-2 ID MOUSE EPIDERMAL-CELLS; MALIGNANT CONVERSION; DISPLAY TECHNIQUE; V-FOS; SPLICING FACTOR-SF2; BINDING-PROTEINS; BCL-2 EXPRESSION; MEMBRANE PROTEIN; B-CELLS; RNA AB Previous studies have demonstrated a role for the fos gene in promoting malignant conversion of mouse skin tumors. In the study reported here, differential display was performed to identify fos- and jun-regulated genes that are differentially expressed during premalignant progression. Total RNA isolated from variants of the papilloma cell line SP-1 transduced with retroviral vectors expressing v-jun and v-fos alone or in tandem was analyzed for the presence of differentially expressed transcripts by using 35 different primer combinations. Differentially expressed clones were rescreened by dot-blot analysis by using cDNA from chemically induced tumors with a high or low risk of malignant conversion. Three differentially displayed fragments were isolated in this analysis. Homology searches indicated that these fragments shared significant homology with the apoptosis inhibitor bcl-2, human alternative splicing factor/splicing factor 2 (ASF/SF2), a nd a novel gene not present in the GenBank or EMBL databases. In situ hybridization indicated that the expression levels of the bcl-2 homolog increased with malignant potential in chemically derived mouse skin tumors. A similar analysis indicated that expression of the ASF/SF2 homolog was greater in papillomas than in normal skin or in squamous cell carcinomas. Transcripts for this gene were most abundant in the granular layer. The expression pattern of the third differential display fragment was consistent with that of a tumor suppressor gene. This gene was expressed at very high levels in normal skin and benign papillomas but was essentially undetectable in squamous cell carcinomas. Through this approach, we identified known and novel genes that may contribute to malignant progression in epidermal tumors. (C) 1997 Wiley-Liss, Inc. C1 NCI,CELLULAR CARCINOGENESIS & TUMOR PROMOT LAB,BETHESDA,MD 20892. NR 65 TC 14 Z9 15 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0899-1987 J9 MOL CARCINOGEN JI Mol. Carcinog. PD SEP PY 1997 VL 20 IS 1 BP 88 EP 98 DI 10.1002/(SICI)1098-2744(199709)20:1<88::AID-MC10>3.0.CO;2-5 PG 11 WC Biochemistry & Molecular Biology; Oncology SC Biochemistry & Molecular Biology; Oncology GA XZ343 UT WOS:A1997XZ34300010 PM 9328439 ER PT J AU Cannon, RE Spalding, JW Trempus, CS Szczesniak, CJ Virgil, KM Humble, MC Tennant, RW AF Cannon, RE Spalding, JW Trempus, CS Szczesniak, CJ Virgil, KM Humble, MC Tennant, RW TI Kinetics of wound-induced v-Ha-ras transgene expression and papilloma development in transgenic Tg.AC mice SO MOLECULAR CARCINOGENESIS LA English DT Article; Proceedings Paper CT 2nd International Experimental Skin Carcinogenesis Conference CY OCT 28-31, 1996 CL BASTROP, TX DE Tg.AC transgenic mice; wound repair; gene expression; skin cancer; tumorigenesis ID TUMOR PROMOTION; MOUSE SKIN; STEM-CELLS; CARCINOGENESIS; ACTIVATION; MECHANISM AB The Tg.AC transgenic mouse, which harbors an activated v-Ha-ras coding region that is fused to an embryonic zeta globin transcriptional control region and a 3' simian virus 40 polyadenylation sequence, rapidly develops epidermal papillomas in response to topical application of chemical carcinogens or tumor promoters or to full-thickness wounding of the dorsal skin. In this report, we investigated the localization and temporal induction of v-Ha-ras transgene expression after full-thickness wounding of Tg.AC mouse skin. Surgically inflicted full-thickness incisions 3 cm long yielded four to six papillomas per Tg.AC mouse by 5 wk after wounding. Similar wounding of the FVB/N isogenic host strain did not produce tumors, which implicates a causal role for the v-Ha-ras transgene. Reverse transcription-polymerase chain reaction assays detected the v-Ha-ras transgene transcript in total RNA samples isolated from wound-associated tissue 3 and 4 wk after wounding. Tissues 1-2 wk after wounding and all non-wound-associated tissues were negative for transgene expression. In situ hybridization experiments using transgene-specific S-35-labeled antisense RNA probes localized transgene expression to the basal epidermal cells in wound-induced papillomas. Adjacent normal and hyperplastic skin tissues were negative for transgene expression by this assay. This work supports the hypothesis that the wound repair response leads to the transcriptional activation and continued expression of the v-Ha-ras transgene in specific cells in the skin, which alters normal epithelial differentiation and ultimately results in neoplastic growth. (C) 1997 Wiley-Liss, Inc.dagger RP Cannon, RE (reprint author), NIEHS,LAB ENVIRONM CARCINOGENESIS & MUTAGENESIS,POB 12233,RES TRIANGLE PK,NC 27709, USA. NR 20 TC 45 Z9 46 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0899-1987 J9 MOL CARCINOGEN JI Mol. Carcinog. PD SEP PY 1997 VL 20 IS 1 BP 108 EP 114 DI 10.1002/(SICI)1098-2744(199709)20:1<108::AID-MC12>3.0.CO;2-5 PG 7 WC Biochemistry & Molecular Biology; Oncology SC Biochemistry & Molecular Biology; Oncology GA XZ343 UT WOS:A1997XZ34300012 PM 9328441 ER PT J AU Kim, TW Porter, KL Foley, JF Maronpot, RR Smart, RC AF Kim, TW Porter, KL Foley, JF Maronpot, RR Smart, RC TI Evidence that mirex promotes a unique population of epidermal cells that cannot be distinguished by their mutant Ha-ras genotype SO MOLECULAR CARCINOGENESIS LA English DT Article; Proceedings Paper CT 2nd International Experimental Skin Carcinogenesis Conference CY OCT 28-31, 1996 CL BASTROP, TX DE skin; keratinocytes; proliferating cell nuclear antigen; BrdU; carcinogenesis ID MOUSE SKIN CARCINOGENESIS; DNA POLYMERASE-DELTA; TUMOR PROMOTION; STEM-CELLS; PAPILLOMAS; ANAGEN; 12-O-TETRADECANOYLPHORBOL-13-ACETATE; PROLIFERATION; PROGRESSION; EXPRESSION AB Mirex is a potent tumor promoter in 7,12-dimethylbenz[a]anthracene (DMBA)-initiated female CD-1 mouse skin. Like 12-O-tetradecanoylphorbol-13-acetate (TPA), mirex promotes papillomas that have a Ha-ras mutation; however, unlike TPA promotion, mirex promotion does not involve a general hyperplastic response. We used proliferating cell nuclear antigen (PCNA) and 5-bromo-2'-deoxyuridine (BrdU) immunohistochemical staining to further examine the proliferative capacity of mirex. The numbers of PCNA- and BrdU-positive epidermal S-phase cells were highly concordant in all treatment groups. Unlike a single application of TPA, a single application of mirex had little or no effect on the number of S-phase epidermal cells, and chronic application of mirex to mouse skin produced only minimal increases in S-phase cells. Moreover, mirex did not significantly alter the growth of BALB/MK-2 keratinocytes in media containing either 0.05 or 1.2 mM Ca++. These results suggest that mirex may have highly specific effects on the proliferation of initiated cells and support the existence of a unique mirex mechanism and/or distinct population of mirex-promotable mutant Ha-ras epidermal cells. To begin to address this issue of a distinct population of mirex-promotable mutant Ha-ras cells, we conducted a tandem experiment in which DMBA-initiated mice were treated twice weekly with a maximal promoting dose of mirex. Then, when the number of papillomas reached a plateau, these same mice were treated twice weekly with a maximal promoting dose of TPA. Mice treated with mirex developed a maximum of 6.4 papillomas/mouse. These mice were then promoted with TPA, which produced 8.9 additional papillomas/mouse for a total of 15.3 papillomas/mouse. The maximum tumor yields from other groups of mice treated with only TPA or mirex were 9.8 and 7.3 papillomas/mouse, respectively. Therefore, under these tandem conditions, tumor yields were additive, indicating that there are at least two distinct populations of mutant Ha-ras cells: one promoted by mirex and the other by TPA. (C) 1997 Wiley-Liss, Inc. C1 N CAROLINA STATE UNIV,DEPT TOXICOL,RALEIGH,NC 27695. NIEHS,RES TRIANGLE PK,NC 27709. RI Porter, Karen/A-9591-2009 FU NCI NIH HHS [CA46637]; NIEHS NIH HHS [ES08127] NR 25 TC 11 Z9 11 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0899-1987 J9 MOL CARCINOGEN JI Mol. Carcinog. PD SEP PY 1997 VL 20 IS 1 BP 115 EP 124 DI 10.1002/(SICI)1098-2744(199709)20:1<115::AID-MC13>3.0.CO;2-4 PG 10 WC Biochemistry & Molecular Biology; Oncology SC Biochemistry & Molecular Biology; Oncology GA XZ343 UT WOS:A1997XZ34300013 PM 9328442 ER PT J AU Hennings, H Lowry, DT Yuspa, SH Mock, B Potter, M AF Hennings, H Lowry, DT Yuspa, SH Mock, B Potter, M TI New strains of inbred SENCAR mice with increased susceptibility to induction of papillomas and squamous cell carcinomas in skin SO MOLECULAR CARCINOGENESIS LA English DT Article; Proceedings Paper CT 2nd International Experimental Skin Carcinogenesis Conference CY OCT 28-31, 1996 CL BASTROP, TX DE skin tumors; inbred susceptible mice; squamous cell carcinoma; papilloma; tumor initiation; tumor promotion; SENCAR mice; susceptibility genes ID MALIGNANT CONVERSION; TUMOR PROMOTION; MOUSE SKIN; CHEMICAL CARCINOGENESIS; FEMALE SENCAR; CD-1 MICE; RESISTANT; LINES; DISSOCIATION; PROGRESSION AB To develop mouse strains useful for studies of susceptibility and resistance to the induction of skin tumors, three new inbred SENCAR strains were independently derived by random inbreeding of outbred SENCAR mice. Characterization of these mice for sensitivity to skin tumor development indicated that mice of all three strains displayed increased sensitivity to initiation by 7,12-dimethylbenz[a]anthracene (DMBA), urethane, or N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) and promotion by 12-O-tetradecanoylphorbol-13-acetate (TPA). Promotion by mezerein as well as carcinogenesis by repeated treatment with DMBA or MNNG produced papillomas with a high frequency of conversion to squamous cell carcinomas (SCCs). Compared with outbred SENCAR mice, development of both squamous papillomas and carcinomas was increased at least two-fold by all protocols tested. The F-1 hybrid between SENCARA/Pt males and resistant BALB/cAnPt females was resistant to the induction of both papillomas and SCCs after initiation by 2 mu g of DMBA and promotion by 20 weekly applications of 2 mu g of TPA. Papillomas developed in all of the SENCARA/Pt mice, none of the BALB/cAnPt mice, and 12% of the F-1 progeny. Thus, at these doses of initiator and promoter, resistance was incompletely dominant in the F-1 hybrid. However, the responsiveness of the F-1 mice could be increased substantially by increasing the dose of the promoter. (C) 1997 Wiley-Liss, Inc.dagger C1 NCI,GENET LAB,BETHESDA,MD 20892. RP Hennings, H (reprint author), NCI,CELLULAR CARCINOGENESIS & TUMOR PROMOT LAB,BLDG 37,ROOM 3B26,BETHESDA,MD 20892, USA. NR 27 TC 21 Z9 21 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0899-1987 J9 MOL CARCINOGEN JI Mol. Carcinog. PD SEP PY 1997 VL 20 IS 1 BP 143 EP 150 DI 10.1002/(SICI)1098-2744(199709)20:1<143::AID-MC16>3.0.CO;2-1 PG 8 WC Biochemistry & Molecular Biology; Oncology SC Biochemistry & Molecular Biology; Oncology GA XZ343 UT WOS:A1997XZ34300016 PM 9328445 ER PT J AU Elenkov, IJ Hoffman, J Wilder, RL AF Elenkov, IJ Hoffman, J Wilder, RL TI Does differential neuroendocrine control of cytokine production govern the expression of autoimmune diseases in pregnancy and the postpartum period? SO MOLECULAR MEDICINE TODAY LA English DT Editorial Material ID PITUITARY-ADRENAL AXIS; INTERLEUKIN-10; TH2; CELLS; GLUCOCORTICOIDS; PLACENTA; INCREASE; SYSTEM; STRESS; BLOOD AB 'Pregnancy and the postpartum period are associated with significant changes in levels of several hormones, such as estrogen, progesterone, cortisol and possibly catecholamines, Moreover, several autoimmune diseases such as rheumatoid arthritis tend to remit, develop or exacerbate during pregnancy or the postpartum period, Thus, the question arises: are the changes in the hormones and the expression of autoimmune diseases during these periods causally linked, or are these associations an epiphenomenon? Here we suggest that a causal link might be provided through differential neuroendocrine regulation of Th1-type and Th2-type cytokine production. RP Elenkov, IJ (reprint author), NIAMSD,INFLAMMATORY JOINT DIS SECT,ARTHRITIS & RHEUMATISM BRANCH,NIH,BLDG 10,ROOM 10N262,BETHESDA,MD 20892, USA. NR 25 TC 59 Z9 63 U1 2 U2 3 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, OXON, ENGLAND OX5 1GB SN 1357-4310 J9 MOL MED TODAY JI Mol. Med. Today PD SEP PY 1997 VL 3 IS 9 BP 379 EP 383 PG 5 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA XW161 UT WOS:A1997XW16100007 PM 9302687 ER PT J AU Youngren, B Austin, S AF Youngren, B Austin, S TI Altered ParA partition proteins of plasmid P1 act via the partition site to block plasmid propagation SO MOLECULAR MICROBIOLOGY LA English DT Review ID UNIT-COPY MINIPLASMIDS; DAUGHTER CELLS; HOST FACTOR; SYSTEM; SEGREGATION; SPECIFICITY; REGION; DNA AB The partition system of the P1 plasmid, P1par, consists of the ParA and ParB proteins and a cis-acting site, parS. It is responsible for the orderly segregation of plasmid copies to daughter cells. Plasmids with null mutations in parA or parB replicate normally, but missegregate. ParB binds specifically to the parS site, but the role of ParA and its ATPase activity in partition is unclear. We describe a novel class of parA mutants that cannot be established or maintained as plasmids unless complemented by the wild-type gene. One, parAM314I, is conditional: it can be maintained in cells in minimal medium but cannot be established in cells growing in L broth. The lack of plasmid propagation in L broth-grown cells was shown to be caused by a ParB-dependent activity of the mutant ParA protein that blocks plasmid propagation by an interaction at the parS site. Thus, ParA acts to modify the ParB-parS complex, probably by binding to it. Partition is thought to involve selection of pairs of plasmids before segregation, either by physical pairing of copies or by binding of copies to paired host sites. We suggest that ParA is involved in this reaction and that the mutant ParA protein forms paired complexes that cannot unpair. C1 NCI,FREDERICK CANC RES & DEV CTR,ABL BASIC RES PROGRAM,FREDERICK,MD 21702. NR 22 TC 31 Z9 31 U1 1 U2 1 PU BLACKWELL SCIENCE LTD PI OXFORD PA P O BOX 88, OSNEY MEAD, OXFORD, OXON, ENGLAND OX2 0NE SN 0950-382X J9 MOL MICROBIOL JI Mol. Microbiol. PD SEP PY 1997 VL 25 IS 6 BP 1023 EP 1030 DI 10.1046/j.1365-2958.1997.4761842.x PG 8 WC Biochemistry & Molecular Biology; Microbiology SC Biochemistry & Molecular Biology; Microbiology GA YA907 UT WOS:A1997YA90700003 PM 9350860 ER PT J AU Zhang, JH Belardinelli, L Jacobson, KA Otero, DH Baker, SP AF Zhang, JH Belardinelli, L Jacobson, KA Otero, DH Baker, SP TI Persistent activation by and receptor reserve for an irreversible A(1)-adenosine receptor agonist in DDT1MF-2 cells and in guinea pig heart SO MOLECULAR PHARMACOLOGY LA English DT Article ID ADENOSINE A(3) RECEPTORS; MUSCARINIC RECEPTOR; ADENYLATE-CYCLASE; RADIOLIGAND BINDING; PHOSPHOLIPASE-C; MF-2 CELLS; RAT-BRAIN; STIMULATION; ANTAGONIST; HYDROLYSIS AB The p- and m-isothiocyanate adenosine derivatives N-6-[4-[[[4[[[[2-[[[(p-(m)-isothiocyanatophenyl)amino]thiocarboynyl]amino]ethyl]amino]carbonyl]methyl]anilino]carbonyl]methyl]phenyl]adenosine (p- and m-DITC-ADAC) were examined for irreversible agonist effects at the A(1)-adenosine receptor (A(1)-AdoR) in DDT1 MF-2 (DDT) cells and a functional A(1)-AdoR response in the guinea pig isolated heart. The p- and m-DITC-ADAC inhibited (-)-isoproterenol stimulated cAMP accumulation in DDT cells in the low nanomolar range, and the maximal responses elicited by both compounds were similar to that for N-6-cyclopentyladenosine. Once established, the p-DITC-ADAC-mediated inhibition of cAMP accumulation in DDT cells was not affected by the addition of the AdoR antagonist 8-cyclopentyl-1,3-dipropylxanthine (CPX). Pretreatment of DDT cells with p-DITC-ADAC (1 mu M), followed by washing, reduced [H-3]CPX binding to the A(1)-AdoR by 44% without altering the K-d value for the radioligand to the remaining receptors. The relationship between irreversible A(1)-AdoR occupancy by p-DITC-ADAC and inhibition of cAMP accumulation revealed a relatively large receptor reserve (64%) for the maximal response. In guinea pig isolated hearts, m-DITC-ADAC (5 mu M) prolonged the stimulus to His bundle (SH) interval by 2.1-fold; this response could be prevented by the antagonist 8-cyclopentyltheophylline (5 mu M). However, after the SH interval prolongation was established, extensive washout or the addition of 8-cyclopentyltheophylline had little reversal effect on the m-DITC-ADAC response. Binding of [H-3]CPX to the guinea pig ventricular membranes after m-DITC-ADAC treatment and washing was reduced by 35%. The A(1)-AdoR occupancy response relationship for m-DITC-ADAC to prolong the SH interval indicated a small (10-20%) receptor reserve. Both p- and m-DITC-ADAC seem to be irreversible full agonists at the A(1)-AdoR and may prove to be useful probes to further investigate A(1)-AdoR structure-function relationships. C1 UNIV FLORIDA,DEPT PHARMACOL,GAINESVILLE,FL 32610. UNIV FLORIDA,DEPT MED,GAINESVILLE,FL 32610. NIDDKD,BIOORGAN CHEM LAB,NIH,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]; NHLBI NIH HHS [HL35272] NR 38 TC 16 Z9 16 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0026-895X J9 MOL PHARMACOL JI Mol. Pharmacol. PD SEP PY 1997 VL 52 IS 3 BP 491 EP 498 PG 8 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA XV853 UT WOS:A1997XV85300019 PM 9281612 ER PT J AU Jiang, QL Guo, DP Lee, BX VanRhee, AM Kim, YC Nicholas, RA Schachter, JB Harden, TK Jacobson, KA AF Jiang, QL Guo, DP Lee, BX VanRhee, AM Kim, YC Nicholas, RA Schachter, JB Harden, TK Jacobson, KA TI A mutational analysis of residues essential for ligand recognition at the human P2Y(1) receptor SO MOLECULAR PHARMACOLOGY LA English DT Article ID PROTEIN-COUPLED RECEPTORS; SITE-DIRECTED MUTAGENESIS; ADENOSINE RECEPTORS; P-2Y-PURINOCEPTOR AGONISTS; 3-DIMENSIONAL MODELS; PHOSPHOLIPASE-C; BINDING-SITE; AMINO-ACIDS; PURINOCEPTORS; IDENTIFICATION AB We conducted a mutational analysis of residues potentially involved in the adenine nucleotide binding pocket of the human P2Y(1) receptor. Mutated receptors were expressed in COS-7 cells with an epitope tag that permitted confirmation of expression in the plasma membrane, and agonist-promoted inositol phosphate accumulation was assessed as a measure of receptor activity. Residues in transmembrane helical domains (TMs) 3, 5, 6, and 7 predicted by molecular modeling to be involved in ligand recognition were replaced with alanine and, in some cases, by other amino acids. The potent P2Y(1) receptor agonist 2-methylthio-ATP (2-MeSATP) had no activity in cells expressing the R128A, R310A, and S314A mutant receptors, and a markedly reduced potency of 2-MeSATP was observed with the K280A and Q307A mutants. These results suggest that residues on the exofacial side of TM3 and TM7 are critical determinants of the ATP binding pocket. In contrast, there was no change in the potency or maximal effect of 2-MeSATP with the S317A mutant receptor. Alanine replacement of F131, H132, Y136, F226, or H277 resulted in mutant receptors that exhibited a 7-18-fold reduction in potency compared with that observed with the wild-type receptor. These residues thus seem to subserve a less important modulatory role in ligand binding to the P2Y(1) receptor. Because changes in the potency of 2-methylthio-ADP and 2-(hexylthio)-AMP paralleled the changes in potency of 2-MeSATP at these mutant receptors, the beta- and gamma-phosphates of the adenine nucleotides seem to be less important than the alpha-phosphate in ligand/P2Y(1) receptor interactions. However, T221A and T222A mutant receptors exhibited much larger reductions in triphosphate (89- and 33-fold versus wild-type receptors, respectively) than in diphosphate or monophosphate potency. This result may be indicative of a greater role of these TM5 residues in gamma-phosphate recognition. Taken together, the results suggest that the adenosine and alpha-phosphate moieties of ATP bind to critical residues in TM3 and TM7 on the exofacial side of the human P2Y(1) receptor. C1 NIDDK,MOL RECOGNIT SECT,BIOORGAN CHEM LAB,BETHESDA,MD 20892. UNIV N CAROLINA,SCH MED,DEPT PHARMACOL,CHAPEL HILL,NC 27599. RI Jacobson, Kenneth/A-1530-2009 OI Jacobson, Kenneth/0000-0001-8104-1493 FU Intramural NIH HHS [Z01 DK031116-20, Z99 DK999999] NR 34 TC 95 Z9 95 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0026-895X J9 MOL PHARMACOL JI Mol. Pharmacol. PD SEP PY 1997 VL 52 IS 3 BP 499 EP 507 PG 9 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA XV853 UT WOS:A1997XV85300020 PM 9281613 ER PT J AU Licinio, J Gold, PW Chrousos, GP Sternberg, EM AF Licinio, J Gold, PW Chrousos, GP Sternberg, EM TI Forty years of neuroendocrinology: a tribute to SM McCann SO MOLECULAR PSYCHIATRY LA English DT Editorial Material C1 NICHHD,PEDIAT ENDOCRINOL SECT,DEV ENDOCRINOL BRANCH,NIH,BETHESDA,MD 20892. RP Licinio, J (reprint author), NIMH,UNIT CLIN RES,CLIN NEUROENDOCRINOL BRANCH,INTRAMURAL RES PROGRAM,NIH,BLDG 10,RM 2D46,BETHESDA,MD 20892, USA. RI Licinio, Julio/L-4244-2013 OI Licinio, Julio/0000-0001-6905-5884 NR 0 TC 0 Z9 0 U1 0 U2 0 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE, HAMPSHIRE, ENGLAND RG21 6XS SN 1359-4184 J9 MOL PSYCHIATR JI Mol. Psychiatr. PD SEP PY 1997 VL 2 IS 5 BP 347 EP 349 DI 10.1038/sj.mp.4000330 PG 3 WC Biochemistry & Molecular Biology; Neurosciences; Psychiatry SC Biochemistry & Molecular Biology; Neurosciences & Neurology; Psychiatry GA XX285 UT WOS:A1997XX28500001 PM 9322221 ER PT J AU Webster, EL Elenkov, IJ Chrousos, GP AF Webster, EL Elenkov, IJ Chrousos, GP TI The role of corticotropin-releasing hormone in neuroendocrine-immune interactions SO MOLECULAR PSYCHIATRY LA English DT Review DE stress; hypothalamus; pituitary; adrenal; T helper; catecholamines; glucocorticoids; cellular immunity; humoral immunity; inflammation ID BLOOD MONONUCLEAR-CELLS; FACTOR RECEPTORS; NERVOUS-SYSTEM; MOUSE SPLEEN; SECRETION; GLUCOCORTICOIDS; IDENTIFICATION; LOCALIZATION; MACROPHAGES; CYTOKINES AB Neuroendocrine-immune interactions are profoundly regulated by corticotropin-releasing hormone (CRH) indirectly, through activation of a global stress response, and directly, through pro-inflammatory actions on peripheral immune functions. The indirect effects of stress on immune/inflammatory responses occur via the stress-induced activation of the hypothalamic-pituitary-adrenal (HPA) axis and the sympathetic/adrenomedullary system. We have demonstrated that glucocorticoids and catecholamines favor T helper 2 (TH2) over T helper 1 (TH1) immune cells and mediators, by controlling the production of specific key regulatory cytokines. This could explain the influences of chronic stress on the development, course, and pathology of certain allergic, autoimmune/inflammatory, infectious, and neoplastic diseases. We have also shown that 'immune CRH' is secreted peripherally and plays a direct immunomodulatory role as an autocrine or paracrine mediator of inflammation. Upon release from immune cells and peripheral sensory afferent and/or postganglionic sympathetic nerves, CRH acts locally to elicit pro-inflammatory responses. This would explain the triggering or exacerbation of certain allergic or vasokinetic states by acute stress. RP Webster, EL (reprint author), NICHHD,DEB,PEDIAT ENDOCRINOL SECT,NIH,BLDG 10,ROOM 10N262,10 CTR DR MSC 1862,BETHESDA,MD 20892, USA. NR 37 TC 40 Z9 40 U1 0 U2 0 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE, HAMPSHIRE, ENGLAND RG21 6XS SN 1359-4184 J9 MOL PSYCHIATR JI Mol. Psychiatr. PD SEP PY 1997 VL 2 IS 5 BP 368 EP & DI 10.1038/sj.mp.4000305 PG 7 WC Biochemistry & Molecular Biology; Neurosciences; Psychiatry SC Biochemistry & Molecular Biology; Neurosciences & Neurology; Psychiatry GA XX285 UT WOS:A1997XX28500005 PM 9322225 ER PT J AU Yoshikawa, T Turner, G Esterling, LE Sanders, AR DeteraWadleigh, SD AF Yoshikawa, T Turner, G Esterling, LE Sanders, AR DeteraWadleigh, SD TI A novel human myo-inositol monophosphatase gene, IMP.18p, maps to a susceptibility region for bipolar disorder SO MOLECULAR PSYCHIATRY LA English DT Article DE chromosome 18; lithium; linkage; radiation hybrid mapping ID CHROMOSOME-18; MECHANISM; MARKERS; LINKAGE; LITHIUM; TARGET AB Within the broad susceptibility region for bipolar disorder on the pericentromeric portion of chromosome 18, the highest allele sharing in our 22-pedigree series has been found in markers mapping to 18p11.2. Studies by other investigators on independently ascertained pedigrees have also shown increased sharing in this region, making 18p11.2 a plausible site for a candidate gene search, We found expressed sequence tags (ESTs) mapping within this area that are homologous to the myoinositol-1-phosphate phosphohydrolase (myo-inositol monophosphatase: IMP) gene of Xenopus laevis, Since IMP has been proposed to be the potential target of lithium, a drug commonly used for the treatment of bipolar disorder, we proceeded to characterize the cognate transcript, Northern blot analysis detected a major transcript of 1.5 kb with abundant expression in adult and fetal tissues, but minimal expression in whole brain, In subcortical brain regions, however, substantial levels of transcript were evident, most prominently in the caudate, We have isolated and sequenced the full-length cDNA. The deduced amino acid sequence revealed similar to 54% identity with an existing human IMP, which we found mapped to chromosome 8, and IMP of other species, The sequence also included motifs characteristic of the IMP gene family, To provide a more precise location of this gene, mapping with a panel of radiation hybrids (RH) was conducted, Multipoint RH analysis placed the gene between GNAL and D18S71 within the 18p11.2 region, We, therefore, designated this novel gene as IMP.18p. The physical position and possible function suggest that IMP.18p is an important candidate gene for bipolar disorder. C1 NIDOCD,MOL GENET LAB,NIH,BETHESDA,MD 20892. RP Yoshikawa, T (reprint author), NIMH,UNIT GENE MAPPING & EXPRESS,CLIN NEUROGENET BRANCH,NIH,BLDG 10,RM 3N218,BETHESDA,MD 20892, USA. NR 19 TC 48 Z9 52 U1 1 U2 2 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE, HAMPSHIRE, ENGLAND RG21 6XS SN 1359-4184 J9 MOL PSYCHIATR JI Mol. Psychiatr. PD SEP PY 1997 VL 2 IS 5 BP 393 EP 397 DI 10.1038/sj.mp.4000325 PG 5 WC Biochemistry & Molecular Biology; Neurosciences; Psychiatry SC Biochemistry & Molecular Biology; Neurosciences & Neurology; Psychiatry GA XX285 UT WOS:A1997XX28500014 PM 9322233 ER PT J AU Vandenbergh, DJ Zonderman, AB Wang, J Uhl, GR Costa, PT AF Vandenbergh, DJ Zonderman, AB Wang, J Uhl, GR Costa, PT TI No association between novelty seeking and dopamine D4 receptor (D4DR) exon III seven repeat alleles in Baltimore Longitudinal Study of Aging participants SO MOLECULAR PSYCHIATRY LA English DT Article DE dopamine; receptors; personality; five factor model; genetics; complex disease ID GENE; POLYMORPHISM; VARIANTS AB Recent studies by Ebstein et ar and Benjamin ef al(2) found associations between long repeat polymorphisms in the D4 dopamine receptor gene (D4DR) and individual variation in a human personality trait, identified as 'Novelty Seeking'(NS). Ebstein at al used the Tridimensional Personality Questionnaire (TPQ)(3) to measure NS scores; Benjamin et al used the Revised NEO Personality Inventory (NEO-PI-R)(4) to estimate NS scores, However, Malhotra at al(5) failed to replicate the association between the direct measure of NS using the TPQ and the long alleles of the D4DR genotypes in two Finnish samples. In an attempt to confirm the association found by Benjamin et al using NEO-PI-R estimated NS, the present study used an alternative design extreme groups strategy to select high and low novelty seeking research volunteers from the Baltimore Longitudinal Study of Aging (BLSA).(6) There were no significant associations between long alleles (7-repeat allele) and high novelty seeking groups, The findings of Ebstein and colleagues and those of Benjamin and colleagues do not generalize to this American middle-aged, mixed-gender sample, a conclusion also consistent with the findings of a recent Swedish study.(7) Demographic factors such as the age and gender composition of the samples are important sources of variation in allelic association studies and future research must carefully address whether the D4DR genetic polymorphisms vary substantially across demographic groups. C1 NIA,LAB PERSONAL & COGNIT,NIH,BALTIMORE,MD 21224. NIDA,MOL NEUROBIOL BRANCH,NIH,LEXINGTON,KY. JOHNS HOPKINS UNIV,SCH MED,DEPT NEUROL,BALTIMORE,MD 21218. JOHNS HOPKINS UNIV,SCH MED,DEPT NEUROSCI,BALTIMORE,MD 21218. OI Costa, Paul/0000-0003-4375-1712; Zonderman, Alan B/0000-0002-6523-4778 NR 13 TC 103 Z9 103 U1 0 U2 3 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE, HAMPSHIRE, ENGLAND RG21 6XS SN 1359-4184 J9 MOL PSYCHIATR JI Mol. Psychiatr. PD SEP PY 1997 VL 2 IS 5 BP 417 EP 419 DI 10.1038/sj.mp.4000309 PG 3 WC Biochemistry & Molecular Biology; Neurosciences; Psychiatry SC Biochemistry & Molecular Biology; Neurosciences & Neurology; Psychiatry GA XX285 UT WOS:A1997XX28500019 PM 9322238 ER PT J AU Koffman, BM Dalakas, MC AF Koffman, BM Dalakas, MC TI Effect of high-dose intravenous immunoglobulin on serum chemistry, hematology, and lymphocyte subpopulations: Assessments based on controlled treatment trials in patients with neurological diseases SO MUSCLE & NERVE LA English DT Article DE intravenous immunoglobulin; transient lymphopenia; T-cell subsets ID GUILLAIN-BARRE-SYNDROME; IMMUNE GLOBULIN; GAMMA-GLOBULIN; MYASTHENIA-GRAVIS; THERAPY; INFUSION; DERMATOMYOSITIS; NEUTROPENIA; NEUROPATHY; IVIG AB The effect of intravenous immunoglobulin (IVIG) on various laboratory values was measured immediately before and after completion of serial monthly infusions of IVIG (2 g/kg) or an equal volume of placebo over 3-12 months, in 46 patients with neuromuscular diseases participating in controlled trials. Hematological, lymphocyte subpopulation, and chemistry values were analyzed and compared. After IVIG, but not placebo, a 34% reduction in lymphocytes was noted in 44/46 patients with a selective reduction of the T cells, but not the B or IL2R-positive cells. Counts returned to baseline within 30 days. Creatine kinase levels decreased by 23% and sedimentation rate increased by 275% after IVIG infusion. A nondilutional, artifactual, hyponatremia and hypomagnesemia was noted with IVIG but not placebo. We conclude that IVIG affects a variety of serum chemistry and hematological values either directly or artifactually by interfering with the laboratory method used for the assays. Transient lymphopenia is consistently seen, and may play a role in the immunomodulating effect of IVIG. (C) 1997 John Wiley & Sons, Inc. C1 NINCDS,MED NEUROL BRANCH,NEUROMUSCULAR DIS SECT,BETHESDA,MD 20892. NR 34 TC 46 Z9 46 U1 0 U2 0 PU JOHN WILEY & SONS INC PI NEW YORK PA 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0148-639X J9 MUSCLE NERVE JI Muscle Nerve PD SEP PY 1997 VL 20 IS 9 BP 1102 EP 1107 DI 10.1002/(SICI)1097-4598(199709)20:9<1102::AID-MUS2>3.0.CO;2-C PG 6 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA XR371 UT WOS:A1997XR37100002 PM 9270664 ER PT J AU Eckert, I Caspary, WJ Nusse, M Liechty, M Davis, L Stopper, H AF Eckert, I Caspary, WJ Nusse, M Liechty, M Davis, L Stopper, H TI Micronuclei containing whole chromosomes harbouring the selectable gene do not lead to mutagenesis SO MUTAGENESIS LA English DT Article ID TUMOR-SUPPRESSOR GENES; MAMMALIAN-CELLS; IN-VITRO; MOUSE; ASSAY; HYBRIDIZATION; 5-AZACYTIDINE; CHEMICALS; MUTATION; SITU AB Loss of heterozygosity is one genetic change observed in many tumours, We do not know whether the loss of chromosomal material through micronucleus formation is a viable mechanism associated with, and possibly leading to, genetic disease, Previously, we treated L5178Y mouse lymphoma cells with four aneugens, Although these aneugens induced micronuclei containing predominantly whole chromosomes, they did not induce mutations at Tk1, the selectable gene, under the same non-toxic conditions in which they induced micronuclei, This suggested that the induction of micronuclei containing whole chromosomes was not an early event leading to phenotypically expressed mutations in these cells under the conditions used, However, it is possible that chromosome 11, on which Tk1 resides, may be under-represented in the micronucleus population, To find out the frequency of induction of micronuclei containing chromosome 11, we applied fluorescence in situ hybridization using a chromosome 11 paint to micronuclei induced by colcemid and vinblastine, We found that the numbers of micronuclei containing chromosome 11 are more than sufficient to be detectable as mutations if these micronuclei lead to viable mutants, We conclude that the formation of micronuclei containing whole chromosomes does not lead to viable, dividing mutants in this system. C1 NIH,RES TRIANGLE PK,NC 27709. UNIV WURZBURG,DEPT TOXICOL,D-97078 WURZBURG,GERMANY. GSF MUNICH,FLOW CYTOMETRY,D-85764 NEUHERBERG,GERMANY. APPL GENET LABS INC,MELBOURNE,FL 32901. NR 31 TC 4 Z9 4 U1 0 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD, ENGLAND OX2 6DP SN 0267-8357 J9 MUTAGENESIS JI Mutagenesis PD SEP PY 1997 VL 12 IS 5 BP 379 EP 382 DI 10.1093/mutage/12.5.379 PG 4 WC Genetics & Heredity; Toxicology SC Genetics & Heredity; Toxicology GA XW072 UT WOS:A1997XW07200011 PM 9379918 ER PT J AU Yu, JJ Mu, CJ Lee, KB Okamoto, A Reed, EL Bostick-Bruton, F Mitchell, KC Reed, E AF Yu, JJ Mu, CJ Lee, KB Okamoto, A Reed, EL Bostick-Bruton, F Mitchell, KC Reed, E TI A nucleotide polymorphism in ERCC1 in human ovarian cancer cell lines and tumor tissues SO MUTATION RESEARCH-GENOMICS LA English DT Article DE nucleotide excision repair; codon usage; polymorphism; single strand conformation polymorphism; sequence; ovarian cancer ID REPAIR GENE ERCC-1; INTERSTRAND CROSS-LINKS; MESSENGER-RNA LEVELS; DNA EXCISION-REPAIR; ESCHERICHIA-COLI; SENSITIVITY RESISTANCE; CISPLATIN; P53; TRANSLATION; EXPRESSION AB We studied the DNA sequence of the entire coding region of ERCC1 gene, in five cell lines established from human ovarian cancer (A2780, A2780/CP70, MCAS, OVCAR-3, SK-OV-3), 29 human ovarian cancer tumor tissue specimens, one human T-lymphocyte cell line (H9), and non-malignant human ovary tissue (NHO). Samples were assayed by PCR-SSCP and DNA sequence analyses. A silent mutation at codon 118 (site for restriction endonuclease MaeII) in exon 4 of the gene was detected in MCAS, OVCAR-3 and SK-OV-3 cells, and NHO. This mutation was a C --> T transition, that codes for the same amino acid: asparagine, This transition converts a common codon usage (AAC) to an infrequent codon usage (AAT), whereas frequency of use is reduced two-fold. This base change was associated with a detectable band shift on SSCP analysis. For the 29 ovarian cancer specimens, the same base change was observed in 15 tumor samples and was associated with the same band shift in exon 4. Cells and tumor tissue specimens that did not contain the C --> T transition, did not show the band shift in exon 4. Our data suggest that this alteration at codon lie within the ERCC1 gene, may exist in platinum-sensitive and platinum-resistant ovarian cancer tissues. (C) 1997 Elsevier Science B.V. C1 NCI, Med Branch, Dev Therapeut Dept,Div Clin Sci, Med Ovarian Canc Sect, Bethesda, MD 20892 USA. RP Reed, E (reprint author), NCI, Med Branch, Dev Therapeut Dept,Div Clin Sci, Med Ovarian Canc Sect, Bldg 10,Room 12C103, Bethesda, MD 20892 USA. NR 29 TC 84 Z9 92 U1 1 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1383-5726 J9 MUTAT RES-GENOMICS JI Mutat. Res.-Genomics PD SEP PY 1997 VL 382 IS 1-2 BP 13 EP 20 DI 10.1016/S1383-5726(97)00004-6 PG 8 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology SC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology GA 128LL UT WOS:000076407600003 PM 9360634 ER PT J AU Polinkovsky, A Robin, NH Thomas, JT Irons, M Lynn, A Goodman, FR Reardon, W Kant, SG Brunner, HG vanderBurgt, I Chitayat, D McGaughran, J Donnai, D Luyten, FP Warman, ML AF Polinkovsky, A Robin, NH Thomas, JT Irons, M Lynn, A Goodman, FR Reardon, W Kant, SG Brunner, HG vanderBurgt, I Chitayat, D McGaughran, J Donnai, D Luyten, FP Warman, ML TI Mutations in CDMP1 cause autosomal dominant brachydactyly type C SO NATURE GENETICS LA English DT Letter ID TGF-BETA-SUPERFAMILY; MEMBER; BRACHYPODISM; MOUSE; EYE C1 CASE WESTERN RESERVE UNIV,SCH MED,DEPT GENET,CLEVELAND,OH 44106. CASE WESTERN RESERVE UNIV,SCH MED,DEPT PEDIAT,CLEVELAND,OH 44106. UNIV HOSP CLEVELAND,CTR HUMAN GENET,CLEVELAND,OH 44106. NIDR,CRANIOFACIAL & SKELETAL DIS BRANCH,NIH,BETHESDA,MD 20892. FLOATING HOSP CHILDREN,NEW ENGLAND MED CTR,DIV GENET,BOSTON,MA. INST CHILD HLTH,MOL MED UNIT,LONDON,ENGLAND. INST CHILD HLTH,MOTHERCARE UNIT,CLIN GENET & FETAL MED,LONDON,ENGLAND. UNIV LEIDEN HOSP,DEPT CLIN GENET,NL-2300 RC LEIDEN,NETHERLANDS. UNIV NIJMEGEN HOSP,DEPT CLIN GENET,NL-6500 HB NIJMEGEN,NETHERLANDS. UNIV TORONTO,HOSP SICK CHILDREN,DIV CLIN GENET,TORONTO,ON M5G 1X8,CANADA. ST MARYS HOSP,DEPT CLIN GENET,MANCHESTER M13 0JH,LANCS,ENGLAND. RI Kant, Sarina/F-8596-2010; Brunner, Han/C-9928-2013; McGaughran, Julie/A-2563-2012 FU NIAMS NIH HHS [AR-43827] NR 15 TC 184 Z9 192 U1 1 U2 4 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 SEP PY 1997 VL 17 IS 1 BP 18 EP 19 DI 10.1038/ng0997-18 PG 2 WC Genetics & Heredity SC Genetics & Heredity GA XU724 UT WOS:A1997XU72400011 PM 9288091 ER PT J AU Thomas, JT Kilpatrick, MW Lin, K Erlacher, L Lembessis, P Costa, T Tsipouras, P Luyten, FP AF Thomas, JT Kilpatrick, MW Lin, K Erlacher, L Lembessis, P Costa, T Tsipouras, P Luyten, FP TI Disruption of human limb morphogenesis by a dominant negative mutation in CDMP1 SO NATURE GENETICS LA English DT Article ID FACTOR-BETA SUPERFAMILY; PROTEINS; MEMBER; CHONDRODYSPLASIA; REGULATORS; MOUSE; BMP-7 AB Chondrodysplasia Grebe type (CGT) is an autosomal recessive disorder characterized by severe limb shortening and dysmorphogenesis. We have identified a causative point mutation in the gene encoding the bone morphogenetic protein (BMP)-like molecule, cartilage-derived morphogenetic protein-1 (CDMP-1). The mutation substitutes a tyrosine for the first of seven highly conserved cysteine residues in the mature active domain of the protein, We demonstrate that the mutation results in a protein that is not secreted and is inactive in vitro. It produces a dominant negative effect by preventing the secretion of other, related BMP family members. We present evidence that this may occur through the formation of heterodimers. The mutation and its proposed mechanism of action provide the first human genetic indication that composite expression patterns of different BMPs dictate limb and digit morphogenesis. C1 UNIV CONNECTICUT,CTR HLTH,DEPT PEDIAT,FARMINGTON,CT 06030. HOSP SICK CHILDREN,DEPT GENET,TORONTO,ON M5G 1X8,CANADA. RP Thomas, JT (reprint author), NIDR,CRANIOFACIAL & SKELETAL DIS BRANCH,NIH,BETHESDA,MD 20892, USA. FU NICHD NIH HHS [HD-22610] NR 36 TC 219 Z9 234 U1 1 U2 7 PU NATURE PUBLISHING CO PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 SN 1061-4036 J9 NAT GENET JI Nature Genet. PD SEP PY 1997 VL 17 IS 1 BP 58 EP 64 DI 10.1038/ng0997-58 PG 7 WC Genetics & Heredity SC Genetics & Heredity GA XU724 UT WOS:A1997XU72400018 PM 9288098 ER PT J AU Chen, SG Parchi, P Brown, P Capellari, S Zou, WQ Cochran, EJ VnencakJones, CL Julien, J Vital, C Mikol, J Lugaresi, E AutilioGambetti, L Gambetti, P AF Chen, SG Parchi, P Brown, P Capellari, S Zou, WQ Cochran, EJ VnencakJones, CL Julien, J Vital, C Mikol, J Lugaresi, E AutilioGambetti, L Gambetti, P TI Allelic origin of the abnormal prion protein isoform in familial prion diseases SO NATURE MEDICINE LA English DT Article ID CREUTZFELDT-JAKOB-DISEASE; CODON-178ASN PRNP MUTATION; SCRAPIE PRION; DNA POLYMORPHISM; PRP 27-30; INSOMNIA; GENE; TRANSMISSION; SEPARATION; CONVERSION AB The hallmark of prion diseases is the presence of an aberrant isoform of the prion protein (PrPres) that is insoluble in nondenaturing detergents and resistant to proteases. We investigated the allelic origin of PrPres in brains of subjects heterozygous for the D178N mutation linked to fatal familial insomnia (FFI) and a subtype of Creutzfeldt-Jakob disease (CJD(178)), as well as for insertional mutations associated with another CJD subtype. We found that in FFI and CJD(178) subjects, only mutant PrP was detergent-insoluble and protease-resistant. Therefore, PrPres derives exclusively from the mutant allele carrying the D178N mutation. In contrast, in the CJD subtype harboring insertional mutations, wild-type PrP was also detergent-insoluble and likely to be protease-resistant. Our findings indicate that the participation of the wild-type PrP in the formation of PrPres depends on the type of mutations, providing an insight into the molecular mechanisms underlying the phenotypic heterogeneity in familial prion diseases. C1 NINCDS,CNS STUDIES LAB,NIH,BETHESDA,MD 20892. RUSH PRESBYTERIAN ST LUKES MED CTR,DEPT PATHOL,CHICAGO,IL 60612. VANDERBILT UNIV,MED CTR,DEPT PATHOL,NASHVILLE,TN 37232. CHU BORDEAUX,DEPT NEUROL,F-33604 PESSAC,FRANCE. CHU BORDEAUX,DEPT PATHOL,F-33604 PESSAC,FRANCE. HOP LARIBOISIERE,F-75475 PARIS,FRANCE. UNIV BOLOGNA,INST NEUROL,I-40123 BOLOGNA,ITALY. RP Chen, SG (reprint author), CASE WESTERN RESERVE UNIV,INST PATHOL,DIV NEUROPATHOL,2085 ADELBERT RD,CLEVELAND,OH 44106, USA. RI capellari, sabina/F-5545-2012; Chen, Shu/O-4750-2014; Parchi, Piero/L-9833-2015 OI Chen, Shu/0000-0001-7180-3001; Parchi, Piero/0000-0002-9444-9524 FU NIA NIH HHS [AG08155, AG08992] NR 45 TC 70 Z9 77 U1 1 U2 2 PU NATURE PUBLISHING CO PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 SN 1078-8956 J9 NAT MED JI Nat. Med. PD SEP PY 1997 VL 3 IS 9 BP 1009 EP 1015 DI 10.1038/nm0997-1009 PG 7 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA XT842 UT WOS:A1997XT84200034 PM 9288728 ER PT J AU Clout, NJ Slingsby, C Wistow, GJ AF Clout, NJ Slingsby, C Wistow, GJ TI An eye on crystallins SO NATURE STRUCTURAL BIOLOGY LA English DT Editorial Material ID X-RAY-ANALYSIS; PROTEIN-S; LENS; EVOLUTION C1 UNIV LONDON BIRKBECK COLL,DEPT CRYSTALLOG,LONDON WC1E 7HX,ENGLAND. NEI,SECT MOL STRUCT & FUNCT,NIH,BETHESDA,MD 20892. NR 10 TC 19 Z9 19 U1 0 U2 0 PU NATURE PUBLISHING CO PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 SN 1072-8368 J9 NAT STRUCT BIOL JI Nat. Struct. Biol. PD SEP PY 1997 VL 4 IS 9 BP 685 EP 685 DI 10.1038/nsb0997-685 PG 1 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA XU716 UT WOS:A1997XU71600006 PM 9302991 ER PT J AU Tjandra, N Omichinski, JG Gronenborn, AM Clore, GM Bax, A AF Tjandra, N Omichinski, JG Gronenborn, AM Clore, GM Bax, A TI Use of dipolar H-1-N-15 and H-1-C-13 couplings in the structure determination of magnetically oriented macromolecules in solution SO NATURE STRUCTURAL BIOLOGY LA English DT Article ID 3-DIMENSIONAL STRUCTURES; PROTEINS; NMR; RELAXATION AB Anisotropy of the molecular magnetic susceptibility gives rise to a small degree of alignment, The resulting residual dipolar couplings, which can now be measured with the advent of higher magnetic fields in NMR, contain information on the orientation of the internuclear vectors relative to the molecular magnetic susceptibility tensor, thereby providing information on long range order that is not accessible by any of the solution NMR parameters currently used in structure determination. Thus, the dipolar couplings constitute unique and powerful restraints in determining the structures of magnetically oriented macromolecules in solution, The method is demonstrated on a complex of the DNA-binding domain of the transcription factor GATA-1 with a 16 base pair oligodeoxyribonucleotide. C1 NIDDKD,PHYS CHEM LAB,NIH,BETHESDA,MD 20892. NHLBI,BIOPHYS CHEM LAB,NIH,BETHESDA,MD 20892. RI Clore, G. Marius/A-3511-2008 OI Clore, G. Marius/0000-0003-3809-1027 NR 22 TC 444 Z9 456 U1 0 U2 22 PU NATURE PUBLISHING CO PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 SN 1072-8368 J9 NAT STRUCT BIOL JI Nat. Struct. Biol. PD SEP PY 1997 VL 4 IS 9 BP 732 EP 738 DI 10.1038/nsb0997-732 PG 7 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA XU716 UT WOS:A1997XU71600016 PM 9303001 ER PT J AU Kishan, KVR Scita, G Wong, WT DiFiore, PP Newcomer, ME AF Kishan, KVR Scita, G Wong, WT DiFiore, PP Newcomer, ME TI The SH3 domain of Eps8 exists as a novel intertwined dimer SO NATURE STRUCTURAL BIOLOGY LA English DT Article ID PROLINE-RICH PEPTIDES; LIGAND-BINDING SITE; CRYSTAL-STRUCTURE; HUMAN FYN; KINASE; GRB2; SUBSTRATE; SPECTRIN; PROTEINS; ERRORS AB SH3 domains are structurally well-characterized as monomeric modular units of protein structure that mediate protein-protein recognition in numerous signal transduction proteins, The X-ray crystallographic structure of the Eps8 SH3 domain reveals a novel variation of the canonical SH3 fold: the SH3 domain from Eps8 is a dimer formed by strand interchange, In addition, co-immunoprecipitation experiments show that intact Eps8 is multimeric in vivo. Hence, the SH3 domain of Eps8 may represent a dimerization motif, C1 VANDERBILT UNIV,SCH MED,DEPT BIOCHEM,NASHVILLE,TN 37232. EUROPEAN INST ONCOL,DEPT EXPT ONCOL,MILAN,ITALY. NIDR,CELLULAR DEV & ONCOL LAB,NIH,BETHESDA,MD 20892. FAC MED & CHIRURG,IST MICROBIOL,BARI,ITALY. RI Scita, GIORGIO/J-9670-2012; Di Fiore, Pier Paolo/K-2130-2012; OI Di Fiore, Pier Paolo/0000-0002-2252-0950; Scita, Giorgio/0000-0001-7984-1889 NR 35 TC 70 Z9 73 U1 0 U2 3 PU NATURE PUBLISHING CO PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 SN 1072-8368 J9 NAT STRUCT BIOL JI Nat. Struct. Biol. PD SEP PY 1997 VL 4 IS 9 BP 739 EP 743 PG 5 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA XU716 UT WOS:A1997XU71600017 PM 9303002 ER PT J AU Dosemeci, A Choi, C AF Dosemeci, A Choi, C TI Ca2+-independent autophosphorylation of postsynaptic density-associated Ca2+/calmodulin-dependent protein kinase SO NEUROCHEMICAL RESEARCH LA English DT Article DE postsynaptic density; PSD; Ca2+/calmodulin-dependent protein kinase; autophosphorylation; synaptic plasticity ID LONG-TERM POTENTIATION; II MUTANT MICE; CA-2+ CALMODULIN; INHIBITION; BRAIN; SITE; LTP; PHOSPHORYLATION; IDENTIFICATION; TRANSMISSION AB A major protein in the postsynaptic density fraction is alpha-CAM kinase II, the alpha-subunit of the Ca2+/calmodulin-dependent protein kinase. Autophosphorylation of the postsynaptic density-associated CaM kinase II is likely to be a crucial event in the induction of activity-dependent synaptic modification. This study focuses on the regulation and consequences of Ca2+-independent autophosphorylation of the enzyme. In isolated postsynaptic densities, a sub-stochiometric level of autophosphorylation in the presence of Ca2+ is sufficient to trigger maximal Ca2+-independent autophosphorylation of alpha-CaM Kinase II. A major fraction of the sites phosphorylated in the absence of Ca2+ can be dephosphorylated by the endogenous phosphatase activity in the preparation. Ca2+-independent autophosphorylation is correlated with a drastic decrease in calmodulin binding to postsynaptic densities. This may represent a physiological mechanism that lowers the calmodulin trapping capacity of the organelle, thus increasing the availability of calmodulin to other elements within a spine. RP Dosemeci, A (reprint author), NINCDS,NEUROBIOL LAB,NIH,BLDG 36,2A21,BETHESDA,MD 20892, USA. NR 36 TC 3 Z9 3 U1 0 U2 0 PU PLENUM PUBL CORP PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 SN 0364-3190 J9 NEUROCHEM RES JI Neurochem. Res. PD SEP PY 1997 VL 22 IS 9 BP 1151 EP 1157 DI 10.1023/A:1027373404145 PG 7 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA XM092 UT WOS:A1997XM09200010 PM 9251106 ER PT J AU Metman, LV vandenMunckhof, P Klaassen, AAG Blanchet, P Mouradian, MM Chase, TN AF Metman, LV vandenMunckhof, P Klaassen, AAG Blanchet, P Mouradian, MM Chase, TN TI Effects of supra-threshold levodopa doses on dyskinesias in advanced Parkinson's disease SO NEUROLOGY LA English DT Article ID MOTOR FLUCTUATIONS; OFF FLUCTUATIONS; MECHANISMS; PHARMACOKINETICS; PHARMACODYNAMICS; PATHOGENESIS AB The levodopa (LD) dose-antiparkinsonian response relationship becomes progressively steeper with advancing Parkinson's disease (PD). To establish the dose-response profile for the dyskinesiogenic effect of LD, we administered intravenous LD over a wide dose range to 25 patients with advanced PD. As expected in these patients with nonexistent therapeutic windows, the threshold doses (TD) for both motor effects were similar. Just around the TD, the relationship between LD dose and the magnitude of antiparkinsonian and dyskinesiogenic responses inclined steeply, reaching a plateau above 1.5 x TD. Response duration, however, continued to increase. The findings suggest that attempts to ameliorate dyskinesias in advanced PD patients by giving smaller, more frequent LD doses may be counter-productive due to shorter motor responses, more ''off'' time, and dose failures, while some may, in fact, benefit from higher LD doses to assure a full response and prolong its duration. C1 NINCDS,EXPT THERAPEUT BRANCH,NIH,BETHESDA,MD 20892. OI Mouradian, M. Maral/0000-0002-9937-412X NR 13 TC 36 Z9 36 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0028-3878 J9 NEUROLOGY JI Neurology PD SEP PY 1997 VL 49 IS 3 BP 711 EP 713 PG 3 WC Clinical Neurology SC Neurosciences & Neurology GA XX774 UT WOS:A1997XX77400013 PM 9305328 ER PT J AU Bergey, GK Morris, HH Rosenfeld, W Blume, WT Penovich, PE Morrell, MJ Leiderman, DB Crockatt, JG LaMoreaux, L Garofalo, E Pierce, M AF Bergey, GK Morris, HH Rosenfeld, W Blume, WT Penovich, PE Morrell, MJ Leiderman, DB Crockatt, JG LaMoreaux, L Garofalo, E Pierce, M TI Gabapentin monotherapy .1. An 8-day, double-blind, dose-controlled, multicenter study in hospitalized patients with refractory complex partial or secondarily generalized seizures SO NEUROLOGY LA English DT Article ID PARTIAL-ONSET SEIZURES; ADD-ON THERAPY; FELBAMATE MONOTHERAPY; ANTIEPILEPTIC DRUGS; TRIAL; NEURONTIN; PHENYTOIN; EFFICACY AB We evaluated the efficacy and safety of gabapentin administered as monotherapy in an 8-day, randomized, double-blind, dose-controlled, parallel-group, multicenter study comparing dosages of 300 and 3,600 mg/d gabapentin in 82 hospitalized patients whose antiepileptic medications had been discontinued for seizure monitoring. Seizures under study were complex partial seizures with or without secondary generalization. Patients exited the study if they experienced a protocol-defined exit event indicating lack of efficacy. Time to exit was significantly longer (p = 0.0001) and completion rate was significantly higher (53% versus 17%; p = 0.002) for patients receiving 3,600 mg/d gabapentin. Gabapentin was well tolerated by patients in both dosage groups, and no patients exited the study due to adverse events, despite rapid initiation of full dose within 24 hours. These results demonstrate that gabapentin has anticonvulsant activity and is well tolerated when administered as monotherapy in patients with refractory partial seizures. C1 WARNER LAMBERT PARKE DAVIS, PARKE DAVIS PHARMACEUT RES, ANN ARBOR, MI 48105 USA. UNIV MARYLAND, MED CTR, DEPT NEUROL, BALTIMORE, MD 21201 USA. CLEVELAND CLIN FDN, CLEVELAND, OH 44195 USA. COMPREHENS EPILEPSY CARE CTR CHILDREN & ADULTS, ST LOUIS, MO USA. UNIV WESTERN ONTARIO, DEPT NEUROL, LONDON, ON, CANADA. MINNESOTA EPILEPSY GRP, ST PAUL, MN USA. STANFORD UNIV, DEPT NEUROL, STANFORD, CA 94305 USA. NIH, ROCKVILLE, MD USA. VANDERBILT UNIV, CTR MED, NASHVILLE, TN 37232 USA. UNIV MARYLAND HOSP, BALTIMORE, MD 21201 USA. UNIV MICHIGAN, ANN ARBOR, MI 48109 USA. UNIV WESTERN ONTARIO HOSP, LONDON, ON N6A 5A5, CANADA. UNIV CALIF SAN FRANCISCO, SAN FRANCISCO, CA USA. JOHNS HOPKINS SCH MED, BALTIMORE, MD USA. STANFORD UNIV HOSP, STANFORD, CA 94305 USA. MINNESOTA EPILEPSY GRP, ST PAUL, MN USA. UNIV MIAMI, MIAMI, FL 33152 USA. HENRY FORD HOSP, DETROIT, MI 48202 USA. UNIV COLORADO, CTR HLTH SCI, DENVER, CO USA. NR 20 TC 89 Z9 89 U1 0 U2 1 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0028-3878 J9 NEUROLOGY JI Neurology PD SEP PY 1997 VL 49 IS 3 BP 739 EP 745 PG 7 WC Clinical Neurology SC Neurosciences & Neurology GA XX774 UT WOS:A1997XX77400019 PM 9305334 ER PT J AU Stone, LA Frank, JA Albert, PS Bash, CN Calabresi, PA Maloni, H McFarland, HF AF Stone, LA Frank, JA Albert, PS Bash, CN Calabresi, PA Maloni, H McFarland, HF TI Characterization of MRI response to treatment with interferon beta-1b: Contrast-enhancing MRI lesion frequency as a primary outcome measure SO NEUROLOGY LA English DT Article ID REMITTING MULTIPLE-SCLEROSIS; RESONANCE-IMAGING LESIONS AB MRI is a valuable tool to examine the pathophysiology and natural history of multiple sclerosis (MS), and several large multicenter trials have utilized MRI as a secondary outcome measure. We previously examined the effect of interferon beta-1b on contrast-enhancing lesions on MRI using a baseline versus treatment design, and found that on treatment there is a reduction in mean frequency of enhancing lesions over the group. Using an expanded number of patients and the same trial design, we examined the individual response to treatment more extensively. We find that the effect seen previously is still present, and that there is heterogeneity in the amount of decrease in contrast-enhancing lesions. This expanded number of patients and trial design allows for the discussion of new criteria for individual response to treatment, which are applied in the current trial. These approaches may be useful in the examination, early testing, and comparison of experimental therapeutic agents in MS as well as in the characterization of patients who do or do not have a response seen on MRI. C1 NIH,LAB DIAGNOST RADIOL RES,BETHESDA,MD 20892. NIH,OD,BETHESDA,MD 20892. NHLBI,OFF BIOSTAT RES,NIH,BETHESDA,MD 20892. NINCDS,NEUROIMMUNOL BRANCH,NIH,BETHESDA,MD 20892. RP Stone, LA (reprint author), MAYO CLIN SCOTTSDALE,DEPT NEUROL,13400 SHEA BLVD,SCOTTSDALE,AZ 85259, USA. NR 11 TC 96 Z9 98 U1 0 U2 2 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0028-3878 J9 NEUROLOGY JI Neurology PD SEP PY 1997 VL 49 IS 3 BP 862 EP 869 PG 8 WC Clinical Neurology SC Neurosciences & Neurology GA XX774 UT WOS:A1997XX77400040 PM 9305355 ER PT J AU Chen, R Samii, A Canos, M Wassermann, EM Hallett, M AF Chen, R Samii, A Canos, M Wassermann, EM Hallett, M TI Effects of phenytoin on cortical excitability in humans SO NEUROLOGY LA English DT Article ID TRANSCRANIAL MAGNETIC STIMULATION; HUMAN MOTOR CORTEX; CORTICOCORTICAL INHIBITION; RESPONSES AB We studied the effects of a loading dose of phenytoin on motor cortex excitability in five healthy volunteers. Phenytoin elevated motor thresholds to transcranial magnetic stimulation (TMS) in all subjects, but had no effects on motor-evoked potential amplitudes, silent period durations, and intracortical excitability tested by paired TMS during rest and voluntary muscle activation. These results are consistent with the hypothesis that blockade of voltage-gated sodium channels decreases membrane excitability and elevates the threshold to TMS, but will not reduce intracortical excitability. C1 NINCDS,HUMAN MOTOR CONTROL SECT,MED NEUROL BRANCH,NIH,BETHESDA,MD 20892. RI Chen, Robert/B-3899-2009 OI Chen, Robert/0000-0002-8371-8629 NR 10 TC 154 Z9 155 U1 0 U2 1 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0028-3878 J9 NEUROLOGY JI Neurology PD SEP PY 1997 VL 49 IS 3 BP 881 EP 883 PG 3 WC Clinical Neurology SC Neurosciences & Neurology GA XX774 UT WOS:A1997XX77400046 PM 9305361 ER PT J AU Buckholtz, N AF Buckholtz, N TI Background and purpose of the consortium to establish a registry for Alzheimer's disease SO NEUROLOGY LA English DT Editorial Material RP Buckholtz, N (reprint author), NIA,NIH,GATEWAY BLDG,SUITE 3C307,7201 WISCONSIN AVE,BETHESDA,MD 20892, USA. NR 0 TC 2 Z9 2 U1 1 U2 1 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0028-3878 J9 NEUROLOGY JI Neurology PD SEP PY 1997 VL 49 IS 3 SU 3 BP S1 EP S1 PG 1 WC Clinical Neurology SC Neurosciences & Neurology GA XY150 UT WOS:A1997XY15000001 PM 9310504 ER PT J AU Jacobson, KA Park, KS Jiang, JL Kim, YC Olah, ME Stiles, GL Ji, XD AF Jacobson, KA Park, KS Jiang, JL Kim, YC Olah, ME Stiles, GL Ji, XD TI Pharmacological characterization of novel A(3) adenosine receptor-selective antagonists SO NEUROPHARMACOLOGY LA English DT Article; Proceedings Paper CT 5th Annual Neuropharmacology Conference CY OCT 23-25, 1997 CL NEW ORLEANS, LA DE dihydropyridine; flavonoid; triazoloquinazoline; adenylate cyclase; tumor necrosis factor; guanine nucleotides; adenosine A(3) receptor; adenosine ID TUMOR-NECROSIS-FACTOR; FACTOR-ALPHA; CEREBRAL-ISCHEMIA; MOLECULAR-CLONING; TNF-ALPHA; DERIVATIVES; CELLS; RAT; EXPRESSION; PROTEIN AB The effects of putative A(3) adenosine receptor antagonists of three diverse chemical classes (the flavonoid MRS 1067, the 6-phenyl-1,4-dihydropyridines MRS 1097 and MRS 1191, and the triazoloquinazoline MRS 1220) were characterized in receptor binding and functional assays. MRS 1067, MRS 1191 and MRS 1220 were found to be competitive in saturation binding studies using the agonist radioligand [I-125]AB-MECA (N-6-(4-amino-3-iodobenzyl)adenosine-5'-N-methyluronamide) at cloned human brain A(3) receptors expressed in HEK-293 cells. Antagonism was demonstrated in functional assays consisting of agonist-induced inhibition of adenylate cyclase and the stimulation of binding of [S-35]guanosine 5'-O-(3-thiotriphosphate) ([S-35]GTP-gamma-S) to the associated G-proteins. MRS 1220 and MRS 1191, with K-B values of 1.7 and 92 nM, respectively, proved to be highly selective for human A(3) receptor vs human A(1) receptor-mediated effects on adenylate cyclase. In addition, MRS 1220 reversed the effect of A(3) agonist-elicited inhibition of tumor necrosis factor-alpha formation in the human macrophage U-937 cell line, with an IC50 value of 0.3 mu M. Published by Elsevier Science Ltd. C1 DUKE UNIV,SCH MED,DEPT MED,DURHAM,NC 27710. DUKE UNIV,SCH MED,DEPT PHARMACOL,DURHAM,NC 27710. RP Jacobson, KA (reprint author), NIDDK,MOL RECOGNIT SECT,LBC,NIH,BETHESDA,MD 20892, USA. RI Jacobson, Kenneth/A-1530-2009 OI Jacobson, Kenneth/0000-0001-8104-1493 FU Intramural NIH HHS [Z01 DK031117-20, Z99 DK999999] NR 40 TC 113 Z9 116 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0028-3908 J9 NEUROPHARMACOLOGY JI Neuropharmacology PD SEP PY 1997 VL 36 IS 9 BP 1157 EP 1165 DI 10.1016/S0028-3908(97)00104-4 PG 9 WC Neurosciences; Pharmacology & Pharmacy SC Neurosciences & Neurology; Pharmacology & Pharmacy GA YD892 UT WOS:A1997YD89200005 PM 9364471 ER PT J AU Stark, ME Grafman, J Fertig, E AF Stark, ME Grafman, J Fertig, E TI A restricted 'spotlight' of attention in visual object recognition SO NEUROPSYCHOLOGIA LA English DT Article; Proceedings Paper CT 2nd Annual Meeting of the Cognitive-Neuroscience-Society CY MAR-APR -, 1995 CL SAN FRANCISCO, CA SP Cognit Neurosci Soc DE Alzheimer's disease; restricted visual attention; object recognition ID ALZHEIMERS-DISEASE; FEATURE-INTEGRATION; ILLUSORY CONJUNCTIONS; UNILATERAL NEGLECT; BALINTS SYNDROME; FOCAL ATTENTION; SPATIAL VISION; PERCEPTION; DEMENTIA; AGNOSIA AB We describe a patient (NJ), with a progressive visual disturbance, who showed an impairment in identifying larger visually-presented objects relative to their smaller counterparts. NJ showed this size effect for line drawings of objects, words and single letters. When presented with large letters comprised of smaller letters and asked to give speeded identification responses to either the large or small letters, NJ was grossly impaired at identifying the large letter. Additionally, when presented with a context meant to bias responding to either the large or small letter, NJ showed faster and more accurate responding in the small direction, but not in the large direction. We interpret these results as indicative of an impaired 'spotlight' of attention, which is deployed across the visual array, and is necessary for providing the selective visual attention responsible for the integration of visual features. Published by Elsevier Science Ltd. RP Stark, ME (reprint author), NINCDS,COGNIT NEUROSCI SECT,MED NEUROL BRANCH,NIH,BETHESDA,MD 20892, USA. OI Grafman, Jordan H./0000-0001-8645-4457 NR 77 TC 25 Z9 26 U1 2 U2 6 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 SEP PY 1997 VL 35 IS 9 BP 1233 EP 1249 DI 10.1016/S0028-3932(97)00049-3 PG 17 WC Behavioral Sciences; Neurosciences; Psychology, Experimental SC Behavioral Sciences; Neurosciences & Neurology; Psychology GA XT523 UT WOS:A1997XT52300006 PM 9364494 ER PT J AU Malhotra, AK Pinals, DA Adler, CM Elman, I Clifton, A Pickar, D Breier, A AF Malhotra, AK Pinals, DA Adler, CM Elman, I Clifton, A Pickar, D Breier, A TI Ketamine-induced exacerbation of psychotic symptoms and cognitive impairment in neuroleptic-free schizophrenics SO NEUROPSYCHOPHARMACOLOGY LA English DT Article DE ketamine; NMDA; schizophrenia; cognition; psychosis ID PHENCYCLIDINE; MEMORY; ASPARTATE; RECEPTOR; NEURONS AB The N-methyl-d-aspartate (NMDA) receptor has been implicated in the pathophysiology of schizophrenia. We administered subanesthetic doses of the NMDA receptor antagonist ketamine in it double-blind, placebo-controlled design to 13 neuroleptic-free schizophrenic patients to investigate if schizophrenics will experience an exacerbation of psychotic symptoms and cognitive impairments with ketamine. We also examined whether schizophrenics experienced quantitative or qualitative differences in ketamine response in comparison to normal controls. Schizophrenics experienced a brief ketamine-induced exacerbation of positive and negative symptoms with further decrements in recall and recognition memory. They also displayed greater ketamine-induced impairments in free recall than normals. Qualitative differences included auditory hallucinations and paranoia in patients brit not in normals. These data indicate that ketamine is associated with exacerbation of core psychotic and cognitive symptoms in schizophrenia. Moreover, ketamine may differentially affect cognition in schizophrenics ii? comparison to normal cortrols. (C) 1997 American College of Neuropsychopharmacology. Published by Elsevier Science Inc. RP Malhotra, AK (reprint author), NIMH,EXPT THERAPEUT BRANCH,INTRAMURAL RES PROGRAM,NIH,BLDG 10,ROOM 4N212,10 CTR DR,BETHESDA,MD 20892, USA. NR 30 TC 374 Z9 378 U1 2 U2 13 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 SEP PY 1997 VL 17 IS 3 BP 141 EP 150 PG 10 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA XR375 UT WOS:A1997XR37500003 PM 9272481 ER PT J AU Altschul, SF Madden, TL Schaffer, AA Zhang, JH Zhang, Z Miller, W Lipman, DJ AF Altschul, SF Madden, TL Schaffer, AA Zhang, JH Zhang, Z Miller, W Lipman, DJ TI Gapped BLAST and PSI-BLAST: a new generation of protein database search programs SO NUCLEIC ACIDS RESEARCH LA English DT Article ID ACID SUBSTITUTION MATRICES; DISTANTLY RELATED PROTEINS; NUCLEIC-ACID; SEQUENCE DATABASES; BINDING-SITES; STATISTICAL DISTRIBUTION; ALIGNMENT; GENE; HOMOLOGY; DNA AB The BLAST programs are widely used tools for searching protein and DNA databases for sequence similarities. For protein comparisons, a variety of definitional, algorithmic and statistical refinements described here permits the execution time of the BLAST programs to be decreased substantially while enhancing their sensitivity to weak similarities, A new criterion for triggering the extension of word hits, combined with a new heuristic for generating gapped alignments, yields a gapped BLAST program that runs at approximately three times the speed of the original, In addition, a method is introduced for automatically combining statistically significant alignments produced by BLAST into a position-specific score matrix, and searching the database using this matrix, The resulting Position-Specific Iterated BLAST (PSI-BLAST) program runs at approximately the same speed per iteration as gapped BLAST, but in many cases is much more sensitive to weak but biologically relevant sequence similarities. PSI-BLAST is used to uncover several new and interesting members of the BRCT superfamily. C1 NHGRI,LAB GENET DIS RES,NIH,BETHESDA,MD 20892. PENN STATE UNIV,DEPT COMP SCI & ENGN,UNIVERSITY PK,PA 16802. RP Altschul, SF (reprint author), NIH,NATL LIB MED,NATL CTR BIOTECHNOL INFORMAT,BETHESDA,MD 20894, USA. RI Schaffer, Alejandro/F-2902-2012 FU NLM NIH HHS [LM05110] NR 90 TC 42649 Z9 43867 U1 106 U2 1027 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD, ENGLAND OX2 6DP SN 0305-1048 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD SEP 1 PY 1997 VL 25 IS 17 BP 3389 EP 3402 DI 10.1093/nar/25.17.3389 PG 14 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA XU793 UT WOS:A1997XU79300002 PM 9254694 ER PT J AU Grassi, G Forlino, A Marini, JC AF Grassi, G Forlino, A Marini, JC TI Cleavage of collagen RNA transcripts by hammerhead ribozymes in vitro is mutation-specific and shows competitive binding effects SO NUCLEIC ACIDS RESEARCH LA English DT Article ID OSTEOGENESIS IMPERFECTA; SELF-CLEAVAGE; ANTISENSE; CATALYSIS; FIBROBLASTS; LYMPHOCYTES; EXPRESSION; PROTEIN; ALLELE; CHAIN AB We report here the in vitro use of hammerhead ribozymes as an approach to the gene therapy of osteogenesis imperfecta (OI). Our strategy for the treatment of this dominant genetic disorder is based on selective reduction of the level of the mRNA transcripts from the mutant allele. We studied the in vitro cleavage activity of five different hammerhead ribozymes targeted against synthetic transcripts of two naturally occurring human collagen mutations and against a point mutation introduced into a construct containing a portion of the mouse COL1A1 gene, This is the first demonstration that ribozyme cleavage is absolutely dependent on the presence of the ribozyme cleavage site introduced by the disease-causing mutation. Cleavage specificity and activity were unchanged when the cleavage site was located in transcripts of progressively longer length. Cleavage efficiency depended directly on the ratio of ribozyme/substrate, as well as on the time and temperature of incubation, We investigated the competitive effects of both total RNA and normal synthetic transcripts on ribozyme cleavage activity. The ribozyme was able to localize and cleave its specific target even in the presence of a vast excess of total RNA. However, cleavage efficiency was linearly inhibited by the presence of a non-cleavable competitor substrate which contained a ribozyme binding site identical to the site present in the cleavable target. Although this competition could be eliminated by introducing a mismatch into one ribozyme binding arm, the presence of the mismatch decreased ribozyme cleavage efficiency. The mutation-specificity of ribozyme cleavage demonstrated in this work provides support for in vivo studies aimed at ribozyme development as a treatment for dominant negative genetic disorders. C1 NICHHD, SECT CONNECT TISSUE DISORDERS, HERITABLE DISORDERS BRANCH, BETHESDA, MD 20892 USA. RI Forlino, Antonella/H-5385-2015 OI Forlino, Antonella/0000-0002-6385-1182 NR 28 TC 38 Z9 39 U1 1 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD, ENGLAND OX2 6DP SN 0305-1048 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD SEP 1 PY 1997 VL 25 IS 17 BP 3451 EP 3458 DI 10.1093/nar/25.17.3451 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA XU793 UT WOS:A1997XU79300011 PM 9254703 ER PT J AU Rosenberg, HF Dyer, KD AF Rosenberg, HF Dyer, KD TI Diversity among the primate eosinophil-derived neurotoxin genes: a specific C-terminal sequence is necessary for enhanced ribonuclease activity SO NUCLEIC ACIDS RESEARCH LA English DT Article ID CATIONIC PROTEIN; FAMILY; PURIFICATION; ANGIOGENIN; EVOLUTION AB The human eosinophil-derived neurotoxin (hEDN) is a secretory effector protein from eosinophilic leukocytes that is a member of the ribonuclease A (RNase A) family of ribonucleases. EDN is a rapidly evolving protein, accumulating non-silent mutations at a rate exceeding those of most other functional coding sequences studied in primates, Although all primate EDNs retain the structural and functional residues known to be prerequisites for ribonuclease activity, we have shown previously that recombinant EDN derived from a New World monkey sequence (Saguinus oedipus) had significantly less catalytic activity than the human (hEDN) ortholog. In this work, we have prepared recombinant proteins from EDN from sequences derived from orangutan (Pongo pygmaeus, oEDN) and Old World monkey (Macaca fascicularis, mcEDN) genomic DNAs, and from a second New World monkey sequence (Aotus trivirgatus, omEDN) as well, The catalytic efficiencies [k(cat)/K-m (M-1 s(-1))] determined for both oEDN and mcEDN were similar to that determined previously for hEDN, while omEDN displayed similar to 100-fold less catalytic activity, The relative ribonuclease activities of hEDN/omEDN chimeras pointed to a C-terminal segment as crucial to the enhanced catalytic activity hEDN, and substitution of Arg 132-Ile 133 of hEDN with the Thr-Thr pair at the analogous position in omEDN resulted in an similar to 10-fold reduction in hEDN's catalytic efficiency, However, the reverse substitution, Arg-Ile for Thr-Thr in omEDN, did not enhance the catalytic efficiency of this relatively inactive protein, These results indicate that the Arg and/or Ile residues adjacent to the C-terminus are necessary (but not sufficient) for enhanced ribonuclease activity among the primate EDNs, and will permit prediction of the relative ribonuclease activities based on differences in primary structure. RP Rosenberg, HF (reprint author), NIAID,HOST DEF LAB,NIH,BLDG 10,ROOM 11N104,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 26 TC 19 Z9 20 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD, ENGLAND OX2 6DP SN 0305-1048 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD SEP 1 PY 1997 VL 25 IS 17 BP 3532 EP 3536 DI 10.1093/nar/25.17.3532 PG 5 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA XU793 UT WOS:A1997XU79300023 PM 9254715 ER PT J AU McCormick, KA Cummings, MA Kovner, C AF McCormick, KA Cummings, MA Kovner, C TI The role of the Agency for Health Care Policy and Research in improving outcomes of care SO NURSING CLINICS OF NORTH AMERICA LA English DT Article AB This article describes the various outcomes programs supported by the Agency for Health Care Policy and Research (AHCPR). The mission of the agency is to generate and disseminate information that improves the delivery and quality of health care. The agency is charged with helping consumers, providers, purchasers, health plans, and policy makers meet the challenge of improving the quality: of health care services while reducing spending. AHCPR has been recognized as funding the development of ''gold standard'' clinical practice guidelines and the source of unbiased, science-based information on what works and does not work in health care. C1 AHCPR,CTR OUTCOMES & EFFECTIVENESS RES,ROCKVILLE,MD 20852. AHCPR,CTR PRIMARY CARE RES,ROCKVILLE,MD 20852. RP McCormick, KA (reprint author), AHCPR,CTR INFORMAT TECHNOL,2101 E JEFFERSON ST,SUITE 602,ROCKVILLE,MD 20852, USA. NR 15 TC 8 Z9 8 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0029-6465 J9 NURS CLIN N AM JI Nurs. Clin. North Am. PD SEP PY 1997 VL 32 IS 3 BP 521 EP & PG 23 WC Nursing SC Nursing GA XW400 UT WOS:A1997XW40000004 PM 9254637 ER PT J AU Sigmon, HD Grady, PA Amende, LM AF Sigmon, HD Grady, PA Amende, LM TI The National Institute of Nursing Research explores opportunities in genetics research SO NURSING OUTLOOK LA English DT Article AB Genetics offers many opportunities for nursing research, ranging from basic biologic and behavioral investigations to clinical and population studies, and nurse researchers offer a unique perspective and special expertise that is not otherwise found in genetics research. Nurse researchers can take leadership roles and contribute to basic genetic studies with their biologic, environmental, and behavioral linkages; the genetic determination of physiologic responses; and applied studies aimed at translating basic science findings into interventions to solve clinical problems. C1 NIH,DIV EXTRAMURAL ACTIVITIES,BETHESDA,MD. RP Sigmon, HD (reprint author), NATL INST NURSING RES,NIH,BETHESDA,MD, USA. NR 0 TC 6 Z9 6 U1 0 U2 0 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 SN 0029-6554 J9 NURS OUTLOOK JI Nurs. Outlook PD SEP-OCT PY 1997 VL 45 IS 5 BP 215 EP 219 DI 10.1016/S0029-6554(97)90068-3 PG 5 WC Nursing SC Nursing GA YE161 UT WOS:A1997YE16100006 PM 9364531 ER PT J AU Fitzgerald, ST Hill, MN Santamaria, B Howard, C Jadack, R AF Fitzgerald, ST Hill, MN Santamaria, B Howard, C Jadack, R TI Nurses' perceptions of consensus reports containing recommendations for practice SO NURSING OUTLOOK LA English DT Article ID INFORMATION; DISSEMINATION; GUIDELINE; PROGRAM AB Consensus reports providing guidelines designed to alter clinical practice are being disseminated with increasing frequency by professional associations, the government, and voluntary health agencies. The purpose of this study was to examine nurses' perceptions of consensus reports that contain recommendations designed to alter clinical practice, including the extent to which consensus reports offer relative advantage over other more traditional sources of practice-related information. Strategies for encouraging the use of consensus reports are discussed. C1 JOHNS HOPKINS UNIV,SCH NURSING,BALTIMORE,MD. BALTIMORE VET ADM HOSP,HOSP BASED HOME CARE,BALTIMORE,MD. NHLBI,BETHESDA,MD 20892. OHIO STATE UNIV,COLL NURSING,COLUMBUS,OH 43210. RP Fitzgerald, ST (reprint author), JOHNS HOPKINS UNIV,SCH HYG & PUBL HLTH,615 N WOLFE ST,BALTIMORE,MD, USA. NR 22 TC 1 Z9 1 U1 0 U2 0 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 SN 0029-6554 J9 NURS OUTLOOK JI Nurs. Outlook PD SEP-OCT PY 1997 VL 45 IS 5 BP 229 EP 235 DI 10.1016/S0029-6554(97)90071-3 PG 7 WC Nursing SC Nursing GA YE161 UT WOS:A1997YE16100009 PM 9364534 ER PT J AU Sinha, R Patterson, BH Norkus, EP Ziegler, RG AF Sinha, R Patterson, BH Norkus, EP Ziegler, RG TI Serum ascorbic acid stability over an extended period: Relevance to epidemiological studies SO NUTRITION RESEARCH LA English DT Article DE ascorbic acid; vitamin C; stabilization; epidemiological studies ID INVASIVE CERVICAL-CANCER; VITAMIN-C; PLASMA; RISK AB Epidemiological evidence suggests that intake of vitamin C and of fruit and vegetables rich in vitamin C may reduce the risk of certain cancers. Most epidemiological studies have relied on estimates of vitamin C based on questionnaires because serum ascorbic acid (AA) can be very unstable. The objective of this study was to investigate the effect of extended storage at -70 degrees C and of multiple free-thaws on AA concentration in stabilized human serum from a large multi-center cervical cancer case-control study; the serum samples had been stabilized by acidification with meta-phosphoric acid and stored at -70 degrees C. The results showed that under these conditions human serum samples are stable for periods of at least 2 years. There were indications that sample preparation in the field and freezing and thawing the stabilized serum samples could affect reproducibility and validity. Overall, our results indicate that with this stabilization method, biological material collected in large-scale, multicenter studies remains useful for AA analysis for at least 2 years after collection. Published by Elsevier Science Inc. C1 NCI,BIOMETRY BRANCH,DCPC,BETHESDA,MD 20892. OUR LADY MERCY UNIV,MED CTR,DEPT BIOMED RES,BRONX,NY 10466. RP Sinha, R (reprint author), NCI,NUTR EPIDEMIOL BRANCH,DCEG,EPN RM 430,BETHESDA,MD 20892, USA. RI Sinha, Rashmi/G-7446-2015 OI Sinha, Rashmi/0000-0002-2466-7462 NR 21 TC 0 Z9 0 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0271-5317 J9 NUTR RES JI Nutr. Res. PD SEP PY 1997 VL 17 IS 9 BP 1409 EP 1415 DI 10.1016/S0271-5317(97)00132-2 PG 7 WC Nutrition & Dietetics SC Nutrition & Dietetics GA XR374 UT WOS:A1997XR37400003 ER PT J AU Kant, AK Thompson, FE AF Kant, AK Thompson, FE TI Measures of overall diet quality from a food frequency questionnaire: National Health Interview Survey, 1992 SO NUTRITION RESEARCH LA English DT Article; Proceedings Paper CT Experimental Biology 96 Meeting CY APR 14-18, 1996 CL WASHINGTON, DC DE dietary diversity; diet quality; food frequency questionnaire; National Health Interview Survey ID DIVERSITY; INDEX AB We developed dietary variety based measures of diet quality using food frequency questionnaire (FFQ) data from the National Health Interview Survey (NHIS), 1992. FFQs from 10,799, aged greater than or equal to 18 years, were examined. We grouped the 68 items in the NHIS FFQ into two categories-nutrient-dense, and energy-dense, nutrient-poor. A dietary variety score (DVS), comprised of the number of food items mentioned at least once a week from the nutrient-dense group (54 items), was calculated for each respondent. A dietary variety score for recommended (DVSR) foods was also computed. The DVSR counted at least weekly mentions of foods recommended in current dietary guidance (27 items). The mean+/-SE of DVS and DVSR were 21+/-0.1 and 11.6+/-0.1, respectively. Education, total energy, calcium, vitamin C, carotenoid intakes, and compliance with recommendation of the Food Guide Pyramid correlated positively with the DVS and DVSR. Percent energy from fat was inversely related with DVSR, but was unrelated with DVS. Nutrition knowledge correlated positively with both scores. In conclusion, the scores developed were correlated with nutrient and food group intake, and may be suitable for assessment of these attributes of diet quality when only limited dietary information is available. (C) 1997 Elsevier Science Inc. C1 NCI,NIH,BETHESDA,MD 20892. RP Kant, AK (reprint author), CUNY QUEENS COLL,REMSEN HALL,ROOM 306E,FLUSHING,NY 11367, USA. NR 22 TC 39 Z9 39 U1 0 U2 2 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0271-5317 J9 NUTR RES JI Nutr. Res. PD SEP PY 1997 VL 17 IS 9 BP 1443 EP 1456 DI 10.1016/S0271-5317(97)00135-8 PG 14 WC Nutrition & Dietetics SC Nutrition & Dietetics GA XR374 UT WOS:A1997XR37400006 ER PT J AU Stayner, L Smith, R Bailer, J Gilbert, S Steenland, K Dement, J Brown, D Lemen, R AF Stayner, L Smith, R Bailer, J Gilbert, S Steenland, K Dement, J Brown, D Lemen, R TI Exposure-response analysis of risk of respiratory disease associated with occupational exposure to chrysotile asbestos SO OCCUPATIONAL AND ENVIRONMENTAL MEDICINE LA English DT Article DE chrysotile asbestos; risk assessment; epidemiology ID SAFETY-AND-HEALTH; LUNG-CANCER; MORTALITY; WORKERS; MESOTHELIOMA; INSTITUTE; THRESHOLD; TEXTILE; SMOKING; MODELS AB Objectives-To evaluate alternative models and estimate risk of mortality from lung cancer and asbestosis after occupational exposure to chrysotile asbestos. Methods-Data were used from a recent update of a cohort mortality study of workers in a South Carolina textile factory. Alternative exposure-response models were evaluated with Poisson regression. A model designed to evaluate evidence of a threshold response was also fitted. Lifetime risks of lung cancer and asbestosis were estimated with an actuarial approach that accounts for competing causes of death. Results-A highly significant exposure-response relation was found for both lung cancer and asbestosis. The exposure-response relation for lung cancer seemed to be linear on a multiplicative scale, which is consistent with previous analyses of lung cancer and exposure to asbestos. In contrast, the exposure-response relation for asbestosis seemed to be nonlinear on a multiplicative scale in this analysis. There was no significant evidence for a threshold in models of either the lung cancer or asbestosis, The excess lifetime risk for white men exposed for 45 years at the recently revised OSHA standard of 0.1 fibre/ml was predicted to be about 5/1000 for lung cancer, and 2/1000 for asbestosis. Conclusions-This study confirms the findings from previous investigations of a strong exposure-response relation between exposure to chrysotile asbestos and mortality from lung cancer, and asbestosis. The risk estimates for lung cancer derived from this analysis are higher than those derived from other populations exposed to chrysotile asbestos. Possible reasons for this discrepancy are discussed. C1 MIAMI UNIV,DEPT MATH & STAT,OXFORD,OH 45056. DUKE UNIV,MED CTR,DIV ENVIRONM & OCCUPAT MED,DURHAM,NC 27710. NATL INST ENVIRONM HLTH SCI,RES TRIANGLE PK,NC. RP Stayner, L (reprint author), NIOSH,CTR DIS CONTROL,ROBERT A TAFF LABS,4676 COLUMBIA PKWY,CINCINNATI,OH 45226, USA. NR 27 TC 86 Z9 88 U1 1 U2 4 PU BRITISH MED JOURNAL PUBL GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON, ENGLAND WC1H 9JR SN 1351-0711 J9 OCCUP ENVIRON MED JI Occup. Environ. Med. PD SEP PY 1997 VL 54 IS 9 BP 646 EP 652 PG 7 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA XU791 UT WOS:A1997XU79100005 PM 9423577 ER PT J AU Vaughan, TL Stewart, PA Davis, S Thomas, DB AF Vaughan, TL Stewart, PA Davis, S Thomas, DB TI Work in dry cleaning and the incidence of cancer of the oral cavity, larynx, and oesophagus SO OCCUPATIONAL AND ENVIRONMENTAL MEDICINE LA English DT Article DE neoplasms; larynx; oral cavity; oesophageal; gastric cardia; adenocarcinoma; dry cleaning; perchloroethylene ID OCCUPATIONAL EXPOSURE; PERCHLOROETHYLENE EXPOSURE; RISK-FACTORS; TETRACHLOROETHYLENE; CLEANERS; INDUSTRY; SHOPS AB Objectives-To investigate whether employment in dry cleaning, and potential exposure to perchloroethylene (PCE), were associated with increased risk of carcinoma of the oral cavity and pharynx, larynx, oesophagus, and gastric cardia. Methods-Two population based case-control studies were carried out. There were 491 cases of carcinoma of the oral cavity and pharynx, 235 of the larynx, and 404 of the oesophagus and gastric cardia. 724 controls were selected by random digit dialing. Personal interviews ascertained information on lifetime job histories, cigarette use, alcohol consumption, and other potential risk factors. The probability and level of exposure to PCE were estimated from the scientific literature. Results-People who worked in dry cleaning tended to consume less alcohol and cigarettes than the general population. The adjusted odds ratio (OR) associated with ever having worked in dry cleaning was 1.6 (95% confidence interval (95% CI) = 0.6 to 4.4) for all cancer types together. The strongest associations were with laryngeal (OR 2.7; 95% CI 0.6 to 10.9) and oesophageal squamous cell carcinomas (OR 3.6; 95% CI 0.5 to 27.0). For laryngeal cancer, the relative risk increased with number of years employed in the dry cleaning industry (P = 0.14. The two cases of oesophageal squamous cell carcinomas had worked in dry cleaning for only a short time. Analyses of subsites showed higher risks for supraglottic laryngeal cancer (OR 5.7; 95% CI 1.0 to 32.1) and cancer of the tongue (OR 2.3; 95% CI 0.4 to 12.6). Analyses of exposure to PCE yielded similar results. Conclusions-These findings could easily be explained by chance; nevertheless, they are consistent with previous reports of excess risk of oesophageal, laryngeal, and tongue cancer, and suggest that previous studies of dry cleaners that could not control for alcohol and cigarette use may have underestimated the relative risks of such cancers. C1 FRED HUTCHINSON CANC RES CTR,PROGRAM EPIDEMIOL MP474,SEATTLE,WA 98104. UNIV WASHINGTON,DEPT EPIDEMIOL,SEATTLE,WA 98195. NCI,EPIDEMIOL & BIOSTAT PROGRAM,ROCKVILLE,MD. FU NCI NIH HHS [R01 CA30022, U01 CA57949, R37 CA41530] NR 20 TC 21 Z9 22 U1 1 U2 5 PU BRITISH MED JOURNAL PUBL GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON, ENGLAND WC1H 9JR SN 1351-0711 J9 OCCUP ENVIRON MED JI Occup. Environ. Med. PD SEP PY 1997 VL 54 IS 9 BP 692 EP 695 PG 4 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA XU791 UT WOS:A1997XU79100013 PM 9423585 ER PT J AU Koevary, SB Caspi, RR AF Koevary, SB Caspi, RR TI Prevention of experimental autoimmune uveoretinitis by intrathymic S-antigen injection SO OCULAR IMMUNOLOGY AND INFLAMMATION LA English DT Article DE experimental autoimmune uveoretinitis (EAU); S-antigen; intrathymic; prevention; pertussis ID DONOR-SPECIFIC UNRESPONSIVENESS; ACETYLCHOLINE-RECEPTOR; ISLET TRANSPLANTATION; INDUCTION; TOLERANCE; RATS; UVEITIS; INHIBITION; THYMUS; PROTEIN AB The objective of this paper was to determine whether intrathymic injection of retinal S-antigen (S-Ag) can prevent experimental autoimmune uveoretinitis (EAU) in Lewis rats. Lewis rats were injected intrathymically with 25-100 mu g of S-Ag in 100 mu l split between thymic lobes. Controls received vehicle alone (PBS) or 100 mu g of BSA. Animals were immunized two weeks later with 100 mu g of S-Ag in CFA with or without pertussis toxin (0.5 mu g/rat). Clinical ocular disease was confirmed by histopathology. Splenocytes and lymph node cells were assayed, in vitro, for their ability to proliferate in response to various concentrations of S-Ag. Furthermore, attempts were made to adoptively transfer protection to naive rats using spleen cells from intrathymically injected animals and to adoptively transfer EAU to protected rats using Con A activated cells from affected animals. Intrathymic injection of S-Ag reduced the incidence of EAU in animals subsequently immunized with S-Ag and pertussis, and prevented it entirely in rats immunized in the absence of pertussis. Splenic and lymph node cells from intrathymically injected animals showed reduced reactivity to S-Ag compared to controls, suggesting that intrathymic S-Ag injection may have rendered them tolerant to this antigen. We were unable to adoptively transfer protection to naive rats, nor were intrathymically injected rats protected from EAU induced by the adoptive transfer of primed lymph node cells. These data demonstrate that intrathymic S-Ag injection can be an effective method for protection from EAU, apparently through the induction of immunological tolerance and not active suppression. The tolerance was not absolute and could be overcome by increasing the intensity of the antigenic challenge. C1 NEI,SECT IMMUNOREGULAT,IMMUNOL LAB,NIH,BETHESDA,MD 20892. RP Koevary, SB (reprint author), NEW ENGLAND COLL OPTOMETRY,OCULAR RES CTR,424 BEACON ST,BOSTON,MA 02115, USA. NR 29 TC 5 Z9 5 U1 0 U2 0 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 SEP PY 1997 VL 5 IS 3 BP 165 EP 172 PG 8 WC Ophthalmology SC Ophthalmology GA YC278 UT WOS:A1997YC27800003 PM 9326761 ER PT J AU Yu, JJ Reed, EL Mu, CJ BostickBruton, F Reed, E AF Yu, JJ Reed, EL Mu, CJ BostickBruton, F Reed, E TI Demonstration of a polymorphism in the gene ERCC1 by two DNA sequencing methods SO ONCOLOGY REPORTS LA English DT Article DE ERCC1; DNA repair; ovarian cancer ID EXCISION-REPAIR AB New methodology is important to the advancement of biomedical science. We recently described a polymorphism within exon IV of the ERCC1 gene, which is associated with an approximate 50% decrease in codon usage in some biological systems. In this report we show that this polymorphism can be readily demonstrated by standard manual DNA sequencing, and by a recently developed methodology which relies on spectrophotometric principles. The major advantage of this new methodology is that several-fold more samples can be assessed per unit time, at reduced cost. C1 NCI,MED OVARIAN CANC SECT,MED BRANCH,DEV THERAPEUT DEPT,DIV CLIN SCI,BETHESDA,MD 20892. NR 18 TC 2 Z9 2 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 1021-335X J9 ONCOL REP JI Oncol. Rep. PD SEP-OCT PY 1997 VL 4 IS 5 BP 905 EP 907 PG 3 WC Oncology SC Oncology GA XQ116 UT WOS:A1997XQ11600007 PM 21590163 ER PT J AU Colleoni, M Liessi, G Mastrapasqua, G Boni, L Nelli, P Vicario, G Sgarbossa, G Pancheri, F Manente, P AF Colleoni, M Liessi, G Mastrapasqua, G Boni, L Nelli, P Vicario, G Sgarbossa, G Pancheri, F Manente, P TI Prognostic factors in patients with hepatocellular carcinoma submitted to chemoembolization SO ONCOLOGY REPORTS LA English DT Article DE chemoembolization; intra-arterial chemotherapy; hepatocellular carcinoma ID TRANSCATHETER ARTERIAL EMBOLIZATION; MULTIVARIATE-ANALYSIS; INTRAARTERIAL ADRIAMYCIN; ETHIODIZED OIL; CISPLATIN; CIRRHOSIS; LIPIODOL; INFUSION; SURVIVAL; THERAPY AB The prognosis of unresectable hepatocellular carcinoma is poor. Encouraging response rates have been reported with chemoembolization, but no survival advantage has been demonstrated. Assessment of the impact of the treatment modality on prognosis is complicated by a poor understanding of the prognostic factors in the disease. We therefore evaluated, through univariate and multivariate analysis, the role on prognosis of 16 variables in 63 patients submitted to chemoembolization. Patients were treated with epirubicin (50 mg) plus ethiodized oil and gelatin sponge (22 cases) or with a new program combining i.a, chemotherapy with chemoembolization (41 cases) as follows: L-leucovorin, 100 mg/m(2) i.v.; fluorouracil, 800 mg/m(2) i.a.; carboplatin, 250 mg/m(2) i.a. Chemoembolization with mitoxantrone, 10 mg/m(2), plus ethiodized oil and gelatine sponge was performed immediately after. Median survival for the whole group of patients was 294 days. A multivariate analysis showed a highly significant influence on survival for Child's status (p=0.002) and for TNM stage (p=0.01). Median survival for patients with Child's A disease was 13.9 months and for patients with TNM stage I-II disease 19 months. In conclusion, our data suggest that patients with limited disease and adequate liver function have a longer survival after chemoembolization. C1 CITY HOSP,DIV MED ONCOL,CASTELFRANCO VENE,ITALY. CITY HOSP,SERV RADIOL,CASTELFRANCO VENE,ITALY. CITY HOSP,DIV MED,CASTELFRANCO VENE,ITALY. NATL CANC INST,SERV EPIDEMIOL,GENOA,ITALY. NR 33 TC 1 Z9 1 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 1021-335X J9 ONCOL REP JI Oncol. Rep. PD SEP-OCT PY 1997 VL 4 IS 5 BP 1025 EP 1028 PG 4 WC Oncology SC Oncology GA XQ116 UT WOS:A1997XQ11600032 PM 21590188 ER PT J AU Favara, BE Steele, A AF Favara, BE Steele, A TI Langerhans cell histiocytosis of lymph nodes: A morphological assessment of 43 biopsies SO PEDIATRIC PATHOLOGY & LABORATORY MEDICINE LA English DT Article; Proceedings Paper CT 10th Annual Meeting of the Histiocyte-Society CY OCT 03, 1993 CL SAN FRANCISCO, CA SP Histiocyte Soc DE granuloma; histiocytosis; Langerhans cell histiocytosis; lymph node ID EOSINOPHILIC GRANULOMA; VIRAL ETIOLOGY; DIFFERENTIATION; EXPRESSION; DISEASE; LESIONS AB The morphology of Langerhans cell histiocytosis (LCH) involving lymph nodes was analyzed in 43 biopsies from 39 patients and findings were correlated with clinical data. Five histological motifs were recognized: sinusoidal, limited sinusoidal, epithelioid granulomatous, partial effacement, and total effacement. Lesions were composed of histiocytes of the Langerhans cell (LC) family, macrophages, multinucleated giant histiocytes, T lymphocytes, and eosinophils in varying proportions. Proliferative fractions ranged from 2.6 to 48% and 2 of 25 specimens showed a hyperdiploid aneuploid DNA ploidy profile. Epithelioid granulomas composed of histiocytes with the LC phenotype dominated three abdominal specimens, reflecting a picture of LCH not previously reported. Total effacement, seen in three patients, was associated with unmarked histiocytoid cells, high proliferative fraction, aneuploid DNA ploidy profile, and, In two, a fatal outcome. Different histologic appearances in lesions from separate sites of the same patient were seen in the cases with epithelioid granulomas and in those with total effacement. The diverse histopathology in lymph nodes involved by LCH is considered in the context of current knowledge of this enigmatic disease. C1 NIH,ROCKY MT LABS,PERSISTENT VIRAL DIS LAB,HAMILTON,MT. UNIV UTAH,DEPT PATHOL,SALT LAKE CITY,UT. UNIV S FLORIDA,ALL CHILDRENS HOSP,ST PETERSBURG,FL 33701. NR 39 TC 31 Z9 32 U1 1 U2 1 PU TAYLOR & FRANCIS PI BRISTOL PA 1900 FROST ROAD, SUITE 101, BRISTOL, PA 19007-1598 SN 1077-1042 J9 PEDIATR PATHOL LAB M JI Pediatr. Pathol. Lab. Med. PD SEP-OCT PY 1997 VL 17 IS 5 BP 769 EP 787 DI 10.1080/107710497174471 PG 19 WC Pathology; Pediatrics SC Pathology; Pediatrics GA XR530 UT WOS:A1997XR53000004 PM 9267889 ER PT J AU Munoz, KA KrebsSmith, SM BallardBarbash, R Cleveland, GE AF Munoz, KA KrebsSmith, SM BallardBarbash, R Cleveland, GE TI Food intakes of US children and adolescents compared with recommendations SO PEDIATRICS LA English DT Article DE diet; children; food; RDA; pyramid ID AMERICAN CHILDREN; PRESCHOOL-CHILDREN; DIETARY FIBER; RECALL AB Objectives. To determine the proportion of youth meeting national recommendations for food group intake and to identify food intake patterns. Design. The US Department of Agriculture's 1989-1991 Continuing Surveys of Food Intakes by Individuals were used to estimate food intake. Intake was determined from 3 days of diet by disaggregating foods into their component ingredients and using weights that correspond to servings. Participants. The sample included 3307 youth, 2 to 19 years of age, living in the 48 conterminous United States. Main Outcome Measures. Mean number of servings and percentage of individuals meeting national recommendations for food group intake according to demographic characteristics, patterns of intake, and nutrient profiles associated with each pattern. Results. Mean numbers of servings per day were below minimum recommendations for all food groups except the dairy group (ages 2 to 11). Percentages of youth meeting recommendations ranged from similar to 30% for fruit, grain, meat, and dairy to 36% for vegetables. Sixteen percent of youth did not meet any recommendations, and 1% met all recommendations. The pattern of meeting all recommendations resulted in nutrient intakes above the recommended dietary allowances and was high in fat. Conversely, meeting none of the recommendations resulted in intakes well below the recommended dietary allowances for some nutrients. Total fat and added sugars averaged 35% and 15% of energy, respectively, and levels were similar among most demographic groups. Conclusion. Children and teens in the United States follow eating patterns that do not meet national recommendations. Nutrition education and intervention are needed among US children. C1 NCI,DIV CANC PREVENT & CONTROL,APPL RES BRANCH,NIH,BETHESDA,MD. USDA ARS,BELTSVILLE HUMAN NUTR RES CTR,FOOD SURVEYS RES GRP,RIVERDALE,MD. NR 23 TC 329 Z9 342 U1 2 U2 21 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 SEP PY 1997 VL 100 IS 3 BP 323 EP 329 DI 10.1542/peds.100.3.323 PG 7 WC Pediatrics SC Pediatrics GA XU212 UT WOS:A1997XU21200001 PM 9282700 ER PT J AU Isikay, L Frokiaer, J Marples, D Jorgensen, TM Djurhuus, JC Knepper, MA Nielsen, S AF Isikay, L Frokiaer, J Marples, D Jorgensen, TM Djurhuus, JC Knepper, MA Nielsen, S TI Persistent downregulation of kidney collecting duct water channel AQP2 following release of ureteral obstruction is associated with a urinary concentrating defect. SO PEDIATRICS LA English DT Meeting Abstract C1 AARHUS UNIV,INST EXPT CLIN RES,DK-8000 AARHUS C,DENMARK. AARHUS UNIV,DEPT CELL BIOL,DK-8000 AARHUS C,DENMARK. UNIV LEEDS,DEPT PHYSIOL,LEEDS LS2 9JT,W YORKSHIRE,ENGLAND. NHLBI,NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ACAD PEDIATRICS PI ELK GROVE VILLAGE PA 141 NORTH-WEST POINT BLVD, ELK GROVE VILLAGE, IL 60007-1098 SN 0031-4005 J9 PEDIATRICS JI Pediatrics PD SEP PY 1997 VL 100 IS 3 SU S BP 540 EP 540 PG 1 WC Pediatrics SC Pediatrics GA XU278 UT WOS:A1997XU27800236 ER PT J AU Long, RM AF Long, RM TI What are the high risk high impact (R21) awards supported by the NIGMS? Where is information available about this new program? SO PHARMACEUTICAL RESEARCH LA English DT News Item RP Long, RM (reprint author), NIGMS,PHARMACOL & PHYSIOL SCI BRANCH,DIV PHARMACOL PHYSIOL & BIOL CHEM,NIH,BETHESDA,MD 20892, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 SEP PY 1997 VL 14 IS 9 BP 1103 EP 1103 PG 1 WC Chemistry, Multidisciplinary; Pharmacology & Pharmacy SC Chemistry; Pharmacology & Pharmacy GA XY991 UT WOS:A1997XY99100001 ER PT J AU Graumlich, JF Ludden, TM ConryCantilena, C Cantilena, LR Wang, YH Levine, M AF Graumlich, JF Ludden, TM ConryCantilena, C Cantilena, LR Wang, YH Levine, M TI Pharmacokinetic model of ascorbic acid in healthy male volunteers during depletion and repletion SO PHARMACEUTICAL RESEARCH LA English DT Article DE ascorbic acid; pharmacokinetics; human; models-theoretical; models-nonlinear; bioavailability; ascorbic acid deficiency ID VITAMIN-C; HUMAN-NEUTROPHILS; TRANSPORT; ACCUMULATION; ABSORPTION AB Purpose. To develop a new pharmacokinetic model for ascorbic acid (vitamin C) since no previously published model describes ascorbic acid absorption and disposition over a broad physiologic range of doses and plasma concentrations. Methods. A new model was developed through exploratory simulations. The model was fitted to pharmacokinetic data obtained from seven healthy volunteers who underwent ascorbic acid depletion then gradual repletion. Concentrations of ascorbic acid were measured in plasma and urine. Final pharmacokinetic model parameter estimates were obtained using nonlinear regression analysis. Results. The new model included saturable absorption, distribution and renal tubular reabsorption parameters. The model described ascorbic acid concentrations in plasma, cells, and urine during depletion and gradual repletion phases with a residual error less than 15%. Conclusions. The model was useful for obtaining a new understanding of the likely causes for the complex concentration-time profile observed during gradual repletion. At doses of 200 to 2500 mg per day, the plateau in pre-dose concentrations is largely due to apparent saturation of tissue uptake and less a function of oral bioavailability and renal excretion than previously thought. C1 UNIV NEBRASKA,MED CTR,DEPT PHARMACEUT SCI,OMAHA,NE 68182. NIH,WARREN GRANT MAGNUSON CLIN CTR,DEPT TRANSFUS MED,BETHESDA,MD 20892. UNIFORMED SERV UNIV HLTH SCI,DIV CLIN PHARMACOL,BETHESDA,MD 20814. NIDDKD,MOL & CLIN NUTR SECT,NIH,BETHESDA,MD 20892. NIDDKD,INTRAMURAL NUTR PROGRAM,NIH,BETHESDA,MD 20892. RP Graumlich, JF (reprint author), UNIV ILLINOIS,COLL MED,DEPT BIOMED & THERAPEUT SCI,PEORIA,IL 61656, USA. FU NIDDK NIH HHS [DK-92-0032]; PHS HHS [224-88-3002] NR 28 TC 82 Z9 83 U1 2 U2 11 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 SEP PY 1997 VL 14 IS 9 BP 1133 EP 1139 DI 10.1023/A:1012186203165 PG 7 WC Chemistry, Multidisciplinary; Pharmacology & Pharmacy SC Chemistry; Pharmacology & Pharmacy GA XY991 UT WOS:A1997XY99100007 PM 9327438 ER PT J AU Miner, LL AF Miner, LL TI Cocaine reward and locomotor activity in C57BL/6J and 129/SvJ inbred mice and their F1 cross SO PHARMACOLOGY BIOCHEMISTRY AND BEHAVIOR LA English DT Article DE cocaine; conditioned place preference; locomotor activity; genetics; transgenics ID LONG-TERM POTENTIATION; MUTANT MICE; RECEPTOR; DEFICIENT AB Large individual differences exist among mice in their behavioral responses to drugs of abuse, and many of these differences have a substantial genetic basis. The creation of new animal models using recombinant DNA technology has provided new genetic tools for assessing the role of specific candidate genes in drug response. This study presents a characterization of cocaine activation and reward in the two strains used most commonly for production of knockout mice, C57BL/6J and 129/SvJ, and their outcrossed F1 offspring. Using conditioned place preference, the study demonstrates that there are large strain differences in spontaneous locomotor activity and in the rewarding effects of cocaine. The 129/SvJ strain is hypoactive and is very sensitive to the locomotor activating effects of cocaine but does not develop cocaine-conditioned place preference under conditions that yield significant place preference in C57BL/6J mice. These phenotypes are not inherited in a simple additive manner, but rather the F1 generation resembles the C57BL/6J progenitor strain for a number of the behaviors examined. (C) 1997 Elsevier Science Inc. C1 NIDA,MOL GENET SECT,DIV INTRAMURAL RES,BALTIMORE,MD 21224. NR 23 TC 88 Z9 90 U1 0 U2 1 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 SEP PY 1997 VL 58 IS 1 BP 25 EP 30 DI 10.1016/S0091-3057(96)00465-0 PG 6 WC Behavioral Sciences; Neurosciences; Pharmacology & Pharmacy SC Behavioral Sciences; Neurosciences & Neurology; Pharmacology & Pharmacy GA XP135 UT WOS:A1997XP13500004 PM 9264065 ER PT J AU Heishman, SJ Arasteh, K Stitzer, ML AF Heishman, SJ Arasteh, K Stitzer, ML TI Comparative effects of alcohol and marijuana on mood, memory, and performance SO PHARMACOLOGY BIOCHEMISTRY AND BEHAVIOR LA English DT Article DE alcohol; marijuana; THC; humans; drug abuse; subjective effects; performance; psychomotor; memory; behavioral pharmacology ID DIVIDED ATTENTION PERFORMANCE; PSYCHOMOTOR PERFORMANCE; SMOKED MARIJUANA; CANNABIS USERS; SMOKING; ETHANOL; DELTA-9-TETRAHYDROCANNABINOL; HUMANS; COMBINATION; INTERFERENCE AB This study compared subjective and behavioral effect profiles of alcohol and smoked marijuana using technology that controlled puffing and inhalation parameters. Male volunteers (n = 5) with histories of moderate alcohol and marijuana use were administered three doses of alcohol (0.25, 0.5, or 1.0 g/kg), three doses of marijuana [4, 8, or 16 puffs of 3.55% Delta(9)-tetrahydrocannabinol (THC)], and placebo in random order under double blind conditions in seven separate sessions. Blood alcohol concentration (10-90 mg/dl) and THC levels (63-188 ng/ml) indicated that active drug was delivered to subjects dose dependently. Alcohol and marijuana produced dose-related changes in subjective measures of drug effect. Ratings of perceived impairment were identical for the high doses of alcohol and marijuana. Both drugs produced comparable impairment in digit-symbol substitution and word recall tests, but had no effect in time perception and reaction time tests. Alcohol, but not marijuana, slightly impaired performance in a number recognition test. These data are useful for understanding the relative performance impairment produced by alcohol and marijuana at the delivered doses and the relationship between their subjective and behavioral effects. (C) 1997 Elsevier Science Inc. C1 JOHNS HOPKINS UNIV,SCH MED,DEPT PSYCHIAT & BEHAV SCI,BALTIMORE,MD 21224. RP Heishman, SJ (reprint author), NIDA,ADDICT RES CTR,CLIN PHARMACOL BRANCH,5500 NATHAN SHOCK DR,BALTIMORE,MD 21224, USA. FU NIDA NIH HHS [DA-05880, DA-07209] NR 62 TC 113 Z9 114 U1 2 U2 21 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 SEP PY 1997 VL 58 IS 1 BP 93 EP 101 DI 10.1016/S0091-3057(96)00456-X PG 9 WC Behavioral Sciences; Neurosciences; Pharmacology & Pharmacy SC Behavioral Sciences; Neurosciences & Neurology; Pharmacology & Pharmacy GA XP135 UT WOS:A1997XP13500015 PM 9264076 ER PT J AU Lachowicz, JE Sibley, DR AF Lachowicz, JE Sibley, DR TI Molecular characteristics of mammalian dopamine receptors SO PHARMACOLOGY & TOXICOLOGY LA English DT Review ID INSITU HYBRIDIZATION HISTOCHEMISTRY; HAMSTER OVARY CELLS; RAT-BRAIN; MESSENGER-RNA; D2 RECEPTOR; D1 RECEPTOR; D2-DOPAMINE RECEPTOR; FUNCTIONAL-CHARACTERIZATION; CHROMOSOMAL LOCALIZATION; DIFFERENTIAL EXPRESSION AB Dopamine receptors belong to a large super-gene family of receptors which are linked to their signal transduction pathways through heterotrimeric G proteins. A variety of signalling events are known to be regulated by dopamine receptors including adenylate cyclase and phospholipase activities and various ion channels. Prior to the advent of molecular cloning technology, dopamine receptors were believed to belong to two subtypes, D-1 and D-2 This distinction was based on both pharmacological and functional criteria. We now know that at least five different dopamine receptors exist although they can still be described as to belonging within ''D-1'' and ''D-2'' subfamilies. The D-1 subfamily consists of two receptors - the D-1 and D-5, whereas the D-2, D-3 and D-4 receptors comprise the D-2 subfamily. The cloning and molecular characteristics of these five receptors are described in this review. C1 NINCDS,MOL NEUROPHARMACOL SECT,EXPT THERAPEUT BRANCH,NIH,BETHESDA,MD 20892. INDIANA UNIV,SCH MED,DEPT PEDIAT,NEUROENDOCRINE SECT,INDIANAPOLIS,IN 46202. NR 100 TC 89 Z9 89 U1 0 U2 9 PU MUNKSGAARD INT PUBL LTD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0901-9928 J9 PHARMACOL TOXICOL JI Pharmacol. Toxicol. PD SEP PY 1997 VL 81 IS 3 BP 105 EP 113 PG 9 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA XX553 UT WOS:A1997XX55300001 PM 9335067 ER PT J AU Pagano, G Bonassi, S DeBiase, A Degan, P Deeva, IB Doronin, YK Iaccarino, M Oral, R Warnau, M Korkina, LG AF Pagano, G Bonassi, S DeBiase, A Degan, P Deeva, IB Doronin, YK Iaccarino, M Oral, R Warnau, M Korkina, LG TI L-methionine induces stage-dependent changes of differentiation and oxidative activity in sea urchin embryogenesis SO PHARMACOLOGY & TOXICOLOGY LA English DT Article ID SUPEROXIDE-DISMUTASE; DNA METHYLATION; HYDROGEN-PEROXIDE; IN-VITRO; OXYGEN; FERTILIZATION; STRESS; 8-HYDROXY-2'-DEOXYGUANOSINE; GLUTATHIONE; ALUMINUM AB This study was to investigate developmental toxicity of some selected low molecular weight antioxidants, by utilising sea urchin embryos and gametes as model system. Sea urchin embryos or sperm were exposed at different developmental stages to L-methionine or some selected low molecular weight antioxidants: a) N-acetylcysteine; b) L-carnosine; c) L-homocarnosine, and d) L-anserine. L-methionine displayed developmental toxicity at levels greater than or equal to 10(-5) M, whereas the other agents tested were mostly active at levels greater than or equal to 10(-4) M. When embryos were exposed to 10(-4) M L-methionine or N-acetylcysteine at different developmental stages, the most severe effects were exerted by early exposures (0 to 2 hr after fertilisation), whereas later exposures turned to lesser or no effects. Cytogenetic analysis of L-methionine-exposed embryos showed a significant mitogenic effect and increase of mitotic aberrations. Fertilisation success was decreased by L-methionine (10(-6) M to 10(-3) M) added at the moment of fertilisation, with increasing developmental and cytogenetic abnormalities in the offspring. The formation of reactive oxygen species in embryos and gametes was determined by: a) analysing the DNA oxidative product, 8-hydroxy-2'-deoxyguanosine (8-OHdG), and b) luminol-dependent chemiluminescence. The results showed that: 1) 8-OHdG levels were increased during embryogenesis; 2) fertilisation was associated with a double-wave luminol-dependent chemiluminescence emission; 3) luminol-dependent chemiluminescence was maximal in cleavage, declining down to zero in plutei, and 4) an embryotoxic L-methionine or N-acetylcysteine level (10(-4) M) turned to a decrease in reactive oxygen species formation. The data suggest that L-methionine- or N-acetylcysteine-induced developmental toxicity is confined to early stages. A role for oxidative activity is suggested in modulating cell differentiation and embryogenesis, consistent with antioxidant-induced damage to early life stages. C1 NATL CANC INST,I-16132 GENOA,ITALY. FREE UNIV BRUSSELS,B-1050 BRUSSELS,BELGIUM. INST PAEDIAT HAEMATOL,MOSCOW 117437,RUSSIA. RP Pagano, G (reprint author), G PASCALE FDN,NATL CANC INST,VIA M SEMMOLA,I-80131 NAPLES,ITALY. OI bonassi, stefano/0000-0003-3833-6717 NR 53 TC 10 Z9 10 U1 0 U2 4 PU MUNKSGAARD INT PUBL LTD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0901-9928 J9 PHARMACOL TOXICOL JI Pharmacol. Toxicol. PD SEP PY 1997 VL 81 IS 3 BP 134 EP 143 PG 10 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA XX553 UT WOS:A1997XX55300005 PM 9335071 ER PT J AU Cott, JM AF Cott, JM TI In vitro receptor binding and enzyme inhibition by Hypericum perforatum extract SO PHARMACOPSYCHIATRY LA English DT Article ID LOCOMOTOR STIMULATION; DEPRESSION; GABA; PSEUDOHYPERICIN; SUPPRESSION; TOXICITY; AGENTS; DRUGS AB Hypericum perforatum L. Hypericaceae (St. John's wort), has been used since the time of ancient Greece for its many medicinal properties, Modern usage is still quite diverse and includes wound healing, kidney and lung ailments, insomnia and depression. This plant has been known to contain a red pigment, hypericin, and similar compounds, which have been assumed to be the primary active constituent(s) in this plant genus. A crude Hypericum extract was tested in a battery of 39 in vitro receptor assays, and two enzyme assays. A sample of pure hypericin was also tested. Hypericin had affinity only for NMDA receptors while the crude extract had significant receptor affinity for adenosine (nonspecific), GABA(A), GABA(B), benzodiazepine, inositol triphosphate, and monoamine oxidase (MAO) A and B. With the exception of GABA(A) and GABA(B), the concentrations of Hypericum exact required for these in vitro activities are unlikely to be attained after oral administration in whole animals or humans, These data are consistent with recent pharmacologic evidence suggesting that other constituents of this plant may be of greater importance for the reported psychotherapeutic activity, Alternative pharmacologic mechanisms for Hypericum's antidepressant activity are critically reviewed and the possible importance of GABA receptor binding in the pharmacology of Hypericum is highlighted. Some of these results have been previously reported (Cott, 1995; Cott, 1996; Cott and Misra, 1997). RP Cott, JM (reprint author), NIMH,PHARMACOL TREATMENT RES PROGRAM,NIH,5600 FISHERS LANE,ROOM 18-105,ROCKVILLE,MD 20857, USA. NR 37 TC 123 Z9 129 U1 1 U2 7 PU GEORG THIEME VERLAG PI STUTTGART PA P O BOX 30 11 20, D-70451 STUTTGART, GERMANY SN 0176-3679 J9 PHARMACOPSYCHIATRY JI Pharmacopsychiatry PD SEP PY 1997 VL 30 SU 2 BP 108 EP 112 DI 10.1055/s-2007-979529 PG 5 WC Pharmacology & Pharmacy; Psychiatry SC Pharmacology & Pharmacy; Psychiatry GA XZ839 UT WOS:A1997XZ83900009 PM 9342770 ER PT J AU Goldspiel, BR AF Goldspiel, BR TI Clinical overview of the taxanes SO PHARMACOTHERAPY LA English DT Article; Proceedings Paper CT University-of-Maryland-Cancer-Center Conference on Antineoplastics CY SEP 27-28, 1996 CL SAN FRANCISCO, CA SP Univ Maryland Canc Ctr ID PHASE-II TRIAL; METASTATIC BREAST-CANCER; CELL LUNG-CANCER; GYNECOLOGIC-ONCOLOGY-GROUP; EPITHELIAL OVARIAN-CANCER; 3-HOUR INFUSION; ACTIVE-DRUG; STAGE-III; PHARMACOKINETIC PROPERTIES; ANTHRACYCLINE-RESISTANT AB Paclitaxel and docetaxel are taxane antineoplastic agents with broad antitumor activity. Since being introduced, they have become increasingly important in the treatment of a number of major solid tumors. Paclitaxel plus a platinum analog is now considered first-line therapy for advanced ovarian cancer, and both paclitaxel and docetaxel have significant activity as single agents in recurrent ovarian cancer. Docetaxel may be useful in some of these women with ovarian cancer who fail or progress after paclitaxel-containing treatments. Both drugs have significant response rates in the treatment of breast cancer and are options for patients with advanced disease, including anthracycline-refractory disease. Administration of taxanes in new combination regimens and as adjuvant therapy for breast cancer is under investigation; for example, the combination of paclitaxel and doxorubicin is highly active, and comparative studies of taxanes and anthracyclines should help clarify optimal treatment regimens in breast cancer. Both drugs have significant activity alone in the treatment of advanced non-small cell lung cancer (NSCLC) and head and neck cancers. For the former, paclitaxel-cisplatin is now standard treatment in cooperative group combination therapy trials. As a result of its radiosensitizing properties, paclitaxel is undergoing extensive evaluation as combined modality treatment for advanced NSCLC and head and neck cancer. Both taxanes will probably be useful in combination regimens in head and neck cancer. Research is continuing to define further their roles and relative usefulness in other malignancies. RP Goldspiel, BR (reprint author), NIH,10 CTR DR,MSC 1196,BLDG 10,ROOM 1N-257,BETHESDA,MD 20892, USA. NR 156 TC 43 Z9 45 U1 0 U2 5 PU PHARMACOTHERAPY PUBLICATIONS INC PI BOSTON PA NEW ENGLAND MEDICAL CENTER BOX 806 171 HARRISON AVE, BOSTON, MA 02111 SN 0277-0008 J9 PHARMACOTHERAPY JI Pharmacotherapy PD SEP-OCT PY 1997 VL 17 IS 5 BP S110 EP S125 PN 2 PG 16 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA XX706 UT WOS:A1997XX70600004 PM 9322878 ER PT J AU Albro, PW Bilski, P Corbett, JT Schroeder, JL Chignell, CF AF Albro, PW Bilski, P Corbett, JT Schroeder, JL Chignell, CF TI Photochemical reactions and phototoxicity of sterols: Novel self-perpetuating mechanism for lipid photooxidation SO PHOTOCHEMISTRY AND PHOTOBIOLOGY LA English DT Article ID NEAR-ULTRAVIOLET RADIATIONS; SINGLET MOLECULAR-OXYGEN; HUMAN-SKIN FIBROBLASTS; XERODERMA-PIGMENTOSUM; CATIONIC SURFACTANT; ANTIOXIDANT DEFENSE; FAR-ULTRAVIOLET; ROSE-BENGAL; INDUCTION; DNA AB Sterols are important lipid components that may contribute to phototoxicity. We have found that phototoxic response in earthworms is related to sterols extractable with lipophilic solvents, The photochemically active compounds in worm lipids are 5,7,9(11),22-ergostatetraen-3 beta-ol (9-DHE) and 5,7,9(11)-cholestatrien-3 beta-ol (9-DDHC), respectively. Human skin lipids art: known to contain 9-DHE, We have also found 9-DDHC in human skin, which is reported here for the first rime, In the presence of an excess of the corresponding 5,7-dienes (ergosterol or 7-dehydrocholesterol), these photoactive sterols constitute a self-regenerating source of singlet molecular oxygen (O-1(2) during irradiation in vivo or in vitro with UVA (315-400 nm), The quantum yield for photosensitization of O-1(2) by 9-DHE was Estimated to be 0,09. The O-1(2), is scavenged by the dienes and the rate constant for O-1(2) quenching by ergosterol was found to be 1.2 X 10(7) M-1 s(-1) in methyl t-butyl ether (MTBE). This scavenging ultimately leads to the production of 5,8-endo-peroxide and hydrogen peroxide, Photochemically induced superoxide radical was also produced on irradiation of sterol 5,7,9-trienes and trapped with the spin trap 5,5-dimethyl-1-pyrroline N-oxide (DMPO). The production of singlet oxygen, peroxides and radicals by the sterols map be significant in the cell damaging and tumor promoting action of WA light on skin. C1 NIEHS, MOL BIOPHYS LAB, RES TRIANGLE PK, NC 27709 USA. NR 51 TC 41 Z9 42 U1 0 U2 1 PU AMER SOC PHOTOBIOLOGY PI AUGUSTA PA BIOTECH PARK, 1021 15TH ST, SUITE 9, AUGUSTA, GA 30901-3158 SN 0031-8655 J9 PHOTOCHEM PHOTOBIOL JI Photochem. Photobiol. PD SEP PY 1997 VL 66 IS 3 BP 316 EP 325 DI 10.1111/j.1751-1097.1997.tb03154.x PG 10 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA XW728 UT WOS:A1997XW72800006 PM 9297976 ER PT J AU Weiss, GH Gandjbakhche, AH AF Weiss, GH Gandjbakhche, AH TI Effects of nonlocalized target shape in the random walk description of transillumination experiments for optical imaging SO PHYSICAL REVIEW E LA English DT Article ID TISSUE; MEDIA AB A lattice random walk theory has been successfully used to interpret and analyze a variety of experimental data related to applications in optical imaging. A major advantage of the lattice theory is that it replaces cumbersome eigenfunction expansions resulting from diffusion theory by simpler relations expressed in terms of generating functions. The transillumination experiment has previously been analyzed by representing a region of increased absorptive properties in tissue by a single anomalous point. Here we extend the analysis to allow for k anomalous sites, thus providing a tool for studying the effects of nonlocality of the anomalous region. We show that if the absorption coefficient in the anomalous region is sufficiently small, the simple approximation based on the use of a single point with an anomalous absorption coefficient yields quite good results as compared to data obtained from phantoms. It is shown that the neglect of correlation effects leads to an underestimate of the absorption coefficient in an anomalous region. C1 NICHHD,OFF DIRECTOR,NIH,BETHESDA,MD 20892. RP Weiss, GH (reprint author), NIH,DIV COMP RES & TECHNOL,PHYS SCI LAB,BETHESDA,MD 20892, USA. NR 22 TC 4 Z9 4 U1 0 U2 0 PU AMERICAN PHYSICAL SOC PI COLLEGE PK PA ONE PHYSICS ELLIPSE, COLLEGE PK, MD 20740-3844 USA SN 1063-651X J9 PHYS REV E JI Phys. Rev. E PD SEP PY 1997 VL 56 IS 3 BP 3451 EP 3459 DI 10.1103/PhysRevE.56.3451 PN B PG 9 WC Physics, Fluids & Plasmas; Physics, Mathematical SC Physics GA XY130 UT WOS:A1997XY13000044 ER PT J AU Gitterman, M Shrager, RI Weiss, GH AF Gitterman, M Shrager, RI Weiss, GH TI Stochastic resonance and symmetry breaking in a one-dimensional system SO PHYSICAL REVIEW E LA English DT Article ID PASSAGE TIME PROBLEMS; NOISE; SIGNAL; DRIVEN AB We derive and discuss properties of an exact solution for the average time for trapping of a Brownian particle driven by a random, asymmetric but unbiased, telegraph signal. The particle moves along a line segment terminated by either two traps or a trap and a reflecting point. Numerical results suggest that stochastic resonance, defined as a nonmonotonic behavior of the mean trapping time, is absent in the first case but present in the second. This generalizes a result obtained earlier by Doering and Gadoua [Phys. Rev. Lett. 69, 2318 (1992)] and implies that symmetry breaking alone does not necessarily create stochastic resonance. C1 NIH,DIV COMP SCI & TECHNOL,BETHESDA,MD 20892. RP Gitterman, M (reprint author), BAR ILAN UNIV,DEPT PHYS,IL-52900 RAMAT GAN,ISRAEL. NR 21 TC 5 Z9 5 U1 0 U2 3 PU AMERICAN PHYSICAL SOC PI COLLEGE PK PA ONE PHYSICS ELLIPSE, COLLEGE PK, MD 20740-3844 USA SN 1063-651X J9 PHYS REV E JI Phys. Rev. E PD SEP PY 1997 VL 56 IS 3 BP 3713 EP 3716 DI 10.1103/PhysRevE.56.3713 PN B PG 4 WC Physics, Fluids & Plasmas; Physics, Mathematical SC Physics GA XY130 UT WOS:A1997XY13000076 ER PT J AU Klausner, R AF Klausner, R TI Supplemental issue: Priorities in behavioral research in cancer prevention and control - Preface SO PREVENTIVE MEDICINE LA English DT Editorial Material RP Klausner, R (reprint author), NCI,BETHESDA,MD 20892, USA. NR 0 TC 0 Z9 0 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 0091-7435 J9 PREV MED JI Prev. Med. PD SEP-OCT PY 1997 VL 26 IS 5 SU S BP S1 EP S1 DI 10.1006/pmed.1997.0236 PN 2 PG 1 WC Public, Environmental & Occupational Health; Medicine, General & Internal SC Public, Environmental & Occupational Health; General & Internal Medicine GA XY879 UT WOS:A1997XY87900001 ER PT J AU Weed, DL AF Weed, DL TI The behavior-biology interface in cancer prevention and control science SO PREVENTIVE MEDICINE LA English DT Article; Proceedings Paper CT NCI/National-Cancer-Advisory-Board Workshop on Behavioral Research in Cancer Prevention and Control CY JUL 06-07, 1995 CL WASHINGTON, DC SP NCI, Natl Canc Advisory Board ID CERVICAL-CANCER; CAUSAL INFERENCE; BLACK-BOX; EPIDEMIOLOGY; SMOKING; ETHICS; BREAST RP Weed, DL (reprint author), NCI,PREVENT ONCOL BRANCH,EPS T-41,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 33 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 0091-7435 J9 PREV MED JI Prev. Med. PD SEP-OCT PY 1997 VL 26 IS 5 SU S BP S37 EP S41 DI 10.1006/pmed.1997.0208 PN 2 PG 5 WC Public, Environmental & Occupational Health; Medicine, General & Internal SC Public, Environmental & Occupational Health; General & Internal Medicine GA XY879 UT WOS:A1997XY87900006 PM 9327491 ER PT J AU Stratakis, CA Lin, JP Pras, E Rennert, OM Bourdony, CJ Chan, WY AF Stratakis, CA Lin, JP Pras, E Rennert, OM Bourdony, CJ Chan, WY TI Segregation of Allgrove (triple-A) syndrome in Puerto Rican kindreds with chromosome 12 (12q13) polymorphic markers SO PROCEEDINGS OF THE ASSOCIATION OF AMERICAN PHYSICIANS LA English DT Article DE linkage; adrenal gland; achalasia; alacrima; genetics ID FAMILIAL GLUCOCORTICOID DEFICIENCY; ADRENOCORTICOTROPIN RECEPTOR; ACTH INSENSITIVITY; LINKAGE ANALYSIS; ACHALASIA; GENE; ALACRIMA; ABNORMALITIES; HORMONE; CARDIA AB Allgrove syndrome (AS), also known as triple-A syndrome, is a rare cause of congenital adrenal insufficiency due to adrenocorticotropic hormone resistance. It is inherited in an autosomal recessive manner and is associated with achalasia, alacrima, and other neurological abnormalities, including autonomic, sensory, and upper- and lower-motor neuropathy, deafness, and mental retardation. Although the etiology of AS remains unknown, recently the disease was linked to a chromosome 12 locus (corresponding cytogenetic band 12q13) in consanguineous families of European ancestry. In the present study, we investigated four nonconsanguineous families with documented inheritance of AS for linkage with the reported 12q13 locus. Eighteen subjects were studied, of whom five were affected by AS. DNA was extracted from peripheral blood lymphocytes and amplified by standard methods with primers from polymorphic sequence tagged sites (STSs) located in the chromosome 12q13 region. Two-point logarithm-of-odds (LOD) score analysis revealed a maximum LOD score of 1.7 for STSs D12S361 and D12S368 without any recombinants [recombination distance (theta) = 0]. Multipoint linkage analysis defined an area of estimated genetic distance less than 0.5 cM (approximately 500,000 bp) between STSs D12S361 and D12S359 that is most likely to contain the AS gene(s). We conclude that, in Puerto Rican families, AS segregates with polymorphic markers that have been mapped to the chromosome 12q13 locus, revealing the absence of heterogeneity for this syndrome in a genetically distinct population. Candidate genes in the region include those that code for several of the keratin proteins, transcription factors, and others. C1 NIAMSD,GENET STUDIES SECT,SKIN BIOL LAB,NIH,BETHESDA,MD 20892. NIAMSD,ARTHRIT & RHEUMATISM BRANCH,NIH,BETHESDA,MD 20892. GEORGETOWN UNIV,DEPT PEDIAT,WASHINGTON,DC 20057. GEORGETOWN UNIV,DEPT CELL BIOL & BIOCHEM,WASHINGTON,DC 20057. SAN JUAN CITY HOSP,DEPT PEDIAT,SAN JUAN,PR. RP Stratakis, CA (reprint author), NICHHD,UNIT GENET & ENDOCRINOL,SECT PEDIAT ENDOCRINOL,DEV ENDOCRINOL BRANCH,NIH,BLDG 10,BETHESDA,MD 20892, USA. FU NICHD NIH HHS [HD-31553] NR 33 TC 33 Z9 34 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 SN 1081-650X J9 P ASSOC AM PHYSICIAN JI Proc. Assoc. Am. Phys. PD SEP PY 1997 VL 109 IS 5 BP 478 EP 482 PG 5 WC Medicine, General & Internal; Medicine, Research & Experimental SC General & Internal Medicine; Research & Experimental Medicine GA XU075 UT WOS:A1997XU07500004 PM 9285947 ER PT J AU Xu, D Tsai, CJ Nussinov, R AF Xu, D Tsai, CJ Nussinov, R TI Hydrogen bonds and salt bridges across protein-protein interfaces SO PROTEIN ENGINEERING LA English DT Article DE bound water; hydrogen bond; molecular recognition; protein association; salt bridge; statistical analysis ID GLOBULAR-PROTEINS; SHAPE COMPLEMENTARITY; WATER-MOLECULES; DOCKING; RECOGNITION; STABILITY; COMPLEX; STABILIZATION; INHIBITORS; BINDING AB To understand further, and to utilize, the interactions across protein-protein interfaces, we carried out an analysis of the hydrogen bonds and of the salt bridges in a collection of 319 non-redundant protein-protein interfaces derived from high-quality X-ray structures, We found that the geometry of the hydrogen bonds across protein interfaces is generally less optimal and has a wider distribution than typically observed within the chains, This difference originates from the more hydrophilic side chains buried in the binding interface than in the folded monomer interior, Protein folding differs from protein binding, Whereas in folding practically all degrees of freedom are available to the chain to attain its optimal configuration, this is not the case for rigid binding, where the protein molecules are already folded, with only six degrees of translational and rotational freedom available to the chains to achieve their most favorable bound configuration, These constraints enforce many polar/charged residues buried in the interface to form weak hydrogen bonds with protein atoms, rather than strongly hydrogen bonding to the solvent, Since interfacial hydrogen bonds are weaker than the intra-chain ones to compete with the binding of water, more water molecules are involved in bridging hydrogen bond networks across the protein interface than in the protein interior, Interfacial water molecules both mediate non-complementary donor-donor or acceptor-acceptor pairs, and connect non-optimally oriented donor-acceptor pairs, These differences between the interfacial hydrogen bonding patterns and the intra-chain ones further substantiate the notion that protein complexes formed by rigid binding may be far away from the global minimum conformations, Moreover, we summarize the pattern of charge complementarity and of the conservation of hydrogen bond network across binding interfaces, We further illustrate the utility of this study in understanding the specificity of protein-protein associations, and hence in docking prediction and molecular (inhibitor) design. C1 NCI, Math Biol Lab, IRSP, SAIC Frederick,FCRDC, Frederick, MD 21702 USA. Tel Aviv Univ, Sackler Inst Mol Med, IL-69978 Tel Aviv, Israel. RP Nussinov, R (reprint author), NCI, Math Biol Lab, IRSP, SAIC Frederick,FCRDC, Frederick, MD 21702 USA. FU NCI NIH HHS [1-CO-74102] NR 57 TC 250 Z9 257 U1 1 U2 26 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0269-2139 J9 PROTEIN ENG JI Protein Eng. PD SEP PY 1997 VL 10 IS 9 BP 999 EP 1012 DI 10.1093/protein/10.9.999 PG 14 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology GA YP655 UT WOS:000071300700003 PM 9464564 ER PT J AU Tsai, CJ Xu, D Nussinov, R AF Tsai, CJ Xu, D Nussinov, R TI Structural motifs at protein-protein interfaces: Protein cores versus two-state and three-state model complexes SO PROTEIN SCIENCE LA English DT Article DE hydrophobic effect; motifs; protein folding; protein-protein interfaces; protein-protein recognition; structural comparison ID GLOBULAR-PROTEINS; SUBUNIT INTERFACES; FOLD FAMILIES; DATA-BANK; CLASSIFICATION; SEQUENCES; IDENTIFICATION; SIMILARITIES; RECOGNITION; DYNAMICS AB The general similarity in the forces governing protein folding and protein-protein associations has led us to examine the similarity in the architectural motifs between the interfaces and the monomers. We have carried out extensive, all-against-all structural comparisons between the single-chain protein structural dataset and the interface dataset, derived both from all protein-protein complexes in the structural database and from interfaces generated via an automated crystal symmetry operation. We show that despite the absence of chain connections, the global features of the architectural motifs, present in monomers, recur in the interfaces, a reflection of the limited set of the folding patterns. However, although similarity has been observed, the details of the architectural motifs vary. In particular, the extent of the similarity correlates with the consideration of how the interface has been formed. Interfaces derived from two-state model complexes, where the chains fold cooperatively, display a considerable similarity to architectures in protein cores, as judged by the quality of their geometric superposition. On the other hand, the three-state model interfaces, representing binding of already folded molecules, manifest a larger variability and resemble the monomer architecture only in general outline. The origin of the difference between the monomers and the three-state model interfaces can be understood in terms of the different nature of the folding and the binding that are involved. Whereas in the former all degrees of freedom are available to the backbone to maximize favorable interactions, in rigid body, three-state model binding, only six degrees of freedom are allowed. Hence, residue or atom pair-wise potentials derived from protein-protein associations are expected to be less accurate, substantially increasing the number of computationally acceptable alternate binding modes (Finkelstein et al., 1995). C1 NCI,FREDERICK CANC RES & DEV CTR,MATH BIOL LAB,SAIC,FREDERICK,MD 21702. TEL AVIV UNIV,SACKLER INST MOL MED,IL-69978 TEL AVIV,ISRAEL. FU NCI NIH HHS [1-CO-74102] NR 46 TC 53 Z9 55 U1 0 U2 3 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 SEP PY 1997 VL 6 IS 9 BP 1793 EP 1805 PG 13 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA XV801 UT WOS:A1997XV80100001 PM 9300480 ER PT J AU Moscicki, EK AF Moscicki, EK TI Identification of suicide risk factors using epidemiologic studies SO PSYCHIATRIC CLINICS OF NORTH AMERICA LA English DT Review ID SAN-DIEGO SUICIDE; ADRENERGIC-RECEPTOR BINDING; ADOLESCENT SUICIDE; MENTAL-DISORDERS; COMPLETED SUICIDE; TEENAGE SUICIDE; PANIC DISORDER; SEXUAL ORIENTATION; GENERAL POPULATION; SUBSTANCE ABUSE AB Suicide is a complex outcome of multiple, inter-related factors. This article presents the epidemiology of completed and attempted suicide and discusses the known risk factors for suicide within a framework designed to encourage a systematic approach to theory testing and prevention. Mental and addictive disorders, frequently in co-occurrence, are the most powerful risk factors for suicide in all age groups, accounting for over 90 percent of all completed suicides. In combination with proximal risk factors such as access to firearms or other lethal means, recent and severe stressful life events, and intoxication, they can form the necessary and sufficient conditions for suicide. RP Moscicki, EK (reprint author), NIMH,PREVENT & BEHAV MED RES BRANCH,NIH,ROOM 10-85,5600 FISHERS LANE,ROCKVILLE,MD 20857, USA. NR 125 TC 280 Z9 293 U1 5 U2 22 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0193-953X J9 PSYCHIAT CLIN N AM JI Psychiatr. Clin. North Amer. PD SEP PY 1997 VL 20 IS 3 BP 499 EP & DI 10.1016/S0193-953X(05)70327-0 PG 20 WC Psychiatry SC Psychiatry GA XY569 UT WOS:A1997XY56900002 PM 9323310 ER PT J AU Morasso, G Alberisio, A Capelli, M Rossi, C Baracco, G Costantini, M AF Morasso, G Alberisio, A Capelli, M Rossi, C Baracco, G Costantini, M TI Illness awareness in cancer patients: A conceptual framework and a preliminary classification hypothesis SO PSYCHO-ONCOLOGY LA English DT Article ID BREAST-CANCER; COMMUNICATION; CARE AB The study describes the initial phases of research aimed at developing a methodology for assessing awareness in cancer patients. A first sample of cancer patients (n = 36) was interviewed about their knowledge of the diagnosis and their perception of treatment goals and outcomes. Thirteen domains which refer both to cognitive and emotional areas were identified, and considered as content valid by a panel of six experts. A second sample of patients (n = 54) participated in a semi-structured interview developed to explore awareness by means of the domains identified. Seven patterns of awareness were identified, ranging from 'completely aware patient' to 'completely unaware patient'. Twenty of the 54 patients (37.0%) were completely aware, 19 (35.2%) were partially aware with defence mechanisms and 15 (27.8%) were not aware of their diagnosis. patients from the National Cancer Institute were more frequently aware (54.3%) compared with the patients interviewed in the community hospitals (5.3%) (p < 0.001). A computerized content analysis allowed the identification of two main groups of patients on the basis of the content of the recorded interviews. This independent classification agreed with the classification of the patients performed by the psychologists, suggesting the validity of the procedure of awareness evaluation proposed in this study. (C) 1997 John Wiley gi Sons, Ltd. C1 NATL CANC INST,UNIT CLIN EPIDEMIOL & TRIALS UNIT,I-16132 GENOA,ITALY. RP Morasso, G (reprint author), NATL CANC INST,PSYCHOL SERV,LARGO R BENZI 10,I-16132 GENOA,ITALY. RI costantini, massimo/G-1443-2012; OI costantini, massimo/0000-0002-5293-7079 NR 14 TC 14 Z9 14 U1 0 U2 0 PU JOHN WILEY & SONS LTD PI W SUSSEX PA BAFFINS LANE CHICHESTER, W SUSSEX, ENGLAND PO19 1UD SN 1057-9249 J9 PSYCHO-ONCOL JI Psycho-Oncol. PD SEP PY 1997 VL 6 IS 3 BP 212 EP 217 DI 10.1002/(SICI)1099-1611(199709)6:3<212::AID-PON275>3.0.CO;2-X PG 6 WC Oncology; Psychology; Psychology, Multidisciplinary; Social Sciences, Biomedical SC Oncology; Psychology; Biomedical Social Sciences GA XX769 UT WOS:A1997XX76900006 PM 9313287 ER PT J AU Kessler, RC Rubinow, DR Holmes, C Abelson, JM Zhao, S AF Kessler, RC Rubinow, DR Holmes, C Abelson, JM Zhao, S TI The epidemiology of DSM-III-R bipolar I disorder in a general population survey SO PSYCHOLOGICAL MEDICINE LA English DT Article ID NATIONAL-COMORBIDITY-SURVEY; PSYCHIATRIC-DISORDERS; MENTAL-DISORDERS; SUBSTANCE-ABUSE; UNITED-STATES; CO-MORBIDITY; PREVALENCE; COMMUNITY; UNIPOLAR; LIFETIME AB Background. Data are presented on the general population epidemiology of DSM-III-R bipolar I disorder in the United States. Methods. Data come from the US National Comorbidity Survey (NCS), a general population survey of DSM-III-R disorders. A modified version of the Composite International Diagnostic Interview was used to make diagnoses. Results, A small (N = 59) clinical reappraisal study showed that the only manic symptom profile that could validly be assessed with the CIDI is characterized by euphoria, grandiosity and the ability to maintain energy without sleep, which described approximately half of all clinically validated bipolar I cases in the NCS. Further analysis focused on this symptom profile, which involved N = 29 cases in the total sample. Lifetime prevalence was estimated to be 0.4 % and 12-month prevalence only slightly lower. Caseness was negatively related to income, education and age, positively related to urbanicity, and elevated among the previously married, never married and non-whites. All cases reported at least one other NCS/DSM-III-R disorder and 59.3 % reported that their episode of bipolar disorder (either mania or depression) occurred at a later age than at least one other NCS/DSM-III-R disorder. Although 93.2 % of lifetime cases reported some lifetime treatment, only 44.7 % of recent cases were in treatment. Conclusions. The type of bipolar disorder examined here is highly chronic, co-morbid and impairing. Increased efforts are required to attract current cases into appropriate treatment. Methodological research is needed to develop more accurate measures of other bipolar symptom profiles for use in general population epidemiological studies. C1 NIMH,BETHESDA,MD 20892. UNIV MICHIGAN,INST SOCIAL RES,ANN ARBOR,MI 48109. TEMPLE UNIV,DEPT SOCIOL,PHILADELPHIA,PA 19122. RP Kessler, RC (reprint author), HARVARD UNIV,SCH MED,DEPT HLTH CARE POLICY,25 SHATTUCK ST,PARCEL B,1ST FLOOR,BOSTON,MA 02115, USA. FU NIMH NIH HHS [R01 MH46376, R01 MH49098, R01 MH52861] NR 65 TC 375 Z9 385 U1 11 U2 22 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 40 WEST 20TH STREET, NEW YORK, NY 10011-4211 SN 0033-2917 J9 PSYCHOL MED JI Psychol. Med. PD SEP PY 1997 VL 27 IS 5 BP 1079 EP 1089 DI 10.1017/S0033291797005333 PG 11 WC Psychology, Clinical; Psychiatry; Psychology SC Psychology; Psychiatry GA XV800 UT WOS:A1997XV80000010 PM 9300513 ER PT J AU Flisher, AJ Kramer, RA Grosser, RC Alegria, M Bird, HR Bourdon, KH Goodman, SH Greenwald, S Horwitz, SM Moore, RE Narrow, WE Hoven, CW AF Flisher, AJ Kramer, RA Grosser, RC Alegria, M Bird, HR Bourdon, KH Goodman, SH Greenwald, S Horwitz, SM Moore, RE Narrow, WE Hoven, CW TI Correlates of unmet need for mental health services by children and adolescents SO PSYCHOLOGICAL MEDICINE LA English DT Article ID GLOBAL ASSESSMENT SCALE; CARE ASSESSMENT; MRC NEEDS; PSYCHIATRIC EPIDEMIOLOGY; DISORDERS; POPULATION; PREVALENCE AB Background. Little is known about the extent and correlates of unmet need for mental health services in community samples of children and adolescents. Methods. Data were obtained from the 1285 parent/youth pairs interviewed at four sites in the USA and Puerto Rico in the Methods for the Epidemiology of Child and Adolescent Mental Disorders (MECA) Study. Unmet need was defined to exist if psychopathology and associated functional impairment were present but no mental health services had been received in the previous 6 months. Results. Of the total sample, 17.1 % had unmet need. Adjusting for demographic variables, logistic regression analyses revealed that unmet need was significantly associated with: indicators of economic disadvantage, such as being on public assistance and not being covered by health insurance; opinions of the parents and children or adolescents that the latter had poor mental health; parental psychopathology; poor school grades; and parent-reported access barriers such as concern that the child would want to solve the problem unassisted, would refuse to attend mental health services, or would be hospitalized or taken away against the parent's will. No youth-reported access barriers were significantly associated with unmet need. Conclusions. The economic correlates of unmet need may attain increased importance in the light of current reform in health care financing in the USA. Access may be facilitated by increasing parental knowledge of mental health services and enabling children and adolescents to initiate contact with services independently of their families. C1 COLUMBIA UNIV,NEW YORK STATE PSYCHIAT INST,DIV CHILD & ADOLESCENT PSYCHIAT,NEW YORK,NY 10027. NEW YORK STATE OFF MENTAL HLTH,ALBANY,NY. NIMH,DIV EPIDEMIOL & MENTAL HLTH,ROCKVILLE,MD 20857. EMORY UNIV,DEPT PSYCHOL,ATLANTA,GA 30322. YALE UNIV,DEPT EPIDEMIOL & PUBL HLTH,NEW HAVEN,CT 06520. UNIV CAPE TOWN,DEPT PSYCHIAT,ZA-7700 RONDEBOSCH,SOUTH AFRICA. UNIV PUERTO RICO,SCH PUBL HLTH,SAN JUAN,PR 00936. FU NIMH NIH HHS [MH-43878, MH-46091, U01 MH46725] NR 35 TC 114 Z9 114 U1 3 U2 8 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 40 WEST 20TH STREET, NEW YORK, NY 10011-4211 SN 0033-2917 J9 PSYCHOL MED JI Psychol. Med. PD SEP PY 1997 VL 27 IS 5 BP 1145 EP 1154 DI 10.1017/S0033291797005412 PG 10 WC Psychology, Clinical; Psychiatry; Psychology SC Psychology; Psychiatry GA XV800 UT WOS:A1997XV80000015 PM 9300518 ER PT J AU GeterDouglass, B Witkin, JM AF GeterDouglass, B Witkin, JM TI Dizocilpine-like discriminative stimulus effects of competitive NMDA receptor antagonists in mice SO PSYCHOPHARMACOLOGY LA English DT Article DE NMDA receptor antagonists; Drug discrimination; T-maze; dizocilpine; TCP; phencyclidine; dextrorphan; SKF 10,047; CGS 19755; NPC 17742; CPP; LY 274614; LY 235959; LY 233536; ACPC; ifenprodil; NBQX; mice ID D-ASPARTATE RECEPTOR; EXCITATORY AMINO-ACIDS; BEHAVIORAL PHARMACOLOGY; GLUTAMATE ANTAGONISTS; CHANNEL COMPLEX; PARTIAL AGONIST; RHESUS-MONKEYS; PHENCYCLIDINE; MK-801; SITE AB Several non-competitive NMDA receptor ion channel blockers, competitive NMDA antagonists and compounds acting at other sites on the NMDA receptor complex were examined for their ability to substitute for the discriminative stimulus effects of dizocilpine. Swiss-Webster mice were trained with food to discriminate the non-competitive NMDA receptor antagonist, dizocilpine (0.17 mg/kg), from saline in a T-maze. Mice rapidly acquired the discrimination with minimal amounts of drugs required for training and testing. Several non-competitive antagonists dose-dependently substituted for dizocilpine with a rank order of potency of dizocilpine>TCP>(-)-MK-801>SKF 10,047>dextrorphan>PCP. There was a positive correlation between the potencies of the compounds that substituted for dizocilpine and their previously reported affinities for the [H-3]dizocilpine binding site of the NMDA receptor ion channel. Compounds acting at other sites on the NMDA receptor complex, including NMDA, the partial agonist at the strychnine-insensitive glycine site, ACPC, and the polyamine antagonist, ifenprodil, failed to substitute fully. In addition, the AMPA antagonist: NBQX, the monoamine uptake inhibitor, cocaine, and the GABA(A) receptor agonists, diazepam and phenobarbital, failed to substitute fully for dizocilpine. However, like the ion channel blockers, the competitive NMDA antagonists, CGS 19755, NPC 17742, (+/-)CPP and LY 233536 dose-dependently substituted for dizocilpine. The competitive antagonist, LY 274614, and its active enantiomer, LY 235959, failed to substitute for dizocilpine, each producing severe disruptions in locomotor activity. That most of the competitive antagonists substituted for dizocilpine is in accordance with other behavioral data (e.g., ataxia, locomotor activity) documenting similarities in the effects of non-competitive and competitive antagonists. These findings are also consistent with results of clinical investigations suggesting overlap in the behavioral and subjective profiles of competitive and non-competitive NMDA blockers. RP GeterDouglass, B (reprint author), NIDA,DRUG DEV GRP,PRECLIN PHARMACOL LAB,ADDICT RES CTR,NIH,POB 5180,BALTIMORE,MD 21224, USA. NR 45 TC 20 Z9 20 U1 3 U2 3 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0033-3158 J9 PSYCHOPHARMACOLOGY JI Psychopharmacology PD SEP PY 1997 VL 133 IS 1 BP 43 EP 50 DI 10.1007/s002130050369 PG 8 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA XX555 UT WOS:A1997XX55500006 PM 9335079 ER PT J AU Mihara, K Otani, K Suzuki, A Yasui, N Nakano, H Meng, XM Ohkubo, T Nagasaki, T Kaneko, S Tsuchida, S Sugawara, K Gonzalez, FJ AF Mihara, K Otani, K Suzuki, A Yasui, N Nakano, H Meng, XM Ohkubo, T Nagasaki, T Kaneko, S Tsuchida, S Sugawara, K Gonzalez, FJ TI Relationship between the CYP2D6 genotype and the steady-state plasma concentrations of trazodone and its active metabolite m-chlorophenylpiperazine SO PSYCHOPHARMACOLOGY LA English DT Article DE CYP2D6 genotype; trazodone; m-chlorophenylpiperazine; steady-state plasma concentration; metabolism ID DEBRISOQUINE HYDROXYLATION; DEPRESSED-PATIENTS; POOR METABOLIZERS; GENETIC-ANALYSIS; SPARTEINE; PHENOTYPE; DELETION; ALLELE; LOCUS; IDENTIFICATION AB The relationship between the cytochrome P450 (CYP) 2D6 genotype and the steady-state plasma concentrations (Css) of trazodone and its active metabolite m-chlorophenylpiperazine (mCPP) was studied in 54 depressed Japanese patients receiving trazodone 150 mg at bedtime. By use of allele-specific PCR analysis, the wild type allele, three mutated alleles causing absent enzyme activity (CYP2D6A, CYP2D6B and CYP2D6D) and one mutated allele causing decreased enzyme activity (CYPZD6 Ch) were identified. The means (ranges) of the Css of trazodone, corrected to the median body weight in 17 cases with no mutated allele, 27 cases with one mutated allele and 10 cases with two mutated alleles, were 556 (281-1115), 643 (302-1362) and 671 (234-1418) ng/ml, respectively, while the values of mCPP were 60 (35-121), 65 (33-99) and 58 (38-112) ng/ml, respectively. Neither the Css of trazodone (F = 0.80, P = 0.45) nor that of mCPP (F = 0.49, P = 0.61) significantly differed among the three groups. The present study thus suggests that the CYP2D6 genotype cannot predict the Css of these compounds. C1 HIROSAKI UNIV HOSP,DEPT NEUROPSYCHIAT,HIROSAKI,AOMORI 036,JAPAN. HIROSAKI UNIV HOSP,DEPT BIOCHEM 2,HIROSAKI,AOMORI 036,JAPAN. HIROSAKI UNIV HOSP,DEPT PHARM,HIROSAKI,AOMORI 036,JAPAN. GOSHOGAWARA CITY HOSP,DEPT PHARM,GOSHOGAWARA 037,JAPAN. NCI,MOL CARCINOGENESIS LAB,NIH,BETHESDA,MD 20014. RI Tsuchida, Shigeki/L-3382-2013 OI Tsuchida, Shigeki/0000-0002-4404-5599 NR 23 TC 25 Z9 25 U1 0 U2 2 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0033-3158 J9 PSYCHOPHARMACOLOGY JI Psychopharmacology PD SEP PY 1997 VL 133 IS 1 BP 95 EP 98 DI 10.1007/s002130050376 PG 4 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA XX555 UT WOS:A1997XX55500013 PM 9335086 ER PT J AU Breen, N Feuer, EJ Depury, S Zapka, J AF Breen, N Feuer, EJ Depury, S Zapka, J TI The effect of medicine reimbursement for screening mammography on utilization and payment SO PUBLIC HEALTH REPORTS LA English DT Article ID BREAST-CANCER; OLDER WOMEN; PHYSICIAN COMPLIANCE; UNITED-STATES; PRIMARY-CARE; COMMUNITY; INTERVENTION; IMPACT; COST; EDUCATION AB Objective. In January 1991, Medicare extended its mammography benefit to reimburse for breast cancer screening mammograms. in 1991 and again in 1993, the National Cancer institute Breast Cancer Screening Consortium (BCSC) conducted a survey to test the hypothesis that this benefit would increase mammography use among women over the age of 65. Methods. The authors analyzed data on non-Hispanic white women ages 65 to 74 living in 11 geographic areas targeted by the BCSC for an earlier study-six that had received cancer screening educational interventions and five control subsites-to measure the impact of the newly adopted Medicare benefit on the use of mammography and use of Medicare to reimburse mammography costs. Results. The data show little overall increase between 1991 and 1993 in reported mammography use among respondents to the survey. However, in six intervention and five control subsites there was an increase in the percentage of women who reported using public payment sources to at least partially reimburse the cost of mammograms. In three intervention subsites, the increase from 1991 to 1993 in the percentage of women using public sources of payment was greater than in the corresponding control subsites. Conclusions. These findings suggest that public health interventions are more likely to succeed when educational promotion accompanies a financial benefit. RP Breen, N (reprint author), NCI,APPL RES BRANCH,NIH,BREAST CANC SCREENING CONSORTIUM,EPN 313,6130 EXECUT BLVD,MSC 7344,BETHESDA,MD 20892, USA. NR 31 TC 22 Z9 22 U1 2 U2 2 PU US GOVERNMENT PRINTING OFFICE PI WASHINGTON PA SUPT OF DOCUMENTS, WASHINGTON, DC 20402-9325 SN 0033-3549 J9 PUBLIC HEALTH REP JI Public Health Rep. PD SEP-OCT PY 1997 VL 112 IS 5 BP 423 EP 432 PG 10 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA XW236 UT WOS:A1997XW23600027 PM 9323395 ER PT J AU Tucker, JD Tawn, EJ Holdsworth, D Morris, S Langlois, R Ramsey, MJ Kato, P Boice, JD Tarone, RE Jensen, RH AF Tucker, JD Tawn, EJ Holdsworth, D Morris, S Langlois, R Ramsey, MJ Kato, P Boice, JD Tarone, RE Jensen, RH TI Biological dosimetry of radiation workers at the Sellafield nuclear facility SO RADIATION RESEARCH LA English DT Article ID SOMATIC-CELL MUTATIONS; ATOMIC-BOMB SURVIVORS; GLYCOPHORIN-A LOCUS; FLUORESCENCE INSITU HYBRIDIZATION; STABLE CHROMOSOME-ABERRATIONS; RETROSPECTIVE DOSE ESTIMATION; HUMAN PERIPHERAL LYMPHOCYTES; IN-SITU HYBRIDIZATION; IONIZING-RADIATION; CANCER MORTALITY AB The British Nuclear Fuels pie facility at Sellafield performs a range of nuclear-related activities. The site has been in operation since 1950 and has, in general, employed a stable work force, many of whom have accumulated relatively high occupational exposures to ionizing radiation. This paper compares the physical dosimetry with two biological end points for evaluating radiation exposure: fluorescence in situ hybridization with whole-chromosome painting probes to quantify stable chromosome aberrations (translocations and insertions), and glycophorin A (GPA) analysis of variant erythrocytes. For the cytogenetic analyses, 81 workers were evaluated in five dose categories, including 23 with minimal radiation exposure (less than or equal to 50 mSv) and 58 with exposures ranging from 173 to 1108 mSv, all but 3 being >500 mSv. In a univariate analysis, the mean stable chromosome aberration frequencies showed a significant increase with dose category (P = 0.032), and with cumulative dose when dose is treated as a continuous variable (P = 0.015). The slope of the dose response for stable aberrations is 0.79 +/- 0.22 aberrations per 100 cells per sievert (adjusted for smoking status), which is less than that observed among atomic bomb survivors, and suggests a dose and dose-rate effectiveness factor for chronic exposure of about 6. Analyses of the data for GPA N/O and N/N variants from 36 workers revealed no correlation with dose. Neither was there a correlation between the frequencies of N/O GPA variants and stable aberrations, although a weak negative association was observed between N/N variant frequency and stable aberrations (r = -0.38, P = 0.05). These results provide clear evidence for the accumulation of stable aberrations under conditions of chronic occupational exposure to ionizing radiation and show that stable chromosome aberrations are a more sensitive indicator for chronic radiation exposure than GPA variants. In comparison with human studies of brief exposure, chronic low-dose exposures appear substantially less effective for producing somatic effects as reflected by stable chromosome aberrations. (C) 1997 by Radiation Research Society. C1 GEOFFREY SCHOFIELD LABS, WESTLAKES RES INST, GENET UNIT, MOOR ROW CA24 3JZ, CUMBRIA, ENGLAND. BRITISH NUCL FUELS PLC, DEPT OCCUPAT HLTH, SEASCALE, SELLAFIELD CA20 1PG, CUMBRIA, ENGLAND. NCI, DIV CANC EPIDEMIOL & GENET, NIH, BETHESDA, MD 20892 USA. UNIV CALIF SAN FRANCISCO, SCH MED, DEPT LAB MED, CTR CANC, SAN FRANCISCO, CA 94143 USA. RP Tucker, JD (reprint author), LAWRENCE LIVERMORE NATL LAB, BIOL & BIOTECHNOL RES PROGRAM, POB 808, L-452, LIVERMORE, CA 94551 USA. FU NCI NIH HHS [CP 10550-51]; PHS HHS [10561] NR 61 TC 75 Z9 81 U1 0 U2 3 PU RADIATION RESEARCH SOC PI LAWRENCE PA 810 E TENTH STREET, LAWRENCE, KS 66044 USA SN 0033-7587 J9 RADIAT RES JI Radiat. Res. PD SEP PY 1997 VL 148 IS 3 BP 216 EP 226 DI 10.2307/3579605 PG 11 WC Biology; Biophysics; Radiology, Nuclear Medicine & Medical Imaging SC Life Sciences & Biomedicine - Other Topics; Biophysics; Radiology, Nuclear Medicine & Medical Imaging GA XU087 UT WOS:A1997XU08700003 PM 9291352 ER PT J AU Bucci, TJ Bolon, B Warbritton, AR Chen, JJ Heindel, JJ AF Bucci, TJ Bolon, B Warbritton, AR Chen, JJ Heindel, JJ TI Influence of sampling on the reproducibility of ovarian follicle counts in mouse toxicity studies SO REPRODUCTIVE TOXICOLOGY LA English DT Article DE follicle; ovary; mouse; reproductive toxicity; female; differential count; power analysis ID POLYCYCLIC AROMATIC-HYDROCARBONS; OOCYTE DESTRUCTION; IMPLANTATION; LOCALIZATION; OOGENESIS; SMOKING; RAT AB Different ovarian follicle counting procedures were investigated to reduce labor while retaining statistical power, Intact ovaries of untreated CD-1 mice (20/group) from National Toxicology Program Reproductive Assessment by Continuous Breeding (RACB) studies were serially sectioned at 6 mu m. Mean numbers of small and growing follicles were used to assess sampling efficiency, In 10 mice per group, comparisons were made between 10% nonrandom samples from every 10th section starting at either the first or sixth section having follicles (approximately 40 sections per ovary), These 10% counts were compared with 5% (20 sections) and 20% (80 sections) nonrandom samples and with 1% (4 sections), 5%, or 10% random samples from the same 10 animals, For two studies, a 10% nonrandom sample was analyzed from 20 mice per group, Follicle counts for each group were comparable regardless of the sampling paradigm, Four to 10 animals provided 90% confidence that a 20% difference in mean counts would be detected, The 1% sample had a larger error term and, thus, slightly reduced statistical power, These data suggest that follicle counts from 1% or 5% random samples may provide a suitable screen for ovarian toxicity. C1 NATL CTR TOXICOL RES,DIV BIOMETRY & RISK ASSESSMENT,JEFFERSON,AR 72079. NIEHS,NATL TOXICOL PROGRAM,DEV & REPROD TOXICOL GRP,RES TRIANGLE PK,NC 27709. RP Bucci, TJ (reprint author), NATL CTR TOXICOL RES,PATHOL ASSOCIATES INT,POB 26,JEFFERSON,AR 72079, USA. FU PHS HHS [224-85-005] NR 36 TC 42 Z9 42 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0890-6238 J9 REPROD TOXICOL JI Reprod. Toxicol. PD SEP-OCT PY 1997 VL 11 IS 5 BP 689 EP 696 DI 10.1016/S0890-6238(97)00034-8 PG 8 WC Reproductive Biology; Toxicology SC Reproductive Biology; Toxicology GA XW708 UT WOS:A1997XW70800006 PM 9311577 ER PT J AU Kulkarni, AB Karlsson, S AF Kulkarni, AB Karlsson, S TI Inflammation and TGF beta 1: lessons from the TGF beta 1 null mouse SO RESEARCH IN IMMUNOLOGY LA English DT Article ID GROWTH-FACTOR-BETA; EXPERIMENTAL ALLERGIC ENCEPHALOMYELITIS; TGF-BETA; ANTIGEN EXPRESSION; KNOCKOUT MICE; IN-VIVO; FACTOR-BETA-1; VASCULOGENESIS; HEMATOPOIESIS; DEATH C1 Univ Lund, Gene Therapy Ctr, S-22362 Lund, Sweden. Univ Lund Hosp, S-22362 Lund, Sweden. NIDR, Gene Targeting Res & Core Facil, NIH, Bethesda, MD 20892 USA. RP Karlsson, S (reprint author), Univ Lund, Gene Therapy Ctr, Solvegatan 17, S-22362 Lund, Sweden. NR 27 TC 24 Z9 25 U1 0 U2 0 PU EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER PI PARIS CEDEX 15 PA 23 RUE LINOIS, 75724 PARIS CEDEX 15, FRANCE SN 0923-2494 J9 RES IMMUNOL JI Res. Immunol. PD SEP PY 1997 VL 148 IS 7 BP 453 EP 456 DI 10.1016/S0923-2494(97)82669-7 PG 4 WC Immunology SC Immunology GA ZJ142 UT WOS:000073183700004 PM 9498004 ER PT J AU Lorenz, MGO Radbruch, A AF Lorenz, MGO Radbruch, A TI Insights into the control of immunoglobulin class switch recombination from analysis of targeted mice SO RESEARCH IN IMMUNOLOGY LA English DT Article ID PRE-B-CELLS; REGION SEQUENCES; TRANSCRIPTION C1 Univ Cologne, Inst Genet, D-50931 Cologne, Germany. RP Lorenz, MGO (reprint author), NCI, Tumor Immunol & Biol Lab, NIH, Bldg 10,Room 5B38, Bethesda, MD 20892 USA. NR 18 TC 3 Z9 3 U1 0 U2 0 PU EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER PI PARIS CEDEX 15 PA 23 RUE LINOIS, 75724 PARIS CEDEX 15, FRANCE SN 0923-2494 J9 RES IMMUNOL JI Res. Immunol. PD SEP PY 1997 VL 148 IS 7 BP 460 EP 463 DI 10.1016/S0923-2494(97)82671-5 PG 4 WC Immunology SC Immunology GA ZJ142 UT WOS:000073183700006 PM 9498006 ER PT J AU Ott, DE AF Ott, DE TI Cellular proteins in HIV virions SO REVIEWS IN MEDICAL VIROLOGY LA English DT Review ID HUMAN-IMMUNODEFICIENCY-VIRUS; INTERCELLULAR-ADHESION MOLECULE-1; CLASS-II HISTOCOMPATIBILITY; CYCLOPHILIN-A; HLA-DR; ACCESSORY PROTEINS; MEMBRANE-PROTEINS; LEUKOCYTE ANTIGEN; HOST-CELLS; TYPE-1 AB Human immunodeficiency virus type-1 (HIV-I) virions contain both virus-encoded and cellular proteins. Recent advances in the detection, isolation, and functional characterisation of host proteins incorporated in the virion have begun to provide for new perspectives on the interactions between virus and cell. The acquisition of host proteins by HIV-I may also influence viral pathology in vivo. This article reviews detection and analysis of host proteins found in HIV-1 particles and presents some potential roles that these proteins might play in the biology of this important virus. (C) 1997 by John Wiley & Sons, Ltd. RP Ott, DE (reprint author), NCI,FREDERICK CANC RES & DEV CTR,SAIC FREDERICK,AIDS VACCINE PROGRAM,FREDERICK,MD 21702, USA. NR 67 TC 96 Z9 97 U1 0 U2 2 PU JOHN WILEY & SONS LTD PI W SUSSEX PA BAFFINS LANE CHICHESTER, W SUSSEX, ENGLAND PO19 1UD SN 1052-9276 J9 REV MED VIROL JI Rev. Med. Virol. PD SEP PY 1997 VL 7 IS 3 BP 167 EP 180 DI 10.1002/(SICI)1099-1654(199709)7:3<167::AID-RMV199>3.3.CO;2-B PG 14 WC Virology SC Virology GA XW810 UT WOS:A1997XW81000006 ER PT J AU Lin, JH Levin, HL AF Lin, JH Levin, HL TI Self-primed reverse transcription is a mechanism shared by several LTR-containing retrotransposons SO RNA-A PUBLICATION OF THE RNA SOCIETY LA English DT Letter ID GENOME C1 NICHHD,LAB EUKARYOT GENE REGULAT,NIH,BETHESDA,MD 20892. NR 9 TC 16 Z9 18 U1 0 U2 1 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 SEP PY 1997 VL 3 IS 9 BP 952 EP 953 PG 2 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA XU421 UT WOS:A1997XU42100003 PM 9292494 ER PT J AU Wilson, PWF AF Wilson, PWF TI Newer metabolic risk factors for heart disease: a brief review SO SAUDI MEDICAL JOURNAL LA English DT Review DE coronary heart disease; risk factors ID CORONARY-ARTERY DISEASE; LOW-DENSITY-LIPOPROTEIN; PREVALENT CARDIOVASCULAR-DISEASE; PRIMARY-PREVENTION TRIAL; VITAMIN-E CONSUMPTION; MYOCARDIAL-INFARCTION; PLASMA TRIGLYCERIDE; PARTICLE-SIZE; BETA-CAROTENE; FOLLOW-UP AB The classic risk factors for coronary heart disease (CHD) have included blood cholesterol level, arterial blood pressure and cigarette smoking, but these factors do not fully explain the occurrence of cardiovascular disease. Newer risk factors, particularly those with a metabolic origin, are now being considered in population studies. The major groupings for these factors include lipids, intermediary glucose metabolism, hematology and the vascular endothelium. Within the lipid group some of the factors included the impact of lipoprotein cholesterol fractions, lipoprotein (a) and the role of oxidized lipids. Diabetes mellitus is well-recognized as a risk factor for CHD and the impact of hyperglycemia, hyperinsulinemia, impaired glucose tolerance and glycosylated hemoglobin levels are being evaluated as potential risk factors. Hematologic factors under study include leucocyte count, fibrinogen, factor VII, von Willebrand's antigen and fibrinolytic measures such as tPA antigen and plasminogen activator inhibitor (PAI-a). Platelet count and activation also appear to be related to coronary disease occurrence and to the time of day at which coronary events occur. Processes that may affect the vascular endothelium include infectious agents and factors that may be toxic to endothelial surfaces, such as homocysteine. In the latter circumstance, higher levels of homocysteine appear to be associated with increased vascular disease and are associated with decreased levels of vitamins B6, B12 and folate. The overall impact of these newer cardiovascular risk factors and an assessment of genetic factors which may provide the underpinnings of their role, is under active investigation and only population-based studies will provide proper evaluation of their importance. RP Wilson, PWF (reprint author), NHLBI, FRAMINGHAM HEART STUDY, 5 THURBER ST, FRAMINGHAM, MA 01701 USA. NR 81 TC 1 Z9 1 U1 0 U2 1 PU SAUDI MED J DEPT OF EXP PATH PI LONDON PA ST BARTHOLOMEW'S HOSP, LONDON, UNITED KINGDOM EC1A 7BE SN 0379-5284 J9 SAUDI MED J JI Saudi Med. J. PD SEP-OCT PY 1997 VL 18 IS 5 BP 439 EP 446 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA YA407 UT WOS:A1997YA40700001 ER PT J AU OBrien, SJ Dean, M AF OBrien, SJ Dean, M TI In search of AIDS-resistance genes SO SCIENTIFIC AMERICAN LA English DT Article RP OBrien, SJ (reprint author), NCI,LAB GENOM DIVERS,BETHESDA,MD 20892, USA. OI Dean, Michael/0000-0003-2234-0631 NR 4 TC 44 Z9 47 U1 0 U2 1 PU SCI AMERICAN INC PI NEW YORK PA 415 MADISON AVE, NEW YORK, NY 10017 SN 0036-8733 J9 SCI AM JI Sci.Am. PD SEP PY 1997 VL 277 IS 3 BP 44 EP 51 PG 8 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA XR929 UT WOS:A1997XR92900021 PM 9274039 ER PT J AU BirkedalHansen, H AF BirkedalHansen, H TI Hot papers - Cell biology - Proteolytic remodeling of extracellular matrix by H. Birkedal-Hansen - Comments SO SCIENTIST LA English DT Editorial Material AB Dental researcher Henning Birkedal-Hansen discusses his review paper on remodeling of the extracellular matrix. RP BirkedalHansen, H (reprint author), NIDR,BETHESDA,MD 20892, USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU SCIENTIST INC PI PHILADELPHIA PA 3600 MARKET ST SUITE 450, PHILADELPHIA, PA 19104 SN 0890-3670 J9 SCIENTIST JI Scientist PD SEP 1 PY 1997 VL 11 IS 17 BP 14 EP 14 PG 1 WC Information Science & Library Science; Multidisciplinary Sciences SC Information Science & Library Science; Science & Technology - Other Topics GA XW248 UT WOS:A1997XW24800015 ER PT J AU Hosono, M Kobayashi, H Fujimoto, R Tsutsui, K Kotoura, Y Tsuboyama, T Hayashi, H Nakamura, T Konishi, J AF Hosono, M Kobayashi, H Fujimoto, R Tsutsui, K Kotoura, Y Tsuboyama, T Hayashi, H Nakamura, T Konishi, J TI MR appearance of parasymphyseal insufficiency fractures of the os pubis SO SKELETAL RADIOLOGY LA English DT Article DE insufficiency fracture; pubic bone; MRI ID BONE AB Objective. To clarify the MRI features of parasymphyseal insufficiency fractures of the os pubis, Design and patients. MRI was performed in four postmenopausal women with parasymphyseal insufficiency fractures. The diagnosis was confirmed with plain films in every patient. T1-weighted and T2-weighted images were obtained in four patients using a 1.5-T unit. Postcontrast T1-weighted imaging was also done in three patients. Results and conclusions. MRI of pubic parasymphyseal insufficiency fracture characteristically demonstrates a hyperintense mass lesion with a hypointense rim on T2-weighted imaging, showing peripheral and septal enhancement after contrast administration. It is important to have this entity in mind in patients with osteoporosis, especially in patients with a history of pelvic irradiation for malignant disease, so as not to misinterpret it as a chondroid tumor or bone metastasis. C1 NIH,DEPT NUCL MED,BETHESDA,MD 20892. KYOTO UNIV,FAC MED,DEPT NUCL MED,SAKYO KU,KYOTO 60601,JAPAN. JAPANESE RED CROSS SOC,WAKAYAMA MED CTR,DEPT RADIOL,WAKAYAMA,JAPAN. NAGAHAMA CITY HOSP,DEPT ORTHOPAED SURG,NAGAHAMA,SHIGA,JAPAN. KYOTO UNIV,FAC MED,DEPT ORTHOPAED SURG,KYOTO 606,JAPAN. JAPANESE RED CROSS SOC,WAKAYAMA MED CTR,DEPT ORTHOPAED SURG,WAKAYAMA,JAPAN. NR 7 TC 9 Z9 9 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0364-2348 J9 SKELETAL RADIOL JI Skeletal Radiol. PD SEP PY 1997 VL 26 IS 9 BP 525 EP 528 PG 4 WC Orthopedics; Radiology, Nuclear Medicine & Medical Imaging SC Orthopedics; Radiology, Nuclear Medicine & Medical Imaging GA XY821 UT WOS:A1997XY82100003 PM 9342811 ER PT J AU Howard, G Manolio, TA Burke, GL Wolfson, SK OLeary, DH AF Howard, G Manolio, TA Burke, GL Wolfson, SK OLeary, DH TI Does the association of risk factors and atherosclerosis change with age? - An analysis of the combined ARIC and CHS cohorts SO STROKE LA English DT Article DE atherosclerosis; aging; cigarette smoking; carotid arteries; ultrasonics; risk factors ID INTIMA-MEDIA THICKNESS; CAROTID ATHEROSCLEROSIS; CARDIOVASCULAR HEALTH; DISEASE; HYPERTENSION; ARTERY AB Introduction A decrease in the estimated relative risk of cerebrovascular and cardiovascular diseases associated with known disease risk factors has been observed among elderly cohorts, perhaps suggesting that continued risk factor management in the elderly may not be as efficacious as with younger age groups. In this paper, the differential magnitude of the association of risk factors with atherosclerosis across the age spectrum from 45 years to older than 75 years is presented. Methods Subclinical atherosclerosis as measured by carotid ultrasonography and risk factor prevalence were assessed using similar methods among participants aged 45 to 64 years in the Atherosclerosis Risk in Communities (ARIC) study and among participants 65 years and older in the Cardiovascular Health Study (CHS). Pooling these two cohorts provided data on the relationship of risk factors and atherosclerosis on nearly 19 000 participants over a broad age range. Regression analyses were used to assess the consistency of the magnitude of the association of risk factors with atherosclerosis across the age spectrum separately for black and white participants in cross-sectional analyses. Results As expected, each of the risk factors was globally (across all ages) associated with increased atherosclerosis. However, the magnitude of the association did not differ across the age spectrum for hypertension, low density lipoprotein cholesterol (LDL-c), fibrinogen, or body mass index (BMI). For whites, there was a significantly greater impact of smoking and HDL-C among older age strata but a smaller impact of diabetes. For black women, the impact of HDL-C decreased among the older age strata. Conclusions These data suggest that most risk factors continue to be associated with increased atherosclerosis at older ages, possibly suggesting a continued value in investigation of strategies to reduce atherosclerosis by controlling risk factors at older ages. C1 WAKE FOREST UNIV,BOWMAN GRAY SCH MED,DEPT NEUROL,WINSTON SALEM,NC 27157. NHLBI,DIV EPIDEMIOL & CLIN APPLICAT,BETHESDA,MD 20892. UNIV PITTSBURGH,SCH MED,DEPT SURG,PITTSBURGH,PA. UNIV PITTSBURGH,SCH MED,DEPT NEUROSURG,PITTSBURGH,PA. RP Howard, G (reprint author), WAKE FOREST UNIV,BOWMAN GRAY SCH MED,DEPT PUBL HLTH SCI,MED CTR BLVD,WINSTON SALEM,NC 27157, USA. FU NHLBI NIH HHS [N01-HC-55018, N01-HC-55016, N01-HC-55015] NR 23 TC 86 Z9 88 U1 0 U2 1 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0039-2499 J9 STROKE JI Stroke PD SEP PY 1997 VL 28 IS 9 BP 1693 EP 1701 PG 9 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA XW442 UT WOS:A1997XW44200007 PM 9303011 ER PT J AU George, RK Chan, CC Whitcup, SM Nussenblatt, RB AF George, RK Chan, CC Whitcup, SM Nussenblatt, RB TI Ocular immunopathology of Behcet's disease SO SURVEY OF OPHTHALMOLOGY LA English DT Review DE adhesion molecule; Behcet's syndrome; immunopathology; ocular Behcet's disease; plasma cell; T-lymphocyte; vasculitis ID UVEITIS AB A patient developed progressive, severe, recurrent bilateral iridocyclitis, retinal vasculitis, and hemorrhagic infarction of the retina that led to blindness despite immunosuppressive therapy. Histopathology of an enucleated blind and painful eye revealed marked nongranulomatous uveitis with a predominantly CD4+ T-lymphocytic infiltration, as well as B-cell and plasma cell aggregation. Extensive expression of adhesion molecules on vascular endothelial cells were found. This finding suggests that adhesion molecules play an important role in the vasculitic process, the trademark of Behcet's disease. The ocular pathology and the therapeutic approach to Behcet's disease are briefly reviewed. (C) 1997 by Elsevier Science Inc. All rights reserved. C1 NEI,IMMUNOL LAB,BETHESDA,MD 20892. RP George, RK (reprint author), MADIGAN ARMY MED CTR,DEPT OPHTHALMOL,TACOMA,WA 98431, USA. NR 24 TC 56 Z9 57 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0039-6257 J9 SURV OPHTHALMOL JI Surv. Ophthalmol. PD SEP-OCT PY 1997 VL 42 IS 2 BP 157 EP 162 PG 6 WC Ophthalmology SC Ophthalmology GA YB161 UT WOS:A1997YB16100005 PM 9381369 ER PT J AU Wang, ZX Moody, K Newman, JD Insel, TR AF Wang, ZX Moody, K Newman, JD Insel, TR TI Vasopressin and oxytocin immunoreactive neurons and fibers in the forebrain of male and female common marmosets (Callithrix jaccchus) SO SYNAPSE LA English DT Article DE hypothalamus; stria terminalis; amygdala; sexual dimorphism ID MESSENGER-RNA LEVELS; ADULT-RAT BRAIN; STRIA TERMINALIS; BED NUCLEUS; SUPRACHIASMATIC NUCLEUS; MICROTUS-OCHROGASTER; SEX-DIFFERENCES; LATERAL SEPTUM; PRAIRIE VOLES; EXTRAHYPOTHALAMIC VASOPRESSIN AB Vasopressin (AVP) and oxytocin (OT) immunoreactive (ir) neurons and fibers were examined in the forebrain of male and female common marmosets (Callithrix jacchus). As expected from previous studies of cell, distribution in the rodent and primate brain, AVP-ir cells were most evident in the paraventricularis, supraopticus, and suprachiasmaticus of the hypothalamus. AVP-ir cells were also widely distributed in the lateral hypothalamus and the bed nucleus of the stria terminalis. A sexually dimorphic pattern of AVP-ir cells was found in the bed nucleus of the str ia terminalis, in which males had more AVP-ir cells than females. OT-ir cells were found in the paraventricularis and supraopticus of the hypothalamus as well as in the bed nucleus of the stria terminalis and the medial amygdala. Male and female marmosets did not differ in the distribution of OT-ir cells. Fibers for both AVP and OT were evident outside of the hypothalamic-neurohypophyseal tract, but a plexus of AVP-ir fibers in the lateral septum or lateral habenular nucleus, as seen in the rat brain, could not be detected, for either peptide. (C) 1997 Wiley-Liss, Inc. C1 EMORY UNIV,SCH MED,DEPT PSYCHIAT & BEHAV SCI,ATLANTA,GA 30322. EMORY UNIV,YERKES REG PRIMATE RES CTR,ATLANTA,GA 30322. NICHHD,COMPARAT ETHOL LAB,NIH,POOLESVILLE,MD 20837. FU NCRR NIH HHS [P51-RR00165]; PHS HHS [54368, 54554] NR 46 TC 45 Z9 45 U1 2 U2 7 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 SEP PY 1997 VL 27 IS 1 BP 14 EP 25 DI 10.1002/(SICI)1098-2396(199709)27:1<14::AID-SYN2>3.0.CO;2-G PG 12 WC Neurosciences SC Neurosciences & Neurology GA XP480 UT WOS:A1997XP48000002 PM 9268061 ER PT J AU Mullen, GP Antuch, W Maciejewski, MW Prasad, R Wilson, SH AF Mullen, GP Antuch, W Maciejewski, MW Prasad, R Wilson, SH TI Insights into the mechanism of the beta-elimination catalyzed by the N-terminal domain of DNA polymerase beta SO TETRAHEDRON LA English DT Article ID ENDONUCLEASE-III; ESCHERICHIA-COLI; EXCISION-REPAIR; BINDING; IDENTIFICATION; 5'-PHOSPHATE; SPECTROSCOPY; ENZYME; SITE AB The N-terminal domain of DNA polymerase beta carries an activity for excision of deoxyribose 5-phosphate from DNA at an interaction interface that includes a helix-hairpin-helix motif containing Lys-68 and Lys-72 and an adjacent Omega loop containing His-34 and Lys-35. His-34 displays a low pK(a) (5.7) due to proximity to Lys-35. In a proposed mechanism, Lys-68 protonates the hemiacetal O4' and His-34 stabilizes the protonated aldehyde-type species. possibly accepting the proton. In one of two possible mechanisms, Lys-68 or Lys-72 forms a Schiffs base with the substrate. His-34 can function in C2' deprotonation for the Lys-68 Schiff's base intermediate, while the proton would be transferred to water for the Lys-72 Schiffs base. Lys-35 stabilizes the phosphomonoester leaving group in either case. (C) 1997 Elsevier Science Ltd. C1 NIEHS,RES TRIANGLE PK,NC 27709. RP Mullen, GP (reprint author), UNIV CONNECTICUT,CTR HLTH,DEPT BIOCHEM,263 FARMINGTON AVE,FARMINGTON,CT 06032, USA. NR 22 TC 15 Z9 15 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0040-4020 J9 TETRAHEDRON JI Tetrahedron PD SEP 1 PY 1997 VL 53 IS 35 BP 12057 EP 12066 DI 10.1016/S0040-4020(97)00768-0 PG 10 WC Chemistry, Organic SC Chemistry GA XT721 UT WOS:A1997XT72100011 ER PT J AU Maronpot, RR AF Maronpot, RR TI Comments on the medium-term rat liver focus bioassay SO TOXICOLOGIC PATHOLOGY LA English DT Editorial Material RP Maronpot, RR (reprint author), NIEHS,LAB ANIM PATHOL,POB 12233,RES TRIANGLE PK,NC 27709, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SOC TOXICOLOGIC PATHOLOGISTS PI LAWRENCE PA 1041 NEW HAMPSHIRE ST PO BOX 368, LAWRENCE, KS 66044 SN 0192-6233 J9 TOXICOL PATHOL JI Toxicol. Pathol. PD SEP-OCT PY 1997 VL 25 IS 5 BP 461 EP 461 PG 1 WC Pathology; Toxicology SC Pathology; Toxicology GA XY346 UT WOS:A1997XY34600005 PM 9323834 ER PT J AU Dixon, D Couse, JF Korach, KS AF Dixon, D Couse, JF Korach, KS TI Disruption of the estrogen receptor gene in mice SO TOXICOLOGIC PATHOLOGY LA English DT Article C1 NIEHS,REPROD & DEV TOXICOL LAB,RES TRIANGLE PK,NC 27709. RP Dixon, D (reprint author), NIEHS,LAB EXPT PATHOL,MD C2-09,POB 12233,RES TRIANGLE PK,NC 27709, USA. OI Korach, Kenneth/0000-0002-7765-418X NR 9 TC 7 Z9 7 U1 0 U2 0 PU SOC TOXICOLOGIC PATHOLOGISTS PI LAWRENCE PA 1041 NEW HAMPSHIRE ST PO BOX 368, LAWRENCE, KS 66044 SN 0192-6233 J9 TOXICOL PATHOL JI Toxicol. Pathol. PD SEP-OCT PY 1997 VL 25 IS 5 BP 518 EP 520 PG 3 WC Pathology; Toxicology SC Pathology; Toxicology GA XY346 UT WOS:A1997XY34600016 PM 9323845 ER PT J AU Haseman, JK Boorman, GA Huff, J AF Haseman, JK Boorman, GA Huff, J TI Value of historical control data and other issues related to the evaluation of long-term rodent carcinogenicity studies SO TOXICOLOGIC PATHOLOGY LA English DT Editorial Material ID NATIONAL-TOXICOLOGY-PROGRAM; RISK ASSESSMENT; F344/N RATS; CHEMICAL CARCINOGENESIS; DIETARY RESTRICTION; BIOLOGICAL MODELS; DOSE SELECTION; B6C3F1 MICE; BODY-WEIGHT; CORN-OIL RP Haseman, JK (reprint author), NIEHS,DIV INTRAMURAL RES,POB 12233,RES TRIANGLE PK,NC 27709, USA. NR 54 TC 15 Z9 17 U1 0 U2 0 PU SOC TOXICOLOGIC PATHOLOGISTS PI LAWRENCE PA 1041 NEW HAMPSHIRE ST PO BOX 368, LAWRENCE, KS 66044 SN 0192-6233 J9 TOXICOL PATHOL JI Toxicol. Pathol. PD SEP-OCT PY 1997 VL 25 IS 5 BP 524 EP 527 PG 4 WC Pathology; Toxicology SC Pathology; Toxicology GA XY346 UT WOS:A1997XY34600018 PM 9323846 ER PT J AU Elwell, MR Mahler, JF Rao, GN AF Elwell, MR Mahler, JF Rao, GN TI ''Have you seen this?'' Inflammatory lesions in the lungs of rats SO TOXICOLOGIC PATHOLOGY LA English DT Article C1 NIEHS,RES TRIANGLE PK,NC 27709. RP Elwell, MR (reprint author), EXPT PATHOL LABS,POB 474,HERNDON,VA 22070, USA. NR 0 TC 12 Z9 12 U1 0 U2 0 PU SOC TOXICOLOGIC PATHOLOGISTS PI LAWRENCE PA 1041 NEW HAMPSHIRE ST PO BOX 368, LAWRENCE, KS 66044 SN 0192-6233 J9 TOXICOL PATHOL JI Toxicol. Pathol. PD SEP-OCT PY 1997 VL 25 IS 5 BP 529 EP 531 PG 3 WC Pathology; Toxicology SC Pathology; Toxicology GA XY346 UT WOS:A1997XY34600019 PM 9323847 ER PT J AU Cooper, P Guderian, R Orellana, P Sandoval, C Olalla, H Valdez, M Calvopina, M Guevara, A Griffin, G AF Cooper, P Guderian, R Orellana, P Sandoval, C Olalla, H Valdez, M Calvopina, M Guevara, A Griffin, G TI An outbreak of bartonellosis in Zamora Chinchipe province in Ecuador SO TRANSACTIONS OF THE ROYAL SOCIETY OF TROPICAL MEDICINE AND HYGIENE LA English DT Article DE bartonellosis; Bartonella bacilliformis; animal reservoir; Ecuador AB We report an outbreak of human bartonellosis in Zamora Chinchipe Province in Ecuador, which occurred in 1995-1996. Nineteen cases were seen, of which 18 presented with classical oroya fever (fever and profound anaemia) and one with verruga peruana; 11 of the cases (58%) had positive blood films containing Bartonella bacilliformis. The houses of cases and neighbouring controls were visited; blood samples for thin films and cultures were collected from members of each house and a questionnaire was administered to investigate possible risk factors for disease transmission. In none of those sampled was B. bacilliformis bacteriologically demonstrable. All case houses were located in isolated areas at the margin of forest and the presence of dead rodents was reported only in case houses (P<0.05). We suggest that human bartonellosis is a zoonosis with a natural rodent reservoir and that migrant humans infected in this way may become a temporary reservoir host in populated areas. C1 HOSP VOZANDES,DEPT CLIN INVEST,QUITO,ECUADOR. HOSP CANTONAL ZUMBA,ZUMBA,ECUADOR. ST GEORGE HOSP,SCH MED,DIV INFECT DIS,LONDON,ENGLAND. RP Cooper, P (reprint author), NIH,PARASIT DIS LAB,BLDG 4,ROOM 126,BETHESDA,MD 20892, USA. FU Wellcome Trust NR 13 TC 9 Z9 9 U1 0 U2 0 PU ROYAL SOC TROPICAL MEDICINE PI LONDON PA MANSON HOUSE 26 PORTLAND PLACE, LONDON, ENGLAND W1N 4EY SN 0035-9203 J9 T ROY SOC TROP MED H JI Trans. Roy. Soc. Trop. Med. Hyg. PD SEP-OCT PY 1997 VL 91 IS 5 BP 544 EP 546 DI 10.1016/S0035-9203(97)90019-5 PG 3 WC Public, Environmental & Occupational Health; Tropical Medicine SC Public, Environmental & Occupational Health; Tropical Medicine GA YD434 UT WOS:A1997YD43400015 PM 9463663 ER PT J AU Stroncek, DF AF Stroncek, DF TI Granulocyte immunology: Is there a need to know? SO TRANSFUSION LA English DT Editorial Material ID POLYMERASE CHAIN-REACTION; SEQUENCE-SPECIFIC PRIMERS; FC-RECEPTOR-III; ANTIGEN NB1; LEUKOCYTE ANTIBODIES; GENE-FREQUENCIES; NEUTROPHILS; NEUTROPENIA; ALLOIMMUNIZATION; TRANSPLANTATION RP Stroncek, DF (reprint author), NIH,DEPT TRANSFUS MED,WARREN G MAGNUSON CLIN CTR,BETHESDA,MD 20892, USA. NR 23 TC 2 Z9 2 U1 0 U2 0 PU AMER ASSOC BLOOD BANKS PI BETHESDA PA 8101 GLENBROOK RD, BETHESDA, MD 20814-2749 SN 0041-1132 J9 TRANSFUSION JI Transfusion PD SEP PY 1997 VL 37 IS 9 BP 886 EP 888 DI 10.1046/j.1537-2995.1997.37997454012.x PG 3 WC Hematology SC Hematology GA XW211 UT WOS:A1997XW21100002 PM 9308632 ER PT J AU Scalise, AC Vigue, F Fellowes, VS Carter, CS Read, EJ AF Scalise, AC Vigue, F Fellowes, VS Carter, CS Read, EJ TI Component labeling in a cell processing facility. SO TRANSFUSION LA English DT Meeting Abstract C1 NIH,DEPT TRANSFUS MED,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC BLOOD BANKS PI BETHESDA PA 8101 GLENBROOK RD, BETHESDA, MD 20814-2749 SN 0041-1132 J9 TRANSFUSION JI Transfusion PD SEP PY 1997 VL 37 IS 9 SU S BP A57 EP A57 PG 1 WC Hematology SC Hematology GA XW275 UT WOS:A1997XW27500500 ER PT J AU Barreda, L Procter, JL ConryCantilena, C AF Barreda, L Procter, JL ConryCantilena, C TI Characterization of serologic features in autoimmune lymphoproliferative syndrome. SO TRANSFUSION LA English DT Meeting Abstract C1 NIH,DEPT TRANSFUS MED,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC BLOOD BANKS PI BETHESDA PA 8101 GLENBROOK RD, BETHESDA, MD 20814-2749 SN 0041-1132 J9 TRANSFUSION JI Transfusion PD SEP PY 1997 VL 37 IS 9 SU S BP S278 EP S278 PG 1 WC Hematology SC Hematology GA XW275 UT WOS:A1997XW27500278 ER PT J AU ConryCantilena, C Melpolder, JC Alter, HJ AF ConryCantilena, C Melpolder, JC Alter, HJ TI Intranasal drug use among volunteer whole blood donors: Results of a survey SO TRANSFUSION LA English DT Meeting Abstract C1 NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC BLOOD BANKS PI BETHESDA PA 8101 GLENBROOK RD, BETHESDA, MD 20814-2749 SN 0041-1132 J9 TRANSFUSION JI Transfusion PD SEP PY 1997 VL 37 IS 9 SU S BP S396 EP S396 PG 1 WC Hematology SC Hematology GA XW275 UT WOS:A1997XW27500395 ER PT J AU Eiber, GA Stroncek, DF Dalmasso, AP AF Eiber, GA Stroncek, DF Dalmasso, AP TI Detection and characterization of autoantibodies in children with autoimmune neutropenia. SO TRANSFUSION LA English DT Meeting Abstract C1 AMER RED CROSS,ST PAUL,MN. NIH,DEPT TRANSFUS MED,BETHESDA,MD 20892. VET ADM MED CTR,MINNEAPOLIS,MN. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC BLOOD BANKS PI BETHESDA PA 8101 GLENBROOK RD, BETHESDA, MD 20814-2749 SN 0041-1132 J9 TRANSFUSION JI Transfusion PD SEP PY 1997 VL 37 IS 9 SU S BP S420 EP S420 PG 1 WC Hematology SC Hematology GA XW275 UT WOS:A1997XW27500419 ER PT J AU LeeFischer, J Read, EJ AF LeeFischer, J Read, EJ TI Effect of 24 hour hold on flow cytometric CD34+ cell enumeration in mobilized peripheral blood and leukapheresis samples SO TRANSFUSION LA English DT Meeting Abstract C1 NIH,DEPT TRANSFUS MED,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC BLOOD BANKS PI BETHESDA PA 8101 GLENBROOK RD, BETHESDA, MD 20814-2749 SN 0041-1132 J9 TRANSFUSION JI Transfusion PD SEP PY 1997 VL 37 IS 9 SU S BP S236 EP S236 PG 1 WC Hematology SC Hematology GA XW275 UT WOS:A1997XW27500236 ER PT J AU Leitman, SF Werden, R Garvey, MA Swedo, SE AF Leitman, SF Werden, R Garvey, MA Swedo, SE TI Randomized trial of plasma exchange, immune globulin (IVIG), or steroids in children with Sydenham's chorea. SO TRANSFUSION LA English DT Meeting Abstract C1 NIMH,NIH,BETHESDA,MD 20892. NIH,DEPT TRANSFUS MED,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC BLOOD BANKS PI BETHESDA PA 8101 GLENBROOK RD, BETHESDA, MD 20814-2749 SN 0041-1132 J9 TRANSFUSION JI Transfusion PD SEP PY 1997 VL 37 IS 9 SU S BP S272 EP S272 PG 1 WC Hematology SC Hematology GA XW275 UT WOS:A1997XW27500272 ER PT J AU Leitman, SF Oblitas, JM AF Leitman, SF Oblitas, JM TI Optimization of granulocytapheresis mobilization regimens using granulocyte colony stimulating factor (G-CSF) and dexamethasone (DEXA). SO TRANSFUSION LA English DT Meeting Abstract C1 NIH,DEPT TRANSFUS MED,BETHESDA,MD 20892. NR 0 TC 2 Z9 2 U1 0 U2 0 PU AMER ASSOC BLOOD BANKS PI BETHESDA PA 8101 GLENBROOK RD, BETHESDA, MD 20814-2749 SN 0041-1132 J9 TRANSFUSION JI Transfusion PD SEP PY 1997 VL 37 IS 9 SU S BP S268 EP S268 PG 1 WC Hematology SC Hematology GA XW275 UT WOS:A1997XW27500268 ER PT J AU Moulds, JM Rowe, JA Newbold, CI Miller, LH AF Moulds, JM Rowe, JA Newbold, CI Miller, LH TI Implication of the Knops blood group in P-falciparum malaria and a possible role for the SL(A-) phenotype. SO TRANSFUSION LA English DT Meeting Abstract C1 UNIV TEXAS,SCH MED,HOUSTON,TX. JOHN RADCLIFFE HOSP,OXFORD OX3 9DU,ENGLAND. NIAID,NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC BLOOD BANKS PI BETHESDA PA 8101 GLENBROOK RD, BETHESDA, MD 20814-2749 SN 0041-1132 J9 TRANSFUSION JI Transfusion PD SEP PY 1997 VL 37 IS 9 SU S BP S406 EP S406 PG 1 WC Hematology SC Hematology GA XW275 UT WOS:A1997XW27500405 ER PT J AU Oblitas, JM Sigmon, JM Leitman, SF AF Oblitas, JM Sigmon, JM Leitman, SF TI Prospective comparison of plateletpheresis yields using the Fenwal Amicus versus the CS-3000 Plus cell separators. SO TRANSFUSION LA English DT Meeting Abstract C1 AMER RED CROSS,WASHINGTON,DC 20006. NIH,DEPT TRANSFUS MED,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC BLOOD BANKS PI BETHESDA PA 8101 GLENBROOK RD, BETHESDA, MD 20814-2749 SN 0041-1132 J9 TRANSFUSION JI Transfusion PD SEP PY 1997 VL 37 IS 9 SU S BP S20 EP S20 PG 1 WC Hematology SC Hematology GA XW275 UT WOS:A1997XW27500020 ER PT J AU Robinet, E Certoux, JM Ferrand, C Cahn, JY Minjoz, J Reynolds, C Jacob, W Maples, PB Hardwick, A Herv, P Tiberghien, P AF Robinet, E Certoux, JM Ferrand, C Cahn, JY Minjoz, J Reynolds, C Jacob, W Maples, PB Hardwick, A Herv, P Tiberghien, P TI A closed culture system for the generation of gene-modified cells. SO TRANSFUSION LA English DT Meeting Abstract C1 ETSFC,BESANCON,FRANCE. CHU JEAN MINJOZ,BESANCON,FRANCE. NCI,FDRDC,FREDERICK,MD 21701. GTI,GAITHERSBURG,MD. BAXTER HEALTHCARE CORP,ROUND LAKE,IL 60073. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC BLOOD BANKS PI BETHESDA PA 8101 GLENBROOK RD, BETHESDA, MD 20814-2749 SN 0041-1132 J9 TRANSFUSION JI Transfusion PD SEP PY 1997 VL 37 IS 9 SU S BP S321 EP S321 PG 1 WC Hematology SC Hematology GA XW275 UT WOS:A1997XW27500321 ER PT J AU Smith, JD Leitman, SF AF Smith, JD Leitman, SF TI Filtration of red cell units: Effect of storage time and temperature on filter performance. SO TRANSFUSION LA English DT Meeting Abstract C1 NIH,DEPT TRANSFUS MED,BETHESDA,MD 20892. NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER ASSOC BLOOD BANKS PI BETHESDA PA 8101 GLENBROOK RD, BETHESDA, MD 20814-2749 SN 0041-1132 J9 TRANSFUSION JI Transfusion PD SEP PY 1997 VL 37 IS 9 SU S BP S53 EP S53 PG 1 WC Hematology SC Hematology GA XW275 UT WOS:A1997XW27500053 ER PT J AU Williams, AE Watanabe, K Mayo, DJ Thomson, RA Schreiber, GB AF Williams, AE Watanabe, K Mayo, DJ Thomson, RA Schreiber, GB TI Improving the efficacy of donor risk screening SO TRANSFUSION LA English DT Meeting Abstract C1 NHLBI,REDS STUDY,ROCKVILLE,MD. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC BLOOD BANKS PI BETHESDA PA 8101 GLENBROOK RD, BETHESDA, MD 20814-2749 SN 0041-1132 J9 TRANSFUSION JI Transfusion PD SEP PY 1997 VL 37 IS 9 SU S BP S339 EP S339 PG 1 WC Hematology SC Hematology GA XW275 UT WOS:A1997XW27500338 ER PT J AU Wahl, LM Shankavaram, U Zhang, YH AF Wahl, LM Shankavaram, U Zhang, YH TI Role of macrophages in vascular tissue remodelling SO TRANSPLANT IMMUNOLOGY LA English DT Article; Proceedings Paper CT 2nd International Symposium on the Etiology and Pathobiology of Transplant Vascular Sclerosis CY MAR 05-09, 1997 CL BERMUDA ID PROSTAGLANDIN-H SYNTHASE-2; MATRIX METALLOPROTEINASE PRODUCTION; HUMAN MONOCYTES; ATHEROSCLEROTIC PLAQUES; DEPENDENT MECHANISMS; COLLAGENASE; EXPRESSION; INHIBITION; INDUCTION; INTERLEUKIN-4 RP Wahl, LM (reprint author), NIDR,IMMUNOPATHOL SECT,NIH,BLDG 30,ROOM 325,BETHESDA,MD 20892, USA. NR 20 TC 4 Z9 4 U1 0 U2 0 PU ARNOLD, HODDER HEADLINE PLC PI LONDON PA 338 EUSTON ROAD, LONDON, ENGLAND NW1 3BH SN 0966-3274 J9 TRANSPL IMMUNOL JI Transpl. Immunol. PD SEP PY 1997 VL 5 IS 3 BP 173 EP 176 DI 10.1016/S0966-3274(97)80033-0 PG 4 WC Immunology; Transplantation SC Immunology; Transplantation GA YG724 UT WOS:A1997YG72400003 PM 9402681 ER PT J AU Hengen, PN AF Hengen, PN TI Methods and reagents - bionet.molbio.methds-reagnts - a status report SO TRENDS IN BIOCHEMICAL SCIENCES LA English DT Article AB Methods and reagents is a unique monthly column that highlights current discussions in the newsgroup bionet.molbio.methds-reagnts, available on the Internet. In this, the closing article for the Methods and reagents monthly column, I discuss how the methods group has evolved since the onset of this experimental monthly column, and try to relate its past and present condition to future improvements. For details on how to join the discussions on bionet, see the accompanying box. RP Hengen, PN (reprint author), NCI,FREDERICK CANC RES & DEV CTR,FREDERICK,MD 21702, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 SEP PY 1997 VL 22 IS 9 BP 359 EP 360 DI 10.1016/S0968-0004(97)01112-2 PG 2 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA XV802 UT WOS:A1997XV80200009 PM 9301338 ER PT J AU Wassermann, EM Grafman, J AF Wassermann, Eric M. Grafman, Jordan TI Combining transcranial magnetic stimulation and neuroimaging to map the brain SO TRENDS IN COGNITIVE SCIENCES LA English DT Editorial Material C1 [Wassermann, Eric M.] NINDS, Off Clin Director, Bethesda, MD 20892 USA. [Grafman, Jordan] NINDS, Cognit Neurosci Sect, Med Neurol Branch, Bethesda, MD 20892 USA. RP Wassermann, EM (reprint author), NINDS, Off Clin Director, Bethesda, MD 20892 USA. EM wassermann@nih.gov NR 15 TC 5 Z9 5 U1 0 U2 0 PU ELSEVIER SCIENCE LONDON PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 1364-6613 J9 TRENDS COGN SCI JI TRENDS COGN. SCI. PD SEP PY 1997 VL 1 IS 6 BP 199 EP 200 AR PII S1364-6613(97)01069-3 DI 10.1016/S1364-6613(97)01069-3 PG 2 WC Behavioral Sciences; Neurosciences; Psychology, Experimental SC Behavioral Sciences; Neurosciences & Neurology; Psychology GA V04VC UT WOS:000207084900001 PM 21223902 ER PT J AU Melikyan, GB Chernomordik, LV AF Melikyan, GB Chernomordik, LV TI Membrane rearrangements in fusion mediated by viral proteins SO TRENDS IN MICROBIOLOGY LA English DT Article ID INFLUENZA-VIRUS HEMAGGLUTININ; SEMLIKI-FOREST VIRUS; PLANAR BILAYER-MEMBRANES; INDUCED CELL-FUSION; LOW-PH; ENVELOPE GLYCOPROTEIN; INITIAL-STAGES; CONFORMATIONAL-CHANGES; EXPRESSING CELLS; PORE AB Diverse enveloped viruses enter host cells by fusing their envelopes with cell membranes. The mechanisms of merger of lipid bilayers of two membranes mediated by influenza hemagglutinin and other viral fusion proteins apparently involve local lipidic connections that evolve into a bilayer septum in which a pore forms and expands. C1 NICHHD,LAB CELLULAR & MOL BIOPHYS,NIH,BETHESDA,MD 20892. RP Melikyan, GB (reprint author), RUSH MED COLL,DEPT MOL BIOPHYS & PHYSIOL,1653 W CONGRESS PKWY,CHICAGO,IL 60612, USA. NR 70 TC 24 Z9 24 U1 0 U2 1 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, OXON, ENGLAND OX5 1GB SN 0966-842X J9 TRENDS MICROBIOL JI Trends Microbiol. PD SEP PY 1997 VL 5 IS 9 BP 349 EP 355 DI 10.1016/S0966-842X(97)01107-4 PG 7 WC Biochemistry & Molecular Biology; Microbiology SC Biochemistry & Molecular Biology; Microbiology GA XU801 UT WOS:A1997XU80100006 PM 9294890 ER PT J AU Stanley, EF AF Stanley, EF TI The calcium channel and the organization of the presynaptic transmitter release face SO TRENDS IN NEUROSCIENCES LA English DT Review ID SYNAPTIC VESICLE EXOCYTOSIS; PROTEIN-PROTEIN INTERACTIONS; EATON MYASTHENIC SYNDROME; SQUID GIANT SYNAPSE; N-TYPE; ACTIVE ZONES; OMEGA-CONOTOXIN; CA2+ CHANNELS; HAIR-CELLS; NEUROTRANSMITTER RELEASE AB Calcium influx through ion channels located on the release face, of the presynaptic nerve terminal gates the release of neurotransmitters by the fusion of the secretory vesicle and the discharge of its contents, Recently, several lines of research have indicated that the relationship between the Ca2+ channel and the release site might be more complex than dictated simply by its role as an ion conduit. The evidence suggests that the channel and the transmitter-release mechanism exist as a multimolecular entity and that this interaction has functional consequences, not: only on the mechanism and properties of transmitter release, but also on the behavior of the presynaptic Ca2+ channel itself. RP Stanley, EF (reprint author), NINCDS,SYNAPT MECHANISMS SECT,NIH,BLDG 36,RM 5A25,BETHESDA,MD 20892, USA. NR 62 TC 168 Z9 172 U1 4 U2 21 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, OXON, ENGLAND OX5 1GB SN 0166-2236 J9 TRENDS NEUROSCI JI Trends Neurosci. PD SEP PY 1997 VL 20 IS 9 BP 404 EP 409 DI 10.1016/S0166-2236(97)01091-6 PG 6 WC Neurosciences SC Neurosciences & Neurology GA XT890 UT WOS:A1997XT89000013 PM 9292969 ER PT J AU Walther, MM AF Walther, MM TI Cystic renal disease and tuberous sclerosis in infants SO UROLOGY LA English DT Letter ID KIDNEY RP Walther, MM (reprint author), NCI,DCS,SB,UROL ONCOL SECT,NIH,9000 ROCKVILLE PIKE,BLDG 10,ROOM 2B-43,10 CTR DR,BETHESDA,MD 20898, USA. NR 4 TC 1 Z9 1 U1 0 U2 0 PU CAHNERS PUBL CO PI NEW YORK PA 249 WEST 17 STREET, NEW YORK, NY 10011 SN 0090-4295 J9 UROLOGY JI UROLOGY PD SEP PY 1997 VL 50 IS 3 BP 485 EP 485 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA XW201 UT WOS:A1997XW20100043 PM 9301729 ER PT J AU Nii, A Reynolds, DA Young, HA Ward, JM AF Nii, A Reynolds, DA Young, HA Ward, JM TI Osteochondrodysplasia occurring in transgenic mice expressing interferon-gamma SO VETERINARY PATHOLOGY LA English DT Article DE bone resorption; cartilage; collagen; cytokines; interferon-gamma; osteochondrodysplasia; osteoclast; osteogenesis imperfecta; transgenic mice ID INHIBITS COLLAGEN-SYNTHESIS; NEONATAL MOUSE CALVARIA; PARTIALLY DELETED GENE; BONE-RESORPTION; OSTEOGENESIS IMPERFECTA; IMMUNE INTERFERON; ECTOPIC EXPRESSION; MAC-2 ANTIGEN; INTERLEUKIN-4; MUTATIONS AB In addition to various biological activities, interferon-gamma (IFN-gamma) inhibits bone resorption and collagen synthesis. We produced a transgenic mouse line expressing the murine IFN-gamma gene and protein in the bone marrow and thymus. Forty-five transgenic FVB/NCr mice, 23 days-9 months of age, were studied for anomalies in the skeletal system. The transgenic mice had short, wide, and deformed long bones. Young transgenic mice had epiphyseal plates severely thickened with zones of hypertrophy and degeneration with irregular metaphyseal borders. Cartilagenous masses were also observed in the metadiaphyseal marrow cavities. These lesions were primarily seen in long bones and ribs. Adult transgenic mice had residues of degenerated cartilagenous masses in the diaphyses. Many osteoclasts with well-developed ruffled borders were present on the metaphyseal cartilagenous masses in young transgenic mice. Adult transgenic mice had less prominent primary spongiosa with fewer osteoclasts at the metaphysis as compared with nontransgenic controls. The cortical bones of the transgenic mice were thinner and more immature compared with controls. Transgenic mice also had fractures, disruption of the epiphyseal plate, and degeneration of articular cartilage. Thus, the IFN-gamma transgenic mice developed a complex chondro-osseous lesion that was diagnosed as osteochondrodysplasia. The lesions may originate from primarily decreased matrix synthesis in bone and cartilage and also possible osteoclast-related changes caused by IFN-gamma overexpression in the bone marrow. Our IFN-gamma transgenic mouse will be a useful model to investigate the role of IFN-gamma in bone metabolism. C1 NCI,OFF LAB ANIM SCI,VET & TUMOR PATHOL SECT,FREDERICK,MD 21701. NCI,BIOL RESPONSE MODIFIERS PROGRAM,EXPT IMMUNOL LAB,FREDERICK,MD 21701. NR 47 TC 9 Z9 10 U1 0 U2 0 PU AMER COLL VET PATHOLOGIST PI LAWRENCE PA 810 EAST 10TH STREET, LAWRENCE, KS 66044 SN 0300-9858 J9 VET PATHOL JI Vet. Pathol. PD SEP PY 1997 VL 34 IS 5 BP 431 EP 441 PG 11 WC Pathology; Veterinary Sciences SC Pathology; Veterinary Sciences GA XW975 UT WOS:A1997XW97500007 PM 9381654 ER PT J AU Durbin, AP Hall, SL Siew, JW Whitehead, SS Collins, PL Murphy, BR AF Durbin, AP Hall, SL Siew, JW Whitehead, SS Collins, PL Murphy, BR TI Recovery of infectious human parainfluenza virus type 3 from cDNA SO VIROLOGY LA English DT Article ID COMPLETE NUCLEOTIDE-SEQUENCE; RESPIRATORY SYNCYTIAL VIRUS; STRAND RNA VIRUSES; PARA-INFLUENZA; GENE-EXPRESSION; CLONED CDNA; JS STRAIN; VACCINE; PROTEIN; INFANTS AB Infectious HPIV3 was produced by the intracellular coexpression of four plasmid-borne cDNAs. These separately encoded a complete HPIV3 genome (negative-sense), the HPIV3 nucleocapsid protein N, the phosphoprotein P, and the polymerase protein L. The cDNA-encoded HPIV3 genome differed from the JS wildtype (wt) strain of HPIV3 used in its construction by seven point mutations: four of these are silent mutations in the HN or L gene coding regions that serve as markers of a cDNA-derived virus, two were introduced to create an amino acid substitution that ablates an epitope recognized by the HN-specific monoclonal neutralizing antibody 423/6, and the remaining point mutation results in an incidental amino acid substitution in the HN protein at amino acid position 263. The four plasmids were transfected into HEp-2 cell monolayers and their expression was driven by T7 RNA polymerase supplied by a vaccinia virus recombinant. The titer of virus present in the harvested transfection supernatant was low (<5 PFU/ml), and the recovered recombinant virus (rJS) retained each or the seven mutations present in the cDNA from which it was derived. Despite the introduced and incidental mutations, rJS retained the wt phenotypes as regards replication at elevated temperature in vitro and efficient replication in the upper and lower respiratory tract of hamsters, rJS was also recovered from a cDNA encoding a complete antigenome (positive-sense) with slightly greater efficiency than from the negative-sense construct. The ability to generate infectious HPIV3 from cDNA should greatly enhance our ability to develop new live-attenuated parainfluenza Virus vaccines, including chimeric PIV1 and PIV2 vaccines, and to understand the genetic basis of attenuation of PIV3 candidate vaccines. (C) 1997 Academic Press. RP Durbin, AP (reprint author), NIAID,INFECT DIS LAB,NIH,7 CTR DR,MSC 0720,BETHESDA,MD 20892, USA. NR 33 TC 86 Z9 88 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 SEP 1 PY 1997 VL 235 IS 2 BP 323 EP 332 DI 10.1006/viro.1997.8697 PG 10 WC Virology SC Virology GA XV859 UT WOS:A1997XV85900016 PM 9281512 ER PT J AU Funkenstein, B Jakowlew, SB AF Funkenstein, B Jakowlew, SB TI Piscine (Sparus aurata) alpha subunit of the G-protein transducin is homologous to mammalian cone and rod transducin SO VISION RESEARCH LA English DT Article DE transducin; cDNA cloning; teleost; (Sparus aurata); eye ID CYCLIC-GMP; RIBONUCLEIC-ACID; SEQUENCE; CLONING; CHROMATOGRAPHY; IDENTIFICATION; PHOTORECEPTORS; PURIFICATION; EXPRESSION; VISION AB A novel cDNA encoding alpha subunit of the GTP-binding protein, transducin, has been cloned from a marine fish, Sparus aurata. The cDNA contains an open reading frame of 1050 nt (encoding 350 amino acid residues), A high degree of identity was found with known mammalian transducin proteins of cones (G(t2 alpha)) or rods (G(t1 alpha)): human G(t2 alpha) (80.2%), bovine G(t2 alpha) (79.3%), mouse G(t1 alpha) (78.2%), mouse G(t2 alpha) (78%) and bovine G(t1 alpha), (77.9%), Northern blot analysis of different tissues revealed a transcript of about 2.5 kb, which is expressed only in the fish eye and not in other tissues from adult fish, supporting its identification as transducin, Ontogeny of transducin mRNA expression during early development of Sparus aurata, determined by Northern blot analysis, showed very low levels in larvae 3 days after hatching but not earlier, Levels increased 3- and 6-fold on days 4 and 6 (respectively) compared with those on day 3 and remained essentially unchanged thereafter, until day 21 after hatching (the last day studied), Our results suggest that in fish only one cc subunit of transducin is found, which shows similar identity with cone and rod a subunits of mammals, (C) 1997 Elsevier Science Ltd. C1 NCI, BIOMARKERS & PREVENT RES BRANCH, ROCKVILLE, MD 20850 USA. RP Funkenstein, B (reprint author), NATL INST OCEANOG, ISRAEL OCEANOG & LIMNOL RES, POB 8030, IL-31080 HAIFA, ISRAEL. NR 27 TC 6 Z9 7 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0042-6989 EI 1878-5646 J9 VISION RES JI Vision Res. PD SEP PY 1997 VL 37 IS 18 BP 2487 EP 2493 DI 10.1016/S0042-6989(97)00062-X PG 7 WC Neurosciences; Ophthalmology SC Neurosciences & Neurology; Ophthalmology GA XR948 UT WOS:A1997XR94800002 PM 9373680 ER PT J AU Hof, PR Ungerleider, LG Adams, MM Webster, MJ Gattass, R Blumberg, DM Morrison, JH AF Hof, PR Ungerleider, LG Adams, MM Webster, MJ Gattass, R Blumberg, DM Morrison, JH TI Callosally projecting neurons in the macaque monkey V1/V2 border are enriched in nonphosphorylated neurofilament protein SO VISUAL NEUROSCIENCE LA English DT Article DE callosal projections; cytoskeleton; neurochemical coding; neurofilament protein; primate visual system ID CAT VISUAL-CORTEX; CORPUS-CALLOSUM; DIFFERENTIAL EXPRESSION; AREA V2; CONNECTIONS; MORPHOLOGY; AXONS; ORGANIZATION; PHOSPHORYLATION; PATTERNS AB Previous immunohistochemical studies combined with retrograde tracing in macaque monkeys have demonstrated that corticocortical projections can be differentiated by their content of neurofilament protein. The present study analyzed the distribution of nonphosphorylated neurofilament protein in callosally projecting neurons located at the V1/V2 border. All of the retrogradely labeled neurons were located in layer III at the V1/V2 border and at an immediately adjacent zone of area V2. A quantitative analysis showed that the vast majority (almost 95%) of these interhemispheric projection neurons contain neurofilament protein immunoreactivity. This observation differs from data obtained in other sets of callosal connections, including homotypical interhemispheric projections in the prefrontal, temporal, and parietal association cortices, that were found to contain uniformly low proportions of neurofilament protein-immunoreactive neurons. Comparably, highly variable proportions of neurofilament protein-containing neurons have been reported in intrahemispheric corticocortical pathways, including feedforward and feedback visual connections. These results indicate that neurofilament protein is a prominent neurochemical feature that identifies a particular population of interhemispheric projection neurons at the V1/V2 border, and suggest that this biochemical attribute may be critical for the function of this subset of callosal neurons. C1 MT SINAI SCH MED,FISHBERG RES CTR NEUROBIOL,NEW YORK,NY. MT SINAI SCH MED,DEPT GERIATR & ADULT DEV,NEW YORK,NY. MT SINAI SCH MED,DEPT OPHTHALMOL,NEW YORK,NY. NIMH,LAB BRAIN & COGNIT,BETHESDA,MD 20892. NATL INST MENTAL HLTH NEUROSCI CTR ST ELIZABETHS,STANLEY FDN RES PROGRAM,WASHINGTON,DC. UNIV FED RIO DE JANEIRO,INST BIOFIS CARLOS CHAGAS FILHO,DEPT NEUROBIOL,BR-21941900 RIO JANEIRO,BRAZIL. RP Hof, PR (reprint author), CUNY MT SINAI SCH MED,NEUROBIOL AGING LABS,BOX 1639,1 GUSTAVE L LEVY PL,NEW YORK,NY 10029, USA. RI Morrison, John/F-9229-2012 FU NIA NIH HHS [AG06647] NR 56 TC 21 Z9 21 U1 0 U2 0 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 40 WEST 20TH STREET, NEW YORK, NY 10011-4211 SN 0952-5238 J9 VISUAL NEUROSCI JI Visual Neurosci. PD SEP-OCT PY 1997 VL 14 IS 5 BP 981 EP 987 PG 7 WC Neurosciences; Ophthalmology SC Neurosciences & Neurology; Ophthalmology GA XV857 UT WOS:A1997XV85700015 PM 9364733 ER PT J AU Jensen, RT Gibril, F Termanini, B AF Jensen, RT Gibril, F Termanini, B TI Definition of the role of somatostatin receptor scintigraphy in gastrointestinal neuroendocrine tumor localization SO YALE JOURNAL OF BIOLOGY AND MEDICINE LA English DT Article; Proceedings Paper CT Symposium on the Biological and Clinical Relevance of the Somatostatin Receptor CY NOV 24, 1996 CL YALE UNIV SCH MED, NEW HAVEN, CONNECTICUT HO YALE UNIV SCH MED ID PANCREATIC ENDOCRINE TUMORS; ZOLLINGER-ELLISON-SYNDROME; ISLET CELL TUMORS; DYNAMIC BOLUS CT; ENDOSCOPIC ULTRASONOGRAPHY; PREOPERATIVE LOCALIZATION; GASTROENTEROPANCREATIC TUMORS; DUODENAL GASTRINOMAS; HEPATIC METASTASES; CAVERNOUS HEMANGIOMAS AB There are six major steps in the management of patients with neuroendocrine tumors (NETs) (carcinoids and pancreatic endocrine tumors). One of the steps that is increasing in its importance is the need to assess primary tumor location and tumor extent in these patients. Without such information, it is not possible to adequately manage these patients. Conventional imaging studies (CT scan, MRI, ultrasound, angiography), functional localization studies measuring hormonal gradients, endoscopic ultrasound, and most recently, somatostatin receptor scintigraphy (SRS) with [I-125-DTPA-DPhe(1)]-octreotide have all been advocated to localize NETs in different studies. Whereas it is now established that for all NETs, except insulinomas, SRS has the greatest sensitivity, it remains unclear whether this increased sensitivity translates into increased clinical usefulness. It, therefore, remains unclear based on fiscal and clinical considerations what should be the recommended algorithm for the use of the different localization methods. To address this issue, we have recently performed two prospective studies on patients with gastrinomas. In this paper, the methods and results of each are summarized and based on these results, an algorithm for localization studies in NETs is proposed. One study assessed the role of SRS in management in 122 patients and shows that the use of SRS changed management in 47 percent of patients according to six different criteria when the patients were stratified according to their principal management problem. Determining whether liver metastases were present is one of die major goals of tumor localization studies and is frequently a source of confusion because of the difficulty in distinguishing small NETs liver metastases from hemangiomas. In the second study, the ability of SRS and other tumor localization methods to distinguish these two possibilities was assessed in: 15 patients with small hemangiomas and 15 patients with small hepatic metastases (mean size 1.3 cm). SRS correctly identified 93 percent of the patients with liver metastases and was not positive in any patient with a hemangioma, suggesting it was not a liver metastases. SRS had greater negative and positive predictive value than conventional studies. Based on these two studies, and SRS's greater sensitivity and fiscal considerations, it is proposed that SRS should be the initial tumor imaging study in all NETs except insulinomas, and algorithms for the use of other localization studies in both NETs and insulinomas are proposed. C1 NIDDK, NIH, DDT, Digest Dis Branch, Bethesda, MD 20892 USA. RP Jensen, RT (reprint author), NIDDK, NIH, DDT, Digest Dis Branch, Bldg 10,Room 9C-103,10 Ctr Dr MSC 1804, Bethesda, MD 20892 USA. NR 96 TC 27 Z9 28 U1 0 U2 0 PU YALE J BIOL MED INC PI NEW HAVEN PA 333 CEDAR ST, NEW HAVEN, CT 06510 USA SN 0044-0086 J9 YALE J BIOL MED JI Yale J. Biol. Med. PD SEP-DEC PY 1997 VL 70 IS 5-6 BP 481 EP 500 PG 20 WC Biology; Medicine, General & Internal; Medicine, Research & Experimental SC Life Sciences & Biomedicine - Other Topics; General & Internal Medicine; Research & Experimental Medicine GA 139JA UT WOS:000077023800003 PM 9825476 ER PT J AU Gibril, F Jensen, RT AF Gibril, F Jensen, RT TI Comparative analysis of diagnostic techniques for localization of gastrointestinal neuroendocrine tumors SO YALE JOURNAL OF BIOLOGY AND MEDICINE LA English DT Article; Proceedings Paper CT Symposium on the Biological and Clinical Relevance of the Somatostatin Receptor CY NOV 24, 1996 CL YALE UNIV SCH MED, NEW HAVEN, CONNECTICUT HO YALE UNIV SCH MED ID SOMATOSTATIN-RECEPTOR SCINTIGRAPHY; ZOLLINGER-ELLISON-SYNDROME; PANCREATIC ENDOCRINE TUMORS; ISLET CELL TUMORS; ENDOSCOPIC ULTRASONOGRAPHY; GASTROENTEROPANCREATIC TUMORS; PREOPERATIVE LOCALIZATION; METASTATIC GASTRINOMAS; DUODENAL GASTRINOMAS; INSULINOMAS AB In vitro studies have shown that gastroenteropancreatic tumors, with the exception of insulinomas, have a high density of somatostatin receptors and can be imaged in vivo using somatostatin receptor scintigraphy (SRS) with either [I-123-Tyr(3)]octreotide or [In-111 DTPA,DPhe(1)]octreotide. However, the sensitivity in relation to conventional imaging studies (ultrasound, CT, MRI, angiography) remains unclear. To address this question, we performed a prospective study of 80 patients with gastrinomas where SRS was compared with other conventional imaging techniques for detecting extrahepatic gastrinomas or liver metastases. Extrahepatic gastrinomas were identified by SRS in 58 percent of patients, whereas conventional imaging studies detected gastrinomas in 9 percent to 48 percent of patients. In detecting hepatis metastases in 24 patients with histologically-proven metastases, SRS was positive in 92 percent; ultrasound, CT or angiography in 42 percent to 62 percent; and MRI in 71 percent of patients. These results are compared with other studies in detecting gastrinomas as well as series including other PETs, excluding insulinomas, with insulinomas alone, and with carcinoid tumors. An analysis of the ability of SRS to identify gastrinomas found in different sites at surgery was performed. The role of endoscopic ultrasound (EUS) in detecting various PETs, in comparison to that of SRS, is yet to be established, particularly for extrapancreatic PETs. Therefore, the results of EUS in various studies containing patients with PETs are compared to those with SRS and conventional imaging studies. These data suggest that EUS is the first choice of localization methods for detecting insulinoma, which is an intrapancreatic tumor in almost all cases. In other PETs there still is not sufficient data to establish the relative roles of EUS and SRS. C1 NIDDK, NIH, DDB, Bethesda, MD 20892 USA. RP Jensen, RT (reprint author), NIDDK, NIH, DDB, Bldg 10,Rm 9C-103,10 Ctr Dr MSC 1804, Bethesda, MD 20892 USA. NR 57 TC 17 Z9 19 U1 0 U2 0 PU YALE J BIOL MED INC PI NEW HAVEN PA 333 CEDAR ST, NEW HAVEN, CT 06510 USA SN 0044-0086 J9 YALE J BIOL MED JI Yale J. Biol. Med. PD SEP-DEC PY 1997 VL 70 IS 5-6 BP 509 EP 522 PG 14 WC Biology; Medicine, General & Internal; Medicine, Research & Experimental SC Life Sciences & Biomedicine - Other Topics; General & Internal Medicine; Research & Experimental Medicine GA 139JA UT WOS:000077023800005 PM 9825478 ER PT J AU Ernst, M Zametkin, AJ Matochik, JA Pascualvaca, D Cohen, RM AF Ernst, M Zametkin, AJ Matochik, JA Pascualvaca, D Cohen, RM TI Low medial prefrontal dopaminergic activity in autistic children SO LANCET LA English DT Article C1 NIMH,CEREBRAL METAB LAB,NIH,BETHESDA,MD 20892. RP Ernst, M (reprint author), NATL INST DRUG ABUSE INTRAMURAL RES PROGRAM,BRAIN IMAGING CTR,BALTIMORE,MD 21224, USA. NR 5 TC 84 Z9 84 U1 2 U2 5 PU LANCET LTD PI LONDON PA 42 BEDFORD SQUARE, LONDON, ENGLAND WC1B 3SL SN 0140-6736 J9 LANCET JI Lancet PD AUG 30 PY 1997 VL 350 IS 9078 BP 638 EP 638 DI 10.1016/S0140-6736(05)63326-0 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA XU283 UT WOS:A1997XU28300016 PM 9288051 ER PT J AU Park, T Lee, SY AF Park, T Lee, SY TI A test of missing completely at random for longitudinal data with missing observations SO STATISTICS IN MEDICINE LA English DT Article ID PATTERN-MIXTURE MODELS; INCOMPLETE DATA; REGRESSION; MECHANISM AB Liang and Zeger proposed a generalized estimating equations approach to the analysis of longitudinal data Their models assume that missing observations are missing completely at random in the sense of Rubin. However, when this assumption does not hold, their analysis may yield biased results. In this paper, we develop a simple and practical procedure for testing this assumption. The proposed procedure is related to that of Park and Davis. (C) 1997 by John Wiley & Sons, Ltd. C1 NICHHD,BIOMETRY & MATH STAT BRANCH,BETHESDA,MD 20892. SEJONG UNIV,DEPT APPL STAT,KWANGJIN GU,SEOUL 133474,SOUTH KOREA. RP Park, T (reprint author), HANKUK UNIV FOREIGN STUDIES,DEPT STAT,YONGIN GUN 449791,KYUNGKI DO,SOUTH KOREA. NR 18 TC 21 Z9 22 U1 0 U2 1 PU JOHN WILEY & SONS LTD PI W SUSSEX PA BAFFINS LANE CHICHESTER, W SUSSEX, ENGLAND PO19 1UD SN 0277-6715 J9 STAT MED JI Stat. Med. PD AUG 30 PY 1997 VL 16 IS 16 BP 1859 EP 1871 DI 10.1002/(SICI)1097-0258(19970830)16:16<1859::AID-SIM593>3.0.CO;2-3 PG 13 WC Mathematical & Computational Biology; Public, Environmental & Occupational Health; Medical Informatics; Medicine, Research & Experimental; Statistics & Probability SC Mathematical & Computational Biology; Public, Environmental & Occupational Health; Medical Informatics; Research & Experimental Medicine; Mathematics GA XR017 UT WOS:A1997XR01700006 PM 9280038 ER PT J AU Yuan, J McCann, U Ricaurte, G AF Yuan, J McCann, U Ricaurte, G TI Methylphenidate and brain dopamine neurotoxicity SO BRAIN RESEARCH LA English DT Article DE dopamine; neurotoxicity; amphetamine; ADHD; narcolepsy ID STRIATAL DOPAMINE; D-AMPHETAMINE; METHAMPHETAMINE; INCREASES; DEPLETION; DEGENERATION; NARCOLEPSY; RESERPINE; RELEASE; NUCLEUS AB To further evaluate the dopamine (DA) neurotoxic potential of the widely prescribed psychostimulant, methylphenidate, mice were treated with various doses (range: 10-120 mg/kg) and treatment schedules of methylphenidate (every 2 h X 4 or twice daily X 4). Higher doses of methylphenidate produced intense stereotypy, as well as short- (5-day), but not long- (2-week), term depletions of striatal DA axonal markers. By contrast, amphetamine caused not only intense stereotypy, but also profound, long-lasting, dose-related DA deficits. These findings indicate that results of studies of amphetamine neurotoxicity using short (5-day) post-drug survival periods are potentially misleading. Further, the present findings confirm and extend previous results indicating that methylphenidate, unlike amphetamine, lacks DA neurotoxic potential, and strongly suggest that DA efflux, although perhaps necessary, is not sufficient for the expression of amphetamine-induced DA neurotoxicity. (C) 1997 Elsevier Science B.V. C1 NIMH,UNIT ANXIETY DISORDERS,BIOL PSYCHIAT BRANCH,BETHESDA,MD 20892. RP Yuan, J (reprint author), JOHNS HOPKINS MED INST,DEPT NEUROL,BALTIMORE,MD 21224, USA. FU NIDA NIH HHS [KO2 DA00206, R01DA06275] NR 30 TC 30 Z9 30 U1 1 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0006-8993 J9 BRAIN RES JI Brain Res. PD AUG 29 PY 1997 VL 767 IS 1 BP 172 EP 175 DI 10.1016/S0006-8993(97)00771-3 PG 4 WC Neurosciences SC Neurosciences & Neurology GA XY713 UT WOS:A1997XY71300025 PM 9365033 ER PT J AU Overby, LH Carver, GC Philpot, RM AF Overby, LH Carver, GC Philpot, RM TI Quantitation and kinetic properties of hepatic microsomal and recombinant flavin-containing monooxygenases 3 and 5 from humans SO CHEMICO-BIOLOGICAL INTERACTIONS LA English DT Article DE FMO3; FMO5; drug metabolism; ranitidine; methimazole ID ADULT HUMAN LIVER; ESCHERICHIA-COLI; N-OXIDATION; RIBONUCLEIC-ACID; EXPRESSION; RABBIT; FORMS; SULFOXIDATION; PURIFICATION; METABOLISM AB Variable amounts of flavin-containing monooxygenase isoforms 3 and 5 (FMO3 and FMO5) are present in microsomal preparations from adult, male, human liver. Quantitation with monospecific antibodies and recombinant isoforms as standards showed levels of FMO3 and of FMO5 that ranged from 12.5 to 117 and 3.5 to 34 pmol/mg microsomal protein, respectively. The concentration of FMO3 was greater than that of FMO5 in all samples, but the ratio of FMO3 to FMO5 varied from 2:1 to 10:1. Human hepatic microsomal samples also showed variable activities for the S-oxidation of methimazole. This activity was associated totally with FMO3; no participation of FMO5 was apparent. This conclusion was supported by several lines of evidence: first, the catalytic efficiency of FMO3 with methimazole was found to be similar to 5000 times greater than that of FMO5; second, the rate of metabolism showed a direct, quantitative relationship with FMO3 content; third, the plot of the relationship between metabolism and FMO3 content extrapolated close to the origin. A second reaction, the N-oxidation of ranitidine, exhibited a much higher K-m with recombinant FMO3 than did methimazole (2 mM vs. 35 mu M). However, a direct relationship between this reaction and FMO3 content in human hepatic microsomal preparations was also apparent. This result shows that even with a high K-m substrate, FMO3-catalyzed metabolism can account for the majority of the product formation with some drugs. Our findings demonstrate that the contribution of FMO isoforms to human hepatic drug metabolism can be assessed quantitatively on the basis of the characteristics of the enzymes expressed in Escherichia coli. (C) 1997 Elsevier Science Ireland Ltd. C1 NIEHS,LAB SIGNAL TRANSDUCT,RES TRIANGLE PK,NC 27709. NR 45 TC 92 Z9 94 U1 0 U2 6 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 AUG 29 PY 1997 VL 106 IS 1 BP 29 EP 45 DI 10.1016/S0009-2797(97)00055-0 PG 17 WC Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Toxicology SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Toxicology GA XW521 UT WOS:A1997XW52100003 PM 9305407 ER PT J AU Hinnebusch, AG AF Hinnebusch, AG TI Translational regulation of yeast GCN4 - A window on factors that control initiator-tRNA binding to the ribosome SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Review ID NUCLEOTIDE-EXCHANGE FACTOR; OPEN READING FRAMES; TRANSFER-RNA-SYNTHETASES; EIF-2-ALPHA KINASE GCN2; AMINO-ACID BIOSYNTHESIS; SACCHAROMYCES-CEREVISIAE; PROTEIN-KINASE; MESSENGER-RNA; FACTOR-II; START-SITE RP Hinnebusch, AG (reprint author), NICHHD,LAB EUKARYOT GENE REGULAT,NIH,BETHESDA,MD 20892, USA. NR 61 TC 381 Z9 387 U1 0 U2 10 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 AUG 29 PY 1997 VL 272 IS 35 BP 21661 EP 21664 DI 10.1074/jbc.272.35.21661 PG 4 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA XT850 UT WOS:A1997XT85000001 PM 9268289 ER PT J AU Uren, A Jakus, J deMora, JF Yeudall, A Santos, E Gutkind, S Heidaran, MA AF Uren, A Jakus, J deMora, JF Yeudall, A Santos, E Gutkind, S Heidaran, MA TI Carboxyl-terminal domain of p27(Kip1) activates CDC2 SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID CYCLIN-DEPENDENT KINASES; CELL-CYCLE; CDK INHIBITOR; P21; P21(CIP1); BINDING AB A variant form of p27 was unexpectedly detected in a synchronized culture of NIH3T3 cells treated with serum. The expression levels of this form of p27 which lacked its amino (NH2)-terminal region reached maximum during G(2)/M phase. Since the appearance of the NH2-terminal truncated form of p27 coincided with increased expression of Cdc2, we hypothesized that p27 may play a role in regulating Cdc2 catalytic activity. To test this hypothesis, wild type p27, as well as the aminoterminal (Np27) and carboxyl-terminal (Cp27), were individually expressed, purified, and examined for their ability to regulate CDC2 kinase activity in vitro, Our data showed that both p27 and Np27 inhibited CDC2 kinase activity. However, in marked contrast, Cp27 enhanced the CDC2 kinase activity. In vitro kinase assays showed that Cp27 and p27 were phosphorylated by CDC2, whereas Np27 was not. In addition, we demonstrated that deletion of the putative CDC2 phosphorylation site in the carboxyl-terminal domain of Cp27 diminished activation of CDC2 kinase activity otherwise stimulated by Cp27. A similar deletion did not have any effect on the inhibitory function of p27. Together these results suggest that the carboxyl-terminal domain of p27 may activate CDC2 kinase activity in vivo during G(2)/M and that this effect may be regulated by serine/threonine phosphorylation. C1 NCI,NIH,BETHESDA,MD 20892. NIDR,ORAL & PHARYNGEAL CANC BRANCH,BETHESDA,MD 20892. RI Gutkind, J. Silvio/A-1053-2009; Font de Mora, Jaime/H-6304-2015 OI Font de Mora, Jaime/0000-0002-6816-2095 NR 25 TC 19 Z9 19 U1 0 U2 1 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD AUG 29 PY 1997 VL 272 IS 35 BP 21669 EP 21672 DI 10.1074/jbc.272.35.21669 PG 4 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA XT850 UT WOS:A1997XT85000003 PM 9268291 ER PT J AU Hamer, I Haft, CR Paccaud, JP Maeder, C Taylor, S Carpentier, JL AF Hamer, I Haft, CR Paccaud, JP Maeder, C Taylor, S Carpentier, JL TI Dual role of a dileucine motif in insulin receptor endocytosis SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID EPIDERMAL GROWTH-FACTOR; DI-LEUCINE MOTIF; DENSITY-LIPOPROTEIN RECEPTOR; TYROSINE KINASE-ACTIVITY; INTERNALIZATION SIGNALS; TRANSMEMBRANE DOMAIN; MEDIATED INTERNALIZATION; JUXTAMEMBRANE REGION; DOWN-REGULATION; BETA-SUBUNIT AB Two leucines (Leu(986) and Leu(987)) have recently been shown to take part in the control of human insulin receptor (HIR) internalization (Renfrew-Haft, C,, Klausner, R, D,, and Taylor, S, I, (1994) J, Biol, Chem, 269, 26286-26294), The aim of the present study was to further investigate the exact mechanism of this control process, Constitutive and insulin-induced HIR internalizations were studied biochemically and morphologically in NIH 3T3 cells overexpressing either a double alanine (amino acid residues 986-987) mutant NIR (HIR AA1) or HIR truncated at either amino acid residue 981 (HIR Delta 981) or 1000 (HIR Delta 1000). Data collected indicate that: (a) the three mutant HIR show a reduced association with microvilli as compared with HIR wild-type; (b) the two receptors containing the dileucine motif (HIR WT and HIR Delta 1000) show the highest propensity to associate with clathrin-coated pits, independently of kinase activation; (c) the two receptors lacking the dileucine motif but containing two tyrosine-based motifs, previously described as participating in clathrin-coated pit segregation, associate with these surface domains with a lower affinity than the two others, (d) in the presence of the kinase domain, an unmasking of the tyrosine-based motifs mediated by kinase activation is required. These results indicate that the dileucine motif is not sufficient by itself, but participates in anchoring HIR on microvilli and that another sequence, located downstream from position 1000 is crucial for this event, This dileucine motif also plays a role in HIR segregation in clathrin-coated pits, This latter function is additive with that of the tyrosine-based motifs but the role of the dileucine motif predominates, Eventually, the clathrin-coated pit anchoring function of the dileucine motif is independent of receptor kinase activation in contrast to the tyrosine-based motifs. C1 CMU,DEPT MORPHOL,CH-1211 GENEVA 4,SWITZERLAND. NIDDK,DIABET BRANCH,NIH,BETHESDA,MD 20892. NR 48 TC 45 Z9 45 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 AUG 29 PY 1997 VL 272 IS 35 BP 21685 EP 21691 DI 10.1074/jbc.272.35.21685 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA XT850 UT WOS:A1997XT85000007 PM 9268295 ER PT J AU Zhou, X Cahoon, M Rosa, P Hedstrom, L AF Zhou, X Cahoon, M Rosa, P Hedstrom, L TI Expression, purification, and characterization of inosine 5'-monophosphate dehydrogenase from Borrelia burgdorferi SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID IMP DEHYDROGENASE; MYCOPHENOLIC-ACID; SALMONELLA-TYPHIMURIUM; INHIBITION; VIRULENCE; MECHANISM; CELLS AB Inosine 5'-monophosphate dehydrogenase (IMPDH) is the rate limiting enzyme in de novo guanine nucleotide biosynthesis, IMPDH converts IMP to xanthosine 5'-monophosphate with concomitant conversion of NAD(+) to NADH, All IMPDHs characterized to date contain a 130-residue ''subdomain'' that extends from an N-terminal loop of the alpha/beta barrel domain, The role of this subdomain is unknown, An IMPDH homolog has been cloned from Borrelia burgdorferi, the causative agent of Lyme disease (Margolis, N., Hogan, D., Tilly, K., and Rosa, P. A. (1994) J. Bacteriol. 176, 6427-6432), This homolog has replaced the subdomain with a 50-residue segment of unrelated sequence, We have expressed and characterized the B. burgdorferi IMPDH homolog, This protein has IMPDH activity, which unequivocally demonstrates that the subdomain is not required for catalytic activity, The monovalent cation and dinucleotide binding sites of B. burgdorferi IMPDH are significantly different from those of human IMPDH, Therefore, these sites are targets for the design of specific inhibitors for B. burgdorferi IMPDH. Such inhibitors might be new treatments for Lyme disease. C1 BRANDEIS UNIV, DEPT BIOCHEM, WALTHAM, MA 02254 USA. NIAID, MICROBIAL STRUCT & FUNCT LAB, ROCKY MT LABS, NIH, HAMILTON, MT 59840 USA. NR 36 TC 44 Z9 46 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 EI 1083-351X J9 J BIOL CHEM JI J. Biol. Chem. PD AUG 29 PY 1997 VL 272 IS 35 BP 21977 EP 21981 DI 10.1074/jbc.272.35.21977 PG 5 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA XT850 UT WOS:A1997XT85000046 PM 9268334 ER PT J AU Haruki, M Noguchi, E Kanaya, S Crouch, RJ AF Haruki, M Noguchi, E Kanaya, S Crouch, RJ TI Kinetic and stoichiometric analysis for the binding of Escherichia coli ribonuclease HI to RNA-DNA hybrids using surface plasmon resonances SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID TYPE-1 REVERSE-TRANSCRIPTASE; SITE-DIRECTED MUTAGENESIS; DOUBLE-STRANDED-RNA; SACCHAROMYCES-CEREVISIAE; CRYSTAL-STRUCTURE; DOMAIN; SUBSTRATE; SEQUENCE; RECOGNITION; RESOLUTION AB To understand how ribonucleases H recognize RNA-DNA hybrid substrates, we analyzed kinetic parameters of binding of Escherichia coli RNase HI to RNA-DNA hybrids ranging in length from 18 to 36 base pairs (bp) using surface plasmon resonance (BIAcore((TM))). The k(on) and k(off) values for the binding of the enzyme to the 36 bp substrate were 1.5 x 10(6) M-1 s(-1) and 3.2 x 10(-2) s(-1), respectively, Similar values were obtained with the shorter substrates, Using uncleavable 2'-O-methylated RNA-DNA substrates, values for h(on) and h(off) were 2.1 x 10(5) M-1 s(-1) and 1.3 x 10(-1) s(-1) in the absence of Mg2+ that were further reduced in the presence of Mg2+ to 7.4 x 10(3) M-1 s(-1) and 2.6 x 10(-2) s(-1). Kinetic parameters similar to the wild-type enzyme were obtained using an active-site mutant enzyme, Asp(134) replaced by Ala, whereas a greatly reduced on-rate was observed for another inactive mutant enzyme, in which the basic protrusion is eliminated, thereby distinguishing between poor catalysis and inability to bind to the substrate. Stoichiometric analyses of RNase HI binding to substrates of 18, 24, 30, and 36 bp are consistent with previous reports suggesting that RNase HI binds to 9-10 bp of RNA DNA hybrid. C1 NICHHD,MOL GENET LAB,NIH,BETHESDA,MD 20892. OSAKA UNIV,GRAD SCH ENGN,DEPT MAT & LIFE SCI,SUITA,OSAKA 565,JAPAN. PROT ENGN RES INST,SUITA,OSAKA 565,JAPAN. NR 40 TC 50 Z9 50 U1 2 U2 4 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD AUG 29 PY 1997 VL 272 IS 35 BP 22015 EP 22022 DI 10.1074/jbc.272.35.22015 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA XT850 UT WOS:A1997XT85000052 PM 9268340 ER PT J AU Zhan, XY Crouch, RJ AF Zhan, XY Crouch, RJ TI The isolated RNase H domain of murine leukemia virus reverse transcriptase - Retention of activity with concomitant loss of specificity SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; RIBONUCLEASE-H; ESCHERICHIA-COLI; DNA-POLYMERASE; CRYSTAL-STRUCTURE; ANGSTROM RESOLUTION; PRIMER-TEMPLATE; STRAND TRANSFER; TYPE-1; MUTATIONS AB Retroviral RNases H are similar in sequence and structure to Escherichia coli RNase HI and yet have differences in substrate specificities, metal ion requirements, and specific activities. Separation of reverse transcriptase (RT) into polymerase and RNase H domains yields an active RNase H from murine leukemia virus (MuLV) but an inactive human immunodeficiency virus (HN) RNase H. The ''handle region'' present in E. coli RNase HI but absent in HIV RNase H contributes to the binding to its substrate and when inserted into HIV RNase H results in an active enzyme retaining some degree of specificity. Here, we show MuLV protein containing the C-terminal 175 amino acids with its own handle region or that of E. coli RNase HI has the same specific activity as the RNase H of RT, retains a preference for Mn2+ as the cation required for activity, and has association rate (K-A) 10% that of E. coli RNase HI. However, with model substrates, specificities for removal of the tRNA(Pro) primer and polypurine tract stability are lost, indicating specificity of RNase H of MuLV requires the remainder of the RT. Differences in K-A, while significant, appear insufficient to account for the differences in specific activities of the bacterial and viral RNases H. C1 NICHHD,MOL GENET LAB,NIH,BETHESDA,MD 20892. NR 50 TC 27 Z9 27 U1 0 U2 1 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD AUG 29 PY 1997 VL 272 IS 35 BP 22023 EP 22029 DI 10.1074/jbc.272.35.22023 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA XT850 UT WOS:A1997XT85000053 PM 9268341 ER PT J AU Acs, P Bogi, K Lorenzo, PS Marquez, AM Biro, T Szallasi, Z Blumberg, PM AF Acs, P Bogi, K Lorenzo, PS Marquez, AM Biro, T Szallasi, Z Blumberg, PM TI The catalytic domain of protein kinase C chimeras modulates the affinity and targeting of phorbol ester-induced translocation SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID EPSILON-ISOFORM; BINDING-PROTEIN; CELLS; ISOZYMES; ACTIVATION; BETA; DIFFERENTIATION; IDENTIFICATION; LOCALIZATION; FIBROBLASTS AB Emerging evidence suggests important differences among protein kinase C (PKC) isozymes in terms of their regulation and biological functions, PKC is regulated by multiple interdependent mechanisms, including enzymatic activation, translocation of the enzyme in response to activation, phosphorylation, and proteolysis. As part of our ongoing studies to define the factors contributing to the specificity of PKC isozymes, we prepared chimeras between the catalytic and regulatory domains of PKC alpha, -delta, and -epsilon. These chimeras, which preserve the overall structure of the native PKC enzymes, were stably expressed in NIH 3T3 fibroblasts. Their intracellular distribution was similar to that of the endogenous enzymes, and they responded with translocation upon treatment with phorbol 12-myristate 13-acetate (PMA). We found that the potency of PMA for translocation of the PKC alpha/x chimeras from the soluble fraction was influenced by the catalytic domain. The ED50 for translocation of PKC alpha/alpha was 26 nM, in marked contrast to the ED50 of 0.9 nM in the case of the PKC alpha/epsilon chimera. In addition to this increase in potency, the site of translocation was also changed; the PKC alpha/epsilon chimera translocated mainly into the cytoskeletal fraction. PKCx/epsilon chimeras displayed twin isoforms with different mobilities on Western blots. PMA treatment increased the proportion of the higher mobility isoform. The two PKCx/epsilon isoforms differed in their localization; moreover, their localization pattern depended on the regulatory domain, Our results emphasize the complex contributions of the regulatory and catalytic domains to the overall behavior of PKC. C1 NCI,MOL MECH TUMOR PROMOT SECT,CELLULAR CARCINOGENESIS & TUMOR PROMOT LAB,NIH,BETHESDA,MD 20892. UNIFORMED SERV UNIV HLTH SCI,DEPT PHARMACOL,BETHESDA,MD 20814. NR 35 TC 32 Z9 32 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 AUG 29 PY 1997 VL 272 IS 35 BP 22148 EP 22153 DI 10.1074/jbc.272.35.22148 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA XT850 UT WOS:A1997XT85000071 PM 9268359 ER PT J AU Zhong, GM Sousa, CRE Germain, RN AF Zhong, GM Sousa, CRE Germain, RN TI Antigen-unspecific B cells and lymphoid dendritic cells both show extensive surface expression of processed antigen-major histocompatibility complex class II complexes after soluble protein exposure in vivo or in vitro SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article ID RESTRICTED T-CELLS; IN-VIVO; LANGERHANS CELLS; MONOCLONAL-ANTIBODY; PRESENTING CELLS; TOLERANCE; LYMPHOCYTES; INDUCTION; SPLEEN; INVIVO AB Intravenous (i.v.) injection of high amounts of soluble proteins often results in the induction of antigen-specific tolerance or deviation to helper rather than inflammatory T cell immunity. It has been proposed that this outcome may be due to antigen presentation to T cells by a large cohort of poorly costimulatory or IL-12-deficient resting B cells lacking specific immunoglobulin receptors for the protein. However, previous studies using T cell activation in vitro to assess antigen display have failed to support this idea, showing evidence of specific peptide-major histocompatibility complex (MHC) class II ligand only on purified dendritic cells (DC) or antigen-specific B cells isolated from protein injected mice. Here we reexamine this question using a recently derived monoclonal antibody specific for the T cell receptor (TCR) ligand formed by the association of the 46-61 determinant of hen egg lysozyme (HEL) and the mouse MHC class II molecule I-A(k). In striking contrast to conclusions drawn from indirect T cell activation studies, this direct method of TCR ligand analysis shows that i.v. administration of HEL protein results in nearly all B cells in lymphoid tissues having substantial levels of HEL 46-61-A(k) complexes on their surface. DC readily isolated from spleen also display this TCR ligand on their surface. Although the absolute number of displayed ligands is greater on such DC, the relative specific ligand expression compared to total MHC class II levels is similar or greater on B cells. These results demonstrate that in the absence of activating stimuli, both lymphoid DC and antigen-unspecific B cells present to a similar extent class II-associated peptides derived from soluble proteins in extracellular fluid. The numerical advantage of the TCR ligand-bearing B cells may permit them to interact first or more often with naive antigen-specific T cells, contributing to the induction of high-dose T cell tolerance or immune deviation. C1 NIAID,LYMPHOCYTE BIOL SECT,IMMUNOL LAB,DIR,NIH,BETHESDA,MD 20892. NR 43 TC 105 Z9 107 U1 0 U2 1 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 SN 0022-1007 J9 J EXP MED JI J. Exp. Med. PD AUG 29 PY 1997 VL 186 IS 5 BP 673 EP 682 DI 10.1084/jem.186.5.673 PG 10 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA XV741 UT WOS:A1997XV74100006 PM 9271583 ER PT J AU Chertov, O Ueda, H Xu, LL Tani, K Murphy, WJ Wang, JM Howard, OMZ Sayers, TJ Oppenheim, JJ AF Chertov, O Ueda, H Xu, LL Tani, K Murphy, WJ Wang, JM Howard, OMZ Sayers, TJ Oppenheim, JJ TI Identification of human neutrophil-derived cathepsin G and azurocidin/CAP37 as chemoattractants for mononuclear cells and neutrophils SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article ID PROTEASE INHIBITORS; GRANULE DEFICIENCY; HUMAN-MONOCYTES; MAST-CELL; ELASTASE; LYMPHOCYTES; RECEPTORS; ALPHA(1)-ANTICHYMOTRYPSIN; STIMULATION; PROTEINASES AB Macrophage infiltration into inflammatory sites is generally preceded by neutrophils. This suggests neutrophils may be the sourer of chemotactic factors for monocytes. To identify these putative monocyte attractants, we have systematically prepared neutrophil granules, lysed them, and sequentially purified the released proteins by several reverse phase chromatography procedures. Assays for monocyte chemotactic activity of the chromatography fractions yielded a major peak of activity associated with a protein of 30 kD, according to SDS-PAGE analysis. NH2-terminal sequence of the protein revealed this to be identical to cathepsin G. The monocyte chemotactic activity of human cathepsin G was dose dependent with optimal concentration at 0.5-1 mu g/ml. Cathepsin G is chemotactic rather than chemokinetic for monocytes, as demonstrated by checkerboard analysis. Cathepsin G-induced monocyte chemotaxis is partially pertussis toxin sensitive implying the involvement of a G protein-coupled receptor. Enzymatic activity of cathepsin G is associated with its monocyte chemotactic activity, since DFP-or PMSF-inactivated cathepsin G no longer induced monocyte migration. The chemotactic activity of cathepsin G can also be completely blocked by oil antichymotrypsin, a specific inhibitor of-chymotrypsin-like proteinases present in human plasma. In addition, cathepsin G is also a potent chemoattractant for neutrophils and a chemokinetic stimulant for T cells. In the course of pursuing these in vitro studies, we established that the T cell chemoattractant, azurocidin/CAP37 from human neutrophil granules, at doses of 0.05 to 5 mu g/ml, was chemotactic for monocytes and neutrophils. As predicted from the in vitro chemotactic activity, subcutaneous injection of cathepsin G into BALB/c mice led to infiltration of both mononuclear cells and neutrophils. Thus, the transition of inflammatory exudate from neutrophil to mononuclear cells can be mediated, at least in part, by extracellular release of neutrophil granule proteins such as cathepsin G and azurocidin/CAP37. C1 NCI,MOL IMMUNOREGULAT LAB,NIH,FREDERICK CANC RES & DEV CTR,FREDERICK,MD 21702. SCI APPLICAT INT CORP,INTRAMURAL RES SUPPORT PROGRAM,FREDERICK,MD. RI Howard, O M Zack/B-6117-2012; Sayers, Thomas/G-4859-2015 OI Howard, O M Zack/0000-0002-0505-7052; NR 39 TC 162 Z9 166 U1 0 U2 6 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 SN 0022-1007 J9 J EXP MED JI J. Exp. Med. PD AUG 29 PY 1997 VL 186 IS 5 BP 739 EP 747 DI 10.1084/jem.186.5.739 PG 9 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA XV741 UT WOS:A1997XV74100012 PM 9271589 ER PT J AU Itoh, Y Germain, RN AF Itoh, Y Germain, RN TI Single cell analysis reveals regulated hierarchical T cell antigen receptor signaling thresholds and intraclonal heterogeneity for individual cytokine responses of CD4(+) T cells SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article ID INTERLEUKIN-2 TRANSCRIPTION; PHENOTYPE DEVELOPMENT; LYMPHOCYTE-RESPONSES; POSITIVE SELECTION; MEDIATED-IMMUNITY; PARTIAL AGONISTS; GENE-EXPRESSION; IN-VIVO; ACTIVATION; LIGAND AB T cell receptor (TCR) recognition of peptide-major histocompatibility complex antigens can elicit a diverse array of effector activities. Here we simultaneously analyze TCR engagement and the production of multiple cytokines by individual cells in a clonal Th1 CD4(+) cell population. Low concentrations of TCR ligand elicit only interferon-gamma (IFN-gamma) production. Increasing ligand recruits more cells into the IFN-gamma(+) pool, increases IFN-gamma produced per cell, and also elicits IL-2, but only from cells already making IFN-gamma. Most cells producing only IFN-gamma show less TCR downmodulation than cells producing both cytokines, consistent with a requirement for more TCR signaling to elicit IL-2 than to evoke IFN-gamma synthesis. These studies emphasize the hierarchical organization of TCR signaling thresholds for induction of distinct cytokine responses, and demonstrate that this threshold phenomenon applies to individual cells. The existence of such thresholds suggests that antigen dose may dictate not only the extent, but also the quality of an immune response, by altering the ratios of the cytokines produced by activated T cells. The quantitative relationships in this response hierarchy change in response to costimulation through CD28 or LFA-1, as well as the differentiation state of the lymphocyte, explaining how variations in these parameters in the face of a fixed antigen load can qualitatively influence immune outcomes. Finally, although the IFN-gamma/IL-2 hierarchy is seen with most cells, among cells with the greatest TCR downmodulation, some produce only IFN-gamma and not IL-2, and the amount of IFN-gamma exceeds that in double producers. Thus, these single cell analyses also provide clear evidence of nonquantitative intraclonal heterogeneity in cytokine production by long-term Th1 cells, indicating additional complexity of T cell, function during immune responses. C1 NIAID,LYMPHOCYTE BIOL SECT,IMMUNOL LAB,NIH,BETHESDA,MD 20892. NR 48 TC 172 Z9 175 U1 1 U2 3 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 SN 0022-1007 J9 J EXP MED JI J. Exp. Med. PD AUG 29 PY 1997 VL 186 IS 5 BP 757 EP 766 DI 10.1084/jem.186.5.757 PG 10 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA XV741 UT WOS:A1997XV74100014 PM 9271591 ER PT J AU Yu, QS Pei, XF Holloway, HW Greig, NH Brossi, A AF Yu, QS Pei, XF Holloway, HW Greig, NH Brossi, A TI Total syntheses and anticholinesterase activities of (3aS)-N(8)-norphysostigmine, (3aS)-N(8)-norphenserine, their antipodal isomers, and other N(8)-substituted analogues SO JOURNAL OF MEDICINAL CHEMISTRY LA English DT Article ID SODIUM BIS(2-METHOXYETHOXY)ALUMINUM HYDRIDE; ALZHEIMERS-DISEASE; BUTYRYLCHOLINESTERASE; PHYSOSTIGMINE; ACETYLCHOLINESTERASE; (-)-PHYSOVENOL; PHENSERINE; INHIBITION AB N(8)-Benzylesermethole (6) was prepared from 5-methoxytryptamine (1) in five steps. Resolution of compound 6 by dibenzoyl- and ditoluyltartaric acid provided enantiomers (-)- and (+)-7. After demethylation, reaction with isocyanates and catalytic debenzylation over hydrogen, the total syntheses of(-)-and (+)-N(8)-norphysostigmine [(-)-and (+)-11] and (-)-and (+)N(8)-norphenserine [(-)-and (+)-12] were accomplished. (-)-N(8)-Norphysostigmine [(-)-11] and (-)-N(8)-norphenserine [(-)-12] were also obtained by transformations of natural physostigmine [(-)-13] and phenserine [(-)-14] prepared from(-)-13. The absolute configurations and optical purity of compounds (-)-11, (-)-12, (+)-11, and (+)-12 were confirmed by a comparison of their optical rotations with those of the compounds synthesized from physostigmine [(-)-13]. The anticholinesterase activities of N(8)-nor-and N(8)-substituted analogues, (-)-and (+)-9, -10, -11, -12, 15, and 16, were compared with those of physostigmine [(-)-and (+)-13] and phenserine [(-)- and (+)-14] and are reported. C1 NIA,GERONTOL RES CTR,CELLULAR & MOL BIOL LAB,NIH,BALTIMORE,MD 21224. UNIV N CAROLINA,SCH PHARM,CHAPEL HILL,NC 27599. NR 26 TC 43 Z9 44 U1 0 U2 2 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0022-2623 J9 J MED CHEM JI J. Med. Chem. PD AUG 29 PY 1997 VL 40 IS 18 BP 2895 EP 2901 DI 10.1021/jm970210v PG 7 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA XT928 UT WOS:A1997XT92800012 PM 9288171 ER PT J AU Katsura, Y Zhang, XY Homma, K Rice, KC Calderon, SN Rothman, RB Yamamura, HI Davis, P FlippenAnderson, JL Xu, H Becketts, K Foltz, EJ Porreca, F AF Katsura, Y Zhang, XY Homma, K Rice, KC Calderon, SN Rothman, RB Yamamura, HI Davis, P FlippenAnderson, JL Xu, H Becketts, K Foltz, EJ Porreca, F TI Probes for narcotic receptor-mediated phenomena .25. Synthesis and evaluation of N-alkyl-substituted (alpha-piperazinylbenzyl)benzamides as novel, highly selective delta opioid receptor agonists SO JOURNAL OF MEDICINAL CHEMISTRY LA English DT Article ID BINDING-SITES; IN-VITRO; IMMUNE-SYSTEM; MOUSE-BRAIN; RAT-BRAIN; PEPTIDES; BW373U86; DRUGS; CELLS; ANTINOCICEPTION AB A series of N-alkyl- and N,N-dialkyl-4-[alpha-{(2S,5R)-4-allyl-2,5-dimethyl-1-piperazinyl}benzyl]-benzamides were synthesized and evaluated for binding affinities at mu, delta, and kappa opioid receptor subtypes. Several compounds (2e,f,h,i,m) strongly bound to the delta receptor with IC50 values in the nanomolar range. On the other hand, the binding affinities of these compounds for the mu and kappa receptors were in the micromolar or greater range indicating excellent delta opioid receptor subtype selectivities. In this series, two important structure-activity relationships were found for the delta receptor binding affinity. First, the spatial orientation of the alpha-benzylic position influenced the affinities with the alpha R derivatives 2a-n generally showing more than 10-fold greater affinity than the alpha S derivatives 3a-n. Second, the binding affinities were strongly influenced by the number of alkyl substituents on the amide nitrogen. N-Monoalkylbenzamide derivatives 2b-d showed lower affinity than N,N-dialkylbenzamide derivatives 2e-n, and the N-unsubstituted benzamide derivative 2a had the lowest affinity for the delta receptor in the series. The dramatic effect of the amide group substitution pattern on the binding affinity for the delta receptor strongly suggests that the amide function is an important structural element in the interaction of this series of compounds at the delta receptor. Selective compounds in this series were examined for binding affinity in cloned human mu and delta receptors. The results obtained generally paralleled those from the rat brain binding assay. Compounds 2e,f with potent delta binding affinities and high delta selectivities were shown to be delta agonists with high selectivity by studies in the guinea pig ileum (GPI) and mouse vas deferens (MVD) preparations. Compound 2f was the most selective compound in the rat brain and GPI/MVD assays with 1755- and 958-fold delta vs mu selectivity, respectively. C1 NIDDKD, MED CHEM LAB, NIH, BETHESDA, MD 20892 USA. NIDA, ADDICT RES CTR, CLIN PSYCHOPHARMACOL SECT, BALTIMORE, MD 21224 USA. UNIV ARIZONA, COLL MED, DEPT PHARMACOL, TUCSON, AZ 85724 USA. USN, RES LAB, STRUCT MATTER LAB, WASHINGTON, DC 20375 USA. NR 41 TC 23 Z9 23 U1 0 U2 3 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 AUG 29 PY 1997 VL 40 IS 18 BP 2936 EP 2947 DI 10.1021/jm970106d PG 12 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA XT928 UT WOS:A1997XT92800017 PM 9288176 ER PT J AU Tomatis, R Marastoni, M Balboni, G Guerrini, R Capasso, A Sorrentino, L Santagada, V Caliendo, G Lazarus, LH Salvadori, S AF Tomatis, R Marastoni, M Balboni, G Guerrini, R Capasso, A Sorrentino, L Santagada, V Caliendo, G Lazarus, LH Salvadori, S TI Synthesis and pharmacological activity of deltorphin and dermorphin-related glycopeptides SO JOURNAL OF MEDICINAL CHEMISTRY LA English DT Article ID BLOOD-BRAIN-BARRIER; OPIOID RECEPTOR-BINDING; SOLID-PHASE SYNTHESIS; BIOLOGICAL-ACTIVITY; MU-RECEPTOR; ANALOGS; PEPTIDES; SKIN; REQUIREMENTS; SELECTIVITY AB The solid phase procedure, based on the Fmoc chemistry, was used to prepare some opioid deltorphin (H-Tyr-D-Ala-Phe-Asp-Val-Val-Gly-NH2, DEL C) and dermorphin (H-Tyr-D-Ala-Phe-Gly-Tyr-Pro-Ser-NH2, DER) analogues in which a D-glucopyranosyl moiety is beta-O-glycosidically linked to a Thr(4) or Thr(7) side chain. Their activities were determined in binding studies based on displacement of mu- and delta-receptor selective radiolabels from rat brain membrane synaptosomes, in guinea pig ileum and rabbit jejenum bioassays, and, in vivo, by a mouse tail-flick test after intracerebroventricular (icy) and subcutaneous (sc) administrations. The glyco analogues modified at position 4 displayed low opioid properties, while Thr(7)-glycosylated peptides retained high delta- or mu-selectivity and remarkable activity in vivo. In particular, as systemic antinociceptive agents, the latter glucoside-bearing compounds were more potent than the parent unglycosylated peptide counterparts, showing a high blood to brain rate of influx which may be due to the glucose transporter GLUT-1. C1 UNIV FERRARA,CTR BIOTECHNOL,I-44100 FERRARA,ITALY. UNIV SALERNO,SCH PHARM,SALERNO,ITALY. UNIV NAPLES,DEPT EXPT PHARMACOL,I-80138 NAPLES,ITALY. UNIV NAPLES,DEPT PHARMACEUT SCI,I-80138 NAPLES,ITALY. NIEHS,RES TRIANGLE PK,NC 27709. RP Tomatis, R (reprint author), UNIV FERRARA,DEPT PHARMACEUT SCI,I-44100 FERRARA,ITALY. OI CAPASSO, Anna/0000-0002-6579-7802; Guerrini, Remo/0000-0002-7619-0918; Caliendo, Giuseppe/0000-0002-5098-6045; SALVADORI, Severo/0000-0002-8224-2358 NR 39 TC 40 Z9 40 U1 0 U2 4 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 AUG 29 PY 1997 VL 40 IS 18 BP 2948 EP 2952 DI 10.1021/jm970119r PG 5 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA XT928 UT WOS:A1997XT92800018 PM 9288177 ER PT J AU Li, GY Xiao, W Torrence, PF AF Li, GY Xiao, W Torrence, PF TI Synthesis and properties of second generation 2-5A-antisense chimeras with enhanced resistance to exonucleases SO JOURNAL OF MEDICINAL CHEMISTRY LA English DT Article ID ANTISENSE OLIGONUCLEOTIDES; THERAPEUTIC AGENTS; 2-5A ANTISENSE; MESSENGER-RNA; STABILITY; DEGRADATION; TARGET; OLIGODEOXYNUCLEOTIDES; RIBONUCLEASE; SPECIFICITY AB In order to stabilize 2-5A-antisense chimeras to exonucleases, we have synthesized chimeric oligonucleotides in which the last phosphodiester bond at the 3'-terminus of the antisense domain was inverted from the usual 3',5'-linkage to a 3',3'-linkage. The preparation of such analogues was accomplished through standard phosphoramidite chemistry with the use of a controlled pore glass solid support with a nucleoside attached through its 5'-hydroxyl, thereby permitting elongation at the S'-hydroxyl. The structures of such terminally inverted linkage chimeras of the general formula pA(4)-[pBu](2)-(pdN(n)3'-3'dN) were corroborated by a combination of snake venom phosphodiesterase digestion in the presence or absence of bacterial alkaline phosphatase. Most characteristically, the presence of the 3'-terminal-inverted phosphodiester linkage produced an unnatural dinucleotide of general composition dN3'p3'dM. These structures could be confirmed by independent synthesis and fast atom bombardment mass spectroscopy (FAB). 2-5A-Antisense chimeras of this structural class, pA(4)-[pBu](2)-(pdN(n),3'-3'dN), were 5-6-fold more stable than their unmodified congeners, pA(4)-[pBu](2)-(pdN)(n), to degradation by a representative phosphodiesterase from snake venom. In 10% human serum, the new 2-5A-antisense chimeras, pA(4)-[pBu](2)-(pdN(n),3'-3'dN), possessed a half-life that was 28-fold longer than that of the unmodified chimeras. These results provide entry to a second generation of 2-5A-antisense chimeras. C1 NIDDKD,SECT BIOMED CHEM,MED CHEM LAB,NIH,BETHESDA,MD 20892. NR 41 TC 17 Z9 17 U1 0 U2 2 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0022-2623 J9 J MED CHEM JI J. Med. Chem. PD AUG 29 PY 1997 VL 40 IS 18 BP 2959 EP 2966 DI 10.1021/jm970227d PG 8 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA XT928 UT WOS:A1997XT92800020 PM 9288179 ER PT J AU Shimizu, M Hochadel, JF Waalkes, MP AF Shimizu, M Hochadel, JF Waalkes, MP TI Effects of glutathione depletion on cadmium-induced metallothionein synthesis, cytotoxicity, and proto-oncogene expression in cultured rat myoblasts SO JOURNAL OF TOXICOLOGY AND ENVIRONMENTAL HEALTH LA English DT Article ID INDUCED GENOTOXICITY; CALCIUM CHANNELS; GENE-EXPRESSION; LIVER-CELLS; TOXICITY; FOS; JUN; ACTIVATION; INDUCTION; ZINC AB Cadmium (Cd) is a highly toxic metal and a known carcinogen. Although the carcinogenic mechanism of action is unknown, Cd will induce transcriptional activation of c-myc and c-jun. We have previously found that the extent of Cd-induced oncogene expression is limited by the presence of cellular metallothionein (MT) in rat L6 myoblasts. Glutathione (GSH) is thought to play an important role in protection against Cd before the onset of MT synthesis. Thus, this study examined the effects of GSH depletion on Cd-induced MT synthesis, cytotoxicity, and proto-oncogene expression in rat L6 myoblasts after pretreatment with L-buthionine sulfoximine (BSO), a potent inhibitor gamma-glutamylcysteine synthetase, which effectively depletes GSH. Exposure of L6 cells to BSO (5 or 25 mu M) resulted in a dose-dependent decrease in cellular GSH levels, GSH depletion had no effect on Cd- or zinc-induced MT synthesis. Although the depletion of GSH was not itself cytotoxic in L6 cells, BSO pretreatment, particularly at the higher dose (25 mu M), resulted in a dose-dependent increase in the sensitivity to Cd cytotoxicity, as assessed by a tetrazolium-based dye (MTT) assay. Low levels of Cd (1 mu M) slightly increased the expression of both c-myc and c-jun as assessed by increases in gene-specific mRNA levels, in accordance with previous studies. GSH depletion (5 mu M BSO) likewise caused an increase in expression of c-myc and c-jun. However, combined GSH depletion and Cd exposure decreased levels of c-myc and c-jun transcription well below control levels. These results suggest that increased cytotoxicity resulting from exposure to Cd after BSO depletion of cellular GSH abrogates the oncogene activation observed after either treatment alone. Thus proto-oncogene expression induced by Cd appears to be dependent on the absence of overt Cd-induced cytotoxicity. C1 NCI,FREDERICK CANC RES & DEV CTR,FREDERICK,MD. NCI,FREDERICK CANC RES & DEV CTR,SAIC FREDERICK,FREDERICK,MD. NR 45 TC 33 Z9 35 U1 0 U2 0 PU TAYLOR & FRANCIS PI BRISTOL PA 1900 FROST ROAD, SUITE 101, BRISTOL, PA 19007-1598 SN 0098-4108 J9 J TOXICOL ENV HEALTH JI J. Toxicol. Environ. Health PD AUG 29 PY 1997 VL 51 IS 6 BP 609 EP 621 DI 10.1080/009841097159863 PG 13 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA XM553 UT WOS:A1997XM55300006 PM 9242231 ER PT J AU Post, RM Kramlinger, KG Joffe, RT RoyByrne, PP Rosoff, A Frye, MA Huggins, T AF Post, RM Kramlinger, KG Joffe, RT RoyByrne, PP Rosoff, A Frye, MA Huggins, T TI Rapid cycling bipolar affective disorder: lack of relation to hypothyroidism SO PSYCHIATRY RESEARCH LA English DT Article DE affective disorder; rapid cycling; hypothyroidism; thyroxine; triiodothyronine; lithium ID THYROTROPIN-RELEASING-HORMONE; HIGH-DOSE THYROXINE; THYROID-FUNCTION; ENDOGENOUS-DEPRESSION; PSYCHIATRIC-PATIENTS; LITHIUM-CARBONATE; ILLNESS; TRH; ANTIDEPRESSANTS; CARBAMAZEPINE AB Thyroid indices were measured after an extended period of medication-free evaluation averaging 6 weeks in 67 consecutively admitted patients with bipolar illness. Thyroid hormone levels - thyroxine (T-4), free T-4 and triiodothyronine (T-3) - were not significantly different in the 31 rapid cyclers (greater than or equal to 4 affective episodes/year) than in 36 non-rapid cyclers. Analysis of covariance indicated a non-significant trend relation between higher T-4 and a greater number of affective episodes in the year prior to admission and male gender when age was covaried. Several previous reports, primarily in medicated subjects, have suggested a link between rapid cycling patients and decreased peripheral thyroid indices (low hormone levels and elevated TSH), but now the majority of studies do not support such a relation. Among those in the literature, this study includes patients studied for the longest time off medications and further suggests that the commonly-cited relation between subclinical hypothyroidism and rapid cycling bipolar illness be reevaluated. (C) 1997 Elsevier Science Ireland Ltd. C1 MAYO CLIN & MAYO FDN,MAYO MED SCH,DEPT PSYCHIAT,ROCHESTER,MN 55905. MCMASTER UNIV,MED CTR,DEPT PSYCHIAT,HAMILTON,ON,CANADA. UNIV WASHINGTON,HARBORVIEW MED CTR,DEPT PSYCHIAT,SEATTLE,WA 98104. RP Post, RM (reprint author), NIMH,BIOL PSYCHIAT BRANCH,BLDG 10,ROOM 3N212,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 51 TC 33 Z9 35 U1 0 U2 1 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0165-1781 J9 PSYCHIAT RES JI Psychiatry Res. PD AUG 29 PY 1997 VL 72 IS 1 BP 1 EP 7 DI 10.1016/S0165-1781(97)00076-0 PG 7 WC Psychiatry SC Psychiatry GA YB640 UT WOS:A1997YB64000001 PM 9355813 ER PT J AU Kadowaki, H Takahashi, Y Ando, A Momomura, K Kaburagi, Y Quin, JD MacCuish, AC Koda, N Fukushima, Y Taylor, SI Akanuma, Y Yazaki, Y Kadowaki, T AF Kadowaki, H Takahashi, Y Ando, A Momomura, K Kaburagi, Y Quin, JD MacCuish, AC Koda, N Fukushima, Y Taylor, SI Akanuma, Y Yazaki, Y Kadowaki, T TI Four mutant alleles of the insulin receptor gene associated with genetic syndromes of extreme insulin resistance SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article ID POLYMERASE CHAIN-REACTION; TYROSINE KINASE DOMAIN; NONSENSE MUTATION; POINT MUTATION; LEPRECHAUNISM; AMPLIFICATION; MECHANISMS; DELETION; PATIENT AB We identified four novel mutant alleles of the insulin receptor gene in three patients with genetic syndromes associated with insulin resistance. Two mutant alleles of the insulin receptor gene were identified in a patient with the Rabson-Mendenhall syndrome who was a compound heterozygote for a mutation at the 3'-splice acceptor site of intron 4 (AG-->GG;), the first mutation causing an aberrant splicing at this locus, and a deletion of eight base pairs in exon 12. The second patient with leprechaunism was also a compound heterozygote for a deletion of one base pair in exon 19 and a mutation, Thr(910)-->Met, which causes impaired receptor processing. interestingly, the third patient with type A syndrome was a simple heterozygote for the identical one base pair deletion. The fact that the same one base pair deletion links to type A in a simple heterozygote and to leprechaunism in a compound heterozygote appears consistent with the hypothesis that the severity of mutations will determine the phenotype. (C) 1997 Academic Press. C1 UNIV TOKYO,FAC MED,DEPT INTERNAL MED 3,BUNKYO KU,TOKYO 113,JAPAN. ASAHI LIFE FDN,INST DIABET CARE & RES,TOKYO,JAPAN. STIRLING ROYAL INFIRM,GLASGOW,LANARK,SCOTLAND. SAITAMA CHILDRENS MED CTR,IWATSUKI,SAITAMA,JAPAN. NIDDKD,DIABET BRANCH,NIH,BETHESDA,MD 20892. NR 22 TC 15 Z9 18 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 AUG 28 PY 1997 VL 237 IS 3 BP 516 EP 520 DI 10.1006/bbrc.1997.7181 PG 5 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA XV796 UT WOS:A1997XV79600008 PM 9299395 ER PT J AU Mishina, Y Tizard, R Deng, JM Pathak, BG Copeland, NG Jenkins, NA Cate, RL Behringer, RR AF Mishina, Y Tizard, R Deng, JM Pathak, BG Copeland, NG Jenkins, NA Cate, RL Behringer, RR TI Sequence, genomic organization, and chromosomal location of the mouse Mullerian-inhibiting substance type II receptor gene SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article ID MAMMALIAN SEXUAL DEVELOPMENT; ACTIVIN RECEPTOR; KINASE RECEPTORS; LINKAGE MAP; HORMONE; EXPRESSION; DIFFERENTIATION; EXONS; DUCT AB We have determined the sequence and structure of the mouse Mullerian-inhibiting substance (MIS) type II receptor gene. Sequence comparisons demonstrate that the mouse, rat, rabbit, and human MIS type II receptors are highly conserved. The mouse MIS type II receptor gene is encoded by 11 exons and spans approximately 9-kb. Only half of the intron/exon boundaries of its kinase domain are conserved in comparison to the kinase domain of the related activin type II receptor, Whereas the activin type II receptor gene contains large introns (>40-kb), the largest intron of the MIS type II receptor gene is only 4.3-kb. The MIS type II receptor gene (Amhr) is closely linked to Hoxc on mouse chromosome 15. Knowledge of the sequence and genomic structure of Amhr provides important information for the genetic manipulation of the Amhr locus. (C) 1997 Academic Press. C1 UNIV TEXAS, MD ANDERSON CANCER CTR, DEPT MOL GENET, HOUSTON, TX 77030 USA. BIOGEN INC, CAMBRIDGE, MA 02142 USA. NCI, FREDERICK CANC RES & DEV CTR, ABL BASIC RES PROGRAM, MAMMALIAN GENET LAB, FREDERICK, MD 21702 USA. FU NCI NIH HHS [CA16672]; NICHD NIH HHS [HD30284] NR 28 TC 15 Z9 18 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 0006-291X EI 1090-2104 J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD AUG 28 PY 1997 VL 237 IS 3 BP 741 EP 746 DI 10.1006/bbrc.1997.7224 PG 6 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA XV796 UT WOS:A1997XV79600050 PM 9299437 ER PT J AU Michelotti, EF Sanford, S Levens, D AF Michelotti, EF Sanford, S Levens, D TI Marking of active genes on mitotic chromosomes SO NATURE LA English DT Article ID PROMOTER; DISPLACEMENT; PROPAGATION; REPLICATION; CHROMATIN; INVIVO AB During development and differentiation, cellular phenotypes are stably propagated through numerous cell divisions(1). This epigenetic 'cell memory' helps to maintain stable patterns of gene expression(2). DNA methylation(3) and the propagation of specific chromatin structures may both contribute to cell memory(4). There are two impediments during the cell cycle that can hinder the inheritance of specific chromatin configurations: first, the pertinent structures must endure the passage of DNA-replication forks in S phase(5); second, the chromatin state must survive mitosis, when chromatin condenses, transcription is turned off, and almost all double-stranded DNA-binding proteins are displaced(6,7). After mitosis, the previous pattern of expressed and silent genes must be restored. This restoration might be governed by mass action, determined by the binding affinities and concentrations of individual components, Alternatively, a subset of factors might remain bound to mitotic chromosomes, providing a molecular bookmark to direct proper chromatin reassembly, Here we analyse DNA at transcription start sites during mitosis in vivo and find that it is conformationally distorted in genes scheduled for reactivation but is undistorted in repressed genes. These protein-dependent conformational perturbations could help to re-establish transcription after mitosis by 'marking' genes for re-expression. C1 NCI,PATHOL LAB,GENE REGULAT SECT,NIH,BETHESDA,MD 20892. RI Levens, David/C-9216-2009 OI Levens, David/0000-0002-7616-922X NR 21 TC 99 Z9 102 U1 0 U2 3 PU MACMILLAN MAGAZINES LTD PI LONDON PA PORTERS SOUTH, 4 CRINAN ST, LONDON, ENGLAND N1 9XW SN 0028-0836 J9 NATURE JI Nature PD AUG 28 PY 1997 VL 388 IS 6645 BP 895 EP 899 DI 10.1038/42282 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA XT754 UT WOS:A1997XT75400054 PM 9278053 ER PT J AU Appel, LJ Moore, TJ Obarzanek, E AF Appel, LJ Moore, TJ Obarzanek, E TI Dietary patterns and blood pressure - Reply SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Letter C1 BRIGHAM & WOMENS HOSP,BOSTON,MA 02115. NHLBI,BETHESDA,MD 20892. RP Appel, LJ (reprint author), JOHNS HOPKINS UNIV,BALTIMORE,MD 21205, USA. NR 2 TC 0 Z9 0 U1 0 U2 2 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 AUG 28 PY 1997 VL 337 IS 9 BP 637 EP 638 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA XT394 UT WOS:A1997XT39400016 ER PT J AU Sheikh, MS Carrier, F Johnson, AC Ogdon, SE Fornace, AJ AF Sheikh, MS Carrier, F Johnson, AC Ogdon, SE Fornace, AJ TI Identification of an additional p53-responsive site in the human epidermal growth factor receptor gene promotor SO ONCOGENE LA English DT Article DE p53; EGF-R promotor; transactivation ID TUMOR-SUPPRESSOR PROTEIN; HUMAN BREAST-CARCINOMA; DNA-BINDING FUNCTION; WILD-TYPE P53; TRANSCRIPTIONAL REGULATION; INDUCED APOPTOSIS; CELLS; EXPRESSION; RADIATION; ACTIVATION AB Exogenously introduced wild-type and mutant p53 have recently been reported to enhance the human epidermal growth factor receptor (EGF-R) gene promoter activity in p53-deficient Saos2 osteosarcoma cells. A p53 binding site residing at position -265/-239 in the EGF-R proximal promoter has also been identified. We investigated the p53 regulation of EGF-R core promoter activity in human cell lines with varying endogenour p53 status. Wild-type and mutant p53(Ala143) enhanced the EGF-R core promotor activity in cells that were either p53-deficient or contained wild-type or mutant endogenous p53. Upon further characterization of the various deletion fragments of the EGF-R promoter, we identified a wild-type p53 responsive 62 bp region residing at position -167/-105. The -167/-105 segment was responsive only to wild-type p53 but not to mutant p53(Ala143) Or p53(His273). The -167/-105 segment of the EGF-R promotor contains one perfect and several imperfect consensus p53-binding half sites; indeed in gel shift experiments the 62 bp -167/-105 segment as well as the oligonucleotides corresponding to two p53 consensus half-sites within the 62 bp fragment, exhibited binding to p53-containing protein complexes. Thus, we have identified an additional wild-type p53 responsive site in the human EGF-R promoter. This site containing consensus p53-binding sequences resides at position -167/-105 and is proximal to recently identified p53 binding element located at position -265/-239 in the EGF-R promotor. C1 NCI,MOL BIOL LAB,NIH,BETHESDA,MD 20892. RP Sheikh, MS (reprint author), NCI,MOL PHARMACOL LAB,NIH,BETHESDA,MD 20892, USA. RI Carrier, France/C-3063-2008; Fornace, Albert/A-7407-2008 OI Fornace, Albert/0000-0001-9695-085X NR 56 TC 36 Z9 36 U1 0 U2 0 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE, HAMPSHIRE, ENGLAND RG21 6XS SN 0950-9232 J9 ONCOGENE JI Oncogene PD AUG 28 PY 1997 VL 15 IS 9 BP 1095 EP 1101 DI 10.1038/sj.onc.1201264 PG 7 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA XT161 UT WOS:A1997XT16100011 PM 9285564 ER PT J AU Hoeg, JM AF Hoeg, JM TI Expanding and understanding risk factors for coronary heart disease - Reply SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Letter RP Hoeg, JM (reprint author), NIH, BLDG 10, 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 60654-0946 USA SN 0098-7484 EI 1538-3598 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD AUG 27 PY 1997 VL 278 IS 8 BP 636 EP 636 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA XR547 UT WOS:A1997XR54700034 ER PT J AU Ottiger, M Bax, A AF Ottiger, M Bax, A TI An empirical correlation between amide deuterium isotope effects on C-13(alpha) chemical shifts and protein backbone conformation SO JOURNAL OF THE AMERICAN CHEMICAL SOCIETY LA English DT Article ID COUPLING-CONSTANTS; HUMAN UBIQUITIN; C-ALPHA; SECONDARY STRUCTURE; ANGULAR-DEPENDENCE; ENRICHED PROTEINS; NMR-SPECTROSCOPY; C-13 RESONANCES; ASSIGNMENT; SPECTRA AB Three-dimensional, triple resonance NMR techniques are described for measurement of two-bond (intraresidual) and three-bond (sequential) amide deuterium isotope effects on C-13(alpha) chemical shifts. Measurements were carried out for uniformly N-15 and C-13 labeled human ubiquitin equilibrated in a 50% H2O/50% D2O mixed solvent. The three-bond isotope shift, (3) Delta C-alpha(ND), ranges from about 10-50 ppb, and, except for residues with positive phi angles and residues followed by Gly, its magnitude is described by (3) Delta C-alpha(ND) = 30.1 + 22.2 sin(psi) +/- 3.4 ppb. The two-bond isotope shift, (2) Delta C-alpha(ND), ranges from 70 to 116 ppb and is also dominated by the local backbone geometry at the C-alpha position: (2) Delta C-alpha(ND) = 93.1 + 10.1 sin(phi+62 degrees) + 12.0 sin(psi+42 degrees) +/- 4.1 ppb. C1 NIDDKD,CHEM PHYS LAB,NIH,BETHESDA,MD 20892. NR 49 TC 46 Z9 46 U1 0 U2 2 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0002-7863 J9 J AM CHEM SOC JI J. Am. Chem. Soc. PD AUG 27 PY 1997 VL 119 IS 34 BP 8070 EP 8075 DI 10.1021/ja9707466 PG 6 WC Chemistry, Multidisciplinary SC Chemistry GA XT922 UT WOS:A1997XT92200020 ER PT J AU Tjandra, N Bax, A AF Tjandra, N Bax, A TI Solution NMR measurement of amide proton chemical shift anisotropy in N-15-enriched proteins. Correlation with hydrogen bond length SO JOURNAL OF THE AMERICAN CHEMICAL SOCIETY LA English DT Article ID SECONDARY STRUCTURE; SOLID-STATE; N-15 NMR; CORRELATION SPECTROSCOPY; RELAXATION MEASUREMENTS; ROTATIONAL DIFFUSION; BACKBONE DYNAMICS; HIV PROTEASE; C-13 NMR; SPECTRA AB Cross-correlation between N-15-H-1 dipolar interactions and H-1(N) chemical shift anisotropy (CSA) gives rise to different relaxation rates of the doublet components of H-1-{N-15} peptide backbone amides. Two schemes for quantitative measurement of this effect are described and demonstrated for samples of uniformly N-15-enriched ubiquitin and perdeuterated N-15-enriched HIV-1 protease. The degree of relaxation interference correlates with the isotropic H-1(N) chemical shift, and results indicate that an upfield change of the most shielded principal components of the CSA tensor is correlated with an approximately 2-fold larger downfield shift of the average of the other two components. The magnitude of the relaxation interference is large in beta-sheet and considerably smaller in alpha-helices. This correlation is not dominated by the backbone geometry bur reflects the slightly longer hydrogen bond length in helices compared to beta-sheet. The smallest relaxation interference effect in ubiquitin is observed for Ser(20)-H-N and Ile(36)-H-N, which are the only two amide protons that are not hydrogen bonded in the crystal structure of ubiquitin, inaccessible to solvent, and not highly mobile. C1 NIDDK,CHEM PHYS LAB,NIH,BETHESDA,MD 20892. NHLBI,BIOPHYS CHEM LAB,NIH,BETHESDA,MD 20892. NR 59 TC 125 Z9 125 U1 1 U2 17 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0002-7863 J9 J AM CHEM SOC JI J. Am. Chem. Soc. PD AUG 27 PY 1997 VL 119 IS 34 BP 8076 EP 8082 DI 10.1021/ja970876e PG 7 WC Chemistry, Multidisciplinary SC Chemistry GA XT922 UT WOS:A1997XT92200021 ER PT J AU Raptis, L Brownell, HL Lu, Y Preston, T Narsimhan, RP Anderson, S Schaefer, E Haliotis, T AF Raptis, L Brownell, HL Lu, Y Preston, T Narsimhan, RP Anderson, S Schaefer, E Haliotis, T TI v-Ras and v-Raf block differentiation of transformable C3H10T1/2-derived preadipocytes at lower levels than required for neoplastic transformation SO EXPERIMENTAL CELL RESEARCH LA English DT Article ID EPIDERMAL GROWTH-FACTOR; MESENCHYMAL STEM-CELLS; SIGNAL-TRANSDUCTION; GENE-EXPRESSION; CELLULAR-TRANSFORMATION; GUANINE-NUCLEOTIDES; PC12 CELLS; H-RAS; ONCOGENE; INSULIN AB To investigate the functional relationship between the transforming ability of Ras and its role as an integral component of the differentiative insulin signaling pathway, we introduced a leu61-activated ms gene into a Ras-transformable, C3H1OT1/2-derived preadipocytic cell line. The results demonstrate that ras(leu61) expression in this Line blocks differentiation and that this block. appears at lower levels than required for full. neoplastic transformation, In addition, to examine whether the inability of Ras(leu61) to induce differentiation by replacing the insulin signal could be attributed to its transforming effect in this system, we examined the effect of Ras(leu61) at levels below the baseline, by expressing ras(leu61) in a series of preadipocytes which were rendered deficient in endogenous c-Ras activity, The results show that even very low Ras(leu61) levels, insufficient to restore the growth rate of these cells to normal, blocked rather than enhanced differentiation, indicating that ras(leu61) expression alone is not sufficient to promote adipocytic differentiation in this system, even in the absence of neoplastic transformation. Consistent with its established role as a downstream effector of Ras, v-Raf expression mirrored the v-Ras effects upon adipocytic differentiation and transformation. (C) 1997 Academic Press. C1 QUEENS UNIV,DEPT PATHOL,KINGSTON,ON,CANADA. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,CAMBRIDGE,MA 02138. NCI,FREDERICK,MD 21702. PROMEGA CORP,MADISON,WI 53711. RP Raptis, L (reprint author), QUEENS UNIV,DEPT MICROBIOL & IMMUNOL,KINGSTON,ON,CANADA. NR 42 TC 12 Z9 12 U1 0 U2 2 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0014-4827 J9 EXP CELL RES JI Exp. Cell Res. PD AUG 25 PY 1997 VL 235 IS 1 BP 188 EP 197 DI 10.1006/excr.1997.3646 PG 10 WC Oncology; Cell Biology SC Oncology; Cell Biology GA XV968 UT WOS:A1997XV96800024 PM 9281368 ER PT J AU Coursen, JD Bennett, WP Gollahon, L Shay, JW Harris, CC AF Coursen, JD Bennett, WP Gollahon, L Shay, JW Harris, CC TI Genomic instability and telomerase activity in human bronchial epithelial cells during immortalization by human papillomavirus-16 E6 and E7 genes SO EXPERIMENTAL CELL RESEARCH LA English DT Article ID HUMAN-DIPLOID FIBROBLASTS; P53 DNA-BINDING; LARGE T-ANTIGEN; HUMAN KERATINOCYTES; TYPE-18 E6; CELLULAR SENESCENCE; HPV-16 E6; PROTEIN; DEGRADATION; EXPRESSION AB Human papilloma virus types 16 and 18 contribute to the development of cervical carcinomas in which the E6 and E7 genes are frequently retained and expressed in the tumors. Our study explored the ability of the E6 and/or E7 genes to immortalize normal human bronchial epithelial (NHBE) cells and to reactivate telomerase expression in these cells. We have introduced the human papillomavirus type 16 E6 or E7 genes alone or in combination (E6/E7) into NHBE cells using the retroviral construct pLXSN. Cells expressing either the E6 or the E7 oncoproteins alone displayed an increased colony-forming efficiency and a slightly extended in vitro life span before entering a crisis, from which immortalized cell lines were not obtained. Telomerase activity was not detected in cells expressing either E6 or E7 individually. Cells expressing the E6/E7 oncoproteins in combination had a substantially increased life span before entering crisis. A subpopulation of these cells escaped from crisis and achieved 130 population doublings, suggesting immortalization. Telomerase activity was detected in these postcrisis cells, but was not detected prior to crisis. In addition, karyotypic analysis showed evidence of genomic instability in mass cultures as well as clones expressing E6, E7, or E6/E7. Abnormalities included numerous monosomies and trisomies, chromatid gaps and breaks, double minutes, and aberrant chromosomes. These results demonstrate that expression of E6 and/or E7 is sufficient to induce genomic instability and an extended life span to NHBE cells, but the presence of both E6 and E7, along with at least one additional genetic or epigenetic event achieved during crisis, was required for reactivation of telomerase and the immortalization in this human cell type. (C) 1997 Academic Press. C1 NCI,HUMAN CARCINOGENESIS LAB,NIH,BETHESDA,MD 20892. UNIV TEXAS,SW MED CTR,DEPT CELL BIOL & NEUROSCI,DALLAS,TX 75235. RI Shay, Jerry/F-7878-2011 NR 70 TC 27 Z9 32 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 AUG 25 PY 1997 VL 235 IS 1 BP 245 EP 253 DI 10.1006/excr.1997.3670 PG 9 WC Oncology; Cell Biology SC Oncology; Cell Biology GA XV968 UT WOS:A1997XV96800030 PM 9281374 ER PT J AU Hoet, P Graf, MLM Bourdi, M Pohl, LR Duray, PH Chen, WQ Peter, RM Nelson, SD Verlinden, N Lison, D AF Hoet, P Graf, MLM Bourdi, M Pohl, LR Duray, PH Chen, WQ Peter, RM Nelson, SD Verlinden, N Lison, D TI Epidemic of liver disease caused by hydrochlorofluorocarbons used as ozone-sparing substitutes of chlorofluorocarbons SO LANCET LA English DT Article ID HALOTHANE-ASSOCIATED HEPATITIS; ANTIBODIES; HEPATOTOXICITY; 1,1-DICHLORO-2,2,2-TRIFLUOROETHANE; HEPATOCYTES; METABOLISM; EXPOSURE; HCFC-123; SERA AB Background Hydrochlorofluorocarbons (HCFCs) are used increasingly in industry as substitutes for ozone-depleting chlorofluorocarbons (CFCs). Limited studies in animals indicate potential hepatotoxicity of some of these compounds. We investigated an epidemic of liver disease in nine industrial workers who had had repeated accidental exposure to a mixture of 1,1-dichloro-2,2,2-trifluoroethane (HCFC, 123) and 1-chloro-1,2,2,2-tetrafluoroethane (HCFC 124). All nine exposed workers were affected to various degrees. Both compounds are metabolised in the same way as 1-bromo-1-chloro-2,2,2-trifluoroethane (halothane) to form reactive trifluoroacetyl halide intermediates, which have been implicated in the hepatotoxicity of halothane. We aimed to test whether HCFCs 123 and 124 can result in serious liver disease. Methods For one severely affected worker liver biopsy and immunohistochemical stainings for the presence of trifluoroacetyl protein adducts were done. The serum of six affected workers and five controls was tested for autoantibodies that react with human liver cytochrome-P450 2E1 (P450 2E1) and P58 protein disulphide isomerase isoform (P58). Findings The liver biopsy sample showed hepatocellular necrosis which was prominent in perivenular zone three and extended focally from portal tracts to portal tracts and centrilobular areas (bridging necrosis). Trifluoroacetyl-adducted proteins were detected in surviving hepatocytes. Autoantibodies against P450 2E1 or P58, previously associated with halothane hepatitis, were detected in the serum of five affected workers. Interpretation Repeated exposure of human beings to HCFCs 123 and 124 can result in serious liver injury in a large proportion of the exposed population. Although the exact mechanism of hepatotoxicity of these agents is not known, the results suggest that trifluoroacetyl-altered liver proteins are involved. In view of the potentially widespread use of these compounds, there is an urgent need to develop safer alternatives. C1 NHLBI,MOL & CELLULAR TOXICOL SECT,LAB MOL IMMUNOL,NIH,BETHESDA,MD 20892. NCI,DEPT PATHOL,NIH,BETHESDA,MD 20892. JOHNS HOPKINS MED INST,DEPT ANESTHESIOL & CRIT CARE MED,BALTIMORE,MD 21205. UNIV WASHINGTON,SCH PHARM,DEPT MED CHEM,SEATTLE,WA 98195. RP Hoet, P (reprint author), UNIV CATHOLIQUE LOUVAIN,FAC MED,IND TOXICOL & OCCUPAT MED UNIT,CLOS CHAPELLE AUX CHAMPS 30-54,B-1200 BRUSSELS,BELGIUM. FU NIGMS NIH HHS [GM 32165] NR 17 TC 55 Z9 55 U1 0 U2 1 PU LANCET LTD PI LONDON PA 42 BEDFORD SQUARE, LONDON, ENGLAND WC1B 3SL SN 0140-6736 J9 LANCET JI Lancet PD AUG 23 PY 1997 VL 350 IS 9077 BP 556 EP 559 DI 10.1016/S0140-6736(97)03094-8 PG 4 WC Medicine, General & Internal SC General & Internal Medicine GA XT221 UT WOS:A1997XT22100011 PM 9284778 ER PT J AU Aksentijevich, I Centola, M Deng, ZM Sood, R Balow, JE Wood, G Zaks, N Mansfield, E Chen, X Eisenberg, S Vedula, A Shafran, N Raben, N Pras, E Pras, M Kastner, DL Blake, T Baxevanis, AD Robbins, C Krizman, D Collins, FS Liu, PP Chen, XG Shohat, M Hamon, M Kahan, T Cercek, A Rotter, JI FischelGhodsian, N Richards, N Shelton, DA Gumucio, D Yokoyama, Y Mangelsdorf, M Orsborn, A Richards, RI Ricke, DO Buckingham, JM Moyzis, RK Deaven, LL Doggett, NA AF Aksentijevich, I Centola, M Deng, ZM Sood, R Balow, JE Wood, G Zaks, N Mansfield, E Chen, X Eisenberg, S Vedula, A Shafran, N Raben, N Pras, E Pras, M Kastner, DL Blake, T Baxevanis, AD Robbins, C Krizman, D Collins, FS Liu, PP Chen, XG Shohat, M Hamon, M Kahan, T Cercek, A Rotter, JI FischelGhodsian, N Richards, N Shelton, DA Gumucio, D Yokoyama, Y Mangelsdorf, M Orsborn, A Richards, RI Ricke, DO Buckingham, JM Moyzis, RK Deaven, LL Doggett, NA TI Ancient missense mutations in a new member of the RoRet gene family are likely to cause familial Mediterranean fever SO CELL LA English DT Article ID IMMUNODEFICIENCY-VIRUS TYPE-1; PROTEIN SECONDARY STRUCTURE; SHORT ARM; EXPRESSION; CLONING; FINGER; IDENTIFICATION; CHROMOSOME-16; EVOLUTIONARY; AMYLOIDOSIS AB Familial Mediterranean fever (FMF) is a recessively inherited disorder characterized by dramatic episodes of fever and serosal inflammation. This report describes the cloning of the gene likely to cause FMF from a 115-kb candidate interval on chromosome 16p. Three different missense mutations were identified in affected individuals, but not in normals. Haplotype and mutational analyses disclosed ancestral relationships among carrier chromosomes in populations that have been separated for centuries. The novel gene encodes a 3.7-kb transcript that is almost exclusively expressed in granulocytes. The predicted protein, pyrin, is a member of a family of nuclear factors homologous to the Ro52 autoantigen. The cloning of the FMF gene promises to shed light on the regulation of acute inflammatory responses. C1 NIAMSD,ARTHRIT & RHEUMATISM BRANCH,BETHESDA,MD 20892. CHAIM SHEBA MED CTR,HELLER INST MED RES,DEPT MED C,IL-52621 TEL HASHOMER,ISRAEL. NHGRI,CANC GENET LAB,BETHESDA,MD 20892. NHGRI,LAB GENE TRANSFER,BETHESDA,MD 20892. NHGRI,GENOME TECHNOL BRANCH,BETHESDA,MD 20892. CEDARS SINAI MED CTR,DEPT PEDIAT,LOS ANGELES,CA 90048. CEDARS SINAI MED CTR,DEPT MED GENET,LOS ANGELES,CA 90048. BEILINSON MED CTR,DEPT MED GENET,IL-49100 PETAH TIQWA,ISRAEL. UNIV MICHIGAN,DEPT ANAT & CELL BIOL,ANN ARBOR,MI 48109. ADELAIDE WOMENS & CHILDRENS HOSP,DEPT CYTOGENET & MOL GENET,ADELAIDE,SA 5006,AUSTRALIA. LOS ALAMOS NATL LAB,CTR HUMAN GENOME STUDIES,LOS ALAMOS,NM 87545. RI Liu, Paul/A-7976-2012; Hamon, Melanie/B-3501-2013; Mangelsdorf, Marie/A-2318-2013 OI Liu, Paul/0000-0002-6779-025X; Mangelsdorf, Marie/0000-0002-7855-7701 NR 48 TC 805 Z9 820 U1 1 U2 21 PU CELL PRESS PI CAMBRIDGE PA 1050 MASSACHUSETTES AVE, CIRCULATION DEPT, CAMBRIDGE, MA 02138 SN 0092-8674 J9 CELL JI Cell PD AUG 22 PY 1997 VL 90 IS 4 BP 797 EP 807 PG 11 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA XT066 UT WOS:A1997XT06600022 ER PT J AU BenShahar, S Cassouto, B Novak, L Porgador, A Reiss, Y AF BenShahar, S Cassouto, B Novak, L Porgador, A Reiss, Y TI Production of a specific major histocompatibility complex class I-restricted epitope by ubiquitin-dependent degradation of modified ovalbumin in lymphocyte lysate SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID MULTICATALYTIC PROTEINASE COMPLEX; PROTEOLYTIC PATHWAY; INTERFERON-GAMMA; 20-S PROTEASOME; PEPTIDES; ANTIGEN; ACTIVATOR; CELLS; PURIFICATION; MOLECULES AB Peptide epitopes presented through class I major histocompatability complex (MHC class I) on the cell! surface, are generated by proteolytic processing of protein-antigens in the cytoplasm. The length and amino acid sequence determine whether a given peptide can fit into the peptide binding groove of class I heavy chain molecules and subsequently be presented to the immune system. The mode ai action of the processing pathway Is therefore of great interest. go study the processing mechanism of MHC class I-restricted intracellular antigens, me reconstituted the proteolytic processing of a model antigen in a cell-free system. Incubation of oxidized and urea-treated OVA in lymphocyte lysate resulted in partial degradation of the antigen, Degradation of the antigen depended on the presence of ATP, Addition of methylated ubiquitin abolished the reaction which was then restored by addition of am excess of native ubiquitin, indicating that the breakdown of the antigen in lymphocyte lysate is mediated by the ubiquitin proteolytic system, Upon incubation of modified OVA in lymphocyte lysate, a specific antigenic peptide was generated. The peptide was recognized by cytotoxic T lymphocytes directed against OVA-derived, H-2K(b)-restricted peptide (SIINFEKL), and by st monoclonal antibody that recognizes cell-bound K-b-SIINFEKL complexes. Formation of the peptide epitope depended on the presence of ATP and ubiquitin. These results indicate that proteolytic processing of modified OVA is carried out by the ubiquitin-mediated degradation system. The experimental system described provides a tool to analyze else molecular mechanisms underlying the generation of specific, MHC class I-restricted peptide epitopes. C1 TEL AVIV UNIV,GEORGE S WISE FAC LIFE SCI,DEPT BIOCHEM,IL-69978 TEL AVIV,ISRAEL. NIAID,LYMPHOCYTE BIOL SECT,IMMUNOL LAB,BETHESDA,MD 20892. NR 43 TC 12 Z9 12 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 AUG 22 PY 1997 VL 272 IS 34 BP 21060 EP 21066 DI 10.1074/jbc.272.34.21060 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA XR789 UT WOS:A1997XR78900018 PM 9261108 ER PT J AU Ambudkar, SV Cardarelli, CO Pashinsky, I Stein, WD AF Ambudkar, SV Cardarelli, CO Pashinsky, I Stein, WD TI Relation between the turnover number for vinblastine transport and for vinblastine-stimulated ATP hydrolysis by human P-glycoprotein SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID RESISTANT TUMOR-CELLS; EHRLICH ASCITES TUMOR; MULTIDRUG-RESISTANCE; WILD-TYPE; EXPRESSION; RECONSTITUTION; PURIFICATION; LEUKEMIA; CDNA AB Considerable uncertainty surrounds the stoichiometry of coupling of ATP hydrolysis to drug pumping by P-glycoprotein, the multidrug transporter. To estimate relative turnovers far pumping of the drug vinblastine and ATP hydrolysis, we began by measuring the number of P-glycoprotein molecules an the surface of murine NIH3T3 cells expressing the human MDR1 gene, Fluorescence of cells treated with monoclonal antibody UIC2 was determined as a function of (i) amount of antibody at a fixed number of cells and (ii) increasing cell number at constant antibody, The two together gives 1.95 x 10(6) P-glycoprotein molecules/cell. Initial uptake rates of vinblastine +/- verapamil measure the ability of P-glycoprotein to extract vinblastine from the plasma membrane before it enters the cell, As a function of [vinblastine] at 37 degrees C, they give the maximum rats of this component of outward pumping as 2,1. x 10(6) molecules s(-1) cell(-1) or a turnover number of 1.1 s(-1), Initial rates of one-way efflux as a function of [vinblastine] at 25 degrees C +/- glucose give the maximum rate of this component of pumping as 0.59 x 10(6) molecules s(-1) cell(-1). The ratio of ATPase activity of P-glycoprotein at 31 and 25 degrees C is 4.6. Appropriating this ratio for pumping, maximum one-way efflux at 37 degrees C is 4.6 x 0.59 = 2.7 x 10(6) molecules s(-1) cell(-1), a turnover number of 1.4 s(-1), The vinblastine-stimulated ATPase activity of P-glycoprotein has a turnover number of 3.5 s(-1) at 37 degrees C, giving 2.8 molecules of AITP hydrolyzed for every vinblastine molecule transported in a particular direction, These calculations involve several approximations, but turnover numbers for pumping of vinblastine and for vinblastine-stimulated ATP hydrolysis are comparable, Thus, ATP hydrolysis is probably directly linked to drug transport by P-glycoprotein. C1 NCI,DIV BASIC SCI,MOL BIOL LAB,NIH,BETHESDA,MD 20892. HEBREW UNIV JERUSALEM,SILBERMAN INST LIFE SCI,DEPT BIOCHEM,IL-91904 JERUSALEM,ISRAEL. RP Ambudkar, SV (reprint author), NCI,CELL BIOL LAB,NIH,BLDG 37,RM 1B-17,37 CONVENT DR,MSC 4255,BETHESDA,MD 20892, USA. RI Ambudkar, Suresh/B-5964-2008 NR 35 TC 146 Z9 149 U1 0 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 AUG 22 PY 1997 VL 272 IS 34 BP 21160 EP 21166 DI 10.1074/jbc.272.34.21160 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA XR789 UT WOS:A1997XR78900031 PM 9261121 ER PT J AU MontroseRafizadeh, C Yang, H Rodgers, BD Beday, A Pritchette, LA Eng, J AF MontroseRafizadeh, C Yang, H Rodgers, BD Beday, A Pritchette, LA Eng, J TI High potency antagonists of the pancreatic glucagon-like peptide-1 receptor SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID GUINEA-PIG PANCREAS; FUNCTIONAL EXPRESSION; REPLACEMENT ANALOGS; DISPERSED ACINI; POLYPEPTIDE; EXENDIN-4; IDENTIFICATION; DEGRADATION; CLONING; BINDING AB GLP-1-(7-36)-amide and exendin-4-(1-39) are glucagon-like peptide-1 (GLP-1) receptor agonists, whereas exendin-(9-39) is the only known antagonist, To analyze the transition from agonist to antagonist and to identify the amino acid residues involved in ligand activation of the GLP-1 receptor, we used exendin analogs with successive N-terminal truncations, Chinese hamster ovary cells stably transfected with the rat GLP-1 receptor were assayed for changes in intracellular cAMP caused by the test peptides in the absence or presence of half-maximal stimulatory doses of GLP-1. N-terminal truncation of a single amino acid reduced the agonist activity of the exendin peptide, whereas N-terminal truncation of 3-7 amino acids produced antagonists that were 4-10-fold more potent than exendin-(9-39), N-terminal truncation of GLP-1 by 2 amino acids resulted in weak agonist activity, but an 8-amino acid N-terminal truncation inactivated the peptide, Binding studies performed using I-125-labeled GLP-1 confirmed that all bioactive peptides specifically displaced tracer with high potency, In a set of exendin/GLP-1 chimeric peptides, substitution of GLP-1 sequences into exendin-(3-39) produced loss of antagonist activity with conversion to a weak agonist, The results show that receptor binding and activation occur in separate domains of exendin, but they are more closely coupled in GLP-1. C1 NIA,LAB CLIN PHYSIOL,NIH,BALTIMORE,MD 21224. VET ADM MED CTR,DEPT MED,BRONX,NY 10468. CUNY MT SINAI SCH MED,NEW YORK,NY 10029. NR 28 TC 112 Z9 113 U1 3 U2 8 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 AUG 22 PY 1997 VL 272 IS 34 BP 21201 EP 21206 DI 10.1074/jbc.272.34.21201 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA XR789 UT WOS:A1997XR78900037 PM 9261127 ER PT J AU Kuroda, A Murphy, H Cashel, M Kornberg, A AF Kuroda, A Murphy, H Cashel, M Kornberg, A TI Guanosine tetra- and pentaphosphate promote accumulation of inorganic polyphosphate in Escherichia coli SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID PPGPP; EXOPOLYPHOSPHATASE; PURIFICATION; MUTANTS; GENE AB High levels of guanosine tetraphosphate (ppGpp) and guanosine pentaphosphate (pppGpp), generated in response to amino acid starvation in Escherichia coli, lead to massive accumulations of inorganic polyphosphate (polyP). Inasmuch as the activities of the principal enzymes that synthesize and degrade polyP fluctuate only slightly, the polyP accumulation can be attributed to a singular and profound inhibition by pppGpp and/or ppGpp of the hydrolytic breakdown of polyP by exopolyphosphatase, thereby blocking the dynamic turnover of polyP. The K-i values of 10 mu M for pppGpp and 200 mu M for ppGpp are far below the concentrations of these nucleotides in nutritionally stressed cells. In the complex metabolic network of pppGpp and ppGpp, the greater inhibitory effect of pppGpp (compared with ppGpp) leading to the accumulation of polyP, may have some significance in the relative roles played by these regulatory compounds. C1 STANFORD UNIV,SCH MED,DEPT BIOCHEM,STANFORD,CA 94305. NICHHD,MOL GENET LAB,NIH,BETHESDA,MD 20892. NR 19 TC 141 Z9 142 U1 1 U2 10 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 AUG 22 PY 1997 VL 272 IS 34 BP 21240 EP 21243 DI 10.1074/jbc.272.34.21240 PG 4 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA XR789 UT WOS:A1997XR78900043 PM 9261133 ER PT J AU Grossmann, M Wong, R Szkudlinski, MW Weintrauab, BD AF Grossmann, M Wong, R Szkudlinski, MW Weintrauab, BD TI Human thyroid-stimulating hormone (hTSH) subunit gene fusion produces hTSH with increased stability and serum half-life and compensates for mutagenesis-induced defects in subunit association SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID HUMAN CHORIONIC-GONADOTROPIN; GLYCOPROTEIN HORMONES; ALPHA-SUBUNIT; BETA-SUBUNITS; METABOLIC-CLEARANCE; HUMAN THYROTROPIN; EXPRESSION; BIOACTIVITY; EVOLUTION; PITUITARY AB The human thyroid-stimulating hormone (hTSH) subunits alpha and beta are transcribed from different genes and associate noncovalently to form the bioactive hTSH heterodimer, Dimerization is rate-limiting for hTSH secretion, and dissociation leads to hormone inactivation, Previous studies on human chorionic gonadotropin (hCG) and human follicle-stimulating hormone had shown that if was possible by subunit gene fusion to produce a bioactive, single chain hormone. However, neither the stability nor the clearance from the circulation of such fused glycoprotein hormones has been studied. We show here that genetic fusion of the hTSH alpha- and beta-subunits using the carboxyl-terminal peptide of the hCG beta-subunit as a linker created unimolecular hTSH whose receptor binding and bioactivity were comparable to native hTSH. Interestingly; the fused hTSH had higher thermostability and a longer plasma half-life than either native or dimeric hTSH containing the hCG beta-subunit-carboxyl-terminal peptide, suggesting that dimer dissociation may contribute to glycoprotein hormone inactivation in vivo. In addition, we show for the first time that synthesis of hTSH as a single polypeptide chain could overcome certain mutagenesis-induced defects in hTSH secretion, therefore enabling functional studies of such mutants, Thus, in addition to prolongation of plasma half-life, genetic fusion of hTSH subunits should be particularly relevant for the engineering of novel analogs where desirable features are offset by decreased dimer formation or stability, Such methods provide a general approach to expand the spectrum of novel recombinant glycoprotein hormones available for in vitro and in vivo study. C1 NHLBI,NIH,BETHESDA,MD 20892. UNIV MARYLAND,SCH MED,DEPT MED,MOL ENDOCRINOL LAB,BALTIMORE,MD 21201. RP Grossmann, M (reprint author), UNIV MARYLAND,CTR MED BIOTECHNOL,INST HUMAN VIROL,MOL ENDOCRINOL LAB,725 W LOMBARD ST N457,BALTIMORE,MD 21201, USA. NR 32 TC 37 Z9 37 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD AUG 22 PY 1997 VL 272 IS 34 BP 21312 EP 21316 DI 10.1074/jbc.272.34.21312 PG 5 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA XR789 UT WOS:A1997XR78900053 PM 9261143 ER PT J AU Araki, T Zimonjic, DB Popescu, NC Milbrandt, J AF Araki, T Zimonjic, DB Popescu, NC Milbrandt, J TI Mechanism of homophilic binding mediated by ninjurin, a novel widely expressed adhesion molecule SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID DILATED CARDIOMYOPATHY; MASA SYNDROME; GENE; CELLS; HYBRIDIZATION; LOCALIZATION; RECEPTORS; MUTATIONS; FISH; RNA AB Ninjurin is a novel protein that is up-regulated after nerve injury both in dorsal root ganglion (DRG) neurons and in Schwann cells, We previously reported that ninjurin demonstrates properties of a homophilic adhesion molecule and promotes neurite outgrowth from primary cultured DRG neurons, We have now found that ninjurin is widely expressed in both adult and embryonic tissues, primarily in those of epithelial origin, Aggregation assays were used to demonstrate that ninjurin-mediated adhesion requires divalent cations and is an energy-dependent process, The critical domain for ninjurin-mediated homophilic adhesion was localized to an Ii-residue region (between Pro(26) and Asn(37)) by mutagenesis and by employing synthetic oligopeptides as competitive inhibitors of ninjurin-mediated adhesion, Of particular importance are the Trp residue at position 29 and the 3 arginines in the region, Furthermore, we show that the peptide which inhibits aggregation of Jurkat cells expressing ninjurin is also capable of blocking the ability of ninjurin to promote neurite extension from DRG neurons, Using FISH analysis, the ninjurin gene was localized to human chromosome 9q22. Several genetic diseases of unknown etiology have been mapped to this region, including hereditary sensory neuropathy type 1, self-healing squamous epithelioma, split-hand/foot deformity type 1, and familial dilated cardiomyopathy. C1 WASHINGTON UNIV, SCH MED, DEPT PATHOL & MED, DIV LAB MED, ST LOUIS, MO 63110 USA. NCI, MOL CYTOGENET SECT, EXPT CARCINOGENESIS LAB, NIH, BETHESDA, MD 20892 USA. FU NCI NIH HHS [CA 53524] NR 33 TC 38 Z9 41 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 AUG 22 PY 1997 VL 272 IS 34 BP 21373 EP 21380 DI 10.1074/jbc.272.34.21373 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA XR789 UT WOS:A1997XR78900061 PM 9261151 ER PT J AU Hung, IH Suzuki, M Yamaguchi, Y Yuan, DS Klausner, RD Gitlin, JD AF Hung, IH Suzuki, M Yamaguchi, Y Yuan, DS Klausner, RD Gitlin, JD TI Biochemical characterization of the Wilson disease protein and functional expression in the yeast Saccharomyces cerevisiae SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID COPPER TRANSPORTING ATPASE; P-TYPE ATPASES; MANNOSE 6-PHOSPHATE; IRON UPTAKE; GENE; CELLS; CERULOPLASMIN; ORGANIZATION; BIOGENESIS; MECHANISMS AB Wilson disease is a disorder of copper metabolism characterized by hepatic cirrhosis and neuronal degeneration due to inherited mutations in a gene encoding a putative copper-transporting P-type ATPase. Polyclonal antisera generated against the amino terminus of the Wilson protein detected a specific 165-kDa protein in HepG2 and CaCo cell lysates, Further analysis revealed that this protein is synthesized as a single-chain polypeptide and localized to the trans-Golgi network under steady state conditions. An increase in the copper concentration resulted in the rapid movement of this protein to a cytoplasmic vesicular compartment. This copper-specific cellular redistribution of the Wilson protein is a reversible process that occurs independent of a new protein synthesis. Expression of the wild-type but not mutant Wilson protein in the ccc2 Delta strain of Saccharomyces cerevisiae restored copper incorporation into the multicopper oxidase Fet3p, providing direct evidence of copper transport by the Wilson protein. Taken together these data reveal a remarkable evolutionary conservation in the cellular mechanisms of copper metabolism and provide a unique model for the regulation of copper transport into the secretory pathway of eucaryotic cells. C1 WASHINGTON UNIV,SCH MED,EDWARD MALLINCKRODT DEPT PEDIAT,ST LOUIS,MO 63110. NICHHD,CELL BIOL & METAB BRANCH,NIH,BETHESDA,MD 20892. FU NICHD NIH HHS [K08 HD058219]; NIDDK NIH HHS [DK44464] NR 40 TC 254 Z9 254 U1 0 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 AUG 22 PY 1997 VL 272 IS 34 BP 21461 EP 21466 DI 10.1074/jbc.272.34.21461 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA XR789 UT WOS:A1997XR78900073 PM 9261163 ER PT J AU Meng, JJ Bornslaeger, EA Green, KJ Steinert, PM Ip, W AF Meng, JJ Bornslaeger, EA Green, KJ Steinert, PM Ip, W TI Two-hybrid analysis reveals fundamental differences in direct interactions between desmoplakin and cell type-specific intermediate filaments SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID BULLOUS PEMPHIGOID ANTIGEN; PROTEIN-PROTEIN INTERACTIONS; DESMOSOMAL PLAQUE; SACCHAROMYCES-CEREVISIAE; CULTURED-CELLS; KERATIN; YEAST; TERMINUS; NETWORKS; PLECTIN AB Desmosomes are cell junctions that act as sites of strong intercellular adhesion and also serve to anchor the intermediate filament (IF) cytoskeleton to the plasma membrane of a variety of cell types, Previous studies demonstrated that the COOH terminus of the desmosomal plaque protein, desmoplakin (DP), is required for the association of DP with IF networks in cultured cells and that this domain interacts directly with type II epidermal keratin polypeptides in vitro. However, these studies left open the question of how desmosomes might anchor other IF types known to associate with these junctions. In this report we used yeast two-hybrid and in vitro dot blot assays to further examine the requirements for direct interactions between desmoplakin and various IF types. Our results confirm the ability of the DP COOH terminus (DPCT) to interact with at least two regions of the head domain of the type II epidermal keratin K1 and also demonstrate that DPCT can interact with the type III IF family members, vimentin and desmin, as well as simple epithelial keratins. Unlike the situation for type II epidermal keratins, the interaction between DPCT and simple epithelial keratins appears to depend on heterodimerization of the type I and II keratin polypeptides, since both are required to detect an interaction. Furthermore, although the interaction between DPCT and K1 requires the keratin head domain, deletion of this domain from the simple epithelial keratins does not compromise interaction with DPCT. The interaction between DPCT and type III or simple epithelial keratins also appeared to be less robust than that between DPCT and K1, In the case of K8/K18, however, the interaction as assessed by yeast two-hybrid assays increased 9-fold when a serine located in a protein kinase A consensus phosphorylation site 23 residues from the end of DP was altered to a glycine. Taken together, these data indicate that DP interacts directly with different IF types in specific ways. C1 UNIV CINCINNATI,COLL MED,DEPT ANAT CELL BIOL & NEUROBIOL,CINCINNATI,OH 45267. NORTHWESTERN UNIV,SCH MED,DEPT PATHOL,CHICAGO,IL 60611. NORTHWESTERN UNIV,SCH MED,DEPT DERMATOL,CHICAGO,IL 60611. NIAMS,SKIN BIOL LAB,NIH,BETHESDA,MD 20892. FU NIAMS NIH HHS [R01 AR35973, R01 AR43380] NR 54 TC 118 Z9 118 U1 0 U2 5 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD AUG 22 PY 1997 VL 272 IS 34 BP 21495 EP 21503 DI 10.1074/jbc.272.34.21495 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA XR789 UT WOS:A1997XR78900078 PM 9261168 ER PT J AU Wijkander, J Holst, LS Rahn, T Resjo, S Castan, I Manganiello, V Belfrage, P Degerman, E AF Wijkander, J Holst, LS Rahn, T Resjo, S Castan, I Manganiello, V Belfrage, P Degerman, E TI Regulation of protein kinase B in rat adipocytes by insulin, vanadate, and peroxovanadate - Membrane translocation in response to peroxovanadate SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID MOLECULAR-CLONING; PHOSPHATIDYLINOSITOL 3,4,5-TRISPHOSPHATE; GLUCOSE-TRANSPORT; SER/THR KINASE; AKT; HOMOLOGY; DOMAIN; PHOSPHORYLATION; ACTIVATION; 3-KINASE AB Protein kinase B (PKB) (also referred to as RAC/Akt kinase) has been shown to be controlled by various growth factors, including insulin, using cell lines and transfected cells, However, information is so far scarce regarding its regulation in primary insulin-responsive cells, We have therefore used isolated rat adipocytes to examine the mechanisms, including membrane translocation, whereby insulin and the insulin-mimicking agents vanadate and peroxovanadate control PKB. Stimulation of adipocytes with insulin, vanadate, or peroxovanadate caused decreased PKB mobility on sodium dodecyl sulfate-polyacrylamide gels, indicative of increased phosphorylation, which correlated with an increase in kinase activity detected with the peptide KKRNRTLTK. This peptide was found to detect activated PKB selectively in crude cytosol and partially purified cytosol fractions from insulin-stimulated adipocytes. The decrease in electrophoretic mobility and activation of PKB induced by insulin was reversed both in vitro by treatment of the enzyme with alkaline phosphatase and in the intact adipocyte upon removal of insulin or addition of the phosphatidylinositol 3-kinase (PI I-kinase) inhibitor wortmannin. Significant translocation of PKB to membranes could not Its demonstrated after insulin stimulation, but peroxovanadate, which appeared to activate PI 3-kinase to a higher extent than insulin, induced substantial translocation, The translocation was prevented by wortmannin, suggesting that PI 3-kinase and/or the 3-phosphorylated phosphoinositides generated by PI 3-kinase are indeed involved in the membrane targeting of PKB. C1 NHLBI,NIH,BETHESDA,MD 20892. RP Wijkander, J (reprint author), LUND UNIV,DEPT CELL & MOL BIOL,SECT MOL SIGNALING,POB 94,S-22100 LUND,SWEDEN. NR 40 TC 72 Z9 74 U1 0 U2 1 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD AUG 22 PY 1997 VL 272 IS 34 BP 21520 EP 21526 DI 10.1074/jbc.272.34.21520 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA XR789 UT WOS:A1997XR78900081 PM 9261171 ER PT J AU Mouton, PR Price, DL Walker, LC AF Mouton, PR Price, DL Walker, LC TI Empirical assessment of synapse numbers in primate neocortex SO JOURNAL OF NEUROSCIENCE METHODS LA English DT Article DE Cavalieri principle; optical disector; unbiased stereology; synapses; synaptophysin; neocortex ID ALZHEIMERS-DISEASE; MACAQUE MONKEY; FRONTAL-CORTEX; VISUAL-CORTEX; AGED RATS; DENSITY; NEURONS; SYNAPTOPHYSIN; DEMENTIA; VESICLES AB Reliable methods are needed to assess the impact of synaptic loss on brain function. In this empirical study we demonstrate a novel and efficient method using immunocytochemistry (ICC) and modern stereological techniques to quantify synapses in neocortex of adult primates (Macaca fascicularis). Systematic-uniform-random sections through forebrain from two 10-year-old monkeys were immunostained for estimation of synaptophysin-immunoreactive (synaptophysin-IR) presynaptic boutons (synapses). Adjacent sections were stained with cresyl violet for estimation of total number of neuronal cell bodies. The unbiased Cavalieri method was used to estimate total forebrain and neocortical volumes to a high level of precision (coefficient of error (CE)less than or equal to 0.10)). Synapse-to-neuron ratios varied from 860 in frontal cortex to 2300 in parietal-temporal cortex. The combination of Cavalieri and optical disector methods provided a direct means of estimating approximate to 1.25 trillion (x10(12)) total synaptophysin-immunopositive boutons and approximate to 1.01 billion (x10(9)) cell bodies in neocortex, with low CEs (0.12). Time required to make precise estimates of total neocortical and forebrain volumes and total numbers of synapses and neurons in neocortex was approximate to 2-3 h per case from stained sections. The approach is a direct and efficient technique to quantify total synapse and neuron numbers within a defined brain structure. (C) 1997 Elsevier Science B.V. C1 JOHNS HOPKINS UNIV,SCH MED,NEUROPATHOL LAB,BALTIMORE,MD 21205. JOHNS HOPKINS UNIV,SCH MED,DEPT NEUROL & NEUROSCI,BALTIMORE,MD 21205. NIA,GERONTOL RES CTR,BALTIMORE,MD 21224. WARNER LAMBERT PARKE DAVIS,PARKE DAVIS PHARMACEUT RES,ANN ARBOR,MI 48105. RP Mouton, PR (reprint author), JOHNS HOPKINS UNIV,SCH MED,DEPT PATHOL,558 ROSS RES BLDG,BALTIMORE,MD 21205, USA. RI Walker, L/J-6541-2015 OI Walker, L/0000-0001-9166-3261 FU NIA NIH HHS [AG 05146]; NINDS NIH HHS [NS 07179, NS 20471] NR 42 TC 27 Z9 27 U1 2 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-0270 J9 J NEUROSCI METH JI J. Neurosci. Methods PD AUG 22 PY 1997 VL 75 IS 2 BP 119 EP 126 DI 10.1016/S0165-0270(97)00058-7 PG 8 WC Biochemical Research Methods; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA XU681 UT WOS:A1997XU68100002 PM 9288643 ER PT J AU Stocking, EM Schwarz, JN Senn, H Salzmann, M Silks, LA AF Stocking, EM Schwarz, JN Senn, H Salzmann, M Silks, LA TI Synthesis of L-selenocystine, L-[Se-77]selenocystine and L-tellurocystine SO JOURNAL OF THE CHEMICAL SOCIETY-PERKIN TRANSACTIONS 1 LA English DT Article ID MAGNETIC-RESONANCE SPECTROSCOPY; SE-77 NMR-SPECTROSCOPY; DISPOSED CHIRAL CENTERS; DIHYDROFOLATE-REDUCTASE; AMINO-ACIDS; ESCHERICHIA-COLI; OXAZOLIDINE-2-SELONES; PROTEINS; TELLUROMETHIONINE; SELENOSUBTILISIN AB Synthetic routes for the synthesis of stable isotope labelled amino acids which contain either a selenium or a tellurium atom have been explored. L-Selenocystine, L-[Se-77]selenocystine and L-tellurocystine have been constructed in four steps from commercially available methyl (2S)-2-[(tert-butoxycarbonyl)amino]-3-hydroxypropionate. The sequence of reactions has been successfully scaled up giving significant quantities of the chalcogen based amino acids in fair to good overall yield. C1 NIH NATL STABLE ISOTOPE RESOURCE,LOS ALAMOS NATL LAB,LOS ALAMOS,NM 87545. HOFFMANN LA ROCHE AG,PHARMA RES NEW TECHNOL,CH-4002 BASEL,SWITZERLAND. NR 34 TC 45 Z9 46 U1 1 U2 6 PU ROYAL SOC CHEMISTRY PI CAMBRIDGE PA THOMAS GRAHAM HOUSE, SCIENCE PARK, MILTON ROAD, CAMBRIDGE, CAMBS, ENGLAND CB4 4WF SN 0300-922X J9 J CHEM SOC PERK T 1 JI J. Chem. Soc.-Perkin Trans. 1 PD AUG 21 PY 1997 IS 16 BP 2443 EP 2447 DI 10.1039/a600180g PG 5 WC Chemistry, Organic SC Chemistry GA XR712 UT WOS:A1997XR71200028 ER PT J AU Chinnaiyan, AM Chaudhary, D ORourke, K Koonin, EV Dixit, VM AF Chinnaiyan, AM Chaudhary, D ORourke, K Koonin, EV Dixit, VM TI Role of CED-4 in the activation of CED-3 SO NATURE LA English DT Letter ID PHOTOAFFINITY C1 NIH,NATL CTR BIOTECHNOL INFORMAT,NATL LIB MED,BETHESDA,MD 20894. GENENTECH INC,SAN FRANCISCO,CA 94080. RP Chinnaiyan, AM (reprint author), UNIV MICHIGAN,SCH MED,DEPT PATHOL,1301 CATHERINE ST,BOX 0602,ANN ARBOR,MI 48109, USA. RI dixit, vishva/A-4496-2012 OI dixit, vishva/0000-0001-6983-0326 NR 13 TC 149 Z9 157 U1 0 U2 3 PU MACMILLAN MAGAZINES LTD PI LONDON PA PORTERS SOUTH, 4 CRINAN ST, LONDON, ENGLAND N1 9XW SN 0028-0836 J9 NATURE JI Nature PD AUG 21 PY 1997 VL 388 IS 6644 BP 728 EP 729 DI 10.1038/41913 PG 2 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA XR667 UT WOS:A1997XR66700033 PM 9285582 ER PT J AU Wilson, PWF Hoeg, JM DAgostino, RB Silbershatz, H Belanger, AM Poehlmann, H OLeary, D Wolf, PA AF Wilson, PWF Hoeg, JM DAgostino, RB Silbershatz, H Belanger, AM Poehlmann, H OLeary, D Wolf, PA TI Cumulative effects of high cholesterol levels, high blood pressure, and cigarette smoking on carotid stenosis SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID CORONARY HEART-DISEASE; ARTERY WALL THICKNESS; ELEVATED SERUM-CHOLESTEROL; RISK FACTOR; FAMILIAL HYPERCHOLESTEROLEMIA; CARDIOVASCULAR HEALTH; ATHEROSCLEROSIS RISK; OLDER PERSONS; FRAMINGHAM; LIPOPROTEIN AB Background Single measurements of cardiovascular risk factors may not accurately reflect a person's past exposure to those risk factors. We therefore studied the long-term associations of cardiovascular risk factors such as high serum cholesterol levels, high blood pressure, and cigarette smoking with the prevalence of carotid stenosis. Methods We studied cross-sectional and longitudinal information from a sample of 429 men and 661 women in the Framingham Heart Study who underwent B-mode ultrasound measurements of the carotid artery. Their mean age was 75 years, and each had attended most of the biennial clinic examinations over the 34 years before the carotid ultrasound study. We used time-integrated measurements to assess the associations between various cardiovascular risk factors and the degree of carotid stenosis. Results Moderate carotid stenosis (greater than or equal to 25 percent) was present in 189 men and 226 women. We assessed the odds ratios for this degree of stenosis as compared with minimal stenosis (<25 percent) according to increases in risk factors. In the men, the odds ratio for moderate carotid stenosis associated with an increase of 20 mm Hg in systolic blood pressure was 2.11 (95 percent confidence interval, 1.51 to 2.97). The odds ratio for an increase of 10 mg per deciliter (0.26 mmol per liter) in the cholesterol level was 1.10 (95 percent confidence interval, 1.03 to 1.16), and for an increase of five pack-years of smoking it was 1.03 (95 percent confidence interval, 1.03 to 1.13). The results were similar in the women. Time-integrated measurements of diastolic blood pressure showed significant associations with carotid stenosis in men and insignificant associations in women. Conclusions Over the long term, high systolic blood pressure, high cholesterol levels, and smoking were associated with an increased risk of carotid stenosis in this elderly population. (C) 1997, Massachusetts Medical Society. C1 NHLBI, BETHESDA, MD 20892 USA. BOSTON UNIV, DEPT MATH, BOSTON, MA 02215 USA. BOSTON UNIV, SCH MED, DEPT NEUROL, BOSTON, MA 02118 USA. TUFTS UNIV, MED CTR, DEPT RADIOL, MEDFORD, MA 02155 USA. RP Wilson, PWF (reprint author), NHLBI, FRAMINGHAM HEART STUDY, 5 THURBER ST, FRAMINGHAM, MA 01701 USA. FU NHLBI NIH HHS [N01-HC-38038]; NINDS NIH HHS [5R01-NS17950] NR 46 TC 166 Z9 172 U1 2 U2 4 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 EI 1533-4406 J9 NEW ENGL J MED JI N. Engl. J. Med. PD AUG 21 PY 1997 VL 337 IS 8 BP 516 EP 522 DI 10.1056/NEJM199708213370802 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA XR548 UT WOS:A1997XR54800002 PM 9262494 ER PT J AU Rabkin, CS Janz, S Zhuang, ZP AF Rabkin, CS Janz, S Zhuang, ZP TI Clonality in Kaposi's sarcoma - reply SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Letter ID HISTIOCYTOSIS; DISEASE RP Rabkin, CS (reprint author), NCI,ROCKVILLE,MD 20892, USA. NR 5 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 AUG 21 PY 1997 VL 337 IS 8 BP 571 EP 572 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA XR548 UT WOS:A1997XR54800023 ER PT J AU Tucker, MA Hartge, P Halpern, A Elder, DE Gerry, D Clark, WH Holly, EA Sagebiel, RW AF Tucker, MA Hartge, P Halpern, A Elder, DE Gerry, D Clark, WH Holly, EA Sagebiel, RW TI Differentiating dysplastic nevi from melanoma - Reply SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Letter C1 UNIV PENN,SCH MED,PHILADELPHIA,PA 19104. UNIV CALIF SAN FRANCISCO,SAN FRANCISCO,CA 94143. RP Tucker, MA (reprint author), NIH,BLDG 10,BETHESDA,MD 20892, USA. RI Tucker, Margaret/B-4297-2015 NR 2 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 AUG 20 PY 1997 VL 278 IS 7 BP 548 EP 549 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA XQ986 UT WOS:A1997XQ98600020 ER PT J AU Hildesheim, A Anderson, LM Chen, CJ Cheng, YJ Brinton, LA Daly, AK Reed, CD Chen, IH Caporaso, NE Hsu, MM Chen, JY Idle, JR Hoover, RN Yang, CS Chhabra, SK AF Hildesheim, A Anderson, LM Chen, CJ Cheng, YJ Brinton, LA Daly, AK Reed, CD Chen, IH Caporaso, NE Hsu, MM Chen, JY Idle, JR Hoover, RN Yang, CS Chhabra, SK TI CYP2E1 genetic polymorphisms and risk of nasopharyngeal carcinoma in Taiwan SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID EPSTEIN-BARR-VIRUS; VOLATILE NITROSAMINE LEVELS; RESPIRATORY NASAL-MUCOSA; CIGARETTE-SMOKING; UNITED-STATES; LUNG-CANCER; HUMAN CYTOCHROME-P450IIE1; 5'-FLANKING REGION; SALTED FISH; METABOLISM AB Background: Nasopharyngeal carcinoma occurs disproportionately among individuals of Chinese descent. The cytochrome P450 2E1 enzyme (CYP2E1) is known to activate nitrosamines and other carcinogens that are possibly involved in the development of this disease. Certain alleles of the CYP2E1 gene are thought to be more highly expressed than others, and their distribution varies between Asian and Caucasian populations. We conducted a case-control study to investigate whether such variations affect the risk of developing nasopharyngeal cancer. Methods: Three hundred sixty-four patients with nasopharyngeal carcinoma (96% of 378 eligible patients) and 320 control subjects (86% of 374 eligible subjects) were studied. A risk factor questionnaire was administered to participants to assess factors postulated to be linked to nasopharyngeal carcinoma, Peripheral blood was obtained from all subjects and DNA was purified from nucleated cells. A polymerase chain reaction-based restriction fragment length polymorphism assay that used the restriction enzymes Rsa I and Dra I was used to detect wild-type and variant forms of the CYP2E1 gene. Results: Individuals homozygous for an allele of the CYPSE1 gene that is detected by Rsa I digestion (c2 allele) were found to have an increased risk of nasopharyngeal carcinoma (relative risk [RR] 2.6; 95% confidence interval [CI] 1.2-5.7); this effect was limited to nonsmokers (RR = 9.3; 95% CI = 2.7-32) and was not affected by alcohol consumption, Conclusions: Our findings suggest that the CYP2E1 genotype is a determinant of nasopharyngeal carcinoma risk. C1 NATL CANC INST,DIV CANC EPIDEMIOL & GENET,BETHESDA,MD. NCI,COMPARAT CARCINOGENESIS LAB,FREDERICK CANC RES & DEV CTR,FREDERICK,MD 21702. NATL TAIWAN UNIV,COLL PUBL HLTH,INST EPIDEMIOL,TAIPEI 10764,TAIWAN. NATL TAIWAN UNIV,COLL MED,INST MICROBIOL,TAIPEI 10764,TAIWAN. GENOTYPE LTD,NEWCASTLE TYNE,TYNE & WEAR,ENGLAND. MCKAY MEM HOSP,DEPT OTOLARYNGOL,TAIPEI,TAIWAN. NATL TAIWAN UNIV HOSP,DEPT OTOLARYNGOL,TAIPEI,TAIWAN. RI Chen, Chien-Jen/C-6976-2008; Daly, Ann/H-3144-2011; Chen, Jen-Yang/D-2085-2010; Brinton, Louise/G-7486-2015; OI Daly, Ann/0000-0002-7321-0629; Brinton, Louise/0000-0003-3853-8562; Idle, Jeff/0000-0002-6143-1520 NR 47 TC 129 Z9 140 U1 1 U2 2 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 AUG 20 PY 1997 VL 89 IS 16 BP 1207 EP 1212 DI 10.1093/jnci/89.16.1207 PG 6 WC Oncology SC Oncology GA XR149 UT WOS:A1997XR14900009 PM 9274915 ER PT J AU Weiderpass, E Gridley, G Nyren, O Ekbom, A Persson, I Adami, HO AF Weiderpass, E Gridley, G Nyren, O Ekbom, A Persson, I Adami, HO TI Diabetes mellitus and risk of large bowel cancer - Response SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Letter C1 UNIV HOSP,DEPT CANC EPIDEMIOL,UPPSALA,SWEDEN. NATL CANC INST,DIV CANC EPIDEMIOL & GENET,BETHESDA,MD. HARVARD UNIV,SCH PUBL HLTH,DEPT EPIDEMIOL,BOSTON,MA 02115. RI Weiderpass, Elisabete/M-4029-2016 OI Weiderpass, Elisabete/0000-0003-2237-0128 NR 3 TC 1 Z9 1 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 AUG 20 PY 1997 VL 89 IS 16 BP 1232 EP 1233 PG 2 WC Oncology SC Oncology GA XR149 UT WOS:A1997XR14900015 ER PT J AU Sakaguchi, K Sakamoto, H Lewis, MS Anderson, CW Erickson, JW Appella, E Xie, D AF Sakaguchi, K Sakamoto, H Lewis, MS Anderson, CW Erickson, JW Appella, E Xie, D TI Phosphorylation of serine 392 stabilizes the tetramer formation of tumor suppressor protein p53 SO BIOCHEMISTRY LA English DT Article ID DNA-BINDING FUNCTION; CELL-CYCLE CHECKPOINTS; CASEIN KINASE-II; OLIGOMERIZATION DOMAIN; STRUCTURAL STABILITY; CALORIMETER; SEQUENCES; ACTIVATE; REGIONS; MUTANTS AB Tumor suppressor protein p53 is a tetrameric phosphoprotein that activates transcription from several cell cycle regulating genes in response to DNA damage. Tetramer formation is critical to p53's ability to activate transcription; however, posttranslational modifications and protein stabilization also contribute to p53's ability to activate transcription. To determine if phosphorylation affects tetramer formation, we synthesized phosphopeptides corresponding to residues 303-393 of human p53, which includes the domain responsible for tetramer formation, Phosphate was chemically incorporated at Ser315, Ser378, or Ser392 and also at both Ser315 and Ser392. Equilibrium ultracentrifugal analyses showed that phosphorylation at Ser392 increased the association constant for reversible tetramer formation nearly 10-fold. Phosphorylation of either Ser315 or Ser378 had little effect on tetramer formation, but phosphorylation of Ser315 largely reversed the effect of phosphorylation at Ser392. Analyses by calorimetry demonstrated that phosphorylation may influence subunit affinity (and, in turn, DNA binding) by an enthalpy-driven process, possibly between the C-terminal residues and the region immediately adjacent to Ser315. The K-d for the tetramer-monomer transition of the unphosphorylated p53 C-terminal domain was determined to be similar to 1-10 mu M. Thus, in normal, undamaged cells p53 may be largely monomeric. Enhancement of tetramer formation through phosphorylation of Ser392, coupled with a DNA-damage-induced increase in its nuclear concentration, could provide a switch that activates p53 as a transcription factor in response to DNA damage. C1 NIH,NATL CTR RES RESOURCES,BIOMED ENGN & INSTRUMENTAT PROGRAM,BETHESDA,MD 20892. BROOKHAVEN NATL LAB,UPTON,NY 11973. NCI,FREDERICK CANC RES & DEV CTR,STRUCT BIOCHEM PROGRAM,FREDERICK,MD 21702. RP Sakaguchi, K (reprint author), NCI,CELL BIOL LAB,NIH,BLDG 37,BETHESDA,MD 20892, USA. RI Sakamoto, Hiroshi/A-3181-2011 NR 47 TC 194 Z9 196 U1 2 U2 8 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD AUG 19 PY 1997 VL 36 IS 33 BP 10117 EP 10124 DI 10.1021/bi970759w PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA XR735 UT WOS:A1997XR73500019 PM 9254608 ER PT J AU Kiefe, CI Williams, OD Bild, DE Lewis, CE Hilner, JE Oberman, A AF Kiefe, CI Williams, OD Bild, DE Lewis, CE Hilner, JE Oberman, A TI Regional disparities in the incidence of elevated blood pressure among young adults - The CARDIA study SO CIRCULATION LA English DT Article DE blood pressure; epidemiology; risk factors; hypertension; prevention ID 15-YEAR FOLLOW-UP; UNITED-STATES; POPULATION; MORTALITY; AGE; HYPERTENSION; HEALTH; WOMEN; MEN AB Background Within the United States, little is known about regional disparities in blood pressure (BP), their changes over time. or explanations for their existence. Methods and Results A population-based cohort of 5115 black and white men and women, 18 to 30 years old in 1985-1986 (balanced on age, race, sex, and education), was followed up for 7 years in four centers: Birmingham, Ala; Chicago, III; Minneapolis, Minn; and Oakland, Calif. Differences in elevated BP (EBP) prevalence among centers at years 0, 2, 5, and 7 and in 7-year incidence of EBP were assessed. Sociodemographic and dietary variables, physical activity, weight, smoking and alcohol were considered. Ar year 0, no regional differences were seen. Seven years later, there was marked variability in prevalence of EBP overall and fur both black and white men, from a low in Chicago (9% for black men and 5% for white men) to a high in Birmingham (25% for black men and 14% for white men). Birmingham also had the highest 7-year incidence (11%) and overall prevalence at year 7 (14%). The adjusted odds ratios, with Birmingham as referent (95% CIs), for 7-year incidence of EBP overall were 0.38 (0.24, 0.60) for Chicago, 0.37 (0.24, 0.57) for Minneapolis, and 0.74 (0.52, 1.07) for Oakland. Conclusions Regional disparities are absent at baseline but become apparent as the cohort ages. These differences are not fully explained by the available behavioral and sociodemographic characteristics. C1 BIRMINGHAM VA MED CTR,BIRMINGHAM,AL. NHLBI,NIH,BETHESDA,MD 20892. RP Kiefe, CI (reprint author), UNIV ALABAMA,DIV PREVENT MED,1717 11TH AVE S,MT 700,BIRMINGHAM,AL 35205, USA. FU NHLBI NIH HHS [N01-HC-48047, N01-HC-48048, N01-HC-48049] NR 35 TC 22 Z9 23 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 AUG 19 PY 1997 VL 96 IS 4 BP 1082 EP 1088 PG 7 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA XR082 UT WOS:A1997XR08200008 PM 9286933 ER PT J AU Folsom, AR Wu, KK Rosamond, WD Sharrett, AR Chambless, LE AF Folsom, AR Wu, KK Rosamond, WD Sharrett, AR Chambless, LE TI Prospective study of hemostatic factors and incidence of coronary heart disease - The Atherosclerosis Risk in Communities (ARIC) Study SO CIRCULATION LA English DT Article DE coagulation; coronary disease; von Willebrand factor; fibrinogen; leukocytes ID VON-WILLEBRAND-FACTOR; IMPROVED LIPOLYTIC EFFICIENCY; BLOOD-CELL COUNT; MYOCARDIAL-INFARCTION; CARDIOVASCULAR-DISEASE; FACTOR-VII; ENZYMATIC DETERMINATION; VASCULAR-DISEASE; HEALTHY-MEN; FIBRINOGEN AB Background Although hemostatic factors contribute to acute coronary syndromes and atherogenesis, few studies have prospectively evaluated the association between multiple hemostatic factors and coronary heart disease incidence, Methods and Results The atherosclerosis Risk in Communities Study recruited 14 477 adults from 45 to 64 years of age who were initially free of coronary heart disease. Coronary disease risk factors and several plasma hemostatic factors were measured, and incidence of coronary heart disease was ascertained during an average follow-up of 5.2 years. Age-, race-, and field center-adjusted relative risks of coronary heart disease were significantly elevated (P less than or equal to.05) per higher value of fibrinogen (relative risk: men, 1.76; women, 1.54), white blood cell count (men, 1.68; women, 2.23), factor VIII coagulant activity (women, 1.25), and van Willebrand factor antigen (men, 1.20, women, 1.18). Adjustment for other risk factors attenuated these associations for fibrinogen (adjusted relative risk: men, 1.48; women, 1.21), and it eliminated the white blood cell count, factor VIII, and von Willebrand factor associations, consistent with the other risk factors either confounding or partly operating through their effects on the hemostatic variables. Adjusted standardized relative risks of total mortality, ranging from 1.13 to 1.37, were also elevated (P<.05) in relation to these four factors. There was no association of coronary disease incidence with factor VII, protein C, antithrombin III, or platelet count. Conclusions Elevated levels of fibrinogen, white blood cell count, factor VIII, and von Willebrand factor are risk factors and may play causative roles in coronary heart disease. However, their measurement in healthy adults appears to add little to prediction of coronary events beyond that of more established risk factors. C1 UNIV TEXAS,SCH MED,DIV HEMATOL,HOUSTON,TX. COLLABORAT STUDIES COORDINATING CTR,CHAPEL HILL,NC. NHLBI,NIH,BETHESDA,MD 20892. RP Folsom, AR (reprint author), UNIV MINNESOTA,SCH PUBL HLTH,DIV EPIDEMIOL,SUITE 300,1300 S 2ND ST,MINNEAPOLIS,MN 55454, USA. RI Wu, Kenneth Kun-Yu/B-1070-2010 FU NHLBI NIH HHS [N01-HC-55015, N01-HC-55016, N01-HC-55018] NR 43 TC 549 Z9 564 U1 1 U2 6 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD AUG 19 PY 1997 VL 96 IS 4 BP 1102 EP 1108 PG 7 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA XR082 UT WOS:A1997XR08200011 PM 9286936 ER PT J AU Wagner, PD Steeg, PS Vu, ND AF Wagner, PD Steeg, PS Vu, ND TI Two-component kinase-like activity of nm23 correlates with its motility-suppressing activity SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID NUCLEOSIDE-DIPHOSPHATE KINASE; 2-COMPONENT REGULATORS; DROSOPHILA GENE; MELANOMA-CELLS; GROWTH ARREST; PROTEIN; PHOSPHORYLATION; PRUNE; EXPRESSION; PRODUCT AB Nm23 genes, which encode nucleoside diphosphate kinases, have been implicated in suppressing tumor metastasis. The motility of human breast carcinoma cells can be suppressed by transfection with wild-type nm23-H1, but not by transfections with two nm23-H1 mutants, nm23-N1(S120G) and nm23-H1(P96S). Here we report that nm23-H1 can transfer a phosphate from its catalytic histidine to aspartate or glutamate residues on 43-kDa membrane proteins, One of the 43-kDa membrane proteins was not phosphorylated by either nm23-H1(P96S) or nm23-H1(S120G), and another was phosphorylated much more slowly by nm23-H1(P96S) and by nm23-H1(S120G) than by wild-type nm23-H1. Nm23-H1 also can transfer phosphate from its catalytic histidine to histidines on ATP-citrate lyase and succinic thiokinase. The rates of phosphorylation of ATP-citrate lyase by nm23-H1(S120G) and nm23-H1(P96S) were similar to that by wild-type nm23-H1. The rate of phosphorylation of succinic thiokinase by nm23-H1(S120) was similar to that by mild-type nm23-H1, and the rate of phosphorylation of succinic thiokinase by nm23-H1(P96S) mas about half that by wild-type nm23-H1. Thus, the transfer of phosphate from nm23-H1 to aspartates or glutamates on other proteins appeals to correlate better with the suppression of motility than does the transfer to histidines. C1 NCI,DIV CLIN SCI,PATHOL LAB,WOMENS CANC SECT,BETHESDA,MD 20892. RP Wagner, PD (reprint author), NCI,BIOCHEM LAB,DIV BASIC SCI,BLDG 37,ROOM 4C24,BETHESDA,MD 20892, USA. NR 36 TC 102 Z9 105 U1 0 U2 5 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD AUG 19 PY 1997 VL 94 IS 17 BP 9000 EP 9005 DI 10.1073/pnas.94.17.9000 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA XR765 UT WOS:A1997XR76500018 PM 9256424 ER PT J AU Gnarra, JR Ward, JM Porter, FD Wagner, JR Devor, DE Grinberg, A EmmertBuck, MR Westphal, H Klausner, RD Linehan, WM AF Gnarra, JR Ward, JM Porter, FD Wagner, JR Devor, DE Grinberg, A EmmertBuck, MR Westphal, H Klausner, RD Linehan, WM TI Defective placental vasculogenesis causes embryonic lethality in VHL-deficient mice SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID ENDOTHELIAL GROWTH-FACTOR; TUMOR-SUPPRESSOR PROTEIN; HYPOXIA; GENE; IDENTIFICATION; TRANSCRIPTION; ANGIOGENESIS; ELONGATION AB Inheritance of an inactivated form of the VHL tumor suppressor gene predisposes patients to develop von Hippel-Lindau disease, and somatic VHL inactivation is an early genetic event leading to the development of sporadic renal cell carcinoma, The VHL gene was disrupted by targeted homologous recombination in murine embryonic stem cells, and a mouse line containing an inactivated VHL allele was generated, While heterozygous VHL (+/-) mice appeared phenotypically normal, VHL -/- mice died in utero at 10.5 to 12.5 days of gestation (E10.5 to E12.5). Homozygous VHL -/- embryos appeared to develop normally until E9.5 to E10.5, when placental dysgenesis developed, Embryonic vasculogenesis of the placenta failed to occur in VHL -/- mice, and hemorrhagic lesions developed in the placenta, Subsequent hemorrhage in VHL -/- embryos caused necrosis and death, These results indicate that VHL expression is critical for normal extraembryonic vascular development. C1 NCI,UROL ONCOL BRANCH,DIV CLIN SCI,BETHESDA,MD 20892. NCI,PATHOL LAB,BETHESDA,MD 20892. NCI,OFF DIRECTOR,BETHESDA,MD 20892. NCI,VET & TUMOR PATHOL SECT,OFF LAB ANIM SCI,BETHESDA,MD 20892. NICHHD,LAB MAMMALIAN GENES & DEV,BETHESDA,MD 20892. NR 29 TC 232 Z9 236 U1 1 U2 2 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD AUG 19 PY 1997 VL 94 IS 17 BP 9102 EP 9107 DI 10.1073/pnas.94.17.9102 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA XR765 UT WOS:A1997XR76500036 PM 9256442 ER PT J AU Duesbery, NS Choi, TS Brown, KD Wood, KW Resau, J Fukasawa, K Cleveland, DW VandeWoude, GF AF Duesbery, NS Choi, TS Brown, KD Wood, KW Resau, J Fukasawa, K Cleveland, DW VandeWoude, GF TI CENP-E is an essential kinetochore motor in maturing oocytes and is masked during Mos-dependent, cell cycle arrest at metaphase II SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID PROTO-ONCOGENE PRODUCT; MAP KINASE KINASE; XENOPUS-OOCYTES; PARTHENOGENETIC ACTIVATION; PROTOONCOGENE PRODUCT; MEIOTIC MATURATION; MOUSE OOCYTES; FREE-EXTRACTS; EGGS; ANAPHASE AB CENP-E, a kinesin-like protein that is known to associate with kinetochores during all phases of mitotic chromosome movement, is shown here to be a component of meiotic kinetochores as well, CENP-E is detected at kinetochores during metaphase I in both mice and frogs, and, as in mitosis, is relocalized to the midbody during telophase, CENP-E function is essential for meiosis I because injection of an antibody to CENP-E into mouse oocytes in prophase completely prevented progression of those oocytes past metaphase I, Beyond this, CENP-E is modified or masked during the natural, Mos-dependent, cell cycle arrest that occurs at metaphase II, although it is readily detectable at the kinetochores in metaphase II oocytes derived from mos-deficient (MOS-/-) mice that fail to arrest at metaphase II, This must reflect a masking of some CENP-E epitopes, not the absence of CENP-E, in meiosis II because a different polyclonal antibody raised to the tail of CENP-E detects CENP-E at kinetochores of metaphase II-arrested eggs and because CENP-E reappears in telophase of mouse oocytes activated in the absence of protein synthesis. C1 NCI,FREDERICK CANC RES & DEV CTR,ABL BASIC RES PROGRAM,FREDERICK,MD 21702. JOHNS HOPKINS UNIV,SCH MED,DEPT BIOL CHEM,BALTIMORE,MD 21205. UNIV CALIF SAN DIEGO,LA JOLLA,CA 92093. LUDWIG INST CANC RES,LA JOLLA,CA 92093. OI DUESBERY, NICK/0000-0002-4258-5655 FU NIGMS NIH HHS [GM 29513, R01 GM029513, R37 GM029513] NR 53 TC 45 Z9 45 U1 0 U2 4 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD AUG 19 PY 1997 VL 94 IS 17 BP 9165 EP 9170 DI 10.1073/pnas.94.17.9165 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA XR765 UT WOS:A1997XR76500047 PM 9256453 ER PT J AU Alimzhanov, MB Kuprash, DV KoscoVilbois, MH Luz, A Turetskaya, RL Tarakhovsky, A Rajewsky, K Nedospasov, SA Pfeffer, K AF Alimzhanov, MB Kuprash, DV KoscoVilbois, MH Luz, A Turetskaya, RL Tarakhovsky, A Rajewsky, K Nedospasov, SA Pfeffer, K TI Abnormal development of secondary lymphoid tissues in lymphotoxin beta-deficient mice SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID TUMOR-NECROSIS-FACTOR; FACTOR TNF-ALPHA; HUMAN B-CELLS; GERMINAL-CENTERS; T-CELL; RECEPTOR; EXPRESSION; MOUSE; GENE; MONOCYTOGENES AB The tumor necrosis factor (TNF) family cytokines lymphotoxin (LT) alpha and LT beta form heterotrimers that are expressed on the surface of activated lymphocytes and natural killer cells; LT alpha homotrimers can be secreted as well, Mice with a disrupted LT alpha gene lack lymph nodes (LN), Fever's patches (PP), and follicular dendritic cell (FDC) networks and reveal profound defects of the splenic architecture, However, it is unclear which of these abnormalities is the result of the absence in LT alpha homotrimers or LT alpha beta heterotrimers. To distinguish between these two possibilities, a mouse strain deficient in LT beta was created employing Cre/loxP-mediated gene targeting, Mice deficient in LT beta reveal severe defects in organogenesis of the lymphoid system similar to those of LT alpha(-/-)mice, except that mesenteric and cervical LN are present in most LT beta-deficient mice, Both LT alpha- and LT alpha-deficient mice show significant lymphocytosis in the circulation and peritoneal cavity and lymphocytic infiltrations in lungs and liver. After immunization, PNA-positive B cell clusters were detected in the splenic white pulp of LT beta-deficient mice, but FDC networks were severely underdeveloped, Collectively, these results indicate that LT alpha can signal independently from LT beta in the formation of PNA-positive foci in the spleen, and especially in the development of mesenteric and cervical LN. C1 TECH UNIV MUNICH, INST MED MICROBIOL IMMUNOL & HYG, D-81675 MUNICH, GERMANY. NCI, FREDERICK CANC RES & DEV CTR, MOL IMMUNOREGULAT LAB, DIV BASIC SCI, FREDERICK, MD 21702 USA. NCI, FREDERICK CANC RES & DEV CTR, INTRAMURAL RES SUPPORT PROGRAM, SCI APPLICAT INT CORP FREDERICK, FREDERICK, MD 21702 USA. GLAXO WELLCOME RES & DEV LTD, GENEVA BIOMED RES INST, CH-1228 GENEVA, SWITZERLAND. GESELL STRAHLEN & UMWELTFORSCH MBH, INST PATHOL, NATL RES CTR ENVIRONM & HLTH, D-85758 OBERSCHLEISSHEIM, GERMANY. UNIV COLOGNE, INST GENET, D-50931 COLOGNE, GERMANY. VA ENGELHARDT MOL BIOL INST, MOSCOW 117984, RUSSIA. BELOZERSKY INST PHYSICOCHEM BIOL, MOSCOW 117984, RUSSIA. RI Nedospasov, Sergei/J-5936-2013; Nedospasov, Sergei/L-1990-2015; Kuprash, Dmitry/O-4899-2015; Nedospasov, Sergei/Q-7319-2016 OI Kuprash, Dmitry/0000-0002-1488-4148; NR 43 TC 266 Z9 267 U1 1 U2 4 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 AUG 19 PY 1997 VL 94 IS 17 BP 9302 EP 9307 DI 10.1073/pnas.94.17.9302 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA XR765 UT WOS:A1997XR76500071 PM 9256477 ER PT J AU Panda, D Kundu, GC Lee, BI Peri, A Fohl, D Chackalaparampil, I Mukherjee, BB Li, XD Mukherjee, DC Seides, S Rosenberg, J Stark, K Mukherjee, AB AF Panda, D Kundu, GC Lee, BI Peri, A Fohl, D Chackalaparampil, I Mukherjee, BB Li, XD Mukherjee, DC Seides, S Rosenberg, J Stark, K Mukherjee, AB TI Potential roles of osteopontin and alpha(v)beta(3) integrin in the development of coronary artery restenosis after angioplasty SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID SMOOTH-MUSCLE CELLS; HUMAN ATHEROSCLEROTIC PLAQUES; MESSENGER-RNA; IN-VITRO; EXPRESSION; PROTEINS; INVITRO; GENE; PHOSPHOPROTEINS; PROLIFERATION AB Angioplasty procedures are increasingly used to reestablish blood flow in blocked atherosclerotic coronary arteries, 4 serious complication of these procedures is reocclusion (restenosis), which occurs in 30-50% of patients. Migration of coronary artery smooth muscle cells (CASMCs) to the site of injury caused by angioplasty and subsequent proliferation are suggested mechanisms of reocclusion. Using both cultured human CASMCs and coronary atherectomy tissues, we studied the roles of osteopontin (OPN) and one of its receptors, alpha(v) beta(3) integrin, in the pathogenesis of coronary restenosis. We also measured the plasma levels of OPN before and after angioplasty and determined the effect of exogenous OPN an CASMC migration, extracellular matrix invasion, and proliferation. We found that cultured CASMCs during log phase of growth and smooth muscle cell layer of the coronary atherosclerotic tissues of patients express both OPN mRNA and protein at a significantly elevated level compared with controls, Interestingly, whereas the baseline plasma OPN levels in control samples were virtually undetectable, those in patient plasma were remarkably high, We also found that interaction of OPN with alpha(v) beta(3) integrin, expressed on CASMCs, causes migration, extracellular matrix invasion, and proliferation, These effects were abolished when OPN or alpha(v) beta(3) integrin gene expression in CASMCs was inhibited bg specific antisense S-oligonucleotide treatment or OPN-alpha(v) beta(3) interaction was blocked by treatment of CASMCs with antibodies against OPN or alpha(v) beta(3) integrin, Our results demonstrate that OPN and alpha(v) beta(3) integrin play critical roles in regulating cellular functions deemed essential for restenosis. In addition, these results raise the possibility that transient inhibition of OPN gene expression or blocking of OPN-alpha(v) beta(3) interaction may provide a therapeutic approach to preventing restenosis. C1 NCI,SECT DEV GENET,HERITABLE DISORDERS BRANCH,NIH,BETHESDA,MD 20892. WASHINGTON HOSP CTR,CARDIOL ASSOCIATES,WASHINGTON,DC 20010. MEDLANTIC RES FDN,WASHINGTON,DC 20010. MCGILL UNIV,DEPT BIOL,MONTREAL,PQ H3A 1B1,CANADA. NR 36 TC 141 Z9 157 U1 1 U2 2 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD AUG 19 PY 1997 VL 94 IS 17 BP 9308 EP 9313 DI 10.1073/pnas.94.17.9308 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA XR765 UT WOS:A1997XR76500072 PM 9256478 ER PT J AU Cordelier, P Esteve, JP Bousquet, C Delesque, N OCarroll, AM Schally, AV Vaysse, N Susini, C Buscail, L AF Cordelier, P Esteve, JP Bousquet, C Delesque, N OCarroll, AM Schally, AV Vaysse, N Susini, C Buscail, L TI Characterization of the antiproliferative signal mediated by the somatostatin receptor subtype sst5 SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE cyclic GMP; cholecystokinin receptor; mitogen-activated protein kinase; somatostatin analogue RC-160; decreased cell growth ID ACTIVATED PROTEIN-KINASE; PANCREATIC ACINAR-CELLS; HUMAN-COLON CANCER; TYROSINE PHOSPHATASE; ANALOG RC-160; IN-VIVO; GROWTH; PROLIFERATION; RAT; INHIBITION AB We investigated cell proliferation modulated by cholecystokinin (CCK) and somatostatin analogue RC-160 in CHO cells bearing endogenous CCKA receptors and stably transfected by human subtype sst5 somatostatin receptor, CCK stimulated cell proliferation of CHO cells, This effect was suppressed by inhibitor of the soluble guanylate cyclase, LY 83583, the inhibitor of the cGMP dependent kinases, KT 5823, and the inhibitor of mitogen-activated protein (MAP) kinase kinase, PD 98059, CCK treatment induced an increase of intracellular cGMP concentrations, but concomitant addition of LY 83583 virtually suppressed this increase, CCK also activated both phosphorylation and activity of p42-MAP kinase; these effects were inhibited by KT 5823. All the effects of CCK depended on a pertussis toxin-dependent G protein. Somatostatin analogue RC-160 inhibited CCK-induced stimulation of cell proliferation but it did not potentiate the suppressive effect of the inhibitors LY 83583 and KT 5823. RC-160 inhibited both CCK-induced intracellular cGMP formation as well as activation of p42-MAP kinase phosphorylation and activity, This inhibitory effect was observed at doses of RC-160 similar to those necessary to occupy the sst5 recombinant receptor and to inhibit CCK-induced cell proliferation, We conclude that, in CHO cells, the proliferation and the MAP kinase signaling cascade depend on a cGMP-dependent pathway, These effects are positively regulated by CCK and negatively influenced by RC-160. interacting through CCKA and sst5 receptors, respectively, These studies provide a characterization of the antiproliferative signal mediated by sst5 receptor. C1 CHU RANGUEIL,INST LOUIS BUGNARD,INSERM,U151,F-31403 TOULOUSE 04,FRANCE. NIMH,BETHESDA,MD 20892. TULANE UNIV,SCH MED,NEW ORLEANS,LA 70112. VET AFFAIRS MED CTR,NEW ORLEANS,LA 70112. RI Bousquet, Corinne/P-2917-2014; Cordelier, Pierre/D-1150-2014; OI Schally, Andrew/0000-0003-1273-6747 NR 37 TC 102 Z9 105 U1 0 U2 6 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD AUG 19 PY 1997 VL 94 IS 17 BP 9343 EP 9348 DI 10.1073/pnas.94.17.9343 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA XR765 UT WOS:A1997XR76500078 PM 9256484 ER PT J AU Bing, GY Wilson, B Hudson, P Jin, L Feng, ZH Zhang, WQ Bing, RJ Hong, JS AF Bing, GY Wilson, B Hudson, P Jin, L Feng, ZH Zhang, WQ Bing, RJ Hong, JS TI A single dose of kainic acid elevates the levels of enkephalins and activator protein-1 transcription factors in the hippocampus for up to 1 year SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID NORADRENERGIC-INDUCED EXPRESSION; C-FOS EXPRESSION; RAT HIPPOCAMPUS; NEUROPEPTIDE REGULATION; ELECTRICAL-STIMULATION; INDUCED SEIZURES; OPIOID-PEPTIDES; BRAIN; PROENKEPHALIN; LOCALIZATION AB Neuronal plasticity plays a very important role in brain adaptations to environmental stimuli, disease, and aging processes. The kainic acid model of temporal lobe epilepsy was used to study the long-term anatomical and biochemical changes in the hippocampus after seizures. Using Northern blot analysis, immunocytochemistry, and Western blot analysis, we have found a long-term elevation of the proconvulsive opioid peptide, enkephalin, in the rat hippocampus. We have also demonstrated that an activator protein-1 transcription factor, the 35-kDa fos-related antigen, can be induced and elevated for at least 1 year after kainate treatment. This study demonstrated that a single systemic injection of kainate produces almost permanent increases in the enkephalin and an activator protein-1 transcription factor, the 35-kDa fos-related antigen, in the rat hippocampus, and it is likely that these two events are closely associated with the molecular mechanisms of induction of long-lasting enhanced seizure susceptibility in the kainate-induced seizure model. The long-term expression of the proenkephalin mRNA and its peptides in the kainate-treated rat hippocampus also suggests an important role in the recurrent seizures of temporal lobe epilepsy. RP Bing, GY (reprint author), NIEHS,TOXICOL LAB,NEUROPHARMACOL SECT,NIH,POB 12233,MD F1-01,RES TRIANGLE PK,NC 27709, USA. RI bing, guoying/F-7084-2012; OI Bing, Guoying/0000-0003-0609-8152 NR 44 TC 54 Z9 55 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 AUG 19 PY 1997 VL 94 IS 17 BP 9422 EP 9427 DI 10.1073/pnas.94.17.9422 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA XR765 UT WOS:A1997XR76500092 PM 9256498 ER PT J AU Lachowicz, JE Sibley, DR AF Lachowicz, JE Sibley, DR TI Chimeric D-2/D-3 dopamine receptor coupling to adenylyl cyclase SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article ID HAMSTER OVARY CELLS; MOLECULAR-BIOLOGY; ANTIBODIES; DOMAINS AB We have sought to determine which area of the D-2 dopamine receptor's third intracellular loop contributes to G-protein coupling by constructing reciprocal chimeric D-2/D-3 receptors with fusion points near the center of the third intracellular loop. Both receptor chimeras were expressed equally well in Chinese Hamster Ovary (CHO) cells and exhibited ligand binding properties similar to those of the wild type receptors. Surprisingly, both of the D-2/D-3 receptor chimeras were able to effectively inhibit adenylyl cyclase activity to almost the same extent as that seen with the D-2 receptor whereas the D-3 receptor was without effect. These results suggest that the D-2 receptor possesses two redundant and independent domains for G-protein coupling and inhibition of adenylyl cyclase activity. (C) 1997 Academic Press. C1 NINCDS,MOL NEUROPHARMACOL SECT,EXPT THERAPEUT BRANCH,NIH,BETHESDA,MD 20892. NR 28 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 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD AUG 18 PY 1997 VL 237 IS 2 BP 394 EP 399 DI 10.1006/bbrc.1997.7146 PG 6 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA XT770 UT WOS:A1997XT77000036 PM 9268722 ER PT J AU Laezza, C Wolff, J Bifulco, M AF Laezza, C Wolff, J Bifulco, M TI Identification of a 48-kDa prenylated protein that associates with microtubules as 2',3'-cyclic nucleotide 3'-phosphodiesterase in FRTL-5 cells SO FEBS LETTERS LA English DT Article DE 2',3'-cyclic nucleotide 3'-phosphodiesterase; microtubule-associated proteins; prenylation; FRTL-5 thyroid cells ID MYELIN-ASSOCIATED ENZYME; CENTRAL-NERVOUS-SYSTEM; EPITHELIAL-CELLS; MAMMALIAN-CELLS; MEMBRANE; CYTOSKELETON; BRAIN; ORGANIZATION; MORPHOLOGY; TUBULIN AB In an effort to study the nature of tubulin attachment to membranes, we have previously observed that after blocking prenylation in FRTL-5 thyroid cells, the microtubules become disconnected from the plasma membrane region [Bifulco M. et al. (1983) J. Cell. Physiol. 155, 340-348]. In this study we show that several [H-3]mevalonate labeled proteins in FRTL-5 cells associate with membrane and cytoskeleton and, among these, we describe the presence of a 48-kDa prenylated protein, identified by immunoprecipitation as 2',3'-cyclic nucleotide 3'-phosphodiesterase (CNP), that associates with microtubules, This latter association persists through several polymerization/depolymerization cycles, whereas other prenylated proteins are lost, It is suggested that CNP can be a novel microtubule-associated protein (MAP) and a promising candidate as a membrane anchor for microtubules. (C) 1997 Federation of European Biochemical Societies. C1 UNIV NAPLES FEDERICO II,CNR,CEOS,I-80131 NAPLES,ITALY. UNIV NAPLES FEDERICO II,DIPARTIMENTO BIOL & PATOL CELLULARE & MOL L CALIF,I-80131 NAPLES,ITALY. UNIV REGGIO CALABRIA,DIPARTIMENTO MED SPERIMENTALE & CLIN,I-88100 CATANZARO,ITALY. NIDDK,BIOCHEM PHARMACOL LAB,NIH,BETHESDA,MD 20892. OI Bifulco, Maurizio/0000-0002-1771-4531 NR 31 TC 33 Z9 33 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0014-5793 J9 FEBS LETT JI FEBS Lett. PD AUG 18 PY 1997 VL 413 IS 2 BP 260 EP 264 DI 10.1016/S0014-5793(97)00924-1 PG 5 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA XT085 UT WOS:A1997XT08500015 PM 9280293 ER PT J AU Gulnik, SV Suvorov, LI Majer, P Collins, J Kane, BP Johnson, DG Erickson, JW AF Gulnik, SV Suvorov, LI Majer, P Collins, J Kane, BP Johnson, DG Erickson, JW TI Design of sensitive fluorogenic substrates for human cathepsin D SO FEBS LETTERS LA English DT Article DE cathepsin D; fluorogenic substrate; structure-based modeling ID MOLECULES; PROTEASES; SEQUENCE; ENZYMES; FORMS; AMINO; CDNA; BETA AB Cathepsin D is a lysosomal aspartic proteinase that has been implicated in several pathological processes such as breast cancer and Alzheimer's disease, We designed and synthesized a number of quenched fluorogenic substrates with P2 variations in the series AcEE(EDANS)KPIXFFRLGK(DABCYL)E-NH2, where X=cysteine, methylcysteine, ethylcysteine, tert-butylcysteine, carboxymethylcysteine, methionine, valine or isoleucine, Most of the fluorogenic substrates exhibited greater k(cat)/K-m ratios than the best cathepsin D substrates described so far, Differences in kinetic constants, which were rationalized using structure-based modeling, might make certain substrates useful for particular applications, such as active site titrations or initial velocity determination using a fluorescent plate reader, (C) 1997 Federation of European Biochemical Societies. C1 NCI, FREDERICK CANC RES & DEV CTR, SAIC FREDERICK, AIDS VACCINE PROGRAM, FREDERICK, MD 21702 USA. RP Gulnik, SV (reprint author), NCI, FREDERICK CANC RES & DEV CTR,SAIC FREDERICK, STRUCT BIOCHEM PROGRAM,BLDG 322, POB B, FREDERICK, MD 21702 USA. NR 25 TC 43 Z9 44 U1 3 U2 7 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0014-5793 J9 FEBS LETT JI FEBS Lett. PD AUG 18 PY 1997 VL 413 IS 2 BP 379 EP 384 DI 10.1016/S0014-5793(97)00886-7 PG 6 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA XT085 UT WOS:A1997XT08500038 PM 9280316 ER PT J AU Bacik, I Snyder, HL Anton, LC Russ, G Chen, WS Bennink, JR Urge, L Otvos, L Dudkowska, B Eisenlohr, L Yewdell, JW AF Bacik, I Snyder, HL Anton, LC Russ, G Chen, WS Bennink, JR Urge, L Otvos, L Dudkowska, B Eisenlohr, L Yewdell, JW TI Introduction of a glycosylation site into a secreted protein provides evidence for an alternative antigen processing pathway: Transport of precursors of major histocompatability complex class I-restricted peptides from the endoplasmic reticulum to the cytosol SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article ID TOXIC LYMPHOCYTES-T; INFLUENZA HEMAGGLUTININ; CELL RECOGNITION; BINDING-SITE; TAP; MOLECULES; ICP47; DEGRADATION; SPECIFICITY; EXPRESSION AB We found that the presentation of a H-2K(d)-restricted determinant from influenza virus nucleoprotein (NP) to T cells is strictly dependent on expression of the transporter associated with antigen presentation (TAP), regardless of whether NP is expressed as a cytosolic or secreted NP (SNP). Introducing an N-linked glycosylation site into the determinant selectively reduced presentation of SNP. This indicates that glycosylation does not interfere with TAP-transported peptides, and therefore that cytosolic peptides derived from SNP must have been exposed to the glycosylation machinery of the endoplasmic reticulum (ER) before their existence in the cytosol. Based on these findings, we propose that TAP-dependent processing of at least some ER-targeted proteins entails the reimportation of protein from the secretory pathway to the cytosol where the protein is processed via the classical pathway. C1 NIAID,VIRAL DIS LAB,BETHESDA,MD 20892. WISTAR INST ANAT & BIOL,PHILADELPHIA,PA 19104. THOMAS JEFFERSON UNIV,JEFFERSON CANC INST,PHILADELPHIA,PA 19107. RI yewdell, jyewdell@nih.gov/A-1702-2012; Chen, Weisan/E-7828-2012; Anton, Luis/C-4740-2013 OI Anton, Luis/0000-0001-9665-011X FU NIAID NIH HHS [AI-36331, R01 AI036331] NR 42 TC 62 Z9 62 U1 0 U2 2 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 SN 0022-1007 J9 J EXP MED JI J. Exp. Med. PD AUG 18 PY 1997 VL 186 IS 4 BP 479 EP 487 DI 10.1084/jem.186.4.479 PG 9 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA XT787 UT WOS:A1997XT78700001 PM 9254646 ER PT J AU Harrison, EH Rojas, CJ Kempner, ES AF Harrison, EH Rojas, CJ Kempner, ES TI Size of the catalytically active unit of rat hepatic carboxylester lipase in the presence and absence of bile salt SO BIOCHIMICA ET BIOPHYSICA ACTA-LIPIDS AND LIPID METABOLISM LA English DT Article ID PANCREATIC CHOLESTEROL ESTERASE; PALMITATE HYDROLASE ACTIVITY; RADIATION INACTIVATION; MOLECULAR-WEIGHT; LIVER; CLONING; LYSOPHOSPHOLIPASE; BINDING; JUICE; CDNA AB Carboxylester lipase (GEL) catalyzes the hydrolysis of cholesteryl esters, retinyl esters, and triacylglycerols. CEL monomer has a MW of approximate to 70000. Hydrolysis of these esters is stimulated by: millimolar trihydroxy bile salts such as cholate, that also induce aggregation. Liver cytosols from 12 rats were frozen and irradiated at -135 degrees C with high energy electrons. In several experiments, paired samples of cytosol were adjusted to 20 mM cholate before irradiation. All samples were assayed for CEL using cholesteryl oleate as substrate. In untreated cytosols, CEL activity surviving radiation exposure could be fit to a single exponential function, the slope of which yielded a target size of 91 +/- 18 kDa. Tn a subset of these cytosols irradiated in the presence of cholate the calculated target size was 100 +/- 19 kDa, a value indistinguishable from that obtained for untreated cytosols. Some samples were also assayed using retinyl palmitate and triolein as substrates. With retinyl palmitate the mean target sizes were 96 and 108 kDa in the absence and presence of cholate, respectively, approximately the same as those observed when using cholesteryl oleate. When triolein was used as substrate the target sizes in the absence of cholate were smaller than for the other two esters (67 +/- 18 kDa) and closer to the known monomer molecular weight, but again cholate had no significant effect on this size. The structure responsible for CEL activity contains no more than one 70 000 MW monomer and the results show that cholate-induced oligomerization is not required for catalytic activity. (C) 1997 Elsevier Science B.V. C1 NIAMS, PHYS BIOL LAB, NIH, BETHESDA, MD USA. RP MED COLL PENN & HAHNEMANN UNIV, DEPT BIOCHEM, 2900 QUEEN LANE, PHILADELPHIA, PA 19129 USA. FU NIDDK NIH HHS [DK 44498, R01 DK044498] NR 21 TC 3 Z9 3 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0005-2760 J9 BBA-LIPID LIPID MET JI Biochim. Biophys. Acta-Lipids Lipid Metab. PD AUG 16 PY 1997 VL 1347 IS 2-3 BP 177 EP 182 DI 10.1016/S0005-2760(97)00052-0 PG 6 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA XU601 UT WOS:A1997XU60100006 PM 9295161 ER PT J AU Miller, MJ Yuan, BZ AF Miller, MJ Yuan, BZ TI Semiautomated resolution of overlapping stutter patterns in genomic microsatellite analysis SO ANALYTICAL BIOCHEMISTRY LA English DT Article ID DNA-POLYMERASE; MICRODISSECTION; POLYMORPHISMS; AMPLIFICATION AB Microsatellites are polymorphic, short nucleotide repeating units scattered more or less randomly throughout the genome, They are readily detectable by polymerase chain reaction (PCR) and often used as genomic markers. One problem in the analysis of microsatellite data is the appearance of secondary bands during PCR that result in extended banding patterns. These ''stutter'' patterns may overlap in heterozygous alleles and obscure the overall pattern, severely interfering with analysis. This paper develops a model that successfully predicts the general shape of stutter patterns, It then presents techniques for measuring the intensity of the individual contributing alleles, The model is based on the assumption that there is a certain probability of losing or gaining a microsatellite repeat unit during each PCR cycle, The effect is cumulative, with the chance of losing a repeat unit being much greater than that of gaining one, which leads to a gradual reduction in the mean length of the pattern with increased PCR cycles. This can be modeled quantitatively to predict the shape of the stutter pattern, a prediction borne out by experiment. Next, a least-squares technique is presented that is used to analyze the overlapping stutter patterns and determine the relative concentration of each microsatellite in heterozygous alleles. The technique is based on the observation that, at least for microsatellites of approximately the same length, the relative intensity of each band in the stutter pattern is approximately the same for each allele. The stutter shape is most easily determined from homozygous alleles. It can also be approximated from heterozygous samples if the difference between the lengths of the primary microsatellite bands can be determined. (C) 1997 Academic Press. RP Miller, MJ (reprint author), NCI,EXPT CARCINOGENESIS LAB,NIH,BLDG 37,RM 3C28,37 CONVENT DR,MSC4255,BETHESDA,MD 20892, USA. NR 17 TC 19 Z9 21 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 0003-2697 J9 ANAL BIOCHEM JI Anal. Biochem. PD AUG 15 PY 1997 VL 251 IS 1 BP 50 EP 56 DI 10.1006/abio.1997.2234 PG 7 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA XT972 UT WOS:A1997XT97200007 PM 9300082 ER PT J AU Basi, NS Rebois, RV AF Basi, NS Rebois, RV TI Rate zonal sedimentation of proteins in one hour or less SO ANALYTICAL BIOCHEMISTRY LA English DT Article ID PREPARATIVE ULTRA-CENTRIFUGE; STIMULATORY G-PROTEIN; ALPHA-SUBUNIT; REGULATORY COMPONENT; ADENYLATE-CYCLASE; ADP-RIBOSYLATION; MOLECULAR-WEIGHT; AUTOMATED-METHOD; GTP-BINDING; PURIFICATION AB Rate zonal sedimentation gives information about the shape and size of proteins, and is useful for investigating protein-protein interactions. However, rate zonal sedimentation experiments typically last approximately 1 day. In contrast, this report describes a rate zonal sedimentation method requiring 1 h or less. This was accomplished by centrifuging small density gradients (200 mu l) prepared with sucrose or OptiPrep in a fixed-angle rotor at high relative centrifugal force, By using small gradient volumes, the sample dilution that occurs with larger gradients and with many chromatographic techniques was also avoided. For a variety of proteins, plots of S-20,S-w versus distance sedimented during centrifugation in a TLA 120.2 rotor were linear, As a practical application, sedimentation of the heterotrimeric stimulatory G protein and its dissociated alpha-subunit were determined. The results were similar to those obtained with 17- to 22-h centrifugations in an SW 50.1 rotor and agreed with previously published values. Long periods of centrifugation might preclude the study of some unstable proteins or the investigation of protein-protein interactions whose affinities are to low to survive the lengthy centrifugations required to carry out traditional rate zonal sedimentation experiments, A rate zonal sedimentation technique that rivals many chromatographic methods in celerity will help to circumvent these problems. (C) 1997 Academic Press. C1 NINCDS,MOL & CELLULAR NEUROBIOL LAB,MEMBRANE BIOCHEM SECT,NIH,BETHESDA,MD 20892. NR 22 TC 4 Z9 4 U1 0 U2 2 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0003-2697 J9 ANAL BIOCHEM JI Anal. Biochem. PD AUG 15 PY 1997 VL 251 IS 1 BP 103 EP 109 DI 10.1006/abio.1997.2255 PG 7 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA XT972 UT WOS:A1997XT97200014 PM 9300089 ER PT J AU Moore, KA Sethi, R Doanes, AM Johnson, TM Pracyk, JB Kirby, M Irani, K GoldschmidtClermont, PJ Finkel, T AF Moore, KA Sethi, R Doanes, AM Johnson, TM Pracyk, JB Kirby, M Irani, K GoldschmidtClermont, PJ Finkel, T TI Rac1 is required for cell proliferation and G2/M progression SO BIOCHEMICAL JOURNAL LA English DT Article ID GTP-BINDING PROTEINS; RAS PROTEINS; TRANSFORMATION; ACTIVATION; GTPASES; CALCIUM; GROWTH; EMBRYO; GENE; RHO AB We have transiently expressed a dominant negative form of rad (N17rac1) using adenoviral-mediated gene transfer. The level of N17rac1 expression is demonstrated to be proportional to the multiplicity of infection. Expression of N17rac1 in Rat 2 fibroblasts results in cytostatic growth arrest. Cell-cycle analysis demonstrates that cells expressing N17rac1 accumulate in G2/M. These results suggest that rad is required for cell proliferation and provide the first demonstration in mammalian cells of a role for small GTP-binding proteins in the G2/M transition. C1 NHLBI,CARDIOL BRANCH,NATL INST HLTH,BETHESDA,MD 20892. NHLBI,HEMATOL BRANCH,BETHESDA,MD 20892. JOHNS HOPKINS UNIV HOSP,DIV CARDIOL,BALTIMORE,MD 21287. OHIO STATE UNIV,HEART & LUNG INST,COLUMBUS,OH 43210. NR 33 TC 57 Z9 57 U1 0 U2 1 PU PORTLAND PRESS PI LONDON PA 59 PORTLAND PLACE, LONDON, ENGLAND W1N 3AJ SN 0264-6021 J9 BIOCHEM J JI Biochem. J. PD AUG 15 PY 1997 VL 326 BP 17 EP 20 PN 1 PG 4 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA XR058 UT WOS:A1997XR05800002 PM 9337845 ER PT J AU Higley, JD Linnoila, M Mehlman, PT Taub, DM Poland, RE Suomi, SJ AF Higley, JD Linnoila, M Mehlman, PT Taub, DM Poland, RE Suomi, SJ TI Social dominance as a confounding factor in studies of primate aggression and serotonin - Response SO BIOLOGICAL PSYCHIATRY LA English DT Letter ID FLUID 5-HYDROXYINDOLEACETIC ACID; VERVET MONKEYS; AMINE METABOLITES; RHESUS-MONKEYS; BEHAVIOR; 5-HIAA C1 LAB ANIM BREEDERS & SERV,YEMASSEE,SC. HARBOR UCLA MED CTR,DIV BIO PSYCHIAT,TORRANCE,CA 90509. NICHHD,LAB COMPARAT ETIOL,NIH,ANIM CTR,POOLESVILLE,MD 20837. RP Higley, JD (reprint author), NIAAA,CLIN STUDIES LAB,DICBR,BETHESDA,MD 20892, USA. NR 23 TC 3 Z9 3 U1 1 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD AUG 15 PY 1997 VL 42 IS 4 BP 306 EP 307 PG 2 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA XM389 UT WOS:A1997XM38900013 ER PT J AU Huang, S Apasov, S Koshiba, M Sitkovsky, M AF Huang, S Apasov, S Koshiba, M Sitkovsky, M TI Role of A2a extracellular adenosine receptor-mediated signaling in adenosine-mediated inhibition of T-cell activation and expansion SO BLOOD LA English DT Article ID PYRIMIDINE STARVATION; DEAMINASE DEFICIENCY; LYMPHOCYTE; MONOPHOSPHATE; AGENTS; IMMUNODEFICIENCIES; ACCUMULATION; EXPRESSION; THYMOCYTES AB Accumulation of adenosine and of deoxyadenosine in the absence of adenosine deaminase activity (ADA) activity results in lymphocyte depletion and in severe combined immunodeficiency (ADA SCID), which is currently explained by direct cell death-causing effects of intracellular products of adenosine metabolism, We explored the alternative mechanisms of peripheral T-cell depletion as due to inhibition of T-cell expansion by extracellular adenosine mediated signaling through purinergic receptors, The strong inhibition of the T-cell receptor (TCR)-triggered proliferation and of upregulation of interleukin-2 receptor alpha chain (CD25) molecules, but not the direct lymphotoxicity, were observed at low concentrations of extracellular adenosine. These effects of extracellular adenosine (Ado) are likely to be mediated by A2a receptor-mediated signaling rather than by intracellular toxicity of adenosine catabolites, because (1) poorly metabolized adenosine analogs cause the accumulation of cAMP and strong inhibition of TCR-triggered CD25 upregulation; (2) the A2a, but not the A? or A3, receptors are the major expressed and functionally coupled adenosine receptors in mouse peripheral T and B lymphocytes, and the adenosine-induced cAMP accumulation in lymphocytes correlates with the expression of A2a receptors; (3) the specific agonist of A2a receptor, CGS21680, induces increases in [cAMP]i in lymphocytes, whereas the specific antagonist of A2a receptor, CSC, inhibits the effects of Ado and CGS21680; and (4) the increases in [cAMP]i mimic the adenosine-induced inhibition of TCR-triggered CD25 upregulation and splenocyte proliferation. These studies suggest the possible Pole of adenosine receptors in the regulation of lymphocyte expansion and point to the downregulation of A2a purinergic receptors on T cells as a potentially attractive pharmacologic target. (C) 1997 by The American Society of Hematology. C1 NIAID,IMMUNOL LAB,NIH,BETHESDA,MD 20892. NR 40 TC 258 Z9 266 U1 1 U2 6 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 AUG 15 PY 1997 VL 90 IS 4 BP 1600 EP 1610 PG 11 WC Hematology SC Hematology GA XR218 UT WOS:A1997XR21800029 PM 9269779 ER PT J AU Pant, AC Veeranna Pant, HC Amin, N AF Pant, AC Veeranna Pant, HC Amin, N TI Phosphorylation of human high molecular weight neurofilament protein (hNF-H) by neuronal cyclin-dependent kinase 5 (cdk5) SO BRAIN RESEARCH LA English DT Article DE hNF-H; cdk5; phosphorylation; SDS-PAGE; IPTG ID AMYOTROPHIC-LATERAL-SCLEROSIS; NF-H; INTERMEDIATE FILAMENTS; AXONAL-TRANSPORT; BOVINE BRAIN; MOUSE MODEL; SUBUNIT; GENE; RAT; IDENTIFICATION AB Neurofilaments (NFs), the neuron-specific intermediate (i.e. similar to 10-nm diameter) filaments are major cytoskeletal components of most neurons. In a mature mammalian neuron, NFs are co-assembled from three subunits, NF-L (low), NF-M (medium), and NF-H (high), with molecular masses of 68, 95, and 115 kDa, respectively. Neurofilament proteins (NF-Ps), particularly, NF-H, are most extensively phosphorylated in large myelinated axons under normal conditions. This phosphorylation occurs on the serine residues of the lysine (Lys)-serine (Ser)-proline (Pro) (KSP) multiple amino acid repeats of the carboxy-terminal tail domain. Phosphorylation of KSP motifs affects physical, biochemical, and immunological properties of NF-H. For example, phosphorylation is thought to play a pivotal role in the maintenance of the neuronal cytoskeletal structure which influences the conduction velocity of the nerve fiber. The key components responsible for phosphorylation are not known. In this study, an identified cyclin-dependent kinase 5 (cdk5), isolated from nervous tissue, has been shown to phosphorylate the human NF-H (hNF-H) and affects its electrophoretic mobility. On the basis of the following observations, it is suggested that neuronal cdk5 (cdk5) phosphorylates KSPXK motifs in the human high molecular weight neurofilament (hNF-H) and affects its electrophoretic mobility. (1) A 14-mer synthetic peptide (KSPEKAKSPVKEEA) derived from hNF-H; (2) a 0 bacterially expressed protein containing 14 KSPXK multiple repeats of hNF-H in C-terminal tail domain; and (3) a dephosphorylated hNF-H in neurofilament preparation are phosphorylated by cdk5. The decrease in molecular mass of hNF-H caused by dephosphorylation was completely recovered upon cdk5 phosphorylation. It is proposed that neuronal cdk5 regulates phosphorylation of the KSPXK motif in hNF-H and other cytoskeletal proteins with similar motifs in the nervous system. (C) 1997 Elsevier Science B.V. C1 NINCDS,NEUROCHEM LAB,NIH,BETHESDA,MD 20892. NHLBI,BIOCHEM GENET LAB,NIH,BETHESDA,MD 20892. NR 41 TC 57 Z9 57 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0006-8993 J9 BRAIN RES JI Brain Res. PD AUG 15 PY 1997 VL 765 IS 2 BP 259 EP 266 DI 10.1016/S0006-8993(97)00561-1 PG 8 WC Neurosciences SC Neurosciences & Neurology GA XV686 UT WOS:A1997XV68600009 PM 9313898 ER PT J AU Foster, BA Gingrich, JR Kwon, ED Madias, C Greenberg, NM AF Foster, BA Gingrich, JR Kwon, ED Madias, C Greenberg, NM TI Characterization of prostatic epithelial cell lines derived from transgenic adenocarcinoma of the mouse prostate (TRAMP) model SO CANCER RESEARCH LA English DT Article ID EXPRESSION; CANCER; GENE; P53 AB To develop a syngeneic transplantable system to study immunotherapeutic approaches for the treatment of prostate cancer, three cell lines were established from a heterogeneous 32 week tumor of the transgenic adenocarcinoma mouse prostate (TRAMP) model, TRAMP is a transgenic line of C57BL/6 mice harboring a construct comprised of the minimal -426/+28 rat probasin promoter driving prostate-specific epithelial expression of the SV40 large T antigen, TRAMP males develop histological prostatic intraepithelial neoplasia by 8-12 weeks of age that progress to adenocarcinoma with distant metastases by 24-30 weeks of age. The three cell lines (TRAMP-C1, TRAMP-C2, and TRAMP-C3) express cytokeratin, E-cadherin, and androgen receptor by immunohistochemical analysis and do not appear to have a mutated p53. Although TRAMP-C1 and TRAMP-C2 are tumorigenic when grafted into syngeneic C57BL/6 hosts, TRAMP-C3 grows readily in vitro but does not form tumors, The T antigen oncoprotein is not expressed by the cell lines in vitro or in vivo. The rationale for establishing multiple cell lines was to isolate cells representing various stages of cellular transformation and progression to androgen-independent metastatic disease that could be manipulated in vitro and, in combination with the TRAMP model, provide a system to investigate therapeutic interventions, such as immunotherapy prior to clinical trials. C1 BAYLOR COLL MED,DEPT CELL BIOL,HOUSTON,TX 77030. BAYLOR COLL MED,DEPT UROL,HOUSTON,TX 77030. NHLBI,KIDNEY & ELECTROLYTE METAB LAB,NIH,BETHESDA,MD 20892. FU NCI NIH HHS [CA58204, CA64851] NR 19 TC 295 Z9 301 U1 1 U2 7 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 AUG 15 PY 1997 VL 57 IS 16 BP 3325 EP 3330 PG 6 WC Oncology SC Oncology GA XQ995 UT WOS:A1997XQ99500002 PM 9269988 ER PT J AU Gerhauser, C Lee, SK Kosmeder, JW Moriarty, RM Hamel, E Mehta, RG Moon, RC Pezzuto, JM AF Gerhauser, C Lee, SK Kosmeder, JW Moriarty, RM Hamel, E Mehta, RG Moon, RC Pezzuto, JM TI Regulation of ornithine decarboxylase induction by deguelin, a natural product cancer chemopreventive agent SO CANCER RESEARCH LA English DT Article ID PROTEIN-KINASE-C; TRANSCRIPTIONAL REGULATION; NORDIHYDROGUAIARETIC ACID; TRANSGENIC MICE; IN-VITRO; GENE; INHIBITION; CELLS; MYC; RESPIRATION AB Deguelin, a plant-derived rotenoid, mediates potent chemopreventive responses through transcriptional regulation of phorbol ester-induced ornithine decarboxylase (ODC) activity. To explore the mechanism of this effect, the activity of this compound was evaluated with a number of model systems, Using cultured mouse epidermal 308 cells, the steady-state levels of both 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced ODC mRNA and c-fos were decreased by treatment with deguelin, ODC activity was also inhibited by bullatacin and various antimitotic agents (podophyllotoxin, vinblastine, and colchicine), but only deguelin and bullatacin were active as inhibitors of ODC levels in a TPA-independent c-Myc-mediated induction system using cultured BALB/c c-MycER cells, These results suggest that antimicrotubule effects, as mediated by rotenone, for example, are not responsible for inhibitory activity facilitated by deguelin, This was confirmed by use of an in vitro model of tubulin polymerization in which deguelin and a variety of other rotenoids were investigated and found to be inactive. As anticipated, however, NADH dehydrogenase was inhibited by these rotenoids. Moreover, inhibition of this enzyme correlated with a rapid depletion of ATP levels and potential to inhibit either TPA-or c-Myc-induced ODC activity, It therefore seems that deguelin-mediated interference with transient requirements for elevated energy can inhibit the induction of ODC activity and thereby yield a cancer chemo-preventive response. C1 UNIV ILLINOIS,COLL PHARM,DEPT MED CHEM & PHARMACOGNOSY,CHICAGO,IL 60612. UNIV ILLINOIS,COLL LIBERAL ARTS & SCI,DEPT CHEM,CHICAGO,IL 60612. UNIV ILLINOIS,COLL MED,DEPT SURG ONCOL,CHICAGO,IL 60612. NCI,LAB DRUG DISCOVERY RES & DEV,DEV THERAPEUT PROGRAM,FREDERICK CANC RES & DEV CTR,FREDERICK,MD 21702. FU NCI NIH HHS [P01 CA48112] NR 51 TC 64 Z9 68 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 AUG 15 PY 1997 VL 57 IS 16 BP 3429 EP 3435 PG 7 WC Oncology SC Oncology GA XQ995 UT WOS:A1997XQ99500023 PM 9270009 ER PT J AU Sargent, LM Dragan, YP Sattler, G Xu, YH Wiley, J Pitot, HC AF Sargent, LM Dragan, YP Sattler, G Xu, YH Wiley, J Pitot, HC TI Specific chromosomal changes in albumin simian virus 40 T antigen transgenic rat liver neoplasms SO CANCER RESEARCH LA English DT Article ID GROWTH-FACTOR-II; PRIMARY HEPATOCELLULAR-CARCINOMA; TUMOR-CELL LINE; FREQUENT LOSS; WILMS-TUMOR; IGF-II; HETEROZYGOSITY; MICE; HEPATOBLASTOMA; TUMORIGENESIS AB Hepatocytes isolated from 3-month-old female rats bearing the albumin promoter/enhancer SV40 T antigen construct as a transgene demonstrated a 20% aneuploidy rate and a significant duplication of chromosome 1. Other chromosome changes were observed but were not statistically significant. At this time in the development of hepatic lesions, only a relatively small number of microscopic altered hepatic foci could be noted. By contrast, hepatocytes isolated from the age-matched nontransgenic controls demonstrated only 1% aneuploidy. One hundred % of the metaphase spreads isolated from hepatocellular neoplasms in transgenic rats were aneuploid. Although there were many random changes, 70% of the neoplastic cells demonstrated an amplification of all or portions of chromosome 1q. Only 2% of the neoplastic cells had both a trisomy and a duplication. The smallest region of chromosome 1 that was duplicated was that between bands q3.7 and q4.3. A loss of chromosome 3 was detected in 50% of the neoplasms, as well as a loss of chromosome 6 in 72% of the neoplastic cells. The carcinomas with the highest proliferation rate had also lost at least one copy of chromosome 15 in 70% of the cells. The loss of chromosomes 3, 6, and 15 indicates that these regions may harbor one or more tumor suppressor genes. The amplification of a specific region of chromosome 1 is thus the first karyotypic alteration that can be identified in hepatocytes from livers from which hepatic neoplasms will arise. This indicates that expression or repression of one or more genes in this region may confer a growth advantage to preneoplastic hepatocytes, facilitating their transit to the neoplastic state in the stage of progression. Changes in chromosomes 3, 6, and 15 that occur subsequent to duplication of the q3.7-q4.3 region of chromosome 1 are changes possibly reflecting alteration of tumor suppressor genes with further enhancement of neoplastic growth. C1 UNIV WISCONSIN,SCH MED,MCARDLE LAB CANC RES,MADISON,WI 53706. NCI,CARCINOGENESIS LAB,BETHESDA,MD 20284. E CAROLINA UNIV,GREENVILLE,NC. FU NCI NIH HHS [CA-45700, CA-07175, CA-22484] NR 54 TC 21 Z9 21 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 AUG 15 PY 1997 VL 57 IS 16 BP 3451 EP 3456 PG 6 WC Oncology SC Oncology GA XQ995 UT WOS:A1997XQ99500026 PM 9270012 ER PT J AU Stillwell, WG Kidd, LCR Wishnok, JS Tannenbaum, SR Sinha, R AF Stillwell, WG Kidd, LCR Wishnok, JS Tannenbaum, SR Sinha, R TI Urinary excretion of unmetabolized and phase II conjugates of 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine and 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline in humans: Relationship to cytochrome P4501A2 and N-acetyltransferase activity SO CANCER RESEARCH LA English DT Article ID FOOD-DERIVED MUTAGEN; HETEROCYCLIC AROMATIC-AMINES; HUMAN-LIVER-MICROSOMES; CARCINOGEN 2-AMINO-3,8-DIMETHYLIMIDAZO<4,5-F>QUINOXALINE; METABOLIC-ACTIVATION; PHIP; MEAT; RAT; CHROMATOGRAPHY; PHENOTYPES AB Cooking meat, fish, or poultry at high temperature gives rise to heterocyclic aromatic amines (HAAs), which may be metabolically activated to mutagenic or carcinogenic intermediates, The enzymes cytochrome P4501A2 (CYP1A2) and N-acetyltransferase (NAT2) are principally implicated in such biotransformations. We have determined the relationship between the activity of these two enzymes and the urinary excretion of unmetabolized and Phase II conjugates of the two HAAs MeIQx (2-amino3,8-dimethylimidazo[4,5-f]quinoxaline) and PhIP (2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine) in individuals fed a uniform diet containing high-temperature cooked meat, The subjects in the study ate meat containing known amounts of MeIQx and PhIP, and urine collections were made 0-12 and 12-24 h after a meal. MeIQx and PhIP were measured in urine after acid treatment that quantitatively hydrolyzes the Phase II conjugates to the respective parent amine, The extracts containing the HAAs mere purified by immunoaffinity chromatography and analyzed by liquid chromatography using electrospray ionization-tandem mass spectrometry, The MeIQx content in the 0-12 h urine increased after acid hydrolysis by a factor of 3-21-fold, After acid treatment, the total amount of MeIQx (unmetabolized plus the N-2-glucuronide and sulfamate metabolites) excreted in the 0-12 h urine was 10.5 +/- 3.5% (mean a SD) of the dose, whereas the total amount of PhIP [unmetabolized plus acid-labile conjugate(s)] in the 0-12 h period was 4.3 +/- 1.7% (mean +/- SD) of the dose, The total amount of PhIP in the 12-24 h urine after acid treatment was 0.9 +/- 0.4% (mean +/- SD) of the dose, Linear regression analysis of the amounts of MeIQx and PhIP excreted in the 0-12 h period expressed as a percentage of the ingested dose, for all subjects, gave a low but significant correlation (r = 0.37, P = 0.005), Linear regression analyses showed that lower total MeIQx (unmetabolized plus the N-2-glucuronide and sulfamate metabolites) in urine was associated with higher CYP1A2 activity, whereas total PhIP (unmetabolized plus conjugated) in urine showed no association to CYP1A2 activity, These results indicate that in humans, MeIQx metabolism and disposition are more strongly influenced by CYP1A2 activity than are those of PhIP, Linear regression analysis found no association between NAT2 activity and the levels (unmetabolized plus acid-labile conjugates) of MeIQx or PhIP excreted in urine. C1 MIT,DEPT CHEM,CAMBRIDGE,MA 02139. NATL CANC INST,NUTR EPIDEMIOL BRANCH,DIV CANC EPIDEMIOL & GENET,NIH,ROCKVILLE,MD 20892. RP Stillwell, WG (reprint author), MIT,DIV TOXICOL,ROOM 56-731A,77 MASSACHUSETTS AVE,CAMBRIDGE,MA 02139, USA. RI Wishnok, John/A-3173-2009; Sinha, Rashmi/G-7446-2015 OI Sinha, Rashmi/0000-0002-2466-7462 FU NIEHS NIH HHS [ES05622] NR 32 TC 69 Z9 72 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA PUBLIC LEDGER BLDG, SUITE 816, 150 S. INDEPENDENCE MALL W., PHILADELPHIA, PA 19106 SN 0008-5472 J9 CANCER RES JI Cancer Res. PD AUG 15 PY 1997 VL 57 IS 16 BP 3457 EP 3464 PG 8 WC Oncology SC Oncology GA XQ995 UT WOS:A1997XQ99500027 PM 9270013 ER PT J AU Li, JJ Westergaard, C Ghosh, P Colburn, NH AF Li, JJ Westergaard, C Ghosh, P Colburn, NH TI Inhibitors of both nuclear factor-kappa Beta and activator protein-1 activation block the neoplastic transformation response SO CANCER RESEARCH LA English DT Article ID CELL-PROLIFERATION; EPIDERMAL-CELLS; RETINOIC ACID; INTACT-CELLS; JB6 CELLS; B-ALPHA; C-JUN; AP-1; PROMOTER; TRANSCRIPTION AB Cross-coupling of active protein-1 (AP-1) and nuclear factor (NF)-kappa B has been reported. In the present study, we investigated the possibility that both of these two transcription factors might contribute to the process of tumor promoter-induced transformation. To establish a stable reporter cell system, two reporter genes were stably transfected into a JB6 mouse tumor promotion-sensitive (P+) cell line: a luciferase reporter controlled by a collagenase AP-1 sequence and a chloramphenicol acetyltransferase reporter controlled by an interleukin 6 NF-kappa B sequence. This double-reporter cell line maintained the phenotype of tumor promotion sensitivity and was able to report basal or induced AP-1 and NF-kappa B transactivation. The cytokine tumor promoter tumor necrosis factor (TNF)-alpha transactivated NF-kappa B and AP-1 for both DNA binding and transcriptional activity, Pyrrolidine dithiocarbamate, an antioxidant that acts as an NF-kappa B inhibitor, efficiently inhibited 12-O-tetradecanoylphorbol-13-acetate (TPA) or TNF-alpha induced NF-kappa B as well as AP-1 transactivation and cell transformation, suggesting dependency of transformation on both transcription factors, The AP-1 transrepressing-retinoid SR11302 transrepressed AP-1 and cell transformation when these were TPA induced but not when TNF-alpha induced, indicating different signaling pathways for TNF-alpha and TPA, Supershift electrophoresis mobility shift assay revealed that Jun B and c-Jun were absent from the AP-1/DNA complex following TNF-alpha but present following TPA treatment. Together, these results suggest that both AP-1 and NF-kappa B activation may be required for transformation whether induced by TPA or by TNF, and the differential sensitivity of TPA and TNF-alpha-induced transformation to inhibition by a retinoid might be explained by differences in the composition of the DNA-bound AP-1 complexes. C1 NCI,EXPT IMMUNOL LAB,FREDERICK CANC RES & DEV CTR,NIH,FREDERICK,MD 21701. RP Li, JJ (reprint author), NCI,GENE REGULAT PROGRAM,LAB BIOCHEM PHYSIOL,FREDERICK CANC RES & DEV CTR,NIH,POB B,BLDG 560,FREDERICK,MD 21701, USA. NR 50 TC 194 Z9 202 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 AUG 15 PY 1997 VL 57 IS 16 BP 3569 EP 3576 PG 8 WC Oncology SC Oncology GA XQ995 UT WOS:A1997XQ99500044 PM 9270030 ER PT J AU Jakubczak, JL Chisari, FV Merino, G AF Jakubczak, JL Chisari, FV Merino, G TI Synergy between transforming growth factor alpha and hepatitis B virus surface antigen in hepatocellular proliferation and carcinogenesis SO CANCER RESEARCH LA English DT Article ID LIVER EPITHELIAL-CELLS; TRANSGENIC MICE; TGF-ALPHA; RAT FIBROBLASTS; CARCINOMA; EXPRESSION; OVEREXPRESSION; HEPATOCARCINOGENESIS; HYPERPLASIA; TUMORS AB Chronic infection with hepatitis B virus (HBV) can cause liver cancer in humans, Transgenic mice expressing the major envelope protein of HBV, HBV surface antigen (HBsAg), represent an experimental model for some of the histopathological effects of infection in humans, including prolonged hepatocellular injury, necrosis, hyperplasia, and an elevated incidence of liver tumors, The regenerative hyperplastic response to the chronic liver damage is thought to be a critical factor in the increased risk of cancer, However, little is known about the cellular factors that mediate regenerative proliferation. One candidate is the hepatocyte mitogen transforming growth factor Lr (TGF-alpha); in HBV-infected patients with liver cancer, TGF-alpha and HBsAg accumulate in the same hepatocytes. Transgenic mice overexpressing TGF-a demonstrate enhanced hepatocyte proliferation rates and develop hepatocellular carcinomas, In this study, we have analyzed the effect of TGF-alpha and HBsAg coexpression in the liver using a bitransgenic mouse model. We show that hepatocytes harboring both the TGF-alpha and HBsAg transgenes exhibited an increase in growth relative to hepatocytes with either transgene alone, Furthermore, bitransgenic males but not females had a dramatically accelerated appearance of hepatocellular carcinomas, compared to single transgenic TGF-alpha or HBsAg litter-mates, These results demonstrate synergistic activity between HBsAg and TGF-alpha in the liver, probably by first stimulating quiescent hepatocytes to enter G(1) and by subsequently promoting their transit through the cell cycle, respectively. Moreover, our data support the contention that TGF-alpha participates in HBV-induced hepatocarcinogenesis in infected patients. C1 NCI, MOL GENET SECT, MOL BIOL LAB, NIH, BETHESDA, MD 20892 USA. Scripps Res Inst, DEPT MOL & EXPT MED, LA JOLLA, CA 92037 USA. RI Chisari, Francis/A-3086-2008; OI Chisari, Francis/0000-0002-4832-1044 NR 38 TC 25 Z9 25 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 AUG 15 PY 1997 VL 57 IS 16 BP 3606 EP 3611 PG 6 WC Oncology SC Oncology GA XQ995 UT WOS:A1997XQ99500049 PM 9270035 ER PT J AU Fuhrer, C Sugiyama, JE Taylor, RG Hall, ZW AF Fuhrer, C Sugiyama, JE Taylor, RG Hall, ZW TI Association of muscle-specific kinase MuSK with the acetylcholine receptor in mammalian muscle SO EMBO JOURNAL LA English DT Article DE acetylcholine receptor; agrin; muscle-specific kinase MuSK; neuromuscular junction; tyrosine phosphorylation ID DYSTROPHIN-ASSOCIATED PROTEINS; POSTSYNAPTIC 43-KDA PROTEIN; NERVE GROWTH-FACTOR; TYROSINE PHOSPHORYLATION; AGRIN RECEPTOR; NEUROMUSCULAR-JUNCTIONS; SIGNAL-TRANSDUCTION; CLUSTERING ACTIVITY; TRK PROTOONCOGENE; STAUROSPORINE AB During synaptogenesis at the neuromuscular junction, a neurally released factor, agrin, causes the clustering of acetylcholine receptors (AChRs) in the muscle membrane beneath the nerve terminal. Agrin acts through a specific receptor which is thought to have a receptor tyrosine kinase, MuSK, as one of its components. In agrin-treated muscle cells, both MuSK and the hChR become tyrosine phosphorylated, To determine how the activation of MuSK leads to AChR clustering, we have investigated their interaction in cultured C2 myotubes. Immunoprecipitation experiments showed that MuSK is associated with the AChR and that this association is increased by agrin treatment. Agrin also caused a transient activation of the AChR-associated MuSK, as demonstrated by MuSK phosphorylation, In agrin-treated myotubes, MuSK phosphorylation increased with the same time course as phosphorylation of the beta subunit of the AChR, but declined more quickly, Although both herbimycin and staurosporine blocked agrin-induced AChR phosphorylation, only herbimycin inhibited the phosphorylation of MuSK. These results suggest that although agrin increases the amount of activated MuSK that is associated with the AChR, MuSK is not directly responsible for AChR phosphorylation but acts through other kinases. C1 NIMH,SECT SYNAPT MECHANISMS,LAB CELLULAR & MOL REGULAT,NIH,BETHESDA,MD 20892. NR 65 TC 89 Z9 91 U1 0 U2 3 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD, ENGLAND OX2 6DP SN 0261-4189 J9 EMBO J JI Embo J. PD AUG 15 PY 1997 VL 16 IS 16 BP 4951 EP 4960 DI 10.1093/emboj/16.16.4951 PG 10 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA XT128 UT WOS:A1997XT12800016 PM 9305637 ER PT J AU Ginsburg, GT Kimmel, AR AF Ginsburg, GT Kimmel, AR TI Autonomous and nonautonomous regulation of axis formation by antagonistic signaling via 7-span cAMP receptors and GSK3 in Dictyostelium SO GENES & DEVELOPMENT LA English DT Article DE GSK3; development; PKA; gene expression; pattern formation ID GLYCOGEN-SYNTHASE KINASE-3; DEPENDENT PROTEIN-KINASE; CELL-CYCLE PHASE; GENE-EXPRESSION; EXTRACELLULAR CAMP; DISCOIDEUM; DIFFERENTIATION; PRESTALK; WINGLESS; PATHWAYS AB Early during Dictyostelium development a fundamental cell-fate decision establishes the anteroposterior (prestalk/prespore)! axis. Signaling via the 7-transmembrane cAMP receptor CAR4 is essential for creating and maintaining a normal pattern; car4-null alleles have decreased levels of prestalk-specific mRNAs but enhanced expression of prespore genes. car4(-) cells produce all of the signals required for prestalk differentiation but lack an extracellular factor necessary for prespore differentiation of wild-type cells. This secreted factor decreases the sensitivity of prespore cells to inhibition by the prestalk morphogen DIF-1. At the cell autonomous level, CAR4 is linked to intracellular circuits that activate prestalk but inhibit prespore differentiation. The autonomous action of CAR4 is antagonistic to the positive intracellular signals mediated by another cAMP receptor, CAR1 and/or CAR3. Additional data indicate that these CAR-mediated pathways converge at the serine/threonine protein kinase GSK3, suggesting that the anterior (prestalk)/posterior (prespore) axis of Dictyostelium is regulated by an ancient mechanism that is shared by the Wnt/Fz circuits for dorsoventral patterning during early Xenopus development and establishing Drosophila segment polarity. C1 NIDDKD,CELLULAR & DEV BIOL LAB,NIH,BETHESDA,MD 20892. NR 64 TC 37 Z9 43 U1 1 U2 3 PU COLD SPRING HARBOR LAB PRESS PI PLAINVIEW PA 1 BUNGTOWN RD, PLAINVIEW, NY 11724 SN 0890-9369 J9 GENE DEV JI Genes Dev. PD AUG 15 PY 1997 VL 11 IS 16 BP 2112 EP 2123 DI 10.1101/gad.11.16.2112 PG 12 WC Cell Biology; Developmental Biology; Genetics & Heredity SC Cell Biology; Developmental Biology; Genetics & Heredity GA XU172 UT WOS:A1997XU17200009 PM 9284050 ER PT J AU Shi, HP Shigeta, H Yang, NY Fu, K OBrian, G Teng, CT AF Shi, HP Shigeta, H Yang, NY Fu, K OBrian, G Teng, CT TI Human estrogen receptor-like 1 (ESRL1) gene: Genomic organization, chromosomal localization, and promoter characterization SO GENOMICS LA English DT Article ID VENTROMEDIAL HYPOTHALAMIC NUCLEUS; MOUSE LACTOFERRIN GENE; TRANSCRIPTION FACTOR; STEROIDOGENIC FACTOR-1; BINDING PROTEIN; XENOPUS-LAEVIS; ACTIVATION; EXPRESSION; BETA; ALPHA AB Estrogen receptor-like 1a (ESRL1a; same as estrogen receptor-related orphan receptors, ERR1) belongs to a subfamily of the nuclear receptor superfamily. We have previously shown that human ES-RL1a modulates estrogen responsiveness of the lactoferrin gene promoter in transiently transfected endometrial carcinoma RL95-2 cells. In this study, we cloned and characterized the human ESRL1 gene. Through the fluorescence in situ hybridization method, the ESRL1 gene was localized to the centromere region of chromosome 11q12. Partial sequencing, restriction mapping, and PCR analysis revealed that the ESRL1 gene consists of seven exons and is approximately 20 kb in length. We found that the smallest exon (exon 3) contains 117 bp and the largest exon (exon 7) has 1032 bp. The smallest intron (intron 5) is only 88 bp long and the largest intron (intron 2) is 8 kb long. All introns have the conserved GT and AG dinucleotides present at the donor and acceptor sites, respectively. Like the estrogen receptor, the highly conserved DNA-binding domain of hESRL1a is encoded by exon 2 and exon 3, and the intron/exon junctions (2 and 3) are well conserved between the two genes. Primer extension analysis revealed multiple transcription initiation start sites in human uterine (HeLa, HEC, and RL95-2) cell lines. However, one major initiation start site was found by RNase protection assay. The hESRL1a mRNA is differentially expressed in various human tissues. The nucleotide sequence adjacent to the transcription start sites of the ESRL1 lacks the typical TATA and CAAT boxes but is GC rich and contains 10 consensus Sp1-binding elements and two E boxes. The region that contains these transcription factor-binding elements showed a high level of promoter activity when transiently transfected into RL95-2 cells. (C) 1997 Academic Press. C1 NIEHS,GENE REGULAT GRP,REPROD & DEV TOXICOL LAB,NIH,RES TRIANGLE PK,NC 27709. NR 44 TC 29 Z9 32 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 AUG 15 PY 1997 VL 44 IS 1 BP 52 EP 60 DI 10.1006/geno.1997.4850 PG 9 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA XT456 UT WOS:A1997XT45600007 PM 9286700 ER PT J AU Heuckeroth, RO Kotzbauer, P Copeland, NG Gilbert, DJ Jenkins, NA Zimonjic, DB Popescu, NC Johnson, EM Milbrandt, J AF Heuckeroth, RO Kotzbauer, P Copeland, NG Gilbert, DJ Jenkins, NA Zimonjic, DB Popescu, NC Johnson, EM Milbrandt, J TI Neurturin, a novel neurotrophic factor, is localized to mouse chromosome 17 and human chromosome 19p13.3 SO GENOMICS LA English DT Article ID TYROSINE KINASE; MICE LACKING; RECEPTOR; GDNF; RET; PROTOONCOGENE AB Neurturin is a potent neurotrophic factor closely related to glial cell line-derived neurotrophic factor (GDNF, 40% amino acid sequence identity) and, like GDNF, can promote the survival of numerous neuronal populations including sympathetic, nodose, and dorsal root ganglion sensory neurons. Both neurturin and GDNF signal through the Bet tyrosine kinase and require a glycosylphosphatidylinositol-linked coreceptor. Mutations in Ret and GDNF cause intestinal aganglionosis and renal dysplasia. Activating Bet mutations also cause multiple endocrine neoplasia syndromes (MEN2A and MEN2B). We have isolated mouse and human genomic neurturin clones. The sequence for preproneurturin is encoded by two exons. Mouse and human clones have common intron/exon boundaries. We have used interspecific backcross analysis to localize neurturin to mouse chromosome 17 near the Vav locus and fluorescence in situ hybridization analysis to localize human neurturin to the syntenic region of human chromosome 19p13.3, (C) 1997 Academic Press. C1 WASHINGTON UNIV,SCH MED,DEPT PATHOL,DIV LAB MED,ST LOUIS,MO 63110. WASHINGTON UNIV,SCH MED,DEPT PEDIAT,ST LOUIS,MO 63110. WASHINGTON UNIV,SCH MED,DEPT INTERNAL MED,ST LOUIS,MO 63110. WASHINGTON UNIV,SCH MED,DEPT MOL BIOL & PHARMACOL,ST LOUIS,MO 63110. NCI,MAMMALIAN GENET LAB,ABL BASIC RES PROGRAM,FREDERICK CANC RES & DEV CTR,FREDERICK,MD 21702. NCI,BIOL LAB,NIH,BETHESDA,MD 20892. OI Heuckeroth, Robert/0000-0002-3282-1765 FU NIA NIH HHS [1 RO1 AG13730-01]; NICHD NIH HHS [KO8 HD0 1166-01] NR 13 TC 14 Z9 15 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 0888-7543 J9 GENOMICS JI Genomics PD AUG 15 PY 1997 VL 44 IS 1 BP 137 EP 140 DI 10.1006/geno.1997.4846 PG 4 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA XT456 UT WOS:A1997XT45600017 PM 9286710 ER PT J AU Yamashita, T Moriyama, K Sheng, HZ Westphal, H AF Yamashita, T Moriyama, K Sheng, HZ Westphal, H TI Lhx4, a LIM homeobox gene SO GENOMICS LA English DT Article ID NEUROENDOCRINE TISSUES; EXPRESSION; SYSTEM AB LIM homeobox genes are well conserved in evolution and play important roles as transcriptional regulators of embryonic development. Here we report on the structure of LIM domains of the mouse Lhx4 (Gsh4) gene, The cDNA was generated by modified reverse transcription-PCR from midgestation embryo templates, using a degenerate consensus primer. The deduced amino acid sequence of the first LIM domain reveals 77% identity and that of the second domain reveals 86% identity with the corresponding sequences of the closely related Lhx3 gene. In addition, there is 38-56% similarity to other members of the Lhx gene family. The LIM consensus sequence is well conserved in Lhx4. (C) 1997 Academic Press. C1 NICHHD,LAB MAMMALIAN GENES & DEV,NIH,BETHESDA,MD 20892. SHIMANE MED UNIV,DEPT ANAT,IZUMO,SHIMANE 693,JAPAN. NR 9 TC 19 Z9 21 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0888-7543 J9 GENOMICS JI Genomics PD AUG 15 PY 1997 VL 44 IS 1 BP 144 EP 146 DI 10.1006/geno.1997.4852 PG 3 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA XT456 UT WOS:A1997XT45600019 PM 9286712 ER PT J AU Gail, MH Tan, WY Pee, D Goedert, JJ AF Gail, MH Tan, WY Pee, D Goedert, JJ TI Survival after AIDS diagnosis in a cohort of hemophilia patients SO JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES AND HUMAN RETROVIROLOGY LA English DT Article DE mortality; prognosis; hemophilia; survival ID STAGING SYSTEM; HIV-INFECTION; PATTERNS AB We studied factors affecting survival after the diagnosis of AIDS in a cohort of 1253 patients with hemophilia. The nature of the AIDS-defining condition was found to be as important as age at seroconversion and CD4(+) lymphocyte level in predicting survival. A multivariate analysis yielded estimates of median survival for groups defined by age at seroconversion (0 through 15, 16 through 69), CD4(+) lymphocyte count (<100 cells/mu l versus greater than or equal to 100 cells/mu l), and 10 AIDS-defining disease groups. Estimates of median survival after a single AIDS-defining condition ranged from 3 to 51 months, depending on the diseases. Median survival after a second AIDS-defining condition was about 1.5- to 2.0-fold shorter than after an initial, isolated AIDS-defining condition. HN-related neurologic disease (i.e., AIDS dementia complex or multifocal leukoencephalopathy) was a notable exception. It correlated with the shortest estimates of median survival (3 to 9 months), and this poor prognosis was no worse for patients who had a second AIDS-defining condition. The results of this analysis were consistent in most respects with other published analyses of factors affecting survival. These findings may be useful in the clinical care of persons with AIDS and in estimating the number of persons alive who have had a particular AIDS-defining disease. C1 NCI,VIRAL EPIDEMIOL BRANCH,BETHESDA,MD 20892. INFORMAT MANAGEMENT SERV INC,ROCKVILLE,MD. RP Gail, MH (reprint author), NCI,BIOSTAT BRANCH,EXECUT PLAZA N,ROOM 431,6130 EXECUT BLVD,MSC 7368,BETHESDA,MD 20892, USA. NR 17 TC 7 Z9 7 U1 0 U2 3 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 1077-9450 J9 J ACQ IMMUN DEF SYND JI J. Acquir. Immune Defic. Syndr. Hum. Retrovirol. PD AUG 15 PY 1997 VL 15 IS 5 BP 363 EP 369 PG 7 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA YC364 UT WOS:A1997YC36400006 PM 9342256 ER PT J AU Lechat, MF Shrager, DI Declercq, E Bertrand, F Blattner, WA Blumberg, BS AF Lechat, MF Shrager, DI Declercq, E Bertrand, F Blattner, WA Blumberg, BS TI Decreased survival of HTLV-I carriers in leprosy patients from the Democratic Republic of the Congo: A historical prospective study SO JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES AND HUMAN RETROVIROLOGY LA English DT Article DE HTLV-I; leprosy; Democratic Republic of the Congo; survival ID CELL LEUKEMIA-VIRUS; INFECTION AB In this historical prospective study using sera stored for 22 years, we investigated the effect of HTLV-I infection on survival in a population of leprosy patients in the Democratic Republic of the Congo (formerly Zaire). We also determined the distribution of HTLV-I by subpopulation, age, and gender. Stored sera taken from a population of leprosy patients and controls in 1969 were tested for HTLV-I. Follow-up survival data on these patients were obtained in 1991. The sera collected in 1969 from 520 individuals was used to determine the prevalence of HTLV-I. Included in this number were 328 patients resident in the sanatorium. Survival and other data were available for 327 of these. A multivariate survival analysis using a logistic regression model was performed to evaluate the influence of HTLV-I status, age, type of leprosy, gender, duration of hospitalization, and ethnic group on survival. The overall prevalence of HTLV-I among the 520 individuals in the prevalence study was 34%, with 37.4% in the leprosy group and 25.2% in the control group (p < 0.01). Multivariate analysis using logistic regression showed that females of the Mongo and Ngombe ethnic group taken together were significantly more likely to be infected than the other groups (OR = 3.67, 95% CI: 2.14 to 6.30). A comparison of the death rates directly standardized for age and sex showed that the rate was significantly higher for HTLV-I positive (5.5/100 person-years of observation) compared with HTLV-I negative (3.6/100 person-years of observation). A survival analysis using the Cox model showed a risk ratio of 1.4 (CI: 1.04 to 1.89) for those infected with HTLV-I. An increase in the death rate was associated with HTLV-I infection in leprosy inpatients. The decreased survival associated with HTLV-I infection may result from an increased susceptibility to a variety of diseases. C1 FOX CHASE CANC CTR,PHILADELPHIA,PA 19111. UNIV CATHOLIQUE LOUVAIN,BRUSSELS,BELGIUM. INST HYG & EPIDEMIOL,B-1050 BRUSSELS,BELGIUM. NCI,BETHESDA,MD 20892. FU NCI NIH HHS [CA-06927] NR 16 TC 13 Z9 13 U1 1 U2 1 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 1077-9450 J9 J ACQ IMMUN DEF SYND JI J. Acquir. Immune Defic. Syndr. Hum. Retrovirol. PD AUG 15 PY 1997 VL 15 IS 5 BP 387 EP 390 PG 4 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA YC364 UT WOS:A1997YC36400010 PM 9342260 ER PT J AU Berlett, BS Stadtman, ER AF Berlett, BS Stadtman, ER TI Protein oxidation in aging, disease, and oxidative stress SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Review ID CATALYZED OXIDATION; PROTEOLYSIS; ENZYME; AGE; MECHANISM; DAMAGE; SUSCEPTIBILITY; DEGRADATION; RADIOLYSIS; SYNTHETASE C1 NHLBI, BIOCHEM LAB, NIH, BETHESDA, MD 20892 USA. NR 49 TC 1979 Z9 2039 U1 26 U2 151 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 AUG 15 PY 1997 VL 272 IS 33 BP 20313 EP 20316 DI 10.1074/jbc.272.33.20313 PG 4 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA XR221 UT WOS:A1997XR22100001 PM 9252331 ER PT J AU Alkhatib, G Berger, EA Murphy, PM Pease, JE AF Alkhatib, G Berger, EA Murphy, PM Pease, JE TI Determinants of HIV-1 coreceptor function on CC chemokine receptor 3 - Importance of both extracellular and transmembrane/cytoplasmic regions SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID IMMUNODEFICIENCY-VIRUS TYPE-1; RECOMBINANT VACCINIA VIRUS; ENVELOPE GLYCOPROTEIN; EXPRESSION; IDENTIFICATION; MACROPHAGES; CLONING; RANTES; FUSION; CELLS AB The chemokine receptors CXCR4, CCR2b, CCR3, and CCR5 are cell entry coreceptors for HIV-1. Using an HIV-1 envelope (Env) dependent cell-cell fusion model of entry, we show that CCR3 can interact with Envs from certain macrophage (M)-tropic strains (which also use CCR5), T cell line (TCL)-tropic laboratory-adapted strains (which also use CXCR4), and a dual tropic primary isolate (which also uses CCR2b, CCR5, and CXCR4). Paradoxically, CCR1 is the closest homologue to CCR3 (63% amino acid identity), but lacked HIV-1 coreceptor activity, These results confirm and extend previous reports, Replacing the N-terminal segment of CCR3 with that of CCR1 abolished activity of the resulting chimera for M-tropic and TCL-tropic Envs, but not for the dual-tropic Env, Replacing extracellular loop 2 of CCR3 with that of CCR1 abolished activity for TCL-tropic Envs, but not for M- and dual-tropic Envs, A chimera containing all four extracellular regions of CCR3 on a backbone of CCR1 lacked any activity, Env-CCR3 interactions were strongly inhibited by the major CCR3 ligand eotaxin, but weakly or not at all by other CCR3 ligands, With primary macrophages, eotaxin induced transient calcium flux and partially inhibited fusion with cells expressing M-tropic Envs. We conclude that specificity determinants for different Envs are located in shared and distinct extracellular regions of CCR3, the transmembrane/cytoplasmic domains make major contributions to coreceptor function, and CCR3 may be used by certain HIV-1 strains as a cell fusion factor on macrophages. C1 NIAID,HOST DEF LAB,NIH,BETHESDA,MD 20892. NIAID,VIRAL DIS LAB,NIH,BETHESDA,MD 20892. UNIV SHEFFIELD,KREBS INST,DEPT MOL BIOL & BIOTECHNOL,SHEFFIELD S10 2TN,S YORKSHIRE,ENGLAND. NR 54 TC 59 Z9 59 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 AUG 15 PY 1997 VL 272 IS 33 BP 20420 EP 20426 DI 10.1074/jbc.272.33.20420 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA XR221 UT WOS:A1997XR22100020 PM 9252350 ER PT J AU Coso, OA Montaner, S Fromm, C Lacal, JC Prywes, R Teramoto, H Gutkind, JS AF Coso, OA Montaner, S Fromm, C Lacal, JC Prywes, R Teramoto, H Gutkind, JS TI Signaling from G protein coupled receptors to the c-jun promoter involves the MEF2 transcription factor - Evidence for a novel c-Jun amino-terminal kinase-independent pathway SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID NIH 3T3 CELLS; MAP KINASE; ACTIVATION DOMAIN; FOS; DIFFERENTIATION; PHOSPHORYLATION; TRANSFORMATION; FAMILY; MUSCLE; BINDS AB The c-Jun amino-terminal kinases (JNKs) are a subfamily of mitogen-activated protein kinases that phosphorylate c-Jun and ATF2, and it has been postulated that phosphorylated c-Jun enhances its own expression through AP-1 sites on the c-jun promoter. In this study, we asked whether signals activating JNK regulate the c-jun promoter, Using NIH 3T3 cells expressing G protein-coupled mi acetylcholine receptors as an experimental model, we have recently shown that the cholinergic agonist carbachol, but not platelet derived growth factor, potently elevates JNK activity, Consistent with these findings, carbachol, but not platelet-derived growth factor, increased the activity of a c-jun promoter-driven reporter gene (for chloramphenicol acetyltransferase), However, coexpression of JNK kinase kinase (MEKK) effectively increased JNK activity, but resulted in surprisingly limited induction of the c- jun promoter, This raised the possibility that pathway(s) distinct from JNK control the c-jun promoter, and prompted us to explore which of its regulatory elements participate in transcriptional control. We observed that deletion of the 3' AP-1 site diminished chloramphenicol acetyltransferase activity in response to carbachol, but only to a limited extent, In contrast, deletion of a MEF2 site dramatically reduced expression, and deletion of both the MEF2 and 3' AP-1 sites abolished induction, Furthermore, cotransfection with MEF2C and MEF2D cDNAs potently enhanced the activity of the c-jun promoter in response to carbachol, and stimulation of mi receptors, but not direct JNK activation, induced expression of a MEF2-responsive plasmid. Taken together, these data strongly suggest that MEF2 mediates c-jun promoter expression by G protein-coupled receptors through a yet to be identified pathway, distinct from that of JNK. C1 NIDR,MOL SIGNALING UNIT,ORAL & PHARYNGEAL CANC BRANCH,NIH,BETHESDA,MD 20892. INST INVEST BIOMED,MADRID 28029,SPAIN. COLUMBIA UNIV,DEPT BIOL SCI,NEW YORK,NY 10027. RI Gutkind, J. Silvio/A-1053-2009; Lacal, Juan Carlos/N-9064-2015 OI Lacal, Juan Carlos/0000-0002-1908-2777 NR 31 TC 45 Z9 45 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 AUG 15 PY 1997 VL 272 IS 33 BP 20691 EP 20697 DI 10.1074/jbc.272.33.20691 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA XR221 UT WOS:A1997XR22100059 PM 9252389 ER PT J AU Shibusawa, Y Eriguchi, Y Ito, Y AF Shibusawa, Y Eriguchi, Y Ito, Y TI Purification of lactic acid dehydrogenase from bovine heart crude extract by counter-current chromatography SO JOURNAL OF CHROMATOGRAPHY B LA English DT Article DE lactic acid dehydrogenase; enzymes ID COIL PLANET CENTRIFUGE; PHASE; LIPOPROTEINS; SEPARATION; PROTEINS; SYSTEMS AB To test the utility of counter-current chromatography in purifying proteins, lactic acid dehydrogenase (LDH) was extracted from a crude bovine heart filtrate using a cross-axis coil planet centrifuge. The purification was performed with several polymer phase systems composed of 16% (w/w) poly(ethylene glycol) (PEG) 1000-12.5% (w/w) potassium phosphate buffers and 4.4% (w/w) PEG 8000-7.0 (w/w) dextran T500 at pH values ranging from 6.5 to 11.0. The best purification was achieved using PEG 1000-potassium phosphate buffer system at pH 7.3 by eluting the upper phase at 1.0 ml/min. Fractions were analyzed by LDH enzymatic activity and sodium dodecyl sulfate slab gel electrophoresis (SDS-PAGE), The LDH was purified directly from bovine heart crude extract within 3 h. (C) 1997 Elsevier Science B.V. C1 NHLBI,BIOPHYS CHEM LAB,NIH,BETHESDA,MD 20892. RP Shibusawa, Y (reprint author), TOKYO UNIV PHARM & LIFE SCI,SCH PHARM,DEPT ANALYT CHEM,1432-1 HORINOUCHI,HACHIOJI,TOKYO 19203,JAPAN. NR 15 TC 14 Z9 14 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0378-4347 J9 J CHROMATOGR B JI J. Chromatogr. B PD AUG 15 PY 1997 VL 696 IS 1 BP 25 EP 31 DI 10.1016/S0378-4347(97)00216-8 PG 7 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA XU890 UT WOS:A1997XU89000004 PM 9300905 ER PT J AU Sime, PJ Xing, Z Graham, FL Csaky, KG Gauldie, J AF Sime, PJ Xing, Z Graham, FL Csaky, KG Gauldie, J TI Adenovector-mediated gene transfer of active transforming growth factor-beta 1 induces prolonged severe fibrosis in rat lung SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article DE gene transfer; cytokine; fibrotic; extracellular matrix; pulmonary ID MOLECULAR-WEIGHT COMPLEX; SMOOTH MUSCLE ACTIN; FACTOR TYPE-BETA; PULMONARY FIBROSIS; HUMAN-PLATELETS; IMMUNOHISTOCHEMICAL LOCALIZATION; EXPRESSION; CELLS; MYOFIBROBLASTS; ACTIVATION AB Transforming growth factor (TGF)-beta 1 has been implicated in the pathogenesis of fibrosis based upon its matrix-inducing effects on stromal cells in vitro, and studies demonstrating increased expression of total TGF-beta 1 in fibrotic tissues from a variety of organs, The precise role in vivo of this cytokine in both its latent and active forms, however, remains unclear. Using replication-deficient adenovirus vectors to transfer the cDNA of porcine TGF-beta 1 to rat lung, we have been able to study the effect of TGF-beta 1 protein in the respiratory tract directly, We have demonstrated that transient overexpression of active, but not latent, TGF-beta 1 resulted in prolonged and severe interstitial and pleural fibrosis characterized by extensive deposition of the extracellular matrix (ECM) proteins collagen, fibronectin, and elastin, and by emergence of cells with the myofibroblast phenotype. These results illustrate the role of TGF-beta 1 and the importance of its activation in the pulmonary fibrotic process, and suggest that targeting active TGF-beta 1 and steps involved In TGF-beta 1 activation are likely to be valuable antifibrogenic therapeutic strategies. This new and versatile model of pulmonary fibrosis can be used to study such therapies. C1 MCMASTER UNIV, HLTH SCI CTR, DEPT PATHOL, MOL VIROL & IMMUNOL PROGRAM, HAMILTON, ON L8N 3Z5, CANADA. MCMASTER UNIV, HLTH SCI CTR, DEPT BIOL, HAMILTON, ON L8N 3Z5, CANADA. NEI, NIH, BETHESDA, MD 20892 USA. NR 38 TC 608 Z9 631 U1 1 U2 8 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD AUG 15 PY 1997 VL 100 IS 4 BP 768 EP 776 DI 10.1172/JCI119590 PG 9 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA XT817 UT WOS:A1997XT81700003 PM 9259574 ER PT J AU Hagedorn, M Kleinhans, FW Freitas, R Liu, J Hsu, EW Wildt, DE Rall, WF AF Hagedorn, M Kleinhans, FW Freitas, R Liu, J Hsu, EW Wildt, DE Rall, WF TI Water distribution and permeability of zebrafish embryos, Brachydanio rerio SO JOURNAL OF EXPERIMENTAL ZOOLOGY LA English DT Article ID CATTLE EMBRYOS; MOUSE EMBRYOS; CRYOPRESERVATION; VITRIFICATION; CELL; CRYOPROTECTANT; PRESERVATION; BEHAVIOR; OOCYTES; LAYER AB Teleost embryos have not been successfully cryopreserved. To formulate successful cryopreservation protocols, the distribution and cellular permeability to water must be understood. In this paper, the zebrafish (Brachydanio rerio) was used as a model for basic studies of the distribution to permeability to water. These embryos are a complex multi-compartmental system composed of two membrane-limited compartments, a large yolk (surrounded by the yolk syncytial layer) and differentiating blastoderm cells (each surrounded by a plasma membrane). Due to the complexity of this system, a variety of techniques, including magnetic resonance microscopy and electron spin resonance, was used to measure the water in these compartments. Cellular water was distributed unequally in each compartment. At the 6-somite stage, the percent water (V/V) was distributed as follows: total in embryo = 74%, total in yolk = 42%, and total in blastoderm = 82%. A one-compartment model was used to analyze kinetic, osmotic shrinkage data and determine a phenomenological water permeability parameter, L-p, assuming intracellular isosmotic compartments of either 40 or 300 mosm. This analysis revealed that the membrane permeability changed (P < 0.05) during development. During the 75% epiboly to 3-somite stage, the mean membrane permeability remained constant (L-p = 0.022 +/- 0.002 mu m x min(-1)atm(-1) [mean +/- S.E.M.] assuming isosmotic is 40 mosm or L-p = 0.049 +/- 0.008 mu m x min(-1)atm(-1) assuming isosmotic is 300 mosm). However, at the 6-somite stage, Lp increased twofold (L-p = 0.040 +/- 0.004 mu m x min(-1)atm(-1) assuming isosmotic is 40 mosm or L-p = 0.100 +/- 0.017 mu m x min(-1)atm(-1) assuming isosmotic is 300 mosm). Therefore, the low permeability of the zebrafish embryo coupled with its large size (and consequent low area to volume ratio) led to a very slow osmotic response that should be considered before formulating cryopreservation protocols. (C) 1997 Wiley-Liss, Inc. C1 SMITHSONIAN INST, CONSERVAT RES CTR, WASHINGTON, DC 20008 USA. INDIANA UNIV PURDUE UNIV, DEPT PHYS, INDIANAPOLIS, IN 46202 USA. UNIV TEXAS, DEPT MECH ENGN, AUSTIN, TX 78712 USA. METHODIST HOSP INDIANA, CRYOBIOL RES INST, INDIANAPOLIS, IN 46202 USA. JOHNS HOPKINS UNIV, SCH MED, DEPT BIOMED ENGN, BALTIMORE, MD 21205 USA. NIH, NATL CTR RES RESOURCES, VET RESOURCES PROGRAM, BETHESDA, MD 20892 USA. RP Hagedorn, M (reprint author), SMITHSONIAN INST, NATL ZOOL PK, 301 CONN AVE NW, WASHINGTON, DC 20008 USA. RI Rall, William/C-5104-2008 FU NCRR NIH HHS [R29 RR08769] NR 53 TC 57 Z9 59 U1 1 U2 16 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0022-104X J9 J EXP ZOOL JI J. Exp. Zool. PD AUG 15 PY 1997 VL 278 IS 6 BP 356 EP 367 DI 10.1002/(SICI)1097-010X(19970815)278:6<356::AID-JEZ3>3.0.CO;2-N PG 12 WC Zoology SC Zoology GA XP433 UT WOS:A1997XP43300003 PM 9262005 ER PT J AU Jankovic, D Kullberg, MC Dombrowicz, D Barbieri, S Caspar, P Wynn, TA Paul, WE Cheever, AW Kinet, JP Sher, A AF Jankovic, D Kullberg, MC Dombrowicz, D Barbieri, S Caspar, P Wynn, TA Paul, WE Cheever, AW Kinet, JP Sher, A TI Fc epsilon RI-deficient mice infected with Schistosoma mansoni mount normal Th2-type responses while displaying enhanced liver pathology SO JOURNAL OF IMMUNOLOGY LA English DT Article ID NON-T CELLS; IMMUNOGLOBULIN-E; GRANULOMA-FORMATION; NON-B; PRODUCE INTERLEUKIN-4; HEPATIC-FIBROSIS; RECEPTOR; IL-4; EXPRESSION; EFFECTOR AB The IgE/Fc epsilon RI interaction is postulated to play an important role in resistance to helminths both at the level of anti-parasitic effector cell function and in the initiation of Th2 responses through IL-4 produced by Fc epsilon RI+ non-B, non-T (NBNT) cells. To formally evaluate the role of IgE/Fc epsilon RI signaling in the host response to helminths we studied Schistosoma mansoni infection in Fc epsilon RI knockout (KO) mice, Infected wild-type (wt) and KO animals showed comparable adult worm and tissue egg burdens, arguing against a role for Fc epsilon RI in host resistance, Significantly, NBNT cells from infected KO, in contrast to wt animals, did not secrete IL-4 when stimulated with anti-IgE Ab or soluble parasite Ag, Nevertheless, serum IgE levels and Th2 cytokine production profiles were comparable in both strains of mice, demonstrating that the Ag-dependent stimulation of IL-4 secretion by NBNT cells is not essential for helminth-induced Th2 differentiation, However, when stimulated with low Ag doses, splenocytes from infected Fc epsilon RI-deficient mice produced less IL-4 in vitro than similar cultures from infected wt animals, an effect attributable to their defective NBNT cell function, Moreover, infected KO mice showed enhanced egg granuloma formation and hepatic fibrosis, revealing that the IgE/Fc epsilon RI interaction, while not essential for Th2 response development or resistance to primary infection, plays a significant role in down-regulating host pathology. C1 NIAID,MOL ALLERGY & IMMUNOL SECT,NIH,BETHESDA,MD 20892. NIAID,BIOL RESOURCES BRANCH,NIH,BETHESDA,MD 20892. NIAID,IMMUNOL LAB,NIH,BETHESDA,MD 20892. UNIV STOCKHOLM,DEPT IMMUNOL,S-10691 STOCKHOLM,SWEDEN. RP Jankovic, D (reprint author), NIAID,IMMUNOBIOL SECT,PARASIT DIS LAB,NIH,BLDG 4,ROOM 126,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. RI Wynn, Thomas/C-2797-2011; Dombrowicz, David/F-7044-2013 OI Dombrowicz, David/0000-0002-0485-8923 NR 49 TC 54 Z9 56 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 AUG 15 PY 1997 VL 159 IS 4 BP 1868 EP 1875 PG 8 WC Immunology SC Immunology GA XP438 UT WOS:A1997XP43800037 PM 9257851 ER PT J AU Denkers, EY Yap, G SchartonKersten, T Charest, H Butcher, BA Caspar, P Heiny, S Sher, A AF Denkers, EY Yap, G SchartonKersten, T Charest, H Butcher, BA Caspar, P Heiny, S Sher, A TI Perforin-mediated cytolysis plays a limited role in host resistance to Toxoplasma gondii SO JOURNAL OF IMMUNOLOGY LA English DT Article ID TUMOR-NECROSIS-FACTOR; CD8+ T-CELLS; IMMUNE-DEFICIENCY SYNDROME; NATURAL-KILLER-CELLS; IFN-GAMMA; LYMPHOCYTES-T; CYST NUMBER; MICE; INFECTION; CYTOTOXICITY AB Resistance of perforin knockout (PKO) mice to infection with Toxoplasma gondii was assessed in models of acute infection and during chronic disease. PKO mice vaccinated with the attenuated mutant, ts-4, displayed severely defective CTL responses against tachyzoite-infected targets. Lysis of the NK target, YAC-1, was also severely impaired in PKO mice following ts-4 vaccination. In contrast, wild-type mice developed high levels of CTL and NK lytic activity after ts-4 vaccination. Despite severely defective lytic activity, vaccinated PKO animals were completely resistant to challenge with the virulent strain RH, which normally causes a lethal acute infection. Resistance was attributable to production of IFN-gamma, which remained unimpaired in the PKO animals. In contrast, when PKO mice were infected with low virulence parasite strain ME49, which progresses to the cyst-forming stage after passage through an acute phase, accelerated mortality was observed beginning at 75 days postinfection. A three- to fourfold increase in brain cyst numbers was also found by day 30 in infected PKO animals. Nevertheless, the PKO strain produced normal levels of IFN-gamma after ME49 infection, ruling,out impaired production of the latter cytokine as a cause of increased susceptibility. Together, these results show that perforin-dependent cytolytic function is not required for host resistance to lethal acute infection in preimmunized animals, but that the latter activity contributes to the control of infection during the chronic stage. C1 NIAID,PARASIT DIS LAB,IMMUNOBIOL SECT,NIH,BETHESDA,MD 20892. RP Denkers, EY (reprint author), CORNELL UNIV,COLL VET MED,DEPT IMMUNOL & MICROBIOL,ITHACA,NY 14853, USA. NR 47 TC 101 Z9 105 U1 0 U2 2 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD AUG 15 PY 1997 VL 159 IS 4 BP 1903 EP 1908 PG 6 WC Immunology SC Immunology GA XP438 UT WOS:A1997XP43800041 PM 9257855 ER PT J AU Biddison, WE Kubota, R Kawanishi, T Taub, DD Cruikshank, WW Center, DM Connor, EW Utz, U Jacobson, S AF Biddison, WE Kubota, R Kawanishi, T Taub, DD Cruikshank, WW Center, DM Connor, EW Utz, U Jacobson, S TI Human T cell leukemia virus type I (HTLV-1)-specific CD8(+) CTL clones from patients with HTLV-I-associated neurologic disease secrete proinflammatory cytokines, chemokines, and matrix metalloproteinase SO JOURNAL OF IMMUNOLOGY LA English DT Article ID TROPICAL SPASTIC PARAPARESIS; CENTRAL-NERVOUS-SYSTEM; EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS; LYMPHOCYTE CHEMOATTRACTANT FACTOR; INFLAMMATORY PROTEIN 1-ALPHA; NECROSIS-FACTOR-ALPHA; SPINAL-CORD LESIONS; MULTIPLE-SCLEROSIS; CEREBROSPINAL-FLUID; EXTRACELLULAR-MATRIX AB Human T cell leukemia virus type I (HTLV-I)-associated myelopathy/tropical spastic paraparesis (HAM/TSP) is a chronic, progressive neurologic disease characterized by marked degeneration of the spinal cord and the presence of infiltrating CD8(+) T cells and macrophages, HAM/TSP patients have very high frequencies of HTLV-I-specific CD8(+) CTL in peripheral blood and in cerebrospinal fluid, In this study, we show that HAM/TSP patients also have elevated levels of peripheral blood CD8(+) T cells that produce intracellular IFN-gamma. To address the potential role of soluble mediators secreted by CD8(+) T cells in the pathogenesis of HAM/TSP, we have analyzed the capacity of a panel of nine HTLV-l-specific CD8(+) CTL clones derived from three HAM/TSP patients to secrete cytokines, chemokines, and matrix metalloproteinases. The results demonstrate that the majority of these CTL clones secrete IFN-gamma, TNF-alpha, macrophage-inflammatory protein-1 alpha and -1 beta, IL-16, and matrix metalloproteinase-9. These findings indicate that HTLV-I-specific CD8(+) CTL are an important source of proinflammatory soluble mediators that may contribute significantly to the pathogenesis of HAM/TSP. C1 NCI,FREDERICK CANC RES & DEV CTR,SAIC FREDERICK,FREDERICK,MD 21072. BOSTON UNIV,SCH MED,CTR PULM,BOSTON,MA 02115. NCI,PATHOL LAB,NIH,BETHESDA,MD 20892. CLIN RES INST MONTREAL,IMMUNOL LAB,MONTREAL,PQ H2W 1R7,CANADA. RP Biddison, WE (reprint author), NINCDS,NEUROIMMUNOL BRANCH,NIH,BLDG 10 ROOM 5B-16,BETHESDA,MD 20892, USA. NR 50 TC 100 Z9 102 U1 0 U2 5 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD AUG 15 PY 1997 VL 159 IS 4 BP 2018 EP 2025 PG 8 WC Immunology SC Immunology GA XP438 UT WOS:A1997XP43800055 PM 9257869 ER PT J AU Malkov, VA Sastry, L CameriniOtero, RD AF Malkov, VA Sastry, L CameriniOtero, RD TI RecA protein assisted selection reveals a low fidelity of recognition of homology in a duplex DNA by an oligonucleotide SO JOURNAL OF MOLECULAR BIOLOGY LA English DT Article DE recombination; fidelity; RecA; selection; mismatch ID STRAND EXCHANGE; ESCHERICHIA-COLI; HELIX FORMATION; ATP HYDROLYSIS; RECOMBINATION; MISMATCHES; THERMODYNAMICS; BIOCHEMISTRY; POLYMERASE; EVOLUTION AB We have developed an in vitro selection procedure to elucidate the specificity of RecA assisted oligonucleotide recognition of double stranded DNA. The procedure was based on formation of a synaptic complex between an oligonucleotide-RecA filament and a supercoiled plasmid bearing a homologous partially degenerate region. The specificity of the selection depended on the reaction conditions: starting with a population that had, on average, 2.8 randomly distributed mismatches out of 27 bp, a population selected in the presence of 100 mM KCl had on average 1.0 mismatches, while a population selected at low ionic strength was less specific and had, on average, 2.0 mismatches. From the distributions of mismatches observed we calculated that the average destabilization free energy for one mismatch is 1.7(+/-0.5) kcal/mol. This is substantially less than the free energy for the incorporation of one mismatch in naked DNA duplex or a Py-Pu-Py triplex. Thus, RecA has an ability to decrease the fidelity of the homologous pairing reaction and minimize the cost of pairing between similar but not identical sequences. This ''antiproof-reading'' activity of RecA protein does not require ATP hydrolysis. C1 NIDDK,GENET & BIOCHEM BRANCH,NIH,BETHESDA,MD 20892. NR 31 TC 18 Z9 18 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 AUG 15 PY 1997 VL 271 IS 2 BP 168 EP 177 DI 10.1006/jmbi.1997.1164 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA XR350 UT WOS:A1997XR35000002 PM 9268650 ER PT J AU Papavassiliou, E Gogate, N Proescholdt, M Heiss, JD Walbridge, S Edwards, NA Oldfield, EH Merrill, MJ AF Papavassiliou, E Gogate, N Proescholdt, M Heiss, JD Walbridge, S Edwards, NA Oldfield, EH Merrill, MJ TI Vascular endothelial growth factor (vascular permeability factor) expression in injured rat brain SO JOURNAL OF NEUROSCIENCE RESEARCH LA English DT Article DE astrocytes; brain injury; glial fibrillary acidic protein; gliosis; VEGF ID FIBRILLARY ACIDIC PROTEIN; TUMOR ANGIOGENESIS; DIFFERENTIAL EXPRESSION; CELL-DIFFERENTIATION; FACTOR GENE; HYPOXIA; PROLIFERATION; ASTROCYTES; KERATINOCYTES; NEOPLASMS AB We investigated the expression of vascular endothelial growth factor (VEGF)/vascular permeability factor (VPF) in stab and freeze brain injury models in rats, Immunohistochemical staining with anti-VEGF antibodies demonstrated an increase in VEGF-positive cells in and around both lesions, Morphologically, the injury-induced VEGF-positive cells resembled astrocytes, Double immunofluorescent staining for the astrocytic marker glial fibrillary acidic protein (GFAP) and VEGF demonstrated directly that VEGF-positive cells which appeared in response to these injuries were astrocytes. VEGF expression in astrocytes was maximal on days 3 and 4 after injury in terms of both cell number and affected area, The increase in VEGF-positive cells was more widespread in the freeze lesion than in the stab wound, and occurred in both the lesioned and nonlesioned hemispheres, VEGF-positive cells were still present 3 weeks after both injuries, but their numbers were reduced and their distribution became limited to the immediate vicinity of the lesions, These observations indicate that astrocytes react to injury by increasing VEGF expression, suggesting that VEGF might participate in the central nervous system response to injury. (C) 1997 Wiley-Liss, Inc. C1 NINCDS,SURG NEUROL BRANCH,NIH,BETHESDA,MD 20892. RI Gogtay, Nitin/A-3035-2008 NR 55 TC 63 Z9 64 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0360-4012 J9 J NEUROSCI RES JI J. Neurosci. Res. PD AUG 15 PY 1997 VL 49 IS 4 BP 451 EP 460 DI 10.1002/(SICI)1097-4547(19970815)49:4<451::AID-JNR6>3.0.CO;2-7 PG 10 WC Neurosciences SC Neurosciences & Neurology GA XT099 UT WOS:A1997XT09900006 PM 9285521 ER PT J AU Koylu, E Demirgoren, S London, ED Pogun, S AF Koylu, E Demirgoren, S London, ED Pogun, S TI Sex difference in up-regulation of nicotinic acetylcholine receptors in rat brain SO LIFE SCIENCES LA English DT Article DE nicotine acetylcholine receptor; cystine; nicotine; sex differences; up-regulation; withdrawal ID CHOLINERGIC RECEPTORS; H-3 CYTISINE; TIME COURSE; BINDING; INCREASES; TOLERANCE; INFUSION; SMOKING AB This study tested for sex differences in the effects of chronic nicotine administration and withdrawal on nicotinic acetylcholine receptor binding in brain. Rats received nicotine (0.6 mg/kg, sc) or saline once daily for 15 days, and were sacrificed 1 or 20 days after termination of treatment. Saturation studies of nAChR binding were performed using [H-3]cytisine as the radioligand in whole brain minus cerebellum taken from animals in the chronic treatment groups and from naive rats. Male but not female rats that received chronic nicotine had higher receptor densities than corresponding control groups; up-regulation of nAChR was not seen 20 days after withdrawal. Furthermore, in groups that showed no up-regulation (controls and rats withdrawn for 20 days), nAChR densities were higher in female rats than males. The findings underscore the importance of sex differences in pharmacological responses as well as in basal neurochemical parameters. C1 EGE UNIV,SCH MED,CTR BRAIN RES,DEPT PHYSIOL,TR-35100 BORNOVA,IZMIR,TURKEY. TUBITAK,BASIC NEUROSCI RES UNIT,TR-35100 BORNOVA,IZMIR,TURKEY. NIDA,INTRAMURAL RES PROGRAM,BALTIMORE,MD 21224. RI Koylu, Ersin/A-4539-2011; Pogun, Sakire/A-5816-2010 NR 19 TC 26 Z9 26 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0024-3205 J9 LIFE SCI JI Life Sci. PD AUG 15 PY 1997 VL 61 IS 12 BP PL185 EP PL190 PG 6 WC Medicine, Research & Experimental; Pharmacology & Pharmacy SC Research & Experimental Medicine; Pharmacology & Pharmacy GA XT140 UT WOS:A1997XT14000013 ER PT J AU Gagneten, S Le, YZ Miller, J Sauer, B AF Gagneten, S Le, YZ Miller, J Sauer, B TI Brief expression of a GFPcre fusion gene in embryonic stem cells allows rapid retrieval of site-specific genomic deletions SO NUCLEIC ACIDS RESEARCH LA English DT Article ID GREEN-FLUORESCENT PROTEIN; CRE RECOMBINASE; MAMMALIAN GENOME; TRANSGENIC MICE; MOUSE EMBRYOS; DNA; TRANSFORMATION; MARKER AB The Cre DNA recombinase of bacteriophage P1 has become a useful tool for precise genomic manipulation in embryonic stem (ES) cells that have been gene modified by homologous recombination. We have re-engineered the ore gene to allow ready identification of living Cre(+) cells by constructing a functional fusion between Cre and an enhanced green fluorescent protein from Aequorea victoria (GFPS65T), The GFPcre fusion gene product rapidly targeted the nucleus in the absence of any exogenous nuclear localization signal, Moreover, GFPCre catalyzed efficient DNA recombination in both a mouse 3T3 derivative cell line and in murine ES cells, Fluorescence-activated cell sorting (FAGS) of transiently GFPcre-transfected ES cells not only allowed rapid and efficient isolation of Cre(+) cells after DNA transfection but also demonstrated that a burst of Cre expression is sufficient to commit cells to Cre-mediated 'pop-out' of loxP-tagged DNA from the genome. Thus, GFPcre allows rapid identification of living cells in which loxP-flanked DNA sequences are destined to be removed from the genome by Cre-mediated recombination without reliance on recombinational activation or inactivation of a marker gene at the target locus, In addition, the GFPcre fusion gene will prove useful in tracing tissue-specific Cre expression in transgenic animals, thereby facilitating the generation and analysis of conditional gene knockout mice. C1 NIDDKD,BIOCHEM & METAB LAB,NIH,BETHESDA,MD 20892. NIDDKD,BIOL CHEM LAB,NIH,BETHESDA,MD 20892. NR 35 TC 66 Z9 69 U1 0 U2 2 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD, ENGLAND OX2 6DP SN 0305-1048 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD AUG 15 PY 1997 VL 25 IS 16 BP 3326 EP 3331 DI 10.1093/nar/25.16.3326 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA XR701 UT WOS:A1997XR70100021 PM 9241248 ER PT J AU Smith, MW Dean, M Carrington, M Winkler, C Huttley, GA Lomb, DA Goedert, JJ OBrien, TR Jacobson, LP Kaslow, R Buchbinder, S Vittinghoff, E Vlahov, D Hoots, K Hilgartner, MW OBrien, SJ AF Smith, MW Dean, M Carrington, M Winkler, C Huttley, GA Lomb, DA Goedert, JJ OBrien, TR Jacobson, LP Kaslow, R Buchbinder, S Vittinghoff, E Vlahov, D Hoots, K Hilgartner, MW OBrien, SJ TI Contrasting genetic influence of CCR2 and CCR5 variants on HIV-1 infection and disease progression SO SCIENCE LA English DT Article ID IMMUNODEFICIENCY-VIRUS TYPE-1; MULTICENTER AIDS COHORT; IN-VITRO; CELLS; HEMOPHILIA AB The critical role of chemokine receptors (CCR5 and CXCR4) in human immunodeficiency virus-type 1 (HIV-1) infection and pathogenesis prompted a search for polymorphisms in other chemokine receptor genes that mediate HIV-1 disease progression, A mutation (CCR2-64I) within the first transmembrane region of the CCR2 chemokine and HIV-1 receptor gene is described that occurred at an allele frequency of 10 to 15 percent among Caucasians and African Americans. Genetic association analysis of five acquired immunodeficiency syndrome (AIDS) cohorts (3003 patients) revealed that although CCR2-64I exerts no influence on the incidence of HIV-1 infection, HIV-1-infected individuals carrying the CCR2-64I allele progressed to AIDS 2 to 4 years later than individuals homozygous for the common allele. Because CCR2-64I occurs invariably on a CCR5-+-bearing chromosomal haplotype, the independent effects of CCR5-Delta 32 (which also delays AIDS onset) and CCR2-64I were determined. An estimated 38 to 45 percent of AIDS patients whose disease progresses rapidly (less than 3 years until onset of AIDS symptoms after HIV-1 exposure) can be attributed to their CCR2-+/+ or CCR5-+/+ genotype, whereas the survival of 28 to 29 percent of long-term survivors, who avoid AIDS for 16 years or more, can be explained by a mutant genotype for CCR2 or CCR5. C1 NCI,VIRAL EPIDEMIOL BRANCH,BETHESDA,MD 20892. NCI,SCI APPLICAT INT CORP FREDERICK,FREDERICK,MD 21702. NCI,LAB GENOM DIVERS,FREDERICK,MD 21702. JOHNS HOPKINS MED INST,SCH HYG & PUBL HLTH,DEPT EPIDEMIOL,BALTIMORE,MD 21205. UNIV ALABAMA,DEPT EPIDEMIOL,BIRMINGHAM,AL 35294. DEPT PUBL HLTH,AIDS OFF,SAN FRANCISCO,CA 94102. UNIV TEXAS,SCH MED,DEPT PEDIAT,HOUSTON,TX 77030. UNIV TEXAS,SCH MED,DEPT INTERNAL MED,HOUSTON,TX 77030. CORNELL UNIV,MED CTR,NEW YORK HOSP,DIV PEDIAT HEMATOL & ONCOL,NEW YORK,NY 10021. RI Smith, Michael/B-5341-2012; Dean, Michael/G-8172-2012; Huttley, Gavin/G-5169-2015 OI Dean, Michael/0000-0003-2234-0631; Huttley, Gavin/0000-0001-7224-2074 NR 63 TC 722 Z9 756 U1 3 U2 20 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 SN 0036-8075 J9 SCIENCE JI Science PD AUG 15 PY 1997 VL 277 IS 5328 BP 959 EP 965 DI 10.1126/science.277.5328.959 PG 7 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA XQ985 UT WOS:A1997XQ98500043 PM 9252328 ER PT J AU Anzick, SL Kononen, J Walker, RL Azorsa, DO Tanner, MM Guan, XY Sauter, G Kallioniemi, OP Trent, JM Meltzer, PS AF Anzick, SL Kononen, J Walker, RL Azorsa, DO Tanner, MM Guan, XY Sauter, G Kallioniemi, OP Trent, JM Meltzer, PS TI AIB1, a steroid receptor coactivator amplified in breast and ovarian cancer SO SCIENCE LA English DT Article ID COMPARATIVE GENOMIC HYBRIDIZATION; AMPLIFICATION; SEQUENCE AB Members of the recently recognized SRC-1 family of transcriptional coactivators interact with steroid hormone receptors to enhance ligand-dependent transcription. AIB1, a member of the SRC-1 family, was cloned during a search on the long arm of chromosome 20 for genes whose expression and copy number were elevated in human breast cancers. AIB1 amplification and overexpression were observed in four of five estrogen receptor-positive breast and ovarian cancer cell lines. Subsequent evaluation of 105 unselected specimens of primary breast cancer found AIB1 amplification in approximately 10 percent and high expression in 64 percent of the primary tumors analyzed. AIB1 protein interacted with estrogen receptors in a ligand-dependent fashion, and transfection of AIB1 resulted in enhancement of estrogen-dependent transcription, These observations identify AIB1 as a nuclear receptor coactivator whose altered expression may contribute to development of steroid-dependent cancers. C1 NATL HUMAN GENOME RES INST,CANC GENET LAB,NIH,BETHESDA,MD 20892. UNIV TAMPERE,INST MED TECHNOL,CANC GENET LAB,FIN-33101 TAMPERE,FINLAND. TAMPERE UNIV HOSP,FIN-33101 TAMPERE,FINLAND. UNIV BASEL,INST PATHOL,CH-4003 BASEL,SWITZERLAND. RI Guan, Xin-Yuan/A-3639-2009; Kallioniemi, Olli/H-5111-2011; Kallioniemi, Olli/H-4738-2012 OI Guan, Xin-Yuan/0000-0002-4485-6017; Kallioniemi, Olli/0000-0002-3231-0332; Kallioniemi, Olli/0000-0002-3231-0332 NR 21 TC 1246 Z9 1270 U1 5 U2 31 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 SN 0036-8075 J9 SCIENCE JI Science PD AUG 15 PY 1997 VL 277 IS 5328 BP 965 EP 968 DI 10.1126/science.277.5328.965 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA XQ985 UT WOS:A1997XQ98500044 PM 9252329 ER PT J AU Umbach, DM Weinberg, CR AF Umbach, DM Weinberg, CR TI Designing and analysing case-control studies to exploit independence of genotype and exposure SO STATISTICS IN MEDICINE LA English DT Article ID GENE-ENVIRONMENT INTERACTION; STATISTICAL-ANALYSIS; SUSCEPTIBILITY; ASSOCIATION; SAMPLE; MODELS AB Genetic susceptibility and environmental exposures play a synergistic role in the aetiology of many diseases. We consider a case-control study of a rare disease in relation to a categorical exposure and a genetic factor under the assumption that the genotype and the exposure occur independently in the population under study. Using a logistic model for risk, we describe maximum likelihood methods based on log-linear models that explicitly impose the independence assumption, something the usual logistic regression analyses cannot do. The estimator of the genotype-exposure interaction effect depends only on data from cases. Estimators for genotype and for exposure effects depend also on data from controls, but only through their respective marginal totals. All three estimators have smaller variance than they would were independence not enforced. These results have important implications for design: (i) Case-only studies can efficiently estimate gene-by-environment interactions. (ii) Studies where controls are genotyped anonymously can estimate genotype, exposure, and interaction effects as efficiently as designs where genotype and exposure data are linked. This feature addresses a growing concern of human subjects review boards. (iii) Exposure and interaction effects, but not genotype effects, can be estimated from studies where genetic information is only collected from cases (although one can recover the genotype effect if external gene prevalence data exist). Such designs have the compensatory benefit that the response rate (hence, validity) is higher when controls are not subjected to intrusive tissue sampling. However, the independence assumption can be checked only with linked genotype and exposure data for some controls. We illustrate the methods by applying them to recent study of cleft palate in relation to maternal cigarette smoking and to a variant of the transforming growth factor alpha gene in the child. (C) 1997 by John Wiley & Sons Ltd. RP Umbach, DM (reprint author), NIEHS,BIOSTAT BRANCH,POB 12233,RES TRIANGLE PK,NC 27709, USA. NR 14 TC 117 Z9 119 U1 0 U2 4 PU JOHN WILEY & SONS LTD PI W SUSSEX PA BAFFINS LANE CHICHESTER, W SUSSEX, ENGLAND PO19 1UD SN 0277-6715 J9 STAT MED JI Stat. Med. PD AUG 15 PY 1997 VL 16 IS 15 BP 1731 EP 1743 DI 10.1002/(SICI)1097-0258(19970815)16:15<1731::AID-SIM595>3.0.CO;2-S PG 13 WC Mathematical & Computational Biology; Public, Environmental & Occupational Health; Medical Informatics; Medicine, Research & Experimental; Statistics & Probability SC Mathematical & Computational Biology; Public, Environmental & Occupational Health; Medical Informatics; Research & Experimental Medicine; Mathematics GA XP476 UT WOS:A1997XP47600005 PM 9265696 ER PT J AU Sauer, JM Waalkes, MP Hooser, SB Kuester, RK McQueen, CA Sipes, IG AF Sauer, JM Waalkes, MP Hooser, SB Kuester, RK McQueen, CA Sipes, IG TI Suppression of Kupffer cell function prevents cadmium induced hepatocellular necrosis in the male Sprague-Dawley rat SO TOXICOLOGY LA English DT Article DE cadmium chloride; gadolinium chloride; Kupffer cell; liver injury; hepatotoxicity; metallothionein; primary isolated hepatocytes ID ACETAMINOPHEN HEPATOTOXICITY; LIVER-INJURY; ACTIVATED MACROPHAGES; POTENTIAL ROLE; METALLOTHIONEIN; CARBON; INVOLVEMENT; MODULATION; MECHANISMS; TOXICITY AB Exposure of humans to toxic metals and metalloids is a major environmental problem. Many metals, such as cadmium, can be hepatotoxic. However, the mechanisms by which metals cause acute hepatic injury are in many cases unknown. Previous reports suggest a major role for inflammation in acute cadmium induced hepatotoxicity. In initial experiments we found that a non-hepatotoxic dose of cadmium chloride (CdCl2; 2.0 mg/kg, i.v.) markedly increased the clearance rate of colloidal carbon from the blood, which is indicative of enhanced phagocytic activity by Kupffer cells (resident hepatic macrophages). Thus, the objective these studies was to determine the involvement of Kupffer cells in cadmium induced liver injury by inhibiting their function with gadolinium chloride (GdCl3). Male Sprague-Dawley rats were administered GdCl3 (10 mg/kg, i.v.) followed 24 h later by a single dose of CdCl2 (3.0 and 4.0 mg/kg, i.v.). Twenty four hours after CdCl2 administration animals were killed and the degree of liver toxicity was assessed using plasma alanine aminotransferase (ALT), as well as light microscopy. Cadmium chloride administration produced multifocal hepatocellular necrosis and increased plasma ALT activity. Pretreatment with GdCl3 significantly reduced both the morphological changes and hepatic ALT release caused by CdCl2. However, the protection was specific to the liver, and did not alter CdCl2 induced testicular injury, as determined by histopathological damage. In many cases, the inducible cadmium-binding protein, metallothionein (MT) is often an essential aspect of the acquisition of cadmium tolerance in the liver. Although cadmium caused a dramatic induction of hepatic MT (32-fold), GdCl3 caused only a minor increase (2-fold). Combined CdCl2 and GdCl3 treatment did not induce levels to an extent greater than CdCl2 alone. As expected, GdCl3 also caused a slight increase in the amount of cadmium associated with the liver. In cultured hepatocytes isolated from GdCl3 pretreated rats, CdCl2 induced cytotoxicity was not significantly altered compared to control hepatocytes, indicating that the mechanism of tolerance required the presence of other cell types. Thus, GdCl3 attenuation of CdCl2 induced hepatotoxicity does not appear to be caused by increased tissue MT content or a decreased susceptibility of hepatocytes to cadmium. From these data, we concluded that tolerance to cadmium induced hepatotoxicity involves the inhibition of Kupffer cell function which results in a decreased inflammatory response and an altered progression of hepatic injury. These data further indicate that Kupffer cell function is critical to cadmium induced hepatocellular necrosis. (C) 1997 Elsevier Science Ireland Ltd. C1 UNIV ARIZONA,DEPT PHARMACOL & TOXICOL,CTR TOXICOL,TUCSON,AZ 85721. NCI,FREDERICK CANC RES & DEV CTR,INORGAN CARCINOGENESIS SECT,FREDERICK,MD 21702. PURDUE UNIV,ANIM DIS DIAGNOST LAB,W LAFAYETTE,IN 47907. FU NIEHS NIH HHS [T32-ES-07091-17, P30-ES-06694, ES-06095] NR 39 TC 62 Z9 64 U1 1 U2 10 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 AUG 15 PY 1997 VL 121 IS 2 BP 155 EP 164 DI 10.1016/S0300-483X(97)00062-0 PG 10 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA XK242 UT WOS:A1997XK24200004 PM 9230447 ER PT J AU Bezrukov, SM Vodyanoy, I AF Bezrukov, SM Vodyanoy, I TI Stochastic resonance at the single-cell level - Reply SO NATURE LA English DT Letter ID WEAK ELECTRIC-FIELDS; LIVING CELLS; ION CHANNELS; ENHANCEMENT C1 ST PETERSBURG NUCL PHYS INST,GATCHINA 188350,RUSSIA. EUROPE,OFF NAVAL RES,LONDON NW1 5TH,ENGLAND. RP Bezrukov, SM (reprint author), NIH,DIV COMP RES & TECHNOL,BETHESDA,MD 20892, USA. NR 16 TC 4 Z9 4 U1 0 U2 1 PU MACMILLAN MAGAZINES LTD PI LONDON PA PORTERS SOUTH, 4 CRINAN ST, LONDON, ENGLAND N1 9XW SN 0028-0836 J9 NATURE JI Nature PD AUG 14 PY 1997 VL 388 IS 6643 BP 633 EP 633 DI 10.1038/41688 PG 1 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA XQ863 UT WOS:A1997XQ86300031 ER PT J AU Shankaran, S Papile, LA Wright, LL Ehrenkranz, RA Mele, L Lemons, JA Korones, SB Stevenson, DK Donovan, EF Stoll, BJ Fanaroff, AA Oh, W AF Shankaran, S Papile, LA Wright, LL Ehrenkranz, RA Mele, L Lemons, JA Korones, SB Stevenson, DK Donovan, EF Stoll, BJ Fanaroff, AA Oh, W TI The effect of antenatal phenobarbital therapy on neonatal intracranial hemorrhage in preterm infants SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID BIRTH-WEIGHT INFANTS; INTRAVENTRICULAR HEMORRHAGE; INTRACEREBRAL HEMORRHAGE; PREVENTION; NEWBORN; TRIAL; LESS AB Background The administration of phenobarbital to pregnant women before delivery has been thought to decrease the frequency of intracranial hemorrhage in preterm infants. To evaluate this potential neuroprotective therapy further, we determined the effect of antenatal administration of phenobarbital on the frequency of neonatal intracranial hemorrhage and early death. Methods We studied 610 women who were 24 to 33 weeks pregnant and who were expected to deliver their infants within 24 hours. The women were randomly assigned to receive either phenobarbital (10 mg per kilogram of body weight) or placebo intravenously, followed by maintenance doses until delivery or 34 weeks of gestation. The infants born to these women underwent cranial ultrasonography to detect the presence of intracranial hemorrhage. Results There were 309 women in the phenobarbital group and 301 in the placebo group. A total of 247 women (80 percent) in the phenobarbital group and 235 (78 percent) in the placebo group delivered within 24 hours after infusion of the study drug or administration of the last maintenance dose, Intracranial hemorrhage or early death occurred in 83 of the 344 infants born to the women in the phenobarbital group (24 percent) and in 74 of the 324 born to the women in the placebo group (23 percent; risk ratio for the infants in the phenobarbital group, 1.1; 95 percent confidence interval, 0.8 to 1.4), Among infants born before 34 weeks' gestation in whom ultrasonographic studies were performed, intracranial hemorrhage was diagnosed in 70 of 311 infants in the phenobarbital group (23 percent) and 64 of 279 in the placebo group (23 percent; risk ratio, 1.0; 95 percent confidence interval, 0.8 to 1.4). Conclusions Antenatal administration of phenobarbital does not decrease the risk of intracranial hemorrhage or early death in preterm infants. (C) 1997, Massachusetts Medical Society. C1 WAYNE STATE UNIV,DETROIT,MI. NICHHD,BETHESDA,MD 20892. YALE UNIV,NEW HAVEN,CT. GEORGE WASHINGTON UNIV,CTR BIOSTAT,ROCKVILLE,MD. INDIANA UNIV,INDIANAPOLIS,IN 46204. UNIV TENNESSEE,MEMPHIS,TN. STANFORD UNIV,PALO ALTO,CA 94304. UNIV CINCINNATI,CINCINNATI,OH. EMORY UNIV,ATLANTA,GA 30322. CASE WESTERN RESERVE UNIV,CLEVELAND,OH 44106. BROWN UNIV,WOMEN & INFANTS HOSP,PROVIDENCE,RI. HARVARD UNIV,BOSTON,MA 02115. UNIV ARKANSAS,LITTLE ROCK,AR 72204. UNIV MICHIGAN,ANN ARBOR,MI 48109. FU NICHD NIH HHS [U10 HD21385, U10 HD27881, U10 HD27871] NR 22 TC 35 Z9 37 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 AUG 14 PY 1997 VL 337 IS 7 BP 466 EP 471 DI 10.1056/NEJM199708143370705 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA XQ499 UT WOS:A1997XQ49900005 PM 9250849 ER PT J AU Lorenzi, MV Castagnino, P Chen, Q Chedid, M Miki, T AF Lorenzi, MV Castagnino, P Chen, Q Chedid, M Miki, T TI Ligand-independent activation of fibroblast growth factor receptor-2 by carboxyl terminal alterations SO ONCOGENE LA English DT Article DE FGFs; cell transformation; phosphotyrosine; receptor tyrosine kinases; MAP kinases ID FMS PROTO-ONCOGENE; TRANSFORMED PHENOTYPE; KINASE-ACTIVITY; POINT MUTATION; K-SAM; EXPRESSION; FGF; DOMAIN; CELLS; CLONING AB To assess the effect(s) of the C-terminal domain on FGFR2 function, we engineered a series of mutant FGFR2 cDNAs encoding deletions in the C-terminus of the receptor and compared their growth properties in NIH3T3 fibroblasts, In contrast to FGFR2-WT, receptors with C-terminal truncations induced ligand-independent transformation of NIH3T3 cells and transfectants expressing these mutant receptors efficiently formed colonies in semisolid medium. Introduction of point mutations (Y to F) into the C-terminus of FGFR2 at positions 813, 784 or 780 revealed that these mutant receptors also displayed activities similar to that of C-terminally truncated receptors. C-terminally altered FGF receptors did not show an increase in the basal level of receptor phosphorylation compared to that of FGFR2-WT suggesting that elevated receptor phosphorylation does not underlie the transforming activity of these receptors. Interestingly, expression of transforming FGFR2 derivatives, unlike H-Ras transformed cells, did not result in the activation of the mitogen-activated protein kinases (MAPKs), p42/ERK2 and p44/ERK1, indicating that this pathway is not constitutively active in FGFR2-transformed cells, Finally, we report the overexpression of FGFR2 mRNA and protein in several human tumor cell lines suggesting activation of the receptor in these tumors. RP Lorenzi, MV (reprint author), NCI,CELLULAR & MOL BIOL LAB,BETHESDA,MD 20892, USA. NR 45 TC 17 Z9 17 U1 0 U2 0 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE, HAMPSHIRE, ENGLAND RG21 6XS SN 0950-9232 J9 ONCOGENE JI Oncogene PD AUG 14 PY 1997 VL 15 IS 7 BP 817 EP 826 DI 10.1038/sj.onc.1201242 PG 10 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA XQ117 UT WOS:A1997XQ11700008 PM 9266968 ER PT J AU Huang, CC Papas, TS Bhat, NK AF Huang, CC Papas, TS Bhat, NK TI A variant form of ETS1 induces apoptosis in human colon cancer cells SO ONCOGENE LA English DT Article DE oncogene; tumor suppressor gene; colon cancer; ETS1 protein; epithelial cancer ID TRANSCRIPTION FACTORS; EXPRESSION; GENES; ISOFORMS; PROTEINS; BINDING; FAMILY AB We have previously shown that the human ETS1 protein (pS1-ETS1), when ectopically expressed in colon cancer cell lines, is able to reduce its tumorigenicity without affecting its growth properties, To understand the mechanism of tumor reduction, we have expressed two different forms of ETS1 in colon cancer cell lines, Data presented in this paper indicate that the naturally occurring spliced variant protein, p42-ETS1, lacking the region encoded by ETS1 exon VII, represses the tumorigenicity, while p51-ETS1 reduces the tumorigenicity, Repression of tumorigenicity mediated by p42-ETS1 appears to be caused by its ability to induce apoptosis in epithelial cancer cells, This work can have profound medical significance in that it may open up new insights into the potential role of the p42-ETS1 in the induction of apoptosis in epithelial cell cancers and may provide a rationale for its use for potential gene therapy experiments to initiate cell death in cancer cells. C1 NCI,FREDERICK CANC RES & DEV CTR,SAIC,RECOMBINANT DNA LAB,FREDERICK,MD 21702. RP Huang, CC (reprint author), MED UNIV S CAROLINA,HOLLINGS CANC CTR,CTR MOL & STRUCT BIOL,CHARLESTON,SC 29425, USA. NR 20 TC 39 Z9 39 U1 1 U2 3 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE, HAMPSHIRE, ENGLAND RG21 6XS SN 0950-9232 J9 ONCOGENE JI Oncogene PD AUG 14 PY 1997 VL 15 IS 7 BP 851 EP 856 DI 10.1038/sj.onc.1201408 PG 6 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA XQ117 UT WOS:A1997XQ11700012 PM 9266972 ER PT J AU Peters, R Sikorski, R AF Peters, R Sikorski, R TI The cardiology beat - An Internet education for patients and health professionals SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article C1 HARVARD UNIV,SCH MED,BOSTON,MA. NCI,BETHESDA,MD 20892. RP Peters, R (reprint author), MASSACHUSETTS GEN HOSP,DEPT MED,WANG BLDG,ACC-108,FRUIT ST,BOSTON,MA 02114, USA. NR 0 TC 5 Z9 5 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 AUG 13 PY 1997 VL 278 IS 6 BP 451 EP 452 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA XP243 UT WOS:A1997XP24300001 PM 9256206 ER PT J AU Cohen, JI AF Cohen, JI TI Epstein-Barr virus and the immune system - Hide and seek SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID BURKITTS-LYMPHOMA CELLS; B-CELLS; LYMPHOPROLIFERATIVE DISEASE; EXPRESSION; SURVEILLANCE; LYMPHOCYTES; INFECTION; EBV RP Cohen, JI (reprint author), NIAID,MED VIROL SECT,CLIN INVEST LAB,NIH,BLDG 10,ROOM 11N214,BETHESDA,MD 20892, USA. NR 24 TC 22 Z9 24 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 AUG 13 PY 1997 VL 278 IS 6 BP 510 EP 513 DI 10.1001/jama.278.6.510 PG 4 WC Medicine, General & Internal SC General & Internal Medicine GA XP243 UT WOS:A1997XP24300034 PM 9256227 ER PT J AU Ji, XH Tordova, M ODonnell, R Parsons, JF Hayden, JB Gilliland, GL Zimniak, P AF Ji, XH Tordova, M ODonnell, R Parsons, JF Hayden, JB Gilliland, GL Zimniak, P TI Structure and function of the xenobiotic substrate-binding site and location of a potential non-substrate-binding site in a class pi glutathione S-transferase SO BIOCHEMISTRY LA English DT Article ID 3-DIMENSIONAL STRUCTURE; CRYSTAL-STRUCTURE; CHEMICAL HEPATOCARCINOGENESIS; MACROMOLECULAR STRUCTURES; ANGSTROM RESOLUTION; OPTICAL ENANTIOMERS; HUMAN PLACENTA; ACTIVE-SITE; MOUSE-LIVER; COMPLEX AB Complex structures of a naturally occurring variant of human class pi glutathione S-transferase 1-1 (hGSTP1-1) with either S-hexylglutathione or (9R,10R)-9-(S-glutathionyl)-10-hydroxy-9,10-dihydrophenanthrene [(9R,10R)-GSPhen] have been determined at resolutions of 1.8 and 1.9 Angstrom, respectively. The crystal structures reveal that the xenobiotic substrate-binding site (H-site) is located at a position similar to that observed in class mu GST 1-1 from rat liver (rGSTM1-1). In rGSTM1-1, the H-site is a hydrophobic cavity defined by the side chains of Y6, W7, V9, L12, I111, Y115, F208, and S209. In hGSTP1-1, the cavity is approximately half hydrophobic and half hydrophilic and is defined by the side chains of Y7, F8, V10, R13, V104, Y108, N204, and G205 and five water molecules. A hydrogen bond network connects the five water molecules and the side chains of R13 and N204. V104 is positioned such that the introduction of a methyl group (the result of the V104I mutation) disturbs the H-site water structure and alters the substrate-binding properties of the isozyme. The hydroxyl group of Y7 forms a hydrogen bond (3.2 Angstrom) with the sulfur atom of the product. There is a short hydrogen bond (2.5 Angstrom) between Y108 (OH) and (9R, 10R)-GSPhen (O5), indicating the hydroxyl group of Y108 as an electrophilic participant in the addition of glutathione to epoxides. An N-(2-hydroxethyl)piperazine-N'-2-ethanesulfonic acid (HEPES) molecule is found in the cavity between beta 2 and alpha I. The location and properties of this HEPES-binding site fit a possible non-substrate-binding site that is involved in noncompetitive inhibition of the enzyme. C1 UNIV MARYLAND,INST BIOTECHNOL,CTR ADV RES BIOTECHNOL,ROCKVILLE,MD 20850. NATL INST STAND & TECHNOL,ROCKVILLE,MD 20850. VANDERBILT UNIV,SCH MED,DEPT BIOCHEM,NASHVILLE,TN 37232. VANDERBILT UNIV,SCH MED,CTR MOL TOXICOL,NASHVILLE,TN 37232. UNIV ARKANSAS MED SCI,DEPT MED,LITTLE ROCK,AR 72205. UNIV ARKANSAS MED SCI,DEPT BIOCHEM & MOL BIOL,LITTLE ROCK,AR 72205. JOHN L MCCLELLAN MEM VET ADM MED CTR,LITTLE ROCK,AR 72205. RP Ji, XH (reprint author), NCI,FREDERICK CANC RES & DEV CTR,ABL BASIC RES PROGRAM,FREDERICK,MD 21702, USA. RI Ji, Xinhua/C-9664-2012 OI Ji, Xinhua/0000-0001-6942-1514 FU NIEHS NIH HHS [ES07804]; NIGMS NIH HHS [R01 GM30910] NR 70 TC 78 Z9 79 U1 1 U2 2 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD AUG 12 PY 1997 VL 36 IS 32 BP 9690 EP 9702 DI 10.1021/bi970805s PG 13 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA XQ760 UT WOS:A1997XQ76000008 PM 9245401 ER PT J AU Huttner, KM Kozak, CA Bevins, CL AF Huttner, KM Kozak, CA Bevins, CL TI The mouse genome encodes a single homolog of the antimicrobial peptide human beta-defensin 1 SO FEBS LETTERS LA English DT Article DE antimicrobial peptide; defensin; mouse ID AIRWAY EPITHELIAL-CELLS; EXPRESSION; GENES; CHROMOSOME-8; ANTIBIOTICS; FAMILY; HBD-1 AB The cysteine-rich beta-defensin peptides are broad-spectrum bactericidal agents expressed in epithelial and myeloid tissues, The human beta-defensin-1 (hBD-1) gene maps adjacent to the human alpha-defensin cluster and is expressed in the respiratory, gastrointestinal and genitourinary tracts, Here, we characterize a mouse beta-defensin gene (mBD-1) which is: (1) closely related to hBD-1 both in sequence and gene organization; (2) expressed at high levels in the mouse kidney and at lower levels in brain, heart, lung, uterus, spleen, skeletal muscle, stomach, and small intestine; and (3) maps to mouse chromosome 8 at or near the location of the mouse alpha-defensin genes, These data indicate that mBD-1 is a close homolog of hBD-1, and suggest that analysis of its role in mouse host defense may provide significant insights into human epithelial innate immunity, (C) 1997 Federation of European Biochemical Societies. C1 NIAID,MOL MICROBIOL LAB,BETHESDA,MD 20892. CLEVELAND CLIN FDN,DEPT IMMUNOL,CLEVELAND,OH 44195. CLEVELAND CLIN FDN,DEPT GASTROENTEROL & COLORECTAL SURG,CLEVELAND,OH 44195. RP Huttner, KM (reprint author), CHILDRENS HOSP,JOINT PROGRAM NEONATOL,300 LONGWOOD AVE,BOSTON,MA 02115, USA. FU NIAID NIH HHS [AI32738] NR 24 TC 85 Z9 88 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0014-5793 J9 FEBS LETT JI FEBS Lett. PD AUG 11 PY 1997 VL 413 IS 1 BP 45 EP 49 DI 10.1016/S0014-5793(97)00875-2 PG 5 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA XT084 UT WOS:A1997XT08400009 PM 9287114 ER PT J AU Sumner, MT Shears, SB AF Sumner, MT Shears, SB TI HIV-1 envelope protein, gp120, has no effects on inositol phosphate production and metabolism in the Jurkat T-cell line either in the presence or absence of receptor stimulation SO FEBS LETTERS LA English DT Article DE HIV envelope glycoprotein; signal transduction; CD3/TCR complex; inositol phosphate metabolism ID MONOCLONAL-ANTIBODIES; SIGNAL TRANSDUCTION; RECOMBINANT GP120; CD4; LYMPHOCYTES; ACTIVATION; PATHWAY; GLYCOPROTEIN; AIDS; POLYPHOSPHATES AB We have used HPLC techniques to investigate the effects of gp120 upon inositol phosphate turnover in Jurkat E6-1 CD4(+) T-cells, to pursue previous reports that this viral coat protein: (a) inhibits receptor-activated inositol phosphate release; (b) stimulates basal inositol phosphate release; (c) inhibits inositol polyphosphate 5-phosphatase. Treatment of cells with up to 10 mu g/ml gp120 from between 10 min and 24 h was without effect upon inositol phosphate turnover in both basal cells, and in C305 and OKT3 stimulated cells. This is the first report that biologically competent gp120 does not affect any aspect of inositol phosphate turnover in either basal or receptor-activated lymphocytes. (C) 1997 Federation of European Biochemical Societies. RP Sumner, MT (reprint author), NIEHS,LAB SIGNAL TRANSDUCT,INOSITAL LIPID SECT,NIH,POB 12233,RES TRIANGLE PK,NC 27709, USA. NR 34 TC 1 Z9 1 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 AUG 11 PY 1997 VL 413 IS 1 BP 75 EP 80 DI 10.1016/S0014-5793(97)00880-6 PG 6 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA XT084 UT WOS:A1997XT08400015 PM 9287120 ER PT J AU Rubtsov, YP Zolotukhin, AS Vorobjev, IA Chichkova, NV Pavlov, NA Karger, EM Evstafieva, AG Felber, BK Vartapetian, AB AF Rubtsov, YP Zolotukhin, AS Vorobjev, IA Chichkova, NV Pavlov, NA Karger, EM Evstafieva, AG Felber, BK Vartapetian, AB TI Mutational analysis of human prothymosin alpha reveals a bipartite nuclear localization signal SO FEBS LETTERS LA English DT Article DE prothymosin alpha; PCR-based mutagenesis; cell growth inhibition; nuclear localization signal; Saccharomyces cerevisiae ID YEAST SACCHAROMYCES-CEREVISIAE; MESSENGER-RNA; GENE FAMILY; CELL-CYCLE; PROTEIN; PARATHYMOSIN; MYC; PHOSPHORYLATION; IDENTIFICATION; PROLIFERATION AB Mutants of human prothymosin alpha with impaired ability to inhibit yeast Saccharomyces cerevisiae. cerevisiae cell growth were characterized, Two types of prothymosin alpha-inactivating mutations were observed, Mutations that belong to the first type compromised the nuclear entry of prothymosin alpha by affecting its nuclear localization signal. Analysis of subcellular distribution of GFP-prothymosin alpha fusions revealed a bipartite nuclear localization signal that is both necessary and sufficient for nuclear import of the protein in human cells, Mutations of the second type abrogated the inhibitory action of prothymosin alpha through an unknown mechanism, without influencing the nuclear import of the protein. (C) 1997 Federation of European Biochemical Societies. C1 MOSCOW MV LOMONOSOV STATE UNIV,BELOZERSKY INST PHYSICOCHEM BIOL,MOSCOW 119899,RUSSIA. NCI,FREDERICK CANC RES & DEV CTR,ABL BASIC RES PROGRAM,FREDERICK,MD 21701. RI Vartapetian, Andrey/B-8536-2012; Chichkova, Nina/C-9994-2012; Evstafieva, Alexandra/D-9170-2012; Rubtsov, Yury/A-8227-2014 NR 34 TC 36 Z9 37 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0014-5793 J9 FEBS LETT JI FEBS Lett. PD AUG 11 PY 1997 VL 413 IS 1 BP 135 EP 141 DI 10.1016/S0014-5793(97)00824-7 PG 7 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA XT084 UT WOS:A1997XT08400026 PM 9287131 ER PT J AU Choudhury, BK Kim, J Kung, HF Li, SSL AF Choudhury, BK Kim, J Kung, HF Li, SSL TI Cloning and developmental expression of Xenopus cDNAs encoding the Enhancer of split groucho and related proteins SO GENE LA English DT Article DE nucleotide sequence; protein; gene expression; tissues; phylogenetic tree; amphibian ID LOOP-HELIX PROTEINS; DROSOPHILA-ENHANCER; BETA-SUBUNIT; EARLY NEUROGENESIS; SACCHAROMYCES-CEREVISIAE; MOLECULAR-CLONING; GENE-PRODUCT; MELANOGASTER; LOCUS; COMPLEX AB The two full-length cDNAs encoding ESG1 (Enhancer of split groucho) and related AES (Amino Enhancer of split) proteins of 767 and 197 amino acids, respectively, were cloned and sequenced from the African frog Xenopus laevis. The amino acid sequence of Xenopus ESG1 protein had 61% identity to the full-length Drosophila groucho. Xenopus AES protein exhibited 91%, 58% and 48% identity to the mouse AES, amino-terminal regions of Xenopus ESG1 end Drosophila groucho, respectively. Northern blot analysis showed that widespread RNA expression of ESG1 of 2.8 kb, ESG2 of 3.6 kb and AES of 2.2 kb transcripts were seen in adult tissues, whereas ESG1 and AES transcripts of 2.8 kb and 2.2 kb, respectively, were ubiquitously expressed in the developing embryos. The overall structural relationships of ESG and AES proteins among human, mouse, rat, Xenopus and Drosophila were analysed. (C) 1997 Elsevier Science B.V. C1 NIEHS,MOL GENET LAB,NIH,RES TRIANGLE PK,NC 27709. NCI,BIOCHEM PHYSIOL LAB,NIH,FREDERICK,MD 21702. NATL SUN YAT SEN UNIV,INST LIFE SCI,KAOHSIUNG 80424,TAIWAN. NR 28 TC 28 Z9 31 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0378-1119 J9 GENE JI Gene PD AUG 11 PY 1997 VL 195 IS 1 BP 41 EP 48 DI 10.1016/S0378-1119(97)00150-9 PG 8 WC Genetics & Heredity SC Genetics & Heredity GA XT078 UT WOS:A1997XT07800006 PM 9300818 ER PT J AU Lublin, AL Diehl, NL Hochgeschwender, U AF Lublin, AL Diehl, NL Hochgeschwender, U TI Isolation and characterization of the gene encoding the type 5 mouse (Mus musculus) somatostatin receptor (msst(5)) SO GENE LA English DT Article DE gene cloning; nucleotide sequence; expression; RT-PCR ID MOLECULAR-CLONING; RAT-BRAIN; FUNCTIONAL-CHARACTERIZATION; EXPRESSION; FAMILY; SSTR3; CDNA AB We have isolated and determined the nucleotide sequence of the gene for the fifth mouse somatostatin receptor (msst(5)). The gene can encode a protein of 363 amino acid residues (aa). The deduced aa sequence of msst(5) has 97 and 81% identity to the rat and human sst(5) respectively, while it has lower identities with the four other mouse sst(n)s (msst(1)-48%, msst(2)-55%, msst(3)-56%, and msst4-52%). We show that msst(5) is expressed in brain but not in liver, heart, spleen, or kidney of the adult mouse. (C) 1997 Elsevier Science B.V. C1 NIMH,GENET MOL LAB,NSB,BETHESDA,MD 20892. NR 20 TC 10 Z9 11 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0378-1119 J9 GENE JI Gene PD AUG 11 PY 1997 VL 195 IS 1 BP 63 EP 66 DI 10.1016/S0378-1119(97)00156-X PG 4 WC Genetics & Heredity SC Genetics & Heredity GA XT078 UT WOS:A1997XT07800009 PM 9300821 ER PT J AU Gopalan, G Chan, CSM Donovan, PJ AF Gopalan, G Chan, CSM Donovan, PJ TI A novel mammalian, mitotic spindle-associated kinase is related to yeast and fly chromosome segregation regulators SO JOURNAL OF CELL BIOLOGY LA English DT Article ID TYPE-1 PROTEIN PHOSPHATASE; CELL-CYCLE; LOCALIZATION; CENTROSOME; INTERPHASE; COMPONENTS; APPARATUS; NUCLEUS AB We describe a novel mammalian protein kinase related to two newly identified yeast and fly kinases-Ipl1 and aurora, respectively-mutations in which cause disruption of chromosome segregation. We have designated this kinase as Ipl1- and aurora-related kinase 1 (IAK1). IAK1 expression in mouse fibroblasts is tightly regulated temporally and spatially during the cell cycle. Transcripts first appear at G(1)/S boundary, are elevated at M-phase, and disappear rapidly after completion of mitosis. The protein levels and kinase activity of IAK1 are also cell cycle regulated with a peak at M-phase. IAK1 protein has a distinct subcellular and temporal pattern of localization. It is first identified on the centrosomes immediately after the duplicated centrosomes have separated. The protein remains on the centrosome and the centrosome-proximal part of the spindle throughout mitosis and is detected weakly on midbody microtubules at telophase and cytokinesis, In cells recovering from nocodazole treatment and in taxol-treated mitotic cells, IAK1 is associated with microtubule organizing centers. A wild-type and a mutant form of IAK1 cause mitotic spindle defects and lethality in ipl1 mutant yeast cells but not in wild-type cells, suggesting that IAK1 interferes with Ipl1p function in yeast. Taken together, these data strongly suggest that IAK1 may have an important role in centrosome and/or spindle function during chromosome segregation in mammalian cells. We suggest that IAK1 is a new member of an emerging subfamily of the serine/threonine kinase superfamily. The members of this subfamily may be important regulators of chromosome segregation. C1 NCI, FREDERICK CANC RES & DEV CTR, ABL BASIC RES PROGRAM, CELL BIOL DEV & DIFFERENTIAT GRP, FREDERICK, MD 21702 USA. UNIV TEXAS, DEPT MICROBIOL, AUSTIN, TX 78712 USA. FU NIGMS NIH HHS [GM45185] NR 37 TC 106 Z9 108 U1 0 U2 2 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 950 THIRD AVE, 2ND FLR, NEW YORK, NY 10022 USA SN 0021-9525 EI 1540-8140 J9 J CELL BIOL JI J. Cell Biol. PD AUG 11 PY 1997 VL 138 IS 3 BP 643 EP 656 DI 10.1083/jcb.138.3.643 PG 14 WC Cell Biology SC Cell Biology GA XR478 UT WOS:A1997XR47800014 PM 9245792 ER PT J AU Blechynden, LM Lawson, MA Tabarias, H Garlepp, MJ Sherman, J Raben, N Lawson, CM AF Blechynden, LM Lawson, MA Tabarias, H Garlepp, MJ Sherman, J Raben, N Lawson, CM TI Myositis induced by naked DNA immunization with the gene for histidyl-tRNA synthetase SO HUMAN GENE THERAPY LA English DT Article ID TRANSFER-RNA-SYNTHETASE; INFLAMMATORY MYOPATHY; MOUSE MUSCLE; PLASMID DNA; EXPRESSION; MICE; AUTOANTIBODIES; INJECTION; ANTIBODY; EPITOPE AB Polymyositis is regarded as an autoimmune inflammatory muscle disease, A major subgroup of patients have autoantibodies to cellular histidyl-transfer RNA synthetase (HRS), We have analyzed the role of the autoantigen HRS in the induction of murine myositis in a comparative study of inoculation of BALB/c mice with recombinant HRS protein versus naked DNA coding for HRS, Adult BALB/c mice produced antibodies to human HRS following inoculation with HRS protein and adjuvant, but myositis was not observed, Alternatively, expression plasmid DNA constructs encoding full-length and truncated human HRS were inoculated intramuscularly in gene transfer studies, DNA-inoculated mice produced relatively low anti-HRS antibody titers, However, in contrast to recombinant HRS protein-inoculated mice, HRS gene transfer induced pathology with evidence of cellular infiltration of perivascular and endomysial regions of the inoculated muscle, Multiple inoculations of a plasmid construct encoding a hybrid molecule consisting of HRS and the transferrin receptor cytoplasmic tail induced the highest levels of antibodies and persisting cellular infiltration. Unlike HRS, expression of influenza virus hemagglutinin (HA) following inoculation of an HA plasmid did not induce myositis, Transfer of naked DNA constructs expressing HRS is likely to provide valuable information on the autoimmune response to this protein and its role in the development of myositis. C1 UNIV WESTERN AUSTRALIA,QUEEN ELIZABETH II MED CTR,DEPT MICROBIOL,NEDLANDS,WA 6009,AUSTRALIA. UNIV WESTERN AUSTRALIA,QUEEN ELIZABETH II MED CTR,DEPT MED,NEDLANDS,WA 6009,AUSTRALIA. UNIV WESTERN AUSTRALIA,QUEEN ELIZABETH II MED CTR,AUSTRALIAN NEUROMUSCULAR RES INST,NEDLANDS,WA 6009,AUSTRALIA. NIAMSD,ARTHRIT & RHEUMATISM BRANCH,NIH,BETHESDA,MD 20892. NR 42 TC 18 Z9 20 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 AUG 10 PY 1997 VL 8 IS 12 BP 1469 EP 1480 DI 10.1089/hum.1997.8.12-1469 PG 12 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA XR655 UT WOS:A1997XR65500006 PM 9287147 ER PT J AU Lozier, JN Yankaskas, JR Ramsey, WJ Chen, L Berschneider, H Morgan, RA AF Lozier, JN Yankaskas, JR Ramsey, WJ Chen, L Berschneider, H Morgan, RA TI Gut epithelial cells as targets for gene therapy of hemophilia SO HUMAN GENE THERAPY LA English DT Article ID HUMAN FACTOR-IX; HUMAN FACTOR-VIII; TRANSGENIC MICE; PRIMARY MYOBLASTS; SKIN FIBROBLASTS; EXPRESSION; TRANSPLANTATION; DEFICIENCY; DELIVERY; VECTORS AB Gut epithelium is an attractive target for gene therapy of hemophilia due to the large number of rapidly dividing cells that should be readily accessible to a wide range of vectors by a noninvasive route of administration, We have performed in vitro tests to determine the suitability of gut epithelial cells for gene transfer, protein synthesis, and secretion of coagulation factors VIII and IX, The results with retroviral vectors indicate that transduced epithelial cells from human, rat, or porcine small or large intestine can synthesize significant amounts of factor VIII or factor IX and that two-thirds or more of the recombinant protein is secreted in a basolateral direction (i.e., away from the lumen and toward underlying capillaries and lymphatics). Furthermore, we have demonstrated that intestinal epithelial cells are susceptible to efficient gene transfer by lipofection and adenovirus vectors, In the case of factor IX, we have produced a high-titer adenovirus vector capable of transducing gut epithelial cells resulting in synthesis of factor IX, The results of our in vitro studies indicate that gene transfer targeting gut epithelium as a new approach to hemophilia gene therapy is rational and merits in vivo studies in hemophilia animal models. C1 NHGRI,GENE TRANSFER TECHNOL SECT,CLIN GENE THERAPY BRANCH,NIH,BETHESDA,MD 20892. UNIV N CAROLINA,DEPT MED,DIV PULM MED,CHAPEL HILL,NC 27599. N CAROLINA STATE UNIV,COLL VET MED,RALEIGH,NC 27606. FU NHLBI NIH HHS [HL51818] NR 48 TC 41 Z9 43 U1 1 U2 2 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 AUG 10 PY 1997 VL 8 IS 12 BP 1481 EP 1490 DI 10.1089/hum.1997.8.12-1481 PG 10 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA XR655 UT WOS:A1997XR65500007 PM 9287148 ER PT J AU Chen, Z Grebe, TA Guan, XY Notohamiprodjo, M Nutting, PJ Stone, JF Trent, JM Sandberg, AA AF Chen, Z Grebe, TA Guan, XY Notohamiprodjo, M Nutting, PJ Stone, JF Trent, JM Sandberg, AA TI Maternal balanced translocation leading to partial duplication of 4q and partial deletion of ip in a son: Cytogenetic and FISH studies using band-specific painting probes generated by chromosome microdissection SO AMERICAN JOURNAL OF MEDICAL GENETICS LA English DT Article DE dup(4q); del(1p); chromosome translocation; FISH; chromosome microdissection ID PARTIAL TRISOMY 4Q; FLUORESCENCE INSITU HYBRIDIZATION; 1P; CONFIRMATION; DISORDERS; PATIENT AB A 9-month-old boy with pre- and post-natal growth retardation, microcephaly, plagiocephaly, and several minor anomalies had the initial karyotype: 46,XY,der(1)t(1;?) (p36.1;?), Further analysis showed that the der(1) was derived from an unfavorable segregation of a maternal complex chromosome rearrangement, i.e., 46,XX,der(1)t(1;?) (p36.1;?), der(4)t(4;?)(q?;?). Whole chromosome fluorescence in situ hybridization (FISH) and chromosome microdissection were used to clarify the maternal karyotype as: 46,XX,der(1)t(1;4)(4qter-->4q33:: 1p36.13-->1qter),der(4)t(1;4)inv(4)(4pter--> 4q31.3::1p36.33-->1p36.13::4q33-->4q31.3:: 1p36.33-->1pter). Therefore, the karyotype of the boy actually was 46,XY,der(1)t(1;4) (p36.13;q33). Clinical comparison of the patient's clinical findings showed similarities to individuals with partial del(lp) and dup(4q), To our knowledge the above cytogenetic abnormalities have not been described previously. This case further demonstrates the advantages of chromosome microdissection and FISH in the identification of anomalous chromosome regions and breakpoints. (C) 1997 Wiley-Liss, Inc. C1 GENZYME GENET,SCOTTSDALE,AZ. UNIV ARIZONA,DEPT PEDIAT,INTEGRATED GENET PROGRAM,PHOENIX,AZ. NIH,NATL CTR HUMAN GENOME RES,CANC GENET LAB,BETHESDA,MD 20892. RI Guan, Xin-Yuan/A-3639-2009 OI Guan, Xin-Yuan/0000-0002-4485-6017 NR 29 TC 15 Z9 15 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0148-7299 J9 AM J MED GENET JI Am. J. Med. Genet. PD AUG 8 PY 1997 VL 71 IS 2 BP 160 EP 166 DI 10.1002/(SICI)1096-8628(19970808)71:2<160::AID-AJMG8>3.0.CO;2-1 PG 7 WC Genetics & Heredity SC Genetics & Heredity GA XG894 UT WOS:A1997XG89400008 PM 9217215 ER PT J AU Kirsch, IR AF Kirsch, IR TI Genetics of human cancer: pathogenesis and diagnosis - Keystone, Colorado, January 27 February 2, 1997 SO BIOCHIMICA ET BIOPHYSICA ACTA-REVIEWS ON CANCER LA English DT Editorial Material RP Kirsch, IR (reprint author), NCI,DIV CLIN SCI,MED BRANCH,DEPT GENET,BETHESDA,MD 20892, USA. 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 0304-419X J9 BBA-REV CANCER JI Biochim. Biophys. Acta-Rev. Cancer PD AUG 8 PY 1997 VL 1333 IS 1 BP R1 EP R7 DI 10.1016/S0304-419X(97)00013-9 PG 7 WC Biochemistry & Molecular Biology; Biophysics; Oncology SC Biochemistry & Molecular Biology; Biophysics; Oncology GA XX095 UT WOS:A1997XX09500006 PM 9294019 ER PT J AU Chen, HW Lin, RJ Schiltz, RL Chakravarti, D Nash, A Nagy, L Privalsky, ML Nakatani, Y Evans, RM AF Chen, HW Lin, RJ Schiltz, RL Chakravarti, D Nash, A Nagy, L Privalsky, ML Nakatani, Y Evans, RM TI Nuclear receptor coactivator ACTR is a novel histone acetyltransferase and forms a multimeric activation complex with P/CAF and CBP/p300 SO CELL LA English DT Article ID THYROID-HORMONE RECEPTOR; TRANSCRIPTION FACTOR TFIIB; DEPENDENT TRANSACTIVATION; CO-REPRESSOR; PROTEIN CBP; DOMAIN; SUPERFAMILY; NUCLEOSOME; MEDIATE; BINDING AB We report here the identification of a novel cofactor, ACTR, that directly binds nuclear receptors and stimulates their transcriptional activities in a hormone-dependent fashion. ACTR also recruits two other nuclear factors, CBP and P/CAF, and thus plays a central role in creating a multisubunit coactivator complex. In addition, and unexpectedly, we show that purified ACTR is a potent histone acetyltransferase and appears to define a distinct evolutionary branch to this recently described family. Thus, hormonal activation by nuclear receptors involves the mutual recruitment of at least three classes of histone acetyltransferases that may act cooperatively as an enzymatic unit to reverse the effects of histone cleacetylase shown to be part of the nuclear receptor corepressor complex. C1 HOWARD HUGHES MED INST,LA JOLLA,CA 92037. SALK INST BIOL STUDIES,LA JOLLA,CA 92037. UNIV CALIF SAN DIEGO,SCH MED,GRAD PROGRAM MOL PATHOL,LA JOLLA,CA 92037. NICHHD,LAB MOL GROWTH REGULAT,NATL INST HLTH,BETHESDA,MD 20892. UNIV CALIF DAVIS,MICROBIOL SECT,DIV BIOL SCI,DAVIS,CA 95616. RI Nagy, Laszlo/A-3814-2008 OI Nagy, Laszlo/0000-0001-6653-2155 FU NICHD NIH HHS [HD27183]; NIGMS NIH HHS [GM26444] NR 59 TC 1160 Z9 1173 U1 0 U2 11 PU CELL PRESS PI CAMBRIDGE PA 1050 MASSACHUSETTES AVE, CIRCULATION DEPT, CAMBRIDGE, MA 02138 SN 0092-8674 J9 CELL JI Cell PD AUG 8 PY 1997 VL 90 IS 3 BP 569 EP 580 DI 10.1016/S0092-8674(00)80516-4 PG 12 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA XQ063 UT WOS:A1997XQ06300020 PM 9267036 ER PT J AU Alkhatib, G Ahuja, SS Light, D Mummidi, S Berger, EA Ahuja, SK AF Alkhatib, G Ahuja, SS Light, D Mummidi, S Berger, EA Ahuja, SK TI CC chemokine receptor 5-mediated signaling and HIV-1 co-receptor activity share common structural determinants - Critical residues in the third extracellular loop support HIV-1 fusion SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID RECOMBINANT VACCINIA VIRUS; ENVELOPE GLYCOPROTEIN; EXPRESSION; CELLS AB There is a close correspondence between the ability of RANTES and macrophage inflammatory proteins 1 alpha and 1 beta to activate CC chemokine receptor 5 (CCR5) and the ability to inhibit CCR5-dependent membrane fusion mediated by the envelope glycoprotein of human immuno-deficiency virus (HIV), type 1, This finding suggests that some of the structural determinants for CC chemokine/CCR5 interactions and CCR5 HIV-1 fusion co-receptor activity may be shared, Recent studies rising human CCR5/CCR2B chimeras have suggested that the determinants of CCR5 co-receptor activity are complex and may involve multiple extracellular receptor domains and that viral co-receptor activity is dissociable from ligand-dependent signaling responses, However, conclusive evidence demonstrating an important role for the second and third extracellular regions of human CCR5 is lacking, Furthermore, to determine whether the determinants for CCR5 co-receptor activity overlap with those required for agonist activity, studies that compare the chemokine specificity for inhibition of envelope-mediated cell fusion and the agonist profile of chimeric receptors are necessary, In the present report, using a series of CCR5/CCR2B chimeras we ascribe an important role for the second and third extracellular loop of CCR5 in supporting the co-receptor activity of CCR5, We also provide evidence that the intracytoplasmic tail of CCR5 does not play an important role in supporting HIV-1 entry, The hypothesis that the structural determinants for CC chemokine/CCR5 interactions and CCR5 HIV-1 fusion co-receptor activity may be shared was confirmed by two novel observations: first, the fusion activity supported by two hybrid receptors could be inhibited by both RANTES and monocyte chemoattractant protein-1, chemokines specific to CCR5 and CCR2B, respectively; and second, the chemokine specificity for inhibition of envelope-mediated cell fusion matched the agonist profile of these hybrid receptors. These data shed new light on the structural determinants involved in these distinct activities of CCR5 and may have important implications for the development of CCR5-targeted anti-viral compounds. C1 UNIV TEXAS,HLTH SCI CTR,DEPT MED,SAN ANTONIO,TX 78284. NIAID,VIRAL DIS LAB,NIH,BETHESDA,MD 20892. S TEXAS VET HLTH CARE SYST,SAN ANTONIO,TX 78284. RI Mummidi, Srinivas/C-1004-2008 OI Mummidi, Srinivas/0000-0002-4068-6380 NR 30 TC 74 Z9 74 U1 0 U2 1 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD AUG 8 PY 1997 VL 272 IS 32 BP 19771 EP 19776 DI 10.1074/jbc.272.32.19771 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA XQ059 UT WOS:A1997XQ05900023 PM 9242636 ER PT J AU Saji, M Shong, MH Napolitano, G Palmer, LA Taniguchi, S Ohmori, M Ohta, M Suzuki, K Kirshner, SL Giuliani, C Singer, DS Kohn, LD AF Saji, M Shong, MH Napolitano, G Palmer, LA Taniguchi, S Ohmori, M Ohta, M Suzuki, K Kirshner, SL Giuliani, C Singer, DS Kohn, LD TI Regulation of major histocompatibility complex class I gene expression in thyroid cells - Role of the cAMP response element-like sequence SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID THYROTROPIN RECEPTOR GENE; SYSTEMIC LUPUS-ERYTHEMATOSUS; TRANSCRIPTION FACTOR-I; DNA-BINDING PROTEIN; PANCREATIC-ISLET CELLS; CYCLIC-AMP; FOAMY VIRUS; SOMATOSTATIN EXPRESSION; PROMOTER INTERACTS; INTERFERON THERAPY AB The major histocompatibility complex (MBC) class I gene cAMP response element (CBE)-like site, -107 to - 100 base pairs, is a critical component of a previously unrecognized silencer, -127 to -90 bp, important for thyrotropin (TSH)/cAMP-mediated repression in thyrocytes, TSH/cAMP induced-silencer activity is associated with the formation of novel complexes with the 38-base pair silencer, whose appearance requires the CRE and. involves ubiquitous and thyroid-specific proteins as follows: the CRE-binding protein, a Y-box protein termed thyrotropin receptor (TSHR) suppressor element protein-1 (TSEP-1); thyroid transcription factor-1 (TTF-1); and Pax-8. TTF-1 is as enhancer of Glass I promoter activity; Pax-8 and TSEP-1 are suppressors, TSH/cAMP decreases TTF-1 complex formation with the silencer, thereby decreasing maximal class I expression; TSH/cAMP enhance TSEP-1 and Pax-8 complex formation in association with their repressive actions, Oligonucleotides that bind TSEP-1, not Pax-8, prevent formation of the TSH/cAMP-induced complexes associated with TSH-induced class I suppression, i.e. TSEP-1 appears to be the dominant repressor factor associated with TSH/cAMP-decreased class I activity and formation of the novel complexes. TSEP-1, TTF-1, and/or Pax-8 are involved in TSH/cAMP-induced negative regulation of the TSH receptor Gene in thyrocytes, suppression-of MHC class II, and up-regulation of thyroglobulin. TSH/cAMP coordinate regulation of common transcription factors may, therefore, be the basis fop self-tolerance and the absence of autoimmunity iu. the face of TSHR-mediated increases in gene products that are important for thyroid growth and function but are able to act as autoantigens. C1 NIDDK,METAB DIS BRANCH,NIH,CELL REGULAT SECT,BETHESDA,MD 20892. NCI,EXPT IMMUNOL BRANCH,NIH,BETHESDA,MD 20892. RI Saji, Motoyasu/E-4007-2011 NR 76 TC 53 Z9 54 U1 0 U2 1 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD AUG 8 PY 1997 VL 272 IS 32 BP 20096 EP 20107 DI 10.1074/jbc.272.32.20096 PG 12 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA XQ059 UT WOS:A1997XQ05900070 PM 9242683 ER PT J AU Obiri, NI Murata, T Debinski, W Puri, RK AF Obiri, NI Murata, T Debinski, W Puri, RK TI Modulation of interleukin (IL)-13 binding and signaling by the gamma(c) chain of the IL-2 receptor SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID CELL CARCINOMA-CELLS; FUNCTIONAL COMPONENT; TRANSDUCTION; ACTIVATION; JAK1; SIMILARITIES AB Interleukin (IL)-13 and IL-4 are cytokine products of T(H)2 cells which exert similar effects in a variety of cell types. We recently described IL-ISR expression on human renal cell and colon carcinoma cells and demonstrated that gamma(c) is not a component of IL-13R, or IL-4R systems in these cells, In lymphoid cells such as B cells and monocytes, which respond to IL-13, gamma(c) is a component of IL-4R but does not appear to be a component of IL-13R, Furthermore, while significant IL-13 binding is observed on carcinoma cells, IL-13 barely binds these lymphoid cells and the binding characteristics are different, To better understand the role of gamma(c) in IL-13 binding and signaling, we have transfected a renal cell carcinoma cell line with gamma(c) and examined IL-13 and IL-4 binding and signaling, IL-13 binding as well as IL-13 and IL-4 signaling through the JAK-STAT signaling pathway were severely inhibited, This inhibition was paralleled by a loss of expression of one of the IL-13R chains and intercellular cell adhesion molecule-1. Thus, although gamma(c) has been shown to enhance IL-4 binding and function in some cell types, its influence on IL-13R function in tumor cells appear to be largely negative. C1 PENN STATE UNIV,MILTON S HERSHEY MED CTR,COLL MED,DEPT SURG,DIV NEUROSURG,HERSHEY,PA 17033. RP Obiri, NI (reprint author), US FDA,LAB MOL TUMOR BIOL,DIV CELLULAR & GENE THERAPIES,CTR BIOL EVALUAT & RES,NIH,HFM-530,BETHESDA,MD 20892, USA. NR 33 TC 49 Z9 50 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 AUG 8 PY 1997 VL 272 IS 32 BP 20251 EP 20258 DI 10.1074/jbc.272.32.20251 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA XQ059 UT WOS:A1997XQ05900091 PM 9242704 ER PT J AU Erman, B Bahar, I Jemigan, RL AF Erman, B Bahar, I Jemigan, RL TI Equilibrium states of rigid bodies with multiple interaction sites: Application to protein helices SO JOURNAL OF CHEMICAL PHYSICS LA English DT Article ID MINIMA PROBLEM; SIMULATIONS; RESOLUTION; ALGORITHM; DYNAMICS; SEARCH; FOLD AB Equilibrium configurations of rigid building blocks with multiple embedded interaction sites are investigated, as a coarse-grained approach for conformational sampling of protein structures with known secondary structure. First, hypothetical structures of asymmetric shapes, and pairs of rods composed of multiple interaction sites are considered. The rods are either disconnected or joined by a flexible loop. The sites are assumed to interact with a classical 6-12 Lennard-Jones potential. Subsequently, the investigation is extended to the study of two disconnected alpha helices composed of homogeneous interaction sites and to the ROP monomer, a small protein consisting of two heterogeneous alpha helices connected by a loop. Residue-specific long-range and short-range potentials extracted from a protein database are used, A Monte Carlo procedure combined with an energy minimization algorithm, originally developed by Li and Scheraga [Proc. Natl.-Acad. Sci. USA 84, 6611 (1987)] is used to generate a set of low energy conformations over the full conformational space. Results show that: (i) The potential of mean force between two rods as a whole exhibits an inverse linear dependence on the separation between rods despite the individual sites interacting via a 6-12 Lennard-Jones potential. (ii) As the length of the rods (or helices) increases, they tend to align parallel to one other. (iii) This tendency to become parallel is enhanced when the density of interaction sites is higher. (iv) The angle between the principal axes of the rods is found to scale as n(-5/3) with the number n of sites. (v) The native conformation of the ROP monomer, including the detailed rotational states of the virtual bonds located in the loop connecting the alpha helices is correctly predicted. This lends support to the adoption of such a coarse-grained model and its parameters for future simulations. (C) 1997 American Institute of Physics. C1 TUBITAK,ADV POLYMER MAT RES CTR,TR-80815 BEBEK,ISTANBUL,TURKEY. NCI,MOL STRUCT SECT,LAB EXPT & COMPUTAT BIOL,DIV BASIC SCI,NIH,BETHESDA,MD 20892. RP Erman, B (reprint author), BOGAZICI UNIV,CTR POLYMER RES,TR-80815 BEBEK,ISTANBUL,TURKEY. OI ERMAN, BURAK/0000-0002-2496-6059 NR 27 TC 14 Z9 14 U1 0 U2 3 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 AUG 8 PY 1997 VL 107 IS 6 BP 2046 EP 2059 DI 10.1063/1.474555 PG 14 WC Chemistry, Physical; Physics, Atomic, Molecular & Chemical SC Chemistry; Physics GA XP280 UT WOS:A1997XP28000038 ER PT J AU Hohjoh, H Singer, MF AF Hohjoh, H Singer, MF TI Ribonuclease and high salt sensitivity of the ribonucleoprotein complex formed by the human LINE-1 retrotransposon SO JOURNAL OF MOLECULAR BIOLOGY LA English DT Article DE human LINE-1 (L1Hs); retrotransposon; non-LTR retrotransposon; ribonucleoprotein complex; ribonuclease and high salt treatments ID HUMAN TRANSPOSABLE ELEMENT; VIRUS; PROTEIN; RNA; INSERTION; ENCAPSIDATION; PARTICLES; SEQUENCES; GENE AB P40 is encoded by the first open reading frame of the human LINE-1 retrotransposon and is found ina large cytoplasmic ribonucleoprotein (RNP) complex, the p40 RNP-complex, in association with LINE-1 RNA(s) in human teratocarcinoma cell lines. We report here investigations on the stability of the p40 RNP-complex against various nucleases and high salt (0.5 M NaCl) treatment. The results indicate that (1) the p40 RNP-complex is dissociated after ribonuclease or high salt treatment, (2) DNase I does not disrupt the complex, (3) after dissociation of the complex, p40 maintains protein-protein interactions but in smaller complexes, and (4) p40 is not associated with the LINE-1 RNA(s) after high salt treatment. These observations suggest that the RNA molecule(s) is(are) essential for the stability of the large p40 complex and that the complex has;I structure which allows various nucleases to reach the RNA. These features are distinct from those of typical virus and virus-like particles of retroviruses and other retrotransposons, respectively. Together with the fact that no significant sequence homology exists between p40 and the gag and gag-like proteins, it is likely that the p40 RNP-complex is structuraly different from the typical virus and virus-like particles. (C) 1997 Academic Press Limited. C1 NCI,BIOCHEM LAB,NIH,BETHESDA,MD 20892. CARNEGIE INST WASHINGTON,WASHINGTON,DC 20005. NR 22 TC 21 Z9 21 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 AUG 8 PY 1997 VL 271 IS 1 BP 7 EP 12 DI 10.1006/jmbi.1997.1159 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA XP903 UT WOS:A1997XP90300002 PM 9300051 ER PT J AU Ye, B Yao, ZJ Burke, TR AF Ye, B Yao, ZJ Burke, TR TI Synthesis of a new tyrosine analogue having (chi 1) and (chi 2) angles constrained to values observed for an SH2 domain-bound phosphotyrosyl residue SO JOURNAL OF ORGANIC CHEMISTRY LA English DT Article ID SRC HOMOLOGY-2 DOMAIN; RECEPTOR; INHIBITORS; PEPTIDE; CHAIN; MIMETICS AB Synthesis is reported of a new tricyclic amino acid, (+/-)-(rel-2S,3R)-2-carboxy-1,2,3,4,5,6-hexahydro -8-hydroxy-1,5-methano-3-methyl-3-benzazocine (2), which contains within its structure the elements of a tyrosine moiety having chi(1) and chi(2) angles (168 degrees and -95 degrees, respectively) constrained to values observed for a phosphotyrosyl (pTyr) residue bound to the 56(lck) SH2 domain (chi(1) and chi(2) values of 163 degrees and -94 degrees, respectively). Additionally, the phi angle of N-acylated 2 correlates well with the phi angle of the SH2 domain-bound pTyr residue. Compound 2 represents a unique, highly constrained amino acid which may be of value in signal transduction studies. C1 NCI,DIV BASIC SCI,MED CHEM LAB,NIH,BETHESDA,MD 20892. RI Burke, Terrence/N-2601-2014; Yao, Zhu-Jun/E-7635-2015 NR 23 TC 13 Z9 13 U1 0 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0022-3263 J9 J ORG CHEM JI J. Org. Chem. PD AUG 8 PY 1997 VL 62 IS 16 BP 5428 EP 5431 DI 10.1021/jo9700787 PG 4 WC Chemistry, Organic SC Chemistry GA XP911 UT WOS:A1997XP91100028 ER PT J AU Nomeir, AA Matthews, HB AF Nomeir, AA Matthews, HB TI Metabolism and disposition of dimethyl hydrogen phosphite in rats and mice SO JOURNAL OF TOXICOLOGY AND ENVIRONMENTAL HEALTH LA English DT Article ID EXCRETION AB A study of dimethyl hydrogen phosphite (DMHP) by the National Toxicology Program (NTP) indicated that chronic administration by oral gavage resulted in an increased incidence of neoplastic lesions in the lungs and forestomachs of Fischer 344 rats but not in B6C3F1 mice. The current study was designed to evaluate the metabolic basis, if any, of this species selectivity by studying the metabolism and disposition of [C-14]DMHP in the respective strains of rats and mice. Results of this study indicate that DMHP administered at a range of dose of 10-200 mg/kg was readily and near completely absorbed from the gastrointestinal tracts of rats and mice. DMHP-derived radioactivity was eliminated primarily as CO, in the expired air, 44-57%, and urine, 28-49%, and very little was collected in feces, 1-2%, or as volatile organics, 2-3%. DMHP-derived radioactivity was widely distributed in tissues of rats and mice, with the highest concentrations observed in the liver, kidneys, spleen, lungs, and forestomach, and the lowest in brain, skeletal muscle, and adipose tissue. The disappearance of radioactivity from mouse tissues was approximately twice as rapid as from rat tissues. In vitro, DMHP was metabolized to formaldehyde by the microsomal fractions of liver, lungs, kidneys, forestomach, and glandular stomach. In vivo, DMHP was metabolized to the product of demethylation, monomethyl hydrogen phosphite (MMHP), which was excreted in urine. Results of this study indicate that the NTP carcinogenicity study with DMHP was carried out within the dose range in which the absorption, metabolism, and disposition of DMHP are linear in both species. Apparent species-dependent differences in the metabolism and disposition of DMHP are limited to the more rapid metabolism and elimination by the mouse. Therefore, the species-dependent variations in the carcinogenicity of DMHP are most likely attributable to factors other than metabolism and disposition. C1 NATL INST ENVIRONM HLTH SCI,NATL TOXICOL PROGRAM,TOXICOL RES & TESTING PROGRAM,RES TRIANGLE PK,NC 27709. NR 14 TC 1 Z9 1 U1 1 U2 5 PU TAYLOR & FRANCIS PI BRISTOL PA 1900 FROST ROAD, SUITE 101, BRISTOL, PA 19007-1598 SN 0098-4108 J9 J TOXICOL ENV HEALTH JI J. Toxicol. Environ. Health PD AUG 8 PY 1997 VL 51 IS 5 BP 489 EP 501 PG 13 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA XL414 UT WOS:A1997XL41400006 PM 9233382 ER PT J AU Jakowlew, SB Mariano, JM You, L Mathias, A AF Jakowlew, SB Mariano, JM You, L Mathias, A TI Differential regulation of protease and extracellular matrix protein expression by transforming growth factor-beta 1 in non-small cell lung cancer cells and normal human bronchial epithelial cells SO BIOCHIMICA ET BIOPHYSICA ACTA-GENE STRUCTURE AND EXPRESSION LA English DT Article DE transforming growth factor-beta; plasminogen activator; plasminogen activator inhibitor; extracellular matrix; lung ID PLASMINOGEN-ACTIVATOR INHIBITOR; AMINO-ACID SEQUENCE; TGF-BETA; EMBRYO FIBROBLASTS; STRUCTURAL DOMAINS; FACTOR-BETA-1 GENE; CARCINOMA-CELLS; MESSENGER-RNAS; II RECEPTOR; CLONING AB In addition to autoregulating its own expression, transforming growth factor-beta 1 (TGF-beta 1) also regulates the production of proteases, protease inhibitors and extracellular matrix proteins, To investigate the relationship between plasminogen activator (PA), plasminogen activator inhibitor-1 (PAI-1) and the extracellular matrix in malignant and normal lung epithelial cells and to determine whether malignant lung epithelial cells may be more invasive than normal lung epithelial cells because of differences in expression of these proteins in response to TGF-beta, the regulation of PA, PAI-1, fibronectin, laminin and thrombospondin by TGF-beta 1 in human non-small cell lung cancer (NSCLC) cells was examined and compared with normal human bronchial epithelial (NHBE) cells. TGF-beta 1 caused a persistent increase in expression of the mRNAs for both PA and PAI-1 in NSCLC cells, with the increase in PAI-1 mRNA beginning several hours before that of PA mRNA. By immunoprecipitation analysis, it was shown that TGF-beta 1 also induced a corresponding increase in the amount of PAI-1 protein in these NSCLC cells as well. In contrast, while TGF-beta 1 also increased expression of PAI-I mRNA in NHBE cells, expression of PA mRNA decreased simultaneously. Treatment of NSCLC cells with TGF-beta 1 resulted in a persistent increase in expression of the mRNAs for fibronectin, laminin and thrombospondin; expression of fibronectin protein also increased after treatment with TGF-beta 1 in these cells. When NHBE cells were similarly cultured in the presence of TGF-beta 1, expression of fibronectin mRNA also increased in a persistent manner; however, only an early transient increase in the level of the mRNAs for laminin and thrombospondin was detected in these cells. These data show that there is differential regulation of the genes for PA and PAI-I and the extracellular matrix protein fibronectin in response to TGF-beta 1 not only when NSCLC and NHBE cells are compared, but also when different NSCLC cells are compared with each other. (C) 1997 Elsevier Science B.V. RP Jakowlew, SB (reprint author), NCI, MED BRANCH, 9610 MED CTR DR, SUITE C300, ROCKVILLE, MD 20850 USA. NR 39 TC 27 Z9 28 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0167-4781 J9 BBA-GENE STRUCT EXPR JI Biochim. Biophys. Acta-Gene Struct. Expression PD AUG 7 PY 1997 VL 1353 IS 2 BP 157 EP 170 DI 10.1016/S0167-4781(97)00068-7 PG 14 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA XR499 UT WOS:A1997XR49900011 PM 9294010 ER PT J AU Casalini, P Menard, S Malandrin, SMI Rigo, CM Colnaghi, MI Cultraro, CM Segal, S AF Casalini, P Menard, S Malandrin, SMI Rigo, CM Colnaghi, MI Cultraro, CM Segal, S TI Inhibition of tumorigenicity in lung adenocarcinoma cells by c-erbB-2 antisense expression SO INTERNATIONAL JOURNAL OF CANCER LA English DT Article ID MONOCLONAL-ANTIBODIES; BREAST-CANCER; RECEPTOR; ONCOGENE; GENE; CARCINOMA; OVEREXPRESSION; ONCOPROTEIN; ERBB-2; GROWTH AB The lung carcinoma cell line Calu3, which overexpresses the c-erbB-2 oncogene, was stably transfected with antisense (AS) cDNA constructs encompassing different regions of the c-erbB-2 gene. Transfected cells were analyzed for their tumorigenic properties in vitro and in nude mice. Two independent clones, AS pi (low erbB-2 expressor) and AS B12 (high erbB-2 expressor), as well as the polyclonal Calu3/AS 5', were selected for these analyses. In Calu3/AS 5' transfected cells and in the AS FI clone, c-erbB-2 RNA and protein levels were lower than those detected in the parental cell line and the AS B12 clone. Anchorage-independent growth and tumor take were also significantly reduced. Furthermore, cells derived from primary tumors of Calu3/AS 5', AS FI and AS B12 lost the AS c-erbB-2 DNA insert but retained the gene for G418 resistance. Our results suggest that a correlation between c-erbB2 overexpression and tumorigenicity may exist in the Calu3 lung carcinoma cell line. (C) 1997 Wiley-Liss, Inc. C1 IST NAZL TUMORI,DIV EXPT ONCOL E,I-20133 MILAN,ITALY. USN HOSP,NCI,MED ONCOL BRANCH,BETHESDA,MD 20814. NR 29 TC 15 Z9 16 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 AUG 7 PY 1997 VL 72 IS 4 BP 631 EP 636 DI 10.1002/(SICI)1097-0215(19970807)72:4<631::AID-IJC14>3.0.CO;2-E PG 6 WC Oncology SC Oncology GA XP731 UT WOS:A1997XP73100014 PM 9259403 ER PT J AU Brown, KE Young, NS AF Brown, KE Young, NS TI Hepatitis-associated aplastic anemia - Reply SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Letter RP Brown, KE (reprint author), NHLBI,BLDG 10,BETHESDA,MD 20892, USA. NR 6 TC 1 Z9 1 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 AUG 7 PY 1997 VL 337 IS 6 BP 425 EP 425 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA XP407 UT WOS:A1997XP40700017 ER PT J AU Weinberg, WC Montano, NE Deng, C AF Weinberg, WC Montano, NE Deng, C TI Loss of p21(CIP1/WAF1) does not recapitulate accelerated malignant conversion caused by p53 loss in experimental skin carcinogenesis SO ONCOGENE LA English DT Article DE p53; p21(CIP1/WAF1); epidermal carcinogenesis ID P53-MEDIATED G(1) ARREST; HARVEY SARCOMA-VIRUS; P53-INDEPENDENT PATHWAY; PRIMARY KERATINOCYTES; GENE DOSAGE; EXPRESSION; P21; PROGRESSION; INHIBITOR; WAF1/CIP1 AB The p21(CIP1/WAF1) protein is considered a downstream effector of tumor suppression by p53, We have previously demonstrated that p53 null keratinocytes have lower basal p21(CIP1/WAF1) mRNA levels and that tumors derived from these cells following transduction with the v-ras(Ha) oncogene grow faster than wildtype keratinocytes and rapidly progress to undifferentiated carcinomas (Cancer Res 54: 5584-5592, 1994), In this study, primary keratinocytes differing in p21(CIP1/WAF1) gene dose were transduced with v-ras(Ha) encoding retrovirus and grafted to nude mouse hosts to test whether the p53 null phenotype is mediated through p21(CIP1/WAF1). Resulting tumors from all genotypes were well differentiated papillomas; focal carcinomas were observed in 43, 30 and 44% of papillomas derived from +/+, +/- and -/- keratinocytes, respectively, p21(CIP1/WAF1) deficient keratinocytes expressing v-ras(Ha) do not display the degree of increased growth observed in p53 deficient tumors irt vivo or the decreased responsiveness to negative growth regulation by Ca2+ in vitro. These results suggest that p21(CIP1/WAF1) does not regulate the differentiated phenotype or malignant progression of v-ras(Ha) initiated keratinocytes and that additional functions of the p53 protein other than transcriptional regulation Of the p21(CIP1/WAF1) gene are required for p53 mediated tumor suppression. C1 NIDDKD,BIOCHEM & METAB LAB,NIH,BETHESDA,MD 20892. RP Weinberg, WC (reprint author), NCI,CELLULAR CARCINOGENESIS & TUMOR PROMOT LAB,NIH,BETHESDA,MD 20892, USA. RI Weinberg, Wendy/A-8920-2009; deng, chuxia/N-6713-2016 NR 33 TC 23 Z9 23 U1 0 U2 0 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE, HAMPSHIRE, ENGLAND RG21 6XS SN 0950-9232 J9 ONCOGENE JI Oncogene PD AUG 7 PY 1997 VL 15 IS 6 BP 685 EP 690 DI 10.1038/sj.onc.1201230 PG 6 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA XP683 UT WOS:A1997XP68300008 PM 9264409 ER PT J AU Simon, R Freidlin, B Rubinstein, L Arbuck, SG Collins, J Christian, MC AF Simon, R Freidlin, B Rubinstein, L Arbuck, SG Collins, J Christian, MC TI Accelerated titration designs for phase I clinical trials in oncology SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID CONTINUAL REASSESSMENT METHOD; CANCER; AGENTS; ORDER AB Background: Many cancer patients in phase I clinical trials are treated at doses of chemotherapeutic agents that are below the biologically active level, thus reducing their chances for therapeutic benefit. Current phase I trials often take a long time to complete and provide little information about interpatient variability or cumulative toxicity, Purpose: Our objective mas to develop alternative designs for phase I trials so that fewer patients are treated at subtherapeutic dose levels, trials are of reduced duration, and important information (i.e., cumulative toxicity and maximum tolerated dose) needed to plan phase II trials is obtained. Methods: We fit a stochastic model to data from 20 phase I trials involving the study of nine different drugs. We then simulated new data from the model with the parameters estimated from the actual trials and evaluated the performance of alternative phase I designs on this simulated data. Four designs were evaluated. Design 1 was a conventional design (similar to the commonly used modified Fibonacci method) using cohorts of three to sis patients, with 40% dose-step increments and no intrapatient dose escalation, Designs 2 through 4 included only one patient per cohere until one patient experienced close-limiting toxic effects or two patients experienced grade 2 toxic effects (during their first course of treatment for designs 2 and 3 or during any course of treatment fur design 4). Designs 3 and 4 used 100% dose steps during this initial accelerated phase. After the initial accelerated phase, designs 2 through 4 resorted to standard cohorts of three to six patients, with 40% dose-step increments, Designs 2 through 4 used intrapatient dose escalation if the worst toxicity is grade 0-1 in the previous course for that patient. Results: Only three of the actual trials demonstrated cumulative toxic effects of the chemotherapeutic agents in patients, The average number of patients required for a phase I trial was reduced from 39.9 for design 1 to 24.4, 20.7, and 21.2 for designs 2, 3, and 4, respectively. The average number of patients who would be expected to have grade 0-1 toxicity as their worst toxicity over three cycles of treatment is 23.3 for design 1, but only 7.9, 3.9, and 4.8 for designs 2, 3, and 4, respectively. The average number of patients with grade 3 toxicity as their worst toxicity increases from 5.5 for design 1 to 6.2, 6.8, and 6.2 for designs 2, 3, and 4, respectively, The average number of patients with grade 4 toxicity as their worst toxicity increases from 1.9 for design 1 to 3.0, 4.3, and 3.2 for designs 2, 3, and 4, respectively. Conclusion: Accelerated titration (i.e., rapid intrapatient drug dose escalation) designs appear to effectively reduce the number of patients who are undertreated, speed the completion of phase I trials, and provide a substantial increase in the information obtained. C1 NCI,DIV CANC TREATMENT,CANC THERAPY EVALUAT PROGRAM,BETHESDA,MD 20892. EMMES CORP,POTOMAC,MD. US FDA,ROCKVILLE,MD 20857. NR 18 TC 348 Z9 356 U1 1 U2 13 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 AUG 6 PY 1997 VL 89 IS 15 BP 1138 EP 1147 DI 10.1093/jnci/89.15.1138 PG 10 WC Oncology SC Oncology GA XP270 UT WOS:A1997XP27000013 PM 9262252 ER PT J AU Zhuang, ZP Merino, MJ Vortmeyer, AO Bryant, B Lash, AE Wang, CY Deavers, MT Shelton, WF Kapur, S Chandra, RS AF Zhuang, ZP Merino, MJ Vortmeyer, AO Bryant, B Lash, AE Wang, CY Deavers, MT Shelton, WF Kapur, S Chandra, RS TI Identical genetic changes in different histologic components of Wilms' tumors SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID POLYMERASE CHAIN-REACTION; HUMAN CHROMOSOME-11; DELETION; CELLS; HETEROZYGOSITY; ASSOCIATION; MUTATION; CANCER; LOCUS; WT1 AB Background: In young children and infants, Wilms' tumor is the most common cancer of the kidney. Wilms' tumor exhibits heterogeneous histopathologic features, consisting of rapidly proliferating blastemal and epithelial cells and a stromal component that has heterologous elements (e.g,, cartilage, bone, and striated muscle), Ia. is unclear whether the stromal and heterologous components of sporadic Wilms' tumor are neoplastic or should be considered non-neoplastic, Purpose: Our purpose was twofold: 1) to selectively analyze the different histologic tissue components of sporadic Wilms' tumors, including blastemal, epithelial, stromal, and heterologous elements, for loss of heterozygosity (LOH) of the WT1 gene and for expression of the WT1 gene and 2) to determine the! role of WT1 gene expression in the development of these tissues, Methods: By use of tissue microdissection techniques, various histologic elements (blastema, stroma, epithelium, and striated muscle) of sporadic Wilms' tumor were obtained from specimens taken from 18 patients. DNA was extracted from the dissected tissue fragments, and DNA solutions were amplified by use of the polymerase chain reaction and the polymorphic genomic markers D11S1392 and D11S904 to detect LOH at the WT1 gene locus (11p13). Three selected specimens with heterologous elements and LOH af 11p13 were analyzed for expression of the WT1 gene hv means of the in situ reverse transcr iption-polymerase chain reaction. Results: Nine (50%) of the 18 spesimens showed LOH at the WT1 locus. Although identical WTB. gene deletion was consistently observed in all of the various histologic components; of these nine specimens, WT1 gene expression was high in the blastemal and epithelial elements and low in the stromal and heterologous elements, Conclusions and Implications: Identical allelic deletion at 11p13 in all components of the sporadic Wilms' tumors examined suggests that the stromal tissue components are neoplastic rather than noneoplastic, In conjunction with variable WT1 gene expression in the different histologic components, the results raise the possibility that undifferentiated blastemal cells are the? precursors of the stromal and heterologous elements. Morphologically benign stromal and heterologous elements may therefore be derived. from neoplastic cells. The developmental state of the various tissue components of Wilms' tumor may he attributed to an altered residual WT1 gene that is required for the maturation of blastemal and epithelial cells hut flat is not required for the maturation of stromal and heterologous elements. C1 NCI,PATHOL LAB,BETHESDA,MD 20892. WALTER REED ARMY MED CTR,DEPT PATHOL,WASHINGTON,DC 20307. CHILDRENS NATL MED CTR,DEPT PATHOL,WASHINGTON,DC 20010. OI Lash, Alex/0000-0003-3787-1590 NR 25 TC 24 Z9 28 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 AUG 6 PY 1997 VL 89 IS 15 BP 1148 EP 1152 DI 10.1093/jnci/89.15.1148 PG 5 WC Oncology SC Oncology GA XP270 UT WOS:A1997XP27000014 PM 9262253 ER PT J AU Ruffin, MT Krishnan, K Rock, CL Normolle, D Vaerten, MA PetersGolden, M Crowell, J Kelloff, G Boland, CR Brenner, DE AF Ruffin, MT Krishnan, K Rock, CL Normolle, D Vaerten, MA PetersGolden, M Crowell, J Kelloff, G Boland, CR Brenner, DE TI Suppression of human colorectal mucosal prostaglandins: Determining the lowest effective aspirin dose SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID NONSTEROIDAL ANTIINFLAMMATORY DRUGS; INTESTINAL TUMORS; RAT COLON; LIQUID-CHROMATOGRAPHY; RHEUMATOID-ARTHRITIS; RANDOMIZED TRIAL; EPITHELIAL-CELLS; REDUCED RISK; CANCER; INDOMETHACIN AB Background: A variety of studies have supported the finding that regular intake of aspirin (acetylsalicylic acid) or nonsteroidal anti-inflammatory agents san affect colorectal cancer carcinogenesis, These agents inhibit the synthesis of prostagiandins, High levels of prostaglandins are observed in colon cancer tissues. Purpose: Experiments were planned to determine the lowest dose of aspirin that can markedly suppress the levels of mucosal prostaglandins E-2 and F-2 alpha in colorectal mucosa and to determine whether a relationship exists between een these levels and plasma levels of both acetylsalicylic acid and its metabolite, salicylic acid. Methods: Healthy men and women aged 18 years or older participated in the study. The participants took a single, daily dose of aspirin (40.5, 81, 162, 324, or 648 mg) or a placebo for 14 days. Colorectal biopsy specimens were taken at baseline, 24 hours after the first dose of aspirin, and 24-30 hours and 72-78 hours after the last, i.e., fourteenth, daily dose of aspirin. The biopsy specimens were assayed for prostaglandins E-2 and F-2 alpha by use of a competitive enzyme immunoassay, Plasma concentrations of acetylsalicylic acid and salicylic acid were determined by use of high-performance liquid chromatography, All P values are two-sided. Results: A total of 65 subjects (10 receiving placebo, groups of 10 each receiving 40.5, 81, 162, or 324 mg of aspirin, and a group of 15 receiving 648 mg of aspirin) completed the protocol. One subject reported unacceptable drug-induced toxic effects and did not complete the protocol; other subjects reported acceptable side effects. The lowest dose to significantly suppress colorectal mucosal prostaglandin E-2 concentrations from baseline at 24 hours after the first dose (by 22.6 %; P = .002) and at 24-30 hours after the last close (by 14.2%; P = .021) nas 162 mg. At 92-78 hours after the last dose, there was significant suppression for subjects receiving 81 mg (by 23.7%; P = .008). The lowest dose to significantly suppress colorectal mucosal prostaglandin F-2 alpha concentrations from baseline at 24 hours after the first dose (by 18.3%; P = .832) was 324 mg, The lowest dose causing a marked reduction in the level of prostaglandin F-2 alpha at 23-30 hours (by 15.1%; P = .003) and 72-78 hours (by 23.0%; P = .0002) after the last dose was 40.5 mg, NO detectable amounts of acetylsalicylic acid or salicylic acid were present in the plasma at any of the biopsy time points. Conclusions: The lowest doses of aspirin taken daily for 14 days to significantly suppress concentrations of colorectal mucosal prostaglandins E-2 and F-2 alpha were 81 and 40.5 mg, respectively. The suppression occurred without detectable amounts of aspirin or salicylic acid in the plasma at the time points studied. On the basis bf these observations, we recommend a single, daily dose of 81 mg of aspirin in future studies of this drug as a chemopreventive agent far colorectal cancer. C1 UNIV MICHIGAN, SCH MED, DEPT FAMILY PRACTICE, ANN ARBOR, MI 48109 USA. UNIV MICHIGAN, SCH MED, CTR COMPREHENS CANC, ANN ARBOR, MI 48109 USA. UNIV MICHIGAN, SCH MED, DEPT INTERNAL MED, ANN ARBOR, MI 48109 USA. DEPT VET AFFAIRS MED CTR, MED SERV, ANN ARBOR, MI USA. E TENNESSEE STATE UNIV, JAMES H QUILLEN COLL MED, DEPT MED, DIV HEMATOL & ONCOL, JOHNSON CITY, TN 37614 USA. MT HOME VA MED CTR, JOHNSON CITY, TN USA. UNIV CALIF SAN DIEGO, DEPT INTERNAL MED, DIV GASTROENTEROL, SAN DIEGO, CA 92103 USA. UNIV CALIF SAN DIEGO, DEPT FAMILY & PREVENT MED, SAN DIEGO, CA 92103 USA. NCI, DIV CANC PREVENT & CONTROL, CHEMOPREVENT BRANCH, BETHESDA, MD 20892 USA. OI Normolle, Daniel/0000-0001-8675-5014; Ruffin, Mack/0000-0001-8336-478X FU NCI NIH HHS [CN25429]; NCRR NIH HHS [MO1-RR00042] NR 60 TC 66 Z9 67 U1 0 U2 2 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 AUG 6 PY 1997 VL 89 IS 15 BP 1152 EP 1160 DI 10.1093/jnci/89.15.1152 PG 9 WC Oncology SC Oncology GA XP270 UT WOS:A1997XP27000015 PM 9262254 ER PT J AU Ogryzko, VV Brinkmann, E Howard, BH Pastan, I Brinkmann, U AF Ogryzko, VV Brinkmann, E Howard, BH Pastan, I Brinkmann, U TI Antisense inhibition of GAS, the human homologue of the yeast chromosome segregation gene CSE1, interferes with mitosis in HeLa cells SO BIOCHEMISTRY LA English DT Article ID SACCHAROMYCES-CEREVISIAE; SUPPRESSOR ELEMENTS; CLONING; TRANSITION; RESISTANCE; G1 AB We have analyzed the effects on HeLa cells of reduction of the CAS protein, the human homologue to yeast chromosome segregation protein CSE1. Expression of CAS antisense cDNA decreases the amount of CAS protein in HeLa cells and perturbs progression from G2 (retards transition from G2) to G1 in the cell cycle. Increased levels of cyclin B in CAS antisense transfected cells correlated with an arrest in G2 phase or mitosis. This arrest upon CAS attenuation is consistent with observations that yeast with CSE1 mutations are defective in mitosis and cyclin B degradation. C1 NICHHD,LAB MOL GROWTH REGULAT,NIH,BETHESDA,MD 20892. NCI,MOL BIOL LAB,DIV BASIC SCI,NIH,BETHESDA,MD 20892. RI Ogryzko, Vasily/M-6665-2015 OI Ogryzko, Vasily/0000-0002-8548-1389 NR 20 TC 27 Z9 28 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 AUG 5 PY 1997 VL 36 IS 31 BP 9493 EP 9500 DI 10.1021/bi970236o PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA XP631 UT WOS:A1997XP63100026 PM 9235994 ER PT J AU Ho, KKL Moody, GB Peng, CK Mietus, JE Larson, MG Levy, D Goldberger, AL AF Ho, KKL Moody, GB Peng, CK Mietus, JE Larson, MG Levy, D Goldberger, AL TI Predicting survival in heart failure case and control subjects by use of fully automated methods for deriving nonlinear and conventional indices of heart rate dynamics SO CIRCULATION LA English DT Article DE dynamics; Fourier analysis; heart failure; heart rate; survival ID RATE-VARIABILITY; MYOCARDIAL-INFARCTION; PERIOD VARIABILITY; TIME-SERIES; FRAMINGHAM; MORTALITY; DISEASE; RISK AB Background Despite much recent interest in quantification of heart rate variability (HRV), the prognostic value of conventional measures of HRV and of newer indices based on nonlinear dynamics is not universally accepted. Methods and Results We have designed algorithms for analyzing ambulatory ECG recordings and measuring HRV without human intervention, using robust methods for obtaining time-domain measures (mean and SD of heart rate), frequency-domain measures (power in the bands of 0.001 to 0.01 Hz [VLF], 0.01 to 0.15 Hz [LF], and 0.15 to 0.5 Hz [HF] and total spectral power [TP] over all three of these bands), and measures based on nonlinear dynamics (approximate entropy [ApEn], a measure of complexity, and detrended fluctuation analysis [DFA], a measure of long-term correlations). The study population consisted of chronic congestive heart failure (CHF) case patients and sex- and age-matched control subjects in the Framingham Heart Study. After exclusion of technically inadequate studies and those with atrial fibrillation, we used these algorithms to study HRV in 2-hour ambulatory ECG recordings of 69 participants (mean age, 71.7+/-8.1 years). By use of separate Cox proportional-hazards models, the conventional measures SD (P<.01), LF (P<.01), VLF (P<.05), and TP (P<.01) and the nonlinear measure DFA (P<.05) were predictors of survival over a mean follow-up period of 1.9 years; other measures, including ApEn (P>.3), were not. In multivariable models, DFA was of borderline predictive significance (P=.06) after adjustment for the diagnosis of CHF and SD. Conclusions These results demonstrate that HRV analysis of ambulatory ECG recordings based on fully automated methods can have prognostic value in a population-based study and that nonlinear HRV indices may contribute prognostic value to complement traditional HRV measures. C1 MIT,HARVARD MIT DIV HLTH SCI & TECHNOL,CAMBRIDGE,MA 02139. FRAMINGHAM HEART DIS EPIDEMIOL STUDY,FRAMINGHAM,MA 01701. NHLBI,BETHESDA,MD 20892. BOSTON UNIV,SCH MED,BOSTON,MA 02118. RP Ho, KKL (reprint author), BETH ISRAEL DEACONESS MED CTR,DIV CARDIOVASC,330 BROOKLINE AVE,RW-453,BOSTON,MA 02215, USA. RI Peng, Chung-Kang/E-1489-2011 OI Peng, Chung-Kang/0000-0003-3666-9833 FU NHLBI NIH HHS [N01-HC-38038]; NIMH NIH HHS [MH-54081] NR 27 TC 294 Z9 302 U1 0 U2 10 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD AUG 5 PY 1997 VL 96 IS 3 BP 842 EP 848 PG 7 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA XP130 UT WOS:A1997XP13000022 PM 9264491 ER PT J AU Lauer, MS Pashkow, FJ Larson, MG Levy, D AF Lauer, MS Pashkow, FJ Larson, MG Levy, D TI Association of cigarette smoking with chronotropic incompetence and prognosis in the Framingham Heart Study SO CIRCULATION LA English DT Article DE heart rate; exercise; epidemiology; prognosis; smoking ID PHYSICAL-ACTIVITY; EXERCISE; VASOCONSTRICTION; DISEASE; SMOKERS; HEALTH; MEN AB Background In this study, we sought to determine whether cigarette smoking is associated with chronotropic incompetence and to explore prognostic implications of this association. Methods and Results Members of the Framingham Offspring Study (1468 men and 1642 women) underwent graded exercise. Chronotropic incompetence was assessed in two ways: (1) failure to achieve an age-predicted target heart rate and (2) a low chronotropic index, a heart rate response measure that accounts for effects of age, resting heart rate, and physical fitness. Smokers were more likely to fail to reach target heart rate than were nonsmokers (men, 25% versus 15%, odds ratio [OR], 1.97; 95% confidence interval [CI], 1.51 to 2.56; women, 32% versus 18%; OR, 2.10; 95% CI, 1.63 to 2.61) and were more likely to have a low chronotropic index (men, 17% versus 12%; OR, 1.50; 95% CI, 1.12 to 2.03; women, 17% versus 8%; OR, 2.28; 95% CI, 1.68 to 3.09). These associations persisted after adjustment for age, cardiovascular risk factors, pulmonary function, and ST-segment response to graded exercise. During 8 years of follow-up, there were 48 deaths and 90 incident coronary heart disease events among the men. After adjust ment for the same confounders, men who were smokers and failed to achieve target heart rate were at particularly high risk for death (adjusted relative risk [RR], 2.45; 95% CI, 1.14 to 5.24) and for coronary heart disease (adjusted RR, 4.92; 95% CI, 2.84 to 8.53). There were too few end points in women for analysis. Conclusions In this population-based cohort, cigarette smoking was predictive of chronotropic incompetence. Male smokers who manifested chronotropic incompetence were at particularly high risk for death and coronary heart disease events. C1 BOSTON UNIV,DEPT EPIDEMIOL & PREVENT MED,BOSTON,MA 02215. FRAMINGHAM HEART DIS EPIDEMIOL STUDY,FRAMINGHAM,MA. NHLBI,NIH,BETHESDA,MD 20892. RP Lauer, MS (reprint author), CLEVELAND CLIN FDN,DEPT CARDIOL,DESK F-25,9500 EUCLID AVE,CLEVELAND,OH 44195, USA. RI Lauer, Michael/L-9656-2013 OI Lauer, Michael/0000-0002-9217-8177 NR 29 TC 40 Z9 41 U1 1 U2 1 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD AUG 5 PY 1997 VL 96 IS 3 BP 897 EP 903 PG 7 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA XP130 UT WOS:A1997XP13000029 PM 9264498 ER PT J AU Tawa, GJ Martin, RL Pratt, LR AF Tawa, GJ Martin, RL Pratt, LR TI Reaction field spectral shifts with semiempirical molecular orbital theory SO INTERNATIONAL JOURNAL OF QUANTUM CHEMISTRY LA English DT Review ID SOLUTE ELECTRONIC-STRUCTURE; POLARIZABLE CONTINUUM MODEL; CLASSICAL SOLVENT DYNAMICS; NONEQUILIBRIUM SOLVATION; AQUEOUS-SOLUTION; FREE-ENERGIES; TAUTOMERIC EQUILIBRIA; GAS-PHASE; ELECTROSTATIC POTENTIALS; NEUTRAL MOLECULES AB A macroscopic solution polarization free-energy functional is combined with semiempirical molecular orbital theory to study shifts of electronic absorption energies for several molecules in solution. The present method requires calculation of the induced electrostatic potential on the van der Waals surface and this calculation is implemented in a new way. The combined method is tested by calculating absorption energy shifts for several molecules of standard interest. We find the physically reasonable result that there is a correlation between the absorption energy shift and the magnitude of the dipole moments of the initial and final states involved in the absorption transition. (C) 1997 John Wiley & Sons, Inc. C1 LOS ALAMOS NATL LAB, DIV THEORET, MS B268, LOS ALAMOS, NM 87545 USA. RP NCI, STRUCT BIOCHEM PROGRAM, FREDERICK BIOMED SUPERCOMP CTR, SAIC, FREDERICK CANC RES & DEV CTR, FREDERICK, MD 21702 USA. RI Pratt, Lawrence/H-7955-2012 OI Pratt, Lawrence/0000-0003-2351-7451 NR 109 TC 11 Z9 11 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0020-7608 EI 1097-461X J9 INT J QUANTUM CHEM JI Int. J. Quantum Chem. PD AUG 5 PY 1997 VL 64 IS 2 BP 143 EP 155 DI 10.1002/(SICI)1097-461X(1997)64:2<143::AID-QUA1>3.0.CO;2-W PG 13 WC Chemistry, Physical; Mathematics, Interdisciplinary Applications; Physics, Atomic, Molecular & Chemical SC Chemistry; Mathematics; Physics GA XM678 UT WOS:A1997XM67800001 ER PT J AU Szczepanowska, J Zhang, XL Herring, CJ Qin, J Korn, ED Brzeska, H AF Szczepanowska, J Zhang, XL Herring, CJ Qin, J Korn, ED Brzeska, H TI Identification by mass spectrometry of the phosphorylated residue responsible for activation of the catalytic domain of myosin I heavy chain kinase, a member of the PAK/STE20 family SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID AUTOPHOSPHORYLATION AB Myosin I heavy chain kinase from Acanthamoeba castellanii is activated in vitro by autophosphorylation (8-10 mol of P per mol). The catalytically active C-terminal domain produced by trypsin cleavage of the phosphorylated kinase contains 2-3 mol of P per mol. However, the catalytic domain expressed in a baculovirus-insect cell system is fully active as isolated without autophosphorylation in vitro. We now show that the expressed catalytic domain is inactivated by incubation with acid phosphatase and regains activity upon autophosphorylation, The state of phosphorylation of all of the hydroxyamino acids in the catalytic domain were determined by mass spectrometry of unfractionated protease digests. Ser-627 was phosphorylated in the active, expressed catalytic domain, lost its phosphate when the protein was incubated with phosphatase, and was rephosphorylated when the dephosphorylated protein was incubated with ATF, No other residue was significantly phosphorylated in any of the three samples, Thus, phosphorylation of Ser-627, which is in the same position as the Ser and Thr residues that are phosphorylated in many other kinases, is necessary and sufficient for full activity of the catalytic domain, Ser-627 is also phosphorylated when full-length, native kinase is activated by autophosphorylation. C1 NHLBI,CELL BIOL LAB,NIH,BETHESDA,MD 20892. NHLBI,BIOPHYS CHEM LAB,NIH,BETHESDA,MD 20892. RI Korn, Edward/F-9929-2012 NR 26 TC 22 Z9 22 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 AUG 5 PY 1997 VL 94 IS 16 BP 8503 EP 8508 DI 10.1073/pnas.94.16.8503 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA XQ124 UT WOS:A1997XQ12400039 PM 9238006 ER PT J AU Yanagi, M Purcell, RH Emerson, SU Bukh, J AF Yanagi, M Purcell, RH Emerson, SU Bukh, J TI Transcripts from a single full-length cDNA clone of hepatitis C virus are infectious when directly transfected into the liver of a chimpanzee SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID CELL LINE; 3' END; RNA; SEQUENCE; GENOME; REPLICATION; GENOTYPES; MARMOSETS; STRAIN; HCV AB We have succeeded in constructing a stable full-length cDNA clone of strain H77 (genotype la) of hepatitis C virus (HCV), We devised a cassette vector with fixed 5' and 3' termini and constructed multiple full-length cDNA clones of H77 in a single step by cloning of the entire ORF, which was amplified by long reverse transcriptase-PCR, directly into this vector, The infectivity of two complete full-length cDNA clones was tested bg the direct intrahepatic injection of a chimpanzee with RNA transcripts, However, we found no evidence for HCV replication. Sequence analysis of these and 16 additional full-length clones revealed that seven clones were defective for polyprotein synthesis, and the remaining nine clones had 6-28 amino acid mutations in the predicted polyprotein compared with the consensus sequence of H77. Next, we constructed a consensus chimera from four of the full-length cDNA clones with just two ligation steps, Injection of RNA transcripts from this consensus clone into the liver of a chimpanzee resulted in viral replication, The sequence of the virus recovered from the chimpanzee was identical to that of the injected RNA transcripts, This stable infectious molecular clone should be an important tool for developing a better understanding of the molecular biology and pathogenesis of HCV. C1 NIAID,INFECT DIS LAB,HEPATITIS VIRUSES SECT,NIH,BETHESDA,MD 20892. FU NCI NIH HHS [N01-CO-56000]; NIAID NIH HHS [N01-AI-45180, N01-AI-52705, R21 AI052705] NR 40 TC 394 Z9 412 U1 1 U2 12 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 AUG 5 PY 1997 VL 94 IS 16 BP 8738 EP 8743 DI 10.1073/pnas.94.16.8738 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA XQ124 UT WOS:A1997XQ12400080 PM 9238047 ER PT J AU Berman, KF Schmidt, PJ Rubinow, DR Danaceau, MA VanHorn, JD Esposito, G Ostrem, JL Weinberger, DR AF Berman, KF Schmidt, PJ Rubinow, DR Danaceau, MA VanHorn, JD Esposito, G Ostrem, JL Weinberger, DR TI Modulation of cognition-specific cortical activity by gonadal steroids: A positron-emission tomography study in women SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE frontal cortex; regional cerebral blood flow; estrogen; progesterone; Wisconsin Card Sorting Test ID CEREBRAL BLOOD-FLOW; DORSOLATERAL PREFRONTAL CORTEX; CARD SORTING TEST; PHYSIOLOGIC DYSFUNCTION; RHESUS-MONKEY; SCHIZOPHRENIA; DOPAMINE; ESTROGEN; PERFORMANCE; ACTIVATION AB There is considerable evidence from animal studies that gonadal steroid hormones modulate neuronal activity and affect behavior, To study this in humans directly, we used (H2O)-O-15 positron-emission tomography to measure regional cerebral blood flow (rCBF) in young women during three pharmacologically controlled hormonal conditions spanning 4-5 months: ovarian suppression induced by the gonadotropin-releasing hormone agonist leuprolide acetate (Lupron), Lupron plus estradiol replacement, and Lupron plus progesterone: replacement. Estradiol and progesterone were administered in a double-blind cross-over design, On each occasion positron-emission tomography scans were performed during (i) the Wisconsin Card Sorting Test, a neuropsychological test that physiologically activates prefrontal cortex (PFC) and an associated cortical network including inferior parietal lobule and posterior inferolateral temporal gyrus, and (ii) a no-delay matching-to-sample sensorimotor control task, During treatment with Lupron alone (i.e., with virtual absence of gonadal steroid hormones), there was marked attenuation of the typical Wisconsin Card Sorting Test activation pattern even tough task performance did not change, Most strikingly, there was no rCBF increase in PFC. When either progesterone or estrogen nas added to the Lupron regimen, there was normalization of the rCBF activation pattern with augmentation of the parietal and temporal foci and return of the dorsolateral PFC activation, These data directly demonstrate that the hormonal milieu modulates cognition-related neural activity in humans. C1 NIMH,BEHAV ENDOCRINOL BRANCH,INTRAMURAL RES PROGRAM,NIH,BETHESDA,MD 20892. RP Berman, KF (reprint author), NIMH,CLIN BRAIN DISORDERS BRANCH,NIH,BLDG 10,ROOM 4C101,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 35 TC 210 Z9 212 U1 0 U2 9 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 AUG 5 PY 1997 VL 94 IS 16 BP 8836 EP 8841 DI 10.1073/pnas.94.16.8836 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA XQ124 UT WOS:A1997XQ12400097 PM 9238064 ER PT J AU Kashiwaya, Y King, MT Veech, RL AF Kashiwaya, Y King, MT Veech, RL TI Substrate signaling by insulin: A ketone bodies ratio mimics insulin action in heart SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article; Proceedings Paper CT Symposium on Autocrine and Paracrine Signaling Between Contracting Myocardium and Coronary Endothelium During Ischemia - Effect of Insulin Resistance CY SEP 28-29, 1996 CL BADEN BADEN, GERMANY SP Max Grundig Fdn ID ACUTE MYOCARDIAL-INFARCTION; FREE MG2+; PYRUVATE-DEHYDROGENASE; MAGNETIC-RESONANCE; MAGNESIUM; GLUCOSE; TRANSPORT; ENERGY; METABOLISM; LIVER AB The administration of saturating doses of insulin to the glucose perfused, working rat heart acutely increased activity of the glucose transporter 4, GLUT 4, in the plasma membrane (equilibrating extracellular glucose and intracellular [glucose]), activated glycogen synthase (stimulating the rate of glycogen synthesis), and increased mitochondrial acetyl CoA production by the pyruvate dehydrogenase multienzyme complex. Unexpectedly, insulin increased cardiac hydraulic work but decreased net glycolytic flux and O-2 consumption, improving net cardiac efficiency by 28%. These improvements in physiologic performance and metabolic efficiency resulted from reduction of the mitochondrial free [NAD(+)]/[NADH] and oxidation of mitochondrial [coenzyme Q]/[coenzyme QH(2)], increasing the energy of the proton gradient between cytosolic and mitochondrial phases and leading to a doubling of the cytosolic free [Sigma ATP]/[Sigma ADP][Sigma P-i]. The acute metabolic effects of insulin were qualitatively duplicated by addition of a ratio of 4 mM D-beta-hydroxybutyrate and 1 mM acetoacetate, and the increase in the efficiency was the same as with addition of insulin. Addition of both insulin and ketones to the glucose perfusate increased the efficiency of cardiac hydraulic work by 35%. The ability of a physiologic ratio Of ketone bodies to correct most of the metabolic defects of acute insulin deficiency suggests therapeutic roles for these natural substrates during periods of impaired cardiac performance and in insulin-resistant states. C1 NIAAA,LAB MEMBRANE BIOL & BIOPHYS,ROCKVILLE,MD 20852. NR 55 TC 32 Z9 32 U1 1 U2 2 PU EXCERPTA MEDICA INC PI NEW YORK PA 245 WEST 17TH STREET, NEW YORK, NY 10011 SN 0002-9149 J9 AM J CARDIOL JI Am. J. Cardiol. PD AUG 4 PY 1997 VL 80 IS 3A SI SI BP A50 EP A64 DI 10.1016/S0002-9149(97)00458-X PG 15 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA YD983 UT WOS:A1997YD98300009 PM 9293956 ER PT J AU Chawla, MK Gutierrez, GM Young, WS McMullen, NT Rance, NE AF Chawla, MK Gutierrez, GM Young, WS McMullen, NT Rance, NE TI Localization of neurons expressing substance P and neurokinin B gene transcripts in the human hypothalamus and basal forebrain SO JOURNAL OF COMPARATIVE NEUROLOGY LA English DT Review DE tachykinin; in situ hybridization; nucleus basalis of Meynert; mammillary body; diagonal band of Broca; putamen ID CENTRAL-NERVOUS-SYSTEM; PORCINE SPINAL-CORD; VENTRAL PREMAMMILLARY NUCLEUS; SEXUALLY DIMORPHIC NUCLEUS; MIDBRAIN CENTRAL GRAY; MEDIAL PREOPTIC AREA; MALE GOLDEN-HAMSTER; HUMAN-BRAIN; IMMUNOREACTIVE NEURONS; ANTERIOR-PITUITARY AB In situ hybridization histochemistry was used to map the distribution of neurons expressing the substance P (SP) or neurokinin B (NKB) genes in the human hypothalamus and basal forebrain. Hypothalami from five adult males were frozen in isopentane at -30 degrees C and serially sectioned at 20 mu m thickness. Every 20th section was hybridized with [S-35]-labeled, 48-base synthetic cDNA probes that were complementary to either SP or NKB mRNAs. Slides were dipped into nuclear emulsion for visualization of mRNAs at the single-cell level. The location of labeled neurons (greater than x5 background) was mapped by using an image-combining computer microscope system. A distinct and complementary distribution pattern of SP and NKB neurons was observed in the human hypothalamus and basal forebrain. NKB was the predominant tachykinin in the rostral hypothalamus, whereas SP mRNA predominated in the posterior hypothalamus. Numerous NKB neurons were identified in the magnocellular basal forebrain, the bed nucleus of stria terminalis, and the anterior hypothalamic area. Scattered NKB neurons were present in the infundibular and paraventricular nuclei, paraolfactory gyrus, posterior hypothalamic area, lateral division of the medial mammillary nucleus, and amygdala. Numerous neurons expressing SP mRNAs were identified in the premammillary, supramammillary, and medial mammillary nuclei; the posterior hypothalamic area; and the corpus striatum. Scattered SP neurons were also observed in the preoptic area; the infundibular, intermediate, dorsomedial, and ventromedial nuclei; the infundibular stalk; the amygdala; the bed nucleus of stria terminalis; and the paraolfactory gyrus. These studies provide the first description of the location of neurons that express tachykinin gene transcripts in the human hypothalamus. (C) 1997 Wiley-Liss, Inc. C1 UNIV ARIZONA, COLL MED, DEPT PATHOL, TUCSON, AZ 85724 USA. UNIV ARIZONA, COLL MED, DEPT ANAT & CELL BIOL, TUCSON, AZ 85724 USA. UNIV ARIZONA, COLL MED, DEPT NEUROL, TUCSON, AZ 85724 USA. NIMH, LAB CELLULAR & MOL REGULAT, BETHESDA, MD 20892 USA. RI Young, W Scott/A-9333-2009 OI Young, W Scott/0000-0001-6614-5112 FU NIA NIH HHS [AG-09214] NR 104 TC 51 Z9 53 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0021-9967 EI 1096-9861 J9 J COMP NEUROL JI J. Comp. Neurol. PD AUG 4 PY 1997 VL 384 IS 3 BP 429 EP 442 DI 10.1002/(SICI)1096-9861(19970804)384:3<429::AID-CNE8>3.0.CO;2-5 PG 14 WC Neurosciences; Zoology SC Neurosciences & Neurology; Zoology GA XN360 UT WOS:A1997XN36000008 PM 9254037 ER PT J AU Gupta, N Scharenberg, AM Burshtyn, DN Wagtmann, N Lioubin, MN Rohrschneider, LR Kinet, JP Long, EO AF Gupta, N Scharenberg, AM Burshtyn, DN Wagtmann, N Lioubin, MN Rohrschneider, LR Kinet, JP Long, EO TI Negative signaling pathways of the killer cell inhibitory receptor and Fc gamma RIIb1 require distinct phosphatases SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article ID FC-GAMMA-RIIB; CYTOPLASMIC DOMAIN; ANTIGEN RECEPTOR; CROSS-LINKING; NK CELLS; CLASS-I; IMMUNOGLOBULIN; ACTIVATION; LYMPHOCYTES; MOLECULES AB Inhibition of natural killer (NK) cells by the killer cell inhibitory receptor (KIR) involves recruitment of the tyrosine phosphatase SHP-1 by KIR and is prevented by expression of a dominant negative SHP-1 mutant. Another inhibitory receptor, the low affinity Fc receptor for immunoglobulin G (IgG) (Fc gamma RIIb1), has been shown to bind SHP-1 when cocross-linked with the antigen receptor on B cells (BCR). However, coligation of Fc gamma RIIb1 with BCR and with Fc epsilon RI on mast cells leads to recruitment of the inositol 5' phosphatase SHIP and to inhibition of mast cells from SHP-1-deficient mice. In this study, we evaluated the ability of these two inhibitory receptors to block target cell lysis by NK cells, and the contribution of SHP-1 and SHIP to inhibition. Recombinant vaccinia viruses encoding chimeric receptors and dominant negative mutants of SHP-1 and SHIP were used for expression in mouse and human NK cells. When the KIR cytoplasmic tail was replaced by that of Fc gamma RIIb1, recognition of HLA class I on target cells by the extracellular domain resulted in inhibition. A dominant negative mutant of SHP-1 reverted the inhibition mediated by the KIR cytoplasmic tail but not that mediated by Fc gamma RIIb1. In contrast, a dominant negative mutant of SHIP reverted only the inhibition mediated by the Fc gamma RIIb1 tail, providing functional evidence that SHIP plays a role in the Fc gamma RIIb1-mediated negative signal. These data demonstrate that inhibition of NK cells by KIR involves primarily the tyrosine phosphatase SHP-1, whereas inhibition mediated by Fc gamma RIIb1 requires the inositol phosphatase SHIP. C1 NIAID,LIG,NIH,ROCKVILLE,MD 20852. BETH ISRAEL HOSP,DEPT PATHOL,LAB ALLERGY & IMMUNOL,BOSTON,MA 02215. HARVARD UNIV,SCH MED,BOSTON,MA 02215. FRED HUTCHINSON CANC RES CTR,SEATTLE,WA 98104. RI Long, Eric/G-5475-2011 OI Long, Eric/0000-0002-7793-3728 NR 31 TC 77 Z9 77 U1 0 U2 1 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 SN 0022-1007 J9 J EXP MED JI J. Exp. Med. PD AUG 4 PY 1997 VL 186 IS 3 BP 473 EP 478 DI 10.1084/jem.186.3.473 PG 6 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA XP998 UT WOS:A1997XP99800017 PM 9236201 ER PT J AU Ross, J Williams, M Cohen, JI AF Ross, J Williams, M Cohen, JI TI Disruption of the varicella-zoster virus dUTPase and the adjacent ORF9A gene results in impaired growth and reduced syncytia formation in vitro SO VIROLOGY LA English DT Article ID COMPLETE DNA-SEQUENCE; MEMBRANE-PROTEIN; IN-VITRO; SIMPLEX; TYPE-1; IDENTIFICATION; GENERATION; ENCODES; MUTANTS; UL49.5 AB Varicella-zoster virus (VZV) open reading frame 8 (ORF8) is predicted to encode the viral dUTPase and the adjacent gene, ORF9A, is thought to encode a membrane protein homologous to HSV-1 UL49.5, A fusion protein, in which the amino portion of glutathione-S-transferase was fused to amino acids 5 to 396 of VZV ORF8 protein, had dUTPase activity in vitro, Construction of a mutant VZV with stop codons or a deletion in the ORF8 gene resulted in loss of viral dUTPase activity. Antibody to VZV ORF9A protein demonstrated a 7-kDa protein located in the membranes of virus-infected cells. Insertion of stop codons into VZV ORF9A resulted in VZV that produced smaller plaques than parental virus. Inactivation of both VN ORF8 and ORF9A resulted in a virus that grew to lower titers and was impaired for syncytia formation when compared to parental virus. In contrast, a similar mutation in HSV-1 has no effect on growth of the virus in vitro. These results identify loci in the VZV genome that are required for a syncytial phenotype in vitro. (C) 1997 Academic Press. C1 NIAID,MOL VIROL UNIT,CLIN INVEST LAB,NIH,BETHESDA,MD 20892. OHIO STATE UNIV,DEPT MED MICROBIOL & IMMUNOL,COLUMBUS,OH 43210. OHIO STATE UNIV,CTR COMPREHENS CANC,COLUMBUS,OH 43210. NR 28 TC 46 Z9 46 U1 0 U2 1 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0042-6822 J9 VIROLOGY JI Virology PD AUG 4 PY 1997 VL 234 IS 2 BP 186 EP 195 DI 10.1006/viro.1997.8652 PG 10 WC Virology SC Virology GA XQ515 UT WOS:A1997XQ51500002 PM 9268149 ER PT J AU Alkhatib, G Locati, M Kennedy, PE Murphy, PM Berger, EA AF Alkhatib, G Locati, M Kennedy, PE Murphy, PM Berger, EA TI HIV-1 coreceptor activity of CCR5 and its inhibition by chemokines: Independence from G protein signaling and importance of coreceptor downmodulation SO VIROLOGY LA English DT Article ID IMMUNODEFICIENCY-VIRUS TYPE-1; RECOMBINANT VACCINIA VIRUS; ENVELOPE GLYCOPROTEIN; CD4-MEDIATED FUSION; MURINE CELLS; T-CELLS; RECEPTOR; CD4; TRANSDUCTION; INFECTION AB HIV-1 infection requires the presence of specific chemokine receptors on CD4+ target cells to enable the fusion reactions involved in virus entry. CCR5 is a major fusion coreceptor for macrophage-tropic HIV-1 isolates. HIV-1 entry and fusion are mediated by the viral envelope glycoprotein (Env) and are inhibited by CCR5 ligands, but the mechanisms are unknown. Here, we test the role of G protein signaling and CCR5 surface downmodulation by two separate approaches; direct inactivation of CCR5 signaling by mutagenesis and inactivation of G(i)-type G proteins with pertussis toxin. A CCR5 mutant lacking the last 45 amino acids of the cytoplasmic C-terminus (CCR5(306)) was created that was expressed on transfected cells at levels comparable to cells expressing CCR5 and displayed normal chemokine binding affinity, CCR5 ligands induced calcium flux and receptor downmodulation in cells expressing CCR5, but not in cells expressing CCR5(306). Nevertheless, CCR5 or CCR5(306), when coexpressed with CD4, supported comparable HIV-l Env-mediated cell fusion. Consistent with this, treatment of CCR5-expressing cells with pertussis toxin completely blocked ligand-induced transient calcium flux, but did not affect Env-mediated cell fusion or HIV-1 infection. Also, pertussis toxin did not block chemokine inhibition of Env-mediated cell fusion or HIV-1 infection. However, chemokines inhibited Env-mediated cell fusion less efficiently for CCR5(306) than for CCR5. We conclude that the C-terminal domain of CCR5 is critical for G protein signaling and receptor downmodulation from the surface, but that neither function is required for CCR5 fusion coreceptor activity. The contrasting phenotypes of CCR5 and CCR5(306) suggest that coreceptor downmodulation and direct blockage of Env interaction sites both contribute to chemokine inhibition of HIV-1 infection. (C) 1997 Academic Press. C1 NIH,VIRAL DIS LAB,BETHESDA,MD 20892. NIAID,HOST DEF LAB,NIH,BETHESDA,MD 20892. RI Locati, Massimo/H-8404-2015 OI Locati, Massimo/0000-0003-3077-590X NR 45 TC 178 Z9 182 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 AUG 4 PY 1997 VL 234 IS 2 BP 340 EP 348 DI 10.1006/viro.1997.8673 PG 9 WC Virology SC Virology GA XQ515 UT WOS:A1997XQ51500019 PM 9268166 ER PT J AU Park, SH Pepkowitz, SH Kerfoot, C DeRosa, MJ Poukens, V Wienecke, R DeClue, JE Vinters, HV AF Park, SH Pepkowitz, SH Kerfoot, C DeRosa, MJ Poukens, V Wienecke, R DeClue, JE Vinters, HV TI Tuberous sclerosis in a 20-week gestation fetus: Immunohistochemical study SO ACTA NEUROPATHOLOGICA LA English DT Article DE brain development; proliferating cell markers; tuberin; tuberous sclerosis ID GIANT-CELL ASTROCYTOMA; CORTICAL DYSPLASIA; GROWTH SUPPRESSOR; PREMATURE-INFANT; RADIAL GLIA; TUMOR; HETEROZYGOSITY; IDENTIFICATION; EPILEPSY; FEATURES AB We report an autopsy case of tuberous sclerosis complex (TSC) in a 20-week gestational age female fetus, The brain showed lesions suggestive of early cortical tubers and subependymal hamartomatous nodules, The large tells within these nodular clusters were variably immunoreactive for glial fibrillary acidic protein (GFAP) and vimentin and negative for synaptophysin and neurofilament, Subependymal radial glia expressed both vimentin and GFAP, but subpial radial glia either did not express these markers (in contrast to an age-matched control) or were absent. Tuberin expression was noted in heterotopic neurons in the white matter and brain cells consistent with Cajal Retzius cells in the neocortical molecular layer, very weakly in superficial cortical neurons, neurons in the basal ganglia, Purkinje cells and external granular cells of cerebellum, cranial nerve nuclei neurons, occasional germinal matrix cells, ependymal cells, choroid plexus epithelium, and pituitary gland neuroendocrine cells; it was nor seen within the cells of subependymal nodules. The pattern of tuberin immunoreactivity tvas similar to that which we have observed in older TSC patients. Proliferating cell labeling indexes were comparable in the germinal matrix of the TSC patient and an age-matched control. Abnormal subpial radial glia may be responsible for some of the neuronal migration abnormalities that appear to result in neocortical tubers. C1 UNIV CALIF LOS ANGELES, SCH MED, DEPT PATHOL NEUROPATHOL, LOS ANGELES, CA 90095 USA. UNIV CALIF LOS ANGELES, MED CTR, BRAIN RES INST, LOS ANGELES, CA 90095 USA. UNIV CALIF LOS ANGELES, MED CTR, MENTAL RETARDAT RES CTR, LOS ANGELES, CA 90095 USA. CEDARS SINAI MED CTR, DEPT PATHOL, LOS ANGELES, CA 90048 USA. NCI, CELLULAR ONCOL LAB, BETHESDA, MD 20892 USA. RI Park, Sung Hye/B-5325-2011 OI Park, Sung Hye/0000-0002-8681-1597 FU NINDS NIH HHS [P01 NS 28383] NR 38 TC 58 Z9 58 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0001-6322 EI 1432-0533 J9 ACTA NEUROPATHOL JI Acta Neuropathol. PD AUG PY 1997 VL 94 IS 2 BP 180 EP 186 PG 7 WC Clinical Neurology; Neurosciences; Pathology SC Neurosciences & Neurology; Pathology GA XL459 UT WOS:A1997XL45900012 PM 9255394 ER PT J AU Fox, C AF Fox, C TI Lifestyle changes reduce risk of diabetes in high-risk groups SO AMERICAN FAMILY PHYSICIAN LA English DT Editorial Material RP Fox, C (reprint author), NIDDKD,CLIN DIABET & NUTR SECT,4212 N 16TH ST,PHOENIX,AZ 85016, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ACAD FAMILY PHYSICIANS PI KANSAS CITY PA 8880 WARD PARKWAY, KANSAS CITY, MO 64114-2797 SN 0002-838X J9 AM FAM PHYSICIAN JI Am. Fam. Physician PD AUG PY 1997 VL 56 IS 2 BP 565 EP 565 PG 1 WC Primary Health Care; Medicine, General & Internal SC General & Internal Medicine GA XQ779 UT WOS:A1997XQ77900022 ER PT J AU Domanski, MJ Saksena, S Wyse, G Hallstrom, A Schron, EB Nanda, A Nanda, A Kutalek, S AF Domanski, MJ Saksena, S Wyse, G Hallstrom, A Schron, EB Nanda, A Nanda, A Kutalek, S TI Clinical and socioeconomic profile of patients with malignant ventricular arrhythmias in 1993 to 1995 SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article ID SUDDEN CARDIAC DEATH; HEART-DISEASE; MYOCARDIAL-INFARCTION; MORTALITY; MORBIDITY; SURVIVAL; TRENDS; TRIAL AB This report summarizes the clinical and socioeconomic characteristics of the first 542 patients entered into the Antiarrhythmics Versus Implantable Defibrillator (AVID) trial. AVID is a multicenter trial comparing a strategy of initial implantable cardioverter-defibrillator placement to initial antiarrhythmic drug therapy in preventing death in patients resuscitated from cardiac arrest who were not taking amiodarone and who did not have an implantable cardioverter-defibrillator in place at the time of the index event. These patients were randomly assigned to immediate defibrillator placement or to ''best'' medical therapy. Clinical and socioeconomic histories were collected by interview using standard terms developed for the study. Patients without (group 1) and with (group 2) a history of prior cardiac arrest were compared. The mean age of the 542 patients was 65 +/- 10 years, most were men, white, had coronary disease, and were highly functional despite the fact that only a minority were employed. Almost all had some form of health insurance. At the time of the index event, few were taking any therapy to prevent cardiac arrest, even in the group of patients with a history of previous cardiac arrest. Thus, the clinical and socioeconomic profile of patients resuscitated from sudden cardiac death entered into the AVID study is generally as expected. There is a striking absence of any attempt at chronic therapy to prevent cardiac arrest in most patients with a prior ventricular tachycardia or ventricular fibrillation. (C) 1997 by Excerpta Medica, Inc. C1 E HEART INST,ARRHYTHMIA & PACEMAKER SERV,PASSAIC,NJ. FOOTHILLS PROV GEN HOSP,DIV CARDIOL,CALGARY,AB T2N 2T9,CANADA. UNIV WASHINGTON,SEATTLE,WA 98195. MED COLL PENN & HAHNEMANN UNIV,PHILADELPHIA,PA. RP Domanski, MJ (reprint author), NHLBI,CLIN TRIALS GRP,BLDG 10,BETHESDA,MD 20892, USA. NR 18 TC 4 Z9 4 U1 0 U2 2 PU EXCERPTA MEDICA INC PI NEW YORK PA 245 WEST 17TH STREET, NEW YORK, NY 10011 SN 0002-9149 J9 AM J CARDIOL JI Am. J. Cardiol. PD AUG 1 PY 1997 VL 80 IS 3 BP 299 EP 301 PG 3 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA XP486 UT WOS:A1997XP48600008 PM 9264422 ER PT J AU Albanes, D Virtamo, J Taylor, PR Rautalahti, M Pietinen, P Heinonen, OP AF Albanes, D Virtamo, J Taylor, PR Rautalahti, M Pietinen, P Heinonen, OP TI Effects of supplemental beta-carotene, cigarette smoking, and alcohol consumption on serum carotenoids in the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study SO AMERICAN JOURNAL OF CLINICAL NUTRITION LA English DT Article DE beta-carotene; supplementation; carotenoids; alpha-carotene; beta-cryptoxanthin; lutein; lycopene; zeaxanthin; retinol; alcohol; cigarettes; smoking; Beta-Carotine and Retinol Efficacy Trial; alpha-tocopherol; Beta-Carotene Cancer Prevention Study ID VITAMIN-A; LIQUID-CHROMATOGRAPHY; FINNISH FOODS; PLASMA-LEVELS; RETINOL; DIETARY; MEN; CANTHAXANTHIN; ABSORPTION; LYCOPENE AB We determined whether serum carotenoid or retinol concentrations were altered by beta-carotene supplementation in the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study and whether such effects were modified by alcohol consumption or cigarette use. Participants in this substudy were 491 randomly selected men aged 58-76 y from the metropolitan Helsinki study center [237 receiving supplemental beta-carotene (20 mg/d) and 254 not receiving such supplementation]. Dietary carotenoids, retinol, and alcohol, and serum beta-carotene, alpha-tocopherol, retinal, and cholesterol were assessed at baseline. After an average of 6.7 y of supplementation, serum was collected and carotenoid, retinol, and alpha-tocopherol concentrations were determined by HPLC. Serum carotenoid fractions were highly correlated with each other (P less than or equal to 0.0001). Compared with the unsupplemented group, the beta-carotene group had significantly higher serum concentrations of beta-carotene (1483%), alpha-carotene (145%), and beta-cryptoxanthin (67%) (P less than or equal to 0.0001). Retinol concentrations were 6% higher (P = 0.03) and lutein was 11% lower (P = 0.02) in the supplemented group. Serum lycopene, zeaxanthin, and alpha-tocopherol did not differ according to beta-carotene-supplementation status. Although these beta-carotene-group differences were not significantly altered by amount of alcohol consumption, higher consumption (> 12.9 g/d, median) was related to lower (10-38%) concentrations of carotenoids, particularly beta-carotene, alpha-carotene, and beta-cryptoxanthin, in both the supplemented and unsupplemented groups. Smoking status did not significantly influence the supplementation-related differences in serum carotenoid and retinol values but concentrations of carotenoids were generally highest in participants who quit smoking while in the study and lowest ill current smokers of greater than or equal to 20 cigarettes/d. This study showed that serum concentrations of non-beta-carotene: carotenoids are altered by long-term beta-carotene supplementation and confirms the adverse effects of alcohol and cigarette smoking on serum carotenoids. C1 NATL PUBL HLTH INST,HELSINKI,FINLAND. UNIV HELSINKI,FIN-00014 HELSINKI,FINLAND. RP Albanes, D (reprint author), NCI,EXECUT PLAZA N,SUITE 211,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. RI Albanes, Demetrius/B-9749-2015 FU NCI NIH HHS [N01-CN-45165] NR 46 TC 110 Z9 113 U1 0 U2 7 PU AMER SOC CLINICAL NUTRITION PI BETHESDA PA 9650 ROCKVILLE PIKE, SUBSCRIPTIONS, RM L-2310, BETHESDA, MD 20814-3998 SN 0002-9165 J9 AM J CLIN NUTR JI Am. J. Clin. Nutr. PD AUG PY 1997 VL 66 IS 2 BP 366 EP 372 PG 7 WC Nutrition & Dietetics SC Nutrition & Dietetics GA XN547 UT WOS:A1997XN54700019 PM 9250116 ER PT J AU Lewis, L Stock, F Williams, D Weir, S Gill, VJ AF Lewis, L Stock, F Williams, D Weir, S Gill, VJ TI Infections with Roseomonas gilardii and review of characteristics used for biochemical identification and molecular typing SO AMERICAN JOURNAL OF CLINICAL PATHOLOGY LA English DT Article DE Roseomonas; infections; characteristics; typing ID PIGMENTED OXIDATIVE BACTERIA; PINK; PRIMERS AB Roseomonas is a recently described genus of gram-negative coccobacilli formerly designated as ''pink-coccoid'' groups I through IV by the Centers for Disease Control and Prevention (Atlanta, Ga) because of the organism's characteristic pink colonies. Since 1991 we have isolated Roseomonas from eight patients; in seven from blood cultures and in one from a skin lesion. The seven blood isolates were from patients with clinically significant underlying diseases who had central venous catheters in place; the majority were associated with polymicrobial catheter infections. Additional characteristics of their infections are described. The eight isolates had originally been identified by us as Centers for Disease Control(CDC) pink-coccoid group III. These organisms were re-identified using the criteria of Ribs et al, and all isolates fit most closely with Roseomonns gilardii. Antibiotic profiles were fairly homogeneous showing susceptibility to many antibiotics, but uniform resistance to cefoxitin, ceftazidime, and piperacillin. Attempts to determine whether the isolates were the same strain by pulsed-field gel electrophoresis suggested that 3 of the isolates were similar. Random amplified polymorphic DNA analysis, however, demonstrated that each of the eight isolates was a unique strain. C1 NIH,MICROBIOL SERV,DEPT CLIN PATHOL,WARREN GRANT MAGNUSON CLIN CTR,BETHESDA,MD 20892. NCI,PEDIAT BRANCH,BETHESDA,MD 20892. NR 9 TC 22 Z9 24 U1 0 U2 0 PU AMER SOC CLIN PATHOLOGISTS PI CHICAGO PA 2100 W HARRISON ST, CHICAGO, IL 60612 SN 0002-9173 J9 AM J CLIN PATHOL JI Am. J. Clin. Pathol. PD AUG PY 1997 VL 108 IS 2 BP 210 EP 216 PG 7 WC Pathology SC Pathology GA XP070 UT WOS:A1997XP07000013 PM 9260763 ER PT J AU Muehrer, P AF Muehrer, P TI Introduction to the special issue: Mental health prevention science in rural communities and contexts SO AMERICAN JOURNAL OF COMMUNITY PSYCHOLOGY LA English DT Editorial Material C1 NIMH,NIH,BETHESDA,MD 20892. NR 8 TC 8 Z9 8 U1 0 U2 0 PU PLENUM PUBL CORP PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 SN 0091-0562 J9 AM J COMMUN PSYCHOL JI Am. J. Community Psychol. PD AUG PY 1997 VL 25 IS 4 BP 421 EP 424 DI 10.1023/A:1024651420711 PG 4 WC Public, Environmental & Occupational Health; Psychology, Multidisciplinary; Social Work SC Public, Environmental & Occupational Health; Psychology; Social Work GA YB167 UT WOS:A1997YB16700001 PM 9338952 ER PT J AU Yong, LC Brown, CC Schatzkin, A Dresser, CM Slesinski, MJ Cox, CS Taylor, PR AF Yong, LC Brown, CC Schatzkin, A Dresser, CM Slesinski, MJ Cox, CS Taylor, PR TI Intake of vitamins E, C, and A and risk of lung cancer - The NHANES I Epidemiologic Followup Study SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Article DE ascorbic acid; carotenoids; fruit; lung neoplasms; prospective studies; vegetables; vitamin A; vitamin E ID DIETARY BETA-CAROTENE; UNITED-STATES; CONSUMPTION; SMOKING; POPULATION; VEGETABLES; NONSMOKERS; MORTALITY; HEALTH; HAWAII AB The relation between the dietary intake of vitamins E, C, and A (estimated by a 24-hour recall) and lung cancer incidence was examined in the First National Health and Nutrition Examination Survey Epidemiologic Followup Study cohort of 3,968 men and 6,100 women, aged 25-74 years, During a median follow-up period of 19 years (from 1971-1975 to 1992), 248 persons developed lung cancer, Adjusted for potential confounders using Cox proportional hazards regression methods with age as the underlying time variable, the relative risk of lung cancer for subjects in the highest quartile of vitamin C intake compared with those in the lowest quartile was 0.66 (95% confidence interval (CI) 0.45-0.96), For vitamin A intake, a protective effect was observed only for its fruit and vegetable component (carotenoids) among current smokers (relative risk = 0.49, 95% CI 0.29-0.84), but this was modified by the intensity of smoking (a statistically significant effect (relative risk = 0.33, 95% CI 0.13-0.84) was observed only for those in the lowest tertile of pack-years of smoking), The vitamin E intake-lung cancer relation was modified by the intensity of smoking with a significant protective effect confined to current smokers in the lowest tertile of pack-years of smoking (relative risk = 0.36, 95% CI 0.16-0.83), Overall, there was no additional protective effect of supplements of vitamins E, C, and A beyond that provided through dietary intake, When vitamin E, vitamin C, and carotenoid intakes were examined in combination, a strong protective effect was observed for those in the highest compared with those in the lowest quartile of all three intakes (relative risk = 0.32, 95% CI 0.14-0.74), These data provide support for a protective role of dietary vitamins E and C and of carotenoids against lung cancer risk but with a modification in effects by the intensity of cigarette exposure, While smoking avoidance is the most important behavior to reduce lung cancer risk, the daily consumption of a variety of fruits and vegetables that provides a combination of these nutrients and other potential protective factors may offer the best dietary protection against lung cancer. C1 NATL CTR HLTH STAT,DIV EPIDEMIOL,HYATTSVILLE,MD. RP Yong, LC (reprint author), NCI,EPN,DCPC,CANC PREVENT STUDIES BRANCH,ROOM 211,6130 EXECUT BLVD,MSC 7326,ROCKVILLE,MD 20852, USA. NR 54 TC 117 Z9 121 U1 0 U2 2 PU JOHNS HOPKINS UNIV SCHOOL HYGIENE PUB HEALTH PI BALTIMORE PA 111 MARKET PLACE, STE 840, BALTIMORE, MD 21202-6709 SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD AUG 1 PY 1997 VL 146 IS 3 BP 231 EP 243 PG 13 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA XN539 UT WOS:A1997XN53900004 PM 9247007 ER PT J AU MacDorman, MF Cnattingius, S Hoffman, HJ Kramer, MS Haglund, B AF MacDorman, MF Cnattingius, S Hoffman, HJ Kramer, MS Haglund, B TI Sudden infant death syndrome and smoking in the United States and Sweden SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Article DE ethnic groups; smoking; sudden infant death ID MATERNAL SMOKING; RISK-FACTORS; AGE; VALIDATION; PREGNANCY; QUALITY AB The association between sudden infant death syndrome (SIDS) and maternal smoking was compared between the United States and Sweden-two countries with different health care and social support programs and degrees of sociocultural heterogeneity. For 1990-1991 among the five US race/ethnic groups studied, SIDS rates ranged from a high of 3.0 infant deaths per 1,000 live births for American Indians to a low of 0.8 for Hispanics and Asian and Pacific Islanders, The SIDS rate for Sweden (using 1983-1992 data) was 0.9. The strong association between maternal smoking and SIDS persisted after controlling for maternal age and live birth order. Adjusted odds ratios ranged from 1.6 to 2.5 for mothers who smoked 1-9 cigarettes per day during pregnancy (compared with nonsmokers) and from 2.3 to 3.8 for mothers who smoked 10 or more cigarettes per day during pregnancy. Although birth weight had a strong independent effect on SIDS, the addition of birth weight to the models lowered the odds ratios for maternal smoking only slightly, suggesting that the effect of smoking on SIDS is not mediated through birth weight. SIDS rates increased with the amount smoked for all US race/ethnic groups and for Sweden, Smoking is one of the most important preventable risk factors for SIDS, and smoking prevention/intervention programs have the potential to substantially lower SIDS rates in the United States and Sweden and presumably elsewhere as well. C1 UNIV UPPSALA HOSP,DEPT SOCIAL MED,S-75185 UPPSALA,SWEDEN. NIDOCD,EPIDEMIOL STAT & DATA SYST BRANCH,NIH,ROCKVILLE,MD. MCGILL UNIV,DEPT MATERNAL & CHILD HLTH,MONTREAL,PQ,CANADA. NATL BOARD HLTH & WELF,CTR EPIDEMIOL,STOCKHOLM,SWEDEN. RP MacDorman, MF (reprint author), NATL CTR HLTH STAT,DIV VITAL STAT,CTR DIS CONTROL & PREVENT,6525 BELCREST RD,ROOM 840,HYATTSVILLE,MD 20782, USA. NR 28 TC 70 Z9 72 U1 0 U2 1 PU JOHNS HOPKINS UNIV SCHOOL HYGIENE PUB HEALTH PI BALTIMORE PA 111 MARKET PLACE, STE 840, BALTIMORE, MD 21202-6709 SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD AUG 1 PY 1997 VL 146 IS 3 BP 249 EP 257 PG 9 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA XN539 UT WOS:A1997XN53900006 PM 9247009 ER PT J AU Terwilliger, JD Shannon, WD Lathrop, GM Nolan, JP Goldin, LR Chase, GA Weeks, DE AF Terwilliger, JD Shannon, WD Lathrop, GM Nolan, JP Goldin, LR Chase, GA Weeks, DE TI True and false positive peaks in genomewide scans: Applications of length-biased sampling to linkage mapping SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Article ID GENETIC-LINKAGE; COMPLEX TRAITS; RESOLUTION; PARAMETERS; DISSECTION; IDENTITY; DESCENT AB Disease-susceptibility Loci are now being mapped via genomewide scans in which a linkage statistic is computed at each of a large number of markers, Such disease-susceptibility loci may be identified via a peak in the test statistic when the latter is plotted against the genetic map, In this paper we establish, by appealing to renewal theory, that true positive peaks are expected to be longer than false positive peaks, These results are verified by a realistic simulation of a genomewide linkage study based on the affected-sib-pair design, Since longer peaks are more likely to contain a gene of interest than are shorter peaks, these differences may aid in linkage mapping, justifying assignment of lower priority to shorter peaks, However, since these differences are generally small, statistics based on both peak length and height may not be much more powerful than those based on height alone, The results presented here also provide a theoretical framework for methods that use the length of shared haplotypes in populations to map disease genes. C1 UNIV OXFORD,WELLCOME TRUST CTR HUMAN GENET,OXFORD OX3 7BN,ENGLAND. COLUMBIA UNIV,DEPT PSYCHIAT,NEW YORK,NY. COLUMBIA UNIV,COLUMBIA GENOME CTR,NEW YORK,NY. UNIV WASHINGTON,SCH MED,ST LOUIS,MO. AMERICAN UNIV,DEPT MATH & STAT,WASHINGTON,DC 20016. NATL CTR HLTH STAT,NATL INST HLTH,HYATTSVILLE,MD. GEORGETOWN UNIV,MED CTR,WASHINGTON,DC 20007. NIMH,CLIN NEUROGENET BRANCH,BETHESDA,MD 20892. UNIV PITTSBURGH,DEPT HUMAN GENET,PITTSBURGH,PA. RI Weeks, Daniel/B-2995-2012; OI Weeks, Daniel/0000-0001-9410-7228 FU NHGRI NIH HHS [HG00008, HG00719]; Wellcome Trust NR 40 TC 116 Z9 116 U1 0 U2 1 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 S WOODLAWN AVE, CHICAGO, IL 60637 SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD AUG PY 1997 VL 61 IS 2 BP 430 EP 438 DI 10.1086/514855 PG 9 WC Genetics & Heredity SC Genetics & Heredity GA XX701 UT WOS:A1997XX70100022 PM 9311749 ER PT J AU Martin, ER Kaplan, NL Weir, BS AF Martin, ER Kaplan, NL Weir, BS TI Tests for linkage and association in nuclear families SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Article ID DISEQUILIBRIUM AB The transmission/disequilibrium test (TDT) originally was introduced to test for linkage between a genetic marker and a disease-susceptibility locus, in the presence of association. Recently, the TDT has been used to test for association in the presence of linkage. The motivation for this is that linkage analysis typically identifies large candidate regions, and further refinement is necessary before a search for the disease gene is begun, on the molecular level. Evidence of association and linkage may indicate which markers in the region are closest to a disease locus. As a test of linkage, transmissions from heterozygous parents to all of their affected children can be included in the TDT; however, the TDT is a valid chi(2) test of association only if transmissions to unrelated affected children are used in the analysis. If the sample contains independent nuclear families with multiple affected children, then one procedure that has been used to test for association is to select randomly a single affected child from each sibship and to apply the TDT to those data. As an alternative, we propose two statistics that use data from all of the affected children. The statistics give valid chi(2) tests Of the null hypothesis of no association or no linkage and generally are more powerful than the TDT with a single, randomly chosen, affected child from each family. C1 N CAROLINA STATE UNIV,DEPT STAT,PROGRAM STAT GENET,RALEIGH,NC. RP Martin, ER (reprint author), NIEHS,BIOSTAT BRANCH,POB 12233,RES TRIANGLE PK,NC 27709, USA. FU NIGMS NIH HHS [P01 GM45344, T32 GM08443]; NINDS NIH HHS [R01 NS23360] NR 7 TC 174 Z9 178 U1 1 U2 5 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 S WOODLAWN AVE, CHICAGO, IL 60637 SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD AUG PY 1997 VL 61 IS 2 BP 439 EP 448 DI 10.1086/514860 PG 10 WC Genetics & Heredity SC Genetics & Heredity GA XX701 UT WOS:A1997XX70100023 PM 9311750 ER PT J AU Fedorova, OV Bagrov, AY AF Fedorova, OV Bagrov, AY TI Inhibition of Na/K ATPase from rat aorta by two Na/K pump inhibitors, ouabain and marinobufagenin - Evidence of interaction with different alpha-subunit isoforms SO AMERICAN JOURNAL OF HYPERTENSION LA English DT Article DE Na/K ATPase; isoforms; inhibitors; vascular smooth muscle; ouabain; bufodienolides; marinobufagenin ID VALENT CATION-TRANSPORT; DIGITALIS-LIKE FACTORS; NA+/K+-ATPASE; HUMAN-PLASMA; NA,K-ATPASE; NA+,K+-ATPASE; PROTEINS; FIBERS; HEART AB Recently, we have shown that mammalian plasma cross-reacts with an antibody to a bufodienolide Na/K ATPase inhibitor, marinobufagenin. In rat aorta, marinobufagenin induced vasoconstriction via inhibition of the vascular smooth muscle Na/K pump, whereas ouabain had its predominant effect on pumps localized to nerve endings. Na/K ATPase inhibitory effects of ouabain and marinobufagenin were studied in two membrane fractions isolated from Fisher 344xBN rat thoracic aorta by sucrose density gradient centrifugation. One fraction contained predominantly the alpha-3 isoform of Na/K ATPase and represented membranes from the perivascular nerve endings (neuronal plasmalemma). The other membrane fraction, containing predominantly the alpha-1 isoform, was derived from the vascular smooth muscle sarcolemma. The IC50 for inhibition of the Na/K ATPase by ouabain and marinobufagenin were 2.6 nmol/L and 0.14 mu mol/L in the neuronal plasmalemma, and 50 nmol/L and 2.1 nmol/L in sarcolemma, respectively. These results confirm the view that differential responsiveness to endogenous digitalis-like factors is a functional feature of alpha isoforms of Na/K ATPase. (C) 1997 American Journal of Hypertension, Ltd. C1 NIA,CARDIOVASC SCI LAB,NIH,BALTIMORE,MD 21224. IM SECHENOV EVOLUTIONARY PHYSIOL & BIOCHEM INST,PHARMACOL LAB,ST PETERSBURG 194223,RUSSIA. NR 36 TC 70 Z9 71 U1 1 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0895-7061 J9 AM J HYPERTENS JI Am. J. Hypertens. PD AUG PY 1997 VL 10 IS 8 BP 929 EP 935 DI 10.1016/S0895-7061(97)00096-4 PG 7 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA XR034 UT WOS:A1997XR03400014 PM 9270089 ER PT J AU Turenne, MN Port, FK Strawderman, RL Ettenger, RB Alexander, SR Lewy, JE Jones, CA Agodoa, LYC Held, PJ AF Turenne, MN Port, FK Strawderman, RL Ettenger, RB Alexander, SR Lewy, JE Jones, CA Agodoa, LYC Held, PJ TI Growth rates in pediatric dialysis patients and renal transplant recipients SO AMERICAN JOURNAL OF KIDNEY DISEASES LA English DT Article DE pediatric growth rate; height standard deviation score; ESRD; kidney transplant; dialysis; hemodialysis; CAPD; continuous cycling peritoneal dialysis; alternate-day steroid ID HORMONE TREATMENT; KIDNEY-TRANSPLANTATION; DOUBLE-BLIND; CHILDREN; FAILURE AB We compared growth rates by modality over a 6- to 14-month period in 1,302 US pediatric end-stage renal disease (ESRD) patients treated during 1990. Modality comparisons were adjusted for age, sex, race, ethnicity, and ESRD duration using linear regression models by age group (0.5 to 4 years, 5 to 9 years, 10 to 14 years, and 15 to 18 years). Growth rates were higher in young children receiving a transplant compared with those receiving dialysis (ages 0.5 to 4 years, Delta = 3.1 cm/yr v continuous cycling peritoneal dialysis [CCPD], P < 0.01; ages 5 to 9 years, Delta = 2.0 to 2.6 cm/yr v CCPD, chronic ambulatory peritoneal dialysis (CAPD), and hemodialysis, P < 0.01). In contrast, growth rates in older children were not statistically different when comparing transplantation with each dialysis modality, For most age groups of transplant recipients, we observed faster growth with alternate-day versus daily steroids that was not fully explained by differences in allograft function, Younger patients ((15 years) grew at comparable rates with each dialysis modality, while older CAPD patients grew faster compared with hemodialysis or CCPD patients (P < 0.02), There was no substantial pubertal growth spurt in transplant or dialysis patients, This national US study of pediatric growth rates with dialysis and transplantation shows differences in growth by modality that vary by age group. (C) 1997 by the National Kidney Foundation, Inc. C1 UNIV MICHIGAN,US RENAL DATA SYST COORDINATING CTR,ANN ARBOR,MI 48109. UNIV MICHIGAN,DEPT MED,ANN ARBOR,MI 48109. UNIV MICHIGAN,DEPT EPIDEMIOL,ANN ARBOR,MI 48109. UNIV MICHIGAN,DEPT BIOSTAT,ANN ARBOR,MI 48109. UNIV MICHIGAN,DEPT HLTH POLICY & MANAGEMENT,ANN ARBOR,MI 48109. UNIV CALIF LOS ANGELES,SCH MED HLTH SCI,LOS ANGELES,CA. UNIV TEXAS,SW MED CTR,DALLAS,TX. TULANE UNIV,MED CTR,DALLAS,TX. NIDDKD,NIH,BETHESDA,MD 20892. FU NIDDK NIH HHS [N01-DK-3-2202] NR 27 TC 34 Z9 35 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0272-6386 J9 AM J KIDNEY DIS JI Am. J. Kidney Dis. PD AUG PY 1997 VL 30 IS 2 BP 193 EP 203 DI 10.1016/S0272-6386(97)90052-4 PG 11 WC Urology & Nephrology SC Urology & Nephrology GA XQ783 UT WOS:A1997XQ78300005 PM 9261029 ER PT J AU Held, PJ Port, FK Webb, RL Wolfe, RA Bloembergen, WE Hirth, R Young, EW Ojo, AO Strawderman, RL Woods, JD Tedeschi, PJ Loos, E HulbertShearon, T Leggat, J Ashby, VB Callard, S Dickinson, D Erickson, R Levine, GN Orzol, SM Segieda, G Jones, CA Greer, JW Agodoa, LYC AF Held, PJ Port, FK Webb, RL Wolfe, RA Bloembergen, WE Hirth, R Young, EW Ojo, AO Strawderman, RL Woods, JD Tedeschi, PJ Loos, E HulbertShearon, T Leggat, J Ashby, VB Callard, S Dickinson, D Erickson, R Levine, GN Orzol, SM Segieda, G Jones, CA Greer, JW Agodoa, LYC TI Excerpts from The USRDS 1997 Annual Data Report SO AMERICAN JOURNAL OF KIDNEY DISEASES LA English DT Review DE data files; database; data access; standardized mortality; World Wide Web; cause of ESRD; diabetic ESRD; dialysis patient counts; ESRD growth rates; ESRD incidence; ESRD Medical Evidence Form 2728; ESRD Medicare; ESRD prevalence; gender; HCFA data; race; anemia; dialysis dose; dialyzer membrane; ESRD modality; hemodialysis; home hemodialysis; peritoneal dialysis; transplant, renal; CAPD automated peritoneal dialysis; CAPD; cycling peritoneal dialysis; dialysate volume; phosphate binders; pre-ESRD care; residual renal function; Tenckhoff catheter; vascular access; dialysis outcomes; dialysis-unrelated deaths; ESRD mortality; ESRD survival; expected remaining lifetimes; long-term survival; standardized mortality ratios; unit-specific reports; US death rates; AIDS; cardiac deaths; death rates; diabetic ESRD; hemodialysis; infection in ESRD; malignancy in dialysis; peritoneal dialysis; transplant; withdrawal from dialysis; access to transplantation; cadaveric graft loss; cadaveric renal transplants; gender in transplantation; living related renal transplants; organ allocation; race in transplantation; renal graft survival; transplant patient survival; CAPD in children; causes of pediatric ESRD; ESRD incidence in children; ESRD patient survival in children; pediatric dialysis; pediatric ESRD; renal transplants in children; admissions in ESRD hospitalization; dialysis hospitalization; dialysis unit profit status; hospitalization by regions; standardized hospitalization ratio; consumer price index; cost of ESRD; hemodialysis cost; Medicare claims; peritoneal dialysis cost; physician and supplier files; spending for ESRD; transplantation; vascular access; dialysis certification; dialysis facility; dialysis stations; dialyzer reuse; disinfectant; ESRD network facilities; hemodialysis treatments; transplant center; VA facilities; dialysis certification; dialysis facility; dialysis stations; dialyzer reuse; disinfectant; ESRD network facilities; hemodialysis treatments; transplant center; VA facilities ID STAGE RENAL-DISEASE; AMBULATORY PERITONEAL-DIALYSIS; UNITED-STATES; HEMODIALYSIS-PATIENTS; KIDNEY-TRANSPLANTS; MORTALITY-RATES; SURVIVAL; MORBIDITY; DEATH; THERAPY C1 NIDDK, NIH, DKUHD, BETHESDA, MD 20892 USA. RP Held, PJ (reprint author), UNIV MICHIGAN, USRDS COORDINATING CTR, ANN ARBOR, MI 48109 USA. NR 171 TC 4 Z9 4 U1 1 U2 2 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0272-6386 EI 1523-6838 J9 AM J KIDNEY DIS JI Am. J. Kidney Dis. PD AUG PY 1997 VL 30 IS 2 SU 1 BP S1 EP S213 DI 10.1016/S0272-6386(97)90173-6 PG 213 WC Urology & Nephrology SC Urology & Nephrology GA XR543 UT WOS:A1997XR54300001 ER PT J AU Brost, BC Goldenberg, RL Mercer, BM Iams, JD Meis, PJ Moawad, AH Newman, RB Miodovnik, M Caritis, SN Thurnau, GR Bottoms, SF Das, A McNellis, D AF Brost, BC Goldenberg, RL Mercer, BM Iams, JD Meis, PJ Moawad, AH Newman, RB Miodovnik, M Caritis, SN Thurnau, GR Bottoms, SF Das, A McNellis, D TI The preterm prediction study: Association of cesarean delivery with increases in maternal weight and body mass index SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Article; Proceedings Paper CT 59th Annual Meeting of the South-Atlantic-Association-of-Obstetricians-and-Gynecologists CY JAN 25-28, 1997 CL HOT SPRINGS, VA SP S Atlantic Assoc Obstetricians & Gynecologists DE body mass index; maternal anthropometrics; cesarean delivery; prepregnancy weight; pregnancy ID PREGNANCY; DYSTOCIA; SECTION; RATES AB OBJECTIVE: Our purpose was to evaluate whether maternal weight and body mass index measured either before or during pregnancy are associated with an increased risk of cesarean delivery. STUDY DESIGN: Maternal weight and height were prospectively collected on 2929 women in the National Institutes of Health Maternal-Fetal Medicine Units Network Preterm Prediction Study. Prepregnancy and 27- to 31-week maternal weight and height were used to calculate the body mass index, and its contribution to the risk of cesarean delivery was determined. Women with prenatally diagnosed congenital anomalies (n = 89) and pregestational diabetes (n = 31) were excluded from analysis. RESULTS: Univariate analysis of risk factors for cesarean delivery in the 2809 eligible women revealed a decreased risk of cesarean delivery with maternal age <18 years and multiparity; increased risk of cesarean delivery was noted with maternal age >35 years and a male fetus. Increases in either prepregnancy or 27- to 31-week maternal weight (5-pound units) or body mass index (1.0 kg/m(2) units) were significantly associated with an increased odds of cesarean delivery (p = 0.0001). Each unit increase in prepregnancy or 27- to 31-week body mass index resulted in a parallel increase in the odds of cesarean delivery of 7.0% and 7.8%, respectively. Multivariable stepwise logistic regression analysis confirmed the association of male fetus, age, nulliparity, and body mass index as significant variables contributing to cesarean delivery risk. CONCLUSIONS: The risk of cesarean delivery is associated with incremental changes in maternal weight and body mass index before and during pregnancy after adjustment for potential confounding factors. Prepregnancy counseling about optimizing maternal weight and monitoring weight gain during pregnancy to decrease the risk of cesarean delivery are supported by this study. C1 NICHHD,MATERNAL FETAL MED UNITS NETWORK,BETHESDA,MD 20892. OI caritis, steve/0000-0002-2169-0712; Brost, Brian/0000-0002-4903-4186 FU NICHD NIH HHS [HD21410, HD21414, HD27860] NR 11 TC 62 Z9 63 U1 0 U2 1 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD AUG PY 1997 VL 177 IS 2 BP 333 EP 337 DI 10.1016/S0002-9378(97)70195-9 PG 5 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA XU865 UT WOS:A1997XU86500024 PM 9290448 ER PT J AU Pezzullo, JC Spong, CY Ghidini, A AF Pezzullo, JC Spong, CY Ghidini, A TI Angiogenin: A marker for preterm delivery in midtrimester amniotic fluid - Reply SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Letter C1 NICHHD,DEV NEUROBIOL LAB,NIH,BETHESDA,MD 20892. GEORGETOWN UNIV,MED CTR,DEPT OBSTET & GYNECOL,WASHINGTON,DC 20007. RP Pezzullo, JC (reprint author), GEORGETOWN UNIV,MED CTR,DEPT BIOSTAT & BIOMATH,3800 RESERVOIR RD NW,WASHINGTON,DC 20007, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD AUG PY 1997 VL 177 IS 2 BP 483 EP 484 PG 2 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA XU865 UT WOS:A1997XU86500068 ER PT J AU Lewis, RA Clogston, P Fainstein, V Gross, R Samo, T Tuttle, C Jabs, DA Apuzzo, L Bartlett, J Coleson, L Dunn, JP Eldred, L Feinberg, J Flynn, T King, R Leslie, J Barron, B Greenspan, D LeCount, C Peyman, G Franklin, R Heinemann, MH Polsky, B Squires, K WiseCampbell, S Friedman, AH Cheung, TW Justin, N Teich, S Sacks, H Severin, C Friedberg, DN Addessi, A Dieterich, D Frost, K Weinberg, D Jampol, L Murphy, R Naughton, K Henderly, D Holland, GN Chafey, S Fall, H Hardy, WD Kimbrell, C MacArthurChang, L Freeman, WR Meixnert, L Peterson, TJ Quiceno, JI Rickman, L Simanello, MA Spector, S ODonnell, J Hoffman, L Irvine, A Jacobson, M Larson, A Seiff, S Wanner, M Davis, J Chuang, E Espinal, M Mendez, P Vandenbroucke, R Cheeseman, SH Gittinger, J Haubrich, R Kachadoorian, H Tolson, K Kline, JM Klemm, AC Stevens, M Webb, R BrownBellamy, J Markowitz, JA Meinert, CL Brookmeyer, R Collins, KB Collison, BJ Dodge, J Donithan, M Fink, N Gerczak, C Gilpin, AMK Holbrook, JT Isaacson, MR Levine, CR Martin, B Min, YI Meinert, JL Owens, RM Nowakowski, DJ Saah, A Singer, S Smith, M Sternberg, AL Tonascia, J VanNatta, ML Davis, MD AgresSegal, M Armstrong, J Brickbauer, J Brothers, R Chop, M Freitag, G Hubbard, L Hurlburt, D Jensen, K Kastorff, L King, B Magli, Y Messing, S Miner, K Neider, M Stoppenbach, V Thomas, S VanderhoofYoung, M Stewart, G Hughes, R Welch, L Mowery, R Ellenberg, S Korvick, J Clark, T Sattler, F Brown, BW Conway, B Grizzle, J Nussenblatt, R Phair, J Smith, H Whitley, R AF Lewis, RA Clogston, P Fainstein, V Gross, R Samo, T Tuttle, C Jabs, DA Apuzzo, L Bartlett, J Coleson, L Dunn, JP Eldred, L Feinberg, J Flynn, T King, R Leslie, J Barron, B Greenspan, D LeCount, C Peyman, G Franklin, R Heinemann, MH Polsky, B Squires, K WiseCampbell, S Friedman, AH Cheung, TW Justin, N Teich, S Sacks, H Severin, C Friedberg, DN Addessi, A Dieterich, D Frost, K Weinberg, D Jampol, L Murphy, R Naughton, K Henderly, D Holland, GN Chafey, S Fall, H Hardy, WD Kimbrell, C MacArthurChang, L Freeman, WR Meixnert, L Peterson, TJ Quiceno, JI Rickman, L Simanello, MA Spector, S ODonnell, J Hoffman, L Irvine, A Jacobson, M Larson, A Seiff, S Wanner, M Davis, J Chuang, E Espinal, M Mendez, P Vandenbroucke, R Cheeseman, SH Gittinger, J Haubrich, R Kachadoorian, H Tolson, K Kline, JM Klemm, AC Stevens, M Webb, R BrownBellamy, J Markowitz, JA Meinert, CL Brookmeyer, R Collins, KB Collison, BJ Dodge, J Donithan, M Fink, N Gerczak, C Gilpin, AMK Holbrook, JT Isaacson, MR Levine, CR Martin, B Min, YI Meinert, JL Owens, RM Nowakowski, DJ Saah, A Singer, S Smith, M Sternberg, AL Tonascia, J VanNatta, ML Davis, MD AgresSegal, M Armstrong, J Brickbauer, J Brothers, R Chop, M Freitag, G Hubbard, L Hurlburt, D Jensen, K Kastorff, L King, B Magli, Y Messing, S Miner, K Neider, M Stoppenbach, V Thomas, S VanderhoofYoung, M Stewart, G Hughes, R Welch, L Mowery, R Ellenberg, S Korvick, J Clark, T Sattler, F Brown, BW Conway, B Grizzle, J Nussenblatt, R Phair, J Smith, H Whitley, R TI Foscarnet-ganciclovir cytomegalovirus retinitis trial .5. Clinical features of cytomegalovirus retinitis at diagnosis SO AMERICAN JOURNAL OF OPHTHALMOLOGY LA English DT Article ID ACQUIRED-IMMUNODEFICIENCY-SYNDROME; VIRUS; AIDS; RETINOPATHY; MANIFESTATIONS; PROPHYLAXIS; INFECTION AB PURPOSE: To examine associations of systemic and ocular characteristics with severity of cytomegalovirus (CMV) retinitis at time of diagnosis and to compare ocular characteristics of eyes with and without CMV retinitis. METHODS: Eleven clinical centers, a data coordinating center, and a fundus photograph reading center participated in a randomized, controlled, multicenter clinical trial comparing foscarnet and ganciclovir as primary therapy for previously untreated CMV retinitis in 240 patients with AIDS. RESULTS: The systemic characteristics marginally associated with the percentage of retina affect ed by CMV in a patient's worse eye at diagnosis were chronic fever, weight loss, and number of HIV-related illnesses. A positive CMV blood culture at diagnosis was similarly associated with bilateral disease. Laboratory measures of disease did not correlate well with measures of CMV retinitis severity. Many eyes with CMV retinitis had no or minimal lesion hemorrhage, but most had signs of inflammation. Patients often reported visual symptoms for involved eyes. The worse eyes (the eye with lesions covering the most retinal area) of patients with bilateral disease had greater retinal involvement, more lesions, and fewer degrees of visual field than did involved eyes of patients with unilateral disease. Visual symptoms, inflammation, indolent retinitis, and hemorrhagic lesions were associated with a greater percentage of retina affected by CMV. CONCLUSIONS: The findings support viremia as a mechanism of spread for untreated disease. Visual symptoms and signs of ocular inflammation were indicators both of the presence of CMV retinitis and of greater extent of retinal area covered by CMV retinitis lesions. C1 JOHNS HOPKINS CTR CLIN TRIALS,SOCA COORDINATING CTR,BALTIMORE,MD 21205. BAYLOR COLL MED,CULLEN EYE INST,HOUSTON,TX 77030. LOUISIANA STATE UNIV,MED CTR,NEW ORLEANS,LA. MEM SLOAN KETTERING CANC CTR,NEW YORK,NY 10021. CORNELL UNIV,MED CTR,NEW YORK HOSP,NEW YORK,NY 10021. MT SINAI SCH MED,NEW YORK,NY. NYU,MED CTR,NEW YORK,NY 10016. NORTHWESTERN UNIV,CHICAGO,IL 60611. UNIV CALIF LOS ANGELES,LOS ANGELES,CA. UNIV CALIF SAN DIEGO,SAN DIEGO,CA 92103. USN HOSP,WASHINGTON,DC. UNIV CALIF SAN FRANCISCO,SAN FRANCISCO,CA 94143. UNIV MIAMI,SCH MED,MIAMI,FL 33152. UNIV MASSACHUSETTS,MED CTR,WORCESTER,MA. JOHNS HOPKINS UNIV,SCH MED,CHAIRMANS OFF,BALTIMORE,MD. JOHNS HOPKINS UNIV,SCH HYG & PUBL HLTH,COORDINATING CTR,BALTIMORE,MD. UNIV WISCONSIN,FUNDUS PHOTOGRAPH READING CTR,MADRID,SPAIN. ERC BIOSERV CORP,DRUG DISTRIBUT CTR,ROCKVILLE,MD. NEI,BETHESDA,MD 20892. NIAID,BETHESDA,MD 20892. OI Murphy, Robert/0000-0003-3936-2052; Weinberg, David/0000-0002-1974-9252 NR 22 TC 32 Z9 32 U1 0 U2 1 PU OPHTHALMIC PUBL CO PI CHICAGO PA 77 WEST WACKER DR, STE 660, CHICAGO, IL 60601 SN 0002-9394 J9 AM J OPHTHALMOL JI Am. J. Ophthalmol. PD AUG PY 1997 VL 124 IS 2 BP 141 EP 157 PG 17 WC Ophthalmology SC Ophthalmology GA XP954 UT WOS:A1997XP95400001 ER PT J AU Magone, MT Nussenblatt, RB Whitcup, SM AF Magone, MT Nussenblatt, RB Whitcup, SM TI Elevation of laser flare photometry in patients with cytomegalovirus retinitis and AIDS SO AMERICAN JOURNAL OF OPHTHALMOLOGY LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; IMMUNE-DEFICIENCY SYNDROME; BLOOD-AQUEOUS BARRIER; RETINAL VASCULOPATHY; CELL METER; INFECTION; HIV; RETINOPATHY; UVEITIS; COUNTS AB PURPOSE: To investigate an alteration of the blood-ocular barriers by laser flare photometry in patients with acquired immunodeficiency syndrome (AIDS) diagnosed with cytomegalovirus retinitis. METHODS: Serial laser flare photometry measurements from 31 eyes of 31 patients with AIDS and newly diagnosed cytomegalovirus retinitis were compared with measurements from 31 control patients with AIDS but without documented eye disease. Location and extent of retinitis, presence of visual symptoms, and CD4 lymphocyte counts were also compared with laser flare photometry readings. RESULTS: Laser flare readings (mean +/- SE) were significantly higher in eyes with (13.0 +/- 1,5 photon counts per msec) than without cytomegalovirus retinitis (4.9 +/- 0.3 photon counts per msec) (P <.001). Lesions within the arcade vessels resulted in significantly higher laser flare photometry readings (17.3 +/- 2.5 photon counts per msec) compared with peripheral retinitis (9.8 +/- 1,5 photon counts per msec) (P =.01). A significant correlation was found between area of involvement of peripheral retinitis and laser flare photometry readings (P =.008). Readings in patients without cytomegalovirus retinitis increased significantly 10 months after the first measurement (9.5 +/- 1,9 photon counts per msec) (P =.04). Readings in patients with cytomegalovirus remained elevated 3 months after successful treat ment of retinitis (12.3 +/- 2.3 photon counts per msec) (P =.6). CONCLUSIONS: Laser flare photometry readings are significantly elevated in eyes with cytomegalo virus retinitis, suggesting a breakdown of the blood ocular barriers. Increasing laser flare photometry readings over time in patients without known ocular disease suggests that HIV infection may cause progressive breakdown of the blood-ocular barrier. C1 NEI,CLIN BRANCH,NIH,BETHESDA,MD 20892. NR 46 TC 21 Z9 22 U1 0 U2 0 PU OPHTHALMIC PUBL CO PI CHICAGO PA 77 WEST WACKER DR, STE 660, CHICAGO, IL 60601 SN 0002-9394 J9 AM J OPHTHALMOL JI Am. J. Ophthalmol. PD AUG PY 1997 VL 124 IS 2 BP 190 EP 198 PG 9 WC Ophthalmology SC Ophthalmology GA XP954 UT WOS:A1997XP95400005 PM 9262542 ER PT J AU Youngren, JF Goldfine, ID Pratley, RE AF Youngren, JF Goldfine, ID Pratley, RE TI Decreased muscle insulin receptor kinase correlates with insulin resistance in normoglycemic Pima Indians SO AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM LA English DT Article DE obesity; diabetes ID DEPENDENT DIABETES-MELLITUS; HUMAN SKELETAL-MUSCLE; TYROSINE-KINASE; PROTEIN-KINASE; GLUCOSE-TOLERANCE; OBESE SUBJECTS; NIDDM; PHOSPHORYLATION; MECHANISM; ACTIVATION AB Defects in insulin receptor tyrosine kinase activity are present in insulin-resistant non-insulin-dependent diabetes mellitus patients and certain nondiabetic individuals. both lean and obese. However, the relationship between insulin receptor function. insulin action, and obesity is unclear. To address this issue, we have employed a new and highly sensitive enzyme-linked immunosorbent assay to measure in vitro insulin-stimulated autophosphorylation of immunocaptured muscle insulin receptors in a group of 25 normoglycemic Pima Indians. Insulin action, determined during two-step euglycemic insulin clamps, varied widely in these subjects. Maximal in vitro insulin stimulation of insulin receptor autophosphorylation strongly correlated with both low (M-low)- and high (M-high)-dose insulin-stimulated glucose disposal (r = 0.62 and 0.51, P < 0.002 and 0.011, respectively). Insulin receptor autophosphorylation was inversely related to percent body fat (r = -0.52, P < 0.009). After control for percent body fat, receptor autophosphorylation remained correlated with M-low (partial r = 0.49, P < 0.025). These data therefore suggest that defects in insulin receptor function are major contributors to insulin resistance in both lean and obese normoglycemic Pima Indians. C1 NIDDKD, CLIN DIABET & NUTR SECT, NIH, PHOENIX, AZ 85016 USA. RP Youngren, JF (reprint author), UNIV CALIF SAN FRANCISCO, MT ZION MED CTR, DIV DIABET & ENDOCINE RES, DEPT MED, BOX 1616, SAN FRANCISCO, CA 94143 USA. FU NIA NIH HHS [T32AG-00212]; NIDDK NIH HHS [DK-44834] NR 35 TC 22 Z9 23 U1 0 U2 0 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0193-1849 EI 1522-1555 J9 AM J PHYSIOL-ENDOC M JI Am. J. Physiol.-Endocrinol. Metab. PD AUG PY 1997 VL 273 IS 2 BP E276 EP E283 PG 8 WC Endocrinology & Metabolism; Physiology SC Endocrinology & Metabolism; Physiology GA XQ274 UT WOS:A1997XQ27400008 PM 9277380 ER PT J AU Kinoshita, H Milstien, S Wambi, C Katusic, ZS AF Kinoshita, H Milstien, S Wambi, C Katusic, ZS TI Inhibition of tetrahydrobiopterin biosynthesis impairs endothelium-dependent relaxations in canine basilar artery SO AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY LA English DT Article DE cerebral artery; nitric oxide; receptors; superoxide anions; sepiapterin ID NITRIC-OXIDE SYNTHASE; RELAXING FACTOR; SMOOTH-MUSCLE; CYCLIC-GMP; SUPEROXIDE; GENERATION; COFACTOR; CELLS; REQUIREMENT; ARGININE AB Tetrahydrobiopterin is an essential cofactor in biosynthesis of nitric oxide. The present study was designed to determine the effect of decreased intracellular tetrahydrobiopterin levels on endothelial function of isolated cerebral arteries. Blood vessels were incubated for 6 h in minimum essential medium (MEM) in the presence or absence of a GTP cyclohydrolase I inhibitor, 2,4-diamino-6-hydroxypyrimidine (DAHP, 10(-2) M). Rings with and without endothelium were suspended for isometric force recording in the presence of a cyclooxygenase inhibitor, indomethacin (10(-5) M). In arteries with endothelium, DAHP significantly reduced intracellular levels of tetrahydrobiopterin. DAHP in combination with a precursor of the salvage pathway of tetrahydrobiopterin biosynthesis, sepiapterin (10(-4) NI), not only restored but increased levels of tetrahydrobiopterin above control values. In DAHP-treated arteries, endothelium-dependent relaxations to bradykinin (10(-10)-10(-6) M) Or calcium ionophore A23187 (10(-9)-10(-6) M) were significantly reduced, whereas endothelium-independent relaxations to a nitric oxide donor, 3-morpholinosydnonimine (10(-9)-10(-4) M), were not affected. When DAHP-treated arteries with endothelium were incubated with sepiapterin (10(-4) M) or superoxide dismutase (150 U/ml), relaxations to bradykinin and A23187 were restored to control levels. In contrast, superoxide dismutase did not affect endothelium-dependent relaxations in arteries incubated in MEM. A nitric oxide synthase inhibitor, N-G-nitro-L-arginine methyl ester (10(-4) M), abolished relaxations to bradykinin or A23187 in control arteries and in DAHP-treated arteries. These studies demonstrate that in cerebral arteries,decreased intracellular levels of tetrahydrobiopterin can reduce endothelium-dependent relaxations. Production of superoxide anions during activation of dysfunctional endothelial nitric oxide synthase appears to be responsible for the impairment of endothelial function. C1 Mayo Clin & Mayo Fdn, Dept Anesthesiol, Rochester, MN 55905 USA. Mayo Clin & Mayo Fdn, Dept Pharmacol, Rochester, MN 55905 USA. NIMH, Lab Cellular & Mol Regulat, NIH, Bethesda, MD 20892 USA. RP Katusic, ZS (reprint author), Mayo Clin & Mayo Fdn, Dept Anesthesiol, 200 1st St SW, Rochester, MN 55905 USA. FU NHLBI NIH HHS [HL-53524] NR 32 TC 60 Z9 61 U1 0 U2 0 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0363-6135 J9 AM J PHYSIOL-HEART C JI Am. J. Physiol.-Heart Circul. Physiol. PD AUG PY 1997 VL 273 IS 2 BP H718 EP H724 PG 7 WC Cardiac & Cardiovascular Systems; Physiology; Peripheral Vascular Disease SC Cardiovascular System & Cardiology; Physiology GA XQ295 UT WOS:A1997XQ29500025 PM 9277488 ER PT J AU Wu, T Levine, SJ Cowan, M Logun, C Angus, CW Shelhamer, JH AF Wu, T Levine, SJ Cowan, M Logun, C Angus, CW Shelhamer, JH TI Antisense inhibition of 85-kDa cPLA(2) blocks arachidonic acid release from airway epithelial cells SO AMERICAN JOURNAL OF PHYSIOLOGY-LUNG CELLULAR AND MOLECULAR PHYSIOLOGY LA English DT Article DE airway inflammation; lipid mediators; asthma ID TUMOR-NECROSIS-FACTOR; CYTOSOLIC PHOSPHOLIPASE A(2); GENE-EXPRESSION; II PHOSPHOLIPASE-A2; INTERFERON-GAMMA; MESANGIAL CELLS; PROTEIN; KINASE; ACTIVATION; LINE AB Inflammatory cytokines play a critical role in the initiation and perpetuation of inflammation. Several cytokines are known to increase the production of arachidonic acid (AA) metabolites, which may mediate cytokine-induced acute and chronic inflammation. Although cytokines upregulate phospholipase A(2) (PLA(2)) in several target cells, the contribution of individual PLA(2) to cytokine-induced AA release and eicosanoid production remains unclear because of the existence of various forms of cellular PLA(2). To examine the role of 85-kDa cytosolic PLA(2) (cPLA(2)) in cytokine-induced AA release, a system was developed to inhibit the expression of cPLA(2) in a human bronchial epithelial cell line (BEAS-2B cells) by antisense RNA. Cells stably expressing antisense cPLA(2) exhibited decreased cPLA(2) protein levels as well as decreased cPLA(2) activity assayed in vitro. The effects of cytokines interferon-gamma (IFN-gamma), tumor necrosis factor-alpha (TNF-alpha), and interleukin-1 alpha (IL-1 alpha) on the release of prelabeled [H-3]AA were then tested in cells stably transfected with vector alone as well as cells transfected with cPLA(2) antisense plasmid. IFN-gamma (300 U/ml), TNF-alpha (20 ng/ml), and IL-1 alpha (20 ng/ml) all induced a significantly increased release of prelabeled [H-3]AA after 15 min to 2 h of treatment in control cells, and their effects were significantly reduced in cells transfected with cPLA(2) antisense vector. These results demonstrate a critical role of cPLA(2) in inflammatory cytokine-induced AA metabolism. C1 NATL INST HLTH, DEPT CRIT CARE MED, BETHESDA, MD 20892 USA. NR 35 TC 21 Z9 21 U1 0 U2 0 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 1040-0605 J9 AM J PHYSIOL-LUNG C JI Am. J. Physiol.-Lung Cell. Mol. Physiol. PD AUG PY 1997 VL 273 IS 2 BP L331 EP L338 PG 8 WC Physiology; Respiratory System SC Physiology; Respiratory System GA XP589 UT WOS:A1997XP58900006 PM 9277444 ER PT J AU Sackett, DL AF Sackett, DL TI Natural osmolyte trimethylamine N-oxide stimulates tubulin polymerization and reverses urea inhibition SO AMERICAN JOURNAL OF PHYSIOLOGY-REGULATORY INTEGRATIVE AND COMPARATIVE PHYSIOLOGY LA English DT Article DE microtubules; betaine; methylamine ID MICROTUBULE-ASSOCIATED PROTEINS; THERMAL-STABILITY; MECHANISM; WATER; FISHES AB The natural osmolyte trimethylamine N-oxide (TMAO) is one of the methylamine compounds often accumulated by diverse organisms in response to osmotic stress and/or to compensate for the deleterious effects of urea. Tubulin polymerization is promoted by TMAO. At 1 M TMAO, tubulin polymers are produced with properties expected of normal steady-state microtubules (MT): polymerization is reversed by exposure to cold or the antimitotic drug podophyllotoxin, a critical concentration for polymerization at 30 degrees C of 1.5 mu M is found, and the morphology of the polymers in electron micrographs is typical of MT and ribbons, or open MT. At 2 M TMAO, polymerization is very rapid and hyperstable polymers are formed. These are resistant to cold-induced depolymerization although still sensitive to podophyllotoxin inhibition. A lower critical concentration of 0.7 mu M M is observed, and electron micrographs reveal MT, ribbons, and other polymer forms not usually stable, such as splayed protofilaments. Inhibition of tubulin polymerization by low concentrations of urea (Sackett, D. L., B. Bhattacharyya, and J. Wolff. Biochemistry 33: 12868-12878, 1994) is largely reversed by the presence of TMAO at one-half the molarity of urea, the physiological ratio observed in cartilaginous fishes. Other methylamines, including betaine, dimethylglycine, glycine, and sarcosine, failed to stimulate MT polymerization or protect against urea inhibition. Trimethylamine, taurine, and glycylglycine inhibit polymerization. TMAO did not interfere with binding of MT-associated proteins (MAP) and protected both tubulin assembly and MAP binding from urea. RP Sackett, DL (reprint author), NIDDKD, BIOCHEM PHARMACOL LAB,NIH,BLDG 8,RM 2A-23, 8 CTR DR, MSC 0830, BETHESDA, MD 20892 USA. NR 35 TC 23 Z9 23 U1 0 U2 3 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0363-6119 J9 AM J PHYSIOL-REG I JI Am. J. Physiol.-Regul. Integr. Comp. Physiol. PD AUG PY 1997 VL 273 IS 2 BP R669 EP R676 PG 8 WC Physiology SC Physiology GA XP269 UT WOS:A1997XP26900027 PM 9277553 ER PT J AU Frokiaer, J Christensen, BM Marples, D Djurhuus, JC Jensen, UB Knepper, MA Nielsen, S AF Frokiaer, J Christensen, BM Marples, D Djurhuus, JC Jensen, UB Knepper, MA Nielsen, S TI Downregulation of aquaporin-2 parallels changes in renal water excretion in unilateral ureteral obstruction SO AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY LA English DT Article DE polyuria; collecting duct; nephrogenic diabetes insipidus; obstructive nephropathy ID COLLECTING DUCT; RAT-KIDNEY; CHANNEL EXPRESSION; VASOPRESSIN; MEMBRANE; FAMILY; DIURESIS; CLONING; PROTEIN; CDNA AB In bilateral ureteral obstruction, both aquaporin-2 (AQP2) levels and urinary concentrating capacity are markedly reduced. However, the mechanisms involved in AQP2 downregulation are unknown. In rats with unilateral ureteral obstruction (WO) the relative role of intrarenal and systemic factors can be evaluated. Semiquantitative immunoblotting revealed a marked decrease in AQP2 in obstructed kidneys to 23 +/- 7% (n = 9) of sham levels. This downregulation persisted 24 h after release of UUO. Furthermore, there was a significant but less extensive downregulation of AQP2 in the nonobstructed kidneys to 75 +/- 7% (n = 9) of sham levels. Consistent with impairment of collecting duct water reabsorption, free water clearance was greatly elevated in the obstructed kidneys (-2 +/- mu l.min(-l).kg(-1), determined immediately after release) and only moderately elevated in nonobstructed kidneys (-44 +/- 5 mu l.min(-1).kg(-1)) compared with sham-operated controls (-59 +/- 3 mu.min(-1).kg(-1)). Also AQP2 mRNA levels were reduced in obstructed kidneys. Immunocytochemistry confirmed the marked decrease in AQP2 expression in obstructed kidneys. In nonobstructed kidneys AQP2 was predominantly found in intracellular vesicles, which together with the reduced expression and elevated free water clearance strongly suggests a role of AQP2 in the observed compensatory diuresis from nonobstructed kidneys. The much lower AQP2 protein and mRNA levels in obstructed vs. nonobstructed kidneys are consistent with intrarenal factors playing a major role for downregulation of AQP2. C1 AARHUS UNIV HOSP, DEPT CLIN PHYSIOL, DK-8000 AARHUS, DENMARK. AARHUS UNIV, INST EXPT CLIN RES, DK-8000 AARHUS, DENMARK. UNIV LEEDS, DEPT PHYSIOL, LEEDS LS2 9NQ, W YORKSHIRE, ENGLAND. AARHUS UNIV, DEPT HUMAN GENET, DK-8000 AARHUS, DENMARK. NHLBI, KIDNEY & ELECTROLYTE METAB LAB, NIH, BETHESDA, MD 20892 USA. RP Frokiaer, J (reprint author), AARHUS UNIV, INST ANAT, DEPT CELL BIOL, DK-8000 AARHUS, DENMARK. NR 30 TC 72 Z9 72 U1 1 U2 3 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1931-857X J9 AM J PHYSIOL-RENAL JI Am. J. Physiol.-Renal Physiol. PD AUG PY 1997 VL 273 IS 2 BP F213 EP F223 PG 11 WC Physiology; Urology & Nephrology SC Physiology; Urology & Nephrology GA XQ971 UT WOS:A1997XQ97100005 PM 9277582 ER PT J AU Rapoport, JL AF Rapoport, JL TI Child psychiatry comes of age: Growing sophistication, evolving strategies SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Editorial Material ID HALOPERIDOL; PIMOZIDE RP Rapoport, JL (reprint author), NIMH,CHILD PSYCHIAT BRANCH,BLDG 10,ROOM 6N240,10 CTR DR,MSC 1600,BETHESDA,MD 20892, USA. NR 10 TC 3 Z9 3 U1 3 U2 3 PU AMER PSYCHIATRIC ASSOCIATION PI WASHINGTON PA 1400 K ST NW, WASHINGTON, DC 20005 SN 0002-953X J9 AM J PSYCHIAT JI Am. J. Psychiat. PD AUG PY 1997 VL 154 IS 8 BP 1043 EP 1045 PG 3 WC Psychiatry SC Psychiatry GA XN537 UT WOS:A1997XN53700001 PM 9247385 ER PT J AU Pietrini, P Dani, A Furey, ML Alexander, GE Freo, U Grady, CL Mentis, MJ Mangot, D Simon, EW Horwitz, B Haxby, JV Schapiro, MB AF Pietrini, P Dani, A Furey, ML Alexander, GE Freo, U Grady, CL Mentis, MJ Mangot, D Simon, EW Horwitz, B Haxby, JV Schapiro, MB TI Low glucose metabolism during brain stimulation in older Down's syndrome subjects at risk for Alzheimer's disease prior to dementia SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Article ID ENDOGENOUS DOPAMINE; TARDIVE-DYSKINESIA; RECEPTORS AB Objective: Down's syndrome is characterized by the genetically programmed accumulation of substantial Alzheimer's disease neuropathology after age 40 and the development of early dementia years later, providing a unique human model to investigate the preclinical phases of Alzheimer's disease. Older nondemented adults with Down's syndrome show normal rates of regional cerebral glucose metabolism at rest before the onset of dementia, indicating that their neurons maintain function at rest. The authors hypothesized that an audiovisual stimulation paradigm, acting as a stress test, would reveal abnormalities in cerebral glucose metabolism before dementia in the neocortical parietal and temporal areas most vulnerable to Alzheimer's disease. Method: Regional cerebral glucose metabolism was assessed by means of positron emission tomography (PET) with [F-18]fluorodeoxyglucose in eight younger (mean age=35 years, SD=2) and eight older (mean age=50, SD=7) healthy, nondemented adults with trisomy 21 Down's syndrome. PET scans were performed at rest and during audiovisual stimulation in the same scanning session. Levels of general intellectual functioning and compliance were similar in the two groups. Results: At rest the two groups showed no difference in glucose metabolism in any cerebral region. In contrast, during audiovisual stimulation the older subjects with Down's syndrome had significantly lower glucose metabolic rates in the parietal and temporal cortical areas. Conclusions: Abnormalities in cerebral metabolism during stimulation appeared in the first cortical regions typically affected in Alzheimer's disease. These results indicate that a stress test paradigm can detect metabolic abnormalities in the preclinical stages of Alzheimer's disease despite normal cerebral metabolism at rest. C1 ELWYN INST, ELWYN, PA USA. RP Pietrini, P (reprint author), NIA, NEUROSCI LAB,NIH,RM 6C414,BLDG 10, 9000 ROCKVILLE PIKE, BETHESDA, MD 20892 USA. RI Furey, Maura/H-5273-2013 NR 31 TC 46 Z9 46 U1 2 U2 2 PU AMER PSYCHIATRIC PUBLISHING, INC PI ARLINGTON PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA SN 0002-953X J9 AM J PSYCHIAT JI Am. J. Psychiat. PD AUG PY 1997 VL 154 IS 8 BP 1063 EP 1069 PG 7 WC Psychiatry SC Psychiatry GA XN537 UT WOS:A1997XN53700006 PM 9247390 ER PT J AU Dukoff, R Sunderland, T AF Dukoff, R Sunderland, T TI Durable power of attorney and informed consent with Alzheimer's disease patients: A clinical study SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Article ID LEGAL ISSUES; DEMENTIA; GUIDELINES; SCALE; AGE AB Objective: Experience with a new surrogate consent system for patients with Alzheimer's disease is reviewed. It was hypothesized that as patients' cognitive status deteriorated surrogate consent through a durable power of attorney would become necessary to facilitate continued involvement in clinical research. Method: The authors retrospectively reviewed the charts of inpatients with Alzheimer's disease who participated in research between January 1989 and December 1994 at the Geriatric Psychiatry Unit of the National Institute of Mental Health. Seventy-nine patients were included. The main outcome measures were the Clinical Dementia Rating, Global Deterioration Scale for primary degenerative dementia, and Mini-Mental State. Results: Most patients were in the mild-to-moderate stage of the illness when they chose to participate in research and assign a durable power of attorney (96% scored 2 or less on the Clinical Dementia Rating, and 92% scored 5 or less on the Global Deterioration Scale). On average, the subjects participated in 3.8 (SD=2.6) studies. For 35 patients with multiple admissions over this period (average=3.1 years), scores on the Clinical Dementia Rating and Global Deterioration Scale declined by 2.0 and 1.5 points, respectively. Conclusions: The durable power of attorney allows research participation for subjects with Alzheimer's disease at all stages. The linchpin is assignment of a durable power of attorney in the early-to-moderate stage of Alzheimer's disease, before subjects lose the capacity to give informed consent. This approach could also be adapted to patients with cognitive decline due to other debilitating diseases. C1 NIMH,GERIATR PSYCHIAT BRANCH,NIH,CTR CLIN,BETHESDA,MD 20892. NR 35 TC 28 Z9 28 U1 0 U2 3 PU AMER PSYCHIATRIC ASSOCIATION PI WASHINGTON PA 1400 K ST NW, WASHINGTON, DC 20005 SN 0002-953X J9 AM J PSYCHIAT JI Am. J. Psychiat. PD AUG PY 1997 VL 154 IS 8 BP 1070 EP 1075 PG 6 WC Psychiatry SC Psychiatry GA XN537 UT WOS:A1997XN53700007 PM 9247391 ER PT J AU Shimon, H Agam, G Belmaker, RH Hyde, TM Kleinman, JE AF Shimon, H Agam, G Belmaker, RH Hyde, TM Kleinman, JE TI Reduced frontal cortex inositol levels in postmortem brain of suicide victims and patients with bipolar disorder SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Article ID LITHIUM AB Objective: This study aimed to evaluate aspects of second messenger function in the brain of suicide victims and patients with bipolar disorder. Method: Inositol and its synthetic enzyme, inositol monophosphatase, were measured in postmortem brain samples of 10 suicide victims, eight patients with bipolar affective disorder, and 10 normal comparison subjects. Results: The frontal cortex inositol levels of the suicide victims and the patients with bipolar disorder were significantly less than those of the normal comparison group. No differences in cerebellum or occipital cortex inositol levels were found among the three groups. The groups also showed no differences in inositol monophosphatase activity in any brain area. Conclusions: These results could suggest a deficiency of second messenger Precursor in patients with bipolar disorder and suicide victims. C1 BEN GURION UNIV NEGEV,FAC HLTH SCI,MINIST HLTH,MENTAL HLTH CTR,IL-84105 BEER SHEVA,ISRAEL. ST ELIZABETH HOSP,CTR NEUROSCI,NIMH,CLIN BRAIN DISORDERS BRANCH,WASHINGTON,DC. NR 10 TC 105 Z9 106 U1 0 U2 5 PU AMER PSYCHIATRIC ASSOCIATION PI WASHINGTON PA 1400 K ST NW, WASHINGTON, DC 20005 SN 0002-953X J9 AM J PSYCHIAT JI Am. J. Psychiat. PD AUG PY 1997 VL 154 IS 8 BP 1148 EP 1150 PG 3 WC Psychiatry SC Psychiatry GA XN537 UT WOS:A1997XN53700021 PM 9247405 ER PT J AU Davis, H Schoendorf, KC Gergen, PJ Moore, RM AF Davis, H Schoendorf, KC Gergen, PJ Moore, RM TI National trends in the mortality of children with sickle cell disease, 1968 through 1992 SO AMERICAN JOURNAL OF PUBLIC HEALTH LA English DT Article ID CLINICAL PRESENTATION; ORAL PENICILLIN; ANEMIA; PROPHYLAXIS; EXPERIENCE; DIAGNOSIS; SURVIVAL AB Objectives. This paper describes national trends in mortality of children with sickle cell disease and the settings in which death occurred. Methods. United States death certificate data from 1968 through 1992 were used to calculate mortality rates of Black children with sickle cell disease 1 to 14 pears old. Deaths from trauma, congenital anomalies, and perinatal conditions were excluded. Results. Between 1968 and 1992, mortality rates of Black children with sickle cell disease decreased 41% for 1- to 4-year-olds, 47% for 5- to 9-year-olds, and 53% for 10- to 14-year-olds. During 1986 through 1992, children who died before hospital admission accounted for 41% of deaths among 1- to 4-year-olds, 27% among 5- to 9-year-olds, and 12% among 10- to 14-year-olds. Conclusions. Survival of Black children with sickle cell disease has improved markedly since 1968. A substantial proportion of deaths continue to occur prior to hospital admission. Trends in sickle cell mortality can be monitored inexpensively with death-certificate data. C1 US DEPT HHS,OFF INT & REFUGEE HLTH,OFF SECRETARY,ROCKVILLE,MD. CTR DIS CONTROL & PREVENT,NATL CTR HLTH STAT,INFANT & CHILD HLTH STUDIES BRANCH,HYATTSVILLE,MD 20782. NIAID,NIH,BETHESDA,MD 20892. NR 34 TC 34 Z9 34 U1 0 U2 0 PU AMER PUBLIC HEALTH ASSOC INC PI WASHINGTON PA 1015 FIFTEENTH ST NW, WASHINGTON, DC 20005 SN 0090-0036 J9 AM J PUBLIC HEALTH JI Am. J. Public Health PD AUG PY 1997 VL 87 IS 8 BP 1317 EP 1322 DI 10.2105/AJPH.87.8.1317 PG 6 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA XR786 UT WOS:A1997XR78600009 PM 9279267 ER PT J AU Irvin, CG Martin, RJ Chinchilli, VM Kunselman, SJ Cherniack, RM Hurd, S Drazen, JM Israel, E McGarry, B Fish, JE Peters, SP Kubis, J Lemanske, RF Sorkness, DC Cox, K Szefler, SJ Pak, J Boushey, HA Lazarus, SC Fahy, JV Ward, T Martel, JK Mauger, EA Zwillich, CW AF Irvin, CG Martin, RJ Chinchilli, VM Kunselman, SJ Cherniack, RM Hurd, S Drazen, JM Israel, E McGarry, B Fish, JE Peters, SP Kubis, J Lemanske, RF Sorkness, DC Cox, K Szefler, SJ Pak, J Boushey, HA Lazarus, SC Fahy, JV Ward, T Martel, JK Mauger, EA Zwillich, CW TI Quality control of peak flow meters for multicenter clinical trials SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Article ID ACCURACY; FLOWMETERS; REPRODUCIBILITY AB Although peak expiratory flow (PEF) measurements are recommended for monitoring and assessing treatment of asthmatic patients, and widely employed to assess outcome in clinical trials and epidemiologic studies, information about performance of peak flow meters (PFM) under field conditions is lacking. We describe a simple testing system consisting of a testing chamber, a spirometer, and a calibration syringe to evaluate the relative accuracy or median relative bias (MRB), precision, or interquartile range (IQR) of the mini-Wright PFM. The relative accuracy ranged from -4.4 to 13.2% (mean, 4.1%) and the precision from 0.06 to 11.5% (mean, 1.2%). Durability of this PFM was assessed during a 26-wk clinical trial in 255 asthmatic subjects at five centers. Seventy-one PFM (19.9%) were identified as having failed to meet acceptance criteria, predominantly because of loss of relative accuracy, by the clinics at follow-up visits (n = 36), and by the Data Coordinating Center on retrospective review of quality control measurements submitted by the clinics (n = 35). This study indicates that a simple device can be used to evaluate the relative accuracy and precision of a given PFM and to ensure the quality of PEF measurements during a clinical trial. To the extent that one can extrapolate these data to other devices, our findings indicate that the failure rate of PFM over time can be high, indicating that quality control of a PFM over time is absolutely essential in clinical trials as well as in routine clinical care. C1 BRIGHAM & WOMENS HOSP,DEPT MED,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT MED,BOSTON,MA. THOMAS JEFFERSON UNIV,DEPT MED,PHILADELPHIA,PA 19107. UNIV WISCONSIN,DEPT MED,MADISON,WI. UNIV CALIF SAN FRANCISCO,DEPT MED,SAN FRANCISCO,CA. PENN STATE UNIV,MILTON S HERSHEY MED CTR,DEPT MED,HERSHEY,PA 17033. NHLBI,DEPT MED,BETHESDA,MD 20892. CHAIRMAN STEERING COMM,DENVER,CO. NHLBI,WASHINGTON,DC. DATA COORDINATING CTR,HERSHEY,PA. RP Irvin, CG (reprint author), UNIV DENVER,DEPT MED,NATL JEWISH CTR IMMUNOL & RESP MED,1400 JACKSON ST,DENVER,CO 80206, USA. FU NHLBI NIH HHS [U10 HL-51831, U10 HL-51843, U10 HL-51834] NR 14 TC 11 Z9 12 U1 0 U2 1 PU AMER LUNG ASSOC PI NEW YORK PA 1740 BROADWAY, NEW YORK, NY 10019 SN 1073-449X J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PD AUG PY 1997 VL 156 IS 2 BP 396 EP 402 PG 7 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA XR408 UT WOS:A1997XR40800007 PM 9279215 ER PT J AU Beck, GJ Sullivan, EJ Stoller, JK Peavy, HH AF Beck, GJ Sullivan, EJ Stoller, JK Peavy, HH TI Lymphangioleiomyomatosis: New insights SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Letter C1 NHLBI,WASHINGTON,DC. RP Beck, GJ (reprint author), CLEVELAND CLIN FDN,9500 EUCLID AVE,CLEVELAND,OH 44195, USA. NR 1 TC 1 Z9 1 U1 0 U2 0 PU AMER LUNG ASSOC PI NEW YORK PA 1740 BROADWAY, NEW YORK, NY 10019 SN 1073-449X J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PD AUG PY 1997 VL 156 IS 2 BP 670 EP 670 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA XR408 UT WOS:A1997XR40800051 PM 9279258 ER PT J AU Avila, NA Dwyer, AJ Falloon, J AF Avila, NA Dwyer, AJ Falloon, J TI Symptomatic appendiceal wall thickening in an HIV-infected patient caused by interleukin-2 therapy SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Article C1 NIAID,DIV INTRAMURAL RES,NIH,BETHESDA,MD 20892. RP Avila, NA (reprint author), NIH,WARREN GRANT MAGNUSON CLIN CTR,DEPT DIAGNOST RADIOL,BLDG 10,RM 1C-660,10 CTR DR,MSC 1182,BETHESDA,MD 20892, USA. NR 7 TC 0 Z9 0 U1 0 U2 0 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 SN 0361-803X J9 AM J ROENTGENOL JI Am. J. Roentgenol. PD AUG PY 1997 VL 169 IS 2 BP 499 EP 500 PG 2 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA XM758 UT WOS:A1997XM75800039 PM 9242763 ER PT J AU Vodovotz, Y Hsing, A Cook, JA Miller, RW Wink, DA Ritt, DM Mitchell, JB Danielpour, D AF Vodovotz, Y Hsing, A Cook, JA Miller, RW Wink, DA Ritt, DM Mitchell, JB Danielpour, D TI Qualitative and quantitative analysis of DNA fragmentation using digital imaging SO ANALYTICAL BIOCHEMISTRY LA English DT Article ID FLOW CYTOMETRIC DETECTION; GROWTH-FACTOR-BETA; NITRIC-OXIDE; ANNEXIN-V; PHOSPHATIDYLSERINE EXPRESSION; CELL-DEATH; APOPTOSIS; FIBROBLASTS; MACROPHAGES; BINDING AB Apoptosis is an important and common pathway of cellular death. Differentiation from cellular necrosis and quantitation of apoptosis within the milieu of necrosis are analytical challenges. We describe the use of the RIT120 digital imaging software package for quantitative and qualitative analysis of apoptotic DNA ladders induced by a variety of agents, such as serum, tumor necrosis factor-alpha, transforming growth factor-beta 1, and nitric oxide, Autoradiographs of DNA ladders are densitometrically scanned to yield a set of curves with peaks corresponding to specific DNA fragments, thereby allowing quantitative subtraction of concurrent DNA degradation from necrotic death. Integration of the areas specifically under the peaks yields a quantitative measure of apoptosis. We provide a useful, rapid, and objective means to quantitate apoptosis, using relatively inexpensive hardware and software. (C) 1997 Academic Press. C1 NCI,CHEMOPREVENT LAB,BETHESDA,MD 20892. NCI,RADIAT ONCOL BRANCH,BETHESDA,MD 20892. RADIOL IMAGING TECHNOL,COLORADO SPRINGS,CO 80919. RP Vodovotz, Y (reprint author), NCI,RADIAT BIOL BRANCH,BLDG 10,ROOM B3B69,BETHESDA,MD 20892, USA. NR 21 TC 6 Z9 6 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0003-2697 J9 ANAL BIOCHEM JI Anal. Biochem. PD AUG 1 PY 1997 VL 250 IS 2 BP 147 EP 152 DI 10.1006/abio.1997.2226 PG 6 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA XM801 UT WOS:A1997XM80100003 PM 9245431 ER PT J AU Takahashi, H Traystman, RJ Hashimoto, K London, ED Kirsch, JR AF Takahashi, H Traystman, RJ Hashimoto, K London, ED Kirsch, JR TI Postischemic brain injury is affected stereospecifically by pentazocine in rats SO ANESTHESIA AND ANALGESIA LA English DT Article ID CEREBRAL-ARTERY OCCLUSION; TRANSIENT FOCAL ISCHEMIA; SIGMA-RECEPTOR LIGAND; BLOOD-FLOW; CATS; NALOXONE; (+)-PENTAZOCINE; ANALGESIA; CHLORIDE; BINDING AB We tested whether rats treated with the sigma(1)-receptor ligand, (+)pentazocine, during transient focal ischemia would have a smaller volume of postischemic brain infarction than rats treated with the nonspecific opioid-receptor ligand (-)-pentazocine. Rats underwent focal cerebral ischemia using the filament occlusion technique for 2 h, followed by 22 h of reperfusion. Rats received (+) or (-)-pentazocine (n = 9 each group) at a dose of 2 mg . kg(-1) . h(-1) by continuous intravenous infusion from 1 h of ischemia to 22 h of reperfusion. Triphenyltetrazolium-determined infarction volume of ipsilateral striatum ([+]-pentazocine, 19 +/- 4 mm(3), mean +/- SEM; [-]-pentazocine, 44 +/- 5 mm(3)) and cerebral cortex ([+]-pentazocine, 26 +/- 12 mm(3); [-]-pentazocine, 134 +/- 29 mm(3)) was smaller in rats treated with (+) compared with (-)-pentazocine. Infarction volume in rats treated with (-)-pentazocine was also very similar to the infarction volume in saline-treated control rats from our previous study (striatum 44 +/- 4 mm(3); hemisphere 136 +/- 27 mm(3)). These data indicate that sigma(1)-receptors may play an important role in the mechanism of injury both in cortex and striatum after 2 h of transient focal ischemia in rat. C1 JOHNS HOPKINS MED INST,DEPT ANESTHESIOL & CRIT CARE MED,BALTIMORE,MD 21287. NATL INST DRUG ABUSE,BRAIN IMAGING SECT,DIV INTRAMURAL RES,BALTIMORE,MD. FU NINDS NIH HHS [NS20020] NR 31 TC 20 Z9 20 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0003-2999 J9 ANESTH ANALG JI Anesth. Analg. PD AUG PY 1997 VL 85 IS 2 BP 353 EP 357 DI 10.1097/00000539-199708000-00020 PG 5 WC Anesthesiology SC Anesthesiology GA XP077 UT WOS:A1997XP07700020 PM 9249113 ER PT J AU Sang, CN Gracely, RH Max, MB AF Sang, CN Gracely, RH Max, MB TI Capsaican-evoked mechanical allodynia and hyperalgesia cross-nerve territories - Reply SO ANESTHESIOLOGY LA English DT Letter C1 ALLEGHENY UNIV HLTH SCI,DEPT NEUROL,PHILADELPHIA,PA 19102. RP Sang, CN (reprint author), NIDR,NEUROBIOL & ANESTHESIOL BRANCH,NIH,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0003-3022 J9 ANESTHESIOLOGY JI Anesthesiology PD AUG PY 1997 VL 87 IS 2 BP 452 EP 452 DI 10.1097/00000542-199708000-00041 PG 1 WC Anesthesiology SC Anesthesiology GA XR406 UT WOS:A1997XR40600041 ER PT J AU Abbott, RD Sharp, DS Burchfiel, CM Curb, JD Rodriguez, BL Hakim, AA Yano, K AF Abbott, RD Sharp, DS Burchfiel, CM Curb, JD Rodriguez, BL Hakim, AA Yano, K TI Cross sectional and longitudinal changes in total and high-density-lipoprotein cholesterol levels over a 20-year period in elderly men: The Honolulu Heart Program SO ANNALS OF EPIDEMIOLOGY LA English DT Review DE total cholesterol; high-density-lipoprotein cholesterol; coronary heart disease; epidemiology; elderly men; cohort study ID HIGH BLOOD CHOLESTEROL; SERUM-CHOLESTEROL; CARDIOVASCULAR-HEALTH; OLDER ADULTS; RISK-FACTORS; DISEASE; MORTALITY AB PURPOSE: The purpose of this report is to describe levels of total cholesterol and high-density-lipoprotein cholesterol (HDL-C) in a group of elderly men and to compare these levels to those that were observed 20 years earlier. METHODS: From 1965-1968, the Honolulu Heart Program began following 8006 men of Japanese ancestry living on the island of Oahu, Hawaii, in a prospective study of coronary heart disease and stroke. This report presents data for 971 men who participated in a separate fasting study of lipids and lipoproteins that first occurred from 1970-1972 and in those who received repeat examinations 10 and 20 years later. Men were aged 71-93 years at the last examination. RESULTS: Over the 20-year period, total cholesterol declined by 1.6-1.8 mg/dL per year (P < 0.001), from average baseline values of 219-222 mg/dL. Levels of HDL-C rose 0.2-0.3 mg/dL per year (P ( 0.001), from average baseline Values of 44-46 mg/dL. After adjustment for baseline cholesterol levers, men with prevalent coronary heart disease at the end of the 20-year follow-up experienced significantly greater reductions in total cholesterol levels than men without disease (P < 0.001). Men who developed coronary heart disease within the first 10 years of follow-up had the greatest yearly decline in total cholesterol (1.9 mg/dL), followed by men who developed heart disease later (1.8 mg/dL) and men who remained disease free (1.5 mg/dL). Differences between men with recent and earlier disease were not statistically significant, although men without coronary disease experienced a significantly smaller decrease in total cholesterol than either of these groups (P < 0.05). CONCLUSIONS: Changes in total cholesterol and HDL-C levels with advancing age may be part of a natural aging process. Some changes, however, such as large reductions in total cholesterol, may signal occult disease or declines in overall health. Selective survival may contribute to these findings since improvements in lipid and lipoprotein levels that are beneficial in younger ages were common in this long-lived cohort of men. (C) 1997 Elsevier Science Inc. C1 NHLBI,HONOLULU EPIDEMIOL RES SECT,EPIDEMIOL & BIOMETRY PROGRAM,HONOLULU,HI. UNIV HAWAII MANOA,JOHN A BURNS SCH MED,DIV CLIN EPIDEMIOL,HONOLULU,HI 96822. KUAKINI MED CTR,HONOLULU HEART PROGRAM,HONOLULU,HI 96817. RP Abbott, RD (reprint author), UNIV VIRGINIA,SCH MED,DIV BIOSTAT,BOX 432,CHARLOTTESVILLE,VA 22908, USA. FU NHLBI NIH HHS [N01-HC-05102] NR 32 TC 42 Z9 43 U1 1 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 1047-2797 J9 ANN EPIDEMIOL JI Ann. Epidemiol. PD AUG PY 1997 VL 7 IS 6 BP 417 EP 424 DI 10.1016/S1047-2797(97)00043-4 PG 8 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA XR647 UT WOS:A1997XR64700007 PM 9279451 ER PT J AU Marriott, BM AF Marriott, BM TI Vitamin D supplementation: A word of caution SO ANNALS OF INTERNAL MEDICINE LA English DT Editorial Material ID CUTANEOUS PRODUCTION; SUNLIGHT C1 NIH,OFF DIS PREVENT,BETHESDA,MD 20892. NIH,OFF DIRECTOR,BETHESDA,MD 20892. RP Marriott, BM (reprint author), NIH,OFF DIETARY SUPPLEMENTS,BLDG 10,7550 WISCONSIN AVE,SUITE 610,BETHESDA,MD 20892, USA. NR 22 TC 19 Z9 19 U1 0 U2 0 PU AMER COLL PHYSICIANS PI PHILADELPHIA PA INDEPENDENCE MALL WEST 6TH AND RACE ST, PHILADELPHIA, PA 19106-1572 SN 0003-4819 J9 ANN INTERN MED JI Ann. Intern. Med. PD AUG 1 PY 1997 VL 127 IS 3 BP 231 EP 233 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA XN129 UT WOS:A1997XN12900009 PM 9245230 ER PT J AU Wienecke, R Guha, A Maize, RL Heideman, RL DeClue, JE Gutmann, DH AF Wienecke, R Guha, A Maize, RL Heideman, RL DeClue, JE Gutmann, DH TI Reduced TSC2 RNA and protein in sporadic astrocytomas and ependymomas SO ANNALS OF NEUROLOGY LA English DT Article ID GENE-PRODUCT; TUBEROUS SCLEROSIS; NEUROFIBROMATOSIS; GAP; IDENTIFICATION; HETEROGENEITY; ENCODES; TISSUES; CANCER; DOMAIN AB Individuals affected with tuberous sclerosis complex (TSC) develop several benign and malignant tumors at increased frequency, including astrocytomas, Tuberin, the protein product of the tuberous sclerosis complex-2 (TSC2) tumor suppressor gene, has been shown to directly inhibit cell growth and is expressed at high levels in normal central nervous system neurons and astrocytes. To determine whether TSC2 RNA and protein are reduced in astrocytomas from individuals without tuberous sclerosis, reverse transcriptase-polymerase chain reaction and immunoblotting analyses were performed on 49 adult astrocytomas, 10 pediatric astrocytomas, and 13 ependymomas. Eighteen of 40 (45%) high-grade (World Health Organization [WHO] grade III/IV) astrocytomas and 4 of 8 (50%) adult low-grade (WHO grade II) astrocytomas demonstrated reduced or absent TSC2 expression, including 1 giant cell astrocytoma, whereas none of the 10 pediatric low-grade astrocytomas analyzed showed a reduction in TSC2 expression, Reduced or absent tuberin was observed in 2 of 6 (33%) ependymomas analyzed. These data demonstrate, for the first time, that reduced or absent TSC2 expression may represent one of the critical genetic events associated with the development of sporadic adult, but not pediatric, astrocytomas. C1 WASHINGTON UNIV, SCH MED, DEPT NEUROL, ST LOUIS, MO 63110 USA. NCI, CELLULAR ONCOL LAB, BETHESDA, MD 20892 USA. ST JUDE CHILDRENS RES HOSP, DIV NEUROONCOL, MEMPHIS, TN 38105 USA. UNIV TORONTO, DIV NEUROSURG, TORONTO, ON, CANADA. NR 28 TC 32 Z9 33 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0364-5134 EI 1531-8249 J9 ANN NEUROL JI Ann. Neurol. PD AUG PY 1997 VL 42 IS 2 BP 230 EP 235 DI 10.1002/ana.410420215 PG 6 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA XQ524 UT WOS:A1997XQ52400014 PM 9266734 ER PT J AU Kudelka, AP Winn, R Edwards, CL Downey, G Greenberg, H Dakhil, SR Freedman, RS LoCoco, S Umbreit, J Delmore, JE Arbuck, S Loyer, E Gacrama, P Fueger, R Kavanagh, JJ AF Kudelka, AP Winn, R Edwards, CL Downey, G Greenberg, H Dakhil, SR Freedman, RS LoCoco, S Umbreit, J Delmore, JE Arbuck, S Loyer, E Gacrama, P Fueger, R Kavanagh, JJ TI An update of a phase II study of paclitaxel in advanced or recurrent squamous cell cancer of the cervix SO ANTI-CANCER DRUGS LA English DT Article DE cervix cancer; granulocyte colony stimulating factor; paclitaxel ID GYNECOLOGIC-ONCOLOGY-GROUP; COLONY-STIMULATING FACTOR; OVARIAN-CANCER; CARCINOMA; TAXOL; ADENOCARCINOMA; DOCETAXEL AB Thirty-two evaluable patients with squamous cell cancer of the cervix were treated with i.v. paclitaxel 250 mg/m(2) over 3 h every 21 days. They received standard premedications and granulocyte colony stimulating factor (G-CSF) support(5 mu g/kg/day). Median (range) age was 49 (29-81) years and performance status Zubrod was 1 (0-2). One patient had a complete response and seven patients had a partial response (25%, 95% CI 8-38%). The median survival was 7.3 months. Granulocytopenia was brief and non-cumulative. G-CSF was used for a median (range) of 8 (1-15) days per cycle. In conclusion: paclitaxel is active in patients with squamous cell cancer of the cervix and is well tolerated in this dose schedule with G-CSF support. C1 GRAND RAPIDS COMMUNITY CLIN ONCOL PROGRAM,GRAND RAPIDS,MI 49503. PROVIDENCE MEM HOSP,EL PASO,TX 79905. WICHITA COMMUNITY CLIN ONCOL PROGRAM,WICHITA,KS 67214. TEXAS CANC ASSOCIATES,FT WORTH,TX 76104. UNIV S ALABAMA,MOBILE,AL 36688. ASSOCIATES WOMENS HLTH,WICHITA,KS 67208. NCI,BETHESDA,MD 20892. RP Kudelka, AP (reprint author), UNIV TEXAS,MD ANDERSON CANCER CTR,SECT GYNECOL MED ONCOL,1515 HOLCOMBE BLVD,HOUSTON,TX 77030, USA. NR 32 TC 38 Z9 38 U1 0 U2 2 PU RAPID SCIENCE PUBLISHERS PI LONDON PA 2-6 BOUNDARY ROW, LONDON, ENGLAND SE1 8NH SN 0959-4973 J9 ANTI-CANCER DRUG JI Anti-Cancer Drugs PD AUG PY 1997 VL 8 IS 7 BP 657 EP 661 DI 10.1097/00001813-199708000-00002 PG 5 WC Oncology; Pharmacology & Pharmacy SC Oncology; Pharmacology & Pharmacy GA XX316 UT WOS:A1997XX31600002 PM 9311440 ER PT J AU Polis, MA Piscitelli, SC Vogel, S Witebsky, FG Conville, PS Petty, B Kovacs, JA Davey, RT Walker, RE Falloon, J Metcalf, JA Craft, C Lane, HC Masur, H AF Polis, MA Piscitelli, SC Vogel, S Witebsky, FG Conville, PS Petty, B Kovacs, JA Davey, RT Walker, RE Falloon, J Metcalf, JA Craft, C Lane, HC Masur, H TI Clarithromycin lowers plasma zidovudine levels in persons with human immunodeficiency virus infection SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY LA English DT Article ID AVIUM COMPLEX DISEASE; AIDS; PHARMACOKINETICS; THERAPY AB The use of antiretroviral agents and drugs for the treatment and prophylaxis of opportunistic infections has lengthened the survival of persons with AIDS, In the era of multidrug therapy, drug interactions are important considerations in designing effective and tolerable regimens, Clarithromycin has had a significant impact on the treatment of disseminated Mycobacterium avium complex infection, and zidovudine is the best-studied and one of the most widely used antiretroviral agents in this population, We conducted a study to determine the maximally tolerated dose of clarithromycin and the pharmacokinetics of clarithromycin and zidovudine individually and in combination, Mixing studies were conducted to simulate potential interaction in the gastric environment, The simultaneous administration of zidovudine and clarithromycin had little impact on the pharmacokinetics of clarithromycin or of its major metabolite, However, coadministration of zidovudine and clarithromycin at three doses (500 mg orally [p,o,] twice daily [b,i,d,], 1,000 mg p,o, b,i,d,, and 2,000 mg p,o, b,i,d,) reduced the maximum concentration of zidovudine by 41% (P < 0.005) and the area under the concentration-time curve from 0 to 4 h for zidovudine by 25% (P < 0.05) and increased the time to maximum concentration of zidovudine by 84% (P < 0,05), compared with zidovudine administered alone, Mixing studies did not detect the formation of insoluble complexes due to chelation, suggesting that the decrease in zidovudine concentrations results from some other mechanism, Simultaneous administration of zidovudine and clarithromycin appears to decrease the levels of zidovudine in serum, and it may be advisable that these drugs not be given at the same time, Drug interactions should be carefully evaluated in persons with advanced human immunodeficiency virus infection who are receiving multiple pharmacologic agents. C1 NIH,WARREN GRANT MAGNUSON CLIN CTR,DEPT CRIT CARE MED,BETHESDA,MD 20982. NIH,WARREN GRANT MAGNUSON CLIN CTR,DEPT PHARM,BETHESDA,MD 20982. NIH,WARREN GRANT MAGNUSON CLIN CTR,DEPT CLIN PATHOL,BETHESDA,MD 20982. ABBOTT LABS,ABBOTT PK,IL 60064. JOHNS HOPKINS UNIV,BALTIMORE,MD 21218. RP Polis, MA (reprint author), NIAID,IMMUNOREGULAT LAB,NIH,BLDG 10,ROOM 11C103,MAILSTOP 1880,BETHESDA,MD 20982, USA. OI Polis, Michael/0000-0002-9151-2268 NR 19 TC 21 Z9 21 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0066-4804 J9 ANTIMICROB AGENTS CH JI Antimicrob. Agents Chemother. PD AUG PY 1997 VL 41 IS 8 BP 1709 EP 1714 PG 6 WC Microbiology; Pharmacology & Pharmacy SC Microbiology; Pharmacology & Pharmacy GA XP605 UT WOS:A1997XP60500015 PM 9257746 ER PT J AU Longnecker, MP Harper, JM Kim, S AF Longnecker, MP Harper, JM Kim, S TI Eating frequency in the Nationwide Food Consumption Survey (USA), 1987-1988 SO APPETITE LA English DT Article ID MEAL-FREQUENCY; CANCER; HUMANS; COLON; RISK AB This study was done to provide basic descriptive data on the variation in meal frequency in the U.S. The data analysed were from the 1987-1988 Nationwide Food Consumption Survey (NFCS), a stratified random sample of American households. Participants were asked to provide one 24-h diet recall and two 1-day diet records. Individuals who were pregnant, lactating, or younger than 19 years old were excluded. If more than one eligible subject per household par participated, one subject was selected at random. Of the 4,078 eligible participants, data for 3,182 were complete for all three days and were included in the analyses. On average participants ate 3.47 times daily (SD 0.90). When eating occasions during which 70 or fewer kcal were excluded (tea, coffee, or diet beverages, primarily), the mean was 3.12 (SD 0.74), and over 90% of subjects ate between 1.50 and 4.49 times daily. The ratio of within-to between-person variance in number of eating times daily was 1.17 (less than or equal to 70 kcal excluded). The day-to-day variation in an individual's eating frequency was relatively large compared with the between-subject variation, suggesting that data for multiple days are needed to measure an individual's eating frequency with precision. (C) 1997 Academic Press Limited. C1 UNIV SO CALIF,DEPT PREVENT MED,LOS ANGELES,CA 90089. UNIV CALIF LOS ANGELES,DEPT EPIDEMIOL,LOS ANGELES,CA. RP Longnecker, MP (reprint author), NIEHS,EPIDEMIOL BRANCH,POB 12233,MD A3-05,RES TRIANGLE PK,NC 27709, USA. OI Longnecker, Matthew/0000-0001-6073-5322 NR 10 TC 20 Z9 20 U1 0 U2 2 PU ACADEMIC PRESS LTD PI LONDON PA 24-28 OVAL RD, LONDON, ENGLAND NW1 7DX SN 0195-6663 J9 APPETITE JI Appetite PD AUG PY 1997 VL 29 IS 1 BP 55 EP 59 DI 10.1006/appe.1997.0094 PG 5 WC Behavioral Sciences; Nutrition & Dietetics SC Behavioral Sciences; Nutrition & Dietetics GA XR795 UT WOS:A1997XR79500006 PM 9268425 ER PT J AU Choi, YS Dubel, SJ Pacioaiou, ML Omori, A Ito, T Copeland, TD Takahashi, M McEnery, MW AF Choi, YS Dubel, SJ Pacioaiou, ML Omori, A Ito, T Copeland, TD Takahashi, M McEnery, MW TI Parallel detection of Na,K-ATPase alpha subunit isoforms by pan-specific monoclonal mAb 9A7 SO ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS LA English DT Article ID TISSUE-SPECIFIC EXPRESSION; CENTRAL-NERVOUS-SYSTEM; BLASTOMA CELL-LINE; (NA+ + K+)-ATPASE; BETA-SUBUNIT; MESSENGER-RNAS; RAT-BRAIN; CATALYTIC SUBUNIT; CALCIUM-CHANNEL; IMMUNOCYTOCHEMICAL LOCALIZATION AB While emphasis has been placed upon those proteins which either mediate or respond to the rapid influx of calcium following depolarization, there has been little emphasis upon those proteins which aid in the reequilibration of the membrane potential, In an effort to identify presynaptic membrane proteins implicated in neurosecretion, monoclonal antibodies were screened against proteins which cosegregated with neuronal voltage-dependent calcium channels (VDCC) following immunoprecipitation. One monoclonal antibody (mAb 9A7) identified a 110-kDa protein, Micropeptide sequencing of (i) the mAb 9A7 immunoaffinity purified antigen and (ii) the 110-kDa protein present in the neuronal (N-type) VDCC preparation (McEnery et al., 1991, Proc, Natl, Acad, Sci, 88, 11095-11099) indicated identity with the alpha subunit(s) of the Na,K-ATPase. Further characterization by Western blotting, immunochemical localization, and immunoaffinity purification indicated that mAb 9A7 not only recognized the alpha3 isoform which is predominant in neuronal tissues but also identified the alpha1 and alpha2 isoforms, mAb 9A7 exhibited a wide cross-species reactivity and recognized human, rat, and mouse alpha subunit isoforms at an internal epitope, The pan-specificity of mAb 9A7 and the differential mobility of the alpha1 isoform relative to the alpha2 and alpha3 permitted parallel detection of multiple alpha isoforms. Western blot analysis of undifferentiated rat pheochromocytoma cell line (PC12) and human neuroblastoma (IMR32) cells indicated coexpression of the alpha1 and alpha3 isozymes, Upon differentiation of IMR32 cells by dibutrylyl-cAMP, a substantial increase in the alpha3 relative to the alpha1 isoform was observed, While the enrichment of total Na,K-ATPase may reflect the increased demand for ATP-dependent ion transport as IMR32 cells become more excitable, the specific increase in the alpha3 isoform suggests a unique role of this isoform during IMR32 cell differentiation. (C) 1997 Academic Press. C1 CASE WESTERN RESERVE UNIV, SCH MED, DEPT PHYSIOL & BIOPHYS, CLEVELAND, OH 44106 USA. NCI, FREDERICK CANC RES & DEV CTR, ABL BASIC RES PROGRAM, FREDERICK, MD 21702 USA. MITSUBISHI KASEI INST LIFE SCI, MACHIDA, TOKYO 194, JAPAN. NR 79 TC 15 Z9 16 U1 0 U2 0 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 AUG 1 PY 1997 VL 344 IS 1 BP 165 EP 175 DI 10.1006/abbi.1997.0183 PG 11 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA XM764 UT WOS:A1997XM76400020 PM 9244394 ER PT J AU Leshner, AI AF Leshner, AI TI Drug abuse and addiction treatment research - The next generation - Commentary SO ARCHIVES OF GENERAL PSYCHIATRY LA English DT Editorial Material ID COMORBIDITY; DISORDERS RP Leshner, AI (reprint author), NIDA, 5600 FISHERS LANE, ROOM 10-05, ROCKVILLE, MD 20857 USA. NR 21 TC 42 Z9 43 U1 21 U2 22 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA SN 0003-990X EI 1538-3636 J9 ARCH GEN PSYCHIAT JI Arch. Gen. Psychiatry PD AUG PY 1997 VL 54 IS 8 BP 691 EP 694 PG 4 WC Psychiatry SC Psychiatry GA XQ037 UT WOS:A1997XQ03700001 PM 9283502 ER PT J AU CritsChristoph, P Siqueland, L Blaine, J Frank, A Luborsky, L Onken, LS Muenz, L Thase, ME Weiss, RD Gastfriend, DR Woody, G Barber, JP Butler, SF Daley, D Bishop, S Najavits, LM Lis, J Mercer, D Griffin, ML Moras, K Beck, AT AF CritsChristoph, P Siqueland, L Blaine, J Frank, A Luborsky, L Onken, LS Muenz, L Thase, ME Weiss, RD Gastfriend, DR Woody, G Barber, JP Butler, SF Daley, D Bishop, S Najavits, LM Lis, J Mercer, D Griffin, ML Moras, K Beck, AT TI The National Institute on Drug Abuse Collaborative Cocaine Treatment Study - Rationale and methods SO ARCHIVES OF GENERAL PSYCHIATRY LA English DT Article ID ADDICTION SEVERITY INDEX; OPIATE ADDICTS; FOLLOW-UP; INTERPERSONAL PSYCHOTHERAPY; INTERACTIONAL THERAPIES; MATCHING ALCOHOLICS; CLINICAL-TRIALS; COPING SKILLS; PHARMACOTHERAPY; PREDICTOR AB The National Institute on Drug Abuse Collaborative Cocaine Treatment Study is a large, multisite psychotherapy clinical trial for outpatients who meet the DSM-IV criteria for cocaine dependence. For 480 randomized patients, the outcomes of 4 treatments are compared for an 18-month period. All treatments include group drug counseling. One treatment also adds cognitive therapy, one adds supportive-expressive psychodynamic therapy, and one adds individual drug counseling; one consists of group drug counseling alone. In addition, 2 specific interaction hypotheses, one involving psychiatric severity and the other involving degree of antisocial personality characteristics, are being tested. This article describes the main aims of the project, the background and rationale for the study design, the rationale for the choice of treatments and patient population, and a brief description of the research plan. C1 UNIV PENN,DEPT PSYCHIAT,PHILADELPHIA,PA 19104. PHILADELPHIA VET HOSP,PHILADELPHIA,PA. NIDA,ROCKVILLE,MD. BROOKSIDE HOSP,NASHUA,NH. UNIV PITTSBURGH,WESTERN PSYCHIAT INST & CLIN,PITTSBURGH,PA 15213. HARVARD UNIV,SCH MED,BOSTON,MA. MCLEAN HOSP,BOSTON,MA. MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. OI Butler, Stephen/0000-0002-6132-5883 FU NIDA NIH HHS [U18-DA07663, U18-DA07673, U18-DA07090, U18 DA007090] NR 42 TC 75 Z9 76 U1 0 U2 3 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0003-990X J9 ARCH GEN PSYCHIAT JI Arch. Gen. Psychiatry PD AUG PY 1997 VL 54 IS 8 BP 721 EP 726 PG 6 WC Psychiatry SC Psychiatry GA XQ037 UT WOS:A1997XQ03700006 PM 9283507 ER PT J AU Ketter, TA Andreason, PJ Lee, CH Gill, DS Parekh, PI Willis, MW Herscovitch, P Post, RM George, MS AF Ketter, TA Andreason, PJ Lee, CH Gill, DS Parekh, PI Willis, MW Herscovitch, P Post, RM George, MS TI Anterior paralimbic mediation of procaine-induced emotional and psychosensory experiences - Reply SO ARCHIVES OF GENERAL PSYCHIATRY LA English DT Letter ID LIDOCAINE; TINNITUS C1 NIH,BETHESDA,MD 20892. MED UNIV S CAROLINA,DEPT PSYCHIAT,CHARLESTON,SC 29425. MED UNIV S CAROLINA,DEPT RADIOL,CHARLESTON,SC 29425. MED UNIV S CAROLINA,DEPT NEUROL,CHARLESTON,SC 29425. RP Ketter, TA (reprint author), STANFORD UNIV,SCH MED,DEPT PSYCHIAT & BEHAV SCI,STANFORD,CA 94305, USA. NR 4 TC 0 Z9 0 U1 0 U2 1 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0003-990X J9 ARCH GEN PSYCHIAT JI Arch. Gen. Psychiatry PD AUG PY 1997 VL 54 IS 8 BP 764 EP 765 PG 2 WC Psychiatry SC Psychiatry GA XQ037 UT WOS:A1997XQ03700015 ER PT J AU Litvan, I Goetz, CG Jankovic, J Wenning, GK Booth, V Bartko, JJ McKee, A Jellinger, K Lai, EC Brandel, JP Verny, M Chaudhuri, KR Pearce, RKB Agid, Y AF Litvan, I Goetz, CG Jankovic, J Wenning, GK Booth, V Bartko, JJ McKee, A Jellinger, K Lai, EC Brandel, JP Verny, M Chaudhuri, KR Pearce, RKB Agid, Y TI What is the accuracy of the clinical diagnosis of multiple system atrophy? A clinicopathologic study SO ARCHIVES OF NEUROLOGY LA English DT Article; Proceedings Paper CT 4th Annual Meeting of the Movement-Disorder-Society CY JUN 16-20, 1996 CL VIENNA, AUSTRIA SP Movement Disorder Soc ID PROGRESSIVE SUPRANUCLEAR PALSY; IDIOPATHIC PARKINSONS-DISEASE; GLIAL CYTOPLASMIC INCLUSIONS; STRIATONIGRAL DEGENERATION; OLIVOPONTOCEREBELLAR ATROPHY; DIFFERENTIAL-DIAGNOSIS; GLUCOSE-METABOLISM; NATURAL-HISTORY; LEWY BODIES; FEATURES AB Background: The presentation of symptoms for multiple system atrophy (MSA) varies. Because there are no specific markers for its clinical diagnosis, the diagnosis rests on the results of the neuropathologic examination. Despite several clinicopathologic studies, the diagnostic accuracy for MSA is unknown. Objectives: To determine the accuracy for the clinical diagnosis of MSA and to identify, as early as possible, those features that would best predict MSA. Design: One hundred five autopsy-confirmed cases of MSA and related disorders (MSA [n = 16], non-MSA [n = 89]) were presented as clinical vignettes to 6 neurologists (raters) who were unaware of the study design. Raters identified the main clinical features and provided a diagnosis based on descriptions of the patients' first and last clinic visits. Methods: Interrater reliability was evaluated with the use of kappa statistics. Raters' diagnoses and those of the primary neurologists (who followed up the patients) were compared with the autopsy-confirmed diagnoses to estimate the sensitivity and positive predictive values at the patients' first and last visits. Logistic regression analysis was used to determine the best predictors to diagnose MSA. Results: For the first visit (median, 42 months after the onset of symptoms), the raters' sensitivity (median, 56%; range, 50%-69%) and positive predictive values (median, 76%; range, 61%-91%) for the clinical diagnosis of MSA were not optimal. For the last visit (74 months after the onset of symptoms), the raters' sensitivity (median, 69%; range, 56%-94%) and positive predictive values (median, 80%; range, 77%-92%) improved. Primary neurologists correctly identified 25% and 50% of the patients with MSA at the first and last visits, respectively. False-negative and -positive misdiagnoses frequently occurred in patients with Parkinson disease and progressive supranuclear palsy. Early severe autonomic;failure, absence of cognitive impairment, early cerebellar symptoms, and early gait disturbances were identified as the best predictive features to diagnose MSA. Conclusions: The low sensitivity for the clinical diagnosis of MSA, particularly among neurologists who followed up these patients in the tertiary centers, suggests that this disorder is underdiagnosed. The misdiagnosis of MSA is usually due to its confusion with Parkinson disease or progressive supranuclear palsy, thus compromising the research on all 3 disorders. C1 NIMH,DEPT EPIDEMIOL & RES STUDIES,NIH,BETHESDA,MD 20892. RUSH MED COLL,DEPT NEUROL,CHICAGO,IL 60612. BAYLOR COLL MED,DEPT NEUROL,HOUSTON,TX 77030. INST PSYCHIAT,NEUROL INST,LONDON,ENGLAND. INST PSYCHIAT,DEPT NEUROL,LONDON SE5 8AF,ENGLAND. PARKINSONS DIS SOC BRAIN TISSUE BANK,LONDON,ENGLAND. MASSACHUSETTS GEN HOSP,DEPT NEUROPATHOL,BOSTON,MA 02114. LAINZ HOSP,LUDWIG BOLTZMANN INST CLIN NEUROBIOL,A-1130 VIENNA,AUSTRIA. HOP LA PITIE SALPETRIERE,RAYMOND ESCOUROLLE NEUROPATHOL LAB,INSERM,U360,PARIS,FRANCE. HOP LA PITIE SALPETRIERE,FEDERAT NEUROL,PARIS,FRANCE. HOP LA PITIE SALPETRIERE,INSERM,U289,PARIS,FRANCE. RP Litvan, I (reprint author), NINCDS,NIH,NEUROEPIDEMIOL BRANCH,FED BLDG,ROOM 714,BETHESDA,MD 20814, USA. OI Litvan, Irene/0000-0002-3485-3445; Ray Chaudhuri, K/0000-0003-2815-0505 NR 55 TC 135 Z9 139 U1 0 U2 2 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0003-9942 J9 ARCH NEUROL-CHICAGO JI Arch. Neurol. PD AUG PY 1997 VL 54 IS 8 BP 937 EP 944 PG 8 WC Clinical Neurology SC Neurosciences & Neurology GA XQ778 UT WOS:A1997XQ77800003 PM 9267967 ER PT J AU Socolar, RRS AmayaJackson, L Eron, LD Howard, B Landsverk, J Evans, J AF Socolar, RRS AmayaJackson, L Eron, LD Howard, B Landsverk, J Evans, J TI Research on discipline - The state of the art, deficits, and implications SO ARCHIVES OF PEDIATRICS & ADOLESCENT MEDICINE LA English DT Editorial Material C1 DUKE UNIV,MED CTR,DURHAM,NC. UNIV MICHIGAN,ANN ARBOR,MI 48109. JOHNS HOPKINS UNIV,SCH MED,BALTIMORE,MD. CHILDRENS HOSP,CTR CHILD PROTECT,SAN DIEGO,CA. NICHHD,BETHESDA,MD 20892. RP Socolar, RRS (reprint author), UNIV N CAROLINA,SCH MED,CHAPEL HILL,NC 27599, USA. NR 9 TC 4 Z9 4 U1 0 U2 2 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 1072-4710 J9 ARCH PEDIAT ADOL MED JI Arch. Pediatr. Adolesc. Med. PD AUG PY 1997 VL 151 IS 8 BP 758 EP 760 PG 3 WC Pediatrics SC Pediatrics GA XQ271 UT WOS:A1997XQ27100001 PM 9265875 ER PT J AU Chen, F Wagner, PD AF Chen, F Wagner, PD TI Pertussis toxin modification of PC12 cells lowers cytoskeletal F-actin and enhances norepinephrine secretion: Involvement of protein kinase C and protein phosphatases SO ARCHIVES OF PHYSIOLOGY AND BIOCHEMISTRY LA English DT Article DE F-actin; NE secretion; PC12 cells; pertussis toxin; protein phosphatases ID ADRENAL CHROMAFFIN CELLS; CATECHOLAMINE RELEASE; FILAMENTOUS ACTIN; N-ETHYLMALEIMIDE; OKADAIC ACID; PC-12 CELLS; CYCLIC-AMP; EXOCYTOSIS; PC12-CELLS; CALCIUM AB We have investigated the relationship between norepinephrine secretion and cytoskeletal F-actin in rat phaeochromocytoma PC12 cells. Stimulation of PC12 cells with extracellular ATP or high K+ caused both the release of norepinephrine and a decrease in F-actin. The stimulation of secretion and the decrease in F-actin were dependent on extracellular Ca2+. The addition of Ca2+ to digitonin-permeabilized PC12 cells also stimulated norepinephrine release and decreased F-actin. Modification of PC12 cells with pertussis toxin caused a 35% decrease in F-actin, and if enhanced ATP-stimulated and K+ stimulated norepinephrine secretion from intact cells and Ca2+-dependent norepinephrine secretion from permeabilized cells. After down regulation of protein kinase C, pertussis toxin still enhanced secretion, but it had no effect on F-actin indicating that the effect of pertussis toxin on F-actin was dependent on protein kinase C activity. The addition of okadaic acid an inhibitor of serine/threonine protein phosphatases, to PC12 cells caused a decrease F-actin, but it had no effect on ATP-stimulated or K+-stimulated norepinephrine secretion. After down regulation of protein kinase C, much higher concentrations of okadaic acid were need to decrease F-actin. The similarity between the effects of pertussis toxin and low concentrations of okadaic acid suggest that the effect of pertussis toxin an cytoskeletal F-actin in PC12 cells may result from an inhibition of protein phosphatase 2A. C1 NCI,BIOCHEM LAB,NIH,BETHESDA,MD 20892. NR 31 TC 2 Z9 2 U1 0 U2 0 PU SWETS ZEITLINGER PUBLISHERS PI LISSE PA P O BOX 825, 2160 SZ LISSE, NETHERLANDS SN 1381-3455 J9 ARCH PHYSIOL BIOCHEM JI Arch. Physiol. Biochem. PD AUG PY 1997 VL 105 IS 4 BP 317 EP 328 DI 10.1076/apab.105.4.317.9472 PG 12 WC Biochemistry & Molecular Biology; Biophysics; Endocrinology & Metabolism; Physiology SC Biochemistry & Molecular Biology; Biophysics; Endocrinology & Metabolism; Physiology GA YH005 UT WOS:A1997YH00500001 ER PT J AU Loeser, RF Varnum, BC Carlson, CS Goldring, MB Liu, ET Sadiev, S Kute, TE Wallin, R AF Loeser, RF Varnum, BC Carlson, CS Goldring, MB Liu, ET Sadiev, S Kute, TE Wallin, R TI Human chondrocyte expression of growth-arrest-specific gene 6 and the tyrosine kinase receptor AXL - Potential role in autocrine signaling in cartilage SO ARTHRITIS AND RHEUMATISM LA English DT Article; Proceedings Paper CT 60th National Scientific Meeting of the American-College-of-Rheumatology CY OCT, 1996 CL ORLANDO, FL SP Amer Coll Rheumatol ID ARTICULAR CHONDROCYTES; EXTRACELLULAR-MATRIX; CULTURE; CELLS; PROTEINS AB Objective. To determine if human articular chondrocytes express the axl tyrosine kinase receptor and its ligand Gas-6, a protein product of growth-arrest-specific gene 6, and to determine if Gas-6 and axl function in the regulation of chondrocyte growth. and survival. Methods. The presence of Gas-6 and axl was examined in situ in human articular cartilage by immunohistochemistry and in vitro in cell culture studies using primary human chondrocytes and immortalized human chondrocytes. The ability of recombinant Gas-6 to mediate adhesion of chondrocytes and to stimulate chondrocyte axl phosphorylation was determined. Studies of the role of Gas-6 and axl in cell proliferation and survival were also performed. Results. Both Gas-6 and axl were detected in cartilage by immunohistochemical staining. Gas-6 and axl messenger RNA (mRNA) and protein were also detected in cultures of primary and immortalized human chondrocytes. Compared with cells cultured in medium containing 10% serum, Gas-6 mRNA levels were increased in immortalized chondrocytes cultured in serum-free medium, while axl expression decreased. Chondrocytes attached to Gas-6-coated plastic, and the attachment was blocked by a soluble Ig fusion protein containing the axl extracellular domain. Recombinant human Gas-6 and serum-free conditioned medium from primary and immortalized human chondrocyte cultures stimulated chondrocyte axl tyrosine phosphorylation. A mitogenic effect was noted both when immortalized chondrocytes were stimulated with recombinant Gas-6 or when they were made to overexpress axl by transfection, Addition of recombinant Gas-6 to serum-free medium resulted in increased survival of primary chondrocytes cultured at low density in agarose. Conclusion. These findings present evidence for an autocrine signaling pathway in cartilage involving Gas-6 and the axl tyrosine kinase adhesion receptor, Stimulation of axl by Gas-6 may play an important role in the control of chondrocyte growth and survival. C1 AMGEN CORP,THOUSAND OAKS,CA 91320. MASSACHUSETTS GEN HOSP,CHARLESTOWN,MA. HARVARD UNIV,SCH MED,CHARLESTOWN,MA. NCI,BETHESDA,MD 20892. RP Loeser, RF (reprint author), WAKE FOREST UNIV,BOWMAN GRAY SCH MED,DEPT INTERNAL MED,MED CTR BLVD,WINSTON SALEM,NC 27157, USA. RI Liu, Edison/C-4141-2008 FU NCRR NIH HHS [NCRR-08562]; NIAMS NIH HHS [AR-41656] NR 22 TC 51 Z9 51 U1 0 U2 2 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD AUG PY 1997 VL 40 IS 8 BP 1455 EP 1465 DI 10.1002/art.1780400814 PG 11 WC Rheumatology SC Rheumatology GA XP456 UT WOS:A1997XP45600013 PM 9259426 ER PT J AU Southan, GJ Gauld, D Lubeskie, A Zingarelli, B Cuzzocrea, S Salzman, AL Szabo, C Wolff, DJ AF Southan, GJ Gauld, D Lubeskie, A Zingarelli, B Cuzzocrea, S Salzman, AL Szabo, C Wolff, DJ TI Inhibition of nitric oxide synthase with pyrazole-1-carboxamidine and related compounds SO BIOCHEMICAL PHARMACOLOGY LA English DT Article DE inhibition; nitric oxide synthase; L-arginine; pyrazole-1-carboxamidine; blood pressure ID INDAZOLE AGENTS; POTENT; ISOTHIOUREAS; GLUTAMATE; CELLS AB Guanidines, amidines, S-alkylisothioureas, and other compounds containing the amidine function (-C(=H)NH2) have been described as inhibitors of the generation of nitric oxide (NO) by NO synthase (NOS). Here we report on the inhibition of the activity of NOS isoforms by compounds in which the amidine function is attached to a nitrogen of 1,2-diazo heterocycles to form N-carboxamidines and related compounds. 1H-Pyrazole 1-carboxamidine HCl (PCA) inhibited the activity of purified inducible NOS (iNOS), endothelial NOS (eNOS), and neuronal NOS (nNOS) isoforms to a similar extent (IC50 = 0.2 mu M). 3-Methyl-PCA and 4-methyl-PCA showed reduced potencies, but a preference for iNOS [IC50 = 5 and 2.4 mu M, respectively; cf. N-G-methyl-L-arginine (NMA) IC50 = 6 mu M]. Inhibition of purified iNOS by PCAs could be reversed completely by excess L-arginine, while their inhibition of NO production by stimulated RAW macrophages could be reversed by transfer to a drug-free medium. This suggests a competitive mode of inhibition. PCA caused potent concentration-dependent inhibition of the acetylcholine-induced, endothelium-dependent relaxations of precontracted rat thoracic aorta (IC50 = 30 mu M). 4-Methyl-PCA inhibited the relaxations only at greater than or equal to 300 mu M. In contrast, 4-methyl-PCA was more effective than both PCA and NMA in restoring the ex vivo contractility of aortic rings taken from lipopolysaccharide-treated rats. PCA and NMA, but not 4-methyl-PCA, caused marked increases in mean arterial pressure when administered i.v. to anesthetized rats. In conclusion, PCA and related compounds caused potent inhibition of NOS. Substitution of the pyrazole ring reduced potency, but improved selectivity towards iNOS as exemplified by 4-methyl-PCA. (C) 1997 Elsevier Science Inc. C1 UNIV MED & DENT NEW JERSEY,ROBERT WOOD JOHNSON MED SCH,DEPT PHARMACOL,PISCATAWAY,NJ 08854. CHILDRENS HOSP,MED CTR,DIV CRIT CARE,CINCINNATI,OH 45229. RP Southan, GJ (reprint author), NCI,FREDERICK CANC RES & DEV CTR,IRSP,SAIC FREDERICK,LAB COMPARAT CARCINOGENESIS,BLDG 538,FREDERICK,MD 21701, USA. FU NHLBI NIH HHS [HL54768] NR 26 TC 14 Z9 15 U1 0 U2 4 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0006-2952 J9 BIOCHEM PHARMACOL JI Biochem. Pharmacol. PD AUG 1 PY 1997 VL 54 IS 3 BP 409 EP 417 DI 10.1016/S0006-2952(97)00196-2 PG 9 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA XR845 UT WOS:A1997XR84500010 PM 9278100 ER PT J AU Katsetos, CD Hyde, TM Herman, MM AF Katsetos, CD Hyde, TM Herman, MM TI Neuropathology of the cerebellum in schizophrenia - An update: 1996 and future directions SO BIOLOGICAL PSYCHIATRY LA English DT Review DE cerebellum; cortex; development; roof nuclei; calbindin-D28k; class III beta-tubulin; cytoskeleton; synaptic proteins; schizophrenia ID CENTRAL-NERVOUS-SYSTEM; III BETA-TUBULIN; HUMAN BRAIN; POSTTRANSLATIONAL MODIFICATIONS; DIFFERENTIAL LOCALIZATION; SYNAPTOPHYSIN EXPRESSION; ADULT SCHIZOPHRENIA; MENTAL-RETARDATION; COGNITIVE FUNCTION; DENTATE NUCLEUS C1 NIMH,NEUROSCI CTR ST ELIZABETHS,INTRAMURAL RES PROGRAM,CLIN BRAIN DISORDERS BRANCH,WASHINGTON,DC 20032. RP Katsetos, CD (reprint author), TEMPLE UNIV,SCH MED,DEPT MICROBIOL & IMMUNOL,KRESGE HALL,ROOM 503,3400 N BROAD ST,PHILADELPHIA,PA 19140, USA. NR 156 TC 64 Z9 64 U1 1 U2 1 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 AUG 1 PY 1997 VL 42 IS 3 BP 213 EP 224 DI 10.1016/S0006-3223(96)00313-7 PG 12 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA XJ890 UT WOS:A1997XJ89000008 PM 9232214 ER PT J AU Gorelick, DA Rothman, RB AF Gorelick, DA Rothman, RB TI Stimulant sensitization in humans SO BIOLOGICAL PSYCHIATRY LA English DT Letter RP Gorelick, DA (reprint author), NIDA,DIV INTRAMURAL RES,NIH,BALTIMORE,MD 21224, USA. NR 3 TC 12 Z9 12 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD AUG 1 PY 1997 VL 42 IS 3 BP 230 EP 230 DI 10.1016/S0006-3223(97)80005-4 PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA XJ890 UT WOS:A1997XJ89000011 PM 9232217 ER PT J AU Johnson, MG Kiyokawa, H Tani, S Koyama, J MorrisNatschke, SL Mauger, A BowersDaines, MM Lange, BC Lee, KH AF Johnson, MG Kiyokawa, H Tani, S Koyama, J MorrisNatschke, SL Mauger, A BowersDaines, MM Lange, BC Lee, KH TI Antitumor agents .167. Synthesis and structure-activity correlations of the cytotoxic anthraquinone 1,4-bis-(2,3-epoxypropylamino)-9,10-anthracenedione, and of related compounds SO BIOORGANIC & MEDICINAL CHEMISTRY LA English DT Article ID ANTI-TUMOR AGENTS; MITOXANTRONE; AMINOANTHRAQUINONES; BISANTRENE; SYSTEM AB 1,4-Bis-(2,3-epoxypropylamino)-9,10-anthracenedione (3) was synthesized in this laboratory and was found to be a patent antitumor agent. Derivatives of this compound containing anthraquinone, naphthoquinone, and quinone skeletons were also prepared and evaluated for in vitro cytotoxic activity in several cell lines. These molecules were designed as bifunctional antitumor agents with the potential to act as (1) intercalating agents due to their planar backbones, and (2) alkylating agents due to the presence of alkylating moieties in their side chains. Compounds with an anthraquinone skeleton and propylamino side chains containing epoxides or halohydrins as the alkylating species showed greater activity than similar compounds with naphthoquinone or quinone skeletons. Compounds without these alkylating functionalities (e.g., with alkene or amino groups) were generally inactive. Hydroxy substitution on the planar skeleton in conjunction with alkylating side chains gave compounds with the most potent cytotoxic activity. The position of the hydroxy groups and side chains could be varied without substantially affecting activity. Activity was retained when an epoxypropyloxy side chain was substituted for the epoxypropylamino side chain in the parent compound. (C) 1997 Elsevier Science Ltd. C1 UNIV N CAROLINA,SCH PHARM CB7360,DIV MED CHEM & NAT PROD,NAT PROD LAB,CHAPEL HILL,NC 27599. NCI,ROCKVILLE,MD 20892. ROHM & HAAS CO,RES LABS,SPRING HOUSE,PA 19477. FU NCI NIH HHS [CA-17625] NR 36 TC 30 Z9 30 U1 1 U2 4 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0968-0896 J9 BIOORGAN MED CHEM JI Bioorg. Med. Chem. PD AUG PY 1997 VL 5 IS 8 BP 1469 EP 1479 DI 10.1016/S0968-0896(97)00097-7 PG 11 WC Biochemistry & Molecular Biology; Chemistry, Medicinal; Chemistry, Organic SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Chemistry GA XX516 UT WOS:A1997XX51600002 PM 9313853 ER PT J AU Beutler, JA Kashman, Y Pannell, LK Cardellina, JH Alexander, MRA Balaschak, MS Prather, TR Shoemaker, RH Boyd, MR AF Beutler, JA Kashman, Y Pannell, LK Cardellina, JH Alexander, MRA Balaschak, MS Prather, TR Shoemaker, RH Boyd, MR TI Isolation and characterization of novel cytotoxic saponins from Archidendron ellipticum SO BIOORGANIC & MEDICINAL CHEMISTRY LA English DT Article ID GLEDITSIA-JAPONICA; TRITERPENOIDAL SAPONINS; MONOTERPENE GLYCOSIDES; STRUCTURE ELUCIDATION; VIBURNUM-ORIENTALE; ALBIZZIAE CORTEX; CONSTITUENTS; PROTON; ACID AB A series of new ester saponins, elliptosides A-J, has been isolated from the tropical plant Archidendron ellipticum (Leguminosae). These saponins were particularly cytotoxic to certain renal and melanoma cancer cell lines in the NCI's 60-cell line human tumor screen. The structures of elliptosides A, E, and F were elucidated by spectroscopic and chemical means. Elliptoside A showed in vivo antitumor activity against the LOX melanoma cell line. Published by Elsevier Science Ltd. C1 NCI, LAB DRUG DISCOVERY RES & DEV, DEV THERAPEUT PROGRAM, DIV CANC BIOL DIAG & CTR, FREDERICK, MD 21702 USA. TEL AVIV UNIV, DEPT CHEM, IL-69978 TEL AVIV, ISRAEL. NIDDKD, ANALYT CHEM LAB, NIH, BETHESDA, MD 20892 USA. SCI APPLICAT INT CORP, FREDERICK, MD 21702 USA. RI Beutler, John/B-1141-2009 OI Beutler, John/0000-0002-4646-1924 NR 32 TC 22 Z9 22 U1 2 U2 6 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0968-0896 J9 BIOORGAN MED CHEM JI Bioorg. Med. Chem. PD AUG PY 1997 VL 5 IS 8 BP 1509 EP 1517 DI 10.1016/S0968-0896(97)00098-9 PG 9 WC Biochemistry & Molecular Biology; Chemistry, Medicinal; Chemistry, Organic SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Chemistry GA XX516 UT WOS:A1997XX51600006 PM 9313857 ER PT J AU Kiesewetter, DO Carson, RE Jagoda, EM Endres, CJ Der, MG Herscovitch, P Eckelman, WC AF Kiesewetter, DO Carson, RE Jagoda, EM Endres, CJ Der, MG Herscovitch, P Eckelman, WC TI In vivo muscarinic binding selectivity of (R,S)- and (R,R)-[F-18]-fluoromethyl QNB SO BIOORGANIC & MEDICINAL CHEMISTRY LA English DT Article ID POSITRON EMISSION TOMOGRAPHY; IODINE-125-LABELED 1-AZABICYCLO<2.2.2>OCT-3-YL ALPHA-HYDROXY-ALPHA-(1-IODO-1-PRO; M2 SUBTYPE; RAT-BRAIN; M3-MUSCARINIC-RECEPTOR SUBTYPES; AUTORADIOGRAPHIC EVIDENCE; BABOON BRAIN; RECEPTORS; LIGAND; BIODISTRIBUTION AB We have developed a multistep radiochemical synthesis of two diastereomers of quinuclidinyl-4-[F-18]-fluoromethylbenzilate ([F-18]-FMeQNB), a high-affinity ligand for muscarinic acetylcholine receptors. Previously, we have shown that the nonradioactive (R,R)-diastereomer displays an eightfold selectivity for M1 over M2 while the nonradioactive (R,S)-diastereomer displays a sevenfold selectivity for M2 over M1 in vitro. This paper reports the results of in vivo comparison studies. In the rat, uptake of (R,S)-[F-18]-FMeQNB was nearly uniform in all brain regions following the concentration of M2 subtype. The uptake was reduced by 36-54% in all brain regions on coinjection with 50 nmol of unlabeled ligand. An injection of (R,S)-[F-18]-FMeQNB followed at 60 min by injection of unlabeled ligand and subsequent sacrifice at 120 min displaced 30-50% of radioactivity in the pens, medulla, and cerebellum, which contain a high proportion of M2 subtype. The most dramatic displacement and inhibition of uptake on coinjection of (R,S)-[F-18]-FMeQNB was observed in the heart. In rhesus monkey, the compound showed prolonged uptake and retention in the brain. In the blood, the parent compound degraded rapidly to a single radiolabeled polar metabolite believed to be fluoride. Within 30 min the parent compound represented less than 5% of the plasma activity. Displacement with (R)-QNB was generally slow, but was more rapid from those tissues which contain a higher proportion of M2 subtype. The results are consistent with the hypothesis that (R,S)-[F-18]-FMeQNB is M2 selective in vivo. On the other hand, (R,R)-[F-18]-FMeQNB showed higher uptake in those brain regions containing a higher concentration of M1 subtype. Uptake in the heart at 60 min was much lower than that observed with the (R,S)-diastereomer. Inhibition of uptake on coinjection with unlabeled (R,S)-FMeQNB is only significant in the heart, thalamus, and pens. Inhibition of uptake on coinjection with unlabeled (R,R)-FMeQNB is quite uniform in all brain regions. Displacement with (R)-QNB shows a more varying amount displaced. These results are consistent with (R,R)-[F-18]-FMeQNB being M1 selective in vivo. Published by Elsevier Science Ltd. RP Kiesewetter, DO (reprint author), NIH,POSITRON EMISS TOMOG DEPT,WARREN G MAGNUSON CLIN CTR,BLDG 10 ROOM 1C495,10 CTR DR MSC 1180,BETHESDA,MD 20892, USA. RI Carson, Richard/H-3250-2011 OI Carson, Richard/0000-0002-9338-7966 FU NIMH NIH HHS [N01MH20003] NR 34 TC 12 Z9 12 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0968-0896 J9 BIOORGAN MED CHEM JI Bioorg. Med. Chem. PD AUG PY 1997 VL 5 IS 8 BP 1555 EP 1567 DI 10.1016/S0968-0896(97)00100-4 PG 13 WC Biochemistry & Molecular Biology; Chemistry, Medicinal; Chemistry, Organic SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Chemistry GA XX516 UT WOS:A1997XX51600010 PM 9313861 ER PT J AU Huster, D Jin, AJ Arnold, K Gawrisch, K AF Huster, D Jin, AJ Arnold, K Gawrisch, K TI Water permeability of polyunsaturated lipid membranes measured by O-17 NMR SO BIOPHYSICAL JOURNAL LA English DT Article ID NUCLEAR-MAGNETIC-RESONANCE; LARGE UNILAMELLAR VESICLES; CHAIN ORIENTATIONAL ORDER; RAPID EXTRUSION PROCEDURE; ACYL-CHAIN; PHOSPHOLIPID-BILAYERS; DIVALENT-CATIONS; ETHANOL; CHOLESTEROL; DIFFUSION AB Diffusion-controlled water permeation across bilayers of polyunsaturated phospholipids was measured by O-17 nuclear magnetic resonance. In 100-nm extruded liposomes containing 50 mM MnCl2, water exchange between internal and external solutions was monitored via changes in the linewidth of the O-17 water resonance of external water. Liposome size and shape were characterized by light scattering methods and determination of liposome trapped volume. At 25 degrees C, the following water permeability coefficients were determined: 18:0-18:1n-9 PC, 155 +/- 24 mu m/s; 18:0-18:3n-3 PC, 330 +/- 88 mu m/s; and 18:0-22:6n-3 PC, 412 +/- 91 mu m/s. The addition of 1 M ethanol reduced permeability coefficients to 66 +/- 15 mu m/s for 18:0-18:1n-9 PC and to 239 +/- 67 mu m/s for 18:0-22:6n-3 PC. Furthermore, the addition of 50 mol% 18:1n-9-18:1n-9 PE reduced the water permeability from 122 +/- 21 mu m/s for pure 18:1n-9-18:1n-9 PC to 74 +/- 15 mu m/s for the mixture. The significant increase in water permeation for membranes with polyunsaturated hydrocarbon chains correlates with looser packing of polyunsaturated lipids at the lipid-water interface and the suggested deeper penetration of water into these bilayers. Ethanol may block water diffusion pathways by occupying points of water entry into bilayers at the interface. The addition of dioleoylphosphatidylethanolamine increases lipid packing density and, consequently, reduces permeation rates. C1 NIAAA,LAB MEMBRANE BIOCHEM & BIOPHYS,NIH,ROCKVILLE,MD 20852. UNIV LEIPZIG,INST MED PHYS & BIOPHYS,D-04103 LEIPZIG,GERMANY. NIH,DCRT,PHYS SCI LAB,BETHESDA,MD 20892. OI Jin, Albert/0000-0003-3826-1081 NR 64 TC 127 Z9 128 U1 2 U2 34 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD AUG PY 1997 VL 73 IS 2 BP 855 EP 864 PG 10 WC Biophysics SC Biophysics GA XM537 UT WOS:A1997XM53700026 PM 9251802 ER PT J AU Radko, SP Chrambach, A AF Radko, SP Chrambach, A TI Electrophoresis of proteins in semidilute polyethylene glycol solutions: Mechanism of retardation SO BIOPOLYMERS LA English DT Article DE electrophoresis; retardation; native proteins; semidilute polymer solution; scaling theory ID POLYACRYLAMIDE-GEL ELECTROPHORESIS; ENTANGLED POLYMER-SOLUTIONS; SCATTERING; SEPARATIONS; PARTICLES; MOBILITY; MODEL AB The retardation of proteins in the M-r range of 15-500 kDa in capillary electrophoresis conducted in semidilute solutions of the polymer polyethylene glycol (M-r range 0.2-8.0 x 10(6)), M as measured The purpose was to test the predictions of the scaling theory with regard to the relation of retardation to (a) the M-r of the polymer (b) the concentration of the polymer, and (c) the radius of the protein particles. These predictions derive from a mechanism that relates retardation to the screening length of the polymer solution viewed as the average distance between the entanglement points of polymer chains. For the molecular weight range from 60 to 500 kDa of (near) spherical proteins, the retardation was found to be related to polymer concentration c as mu/mu(0) = exp(-Ac-0.69) where mu/mu(0) is the retardation expressed as the ratio between the mobility in polymer solution and that in free solution. The value of the exponent of 0.69 is in close agreement with the value of 0.75 predicted by the scaling theory. Parameter A was found (a) to scale as the 0.04th power of M-r (polymer), approximating the predicted value of 0; and (b) to be proportional to particle radius as predicted. All measured values of retardation were independent of electric field strength in the range of 37-370 V/cm. Thus, experimental findings are consistent with the mechanism relating electrophoretic retardation to the screening length of the polymer network in the specified molecular weight range of proteins. Under the same conditions, log(mu/mu(0)) of proteins with M-r's less than 60 kDa (a) scales as the -0.06th power of M-r (polymer), and (b) is proportional to polymer concentration, suggesting a retardation mechanism that is not related to the screening length. (C) 1997 John Wiley & Sons, Inc. C1 NICHHD,MACROMOL ANAL SECT,CELLULAR & MOL BIOPHYS LAB,NIH,BETHESDA,MD 20892. NR 28 TC 24 Z9 24 U1 0 U2 8 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 AUG PY 1997 VL 42 IS 2 BP 183 EP 189 DI 10.1002/(SICI)1097-0282(199708)42:2<183::AID-BIP7>3.3.CO;2-H PG 7 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA XL517 UT WOS:A1997XL51700007 PM 9234997 ER PT J AU Anderlini, P Korbling, M Dale, D Gratwohl, A Schmitz, N Stroncek, D Howe, C Leitman, S Horowitz, M Gluckman, E Rowley, S Przepiorka, D Champlin, R AF Anderlini, P Korbling, M Dale, D Gratwohl, A Schmitz, N Stroncek, D Howe, C Leitman, S Horowitz, M Gluckman, E Rowley, S Przepiorka, D Champlin, R TI Allogeneic blood stem cell transplantation: Considerations for donors SO BLOOD LA English DT Editorial Material ID COLONY-STIMULATING FACTOR; LARGE-VOLUME LEUKAPHERESIS; PROGENITOR CELLS; GRANULOCYTE-MACROPHAGE; HEALTHY-VOLUNTEERS; DRUG-THERAPY; G-CSF; LEUKEMIA; FILGRASTIM; MOBILIZATION AB Allogeneic transplantation of cytokine-mobilized peripheral blood stem cells (PBSCs) is now being increasingly performed, but safety considerations for hematologically normal PBSC donors have not been fully addressed. Progenitors are generally mobilized for collection from normal donors using recombinant human granulocyte colony-stimulating factor (rhG-CSF). Although the short-term safety profile of rhG-CSF seems acceptable, experience remains limited and its optimal dose and schedule have not been defined. Minimal data exist regarding long-term safety of rhG-CSF, primarily derived from experience in patients with chronic neutropenia or cancer. An ''ad hoc'' workshop was recently convened among a group of investigators actively involved in the field of allogeneic stem cell transplantation to discuss the safety issues pertaining to normal PBSC donors. There was agreement on the following points: (1) On the basis of available data, it appears that rhG-CSF treatment and PBSC collection have an acceptable short-term safety profile in normal donors. However, the need for continued safety monitoring was recognized. (2) rhG-CSF doses up to 10 mu g/kg/d show a consistent dose-response relationship with the mobilization (and collection) of CD34(+) progenitor cells, and this dose is acceptable for routine clinical use. Whether higher doses are superior (or cost effective) remains to be determined, and they may produce more severe side effects. The potential risks of marked leukocytosis (arbitrarily defined as a leukocyte count of more than 70 x 10(9)/L) have been a concern, and rhG-CSF dose reduction is performed by many centers to maintain leukocyte counts below this level. (3) Transient post donation cytopenias, involving granulocytes, lymphocytes, and platelets, may occur and are at least partly related to the leukapheresis procedure. These are generally asymptomatic and self-limited; follow-up blood counts are not necessarily required. Reinfusion of autologous platelet-rich plasma should be considered for donors with expected postdonation thrombocytopenia (platelet count < 80 to 100 x 10(9)/L). (4) Donors should meet the eligibility criteria which apply to donors of apheresis platelets, with the exception that pediatric donors may also be considered. Any deviation from these criteria should have supporting documentation. There is insufficient information at this time to clearly establish definite contraindications for PBSC collection in a hematologically normal donor. Potential contraindications include the presence of inflammatory, autoimmune, or rheumatologic disorders, as well as atherosclerotic or cerebrovascular disease. (5) The creation of an International PBSC Donor Registry is desirable to facilitate monitoring the long-term effects of the procedure. Individual institutions or donor centers are encouraged to establish their own PBSC donor follow-up system, preferably with a standardized approach to data collection. (C) 1997 by The American Society of Hematology. C1 UNIV TEXAS,MD ANDERSON CANC CTR,SECT BLOOD & MARROW TRANSPLANTAT,HOUSTON,TX 77030. UNIV WASHINGTON,SEATTLE,WA 98195. CHRISTIAN ALBRECHTS UNIV KIEL,EUROPEAN GRP BLOOD & MARROW TRANSPLANTAT,KIEL,GERMANY. KANTONSSPITAL,CH-4031 BASEL,SWITZERLAND. NATL MARROW DONOR PROGRAM,MINNEAPOLIS,MN. NIH,CTR CLIN,DEPT TRANSFUS MED,BETHESDA,MD 20892. MED COLL WISCONSIN,INT BONE MARROW TRANSPLANT REGISTRY,MILWAUKEE,WI 53226. FRED HUTCHINSON CANC RES CTR,SEATTLE,WA 98104. HOP ST LOUIS,PARIS,FRANCE. NR 63 TC 165 Z9 166 U1 1 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 AUG 1 PY 1997 VL 90 IS 3 BP 903 EP 908 PG 6 WC Hematology SC Hematology GA XN126 UT WOS:A1997XN12600001 PM 9242518 ER PT J AU McNeely, TB Shugars, DC Rosendahl, M Tucker, C Eisenberg, SP Wahl, SM AF McNeely, TB Shugars, DC Rosendahl, M Tucker, C Eisenberg, SP Wahl, SM TI Inhibition of human immunodeficiency virus type 1 infectivity by secretory leukocyte protease inhibitor occurs prior to viral reverse transcription SO BLOOD LA English DT Article ID HUMAN SALIVARY SECRETIONS; III LAV INFECTION; CATHEPSIN-G; PROTEINASE-INHIBITOR; HIV-1 INFECTIVITY; V3 LOOP; ELASTASE; CELLS; INACTIVATION; ACTIVATION AB Infection of monocytes with human immunodeficiency virus type 1(Ba-L) (HIV-1(Ba-L)) is significantly inhibited by treatment with the serine protease inhibitor, secretory leukocyte protease inhibitor (SLPI). SLPI does not appear to act on virus directly, but rather the inhibitory activity is most likely due to interaction with the host cell. The current study was initiated to investigate how SLPI interacts with monocytes to inhibit infection, SLPI was found to bind to monocytes with high affinity to a single class of receptor sites (similar to 7,000 receptors per monocyte, K-D = 3.6 nmol/L), The putative SLPI receptor was identified as a surface protein with a molecular weight of 55 +/- 5 kD. A well-characterized function of SLPI is inhibition of neutrophil elastase and cathepsin G. However, two SLPI mutants (or muteins) that contain single amino acid substitutions and exhibit greatly reduced protease inhibitory activity still bound to monocytes and retained anti-HIV-1 activity. SLPI consists of two domains, of which the C-terminal domain contains the protease inhibiting region. However, when tested independently, neither domain had potent anti-HIV-1 activity. SLPI binding neither prevented virus binding to monocytes nor attenuated the infectivity of any virus progeny that escaped inhibition by SLPI. A polymerase chain reaction (PCR)-based assay for newly generated viral DNA demonstrated that SLPI blocks at or before viral DNA synthesis. Therefore, it most likely inhibits a step of viral infection that occurs after virus binding but before reverse transcription. Taken together, the unique antiviral activity of SLPI, which may be independent of its previously characterized antiprotease activity, appears to reside in disruption of the viral infection process soon after virus binding. This is a US government work. There are no restrictions on its use. C1 NIDR,IMMUNOL LAB,NIH,BETHESDA,MD 20892. DUKE UNIV,MED CTR,DEPT SURG,DURHAM,NC 27710. AMGEN SYNERGEN INC,BOULDER,CO. FU NIDCR NIH HHS [R01DE12162]; NIMH NIH HHS [T32MH15177] NR 43 TC 202 Z9 209 U1 0 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD AUG 1 PY 1997 VL 90 IS 3 BP 1141 EP 1149 PG 9 WC Hematology SC Hematology GA XN126 UT WOS:A1997XN12600029 PM 9242546 ER PT J AU Yan, L Wang, SB Rafferty, SP Wesley, RA Danner, RL AF Yan, L Wang, SB Rafferty, SP Wesley, RA Danner, RL TI Endogenously produced nitric oxide increases tumor necrosis factor-alpha production in transfected human U937 cells SO BLOOD LA English DT Article ID HUMAN MONONUCLEAR PHAGOCYTES; L-ARGININE; PERITONEAL-MACROPHAGES; MESSENGER-RNA; POLYMORPHONUCLEAR LEUKOCYTES; HUMAN-NEUTROPHILS; RELAXING FACTOR; TNF-ALPHA; SYNTHASE; EXPRESSION AB Various functions of human phagocytes are modulated by nitric oxide (NO). We transfected the human U937 monoblastoid cell line with an expression vector containing human endothelial NO synthase (eNOS) or murine inducible NOS (iNOS) cDNA to study the regulatory role of NO without the nonspecific effects associated with exogenous NO sources. Western blot confirmed expression of eNOS or iNOS in respectively transfected cells, but not in naive or empty-vector transfected cells. Transfectants expressing iNOS, a calcium-independent enzyme, but not eNOS, a calcium-dependent enzyme, spontaneously produced NO (P<.001). The NO release from iNOS-transfected cells, as measured by nitrite and nitrate accumulation and by cyclic guanosine monophosphate (cGMP) increases in rat reporter cells, was inhibitable (P<.01 for both) with N-omega-methyl-L-arginine (L-NMA), a NOS inhibitor. The eNOS transfectants were shown to contain functional enzyme by the conversion of L-arginine to L-citrulline in fractionated cells (P=.0001) and by exposing intact cells to calcium ionophore using the cGMP reporter cell assay (P=.0001). After differentiation with phorbol-12-myristate-13-acetate (PMA), iNOS transfectants produced more tumor necrosis factor-alpha (TNF-alpha) (124.9 +/- 25.4 pg/5 x 10(5) cells per 24 hours) than did empty-vector transfected cells (21.9 +/- 1.9 pg/5 x 10(5) cells per 24 hours; P=.02). This effect was inhibited by 500 mu mol/L L-NMA (54.4 +/- 3.1 pg/5 x 10(5) cells per 24 hours; P=.05). However, in the presence of high concentrations of lipopolysaccharide (1 mu g/ mL), which further increased NO production in iNOS transfected cells (P=.044), TNF-alpha production was similar comparing PMA-differentiated iNOS and empty-vector transfectants (12.2 +/- 0.8 and 13.1 +/- 1.7 ng/5 x 10(5) cells per 24 hours, respectively: P=.5). The results show that under certain conditions endogenously produced NO can upregulate TNF-alpha production in human phagocytes. This is a US government work. There are no restrictions on its use. C1 NIAID,DEPT CRIT CARE MED,WARREN GRANT MAGNUSON CLIN CTR,NIH,BETHESDA,MD 20892. NIAID,HOST DEF LAB,NIH,BETHESDA,MD 20892. NR 46 TC 32 Z9 33 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 AUG 1 PY 1997 VL 90 IS 3 BP 1160 EP 1167 PG 8 WC Hematology SC Hematology GA XN126 UT WOS:A1997XN12600031 PM 9242548 ER PT J AU Woodard, JC Donovan, GA Fisher, LW AF Woodard, JC Donovan, GA Fisher, LW TI Pathogenesis of vitamin (A and D)-induced premature growth-plate closure in calves SO BONE LA English DT Article DE vitamin A; premature growth-plate closure; bone and cartilage matrix proteins; immunohistochemistry; premature chondrocyte mineralization; chondrocyte differentiation ID MESSENGER-RNA EXPRESSION; RETINOIC ACID; II COLLAGEN; IN-SITU; CHONDROCYTES; CARTILAGE; BONE; DIFFERENTIATION; AGGRECAN; MATRIX AB The pathogenesis of vitamin A-induced premature growth-plate closure was investigated in calves. A progressive increase in the severity of growth-plate lesions with time and a progressive increase in the extent of growth-plate involvement was observed. There was initial loss of metachromasia from the growth plate in a region that formed a narrow horizontal hand of cartilage composed of the epiphyseal growth zone and a strip of reserve-zone cartilage. Immunostaining revealed there was loss of aggrecan, decorin, and biglycan from this region; however, it was doubtful that the regional loss of proteoglycan was a major contributing factor in the pathogenesis of premature growth-plate closure. This is because this region was the vestige of cartilage that remained when growth-plate closure was almost complete. The major alteration was premature mineralization of columnar cartilage and subsequent endochondral ossification. This caused the depth of the columnar zone to be reduced. Columnar-zone cartilage cells appeared immature where the matrix became mineralized and lacked the morphology of hypertrophic chondrocytes. The depth of the reserve-cartilage zone also was reduced as matrix mineralization of the columnar zone progressed, and further reduction in columnar cartilage depth occurred. Eventually, there was matrix mineralization within the adjacent reserve cartilage. The distribution of reaction product after immunostaining with antibodies to the following proteins was described during normal endochondral ossification: aggrecan, decorin, biglycan, versican, type I collagen propeptide, type I collagen, type II collagen, osteopontin, osteocalcin, osteonectin, bone sialoprotein, and alkaline phosphatase. Biglycan, type I collagen propeptide, type I collagen, osteopontin, osteocalcin, osteonectin, bone sialoprotein, and alkaline phosphatase were localized within the cytoplasm or surrounding matrix of hypertrophic chondrocytes. In vitamin-treated calves, these same proteins were found in regions undergoing premature matrix mineralization even though the chondrocytes did not have a hypertrophic morphology. Therefore, vitamin treatment did not cause just a selective expression, but it caused expression of a large number of matrix proteins normally associated with the hypertrophic chondrocyte phenotype. Finally, completely mineralized columnar and reserve cartilage were removed by a modeling/remodeling process similar to that seen in the metaphysis. (C) 1997 by Elsevier Science Inc. All rights reserved. C1 UNIV FLORIDA,COLL VET MED,DEPT LARGE ANIM CLIN SCI,GAINESVILLE,FL 32610. NIDR,BONE RES BRANCH,NIH,BETHESDA,MD 20892. RP Woodard, JC (reprint author), UNIV FLORIDA,COLL VET MED,DEPT PATHOBIOL,POB 100145,GAINESVILLE,FL 32610, USA. NR 43 TC 24 Z9 24 U1 0 U2 5 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 8756-3282 J9 BONE JI Bone PD AUG PY 1997 VL 21 IS 2 BP 171 EP 182 DI 10.1016/S8756-3282(97)00099-9 PG 12 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA XR606 UT WOS:A1997XR60600007 PM 9267693 ER PT J AU Tian, M Hagg, T Denisova, N Knusel, B Engvall, E Jucker, M AF Tian, M Hagg, T Denisova, N Knusel, B Engvall, E Jucker, M TI Laminin-alpha 2 chain-like antigens in CNS dendritic spines SO BRAIN RESEARCH LA English DT Article DE merosin; synapse; synaptogenesis; basement membrane; hippocampus; brain; regeneration; lesion; rat; rabbit; pig ID CONGENITAL MUSCULAR-DYSTROPHY; LESION-INDUCED SYNAPTOGENESIS; FIBROBLAST GROWTH-FACTOR; LAMININ-BINDING PROTEIN; CENTRAL-NERVOUS-SYSTEM; DENTATE GYRUS; ADULT-RAT; BASEMENT-MEMBRANE; REACTIVE SYNAPTOGENESIS; HIPPOCAMPAL-NEURONS AB The laminin-alpha 2 chain is a component of brain capillary basement membranes and appears also to be present in neurons of rat, rabbit, pig and non-human primate brain as evidenced by immunohistochemistry. In the present study, we have further characterized this very distinct neuronal laminin-alpha 2 chain-like immunoreactivity in the hippocampus of various species. Immunoelectron microscopy with poly- and monoclonal antibodies to the laminin-alpha 2 chain G-domain localized laminin-alpha 2 chain immunoreactivity in adult rat and rabbit hippocampus to dendritic processes, primarily to dendritic spines. In the developing rat hippocampus, spine-associated laminin-alpha 2 chain-like immunoreactivity first appeared at a time corresponding to that of active synaptogenesis. After an entorhinal cortex lesion in adult rats, the time course of denervation-induced loss and reactive reappearance of spines in the molecular layer of the dentate gyrus was correlated closely to the loss and reappearance of laminin-alpha 2 chain immunoreactivity. Immunoblot analysis of normal adult rat, rabbit and pig brain revealed a protein similar in size to the reported 80-kDa laminin-alpha 2 chain fragment of human placenta as well as 140/160-kDa proteins. These results suggest the presence of proteins with antigenic homology to the laminin-alpha 2 chain and/or laminin-alpha 2 isoforms in dendrites and dendritic spines in selected areas of the brain, predominately in the hippocampus and other limbic structures. Given the adhesion and neurite promoting functions of laminins, it is possible that neuronal laminin-alpha 2 chain-like proteins play a role in synaptic function and plasticity in the CNS. (C) 1997 Elsevier Science B.V. C1 UNIV BASEL,INST PATHOL,NEUROPATHOL LAB,CH-4003 BASEL,SWITZERLAND. NIA,GERONTOL RES CTR,CELLULAR & MOL BIOL LAB,NIH,BALTIMORE,MD 21224. DALHOUSIE UNIV,DEPT ANAT & NEUROBIOL,HALIFAX,NS,CANADA. UNIV SO CALIF,ETHEL PERCY ANDRUS GERONTOL CTR,LOS ANGELES,CA 90089. BURNHAM INST,LA JOLLA,CA 92037. NR 57 TC 46 Z9 46 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0006-8993 J9 BRAIN RES JI Brain Res. PD AUG 1 PY 1997 VL 764 IS 1-2 BP 28 EP 38 DI 10.1016/S0006-8993(97)00420-4 PG 11 WC Neurosciences SC Neurosciences & Neurology GA XT768 UT WOS:A1997XT76800004 PM 9295190 ER PT J AU Venters, HD Bonilla, LE Jensen, T Garner, HP Bordayo, EZ Najarian, MM Ala, TA Mason, RP Frey, WH AF Venters, HD Bonilla, LE Jensen, T Garner, HP Bordayo, EZ Najarian, MM Ala, TA Mason, RP Frey, WH TI Heme from Alzheimer's brain inhibits muscarinic receptor binding via thiyl radical generation SO BRAIN RESEARCH LA English DT Article DE Alzheimer's disease; heme; muscarinic receptor; free radical; thiyl radical; antioxidant; estrogen; vitamin E ID ANTAGONIST BINDING; DISEASE; OXYGENASE-1; NEURONS; PROTEINS; DEMENTIA AB An endogenous inhibitor (< 3500 Da) of antagonist binding to the muscarinic acetylcholine receptor (mAChR) has been reported to be elevated 3-fold in Alzheimer's disease (AD) brain, This endogenous inhibitor was found to require the presence of reducing agents such as reduced glutathione (GSH) for optimal activity. In the presence of GSH, the inhibitor was shown to generate thiyl radicals which irreversibly inhibited the mAChR. We now report that the inhibitor contains free heme, a well-established source of oxidative stress capable of generating free radicals and causing neurotoxicity. While FeSO4, microperoxidase and hemin all inhibited antagonist binding to the mAChR, only hemin shared the inhibitor's requirement for GSH. Both the free radical scavengers Trolox and Mn2+, and the metal chelator, EDTA, blocked the activity of the endogenous AD inhibitor and of hemin. Heme oxygenase-1 (HO-1) markedly reduced the activity of both the endogenous AD inhibitor and hemin, indicating that the endogenous inhibitor contains heme. Mass spectrometric analysis confirmed the presence of free heme and heme fragments in fractions of the endogenous AD inhibitor. The antioxidants estrogen, vitamin E and vitamin C all protected the mAChR from irreversible inhibition by the endogenous inhibitor or hemin. These antioxidants may function to protect the integrity of the mAChR in vivo and may have therapeutic potential in AD where free heme could be a source of oxidative stress. (C) 1997 Elsevier Science B.V. C1 ST PAUL RAMSEY MED CTR,ALZHEIMERS TREATMENT & RES CTR,DEPT NEUROL,ST PAUL,MN 55101. UNIV MINNESOTA,DEPT CHEM,MINNEAPOLIS,MN 55455. NIEHS,NIH,RES TRIANGLE PK,NC 27709. OI Frey II, William/0000-0002-6373-0794 NR 26 TC 23 Z9 25 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0006-8993 J9 BRAIN RES JI Brain Res. PD AUG 1 PY 1997 VL 764 IS 1-2 BP 93 EP 100 DI 10.1016/S0006-8993(97)00425-3 PG 8 WC Neurosciences SC Neurosciences & Neurology GA XT768 UT WOS:A1997XT76800011 PM 9295197 ER PT J AU Cook, JA Krishna, MC Pacelli, R DeGraff, W Liebmann, J Mitchell, JB Russo, A Wink, DA AF Cook, JA Krishna, MC Pacelli, R DeGraff, W Liebmann, J Mitchell, JB Russo, A Wink, DA TI Nitric oxide enhancement of melphalan-induced cytotoxicity SO BRITISH JOURNAL OF CANCER LA English DT Article ID LUNG EPITHELIAL-CELLS; BUTHIONINE SULFOXIMINE; GLUTATHIONE DEPLETION; CYTO-TOXICITY; MEDIATED CYTOTOXICITY; OXIDATIVE STRESS; TARGET-CELLS; IN-VIVO; INHIBITION; CANCER AB The effects of the diatomic radical, nitric oxide (NO), on melphalan-induced cytotoxicity in Chinese hamster V79 and human MCF-7 breast cancer cells were studied using clonogenic assays. NO delivered by the NO-releasing agent (C2H5)(2)N[N(O)NO]-Na+ (DEA/NO; 1 mM) resulted in enhancement of melphalan-mediated toxicity in Chinese hamster V79 lung fibroblasts and human breast cancer (MCF-7) cells by 3.6- and 4.3-fold, respectively, at the IC,, level. Nitrite/nitrate and diethylamine, the ultimate end products of DEA/NO decomposition, had little effect on melphalan cytotoxicity, which suggests that NO was responsible for the sensitization. Whereas maximal sensitization of melphalan cytotoxicity by DEA/NO was observed for simultaneous exposure of DEA/NO and melphalan, cells pretreated with DEA/NO were sensitized to melphalan for several hours after NO exposure. Reversing the order of treatment also resulted in a time-dependent enhancement in melphalan cytotoxicity. To explore possible mechanisms of NO enhancement of melphalan cytotoxicity, the effects of DEA/NO on three factors that might influence melphalan toxicity were examined, namely NO-mediated cell cycle perturbations, intracellular glutathione (GSH) levels and melphalan uptake. NO pretreatment resulted in a delayed entry into S phase and a G(2)/M block for both V79 and MCF-7 cells; however, cell cycle redistribution for V79 cells occurred after the cells returned to a level of cell survival, consistent with treatment with melphalan alone. After 15 min exposure of V79 cells to DEA/NO (1 mM), GSH levels were reduced to 40% of control values, however, GSH levels recovered fully after 1 h and were elevated 2 h after DEA/NO incubation. In contrast, DEA/NO (1 mM) incubation did not reduce GSH levels significantly in MCF-7 cells (approximately 10%). Melphalan uptake was increased by 33% after DEA/NO exposure in V79 cells. From these results enhancement of melphalan cytotoxicity mediated by NO appears to be complex and may involve several pathways, including possibly alteration of the repair of melphalan-induced lesions. Our observations may give insights for improving tumour kill with melphalan using either exogenous or possibly endogenous sources of NO. C1 NCI,RADIAT BIOL BRANCH,BETHESDA,MD 20892. UNIV NEW MEXICO,CTR CANC,ALBUQUERQUE,NM 87131. NR 36 TC 40 Z9 42 U1 0 U2 2 PU CHURCHILL LIVINGSTONE PI EDINBURGH PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE, LEITH WALK, EDINBURGH EH1 3AF, MIDLOTHIAN, SCOTLAND SN 0007-0920 J9 BRIT J CANCER JI Br. J. Cancer PD AUG PY 1997 VL 76 IS 3 BP 325 EP 334 DI 10.1038/bjc.1997.386 PG 10 WC Oncology SC Oncology GA XN572 UT WOS:A1997XN57200007 PM 9252199 ER PT J AU Peters, JA Biesecker, BB AF Peters, JA Biesecker, BB TI Genetic counseling and hereditary cancer SO CANCER LA English DT Article ID FAMILIAL-OVARIAN-CANCER; BREAST-CANCER; COST-EFFECTIVENESS; COLORECTAL-CANCER; RISK; SUSCEPTIBILITY C1 JOHNS HOPKINS UNIV,SCH MED,DEPT MED GENET,BALTIMORE,MD. RP Peters, JA (reprint author), NIH,NATL HUMAN GENOME RES INST,MED GENET BRANCH,BLDG 10,ROOM 10C101,10 CTR DR,MSC 1852,BETHESDA,MD 20892, USA. NR 62 TC 17 Z9 17 U1 0 U2 2 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0008-543X J9 CANCER JI Cancer PD AUG 1 PY 1997 VL 80 IS 3 SU S BP 576 EP 586 DI 10.1002/(SICI)1097-0142(19970801)80:3+<576::AID-CNCR7>3.0.CO;2-7 PG 11 WC Oncology SC Oncology GA XW281 UT WOS:A1997XW28100007 ER PT J AU Sinha, R Potter, JD AF Sinha, R Potter, JD TI Diet, nutrition, and genetic susceptibility SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Editorial Material C1 FRED HUTCHINSON CANC RES CTR,SEATTLE,WA 98104. RP Sinha, R (reprint author), NCI,NUTR EPIDEMIOL BRANCH,DIV CANC EPIDEMIOL & GENET,EXECUT PLAZA N,ROOM 430,6130 EXECUT BLVD,ROCKVILLE,MD 20892, USA. RI Sinha, Rashmi/G-7446-2015; OI Sinha, Rashmi/0000-0002-2466-7462; Potter, John/0000-0001-5439-1500 NR 0 TC 12 Z9 12 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 AUG PY 1997 VL 6 IS 8 BP 647 EP 649 PG 3 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA XR010 UT WOS:A1997XR01000015 PM 9264280 ER PT J AU Biesecker, BB AF Biesecker, BB TI Genetic testing for cancer predisposition SO CANCER NURSING LA English DT Article ID OVARIAN-CANCER; BREAST; FAMILIES; DISCRIMINATION; SUSCEPTIBILITY RP Biesecker, BB (reprint author), NIH,GENET COUNSELING RES & TRAINING PROGRAM,NATL CTR HUMAN GENOME RES,BLDG 10,ROOM 10C101,BETHESDA,MD 20892, USA. NR 35 TC 5 Z9 5 U1 0 U2 2 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0162-220X J9 CANCER NURS JI Cancer Nurs. PD AUG PY 1997 VL 20 IS 4 BP 285 EP 296 DI 10.1097/00002820-199708000-00009 PG 12 WC Oncology; Nursing SC Oncology; Nursing GA XP663 UT WOS:A1997XP66300009 PM 9265816 ER PT J AU McAllister, KA HaugenStrano, A Hagevik, S Brownlee, HA Collins, NK Futreal, PA Bennett, LM Wiseman, RW AF McAllister, KA HaugenStrano, A Hagevik, S Brownlee, HA Collins, NK Futreal, PA Bennett, LM Wiseman, RW TI Characterization of the rat and mouse homologues of the BRCA2 breast cancer susceptibility gene SO CANCER RESEARCH LA English DT Article ID LOCALIZATION AB Inherited BRCA2 mutations confer profound susceptibility to human breast and ovarian cancer, The rat and mouse Brca2 homologues share 58% and 59% identity (72% similarity), respectively, with the human BRCA2 protein, The Brca2 proteins also share a potential nuclear localization signal (human codons 3263-3269) and a highly conserved large carboxyl region (77% identity, 86% similarity between human and rodents) that may represent important functional domains, At least sis of eight previously described BRC repeats have been highly conserved in rats and mice, Expression studies demonstrate an 11-12 Kb transcript with rodent tissue-specific patterns of expression consistent with human BRCA2. These results will facilitate studies of Brca2 function during normal and neoplastic development. C1 DUKE UNIV,MED CTR,DEPT SURG,DURHAM,NC 27710. DUKE UNIV,MED CTR,DEPT OBSTET & GYNECOL,DURHAM,NC 27710. DUKE UNIV,MED CTR,DEPT GENET,DURHAM,NC 27710. RP McAllister, KA (reprint author), NIEHS,MOL CARCINOGENESIS LAB,NIH,MAIL DROP C4-06,RES TRIANGLE PK,NC 27709, USA. NR 26 TC 33 Z9 35 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 AUG 1 PY 1997 VL 57 IS 15 BP 3121 EP 3125 PG 5 WC Oncology SC Oncology GA XM812 UT WOS:A1997XM81200011 PM 9242436 ER PT J AU Dlugosz, AA Hansen, L Cheng, C Alexander, N Denning, MF Threadgill, DW Magnuson, T Coffey, RJ Yuspa, SH AF Dlugosz, AA Hansen, L Cheng, C Alexander, N Denning, MF Threadgill, DW Magnuson, T Coffey, RJ Yuspa, SH TI Targeted disruption of the epidermal growth factor receptor impairs growth of squamous papillomas expressing the v-ras(Ha) oncogene but does not block in vitro keratinocyte responses to oncogenic ras SO CANCER RESEARCH LA English DT Article ID MAMMARY EPITHELIAL-CELLS; MOUSE SKIN CARCINOGENESIS; V-HA-RAS; FACTOR-ALPHA; EGF RECEPTOR; DIFFERENTIATION MARKERS; TUMOR PROMOTERS; CARCINOMA CELLS; MICE LACKING; SENCAR MICE AB We have assessed the role of epidermal growth factor receptor (EGFR) signaling in biological responses to the v-ras(Ha) oncogene using primary keratinocytes from Egfr -/- mice and wild-type littermates. On the basis of several criteria, Egfr -/- keratinocytes were unresponsive to either acute or chronic exposure to several EGFR ligands but were stimulated to proliferate in response to several other mitogens, Although conditioned medium from primary keratinocytes transduced with v-ras(Ha) retrovirus (v-ras(Ha) keratinocytes) was a potent mitogen for wild-type but not Egfr -/- keratinocytes, v-ras(Ha) transduction of primary keratinocytes of either genotype resulted in a strong mitogenic response, arguing against an obligatory role for EGPR activation in v-ras(Ha)-mediated stimulation of keratinocyte proliferation, Infection with high-titer v-ras(Ha) retrovirus altered the keratin expression pattern in keratinocytes of both genotypes, suppressing differentiation-specific keratins K1 and K10 while activating aberrant expression of K8 and K18, In wild-type but not Egfr -/- cultures, K1 and K10 were also suppressed following infection at lower retroviral titers, presumably as a result of paracrine EGFR activation on uninfected cells present in these cultures, Squamous papillomas produced by grafting Egfr -/- v-ras(Ha) keratinocytes onto nude mice were only 21% of the size of wild-type v-ras(Ha) tumors, and a striking redistribution of S-phase cells was detected by immunostaining for bromodeoxyuridine. In Egfr -/- v-ras(Ha) papillomas, the fraction of total labeled nuclei detected in suprabasal layers was increased from 19 to 39%, In contrast, the basal layer labeling index of Egfr -/- papillomas was reduced to 34%, compared to 43% in wild-type tumors, Our results indicate that, although autocrine EGFR signaling is not required for keratinocyte responses to oncogenic ras in culture or benign tumor formation in nude mouse grafts, disruption of this pathway impairs growth of v-ras(Ha) papillomas by a mechanism that may involve alterations in keratinocyte cell cycle progression and/or migration in vivo. C1 NCI,CELLULAR CARCINOGENESIS & TUMOR PROMOT LAB,NIH,BETHESDA,MD 20892. CASE WESTERN RESERVE UNIV,DEPT GENET,CLEVELAND,OH 44106. VANDERBILT UNIV,DEPT CELL BIOL,NASHVILLE,TN 37232. VANDERBILT UNIV,DEPT MED,NASHVILLE,TN 37232. RI Threadgill, David/N-4425-2013 OI Threadgill, David/0000-0003-3538-1635 NR 57 TC 67 Z9 67 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 AUG 1 PY 1997 VL 57 IS 15 BP 3180 EP 3188 PG 9 WC Oncology SC Oncology GA XM812 UT WOS:A1997XM81200022 PM 9242447 ER PT J AU Strickler, H AF Strickler, H TI SV40 early region and large T antigen in human brain tumors, peripheral blood cells, and sperm fluids from healthy individuals. SO CANCER RESEARCH LA English DT Letter ID DNA-SEQUENCES RP Strickler, H (reprint author), NCI,VIRAL EPIDEMIOL BRANCH,NIH,BETHESDA,MD 20892, USA. NR 9 TC 3 Z9 3 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 AUG 1 PY 1997 VL 57 IS 15 BP 3319 EP 3320 PG 2 WC Oncology SC Oncology GA XM812 UT WOS:A1997XM81200042 PM 9242467 ER PT J AU Rose, ML Germolec, DR Schoonhoven, R Thurman, RG AF Rose, ML Germolec, DR Schoonhoven, R Thurman, RG TI Kupffer cells are causally responsible for the mitogenic effect of peroxisome proliferators SO CARCINOGENESIS LA English DT Article ID RAT-LIVER; WY-14,643; HEPATOTOXICITY; SUSCEPTIBILITY; ACID; FOCI AB WY-14 643 [4-chloro-6-(2,3-xylidino)pyrimidinylthio-acetic acid] is a web-known non-genotoxic carcinogen and peroxisome proliferator that causes liver cancer in rodents by unknown mechanisms, Its ability to sustain elevated rates of hepatocyte DNA synthesis is most likely pivotal in the ultimate development of tumors, The source of this mitogenic stimulus following treatment of rats,vith WY-14 643 has been hypothesized to be Kupffer cells, the resident hepatic macrophages, since they are activated by peroxisome proliferators in vivo. Therefore, these studies were designed to determine if Kupffer cells are causally responsible for WY-14 643-induced increases in hepatocyte DNA synthesis in vivo, WY-14 643 (100 mg/kg) increased DNA synthesis 8-fold 24 h after treatment; however, inactivation of Kupffer cells with methyl palmitate, a non-hydrolyzable fatty acid ester and known Kupffer cell inhibitor, completely prevented the mitogenic effect of WY-14 643, On the other hand, the ability of WY-14 643 to induce peroxisomes was not affected by methyl palmitate. These data demonstrate that induction of peroxisomes is not dependent on factors from Kupffer cells and support the idea that stimulation of DNA synthesis and induction of peroxisomes occur via distinct mechanisms, Additionally, WY-14 643 increased liver mRNA transcripts of the hepatocyte mitogen tumor necrosis factor alpha (TNF alpha) more than twofold, This increase was also prevented by inactivating Kupffer cells with methyl palmitate, Therefore, it is concluded that Kupffer cells are causally responsible for WY-14 643-induced increases in hepatocyte DNA synthesis most likely by increasing production of TNF alpha, a hepatic mitogen. C1 UNIV N CAROLINA, DEPT PHARMACOL, CURRICULUM TOXICOL, HEPATOBIOL & TOXICOL LAB, CHAPEL HILL, NC 27514 USA. UNIV N CAROLINA, DEPT ENVIRONM SCI & ENGN, CHAPEL HILL, NC USA. NATL INST ENVIRONM HLTH SCI, RES TRIANGLE PK, NC USA. FU NIEHS NIH HHS [ES-04325, 5-T32ES-07126-13] NR 21 TC 78 Z9 79 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD, ENGLAND OX2 6DP SN 0143-3334 J9 CARCINOGENESIS JI Carcinogenesis PD AUG PY 1997 VL 18 IS 8 BP 1453 EP 1456 DI 10.1093/carcin/18.8.1453 PG 4 WC Oncology SC Oncology GA XQ878 UT WOS:A1997XQ87800003 PM 9276615 ER PT J AU Smith, TJ Liao, AM Liu, Y Jones, AB Anderson, LM Yang, CS AF Smith, TJ Liao, AM Liu, Y Jones, AB Anderson, LM Yang, CS TI Enzymes involved in the bioactivation of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone in patas monkey lung and liver microsomes SO CARCINOGENESIS LA English DT Article ID TOBACCO-SPECIFIC NITROSAMINES; DIETARY PHENETHYL ISOTHIOCYANATE; XENOBIOTIC-METABOLIZING ENZYMES; CYTOCHROMES P450; N-NITROSAMINES; MOUSE LUNG; INHIBITION; RATS; CANCER; SMOKE AB 4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) is a potent tobacco-specific carcinogen in animals, Our previous studies indicated that there are differences between rodents and humans for the enzymes involved in the activation of NNK. To determine if the patas monkey is a better animal model for the activation of NNK in humans, we investigated the metabolism of NNK in patas monkey Lung and liver microsomes and characterized the enzymes involved in the activation, In lung microsomes, the formation of 4-oxo-1-(3-pyridyl)-1-butanone (keto aldehyde), 4-(methylnitrosamino)-1-(3-pyridyl-N-oxide)-1-butanone (NNK-N-oxide), 4-hydroxy-1-(3-pyridyl)-1-butanone (keto alcohol), and 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL) was observed, displaying apparent K-m values of 10.3, 5.4, 4.9, and 902 mu M, respectively, NNK metabolism in liver microsomes resulted in the formation of keto aldehyde, keto alcohol, and NNAL, displaying apparent K-m values of 8.1, 8.2, and 474 mu M, respectively, The low K-m values for NNK oxidation in the patas monkey lung and Liver microsomes are different from those in human lung and liver microsomes showing K-m values of 400-653 mu M, although loss of low K-m forms from human tissue as a result of disease, surgery or anesthesia cannot be ruled out, Carbon monoxide (90%) significantly inhibited NNK metabolism in the patas monkey lung and liver microsomes by 38-66% and 82-91%, respectively, Nordihydroguaiaretic acid (a lipoxygenase inhibitor) and aspirin (a cyclooxygenase inhibitor) decreased the rate of formation of keto aldehyde and keto alcohol by 10-20% in the monkey lung microsomes, alpha-Napthoflavone and coumarin markedly decreased the oxidation of NNK in monkey lung and liver microsomes, suggesting the involvement of p450s 1A and 2A6. An antibody against human P450 2A6 decreased the oxidation of NNK hy 12-16% and 22-24% in the patas monkey lung and liver microsomes, respectively, These results are comparable to that obtained with human lung and liver microsomes. Coumarin hydroxylation was observed in the patas monkey lung and liver microsomes at a rate of 16 and 4000 pmol/min/mg protein, respectively, which was 5-fold higher than human lung and liver microsomes, respectively, Immunoblot analysis demonstrated that the P450 2A level in the individual patas monkey liver microsomal sample was 6-fold greater than in an individual human liver microsomal sample. Phenethyl isothiocyanate, an inhibitor of NNK activation in rodents and humans, decreased NNK oxidation in the monkey lung and liver microsomes displaying inhibitor concentration resulting in 50% inhibition of the activity (IC50) values of 0.28-0.8 mu M and 4.2-6.8 mu M, respectively, The results demonstrate the similarities and differences between species in the metabolic activation of NNK, The patas monkey microsomes appear to more closely resemble human microsomes than mouse or rat enzymes and may better reflect the activation of NNK in humans. C1 NCI,FREDERICK CANC RES & DEV CTR,COMPARAT CARCINOGENESIS LAB,FREDERICK,MD 21702. RP Smith, TJ (reprint author), RUTGERS STATE UNIV,COLL PHARM,CANC RES LAB,PISCATAWAY,NJ 08855, USA. FU NCI NIH HHS [CA46535]; NIEHS NIH HHS [ES05022] NR 36 TC 23 Z9 23 U1 1 U2 2 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD, ENGLAND OX2 6DP SN 0143-3334 J9 CARCINOGENESIS JI Carcinogenesis PD AUG PY 1997 VL 18 IS 8 BP 1577 EP 1584 DI 10.1093/carcin/18.8.1577 PG 8 WC Oncology SC Oncology GA XQ878 UT WOS:A1997XQ87800021 PM 9276633 ER PT J AU Peehl, DM Wong, ST Sellers, RG Jin, S Rhim, JS AF Peehl, DM Wong, ST Sellers, RG Jin, S Rhim, JS TI Loss of response to epidermal growth factor and retinoic acid accompanies the transformation of human prostatic epithelial cells to tumorigenicity with v-Ki-ras SO CARCINOGENESIS LA English DT Article ID MALIGNANT PROSTATE; FACTOR RECEPTOR; FACTOR-ALPHA; NEOPLASTIC TRANSFORMATION; CLONAL GROWTH; CANCER CELLS; BENIGN; EXPRESSION; TISSUE; KERATINOCYTES AB Growth factor-independent proliferation and loss of response to differentiation factors are believed to be critical elements in carcinogenesis, We have developed an Qt vitro model of human prostatic carcinogenesis by the introduction of SV40 DNA into normal prostatic epithelial cells to create a transformed, immortal cell line, pRNS-1-1. This non-tumorigenic cell line responded similarly to normal prostatic epithelial cells to most growth- and differentiation-regulatory factors, with the notable exception of loss of response to the inhibitory factor 1,25-dihydroxyvitamin D-3, In this study, we describe the introduction of the ras oncogene into pRNS-1-1 cells to create a tumorigenic cell line, pRNS-1-1/ras. In addition to an attenuated response to 1,25-dihydroxyvitamin D-3, these cells also became unresponsive to retinoic acid and gained the ability to undergo clonal proliferation in the absence of epidermal growth factor (EGF), EGF-independent growth could not be linked to the production of autocrine transforming growth factor-alpha, but instead was likely due to sustained signaling by the ras oncogene, bypassing ligand-activation of the EGF receptor, Ligand-independent proliferation, coupled with the loss of response to the growth-inhibitory and differentiation agent retinoic acid, may be important elements in the conversion of human prostatic epithelial cells to tumorigenicity. C1 NCI,LAB BIOCHEM PHYSIOL,FREDERICK,MD 21702. RP Peehl, DM (reprint author), STANFORD UNIV,SCH MED,DEPT UROL,STANFORD,CA 94305, USA. NR 55 TC 13 Z9 13 U1 0 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD, ENGLAND OX2 6DP SN 0143-3334 J9 CARCINOGENESIS JI Carcinogenesis PD AUG PY 1997 VL 18 IS 8 BP 1643 EP 1650 DI 10.1093/carcin/18.8.1643 PG 8 WC Oncology SC Oncology GA XQ878 UT WOS:A1997XQ87800030 PM 9276642 ER PT J AU Jones, JM Attardi, L Godley, LA Laucirica, R Medina, D Jacks, T Varmus, HE Donehower, LA AF Jones, JM Attardi, L Godley, LA Laucirica, R Medina, D Jacks, T Varmus, HE Donehower, LA TI Absence of p53 in a mouse mammary tumor model promotes tumor cell proliferation without affecting apoptosis SO CELL GROWTH & DIFFERENTIATION LA English DT Article ID WILD-TYPE P53; BREAST-CANCER; HUMAN FIBROBLASTS; EPITHELIAL-CELLS; SUPPRESSOR GENE; TRANSGENIC MICE; GROWTH ARREST; IN-VIVO; PROTEIN; INDUCTION AB Loss or mutation of p53 may have multiple biological and genetic effects that result in accelerated tumor progression, Loss of p53 in some tumors has been correlated with a marked decrease in tumor cell apoptosis, p53 loss may also accelerate tumor growth through an increase in cell proliferation rates, To examine the effects of p53 loss on tumor progression in a controlled experimental context, we previously crossed p53-deficient mice to mammary tumorsusceptible Wnt-1 transgenic (TG) mice. The resulting female Wnt-1 TG offspring of this cross all developed mammary tumors, regardless of p53 status (p53+/+, p53+/-, or p53-/-). However, female p53-/- Wnt-1 TG mice developed tumors much sooner than their p53+/+ counterparts, In this report, we demonstrate that the average growth rates of tumors missing (p53-/-) or losing p53 (p53+/- with loss of heterozygosity) are accelerated compared to tumors with both wild-type p53 alleles (p53+/+), This accelerated growth rate appears to be due primarily to increases in rates of tumor cell proliferation. Tumor cell apoptotic levels were modest and were not measurably different in the presence or absence of wild-type p53, These results differ substantially from other mouse tumor models in which p53 loss was closely correlated with accelerated growth rates through attenuated apoptosis. Thus, the mechanisms by which p53 loss influences tumor progression may differ, depending on the tissue type and/or the oncogenic pathways involved. C1 BAYLOR COLL MED,DIV MOL VIROL,HOUSTON,TX 77030. BAYLOR COLL MED,CELL & MOL BIOL PROGRAM,HOUSTON,TX 77030. BAYLOR COLL MED,DEPT PATHOL,HOUSTON,TX 77030. BAYLOR COLL MED,METHODIST HOSP,HOUSTON,TX 77030. BAYLOR COLL MED,DEPT CELL BIOL,HOUSTON,TX 77030. MIT,CTR CANC RES,CAMBRIDGE,MA 02139. MIT,HOWARD HUGHES MED INST,CAMBRIDGE,MA 02139. NCI,NIH,BETHESDA,MD 20892. NR 59 TC 51 Z9 51 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 AUG PY 1997 VL 8 IS 8 BP 829 EP 838 PG 10 WC Cell Biology SC Cell Biology GA XQ823 UT WOS:A1997XQ82300001 PM 9269892 ER PT J AU Bal, W JezowskaBojczuk, M Kasprzak, KS AF Bal, W JezowskaBojczuk, M Kasprzak, KS TI Binding of nickel(II) and copper(II) to the N-terminal sequence of human protamine HP2 SO CHEMICAL RESEARCH IN TOXICOLOGY LA English DT Article ID UNSCHEDULED DNA-SYNTHESIS; HUMAN-SPERM PROTAMINES; HUMAN BLOOD-PLASMA; SERUM-ALBUMIN; NEUROMEDIN-C; GERM-CELLS; 2 FORMS; COMPLEXES; PROTEINS; PEPTIDE AB A potentiometric and spectroscopic (UV/vis and CD) study of Cu(II) and Ni(II) binding to the N-terminal pentadecapeptide of human protamine HP2 (HP2(1-15)) was performed. The results indicate that the N-terminal tripeptide motif Arg-Thr-His is the exclusive binding site for both metal ions at a metal to HP2(1-15) molar ratio not higher than 1. The very high value of protonation-corrected stability constant (log *K) for Ni(II)-HP2(1-15) complex, -19,29, indicates that HP2 has the potential to sequester Ni(II) from other peptide and protein carriers, including albumin, The same is likely for Cu(II) (log *K = -13.13). The CD spectra of Cu(II) and Ni(II) complexes of HP2(1-15) indicate that the N-terminal metal binding affects the overall conformation of the peptide that, in turn, may alter interaction of HP2 with DNA. These results imply HP2 as a likely target for the toxic metals Ni(II) and Cu(IT). C1 NCI,FREDERICK CANC RES & DEV CTR,COMPARAT CARCINOGENESIS LAB,FREDERICK,MD 21702. UNIV WROCLAW,FAC CHEM,PL-50138 WROCLAW,POLAND. NR 50 TC 64 Z9 64 U1 0 U2 5 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0893-228X J9 CHEM RES TOXICOL JI Chem. Res. Toxicol. PD AUG PY 1997 VL 10 IS 8 BP 906 EP 914 DI 10.1021/tx970028x PG 9 WC Chemistry, Medicinal; Chemistry, Multidisciplinary; Toxicology SC Pharmacology & Pharmacy; Chemistry; Toxicology GA XR507 UT WOS:A1997XR50700010 PM 9282840 ER PT J AU Bal, W Lukszo, J Kasprzak, KS AF Bal, W Lukszo, J Kasprzak, KS TI Mediation of oxidative DNA damage by nickel(II) and copper(II) complexes with the N-terminal sequence of human protamine HP2 SO CHEMICAL RESEARCH IN TOXICOLOGY LA English DT Article ID HYDROGEN-PEROXIDE; ION; SUPEROXIDE; HISTIDINE; PROTEINS; PEPTIDES; BASES; CHROMATIN; RESIDUES; CU(II) AB The potential of Ni(II) and Cu(II) complexes with Arg-Thr-His-Gly-Gln-Ser-His-Tyr-Arg-Arg-Arg-His-Cys-Ser-Arg-amide (Hp2(1-15)), a peptide modeling the N-terminal amino acid sequence of human protamine HP2, to mediate oxidative DNA damage was studied by measurements of 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxo-dG) generation from 2'-deoxyguanosine (dG) and calf thymus DNA and by formation of double-strand breaks in calf thymus DNA. The concentrations of reagents were 0.1 mM dG and the metal-HP2(1-15) complex, 1 mM H2O2, 1.5 mM DNA (per phosphate group), 100 mM phosphate buffer, pH 7.4, ambient O-2. Samples were incubated at 37 degrees C for 16-24 h. The Cu(II)-HP2(1-15) complex was found to be an effective promoter of the formation of 8-oxo-dG from both dG and DNA with ambient Oz (approximately 13- and 3-fold increase versus the oxidant alone, respectively) and H2O2 (approximately 25-fold increase in either case). The Ni(II)-HP2(1-15) complex was ineffective with Oz versus 8-oxo-dG production from both substrates but markedly enhanced the attack of H2O2 on dG and DNA (approximately Ei-fold increase of 8-oxo-dG production in either case). Both Cu(II)- and Ni(II)-HP2(1-15) equally promoted double-strand scission by H2O2 in calf thymus DNA. The promotion by the complexes of dG and DNA oxidation with H2O2 was accompanied by oxidative damage to the complexes themselves, consisting of decreasing contents of their His (to approximately 50% of control in either complex) and especially Tyr (down to 48% of control in Cu(II)- and 19% in Ni(IT)-HP2(1-15)) residues, as well as appearance of aspartic acid, the known oxidation product of His residues in peptides (up to 22% vs Gly for Cu(II)- and 10% for Ni(II)-HP2(1-15)). The above results provide a novel chemical mechanism of Cu(II) and Ni(II) toxicity and may have wide implications for reproductive and transgenerational effects of metal exposure. C1 NCI, FREDERICK CANC RES & DEV CTR, COMPARAT CARCINOGENESIS LAB, FREDERICK, MD 21702 USA. NIAID, MOL STRUCT LAB, ROCKVILLE, MD 20852 USA. NR 48 TC 49 Z9 49 U1 1 U2 2 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0893-228X J9 CHEM RES TOXICOL JI Chem. Res. Toxicol. PD AUG PY 1997 VL 10 IS 8 BP 915 EP 921 DI 10.1021/tx970029p PG 7 WC Chemistry, Medicinal; Chemistry, Multidisciplinary; Toxicology SC Pharmacology & Pharmacy; Chemistry; Toxicology GA XR507 UT WOS:A1997XR50700011 PM 9282841 ER PT J AU Robin, RW Chester, B Rasmussen, JK Jaranson, JM Goldman, D AF Robin, RW Chester, B Rasmussen, JK Jaranson, JM Goldman, D TI Prevalence, characteristics, and impact of childhood sexual abuse in a southwestern American Indian tribe SO CHILD ABUSE & NEGLECT LA English DT Article DE child sexual abuse; victimization; American Indian; intrafamilial abuse; perpetrator ID POSTTRAUMATIC-STRESS-DISORDER; MENTAL-HEALTH; COMMUNITY SURVEY; RISK FACTOR; CHILDREN; WOMEN; VICTIMIZATION; ALCOHOL; SAMPLE; TRAUMA AB Objective: There were two objectives; first, to investigate the prevalence and characteristics of child sexual abuse in an American Indian community, and second, to determine whether persons with histories of child sexual abuse are at greater risk to develop psychiatric disorders and behavioral problems than persons who report no such history. Method: A sample of 582 Southwestern American Indian tribal members was collected for a genetic and linkage study on alcoholism and psychiatric disorders in three large and interrelated pedigrees. Subjects were recruited from the community without knowledge of their clinical histories or those of their relatives. Child sexual abuse and psychiatric disorders were assessed using a semi-structured psychiatric interview. Results: Females were more likely to be sexually abused as children (49%) than were males (14%). Intrafamilial members accounted for 78% of the reported child sexual abuse. Sexually abused males and females were more likely to report childhood and adult behavioral problems than were nonabused subjects. There was a strong relationship between multiple psychiatric disorders and child sexual abuse, with sexually abused males and females more likely to be diagnosed with greater than or equal to 3 psychiatric disorders, both including and excluding alcohol dependence or abuse, than were nonabused subjects. Conclusion: Child sexual abuse in this population is both an index of family dysfunction and community disorganization as well as a predictor of later behavioral patterns and psychopathology. (C) 1997 Elsevier Science Ltd. C1 NIAAA,NEUROGENET LAB,NIH,ROCKVILLE,MD 20852. HOPI FDN,CTR PREVENT & RESOULUT VIOLENCE,TUCSON,AZ. UNIV ARIZONA,DEPT EPIDEMIOL,TUCSON,AZ. UNIV MINNESOTA,ST PAUL RAMSEY MED CTR,DEPT PSYCHIAT,MINNEAPOLIS,MN. RI Goldman, David/F-9772-2010 OI Goldman, David/0000-0002-1724-5405 NR 82 TC 54 Z9 54 U1 0 U2 6 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0145-2134 J9 CHILD ABUSE NEGLECT JI Child Abuse Negl. PD AUG PY 1997 VL 21 IS 8 BP 769 EP 787 DI 10.1016/S0145-2134(97)00038-0 PG 19 WC Family Studies; Psychology, Social; Social Work SC Family Studies; Psychology; Social Work GA XN236 UT WOS:A1997XN23600008 PM 9280382 ER PT J AU Boluyt, MO Zheng, JS Younes, A Long, XL ONeill, L Silverman, H Lakatta, EG Crow, MT AF Boluyt, MO Zheng, JS Younes, A Long, XL ONeill, L Silverman, H Lakatta, EG Crow, MT TI Rapamycin inhibits alpha(1)-adrenergic receptor-stimulated cardiac myocyte hypertrophy but not activation of hypertrophy-associated genes - Evidence for involvement of p70 S6 kinase SO CIRCULATION RESEARCH LA English DT Article DE ribosomal SG-kinase; alpha(1)-adrenergic receptor; immunosuppressant drug; rapamycin; phosphatidylinositol-3 kinase ID SMOOTH-MUSCLE CELLS; PROTEIN-SYNTHESIS; ANGIOTENSIN-II; HEART-CELLS; MAMMALIAN PROTEIN; MESSENGER-RNA; RAT-HEART; IN-VITRO; GROWTH; EXPRESSION AB The 70-kD S6 kinase (p70(S6K)) has been implicated in the regulation of protein synthesis in many cell types and in the angiotensin II-stimulated hypertrophy of cardiac myocytes. Our purpose was to determine whether p70(S6K) plays a role in cardiomyocyte hypertrophy induced by the alpha(1)-adrenergic receptor (alpha(1)-AR) agonist phenylephrine (PE). PE stimulated the activity of p70(S6K) >3-fold, and this increase was blocked by rapamycin, an immunosuppressant macrolide that selectively inhibits p70(S6K). When administered for 3 days, PE stimulated a 30% increase in total protein content, a 2-fold increase in the incorporation of [C-14]phenylalanine (C-14-Phe) into protein, and a 50% increase in two-dimensional myocyte area. Rapamycin pretreatment (greater than or equal to 500 pg/mL) significantly inhibited each of these PE-stimulated changes. Two days of PE treatment resulted in a 1.6-fold increase in total RNA yield per dish, a 2-fold increase in incorporation of [C-14]uridine into myocyte RNA, and increases in relative mRNA levels of the hypertrophy-associated atrial natriuretic factor (ANF, 2.1-fold) and skeletal alpha-actin (SK, 2.2-fold) genes. Although rapamycin abolished the PE-stimulated increases in total RNA and incorporation of [C-14]uridine, it had no effect on the induction of the ANF and SK genes. LY294002, a specific inhibitor of phosphatidylinositol 3-kinase (PI3-K) activity, inhibited PE-stimulatcd increases in p70(S6K) activity and the incorporation of labeled precursors into myocyte protein and RNA. These results demonstrate that p70(S6K) is activated by the hypertrophic agent PE and that a PI3-K or PI3-K-like activity is required for p70(S6K) activation and myocyte hypertrophy. The data suggest that p70(S6K) activation may be required for PE-stimulated hypertrophy of cardiac myocytes. Our results demonstrate that intracellular signaling pathways responsible for transcriptional and translational responses diverge early after alpha(1)-AR stimulation in cardiac myocytes. C1 INST UNIV TECHNOL CLERMONT FERRAND, DEPT APPL BIOL, AUBIERE, FRANCE. JOHNS HOPKINS UNIV HOSP, DIV CARDIOL, BALTIMORE, MD 21287 USA. RP Boluyt, MO (reprint author), NIA, GERONTOL RES CTR, CARDIOVASC SCI LAB, NIH, 4940 EASTERN AVE, BALTIMORE, MD 21224 USA. NR 66 TC 133 Z9 134 U1 0 U2 2 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7330 J9 CIRC RES JI Circ.Res. PD AUG PY 1997 VL 81 IS 2 BP 176 EP 186 PG 11 WC Cardiac & Cardiovascular Systems; Hematology; Peripheral Vascular Disease SC Cardiovascular System & Cardiology; Hematology GA XN585 UT WOS:A1997XN58500005 PM 9242178 ER PT J AU Freay, AD Curtis, SW Korach, KS Rubanyi, GM AF Freay, AD Curtis, SW Korach, KS Rubanyi, GM TI Mechanism of vascular smooth muscle relaxation by estrogen in depolarized rat and mouse aorta - Role of nuclear estrogen receptor and Ca2+ uptake SO CIRCULATION RESEARCH LA English DT Article DE 17 beta-estradiol; 17 alpha-estradiol; estrone; diethylstilbestrol; mice, estrogen receptor-deficient ID ENDOTHELIUM-INDEPENDENT RELAXATION; CORONARY-ARTERY ATHEROSCLEROSIS; BINDING-SITES; PROGESTERONE RECEPTORS; CARDIOVASCULAR-SYSTEM; POSTMENOPAUSAL WOMEN; STEROID-HORMONES; NITRIC-OXIDE; 17-BETA-ESTRADIOL; CELLS AB 17 beta-Estradiol induces vasodilation in vitro and in vivo, which has been suggested to contribute to the cardiovascular protection by this ovarian steroid hormone. However, the exact mechanism of vasorelaxation by estrogens remains to be elucidated. In this study, we analyzed the potential role of genomic mechanisms involving the nuclear estrogen receptor and inhibition of entry of extracellular Ca2+ in 17 beta-estradiol-induced vasorelaxation in depolarized aortic rings, isolated from male and female rats and male mice. In both male and female rat aortic rings without endothelium and in intact male mouse aortic rings treated with N-G-nitro-L-arginine, 17 beta-estradiol caused dose-dependent (0.3 to 30 mu mol/L) relaxation of contraction evoked by high-K+ depolarization (30 and 45 mmol/L KCl, respectively). The estrogen receptor antagonist ICI 164384 had no effect on 17 beta-estradiol-induced relaxations. I-125-17 beta-estradiol binding studies showed the presence of high-affinity cytosolic-nuclear estrogen receptors in control male mouse aortas. Comparable relaxations of aortic rings isolated from control and estrogen receptor-deficient transgenic mice provided direct evidence that the nuclear estrogen receptor is neat involved in this response. 17 beta-Estradiol-induced relaxation of rat aortic rings could not be prevented by cycloheximide or actinomycin D, suggesting that the response was not mediated by de novo protein synthesis or gene transcription. In rat aortic rings. 17 beta-estradiol inhibited the increase of Ca-45 uptake by 30 mmol/L KCl at concentrations (10 and 30 mu mol/L) that caused vasorelaxation in the same tissue, suggesting that inhibition of Ca2+ entry contributes to the response. 17 alpha-Estradiol was less effective, and estrone was devoid of vasorelaxing activity. Vasorelaxation by estrogens in female and male rat aortas was similar, indicating no gender difference in vascular responses under these conditions. C1 BERLEX BIOSCI,DEPT CARDIOVASC RES,RICHMOND,CA 94804. NIEHS,REPROD & DEV TOXICOL LAB,NIH,RES TRIANGLE PK,NC 27709. OI Korach, Kenneth/0000-0002-7765-418X NR 48 TC 93 Z9 96 U1 1 U2 1 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7330 J9 CIRC RES JI Circ.Res. PD AUG PY 1997 VL 81 IS 2 BP 242 EP 248 PG 7 WC Cardiac & Cardiovascular Systems; Hematology; Peripheral Vascular Disease SC Cardiovascular System & Cardiology; Hematology GA XN585 UT WOS:A1997XN58500012 PM 9242185 ER PT J AU Thurau, SR Chan, CC Nussenblatt, RB Caspi, RR AF Thurau, SR Chan, CC Nussenblatt, RB Caspi, RR TI Oral tolerance in a murine model of relapsing experimental autoimmune uveoretinitis (EAU): Induction of protective tolerance in primed animals SO CLINICAL AND EXPERIMENTAL IMMUNOLOGY LA English DT Article DE oral tolerance; chronic relapsing autoimmune uveitis; autoantigens; T lymphocytes ID RETINOID-BINDING PROTEIN; MYELIN BASIC-PROTEIN; GROWTH-FACTOR-BETA; IMMUNE-RESPONSES; II COLLAGEN; S-ANTIGEN; DISEASE; SUPPRESSION; MICE; ENCEPHALOMYELITIS AB Oral administration of uveitogenic retinal antigens suppresses the expression of EAU induced by a subsequent immunization with these antigens. Effectiveness and mechanisms of oral tolerance in EAU have mainly been studied in the acute, monophasic model in Lewis rats by feeding antigen prior to induction of disease. In this study we investigated the effect of oral tolerance induction in the acute as well as the chronic-relapsing models in the B10.A mouse. In acute murine EAU we could effectively suppress disease by induction of oral tolerance prior to immunization. In the chronic-relapsing EAU, antigen feeding was started only after the animals had recovered from their first attack of uveitis. Under these experimental conditions the subsequent relapse was largely prevented. These experiments demonstrate that oral tolerance may have practical clinical implications in uveitis, which is predominantly a chronic-relapsing condition in humans. C1 NEI, IMMUNOL LAB, NIH, BETHESDA, MD 20892 USA. RP UNIV EYE HOSP, IMMUNOBIOL SECT, MATHILDENSTR 8, D-80336 MUNICH, GERMANY. NR 39 TC 104 Z9 112 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0009-9104 EI 1365-2249 J9 CLIN EXP IMMUNOL JI Clin. Exp. Immunol. PD AUG PY 1997 VL 109 IS 2 BP 370 EP 376 DI 10.1046/j.1365-2249.1997.4571356.x PG 7 WC Immunology SC Immunology GA XP310 UT WOS:A1997XP31000021 PM 9276535 ER PT J AU Shapiro, B AF Shapiro, B TI The United States medical scientist training program SO CLINICAL AND INVESTIGATIVE MEDICINE-MEDECINE CLINIQUE ET EXPERIMENTALE LA English DT Article C1 NIH,MED SCI TRAINING PROGRAM,BETHESDA,MD 20892. RP Shapiro, B (reprint author), NIH,DIV CELL BIOL & BIOPHYS,CELLULAR SECT,BLDG 10,BETHESDA,MD 20892, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU CANADIAN MEDICAL ASSOCIATION PI OTTAWA PA 1867 ALTA VISTA DR, OTTAWA ON K1G 3Y6, CANADA SN 0147-958X J9 CLIN INVEST MED JI Clin. Invest. Med.-Med. Clin. Exp. PD AUG PY 1997 VL 20 IS 4 BP 251 EP 254 PG 4 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA XP129 UT WOS:A1997XP12900009 PM 9258581 ER PT J AU Yanovski, JA Friedman, TC Nieman, LK Chrousos, GP Cutler, GB Doppman, JL Kalogeras, KT AF Yanovski, JA Friedman, TC Nieman, LK Chrousos, GP Cutler, GB Doppman, JL Kalogeras, KT TI Inferior petrosal sinus AVP in patients with Cushing's syndrome SO CLINICAL ENDOCRINOLOGY LA English DT Article ID CORTICOTROPIN-RELEASING HORMONE; VASOPRESSIN MESSENGER-RNA; FACTOR RECEPTORS; AUTORADIOGRAPHIC LOCALIZATION; DIFFERENTIAL-DIAGNOSIS; CEREBROSPINAL-FLUID; PITUITARY-GLAND; DISEASE; SECRETION; ADRENOCORTICOTROPIN AB OBJECTIVE In both normal volunteers and patients with Cushing's disease, one dominant inferior petrosal sinus (IFS) contains higher concentrations of AVP and ACTH than the contralateral (non-dominant) IFS, but ovine corticotrophin-releasing hormone (oCRH)-stimulated AVP in the petrosal sinuses is greater in Cushing's disease than in normal volunteers. To distinguish whether greater oGRH-releasable AVP might be specifically related to the presence of a pituitary corticotrophinoma, or be due to hypercortisolism per se, we compared IFS AVP in patients with Cushing's disease with those of patients with other causes of Cushing's syndrome. PATIENTS Twenty-three patients with Cushing's disease, 16 patients with the syndrome of ectopic ACTH and seven patients with Cushing's syndrome of adrenal origin, MEASUREMENTS AVP and ACTH, measured both before and 3, 5 and 10 minutes after oCRH in the petrosal sinuses, and in a peripheral vein. RESULTS In all three groups, AVP concentrations were lateralized such that most of the AVP was found in one, dominant IFS. oCRH significantly increased IFS ACTH only in patients with Cushing's disease (P < 0.001), whereas it significantly increased dominant IFS AVP levels in all three patient groups (P < 0.01). However, neither dominant nor nondominant IPS AVP (basal or oCRH-stimulated) were significantly different among patients with Cushing's disease, ectopic ACTH or Cushing's syndrome of adrenal origin. Basal and oCRH-stimulated IFS AVP were negatively correlated with urine free cortisol. CONCLUSIONS Inferior petrosal sinus AVP levels are similar in ail forms of Cushing's syndrome, and thus the higher inferior petrosal sinus AVP levels in patients with Cushing's disease compared with normal volunteers are unlikely to be related specifically to the presence of the pituitary corticotrophinoma. While AVP may play a role in pituitary corticotroph tumourigenesis or may be secreted by some pituitary corticotroph tumours, the observation that CRH-stimulated inferior petrosal sinus AVP levels are higher in Cushing's disease than in normal volunteers appears most likely to be related to the low endogenous CRH levels induced by hypercortisolism, rather than a consequence of Cushing's disease itself. We hypothesize that low endogenous CRH leads to increased sensitivity of central nervous system CRH receptors to exogenous CRH, and thus to greater ovine CRH-stimulated AVP. C1 NICHHD, WARREN GRANT MAGNUSON CLIN CTR, DEPT DIAGNOST RADIOL, NIH, BETHESDA, MD 20892 USA. NICHHD, DEV ENDOCRINOL BRANCH, NIH, BETHESDA, MD 20892 USA. UNIV CALIF LOS ANGELES, CEDARS SINAI MED CTR,BURNS & ALLEN RES INST, SCH MED,DEPT MED, LOS ANGELES, CA 90048 USA. UNIV MISSISSIPPI, MED CTR,SCH MED,LAB CLIN NEUROENDOCRINOL, DEPT PSYCHIAT & HUMAN BEHAV, JACKSON, MS 39216 USA. RP Yanovski, JA (reprint author), NICHHD, OFF DIRECTOR,NIH,10 CTR DR,MSC 1862, BLDG 10 ROOM 10N262, 9000 ROCKV, BETHESDA, MD 20892 USA. OI Yanovski, Jack/0000-0001-8542-1637 NR 34 TC 6 Z9 6 U1 0 U2 1 PU BLACKWELL SCIENCE LTD PI OXFORD PA P O BOX 88, OSNEY MEAD, OXFORD, OXON, ENGLAND OX2 0NE SN 0300-0664 J9 CLIN ENDOCRINOL JI Clin. Endocrinol. PD AUG PY 1997 VL 47 IS 2 BP 199 EP 206 DI 10.1046/j.1365-2265.1997.2301038.x PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA XR294 UT WOS:A1997XR29400013 PM 9302395 ER PT J AU Perlman, DC ElSadr, WM Nelson, ET Matts, JP Telzak, EE Salomon, N Chirgwin, K Hafner, R AF Perlman, DC ElSadr, WM Nelson, ET Matts, JP Telzak, EE Salomon, N Chirgwin, K Hafner, R TI Variation of chest radiographic patterns in pulmonary tuberculosis by degree of human immunodeficiency virus-related immunosuppression SO CLINICAL INFECTIOUS DISEASES LA English DT Article; Proceedings Paper CT 33rd Annual Meeting of the Infectious-Diseases-Society-of-America CY SEP 16-20, 1995 CL SAN FRANCISCO, CA SP Infect Dis Soc Amer ID T-LYMPHOCYTE COUNT; INFECTION; MANIFESTATIONS; APPEARANCE; SPECTRUM; AIDS AB Our aim was to evaluate the effect of human immunodeficiency virus (HIV) disease stage on chest radiographic (CXR) findings among patients with HIV-related pulmonary tuberculosis (TB), Data are from a prospective multicenter treatment trial for HIV-related TB, Baseline CXR findings and CD4(+) lymphocyte counts were compared among patients with HIV-related TB, Data from published studies describing CXR findings in HIV-infected patients were reviewed and a pooled-data analysis was conducted, Of 135 patients with culture-confirmed HIV-related TB, 128 had both CXR and CD4(+) lymphocyte data, CD4(+) lymphocyte counts of <200/mm(3) (n = 98) were significantly associated with hilar/mediastinal adenopathy on CXR (30%, vs. 7% with counts greater than or equal to 200/mm(3); P = .01); counts of greater than or equal to 200/mm(3) (n = 30) more frequently were associated with cavitation (20% vs. 7%; P = .08), Analyses of these results, pooled with other published data, confirmed these findings, This study demonstrates associations of certain CXR findings with HIV disease stage, Knowledge of the degree of immunosuppression is important when evaluating CXR findings in HIV-infected patients. C1 COLUMBIA UNIV COLL PHYS & SURG,HARLEM HOSP CTR,DIV INFECT DIS,NEW YORK,NY 10032. UNIV MINNESOTA,SCH PUBL HLTH,DIV BIOSTAT,COORDINATING CTR BIOMETR RES,CPCRA STAT CTR,MINNEAPOLIS,MN 55455. BRONX LEBANON HOSP CTR,BRONX,NY 10456. SUNY HLTH SCI CTR,DIV INFECT DIS,NEW YORK,NY. NIAID,DIV AIDS,WASHINGTON,DC. RP Perlman, DC (reprint author), BETH ISRAEL MED CTR,DIV INFECT DIS,1ST AVE & 16TH ST,NEW YORK,NY 10003, USA. FU NIAID NIH HHS [U01 AI046370] NR 24 TC 130 Z9 138 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 AUG PY 1997 VL 25 IS 2 BP 242 EP 246 DI 10.1086/514546 PG 5 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA XT820 UT WOS:A1997XT82000015 PM 9332519 ER PT J AU Piscitelli, SC AF Piscitelli, SC TI Effect of food intake on the bioavailability of itraconazole - Reply SO CLINICAL INFECTIOUS DISEASES LA English DT Letter RP Piscitelli, SC (reprint author), NIH,CTR CLIN,DEPT PHARM,BLDG 10,ROOM 1N-257,BETHESDA,MD 20892, USA. NR 0 TC 0 Z9 0 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 AUG PY 1997 VL 25 IS 2 BP 345 EP 345 PG 1 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA XT820 UT WOS:A1997XT82000046 ER PT J AU Shapiro, BA Wu, JC AF Shapiro, BA Wu, JC TI Predicting RNA H-type pseudoknots with the massively parallel genetic algorithm SO COMPUTER APPLICATIONS IN THE BIOSCIENCES LA English DT Article ID SECONDARY STRUCTURE; COMPUTER-SIMULATION; STABILITY AB Motivation: Using the genetic algorithm (GA) for RNA folding on a massively parallel supercomputer, MasPar MP-2 with 16384 processors, we successfully predicted the existence of H-type pseudoknots in several sequences. Results: The GA is applied to folding the tRNA-like 3' end of turnip yellow mosaic virus (TYMV) RNA sequence with 82 nucleotides, the 3' UTRs of satellite tobacco necrosis virus (STNV)-2 RNA sequence with 619 nucleotides and STNV-1 RNA sequence with 622 nucleotides, and the bacteriophage T2, T4 and T6 gene 32 mRNA sequences with 946, 1340 and 946 nucleotides, respectively. The GA's results march the phylogenetically supported tertiary structures of these sequences. C1 NCI,FREDERICK CANC RES & DEV CTR,FREDERICK BIOMED SUPERCOMP CTR,SAIC FREDERICK,LECB,FREDERICK,MD 21702. RP Shapiro, BA (reprint author), NCI,FREDERICK CANC RES & DEV CTR,IMAGE PROC SECT,LAB EXPT & COMPUTAT BIOL,DIV BASIC SCI,NIH,FREDERICK,MD 21702, USA. NR 20 TC 28 Z9 29 U1 0 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD, ENGLAND OX2 6DP SN 0266-7061 J9 COMPUT APPL BIOSCI JI Comput. Appl. Biosci. PD AUG PY 1997 VL 13 IS 4 BP 459 EP 471 PG 13 WC Computer Science, Interdisciplinary Applications SC Computer Science GA XR673 UT WOS:A1997XR67300016 PM 9283762 ER PT J AU Korn, EL AF Korn, EL TI Assessing quality of life in comparative cancer clinical trials: Does it make a difference? SO CONTROLLED CLINICAL TRIALS LA English DT Editorial Material RP Korn, EL (reprint author), NCI,BIOMETR RES BRANCH,EPN 739,BETHESDA,MD 20892, USA. NR 3 TC 1 Z9 1 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0197-2456 J9 CONTROL CLIN TRIALS JI Controlled Clin. Trials PD AUG PY 1997 VL 18 IS 4 BP 275 EP 276 DI 10.1016/S0197-2456(96)00244-9 PG 2 WC Medicine, Research & Experimental; Pharmacology & Pharmacy SC Research & Experimental Medicine; Pharmacology & Pharmacy GA XP118 UT WOS:A1997XP11800001 PM 9257065 ER PT J AU Green, SB AF Green, SB TI Does assessment of quality of life in comparative cancer trials make a difference? A discussion SO CONTROLLED CLINICAL TRIALS LA English DT Article; Proceedings Paper CT 1995 Joint Statistical Meeting CY AUG 12-17, 1995 CL ORLANDO, FL SP Amer Stat Assoc, Biometr Soc, E & W N Amer Region, Stat Soc Canada DE cancer trials; controlled clinical trials; quality of life; randomized controlled trials; survival analysis AB This paper discusses two accompanying manuscripts addressing the question whether the assessment of quality of life in comparative cancer trials makes a difference. A number of thoughts and comments stimulated by the manuscripts are presented. it is concluded that, when comparing treatment regimens for a disease such as cancer, three measures can be considered in turn. First, the primary endpoint must remain: How long do patients survive? The logical next question is: How well do patients function? Then we have the third question: How well do patients feel? Certainly, these questions are interrelated, but our decisions will be the most rational (and we will provide the most useful information to patients) if we keep these distinctions in mind. Whatever the endpoint of interest, however, the appropriate way to compare different therapeutic interventions reliably is the randomized trial. (C) Published by Elsevier Science Inc. RP Green, SB (reprint author), NCI,EXECUT PLAZA N,FUITE 344,6130 EXECUT BLVD,MSC 735,BETHESDA,MD 20892, USA. NR 3 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 0197-2456 J9 CONTROL CLIN TRIALS JI Controlled Clin. Trials PD AUG PY 1997 VL 18 IS 4 BP 306 EP 310 DI 10.1016/S0197-2456(97)00053-6 PG 5 WC Medicine, Research & Experimental; Pharmacology & Pharmacy SC Research & Experimental Medicine; Pharmacology & Pharmacy GA XP118 UT WOS:A1997XP11800005 PM 9257069 ER PT J AU Canner, PL Thompson, B Knatterud, GL Geller, N Campeau, L Zucker, D AF Canner, PL Thompson, B Knatterud, GL Geller, N Campeau, L Zucker, D TI An application of the Zucker-Wittes modified ratio estimate statistic in the post coronary artery by-pass graft (CABG) clinical trial SO CONTROLLED CLINICAL TRIALS LA English DT Article DE ratio estimate; coronary artery bypass graft surgery; controlled clinical trial AB In the Post Coronary Artery Bypass Graft (POST CABG) clinical trial, the primary outcome is substantial worsening (i.e., narrowing of the lumen diameter) of the vein grafts upon comparison of the baseline and follow-up angiograms. The patients had one to five non-occluded vein grafts at entry, so there may be from one to five primary outcome responses per patient. A modified ratio estimate (MRE) statistic, as described previously by Zucker and Wittes, may be used to analyze data of this kind. In the present paper we propose a more powerful MRE statistic when the event rates and/or intraclass correlations vary according to number of grafts per patient. We also adapt this statistic to the factorial treatment design of the POST CABG clinical trial. (C) Elsevier Science Inc. 1997. C1 NHLBI,BETHESDA,MD 20892. MONTREAL HEART INST,MONTREAL,PQ H1T 1C8,CANADA. HEBREW UNIV JERUSALEM,JERUSALEM,ISRAEL. RP Canner, PL (reprint author), MARYLAND MED RES INST,600 WYNDHURST AVE,BALTIMORE,MD 21210, USA. FU NHLBI NIH HHS [N01-HC-75076] NR 4 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 0197-2456 J9 CONTROL CLIN TRIALS JI Controlled Clin. Trials PD AUG PY 1997 VL 18 IS 4 BP 318 EP 327 DI 10.1016/S0197-2456(96)00232-2 PG 10 WC Medicine, Research & Experimental; Pharmacology & Pharmacy SC Research & Experimental Medicine; Pharmacology & Pharmacy GA XP118 UT WOS:A1997XP11800007 PM 9257071 ER PT J AU Wagtmann, N Rojo, S Eichler, E Mohrenweiser, H Long, EO AF Wagtmann, N Rojo, S Eichler, E Mohrenweiser, H Long, EO TI A new human gene complex encoding the killer cell inhibitory receptors and related monocyte/macrophage receptors SO CURRENT BIOLOGY LA English DT Article ID MAP; DNA AB Activation of various immune cell types can be prevented by negative signaling receptors. Natural killer (NK) cells, which can lyse tumor or virus-infected cells, express inhibitory receptors that recognise distinct 'self' class I molecules of the major histocompatibility complex [1], Recognition of self class I molecules results in a negative signal to prevent NK mediated killing of healthy cells [2]. Human and mouse NK cells express both immunoglobulin-like type I inhibitory receptors - such as the human killer cell inhibitory receptor (KIR) and the mouse gp49B glycoprotein - and lectin-like type II inhibitory receptors - such as the human CD94/NKG2 heterodimer and the mouse Ly-49 receptor family [1], These receptors use tyrosine phosphorylation motifs in their cytoplasmic tails to deliver a dominant-negative signal by recruiting the tyrosine phosphatase SHP-1 [3-5], We have identified a new family of monocyte/macrophage immunoglobulinlike receptors (MIRs) related to KIR, Two cDNA clones with sequence similarity to each other and to the gp49B gene were isolated from human lymphocytes; both encode proteins containing four immunoglobulin domains and the conserved cytoplasmic inhibitory motifs, and transcription of both was detected primarily in monocytes/macrophages, rather than T, NK, or mast cells, The MIR genes are closely linked to the KIR gene family and the gene for Fc alpha R on chromosome 19, at cytogenetic band q13.4, A mouse sequence related to MIR was mapped to a region on mouse chromosome 7 syntenic with human 19q13.4. Our findings should facilitate studies of the evolution and function of the MIR and KIR families. C1 NIAID,IMMUNOGENET LAB,ROCKVILLE,MD 20852. LAWRENCE LIVERMORE NATL LAB,CTR HUMAN GENOME,LIVERMORE,CA 94550. RI Long, Eric/G-5475-2011 OI Long, Eric/0000-0002-7793-3728 NR 24 TC 153 Z9 155 U1 1 U2 1 PU CURRENT BIOLOGY LTD PI LONDON PA 34-42 CLEVELAND STREET, LONDON, ENGLAND W1P 6LB SN 0960-9822 J9 CURR BIOL JI Curr. Biol. PD AUG 1 PY 1997 VL 7 IS 8 BP 615 EP 618 DI 10.1016/S0960-9822(06)00263-6 PG 4 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA XP666 UT WOS:A1997XP66600035 PM 9259559 ER PT J AU Neuwald, AF AF Neuwald, AF TI Barth syndrome may be due to an acyltransferase deficiency SO CURRENT BIOLOGY LA English DT Letter ID CARDIOMYOPATHY; XQ28 RP Neuwald, AF (reprint author), NATL LIB MED,NATL CTR BIOTECHNOL INFORMAT,NIH,BETHESDA,MD 20894, USA. NR 13 TC 100 Z9 101 U1 1 U2 3 PU CURRENT BIOLOGY LTD PI LONDON PA 34-42 CLEVELAND STREET, LONDON, ENGLAND W1P 6LB SN 0960-9822 J9 CURR BIOL JI Curr. Biol. PD AUG 1 PY 1997 VL 7 IS 8 BP R465 EP R466 PG 2 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA XP666 UT WOS:A1997XP66600009 PM 9259571 ER PT J AU Peculis, B AF Peculis, B TI RNA processing: Pocket guides to ribosomal RNA SO CURRENT BIOLOGY LA English DT Article AB The functional role of a recently identified class of small nucleolar (sno)RNAs has been elucidated: the 'box H/ACA' snoRNAs act as guide RNAs, specifying the position of evolutionarily conserved pseudouridines in ribosomal (r)RNA via an rRNA-snoRNA base-pairing interaction that forms a 'pseudouridine pocket'. RP Peculis, B (reprint author), NIDDK,GENET & BIOCHEM BRANCH,NIH,BETHESDA,MD 20892, USA. NR 11 TC 9 Z9 10 U1 0 U2 0 PU CURRENT BIOLOGY LTD PI LONDON PA 34-42 CLEVELAND STREET, LONDON, ENGLAND W1P 6LB SN 0960-9822 J9 CURR BIOL JI Curr. Biol. PD AUG 1 PY 1997 VL 7 IS 8 BP R480 EP R482 DI 10.1016/S0960-9822(06)00242-9 PG 3 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA XP666 UT WOS:A1997XP66600014 PM 9259547 ER PT J AU Sonnhammer, ELL Wootton, JC AF Sonnhammer, ELL Wootton, JC TI Widespread eukaryotic sequences, highly similar to bacterial DNA polymerase I, looking for functions SO CURRENT BIOLOGY LA English DT Letter ID ALIGNMENT; COMPILATION; DAMAGE RP Sonnhammer, ELL (reprint author), NATL LIB MED,NATL CTR BIOTECHNOL INFORMAT,COMPUTAT BIOL BRANCH,NIH,BLDG 38A,BETHESDA,MD 20894, USA. NR 14 TC 5 Z9 5 U1 0 U2 0 PU CURRENT BIOLOGY LTD PI LONDON PA 34-42 CLEVELAND STREET, LONDON, ENGLAND W1P 6LB SN 0960-9822 J9 CURR BIOL JI Curr. Biol. PD AUG 1 PY 1997 VL 7 IS 8 BP R463 EP R465 PG 3 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA XP666 UT WOS:A1997XP66600008 PM 9259570 ER PT J AU Hamer, D AF Hamer, D TI The search for personality genes: Adventures of a molecular biologist SO CURRENT DIRECTIONS IN PSYCHOLOGICAL SCIENCE LA English DT Article ID NOVELTY SEEKING; POLYMORPHISM; ASSOCIATION C1 NCI, Biochem Lab, NIH, Bethesda, MD 20892 USA. RP Hamer, D (reprint author), NCI, Biochem Lab, NIH, NIH Bldg 37,Room 4A13, Bethesda, MD 20892 USA. NR 10 TC 8 Z9 8 U1 6 U2 9 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 40 WEST 20TH STREET, NEW YORK, NY 10011-4211 USA SN 0963-7214 J9 CURR DIR PSYCHOL SCI JI Curr. Dir. Psychol. PD AUG PY 1997 VL 6 IS 4 BP 111 EP 114 DI 10.1111/1467-8721.ep11514443 PG 4 WC Psychology, Multidisciplinary SC Psychology GA ZB660 UT WOS:000072494800007 ER PT J AU Brine, GA Carroll, FI RichardsonLeibert, TM Xu, H Rothman, RB AF Brine, GA Carroll, FI RichardsonLeibert, TM Xu, H Rothman, RB TI Ohmefentanyl and its stereoisomers: Chemistry and pharmacology SO CURRENT MEDICINAL CHEMISTRY LA English DT Article ID RECEPTOR-BINDING CHARACTERISTICS; DIRECTED ACYLATING AGENT; MU-OPIOID RECEPTOR; ANALGESIC ACTIVITY; SYNTHETIC ANALGESICS; MEDIATED PHENOMENA; POTENT ANALGESICS; RAT-BRAIN; ENANTIOMERS; SITE AB Ohmefentanyl, or beta-hydroxy-3-methylfentanyl, is an unique member of the 4-anilidopiperidine class of opiates. This review summarizes both the initial studies on mixtures of ohmefentanyl stereoisomers and some more recent studies on the eight individual stereoisomers, in particular those in which the 3-methyl and 4-propionanilide substituents on the piperidine ring have a cis relationship to each other. Analog studies, also on stereoisomer mixtures, have revealed that structural changes in the beta-hydroxy-beta-phenethyl portion of the molecule have considerable impact on the biological activity in the cis series while changes in the 4-propionanilide portion have smaller effects. The analog data are consistent with the idea that the cis-3-methyl group, the beta-hydroxyl group and the beta-phenethyl group play key roles in cis-ohmefentanyl's unique activity. Biological studies on the four cis-stereoisomers [(beta S,3R,4S)-4a, (beta R,3R,4S)-4b, (beta R,3S,4R)-4c, (beta S,3S,4R)-4d] have shown that they differ considerably in their in vitro and in vivo biological properties. Since these stereoisomers differ from each other in their absolute stereochemistries, which focuses the analysis on asymmetric structural factors and avoids confounding changes in physiochemical characteristics, they constitute a unique set of molecular probes for investigation of mu receptor mediated phenomena. We summarize in this review data showing that these four cis-stereoisomers are characterized by different parameter profiles for ligand-receptor interaction: binding affinity (Ki value), potency (ED50 for receptor activation), efficacy (maximal response) and intrinsic efficacy (relationship between receptor occupation and response). We speculate that the different profiles result from binding to different domains of the mu opioid receptor. Moreover, we expect that continued studies with these stereoisomers, as well as the corresponding stereoisomers of selected cis-ohmefentanyl analogs, will help to elucidate the molecular basis of these parameters and to develop more refined pharmacophores for the opioid mu receptor. This review traces the evolution of ohmefentanyl, or beta-hydroxy-3-methylfentanyl, from the initial papers on the identification of an unexpectedly potent congener of cis-3-methylfentanyl to some of the more recent work involving the four pure cis-stereoisomers and ligands derived from cis-A-ohmefentanyl. While an effort is made to place the discovery of ohmefentanyl into the context of earlier work on 4-anilidopiperidines and then to follow a chronological sequence of events, the review has been organized so that related work from different groups is covered. in the same section. Some of the initial biological data on ohmefentanyl from the Shanghai Institute of Materia Medica was summarized previously in a short review [1]. C1 NIDA,CLIN PSYCHOPHARMACOL SECT,IRP,NIH,BALTIMORE,MD 21224. RP Brine, GA (reprint author), RES TRIANGLE INST,MED CHEM BLDG,ROOM 284,POB 12194,RES TRIANGLE PK,NC 27709, USA. NR 70 TC 6 Z9 6 U1 1 U2 2 PU BENTHAM SCIENCE PUBL BV PI HILVERSUM PA PO BOX 1673, 1200 BR HILVERSUM, NETHERLANDS SN 0929-8673 J9 CURR MED CHEM JI Curr. Med. Chem. PD AUG PY 1997 VL 4 IS 4 BP 247 EP 270 PG 24 WC Biochemistry & Molecular Biology; Chemistry, Medicinal; Pharmacology & Pharmacy SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy GA XW133 UT WOS:A1997XW13300002 ER PT J AU Helm, BA Padlan, EA AF Helm, BA Padlan, EA TI Protein engineering from plants to animals, from big to small, from outside to inside and other advances - Editorial overview SO CURRENT OPINION IN BIOTECHNOLOGY LA English DT Editorial Material C1 NIDDKD,MOL BIOL LAB,NIH,BETHESDA,MD 20892. RP Helm, BA (reprint author), UNIV SHEFFIELD,DEPT MOL BIOL & BIOTECHNOL,KREBS INST BIOMOLEC RES,SHEFFIELD S10 2UH,S YORKSHIRE,ENGLAND. NR 2 TC 0 Z9 0 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 AUG PY 1997 VL 8 IS 4 BP 397 EP 399 DI 10.1016/S0958-1669(97)80059-6 PG 3 WC Biochemical Research Methods; Biotechnology & Applied Microbiology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology GA XN339 UT WOS:A1997XN33900001 PM 9265719 ER PT J AU Lee, B Vasmatzis, G AF Lee, B Vasmatzis, G TI Stabilization of protein structures SO CURRENT OPINION IN BIOTECHNOLOGY LA English DT Review ID ALPHA-HELICAL PROTEIN; GCN4 LEUCINE-ZIPPER; GLOBULAR-PROTEINS; HYDROPHOBIC CORE; COILED COILS; T4 LYSOZYME; X-RAY; STABILITY; MUTATION; MUTANTS AB The technique of protein stabilization has been improving steadily in recent years, but it is only in the past year or two that the stability of some protein molecules has been improved to the level of those from extreme thermophilic organisms, This was achieved by multiple mutations and often by utilizing the knowledge gained from the homologous protein structures from extreme thermophiles. RP Lee, B (reprint author), NCI,MOL BIOL LAB,DIV CANC BIOL,NIH,BLDG 37,ROOM 4B15,37 CONVENT DR,MSC 4255,BETHESDA,MD 20892, USA. NR 65 TC 47 Z9 48 U1 1 U2 7 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 AUG PY 1997 VL 8 IS 4 BP 423 EP 428 DI 10.1016/S0958-1669(97)80063-8 PG 6 WC Biochemical Research Methods; Biotechnology & Applied Microbiology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology GA XN339 UT WOS:A1997XN33900005 PM 9265720 ER PT J AU Schuck, P AF Schuck, P TI Reliable determination of binding affinity and kinetics using surface plasmon resonance biosensors SO CURRENT OPINION IN BIOTECHNOLOGY LA English DT Review ID MACROMOLECULAR INTERACTIONS; DIFFUSION; PROTEINS; RECEPTOR; BILAYERS; BIACORE AB Progress has been made in the identification of experimental and analytical procedures that allow for a more reliable determination of equilibrium and kinetic constants, Possible origins of the frequently observed deviations of the measured binding progress from that expected for chemical binding of pseudo-first order, and appropriate experimental controls have been proposed. Improved analytical approaches include the application of global analysis and analytical corrections for the influence of mass transport. RP Schuck, P (reprint author), NIH,NATL CTR RES RESOURCES,MOL INTERACT RESOURCE,BIOMED ENGN & INSTRUMENTAT PROGRAM,BLD 13,BETHESDA,MD 20892, USA. OI Schuck, Peter/0000-0002-8859-6966 NR 43 TC 123 Z9 124 U1 1 U2 28 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 AUG PY 1997 VL 8 IS 4 BP 498 EP 502 DI 10.1016/S0958-1669(97)80074-2 PG 5 WC Biochemical Research Methods; Biotechnology & Applied Microbiology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology GA XN339 UT WOS:A1997XN33900016 PM 9265731 ER PT J AU Kirchhausen, T Bonifacino, JS Riezman, H AF Kirchhausen, T Bonifacino, JS Riezman, H TI Linking cargo to vesicle formation: receptor tail interactions with coat proteins SO CURRENT OPINION IN CELL BIOLOGY LA English DT Article ID FACTOR-II RECEPTOR; ENDOPLASMIC-RETICULUM; GOLGI MEMBRANES; CLATHRIN COATS; INTERNALIZATION; ENDOCYTOSIS; BINDING; SIGNAL; YEAST; LOCALIZATION AB How soluble cargo molecules concentrate into budding vesicles is the subject of intensive current research. Clathrin-based vesiculation from the plasma membrane and the trans-Golgi network constitutes the best described system that supports this sorting process. Soluble ligands bind to specific transmembrane receptors which have been shown to interact directly with clathrin adaptor complexes, components of clathrin coats. At the same time, these clathrin adaptors facilitate clathrin coat assembly and probably regulate the recruitment of the rest of the coat components. Recent studies have looked at both the interaction of receptor tails with adaptors and the assembly of the clathrin coat. Progress has also been made in elucidating how soluble cargo molecules may be concentrated for exit from the endoplasmic reticulum. C1 HARVARD UNIV,SCH MED,CTR BLOOD RES,BOSTON,MA 02115. NICHHD,CELL BIOL & METAB BRANCH,NIH,BETHESDA,MD 20892. UNIV BASEL,BIOZENTRUM,CH-4056 BASEL,SWITZERLAND. RP Kirchhausen, T (reprint author), HARVARD UNIV,SCH MED,DEPT CELL BIOL,200 LONGWOOD AVE,BOSTON,MA 02115, USA. OI Riezman, Howard/0000-0003-4680-9422; Bonifacino, Juan S./0000-0002-5673-6370 NR 59 TC 338 Z9 340 U1 0 U2 2 PU CURRENT BIOLOGY LTD PI LONDON PA 34-42 CLEVELAND STREET, LONDON, ENGLAND W1P 6LB SN 0955-0674 J9 CURR OPIN CELL BIOL JI Curr. Opin. Cell Biol. PD AUG PY 1997 VL 9 IS 4 BP 488 EP 495 DI 10.1016/S0955-0674(97)80024-5 PG 8 WC Cell Biology SC Cell Biology GA XM844 UT WOS:A1997XM84400005 PM 9261055 ER PT J AU Knepper, MA Inoue, T AF Knepper, MA Inoue, T TI Regulation of aquaporin-2 water channel trafficking by vasopressin SO CURRENT OPINION IN CELL BIOLOGY LA English DT Article ID KIDNEY COLLECTING DUCT; HUMAN ANTIDIURETIC-HORMONE; RAT-KIDNEY; PERMEABILITY; PROTEINS; FAMILY; RECEPTOR; MEMBRANE; PHOSPHORYLATION; ENDOCYTOSIS AB Vasopressin regulates water excretion from the kidney by increasing the osmotic water permeability of the renal collecting duct. The aquaporin-2 water channel has been demonstrated to be the target for this action of vasopressin. Recent studies have demonstrated that vasopressin, acting through cyclic AMP, triggers fusion of aquaporin-2-bearing vesicles with the apical plasma membrane of the collecting duct principal cells. The vesicle-targeting proteins synaptobrevin-2 and syntaxin-4 are proposed to play roles in this process. RP Knepper, MA (reprint author), NHLBI,KIDNEY & ELECTROLYTE METAB LAB,NIH,BLDG 9,ROOM IN105,9 MEM DR,MSC-0951,BETHESDA,MD 20892, USA. NR 46 TC 111 Z9 113 U1 1 U2 3 PU CURRENT BIOLOGY LTD PI LONDON PA 34-42 CLEVELAND STREET, LONDON, ENGLAND W1P 6LB SN 0955-0674 J9 CURR OPIN CELL BIOL JI Curr. Opin. Cell Biol. PD AUG PY 1997 VL 9 IS 4 BP 560 EP 564 DI 10.1016/S0955-0674(97)80034-8 PG 5 WC Cell Biology SC Cell Biology GA XM844 UT WOS:A1997XM84400015 PM 9261056 ER PT J AU Wolfsberg, TG Makalowski, W AF Wolfsberg, TG Makalowski, W TI Web alert - Pattern formation and developmental mechanisms SO CURRENT OPINION IN GENETICS & DEVELOPMENT LA English DT Bibliography RP Wolfsberg, TG (reprint author), NIH,NATL LIB MED,NATL CTR BIOTECHNOL INFORMAT,BLDG 38A,ROOM 8N-805,BETHESDA,MD 20894, USA. RI Makalowski, Wojciech/I-2843-2016 NR 0 TC 0 Z9 0 U1 0 U2 0 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 AUG PY 1997 VL 7 IS 4 BP 453 EP 453 DI 10.1016/S0959-437X(97)80069-X PG 1 WC Cell Biology; Genetics & Heredity SC Cell Biology; Genetics & Heredity GA XU025 UT WOS:A1997XU02500001 ER PT J AU Leonard, WJ AF Leonard, WJ TI Genetic effects on immunity - Protein tyrosine kinases: disease loci for inherited immunodeficiencies - Editorial overview SO CURRENT OPINION IN IMMUNOLOGY LA English DT Editorial Material RP Leonard, WJ (reprint author), NHLBI,LAB MOL IMMUNOL,NIH,BLDG 10,ROOM 7N252,BETHESDA,MD 20892, USA. NR 5 TC 2 Z9 2 U1 1 U2 1 PU CURRENT BIOLOGY LTD PI LONDON PA 34-42 CLEVELAND STREET, LONDON, ENGLAND W1P 6LB SN 0952-7915 J9 CURR OPIN IMMUNOL JI Curr. Opin. Immunol. PD AUG PY 1997 VL 9 IS 4 BP 525 EP 527 DI 10.1016/S0952-7915(97)80105-7 PG 3 WC Immunology SC Immunology GA XT719 UT WOS:A1997XT71900014 PM 9287183 ER PT J AU Emery, S Lane, HC AF Emery, S Lane, HC TI Immune reconstitution in HIV infection SO CURRENT OPINION IN IMMUNOLOGY LA English DT Review ID HUMAN-IMMUNODEFICIENCY-VIRUS; CUBIC MILLIMETER; CD4 CELLS; INTERLEUKIN-2; ZIDOVUDINE; COMBINATION; THERAPY; ADULTS; TRIAL AB Progressive immune deficiency arising during HIV disease reflects the continual degradation and the ultimate deletion of immune specificites defined by the CD4(+) T lymphocyte repertoire. Recent evidence suggests that improvements in the immune function of patients with HIV who receive therapy primarily reflects the expansion of CD4(+) T lymphocyte populations present before therapy commenced. These observations have implications for clinical management, therapeutic strategies, and future research. C1 NIAID,NIH,BETHESDA,MD 20892. RP Emery, S (reprint author), UNIV NEW S WALES,NATL CTR HIV EPIDEMIOL & CLIN RES,2ND FLOOR,376 VICTORIA ST,SYDNEY,NSW 2010,AUSTRALIA. RI Emery, Sean/H-4920-2013 OI Emery, Sean/0000-0001-6072-8309 NR 30 TC 33 Z9 33 U1 0 U2 0 PU CURRENT BIOLOGY LTD PI LONDON PA 34-42 CLEVELAND STREET, LONDON, ENGLAND W1P 6LB SN 0952-7915 J9 CURR OPIN IMMUNOL JI Curr. Opin. Immunol. PD AUG PY 1997 VL 9 IS 4 BP 568 EP 572 DI 10.1016/S0952-7915(97)80112-4 PG 5 WC Immunology SC Immunology GA XT719 UT WOS:A1997XT71900021 PM 9287177 ER PT J AU Henderson, DK AF Henderson, DK TI Healthcare institutions as 'hot zones': emerging and re-emerging pathogens SO CURRENT OPINION IN INFECTIOUS DISEASES LA English DT Review ID HUMAN-IMMUNODEFICIENCY-VIRUS; HEPATITIS-C VIRUS; RESISTANT ENTEROCOCCUS-FAECIUM; INTENSIVE-CARE-UNIT; MYCOBACTERIUM-TUBERCULOSIS; NOSOCOMIAL TRANSMISSION; STAPHYLOCOCCUS-EPIDERMIDIS; OCCUPATIONAL EXPOSURES; NEEDLESTICK INJURIES; B VIRUS AB The rapid development of antimicrobial agents from the 1930s to the 1980s spawned optimism about the potential for conquering bacterial diseases, Unfortunately, the 1980s and 1990s have seen the re-emergence of traditional bacterial pathogens and have become resistant to currently available therapies, These new pathogens of the 1990s present formidable obstacles to healthcare practitioners, in addition, the presence of new bloodborne pathogens in the healthcare workplace has forced a reassessment of occupational risks for those working in this complex environment. This review assesses recent information about occupational and nosocomial pathogens, analysing the potential for healthcare institutions to become 'hot zones'. (C) Rapid Science Publishers. RP Henderson, DK (reprint author), NIH,WARREN A MAGASON CLIN CTR,BETHESDA,MD 20892, USA. NR 130 TC 3 Z9 3 U1 0 U2 1 PU RAPID SCIENCE PUBLISHERS PI LONDON PA 2-6 BOUNDARY ROW, LONDON, ENGLAND SE1 8NH SN 0951-7375 J9 CURR OPIN INFECT DIS JI Curr. Opin. Infect. Dis. PD AUG PY 1997 VL 10 IS 4 BP 310 EP 318 PG 9 WC Infectious Diseases SC Infectious Diseases GA XL802 UT WOS:A1997XL80200013 ER PT J AU Karni, A Bertini, G AF Karni, A Bertini, G TI Learning perceptual skills: behavioral probes into adult cortical plasticity SO CURRENT OPINION IN NEUROBIOLOGY LA English DT Article ID FREQUENCY-DISCRIMINATION TASK; PRIMARY VISUAL-CORTEX; VERNIER ACUITY; OWL MONKEYS; HUMAN VISION; ORIENTATION; IMPROVEMENT; REPRESENTATION; DIRECTION; MEMORY AB Recent studies of the improvement of perceptual performance as a function of training-perceptual learning-have provided new insights into the neuronal substrates of this type of skill learning in the adult brain. Issues such as where in the brain, when and under what conditions practice-related changes occur are under investigation. The results of these studies suggest that a behaviorally relevant degree of plasticity is retained in the adult cortex, even within early, low-level representations in sensory and motor processing streams. The acquisition and retention of skills may share many characteristics with the functional plasticity subserving early-life learning and development. While the specificity of learning provides localization constraints, an important clue to the nature of the underlying neuronal changes is the time course of learning. C1 CHAIM SHEBA MED CTR,DEPT NEUROL,IL-52621 TEL HASHOMER,ISRAEL. WEIZMANN INST SCI,DEPT NEUROBIOL,IL-76100 REHOVOT,ISRAEL. NIMH,LAB BRAIN & COGNIT,BETHESDA,MD 20892. NR 71 TC 152 Z9 154 U1 0 U2 6 PU CURRENT BIOLOGY LTD PI LONDON PA 34-42 CLEVELAND STREET, LONDON, ENGLAND W1P 6LB SN 0959-4388 J9 CURR OPIN NEUROBIOL JI Curr. Opin. Neurobiol. PD AUG PY 1997 VL 7 IS 4 BP 530 EP 535 DI 10.1016/S0959-4388(97)80033-5 PG 6 WC Neurosciences SC Neurosciences & Neurology GA XV562 UT WOS:A1997XV56200012 PM 9287202 ER PT J AU Litvan, I AF Litvan, I TI The clinical and pathologic hallmarks of progressive supranuclear palsy SO CURRENT OPINION IN NEUROLOGY LA English DT Review AB This article reviews recent studies evaluating the clinicopathologic markers of progressive supranuclear palsy, which have helped establish standardized clinical and pathologic diagnostic criteria. Although these criteria increase diagnostic accuracy, the clinical and pathologic overlap between progressive supranuclear palsy and other disorders remains. Factors that may contribute toward managing progressive supranuclear palsy patients better are discussed and the etiopathogenicity of the disorder is hypothesized. C1 NINCDS,NIH,BETHESDA,MD 20892. RP Litvan, I (reprint author), NIH,JACKSON FDN,NEUROPHARMACOL UNIT,DEF & VET HEAD INJURY PROGRAM,FED BLDG,RM 714,BETHESDA,MD 20892, USA. OI Litvan, Irene/0000-0002-3485-3445 NR 23 TC 19 Z9 19 U1 0 U2 0 PU RAPID SCIENCE PUBLISHERS PI LONDON PA 2-6 BOUNDARY ROW, LONDON, ENGLAND SE1 8NH SN 1350-7540 J9 CURR OPIN NEUROL JI Curr. Opin. Neurol. PD AUG PY 1997 VL 10 IS 4 BP 346 EP 350 DI 10.1097/00019052-199708000-00011 PG 5 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA XP427 UT WOS:A1997XP42700011 PM 9266160 ER PT J AU Hurley, JH Grobler, JA AF Hurley, JH Grobler, JA TI Protein kinase C and phospholipase C: Bilayer interactions and regulation SO CURRENT OPINION IN STRUCTURAL BIOLOGY LA English DT Article ID PLECKSTRIN HOMOLOGY DOMAIN; MONOLAYER SURFACE PRESSURE; PHORBOL ESTER BINDING; CYSTEINE-RICH REGION; INTERFACIAL CATALYSIS; ACTIVATION; ASSOCIATION; MECHANISM; COMPLEX; ENZYMES AB Protein kinase C and phospholipase C are interfacially active modular enzymes that contain multiple membrane-binding domains. During the past two years, 3D structures and functional data have been reported for the key domains: pleckstrin homology, protein kinase C homology-l and -2, and the phospholipase C catalytic domain. Roles for membrane bilayer structure and lipid microdomains have become clearly defined. interdependent ligand binding to different protein domains has shown how the domains work together to coordinate regulation. RP Hurley, JH (reprint author), NIDDKD,MOL BIOL LAB,NIH,BETHESDA,MD 20892, USA. NR 70 TC 55 Z9 55 U1 0 U2 0 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 AUG PY 1997 VL 7 IS 4 BP 557 EP 565 DI 10.1016/S0959-440X(97)80122-4 PG 9 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA XP651 UT WOS:A1997XP65100018 PM 9266179 ER PT J AU Porter, FD Drago, J Xu, Y Cheema, SS Wassif, C Huang, SP Lee, E Grinberg, A Massalas, JS Bodine, D Alt, F Westphal, H AF Porter, FD Drago, J Xu, Y Cheema, SS Wassif, C Huang, SP Lee, E Grinberg, A Massalas, JS Bodine, D Alt, F Westphal, H TI Lhx2, a LIM homeobox gene, is required for eye, forebrain, and definitive erythrocyte development SO DEVELOPMENT LA English DT Article DE LIM homeobox; eye; forebrain; erythropoiesis; mouse ID EXPRESSION PATTERNS; VERTEBRATE LIMB; MOUSE; HOMEODOMAIN; PROTEIN; DOMAIN; INDUCTION; CELLS; ZINC; DIFFERENTIATION AB We investigated the function of Lhx2, a LIM homeobox gene expressed in developing B-cells, forebrain and neural retina, by analyzing embryos deficient in functional Lhx2 protein, Lhx2 mutant embryos are anophthalmic, have malformations of the cerebral cortex, and die in utero due to severe anemia, In Lhx2-/- embryos specification of the optic vesicle occurs; however, development of the eye arrests prior to formation of an optic cup, Deficient cellular proliferation in the forebrain results in hypoplasia of the neocortex and aplasia of the hippocampal anlagen, In addition to the central nervous system malformations, a cell non-autonomous defect of definitive erythropoiesis causes severe anemia in Lhx2-/- embryos, Thus Lhx2 is necessary for normal development of the eye, cerebral cortex, and efficient definitive erythropoiesis. C1 NIH,LAB MAMMALIAN GENES & DEV,BETHESDA,MD 20892. MONASH UNIV,DEPT ANAT,CLAYTON,VIC 3168,AUSTRALIA. HARVARD UNIV,CHILDRENS HOSP,SCH MED,HOWARD HUGHES MED INST,BOSTON,MA 02115. HARVARD UNIV,DEPT GENET,SCH MED,CTR BLOOD RES,BOSTON,MA 02115. NIH,LAB GEN TRANSFER,BETHESDA,MD 20892. RP Porter, FD (reprint author), NIH,HERITABLE DISORDERS BRANCH,BLDG 10,BETHESDA,MD 20892, USA. OI Wassif, Christopher/0000-0002-2524-1420 NR 53 TC 323 Z9 326 U1 0 U2 3 PU COMPANY OF BIOLOGISTS LTD PI CAMBRIDGE PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE, CAMBS, ENGLAND CB4 4DL SN 0950-1991 J9 DEVELOPMENT JI Development PD AUG PY 1997 VL 124 IS 15 BP 2935 EP 2944 PG 10 WC Developmental Biology SC Developmental Biology GA XP688 UT WOS:A1997XP68800008 PM 9247336 ER PT J AU Zhu, DH Dix, DJ Eddy, EM AF Zhu, DH Dix, DJ Eddy, EM TI HSP70-2 is required for CDC2 kinase activity in meiosis I of mouse spermatocytes SO DEVELOPMENT LA English DT Article DE cyclin-dependent kinase; cyclin B1; molecular chaperone; HSP70; spermatogenesis; mouse ID HEAT-SHOCK PROTEINS; RING FINGER PROTEIN; CELL-CYCLE; SPERMATOGENIC CELLS; ACTIVATING KINASE; GENE FAMILY; SACCHAROMYCES-CEREVISIAE; GLUCOCORTICOID RECEPTOR; MOLECULAR CHAPERONES; STEROID-RECEPTOR AB Cyclin B-dependent CDC2 kinase activity has a key role in triggering the G(2)/M-phase transition during the mitotic and meiotic cell cycles, The Hsp70-2 gene is expressed only in spermatogenic cells at a significant level. In Hsp70-2 gene knock-out (Hsp70-2(-/-)) mice, primary spermatocytes fail to complete meiosis I, suggesting a link between HSP70-2 heat-shock protein and CDC2 kinase activity during this phase of spermatogenesis, Members of the HSP70 protein family are molecular chaperones that mediate protein de novo folding, translocation and multimer assembly, This study used immunoprecipitation-coupled western blot and in vitro reconstitution experiments to show that HSP70-2 interacts with CDC2 in the mouse testis, appears to be a molecular chaperone for CDC2, and is required for CDC2/cyclin B1 complex formation, Previous studies reported that most CDC2 kinase activity in the mouse testis is present in pachytene spermatocytes. Although CDC2 kinase activity for histone H1 was present in the testis of wild-type mice, it was nearly absent from the testis of Hsp70-2(-/-) mice, probably due to defective CDC2/cyclin B1 complex formation, Furthermore, addition of HSP70-2 to freshly prepared extracts of testis from Hsp 70-2(-/-) mice not only restored CDC2/cyclin B1 complex formation but also reconstituted CDC2 kinase activity in vitro, It appears that one cause of failure to complete meiosis I during spermatogenesis in Hsp70-2(-/-) mice is disruption of CDC2/cyclin B1 assembly in pachytene spermatocytes, thereby preventing development of the CDC2 kinase activity required to trigger G(2)/M-phase transition, These studies provide novel in vivo evidence for a link between an HSP70 molecular chaperone and CDC2 kinase activity essential for the meiotic cell cycle in spermatogenesis. C1 NIEHS,REPROD & DEV TOXICOL LAB,NIH,RES TRIANGLE PK,NC 27709. US EPA,REPROD TOXICOL DIV,NHEERL,RES TRIANGLE PK,NC 27711. NR 64 TC 145 Z9 157 U1 0 U2 3 PU COMPANY OF BIOLOGISTS LTD PI CAMBRIDGE PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE, CAMBS, ENGLAND CB4 4DL SN 0950-1991 J9 DEVELOPMENT JI Development PD AUG PY 1997 VL 124 IS 15 BP 3007 EP 3014 PG 8 WC Developmental Biology SC Developmental Biology GA XP688 UT WOS:A1997XP68800014 PM 9247342 ER PT J AU Schaapveld, RQJ Schepens, HTG Robinson, GW Attema, J Oerlemans, FTJJ Fransen, JAM Streuli, M Wieringa, B Hennighausen, L Hendriks, WJAJ AF Schaapveld, RQJ Schepens, HTG Robinson, GW Attema, J Oerlemans, FTJJ Fransen, JAM Streuli, M Wieringa, B Hennighausen, L Hendriks, WJAJ TI Impaired mammary gland development and function in mice lacking LAR receptor-like tyrosine phosphatase activity SO DEVELOPMENTAL BIOLOGY LA English DT Article ID EMBRYONIC STEM-CELLS; CREATINE-KINASE; TRANSGENIC MICE; EXTRACELLULAR-MATRIX; HOMOPHILIC BINDING; GENE-EXPRESSION; NERVOUS-SYSTEM; DOMAINS; BETA; ISOFORMS AB The LAR receptor-like protein tyrosine phosphatase is composed of two intracellular tyrosine phosphatase domains and a cell adhesion molecule-like extracellular region containing three immunoglubulin-like domains in combination with eight fibronectin type-III like repeats. This architecture suggests that LAR may function in cellular signalling by the regulation of tyrosine phosphorylation through cell-cell or cell-matrix interactions. We used gene targeting in mouse embryonic stem cells to generate mice lacking sequences encoding both LAR phosphatase domains, Northern blot analysis of various tissues revealed the presence of a truncated LAR mRNA lacking the cytoplasmic tyrosine phosphatase domains and indicated that this LAR mutation is not accompanied by obvious changes in the expression levels of one of the LAR-like receptor tyrosine phosphatases PTP delta or PTP sigma. LAR(-/-) mice develop and grow normally and display no appreciable histological tissue abnormalities. However, upon breeding we observed an abnormal neonatal death rate for pups from LAR(-/-) females. Mammary glands of LAR(-/-) females were incapable of delivering milk due to an impaired terminal differentiation of alveoli at late pregnancy. As a result, the glands failed to switch to a lactational state and showed a rapid involution postpartum. In wild-type mice, LAR expression is regulated during pregnancy reaching maximum levels around Day 16 of gestation. Taken together, these findings suggest an important role for LAR-mediated signalling in mammary gland development and function, (C) 1997 Academic Press. C1 UNIV NIJMEGEN,INST CELLULAR SIGNALLING,DEPT CELL BIOL & HISTOL,NL-6525 EK NIJMEGEN,NETHERLANDS. NIDDK,BIOCHEM & METAB LAB,NIH,BETHESDA,MD 20892. DANA FARBER CANC INST,DIV TUMOR IMMUNOL,BOSTON,MA 02115. RI Fransen, Jack/E-8924-2010; Robinson, Gertraud/I-2136-2012; Hendriks, Wiljan/A-5214-2013; Wieringa, Berend/A-5346-2011 OI Hendriks, Wiljan/0000-0001-9481-8281; Wieringa, Berend/0000-0001-9192-8020 NR 60 TC 105 Z9 106 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0012-1606 J9 DEV BIOL JI Dev. Biol. PD AUG 1 PY 1997 VL 188 IS 1 BP 134 EP 146 DI 10.1006/dbio.1997.8630 PG 13 WC Developmental Biology SC Developmental Biology GA XQ251 UT WOS:A1997XQ25100012 PM 9245518 ER PT J AU Yamane, A Mayo, ML Bringas, P Chen, L Huynh, M Thal, K Shum, L Slavkin, HC AF Yamane, A Mayo, ML Bringas, P Chen, L Huynh, M Thal, K Shum, L Slavkin, HC TI TGF-alpha, EGF, and their cognate EGF receptor are co-expressed with desmin during embryonic, fetal, and neonatal myogenesis in mouse tongue development SO DEVELOPMENTAL DYNAMICS LA English DT Article DE mouse; tongue; embryogenesis; myogenesis; desmin; TGF-alpha; EGF; EGFr; mandibular organ culture; occipital somites; cranial neural crest ID EPIDERMAL GROWTH-FACTOR; SKELETAL-MUSCLE; GENE FAMILY; MANDIBULAR MORPHOGENESIS; TRANSGENIC MICE; DNA-BINDING; MYOD FAMILY; Z-DISC; CELLS; PROTEIN AB The developing mouse tongue provides a model for discrete patterns of morphogenesis during short periods of embryonic development. Occipital somite-derived myogenic cells interact with cranial neural crest-derived ectomesenchymal cells to form the musculature of the tongue. The biochemical signals that control close range autocrine and/or paracrine signaling processes required to establish the fast-twitch complex tongue musculature are not known. The present study was designed to test the hypothesis that desmin, epidermal growth factor (EGF), and transforming growth factor-alpha (TGF alpha) and their cognate receptor, epidermal growth factor receptor (EGFr), are co-expressed during tongue myogenesis and define specific developmental stages of tongue muscle cell differentiation. To test this hypothesis, we performed studies to analyze the timing, position, and concentration of desmin, TGF alpha, EGF, and EGFr from embryonic day 9 (E9) through birth in Swiss Webster mouse tongue development, Desmin, TGF alpha, EGF, and EGFr co-localized to cells of myogenic lineage in the four occipital somites and subsequently in myoblasts and myotubes from E9 through E17. By newborn stage, desmin is localized to discrete regions in myofibers corresponding to Z-line delimiting sarcomeres, and A-band within sarcomeres; immunostaining for desmin, TGF alpha, and EGF persisted in differentiated myotubes and striated skeletal muscle, Desmin increased from 0.01% at E11 to 0.5% of the total protein by E17 and at birth. Concomitantly, the patterns and increases in TGF alpha, EGF, and EGFr showed significant increases during the same developmental period. The temporal and positional colocalization of TGF alpha, ECF, and EGFr support the hypothesis that autocrine and paracrine regulation of desmin by actions of growth factor ligand and receptor defines critical stages of tongue myogenesis. (C) 1997 Wiley-Liss, Inc. C1 NIAMSD,CRANIFACIAL DEV SECT,NATL INST HLTH,BONE & CONNECT TISSUE BIOL BRANCH,BETHESDA,MD 20892. UNIV SO CALIF,CTR CRANIOFACIAL MOL BIOL,SCH DENT,LOS ANGELES,CA 90033. FU NIDCR NIH HHS [DE-02848] NR 88 TC 17 Z9 17 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 1058-8388 J9 DEV DYNAM JI Dev. Dyn. PD AUG PY 1997 VL 209 IS 4 BP 353 EP 366 DI 10.1002/(SICI)1097-0177(199708)209:4<353::AID-AJA3>3.0.CO;2-H PG 14 WC Anatomy & Morphology; Developmental Biology SC Anatomy & Morphology; Developmental Biology GA XP500 UT WOS:A1997XP50000003 PM 9264259 ER PT J AU Toyama, R Dawid, IB AF Toyama, R Dawid, IB TI lim6, a novel LIM homeobox gene in the zebrafish: Comparison of its expression pattern with lim1 SO DEVELOPMENTAL DYNAMICS LA English DT Article DE lim1; lim6; LIM domain; homeobox; pronephros ID NEUROENDOCRINE TISSUES; EMBRYONIC EXPRESSION; XENOPUS; HOMEODOMAIN; PROTEIN; XLIM-1; DOMAIN; ORGANIZER; ELEGANS; DIFFERENTIATION AB A novel LIM class homeobox gene, lim6, was isolated from a zebrafish embryonic cDNA library, The encoded protein shares a high degree of sequence similarity with the previously described Lim1 and Lim5 proteins. This study compares the spatial and temporal expression pattern of the closely related lim6 and lim1 genes during early embryogenesis, Generally, lim6 mRNA was found at rather low amounts compared to lim1 mRNA, At the shield stage, lim6 mRNA, similar to lim1 mRNA, was predominantly expressed in the shield, Lim6 was transiently expressed in a restricted region of the anterior neural plate at the bud stage, distinct from the expression of lim1 in the notochord and the pronephros and pronephric ducts, During the segmentation period, the lim6 gene started to be expressed in single cells in the spinal cord, followed by a gradually increasing wide-spread expression throughout the CNS, During this stage, lim1 mRNA disappeared in the notochord and pronephric ducts and was found in the pronephroi and single cells in the CNS, In 24 hr embryos, lim6 and lim1 were expressed in the fore-, mid-, and hindbrain and the spinal cord, except that lim1 mRNA was limited to two small domains in the telencephalon, whereas lim6 mRNA was widely expressed in this region, A comparison of expression of lim1 and lim6 and of the previously characterized lim5 show that, in spite of close sequence similarity, distinct expression patterns imply nonredundant functions for each member of this group of genes. (C) 1997 Wiley-Liss, Inc.dagger C1 NICHHD,MOL GENET LAB,NATL INST HLTH,BETHESDA,MD 20892. NR 47 TC 54 Z9 54 U1 0 U2 1 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 1058-8388 J9 DEV DYNAM JI Dev. Dyn. PD AUG PY 1997 VL 209 IS 4 BP 406 EP 417 DI 10.1002/(SICI)1097-0177(199708)209:4<406::AID-AJA8>3.0.CO;2-M PG 12 WC Anatomy & Morphology; Developmental Biology SC Anatomy & Morphology; Developmental Biology GA XP500 UT WOS:A1997XP50000008 PM 9264264 ER PT J AU Hawa, M Rowe, R Lan, MS Notkins, AL Pozzilli, P Christie, MR Leslie, RDG AF Hawa, M Rowe, R Lan, MS Notkins, AL Pozzilli, P Christie, MR Leslie, RDG TI Value of antibodies to islet protein tyrosine phosphatase-like molecule in predicting type 1 diabetes SO DIABETES LA English DT Article ID GLUTAMIC-ACID DECARBOXYLASE; IDENTICAL-TWINS; TRYPTIC FRAGMENTS; IDDM; IDENTIFICATION; AUTOANTIGEN; SENSITIVITY; EXPRESSION; MARKERS; CLONING AB Islet antigens associated with type 1 diabetes include a recently identified protein tyrosine phosphatase-like molecule IA-2, which contains the intracellular fragment IA-2ic. To determine whether combinations of antibodies including those to IA-2 characterize and predict type 1 diabetes, we studied antibodies to IA-2, IA-aic, glutamic acid decarboxylase (GAD(65)), and islet cell antibodies (ICAs) in 1) 60 newly diagnosed type 1 diabetic patients followed for 1 year, 2) 31 monozygotic twin pairs discordant for type 1 diabetes followed up to 12 years (11 twins developed diabetes), 3) 18 dizygotic twin pairs discordant for type 1 diabetes, and 4) normal healthy control subjects. Newly diagnosed type 1 diabetic patients frequently had antibodies to IA-2 (62%), IA-Sic (67%), GAD(65) (77%), and ICAs (85%). The intracellular fragment of IA-2 probably contains the immunodominant epitope as 137 of 143 samples with IA-2 antibodies from type 1 diabetic patients also had IA-2ic antibodies. Monozygotic twins were usually discordant for antibody specificities. Concordance was higher in monozygotic than matched dizygotic twins for both antibody combinations (33 vs. 6%, P < 0.05) and the development of diabetes (33 vs. 0%, P < 0.01). In monozygotic twins, all the antibodies were highly predictive of type 1 diabetes (positive predictive values all >87%), although antibodies were also detected in twins at low risk of disease. In summary, IA-2 emerges as a major antigen associated with type 1 diabetes and distinct from GAD(65). Type 1 diabetes-associated autoimmunity, which is probably induced by environmental factors, does not necessarily herald progression to the disease. However, genetic factors may influence the development of combinations of disease-associated antibodies and the progression to type 1 diabetes. C1 ST BARTHOLOMEWS HOSP,DEPT DIABET & METAB,LONDON,ENGLAND. NATL INST HLTH,ORAL MED LAB,BETHESDA,MD. UNIV ROMA LA SAPIENZA,MED CLIN 2,ROME,ITALY. KINGS COLL HOSP,DEPT MED,LONDON,ENGLAND. RI Pozzilli, Paolo/A-5235-2010 NR 31 TC 80 Z9 81 U1 0 U2 0 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1660 DUKE ST, ALEXANDRIA, VA 22314 SN 0012-1797 J9 DIABETES JI Diabetes PD AUG PY 1997 VL 46 IS 8 BP 1270 EP 1275 DI 10.2337/diabetes.46.8.1270 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA XM400 UT WOS:A1997XM40000004 PM 9231650 ER PT J AU Odeleye, OE deCourten, M Pettitt, DJ Ravussin, E AF Odeleye, OE deCourten, M Pettitt, DJ Ravussin, E TI Fasting hyperinsulinemia is a predictor of increased body weight gain and obesity in Pima Indian children SO DIABETES LA English DT Article ID INSULIN-RESISTANCE; DIABETES-MELLITUS; LOWER RATES; SECRETION; MAINTENANCE; SENSITIVITY; NERVE AB Hyperinsulinemia is commonly associated with obesity, but it has not been determined which defect comes first. Some have proposed that hyperinsulinemia may precede obesity in populations prone to NIDDM, such as Pima Indians or Pacific Islanders. In contrast, longitudinal studies in adults show that insulin sensitivity and low fasting insulin concentrations are associated with increased weight gain, whereas insulin resistance seems to protect against weight gain. The present study examined whether fasting plasma hyperinsulinemia is a risk factor for weight gain in prepubertal children in the Pima Indian population-a population that is prone to obesity. Fasting plasma insulin concentration was measured in 328 5- to 9-year-old Pima Indian children (147 boys and 181 girls) with normal glucose tolerance. Follow-up weight was obtained an average of 9.3 +/- 1.9 years (means +/- SD) later at age 15-19 years. Fasting plasma insulin concentration correlated with the rate of weight gain per year in both boys (r = 0.42; P < 0.0001) and girls (r = 0.20; P < 0.01) and was associated with the rate of weight gain, independent of known determinants of weight change, i.e., initial relative weight, change in height, age, and sex. Similar relationships were found between fasting plasma insulin concentration and the change in relative weight and in triceps skinfold thickness-two indicators of obesity. In conclusion, fasting hyperinsulinemia may be a risk factor for the development of obesity in young children. C1 NIDDKD,CLIN DIABET & NUTR SECT,NIH,PHOENIX,AZ 85016. RI de Courten, Maximilian/B-3300-2012 OI de Courten, Maximilian/0000-0001-9997-9359 NR 42 TC 156 Z9 159 U1 0 U2 3 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1660 DUKE ST, ALEXANDRIA, VA 22314 SN 0012-1797 J9 DIABETES JI Diabetes PD AUG PY 1997 VL 46 IS 8 BP 1341 EP 1345 DI 10.2337/diabetes.46.8.1341 PG 5 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA XM400 UT WOS:A1997XM40000014 PM 9231660 ER PT J AU Nagi, DK McCormack, LJ MohamedAli, V Yudkin, JS Knowler, WC Grant, PJ AF Nagi, DK McCormack, LJ MohamedAli, V Yudkin, JS Knowler, WC Grant, PJ TI Diabetic retinopathy, promoter (4G/5G) polymorphism of PAI-1 gene, and PAI-1 activity in Pima Indians with type 2 diabetes SO DIABETES CARE LA English DT Article ID PLASMINOGEN-ACTIVATOR INHIBITOR-1; RETINAL ENDOTHELIAL-CELLS; MYOCARDIAL-INFARCTION; ELEVATED GLUCOSE; RISK FACTOR; MELLITUS; EXPRESSION; PLASMA; NIDDM; PREVALENCE AB OBJECTIVE - To examine the relationship between plasma plasminogen activator inhibitor 1(PAI-1) activity and PAI-1 gene (4G/5G) polymorphism and diabetic retinopathy in Pima Indians with type 2 diabetes. RESEARCH DESIGN AND METHODS - We studied 171 Pima Indians with type 2 diabetes between the ages of 30-70 years in a population-based epidemiological survey. Plasma PAI-1 activity was measured by a spectrophotometric assay and PAI-1 4G/5G promoter genotype by the polymerase chain reaction (PCR) using allele-specific primers. Retinopathy was assessed by ophthalmoscopy after pupillary dilation and classified as any retinopathy or as nonproliferative and proliferative. RESULTS - Retinopathy was present in 70 (41%) subjects, and 4 (2.3%) subjects had proliferative retinopathy. Plasma PAI-1 activity was not significantly different among subjects with and without retinopathy (17.1 +/- 9.3 vs. 19.7 +/- 9.1 arbitrary units (AU)/ml, P = 0.09). PAI-1 activity was negatively correlated nith duration of diabetes (rs = -0.18, P = 0.02). In a logistic regression analysis controlled for age, sex, BMI, and duration of diabetes, any retinopathy was significantly associated nith fasting plasma glucose concentrations (P < 0.05), 2-h postload glucose (P = 0.02), and HbA(1c) (P = 0.008), but not with PAI-1 activity (P = 0.48). The prevalence of retinopathy in the three genotype groups differed significantly (4G/4G, 4G/5G, and 5G/5G were 44, 49, and 24%, respectively; chi(2) = 8.22, df = 2, P = 0.016) and remained significant after controlling for age, sex, BMI, duration of diabetes, glycated hemoglobin, and urine albumin-to-creatine ratio in a logistic regression analysis. The odds ratios for retinopathy in subjects with 4G/4G and 4G/5G, compared nith the 5G/5G genotype, were 2.0 and 3.1, respectively. CONCLUSIONS - Although diabetic retinopathy in Pima Indians with type 2 diabetes is not associated with PAI-1 activity, subjects with the 4G/4G and 4G/5G genotype had a higher prevalence of retinopathy compared with 4G/5G PAI-1 genotype. These preliminary findings indicate that in Pima Indians with type 2 diabetes, presence of the 4G allele of the PAI-1 gene was associated nith a higher risk of diabetic retinopathy. C1 NIDDKD, NIH, PHOENIX, AZ USA. UNIV LEEDS, UNIT MOL VASC MED, DIV MED, LEEDS, W YORKSHIRE, ENGLAND. UCL, SCH MED, WHITTINGTON HOSP, DEPT MED, LONDON W1N 8AA, ENGLAND. RI Yudkin, John/C-1988-2008 NR 42 TC 45 Z9 48 U1 0 U2 1 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0149-5992 J9 DIABETES CARE JI Diabetes Care PD AUG PY 1997 VL 20 IS 8 BP 1304 EP 1309 DI 10.2337/diacare.20.8.1304 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA XM224 UT WOS:A1997XM22400017 PM 9250459 ER PT J AU Code, EL Crespi, CL Penman, BW Gonzalez, FJ Chang, TKH Waxman, DJ AF Code, EL Crespi, CL Penman, BW Gonzalez, FJ Chang, TKH Waxman, DJ TI Human cytochrome P4502B6 - Interindividual hepatic expression, substrate specificity, and role in procarcinogen activation SO DRUG METABOLISM AND DISPOSITION LA English DT Article ID HUMAN LIVER-MICROSOMES; CDNA-DIRECTED EXPRESSION; LYMPHOBLASTOID CELL-LINE; INDUCED RAT-LIVER; METABOLIC-ACTIVATION; STABLE EXPRESSION; ENZYME-ACTIVITY; O-DEETHYLASE; F344 RATS; CYCLOPHOSPHAMIDE AB The level of expression and interindividual variation in human hepatic microsomal cytochrome P450 (CYP) 2B6 was characterized using a polyclonal antibody (WB-2B6) raised against rat CYP2B1, Immunoblot analysis using cDNA-expressed human CYPs revealed strong cross-reactivity of this antibody with CYP2B6 (limit of detection < 0.05 pmol) and only minor cross-reactivities with human CYP2A6, CYP2D6, and CYP2E1, all of which could be resolved from CYP2B6 by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, Analysis of human liver microsomes using this antibody revealed immunodetectable CYP2B6 protein in a majority of individual liver samples, with levels up to 74 pmol/mg protein in the CYP2B6-positive samples. Kinetic analysis of cDNA-expressed CYPs identified many of these enzymes as catalysts of 7-ethoxy-4-trifluoromethylcoumarin (7EFC) O-deethylation, but with significantly different apparent K-M values (CYP1A2 < CYP2B6 similar to CYP1A1 < CYP2C19 < CYP2C9 < CYP2E1 < CYP2A6). By assaying liver microsomal 7EFC O-deethylase activity at a low 7EFC concentration (5 mu M) and preincubating human liver microsomes with anti-CYP1A, anti-CYP2C, and anti-CYP2E1 antibodies, we were able to monitor CYP2B6-dependent 7EFC O-deethylase activity in a panel of 17 human liver microsomes and observe a significant correlation (r(2) = 0.80) between this activity and CYP2B6 protein content. The ability of CYP2B6 to activate prodrugs and procarcinogens was examined using gene locus mutation assays in CYP2B6-expressing human lymphoblast cells. CYP2B6-expressing cells were found to be more sensitive than control cells to the cytotoxicity and mutagenicity of cyclophosphamide, aflatoxin B-1, and 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone, CYP2B6 is thus a widely expressed human liver microsomal CYP that can contribute to a broad range of drug metabolism and procarcinogen activation reactions. C1 GENTEST CORP,WOBURN,MA 01801. NCI,MOL CARCINOGENESIS LAB,NIH,BETHESDA,MD 20892. UNIV BRITISH COLUMBIA,FAC PHARMACEUT SCI,VANCOUVER,BC,CANADA. BOSTON UNIV,DEPT BIOL,DIV CELL & MOL BIOL,BOSTON,MA 02215. FU NCI NIH HHS [CA-49248]; NIEHS NIH HHS [P42-ES-04675-10] NR 64 TC 206 Z9 211 U1 0 U2 3 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0090-9556 J9 DRUG METAB DISPOS JI Drug Metab. Dispos. PD AUG PY 1997 VL 25 IS 8 BP 985 EP 993 PG 9 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA XR117 UT WOS:A1997XR11700012 PM 9280407 ER PT J AU Ooi, CE Moreira, JE DellAngelica, EC Poy, G Wassarman, DA Bonifacino, JS AF Ooi, CE Moreira, JE DellAngelica, EC Poy, G Wassarman, DA Bonifacino, JS TI Altered expression of a novel adaptin leads to defective pigment granule biogenesis in the Drosophila eye color mutant garnet SO EMBO JOURNAL LA English DT Article DE adaptin; garnet; granules; pigment; sorting ID CLATHRIN-COATED VESICLES; VIRUS CELL-RECEPTOR; BINDING DOMAIN; PROTEIN; MELANOGASTER; COMPLEXES; CLONING; MELANOSOMES; COMPONENTS; TRANSPORT AB Drosophila eye pigmentation defects have thus far been attributed to mutations in genes encoding enzymes required for biosynthesis of pigments and to ABC-type membrane transporters for pigments or their precursors, We report here that a defect in a gene encoding a putative coat adaptor protein leads to the eye color defect of garnet mutants, We first identified a human cDNA encoding delta-adaptin, a structural homolog of the alpha- and gamma-adaptin subunits of the clathrin coat adaptors AP-1 and AP-2, respectively. Biochemical analyses demonstrated that delta-adaptin is a component of the adaptor-like complex AP-3 in human cells, We then isolated a full-length cDNA encoding the Drosophila ortholog of delta-adaptin and found that transcripts specified by this cDNA are altered in garnet mutant dies, Examination by light and electron microscopy indicated that these mutant flies have reduced numbers of eye pigment granules, which correlates with decreased levels of both pteridine (red) and ommachrome (brown) pigments, Thus, the eye pigmentation defect in the Drosophila garnet mutant may be attributed to compromised function of a coat protein involved in intracellular transport processes required for biogenesis or function of pigment granules. C1 NICHHD,CELL BIOL & METAB BRANCH,BETHESDA,MD 20892. NIDDK,GENET & BIOCHEM BRANCH,NIH,BETHESDA,MD 20892. OI Bonifacino, Juan S./0000-0002-5673-6370 NR 51 TC 118 Z9 121 U1 2 U2 11 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD, ENGLAND OX2 6DP SN 0261-4189 J9 EMBO J JI Embo J. PD AUG 1 PY 1997 VL 16 IS 15 BP 4508 EP 4518 PG 11 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA XR255 UT WOS:A1997XR25500003 PM 9303295 ER PT J AU Sung, TC Roper, RL Zhang, Y Rudge, SA Temel, R Hammond, SM Morris, AJ Moss, B Engebrecht, J Frohman, MA AF Sung, TC Roper, RL Zhang, Y Rudge, SA Temel, R Hammond, SM Morris, AJ Moss, B Engebrecht, J Frohman, MA TI Mutagenesis of phospholipase D defines a superfamily including a trans-Golgi viral protein required for poxvirus pathogenicity SO EMBO JOURNAL LA English DT Article DE phospholipase D (PLD); SPO13; vaccinia; virus; VP37 ID RECOMBINANT VACCINIA VIRUSES; ADP-RIBOSYLATION FACTOR; ENVELOPE ANTIGEN; D ACTIVATION; CELLS; TRANSPHOSPHATIDYLATION; ACETYLCHOLINESTERASE; PHOSPHATIDYLCHOLINE; DISSEMINATION; SELECTION AB Phospholipase D (PLD) genes are members of a superfamily that is defined by several highly conserved motifs, PLD in mammals has been proposed to play a role in membrane vesicular trafficking and signal transduction, Using site-directed mutagenesis, 25 point mutants have been made in human PLD1 (hPLD1) and characterized. We find that a motif (HxKxxxxD) and a serine/threonine conserved in all members of the PLD superfamily are critical for PLD biochemical activity, suggesting a possible catalytic mechanism, Functional analysis of catalytically inactive point mutants for yeast PLD demonstrates that the meiotic phenotype ensuing from PLD deficiency in yeast derives from a loss of enzymatic activity. Finally, mutation of an HxKxxxxD motif found in a vaccinia viral protein expressed in the Golgi complex results in loss of efficient vaccinia virus cell-to-cell spreading, implicating the viral protein as a member of the superfamily and suggesting that it encodes a lipid modifying or binding activity. The results suggest that vaccinia virus and hPLD1 may act through analogous mechanisms to effect viral cellular egress and vesicular trafficking, respectively. C1 SUNY STONY BROOK,DEPT PHARMACOL SCI,STONY BROOK,NY 11794. SUNY STONY BROOK,MOL & CELLULAR BIOL PROGRAM,STONY BROOK,NY 11794. SUNY STONY BROOK,INST CELL & DEV BIOL,STONY BROOK,NY 11794. NIAID,VIRAL DIS LAB,BETHESDA,MD 20892. RI Morris, Andrew/B-7869-2010 FU NICHD NIH HHS [HD29758]; NIGMS NIH HHS [GM4863903, GM50388] NR 48 TC 251 Z9 260 U1 0 U2 8 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD, ENGLAND OX2 6DP SN 0261-4189 J9 EMBO J JI Embo J. PD AUG 1 PY 1997 VL 16 IS 15 BP 4519 EP 4530 DI 10.1093/emboj/16.15.4519 PG 12 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA XR255 UT WOS:A1997XR25500004 PM 9303296 ER PT J AU Georgel, PT Tsukiyama, T Wu, C AF Georgel, PT Tsukiyama, T Wu, C TI Role of histone tails in nucleosome remodeling by Drosophila NURF SO EMBO JOURNAL LA English DT Article DE Drosophila; histone tails; nucleosome remodeling; NURF ID TRANSCRIPTION FACTOR-BINDING; MULTISUBUNIT COMPLEX; FACILITATED BINDING; CHROMATIN STRUCTURE; GENE-PRODUCTS; AMINO TERMINI; YEAST; ACETYLATION; DNA; PROMOTER AB The Drosophila nucleosome remodeling factor NURF utilizes the energy of ATP hydrolysis to perturb the structure of nucleosomes and facilitate binding of transcription factors, The ATPase activity of purified NURF is stimulated significantly more by nucleosomes than by naked DNA or histones alone, suggesting that NURF is able to recognize specific features of the nucleosome. Here, we show that the interaction between NURF and nucleosomes is impaired by proteolytic removal of the N-terminal histone tails and by chemical cross-linking of nucleosomal histones, The ATPase activity of NURF is also competitively inhibited by each of the four Drosophila histone tails er;pressed as GST fusion proteins, A similar inhibition is observed for a histone H4 tail substituted with glutamine at four conserved, acetylatable lysines. These findings indicate a novel role for the flexible histone tails in chromatin remodeling by NURF, and this role may, in part, be independent of histone acetylation. C1 NCI,MOL CELL BIOL LAB,NIH,BETHESDA,MD 20892. NR 53 TC 113 Z9 113 U1 0 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD, ENGLAND OX2 6DP SN 0261-4189 J9 EMBO J JI Embo J. PD AUG 1 PY 1997 VL 16 IS 15 BP 4717 EP 4726 DI 10.1093/emboj/16.15.4717 PG 10 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA XR255 UT WOS:A1997XR25500024 PM 9303316 ER PT J AU LeRoith, D Parrizas, M Blakesley, VA AF LeRoith, D Parrizas, M Blakesley, VA TI The insulin-like growth factor-I receptor and apoptosis - Implications for the aging progress SO ENDOCRINE LA English DT Article DE apoptosis; growth factors; MAP kinase; PI 3'-kinase ID INHIBITOR; 3-KINASE; CELLS; DEATH RP LeRoith, D (reprint author), NIDDK, DIABET BRANCH, NIH, ROOM 8S235A, BLDG 10, BETHESDA, MD 20892 USA. NR 17 TC 34 Z9 34 U1 0 U2 0 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 USA SN 1355-008X EI 1559-0100 J9 ENDOCRINE JI Endocrine PD AUG PY 1997 VL 7 IS 1 BP 103 EP 105 PG 3 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA YJ962 UT WOS:A1997YJ96200019 PM 9449043 ER PT J AU Zeiger, MA Saji, M Gusev, Y Westra, WH Takiyama, Y Dooley, WC Kohn, LD Levine, MA AF Zeiger, MA Saji, M Gusev, Y Westra, WH Takiyama, Y Dooley, WC Kohn, LD Levine, MA TI Thyroid-specific expression of cholera toxin A1 subunit causes thyroid hyperplasia and hyperthyroidism in transgenic mice SO ENDOCRINOLOGY LA English DT Article ID TSH RECEPTOR; CELL-LINES; TUMORS; MUTATIONS; ONCOGENES; CANCER; CARCINOMAS; ADENOMAS; BENIGN; GENE AB Thyroid cell growth and function are regulated by hormones and growth factors binding to cell surface receptors that are coupled via G proteins, Gs and Gq, to the adenylyl cyclase and phospholipase C signal transduction systems, respectively. Activating mutations of the TSH receptor and Gas have been documented in subsets of thyroid neoplasms. To test the oncogenic potential of activated Gels in transgenic mice, we used the cholera toxin Al subunit that constitutively activates G alpha s and used the rat thyroglobulin gene promoter for targeting this transgene (TGCT) to thyroid follicular cells. Three (M1392, F1358, and F1286) of six founders identified were able to transmit the transgene to their offspring and thyroid glands from these mice contained elevated levels of cAMP. Concentrations of serum thyroxine were elevated as early as 2 months of age (M 1392 and F 1286). F1358 mice were euthyroid until 8 months of age, at which time they developed hyperthyroidism. All three TGCT lines developed thyroid hyperplasia independent of their thyroxine levels. DNA image analysis of thyroid follicular cells from both the hyper and euthyroid mice showed that DNA index and ''S+G2/M'' phase were increased compared with normal, changes similar to that seen in poor prognosis human carcinomas. These data suggest that the Gas-adenylyl cyclase-cAMP pathway has an important role in thyroid hyperplasia and the transgenic mouse models reported herein will allow further examination of the role of this pathway in thyroid oncogenesis. C1 JOHNS HOPKINS MED INST, DEPT SURG, BALTIMORE, MD 21205 USA. JOHNS HOPKINS MED INST, DEPT PATHOL, BALTIMORE, MD 21205 USA. JOHNS HOPKINS MED INST, DEPT MED, BALTIMORE, MD 21205 USA. NIDDKD, NIH, BETHESDA, MD 20892 USA. RI Saji, Motoyasu/E-4007-2011; Dooley, William/E-7660-2013; OI Levine, Michael/0000-0003-0036-7809 FU NIDDK NIH HHS [R0-1 DK34281] NR 50 TC 54 Z9 55 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 AUG PY 1997 VL 138 IS 8 BP 3133 EP 3140 DI 10.1210/en.138.8.3133 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA XL842 UT WOS:A1997XL84200008 PM 9231760 ER PT J AU Huo, B Dozin, B Nikodem, VM AF Huo, B Dozin, B Nikodem, VM TI Identification of a nuclear protein from rat developing brain as heterodimerization partner with thyroid hormone receptor-beta SO ENDOCRINOLOGY LA English DT Article ID TISSUE-SPECIFIC REGULATION; 9-CIS RETINOIC ACID; RESPONSE ELEMENT; TRANS-ACTIVATION; GENE-EXPRESSION; CO-REPRESSOR; DNA-BINDING; TRIIODOTHYRONINE; TRANSCRIPTION; PROMOTER AB Thyroid hormone receptors (TR) are ligand-activated transcription factors that modulate the expression of certain target genes in a developmental and tissue-specific manner. These specificities are determined by the tissue distribution of the TR isoforms al and pi, the structure of the thyroid hormone response element (TRE) bound by the receptor, and heterodimerization partners. Among these, retinoid X receptors (RXR) have been recognized as the principal partners for TR. The present work reports the identification of a novel nuclear protein from 19-day-old embryonic rat brain that displays a distinct interaction pattern with TR isoforms at the level of the TRE of two genes known to be differentially expressed and regulated by thyroid hormone (T-3): the ubiquitous malic enzyme and the brain-specific myelin basic protein. Electrophoretic gel mobility shift, assays demonstrate that only TR beta 1 forms a specific complex with the rat brain nuclear factor on the myelin basic protein-TRE, but not on the malic enzyme-TRE. Thus, the interaction is selectively determined by both the receptor isoform and the structure of the TRE. The expression of this brain nuclear factor is restricted to the perinatal period, when myelination is sensitive to T-3. Gel supershift assays with RXR-specific antibodies indicate that this factor is not one of the known RXR isoforms. However, it is most likely a new member of the RXR subfamily because it could be supershifted with an antibody raised against the highly conserved DNA-binding domain of RXRs. C1 NIDDKD,GENET & BIOCHEM BRANCH,NIH,BETHESDA,MD 20892. NR 47 TC 6 Z9 6 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 AUG PY 1997 VL 138 IS 8 BP 3283 EP 3289 DI 10.1210/en.138.8.3283 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA XL842 UT WOS:A1997XL84200027 PM 9231779 ER PT J AU Zhu, XJ Bavari, S Ulrich, R SadeghNasseri, S Ferrone, S McHugh, L Mage, M AF Zhu, XJ Bavari, S Ulrich, R SadeghNasseri, S Ferrone, S McHugh, L Mage, M TI A recombinant single-chain human class II MHC molecule (HLA-DR1) as a covalently linked heterotrimer of a chain, beta chain, and antigenic peptide, with immunogenicity in vitro and reduced affinity for bacterial superantigens SO EUROPEAN JOURNAL OF IMMUNOLOGY LA English DT Article DE single-chain; HLA-DR1; covalent peptide; superantigen ID T-CELL RECEPTOR; SHOCK SYNDROME TOXIN-1; HISTOCOMPATIBILITY ANTIGEN; HLA-DR; 3-DIMENSIONAL STRUCTURE; MONOCLONAL-ANTIBODIES; EXPRESSION; BINDING; EPITOPES; SPECIFICITY AB Major histocompatibility complex (MHC) class II molecules bind to numerous peptides and display these on the cell surface for T cell recognition. In a given immune response, receptors on T cells recognize antigenic peptides that are a minor population of MHC class II-bound peptides. To control which peptides are presented to T cells, it may be desirable to use recombinant MHC molecules with covalently bound antigenic peptides. To study T cell responses to such homogenous peptide-MHC complexes, we engineered an HLA-DR1 cDNA coding for influenza hemagglutinin, influenza matrix, or HIV p24 gag peptides oo covalently attached via a peptide spacer to the N terminus of the DR1 beta chain. Co-transfection with DR alpha cDNA into mouse L cells resulted in surface expression of HLA-DR1 molecules that reacted with monoclonal antibodies (mAb) specific for correctly folded HLA-DR epitopes. This suggested that the spacer and peptide did not alter expression or folding of the molecule. We then engineered an additional peptide spacer between the C terminus of a truncated beta chain (without transmembrane or cytoplasmic domains) and the N terminus of full-length DR alpha chain. Transfection of this cDNA into mouse L cells resulted in surface expression of the entire covalently linked heterotrimer of peptide, beta chain, and alpha chain with the expected molecular mass of approximately 66 kDa. These single-chain HLA-DR1 molecules reacted with mAb specific for correctly folded HLA-DR epitopes, and identified one mAb with [MHC + peptide] specificity. Affinity-purified soluble secreted single-chain molecules with truncated alpha chain moved in electrophoresis as compact class II MHC dimers. Cell surface two-chain or single-chain HLA-DR1 molecules with a covalent HA peptide stimulated HLA-DR1-restricted HA-specific T cells. They were immunogenic in vitro for peripheral blood mononuclear cells. The two-chain and single-chain HLA-DR1 molecules with covalent HA peptide had reduced binding for the bacterial superantigens staphylococcal enterotoxin A and B and almost no binding for toxic shock syndrome toxin-1. The unique properties of these engineered HLA-DR1 molecules may facilitate our understanding of the complex nature of antigen recognition and aid in the development of novel vaccines with reduced superantigen binding. C1 NCI,BIOCHEM LAB,DCBDC,NIH,BETHESDA,MD 20892. FCRDC,AMRIID,DEPT BIOCHEM & CELL BIOL,FREDERICK,MD. JOHNS HOPKINS UNIV,DEPT PATHOL,BALTIMORE,MD. NEW YORK MED COLL,DEPT MICROBIOL & IMMUNOL,VALHALLA,NY 10595. NR 45 TC 8 Z9 8 U1 0 U2 1 PU VCH PUBLISHERS INC PI DEERFIELD BEACH PA 303 NW 12TH AVE, DEERFIELD BEACH, FL 33442-1788 SN 0014-2980 J9 EUR J IMMUNOL JI Eur. J. Immunol. PD AUG PY 1997 VL 27 IS 8 BP 1933 EP 1941 DI 10.1002/eji.1830270817 PG 9 WC Immunology SC Immunology GA XQ080 UT WOS:A1997XQ08000016 PM 9295029 ER PT J AU Curiel, RE Lahesmaa, R Subleski, J Cippitelli, M Kirken, RA Young, HA Ghosh, P AF Curiel, RE Lahesmaa, R Subleski, J Cippitelli, M Kirken, RA Young, HA Ghosh, P TI Identification of a Stat-6-responsive element in the promoter of the human interleukin-4 gene SO EUROPEAN JOURNAL OF IMMUNOLOGY LA English DT Article DE Stat-6; interleukin-4; interleukin-13 ID CD4+ T-CELLS; INTERFERON-GAMMA; DNA-BINDING; IL-4; TRANSCRIPTION; LYMPHOKINE; CYTOKINE; INVITRO; SUBSETS; STAT AB Interleukin (IL)-4 is an immunomodulatory cytokine produced by a number of cell types including T cells, basophils, and mast cells. This pleiotropic cytokine has a number of immunoregulatory functions; however, the molecular mechanisms controlling the transcription of this gene are nor yet completely understood. Several studies have implicated a possible autoregulatory mechanism for its own expression. Here, we have identified a Stat-6-responsive element (Stat-6RE) in the promoter of the human IL-4 gene. Utilizing electrophoretic mobility shift analysis, we have demonstrated the presence of two specific IL-4-responsive DNA-protein complexes in nuclear extracts of both human Th1 and Th2 clones. Phytohemagglutinin-blasted peripheral blood T cells also generated an inducible complex in response to stimulation with IL-4 and the IL-4-like cytokine IL-13. Transient transfection of the murine pre-B cell line BA/F3 stably transfected with the full-length human IL-4 receptor alpha chain demonstrated the ability of multicopy Stat-6RE to initiate transcription from a heterologous promoter upon IL-4 or IL-13 stimulation. These results indicate a possible autocrine mechanism for the regulation of IL-4 gene transcription through the Stat-6RF, as well as a possible mechanism for IL-13 regulation of the human IL-4 promoter. C1 NCI,FREDERICK CANC RES & DEV CTR,EXPT IMMUNOL LAB,DIV BASIC SCI,FREDERICK,MD. NCI,FREDERICK CANC RES & DEV CTR,INTRAMURAL RES SUPPORT PROGRAM,SAIC FREDERICK,FREDERICK,MD. ROCHE BIOSCI,DEPT LEUKOCYTE BIOL,PALO ALTO,CA. OI CIPPITELLI, Marco/0000-0002-9620-538X NR 37 TC 42 Z9 42 U1 0 U2 1 PU VCH PUBLISHERS INC PI DEERFIELD BEACH PA 303 NW 12TH AVE, DEERFIELD BEACH, FL 33442-1788 SN 0014-2980 J9 EUR J IMMUNOL JI Eur. J. Immunol. PD AUG PY 1997 VL 27 IS 8 BP 1982 EP 1987 DI 10.1002/eji.1830270823 PG 6 WC Immunology SC Immunology GA XQ080 UT WOS:A1997XQ08000022 PM 9295035 ER PT J AU Pickworth, WB Rohrer, MS Fant, RV AF Pickworth, WB Rohrer, MS Fant, RV TI Effects of abused drugs on psychomotor performance SO EXPERIMENTAL AND CLINICAL PSYCHOPHARMACOLOGY LA English DT Article ID VIGILANCE PERFORMANCE; MARIJUANA SMOKING; ALCOHOL; AMPHETAMINE; PROFILES; BEHAVIOR; HUMANS AB Some abused drugs have been reported to alter performance on naturalistic tasks such as driving and also on laboratory tasks. The performance effects of several drug classes were examined using a repeated measures design. Eight volunteers were administered 2 doses of ethanol, marijuana, amphetamine, hydromorphone, pentobarbital, or placebo on separate days. The larger dose of each increased subjective drug strength; however, only ethanol and pentobarbital impaired performance on circular lights, digit symbol substitution, and serial math tasks. Both ethanol and pentobarbital impaired performance on card-sorting tasks; impairment was evident at lower doses as the cognitive load increased. Results illustrate differences among drugs in producing performance impairment at doses that cause subjective effects. Increasing cognitive requirements uncovered performance impairment at lower doses. RP Pickworth, WB (reprint author), NIDA,ADDICT RES CTR,INTRAMURAL RES PROGRAM,POB 5180,BALTIMORE,MD 21224, USA. NR 33 TC 19 Z9 19 U1 2 U2 6 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 SN 1064-1297 J9 EXP CLIN PSYCHOPHARM JI Exp. Clin. Psychopharmacol. PD AUG PY 1997 VL 5 IS 3 BP 235 EP 241 DI 10.1037//1064-1297.5.3.235 PG 7 WC Psychology, Biological; Psychology, Clinical; Pharmacology & Pharmacy; Psychiatry SC Psychology; Pharmacology & Pharmacy; Psychiatry GA XQ341 UT WOS:A1997XQ34100006 PM 9260070 ER PT J AU Granholm, AC Mott, JL Bowenkamp, K Eken, S Henry, S Hoffer, BJ Lapchak, PA Palmer, MR vanHorne, C Gerhardt, GA AF Granholm, AC Mott, JL Bowenkamp, K Eken, S Henry, S Hoffer, BJ Lapchak, PA Palmer, MR vanHorne, C Gerhardt, GA TI Glial cell line-derived neurotrophic factor improves survival of ventral mesencephalic grafts to the 6-hydroxydopamine lesioned striatum SO EXPERIMENTAL BRAIN RESEARCH LA English DT Article DE glial cell line-derived neurotrophic factor; striatum; nigrostriatal dopaminergic pathway; transplants; neurotrophic factors ID NERVE GROWTH-FACTOR; MIDBRAIN DOPAMINERGIC-NEURONS; GDNF MESSENGER-RNA; PARKINSONS-DISEASE; SUBSTANTIA-NIGRA; IN-VIVO; NEURAL TRANSPLANTATION; BEHAVIORAL RECOVERY; ROTATIONAL BEHAVIOR; RET PROTOONCOGENE AB One approach to replace lost dopaminergic neurons in Parkinson's disease is to transplant fetal mesencephalic tissue into the striatum. In an attempt to expand the developmental window useful for grafting of mesencephalic tissue and increase the fiber outgrowth from grafted dopaminergic neurons, we have pretreated fetal mesencephalic tissue with the dopaminotrophic factor glial cell line-derived neurotrophic factor (GDNF). Mesencephalic tissue pieces from embryonic day 18-19 Fischer 344 rats were preincubated for 20 min with GDNF (1 mu g/mu l) or vehicle. Two tissue pieces were then transplanted into the striatum of rats that had been unilaterally lesioned by medial forebrain bundle injections of 6-hydroxydopamine, The animals were tested for apomorphine-induced rotations prior to intracranial grafting. Host rats received intrastriatal injections of 10 mu g GDNF or control solution at 10 days and 4 weeks postgrafting. The animals were tested in the rotometer twice monthly following transplantation. Despite the fact that these transplants were from a suboptimal donor stage, the rotations were significantly decreased in both transplanted groups. Immunohistochemical evaluation of the host brains revealed that the overall size of transplanted mesencephalic tissue was significantly increased in the GDNF-treated animals, and that the average size of transplanted tyrosine hydroxylase (TH)-positive neurons was also increased. Furthermore, we found that the innervation density of surrounding host striatal tissue was significantly increased in the GDNF-treated group, as compared with controls. Taken together, these results suggest that treatment of intrastriatal ventral mesencephalon grafts with GDNF can optimize the conditions for intracranial grafting and thus improve the chances for functional recovery following the intrastriatal grafting procedure. C1 UNIV COLORADO,HLTH SCI CTR,DEPT PHARMACOL,DENVER,CO 80262. UNIV COLORADO,HLTH SCI CTR,DEPT PSYCHIAT,DENVER,CO 80262. UNIV COLORADO,HLTH SCI CTR,NEUROSCI TRAINING PROGRAM,DENVER,CO 80262. NIDA,INTRAMURAL RES PROGRAM,BALTIMORE,MD. AMGEN INC,DEPT NEUROSCI,THOUSAND OAKS,CA 91320. HARVARD UNIV,BRIGHAM & WOMENS HOSP,SCH MED,BOSTON,MA 02115. RP Granholm, AC (reprint author), UNIV COLORADO,HLTH SCI CTR,DEPT BASIC SCI,BOX C286,DENVER,CO 80262, USA. OI Lapchak, Paul/0000-0003-4413-7554 FU NIA NIH HHS [AG12122, AG04418]; NIMH NIH HHS [MH49661] NR 73 TC 77 Z9 78 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0014-4819 J9 EXP BRAIN RES JI Exp. Brain Res. PD AUG PY 1997 VL 116 IS 1 BP 29 EP 38 DI 10.1007/PL00005741 PG 10 WC Neurosciences SC Neurosciences & Neurology GA XT503 UT WOS:A1997XT50300005 PM 9305812 ER PT J AU Lowy, RJ Dimitrov, DS AF Lowy, RJ Dimitrov, DS TI Characterization of influenza virus-induced death of J774.1 macrophages SO EXPERIMENTAL CELL RESEARCH LA English DT Article ID TUMOR-NECROSIS-FACTOR; COLONY-STIMULATING FACTOR; PROGRAMMED CELL-DEATH; NF-KAPPA-B; A VIRUS; INFECTED MACROPHAGES; VIRAL-INFECTIONS; APOPTOSIS; LINE; ACTIVATION AB The mechanism and role of influenza virus (IV)-induced pathogenesis of macrophages during respiratory infection are ill defined. Reported here are findings on IV-induced cytopathic effects (CPEs) for an in vitro experimental system using the murine macrophage cell line J774.1. CPE was elicited by 0.2 or greater multiplicity of infection (m.o.i.). CPEs showed a lag of 6-8 h postinfection and occurred most rapidly between 6 and 12 h. J774.1 cells did not support productive IV replication, but immunofluorescence demonstrated that IV protein synthesis occurred. Light microscopy and DNA staining showed that after death cells had very condensed cytoplasm and nuclei. Cell remnants were surrounded by intact plasma membrane (PM) as demonstrated by exclusion of a membrane-impermeant dye. Time-lapse video microscopy recordings between 6 and 10 h postinfection showed sequential structural changes, including previously undescribed events. Notable changes were a rapid cytokinesis (zeiosis; ''cell boiling''), followed by nuclear shrinkage, and an unusual transient blebbing of the PM. DNA fragmentation occurred after 12 h, producing a wide size range, UV-inactivated virus failed to induce CPEs, and CPE was blocked by amantadine, N-Acetylcysteine and pyrrolidine dithiocarbamate, but not other inhibitors of reactive oxygen intermediates, reduced or blocked the CPE. Most changes observed are those attributed to apoptotic processes rather than necrotic cell death, The kinetics and inhibitor effects suggest that IV infection and replication must be initiated to activate CPEs. C1 NCI,SECT MEMBRANE STRUCT & FUNCT,NIH,BETHESDA,MD 20892. RP Lowy, RJ (reprint author), ARMED FORCES RADIOBIOL RES INST,RADIAT PATHOPHYSIOL & TOXICOL DEPT,8901 WISCONSIN AVE,BETHESDA,MD 20889, USA. FU NIAID NIH HHS [AI 35892] NR 54 TC 35 Z9 37 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 0014-4827 J9 EXP CELL RES JI Exp. Cell Res. PD AUG 1 PY 1997 VL 234 IS 2 BP 249 EP 258 DI 10.1006/excr.1997.3602 PG 10 WC Oncology; Cell Biology SC Oncology; Cell Biology GA XQ585 UT WOS:A1997XQ58500008 PM 9260892 ER PT J AU Zhu, WY Jones, CS Kiss, A Matsukuma, K Amin, S De Luca, LM AF Zhu, WY Jones, CS Kiss, A Matsukuma, K Amin, S De Luca, LM TI Retinoic acid inhibition of cell cycle progression in MCF-7 human breast cancer cells SO EXPERIMENTAL CELL RESEARCH LA English DT Article ID RETINOBLASTOMA PROTEIN; TRANSCRIPTION FACTOR; KINASE-ACTIVITY; GROWTH; IDENTIFICATION; FIBROBLASTS; ACTIVATION; EXPRESSION; PHASE; AMPLIFICATION AB Cell cycle analysis indicates that retinoic acid (RA) inhibition of MCF-7 cell growth occurs through induction of G1 arrest with a concomitant reduction in the proportion of cells in S and G2 + M phases. RA did not affect cyclins D1, A, and E and cyclin-dependent kinase 2 (CDK2) expression, but significantly reduced cyclin D3 and CDK4 expression after 24 h. RA also inhibited cyclin B1 and CDC2 expression, possibly responsible for the reduction of the proportion of cells in G2 + M and S phases, RA did not induce p16 and p27 expression, but obviously reduced p21 level in MCF-7 cells, The retinoid markedly reduced pRB protein level and abrogated pRB phosphorylation after 48 h; it also reduced transcription factor E2F1 expression at both the mRNA and protein levels. E2F1 promoter activity was reduced by 60%, which is probably responsible, at least in part, for the reduction of E2F1 expression in RA-treated MCF-7 cells. These observations demonstrate a marked effect of RA on some of the key cell cycle regulatory proteins in MCF-7 cells. Cyclin D3 and CDK4 are likely the early targets of RA, followed by reduced pRB expression and phosphorylation, as well as by the inhibition of the E2F1 transcription factor which controls progression from G1 to S phase. Most of these events precede the observed reduction in MCF-7 cell growth, which begins at Day 3 of RA treatment. (C) 1997 Academic Press. C1 NCI, CELLULAR CARCINOGENESIS & TUMOR PROMOT LAB, BETHESDA, MD 20892 USA. NR 41 TC 78 Z9 81 U1 0 U2 2 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0014-4827 J9 EXP CELL RES JI Exp. Cell Res. PD AUG 1 PY 1997 VL 234 IS 2 BP 293 EP 299 DI 10.1006/excr.1997.3589 PG 7 WC Oncology; Cell Biology SC Oncology; Cell Biology GA XQ585 UT WOS:A1997XQ58500013 PM 9260897 ER PT J AU Shao, RG Shimizu, T Pommier, Y AF Shao, RG Shimizu, T Pommier, Y TI 7-hydroxystaurosporine (UCN-01) induces apoptosis in human colon carcinoma and leukemia cells independently of p53 SO EXPERIMENTAL CELL RESEARCH LA English DT Article ID PROTEIN-KINASE-C; TOPOISOMERASE-II INHIBITORS; DNA FRAGMENTATION; HL-60 CELLS; SELECTIVE INHIBITOR; POLY(ADP-RIBOSE) POLYMERASE; DIFFERENTIAL INDUCTION; ICE/CED-3 PROTEASE; ANTITUMOR-ACTIVITY; IN-VITRO AB 7-hydroxystaurosporine (UCN-01) is a more selective protein kinase C inhibitor than staurosporine. UCN-01 exhibits antitumor activity in experimental tumor models and is presently in clinical trials. Our study reveals that human myeloblastic leukemia HL60 and K562 and colon carcinoma HT29 cells undergo internu cleosomal DNA fragmentation and morphological changes characteristic of apoptosis after UCN-01 treatment. These three cell lines lack functional p53, and K562 and HT29 cells are usually resistant to apoptosis. DNA fragmentation in HT29 and K562 cells occurred after 1 day of treatment while it took less than 4 h in KL60 cells. Cycloheximide prevented UCN-01-induced DNA fragmentation in HT-29 cells, but not in HL60 and K562 cells, suggesting that macromolecular synthesis is selectively required for apoptotic DNA fragmentation in HT29 cells. UCN-01-induced DNA fragmentation was preceded by activation of cyclin B1/cdc2 kinase. Further studies in HL60 cells showed that UCN-01-induced apoptosis was associated with degradation of CPP32, PARP, and lamin B and that the inhibitor of caspases (ICE/CED-3 cysteine proteases), Z-VAD-FMK, and the serine protease inhibitor, DCI, protected HL60 cells from UCN-01-induced DNA fragmentation. However, only DCI and TPCK, but not Z-VAD-FMK, inhibited DNA fragmentation in the HL60 cell-free system, suggesting that serine protease(s) may play a role in the execution phase of apoptosis in HL60 cells treated with UCN-01. Z-VAD-FRIK and DCI also inhibited apoptosis in HT29 cells. These data demonstrate that the protein kinase C inhibitor and antitumor agent, UCN-01 is a potent apoptosis inducer in cell lines that are usually resistant to apoptosis and lack p53 and that caspases and probably serine proteases are activated during UCN-01-induced apoptosis. (C) 1997 Academic Press. C1 NCI,MOL PHARMACOL LAB,DIV BASIC SCI,NIH,BETHESDA,MD 20892. NR 57 TC 82 Z9 86 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 0014-4827 J9 EXP CELL RES JI Exp. Cell Res. PD AUG 1 PY 1997 VL 234 IS 2 BP 388 EP 397 DI 10.1006/excr.1997.3650 PG 10 WC Oncology; Cell Biology SC Oncology; Cell Biology GA XQ585 UT WOS:A1997XQ58500025 PM 9260909 ER PT J AU GrilloLopez, AJ Horning, S Cheson, BD Peterson, B Coiffier, B Hagenbeek, A Hiddeman, W Marcus, R Lister, TA AF GrilloLopez, AJ Horning, S Cheson, BD Peterson, B Coiffier, B Hagenbeek, A Hiddeman, W Marcus, R Lister, TA TI Development of response criteria (RC) for low-grade or follicular lymphomas (LG/F NHL) and application in a 166 patient study. SO EXPERIMENTAL HEMATOLOGY LA English DT Meeting Abstract C1 IDEC PHARMACEUT,SAN DIEGO,CA. STANFORD UNIV,STANFORD,CA 94305. NCI,CTEP,ROCKVILLE,MD. UNIV MINNESOTA,MINNEAPOLIS,MN. CTR HOSP LYON SUD,LYON,FRANCE. DR DANIEL DEN HOED CANC CTR,NL-3008 AE ROTTERDAM,NETHERLANDS. UNIV GOTTINGEN,D-3400 GOTTINGEN,GERMANY. ADDENBROOKES HOSP,CAMBRIDGE,ENGLAND. ST BARTHOLOMEWS HOSP,LONDON,ENGLAND. NR 0 TC 0 Z9 0 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 AUG PY 1997 VL 25 IS 8 BP 17 EP 17 PG 1 WC Hematology; Medicine, Research & Experimental SC Hematology; Research & Experimental Medicine GA XR330 UT WOS:A1997XR33000017 ER PT J AU Samokhvalov, I Hendrikx, PJ Visser, JWM Belyavsky, AV Sotiropoulos, PJ Gu, H AF Samokhvalov, I Hendrikx, PJ Visser, JWM Belyavsky, AV Sotiropoulos, PJ Gu, H TI Hematopoiesis in mice lacking a functional CHK gene is essentially normal. SO EXPERIMENTAL HEMATOLOGY LA English DT Meeting Abstract C1 NEW YORK BLOOD CTR,NEW YORK,NY 10021. VA ENGELHARDT MOL BIOL INST,MOSCOW 117984,RUSSIA. NIAID,NIH,ROCKVILLE,MD. RI Samokhvalov, Igor/J-8196-2013 NR 0 TC 0 Z9 0 U1 0 U2 1 PU CARDEN JENNINGS PUBL CO LTD PI CHARLOTTESVILLE PA BLAKE CTR, STE 200, 1224 W MAIN ST, CHARLOTTESVILLE, VA 22903 SN 0301-472X J9 EXP HEMATOL JI Exp. Hematol. PD AUG PY 1997 VL 25 IS 8 BP 171 EP 171 PG 1 WC Hematology; Medicine, Research & Experimental SC Hematology; Research & Experimental Medicine GA XR330 UT WOS:A1997XR33000165 ER PT J AU Misiewicz, B Poltorak, M Raybourne, RB Gomez, M Listwak, S Sternberg, EM AF Misiewicz, B Poltorak, M Raybourne, RB Gomez, M Listwak, S Sternberg, EM TI Intracerebroventricular transplantation of embryonic neuronal tissue from inflammatory resistant into inflammatory susceptible rats suppresses specific components of inflammation SO EXPERIMENTAL NEUROLOGY LA English DT Article ID PITUITARY-ADRENAL AXIS; CORTICOTROPIN-RELEASING FACTOR; SYMPATHETIC NERVOUS-SYSTEM; CD4+ T-CELLS; LEWIS RATS; IMMUNE INTERACTIONS; INTERLEUKIN-1; ACTIVATION; BRAIN; MODULATION AB To more directly define the role of central nervous system factors in susceptibility to peripheral inflammatory disease, we examined the effect of intracerebroventricular transplantation of neuronal tissue from inflammatory resistant into inflammatory susceptible rats on subcutaneous carrageenan-induced inflammation (a measure of innate immunity), and on the relative percentage of naive and memory T helper cells in peripheral blood (a measure of the anamnestic immune response). Female inflammatory disease susceptible Lewis (LEW/N) rats transplanted with hypothalamic tissue from inflammatory resistant Fischer (F344/N) rats exhibited > 85% decrease in carrageenan inflammation compared to naive LEW/N rats, LEW/N rats transplanted with F344/N spinal cord, or sham-operated animals. LEW/N rats transplanted with LEW/N hypothalamic tissue exhibited > 50% decrease in carrageenan inflammation. In contrast, intracerebroventricular transplantation of neuronal tissue did not affect the characteristically twofold higher percentage of naive versus memory T helper cells in LEW/N rats, suggesting that the central nervous system (CNS) and hypothalamus play a greater role in the innate inflammatory response than in the acquired immune processes. Grafted tissue survived well and did not show extensive gliosis or inflammation. Compared to naive LEW/N rats, LEW/N rats transplanted with F344/N or LEW/N hypothalamic tissue expressed significantly greater hypothalamic corticotropin releasing hormone mRNA. LEW/N rats transplanted with F344/N hypothalamic tissue also showed significant increases in plasma corticosterone responses to lipopolysaccharide. These data indicate that intracerebroventricular transplantation of fetal hypothalamic tissue from inflammatory resistant into inflammatory susceptible rats suppresses peripheral inflammation partially through hypothalamic factors. These findings have implications for understanding the contribution of specific neuronal tissue in regulation of components of the immune/inflammatory response and in susceptibility to inflammatory disease. Furthermore, this model could be used in the development of potential new treatments for inflammatory/autoimmune diseases aimed specifically at sites within the CNS. (C) 1997 Academic Press. C1 NIMH,CLIN NEUROENDOCRINOL BRANCH,BETHESDA,MD 20892. GEORGE WASHINGTON UNIV,DEPT NEUROL,WASHINGTON,DC 20037. NIMH,PRECLIN NEUROSCI SECT,BETHESDA,MD 20892. US FDA,IMMUNOBIOL BRANCH,LAUREL,MD 20708. NR 42 TC 29 Z9 29 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0014-4886 J9 EXP NEUROL JI Exp. Neurol. PD AUG PY 1997 VL 146 IS 2 BP 305 EP 314 DI 10.1006/exnr.1997.6446 PG 10 WC Neurosciences SC Neurosciences & Neurology GA XR256 UT WOS:A1997XR25600002 PM 9270039 ER PT J AU Pazman, C Bengzon, J McKay, RDG Somogyi, R AF Pazman, C Bengzon, J McKay, RDG Somogyi, R TI Novel differentially expressed genes induced by kainic acid in hippocampus: Putative molecular effectors of plasticity and injury SO EXPERIMENTAL NEUROLOGY LA English DT Article ID TEMPORAL-LOBE EPILEPSY; FACTOR MESSENGER-RNA; NERVE GROWTH-FACTOR; RAT DENTATE GYRUS; C-FOS EXPRESSION; NEUROTROPHIC FACTOR; INDUCED SEIZURES; GRANULE CELLS; TRANSCRIPTION FACTORS; STATUS-EPILEPTICUS AB Systemic kainic acid administration in rats induces acute limbic status epilepticus and subsequent neuronal degeneration and development of chronic hyperexcitability with similarities to human temporal lobe epilepsy, The mechanisms mediating the responses to kainic acid likely involve transcriptional changes in genes of importance for cellular injury, protection, and plasticity. We have used an arbitrarily primed PCR technique to identify such changes in the rat dentate gyrus, Three previously uncharacterized transcripts were found to be upregulated in the dentate gyrus 4 h following systemic kainic acid. In situ hybridization using riboprobes transcribed from the cloned PCR fragments were used to confirm differential expression specifically in dentate granule neurons following seizure. Basal expression for all three transcripts is widespread throughout the rat brain, with the highest levels seen in the hippocampal pyramidal and granule cell layers. The novel sequences do not match any known full-length cDNAs and may belong to novel gene families. However, they all showed high homology to human partial cDNA sequences (ESTs) that are expressed in brain as well as several other tissues. Two additional transcripts identified in this study corroborate earlier findings on differential expression of heat-shock proteins after seizure. The navel transcripts found in this study may be involved in epileptogenesis and neuronal responses to damage following seizure. (C) 1997 Academic Press. C1 NINCDS,NEUROPHYSIOL LAB,BETHESDA,MD 20892. NINCDS,MOL BIOL LAB,NIH,BETHESDA,MD 20892. NR 59 TC 11 Z9 11 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 0014-4886 J9 EXP NEUROL JI Exp. Neurol. PD AUG PY 1997 VL 146 IS 2 BP 502 EP 512 DI 10.1006/exnr.1997.6566 PG 11 WC Neurosciences SC Neurosciences & Neurology GA XR256 UT WOS:A1997XR25600024 PM 9270061 ER PT J AU Steven, AC Trus, BL Booy, FP Cheng, NQ Zlotnick, A Caston, JR Conway, JF AF Steven, AC Trus, BL Booy, FP Cheng, NQ Zlotnick, A Caston, JR Conway, JF TI The making and breaking of symmetry in virus capsid assembly: glimpses of capsid biology from cryoelectron microscopy SO FASEB JOURNAL LA English DT Review DE procapsid; symmetry; bacteriophage; antiviral ID STRUCTURAL TRANSITIONS; MOLECULAR COMPOSITION; ANGSTROM RESOLUTION; ICOSAHEDRAL VIRUS; CRYSTAL-STRUCTURE; SIMIAN VIRUS-40; RECONSTRUCTION; REPLICATION; MATURATION; PROTEIN AB Virus capsids constitute a diverse and versatile family of protein-bound containers and compartments ranging in diameter from Angstrom 200 Angstrom (mass similar to 1 MDa) to >1500 Angstrom (mass>250 MDa). Cryoelectron microscopy of capsids, now attaining resolutions down to 10 Angstrom, is disclosing novel structural motifs, assembly mechanisms, and the precise locations of major epitopes. Capsids are essentially symmetric structures, and icosahedral surface lattices have proved to be widespread, However, many capsid proteins exhibit a remarkable propensity for symmetry breaking, whereby chemically identical subunits in distinct lattice sites have markedly different structures and packing relationships. Temporal differences in the conformation of a given subunit are also manifested in the large-scale conformational changes that accompany capsid maturation. Larger and more complex capsids, such as DNA bacteriophages and herpes simplex virus, are formed not by simple self-assembly, but under the control of tightly regulated programs that may include the involvement of viral scaffolding proteins and cellular chaperonins, maturational proteolysis, and conformational changes on an epic scale. In addition to its significance for virology, capsid-related research has implications for biology in general, relating to the still largely obscure assembly processes of macromolecular complexes that perform many important cellular functions. C1 NIAMSD, PROT EXPRESS LAB, NIH, BETHESDA, MD 20892 USA. NIH, COMPUTAT BIOL & ENGN LAB, DIV COMP RES & TECHNOL, BETHESDA, MD 20892 USA. RP Steven, AC (reprint author), NIAMSD, STRUCT BIOL LAB,NIH,BLDG 6,RM B2-34, 6 CENTER DR MSC 2717, BETHESDA, MD 20892 USA. RI Conway, James/A-2296-2010; Caston, Jose/L-5896-2014 OI Conway, James/0000-0002-6581-4748; Caston, Jose/0000-0003-2350-9048 NR 75 TC 39 Z9 39 U1 1 U2 5 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD AUG PY 1997 VL 11 IS 10 BP 733 EP 742 PG 10 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA XR105 UT WOS:A1997XR10500003 PM 9271358 ER PT J AU Chen, XG Brining, SK Nguyen, VQ Yergey, AL AF Chen, XG Brining, SK Nguyen, VQ Yergey, AL TI Simultaneous assessment of conformation and aggregation of beta-amyloid peptide using electrospray ionization mass spectrometry SO FASEB JOURNAL LA English DT Article DE protein conformation; protein aggregation; Alzheimer disease ID AMINO-TERMINAL FRAGMENT; ALZHEIMERS-DISEASE; SECONDARY STRUCTURE; SENILE PLAQUES; CORE PROTEIN; IN-VITRO; DEPOSITION; DETERMINANTS; TRANSITION; PATHOLOGY AB Electrospray ionization mass spectrometry was used to study conformation and aggregation of the synthetic beta-amyloid peptide, residues 140 (beta A4), as a function of concentration and sample aging, All mass spectra showed a major envelope of peaks corresponding to charge states of 7-3 of the monomeric form of beta A4, In addition, weaker envelopes of peaks corresponding to charge states of dimeric, trimeric, and tetrameric beta A4 species were seen under gentle ionization conditions, The average charge state of the envelope associated with the monomeric form decreased by ca. 0.5 z as samples were aged, indicating that the relatively open form (likely random coil) of the peptide was modified into the more compact form (likely beta-sheet) as a function of sample aging, The aggregate forms became weaker and ultimately were absent both in the more dilute solutions and in aged aliquots of the concentrated sample, These aggregates were interpreted as assemblies of the random coil form, We interpret our inability to see an ion envelope that can be associated with aggregates of the beta-sheet form to be a consequence of the presumed very compact nature of this form, A model for the formation of beta A4 fibrils is proposed and discussed. C1 NICHHD,BETHESDA,MD 20892. NIA,NEUROSCI LAB,BETHESDA,MD 20892. NR 51 TC 19 Z9 19 U1 0 U2 3 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 AUG PY 1997 VL 11 IS 10 BP 817 EP 823 PG 7 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA XR105 UT WOS:A1997XR10500012 PM 9271367 ER PT J AU Krause, R AF Krause, R TI Microbial factors in disease emergence illustrated by streptococcal toxic shock syndrome SO FEMS IMMUNOLOGY AND MEDICAL MICROBIOLOGY LA English DT Article; Proceedings Paper CT Conference on Emerging Diseases CY APR, 1997 CL TOKYO, JAPAN SP US Japan Cooperat Med Sci Program DE microbial factors in emerging diseases; streptococcal toxic shock syndrome; scarlet fever ID PYOGENES; INFECTIONS; DIVERSITY RP Krause, R (reprint author), NIH,FOGARTY INT CTR,BLDG 16,ROOM 202B,BETHESDA,MD 20892, USA. NR 20 TC 5 Z9 5 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0928-8244 J9 FEMS IMMUNOL MED MIC JI FEMS Immunol. Med. Microbiol. PD AUG PY 1997 VL 18 IS 4 BP 227 EP 232 DI 10.1016/S0928-8244(97)00052-7 PG 6 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA XX747 UT WOS:A1997XX74700003 PM 9348157 ER PT J AU James, SL AF James, SL TI Emerging parasitic infections SO FEMS IMMUNOLOGY AND MEDICAL MICROBIOLOGY LA English DT Article; Proceedings Paper CT Conference on Emerging Diseases CY APR, 1997 CL TOKYO, JAPAN SP US Japan Cooperat Med Sci Program DE emerging parasitic diseases; Cryptosporidium parvum; Cyclospora cayetanensis; Enterocytozoon bieneusi; Septata intestinalis; Acanthamoeba; Leishmania mexicana; Trypanosoma cruzi; Taenia salium; Echinococcus multilocularis ID MENINGOENCEPHALITIS; CRYPTOSPORIDIUM; HUMANS RP James, SL (reprint author), NIAID,DIV MICROBIOL & INFECT DIS,NIH,SOLAR BLDG,ROOM 3A10,6003 EXECUT BLVD,BETHESDA,MD 20892, USA. NR 16 TC 3 Z9 3 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0928-8244 J9 FEMS IMMUNOL MED MIC JI FEMS Immunol. Med. Microbiol. PD AUG PY 1997 VL 18 IS 4 BP 313 EP 317 DI 10.1016/S0928-8244(97)00063-1 PG 5 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA XX747 UT WOS:A1997XX74700014 PM 9348168 ER PT J AU Fowler, RG Schaaper, RM AF Fowler, RG Schaaper, RM TI The role of the mutT gene of Escherichia coli in maintaining replication fidelity SO FEMS MICROBIOLOGY REVIEWS LA English DT Review DE mutT mutator; replication fidelity; mutagenic oxidative damage; A center dot T->C center dot G transversion; nucleoside triphosphatase; A center dot G mispairing ID DNA POLYMERASE-III; NUCLEOSIDE TRIPHOSPHATE PYROPHOSPHOHYDROLASE; GENERATES G.C->T.A TRANSVERSIONS; SINGLE-STRANDED-DNA; SPONTANEOUS MUTATION; MISMATCH REPAIR; STREPTOCOCCUS-PNEUMONIAE; SPONTANEOUS MUTAGENESIS; MAGNETIC-RESONANCE; IONIZING-RADIATION AB Spontaneous mutation levels are kept low in most organisms by a variety of error-reducing mechanisms, some of which ensure a high level of fidelity during DNA replication. The mutT gene of Escherichia coli is an important participant in avoiding such replication mistakes. An inactive mutT allele is a strong mutator with strict mutational specificity: only A.T --> C.G transversions are enhanced. The biological role of the MutT protein is thought to be the prevention of A.G mispairs during replication, specifically the mispair involving a template A and an oxidized form of guanine, 8-oxoguanine, which results when the oxidized form of dGTP, 8-oxodGTP, is available as a polymerase substrate. MutT is part of an elaborate defense system that protects against the mutagenic effects of oxidized guanine as a part of substrate dGTP and chromosomal DNA. The A.G mispairings prevented by MutT are not well-recognized and/or repaired by other fidelity mechanisms such as proofreading and mismatch repair, accounting in part for the high mutator activity of mutT. MutT is a nucleoside triphosphatase with a preference for the syn form of dGTP, hydrolyzing it to dGMP and pyrophosphate. 8-oxodGTP is hydrolyzed 10 times faster than dGTP, making it a likely biological substrate for MutT. MutT is assumed to hydrolyze 8-oxodGTP in the nucleotide pool before it can be misincorporated. While the broad role of MutT in error avoidance seems resolved, important details that are still unclear are pointed out in this review. C1 NIEHS,MOL GENET LAB,RES TRIANGLE PK,NC 27709. RP Fowler, RG (reprint author), SAN JOSE STATE UNIV,DEPT BIOL SCI,SAN JOSE,CA 95192, USA. NR 89 TC 44 Z9 45 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0168-6445 J9 FEMS MICROBIOL REV JI Fems Microbiol. Rev. PD AUG PY 1997 VL 21 IS 1 BP 43 EP 54 DI 10.1111/j.1574-6976.1997.tb00344.x PG 12 WC Microbiology SC Microbiology GA XV138 UT WOS:A1997XV13800003 PM 9299701 ER PT J AU Chapin, RE Sloane, RA Haseman, JK AF Chapin, RE Sloane, RA Haseman, JK TI The relationships among reproductive endpoints in Swiss mice, using the reproductive assessment by continuous breeding database SO FUNDAMENTAL AND APPLIED TOXICOLOGY LA English DT Article ID SPERM MOTION; FERTILITY; RATS; EPICHLOROHYDRIN AB The database of Continuous Breeding mouse studies was evaluated to determine the relationships between the functional indicators of reproduction (pup measures) and the various necropsy endpoints collected for males and females. Of 72 chemicals studied, both males and females were affected in 33 studies, while females and/or conceptuses were affected in 7, Two compounds affected only males, 17 studies were negative, and in 13 studies with effects it was not possible to clearly determine the affected gender(s), Greater F-0 dam weight was correlated with increased pup mass per litter; this relationship was strongest for the first litter, and weakest for the fifth litter. For both generations of treated females (F-0 and F-1), longer estrous cycles correlated with reduced numbers of pups; the relationship was stronger in F-0 than in F( )females and was not seen in controls. Sperm parameters had different distributions in treated mice than in control mice. Fertility (total live pups/number of pairs cohabited) was reduced if there were > similar to 15% sperm abnormalities or if sperm motility (moving/ not moving) was < approximate to 37%. Both of these relationships appeared to have thresholds. Epididymal sperm count in treated animals, however, was linearly related to fertility, even within the control range, suggesting strongly that other factors are important. Using both treated and control data together, combining sperm count with motility could explain much (r = 0.77) of the variation in fertility; adding morphology did not significantly improve the correlation, The model was almost as strong using count and morphology, in which case adding motility did not strengthen the model, This analysis of these studies shows that while some endpoints (e.g., random-estrous-cycle-point ovary weight) correlate poorly with fertility, other necropsy endpoints (epididymal sperm count and motility, estrous cycle length, and testis and epididymal weights) can be useful (though not complete) surrogates of overall reproductive function, Indeed, over many studies, epididymal sperm count in treated animals correlates with fertility so well that even small reductions (approximate to 20%) in count result in reduced fertility, suggesting that mice may be better models of human fertility than was previously believed. (C) 1997 Society of Toxicology. C1 NIEHS,STAT & BIOMATH BRANCH,RES TRIANGLE PK,NC 27709. RP Chapin, RE (reprint author), NIEHS,REPROD TOXICOL GRP,ENVIRONM TOXICOL PROGRAM,POB 12233,RES TRIANGLE PK,NC 27709, USA. OI Chapin, Robert/0000-0002-5997-1261 NR 20 TC 50 Z9 53 U1 5 U2 14 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0272-0590 J9 FUND APPL TOXICOL JI Fundam. Appl. Toxicol. PD AUG PY 1997 VL 38 IS 2 BP 129 EP 142 DI 10.1006/faat.1997.2341 PG 14 WC Toxicology SC Toxicology GA XZ216 UT WOS:A1997XZ21600004 PM 9299186 ER PT J AU Almekinder, JL Lennard, DE Walmer, DK Davis, BJ AF Almekinder, JL Lennard, DE Walmer, DK Davis, BJ TI Toxicity of methoxyacetic acid in cultured human luteal cells SO FUNDAMENTAL AND APPLIED TOXICOLOGY LA English DT Article ID EXPERIMENTAL HUMAN EXPOSURE; GLYCOL MONOMETHYL ETHER; SPONTANEOUS-ABORTION; GRANULOSA-CELLS; MONOETHYL ETHER; RAT AB Ethylene glycol monomethyl ether (EGME) and its proximate metabolite, 2-methoxyacetic acid (MAA), increase ovarian luteal cell progesterone production in the female rat in vivo and in cultured rat luteal cells in vitro, respectively. In order to better assess the potential hazard of EGME and MAA to women, these studies were conducted to determine whether the same concentrations of MAA increase progesterone in human luteinized granulosa cells as in rat luteal cells. Human cells were collected from healthy anonymous oocyte donors, washed, plated 25,000 viable cells per well, and treated with 10 IU hCG and 0-5 mM MAA for 6-48 hr, Progesterone in media was significantly elevated after 24 hr incubation at greater than or equal to 1 mM MAA. MAA had no effect on ATP levels at 6 or 24 hr, Thus, MAA increased progesterone production in cultured human luteal cells at the same concentration as MAA increased progesterone in rat luteal cells, The implication is that EGME has the potential to alter ovarian luteal function in women, These data should be useful for determining the real health hazards and potential risks of EGME exposure. (C) 1997 Society of Toxicology. C1 NIEHS,REPROD & DEV TOXICOL LAB,RES TRIANGLE PK,NC 27709. DUKE UNIV,MED CTR,DEPT OBSTET & GYNECOL,DURHAM,NC 27710. RP Almekinder, JL (reprint author), NIEHS,LAB EXPT PATHOL,POB 12233,RES TRIANGLE PK,NC 27709, USA. NR 16 TC 12 Z9 12 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 0272-0590 J9 FUND APPL TOXICOL JI Fundam. Appl. Toxicol. PD AUG PY 1997 VL 38 IS 2 BP 191 EP 194 DI 10.1006/faat.1997.2332 PG 4 WC Toxicology SC Toxicology GA XZ216 UT WOS:A1997XZ21600011 PM 9299193 ER PT J AU Kepple, TM Siegel, KL Stanhope, SJ AF Kepple, TM Siegel, KL Stanhope, SJ TI Relative contributions of the lower extremity joint moments to forward progression and support during gait SO GAIT & POSTURE LA English DT Article DE plantar flexors; joint moments; support moments; lower extremity; forward and vertical acceleration ID MUSCLES; WALKING AB A method, which was found to be accurate within 0.54 m/s(2), was developed to estimate the relative contributions of the net joint moments to forward progression and support in the gait of five normal subjects. Forward progression was produced primarily by the ankle plantar flexors with a significant assist from the knee extensors. Support was produced largely by the plantar flexors during single limb support and by a combination of ankle plantar flexors, knee extensors and hip extensors during double limb support. (C) 1997 Elsevier Science B.V. RP Kepple, TM (reprint author), NIH,BIOMECH LAB,DEPT REHABIL MED,WARREN G MAGNUSON CLIN CTR,10 CTR DR,MSC 1604,BLDG 10,BETHESDA,MD 20892, USA. RI Siegel, Karen Lohmann/B-5898-2008; OI Siegel, Karen Lohmann/0000-0002-0788-6612 NR 17 TC 146 Z9 146 U1 1 U2 19 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0966-6362 J9 GAIT POSTURE JI Gait Posture PD AUG PY 1997 VL 6 IS 1 BP 1 EP 8 DI 10.1016/S0966-6362(96)01094-6 PG 8 WC Neurosciences; Orthopedics; Sport Sciences SC Neurosciences & Neurology; Orthopedics; Sport Sciences GA XP398 UT WOS:A1997XP39800001 ER PT J AU Marth, T Neurath, M Cuccherini, BA Strober, W AF Marth, T Neurath, M Cuccherini, BA Strober, W TI Defects of monocyte interleukin 12 production and humoral immunity in Whipple's disease SO GASTROENTEROLOGY LA English DT Article ID INTERFERON-GAMMA; CELLS AB Background & Aims: Whipple's disease (WD) is a systemic infection in which the causative bacteria typically accumulate within macrophages, The aim of this study was to test whether this macrophage dysfunction is the cause or result of previously shown T-cell defects, Methods: In vitro production of interleukin (IL)-12, IL-10, tumor necrosis factor alpha, interferon gamma (IFN-gamma), and transforming growth factor beta (TGF-beta) from purified monocytes and peripheral blood mononuclear cells, cytokine expression on duodenal biopsy specimens, and serum cytokine and immunoglobulin (Ig) levels were tested in 9 patients with WD. Results: Reduced monocyte IL-12 production and decreased IFN-gamma secretion by peripheral blood mononuclear cells in vitro were found, as well as reduced immunohistological staining for IL-12 and IFN-gamma, but no decrease in other cytokines in patients with WD, A similar but less severe defect in 2 relatives with WD argued for a genetic basis of this abnormality. Serum IgG2, an IFN-gamma-dependent Ig subclass, and serum TGF-beta levels were reduced in patients with WD. Conclusions: The described monocyte defects in WD may result in a secondary reduction of IFN-gamma production and IgG2 serum levels, This provides a rationale for additive immunotherapy in patients with antibiotic-refractory WD. C1 NIH,MUCOSAL IMMUN SECT,CLIN INVEST LAB,BETHESDA,MD 20892. UNIV MAINZ KLINIKUM,INNERE MED ABT 1,D-6500 MAINZ,GERMANY. NR 21 TC 80 Z9 82 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 AUG PY 1997 VL 113 IS 2 BP 442 EP 448 DI 10.1053/gast.1997.v113.pm9247462 PG 7 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA XQ410 UT WOS:A1997XQ41000023 PM 9247462 ER PT J AU Karlson, BM Ekbom, A Josefsson, S McLaughlin, JK Fraumeni, JF Nyren, O AF Karlson, BM Ekbom, A Josefsson, S McLaughlin, JK Fraumeni, JF Nyren, O TI The risk of pancreatic cancer following pancreatitis: An association due to confounding? SO GASTROENTEROLOGY LA English DT Article ID DIABETES-MELLITUS; SMOKING; ALCOHOL; CONSUMPTION; CARCINOMA; DIET AB Background & Aims: Chronic pancreatitis has been suggested as a causal risk factor for pancreatic cancer in a recent study, The aim of this study was to clarify the relationship between chronic pancreatitis and pancreatic cancer, Methods: All patients in the Swedish Inpatient Register with a discharge diagnosis of pancreatitis from 1965 to 1983 were identified, They were stratified into subcohorts as follows: (1) one episode of unspecified pancreatitis (n = 823); (2) one episode of acute pancreatitis (n = 24,753); (3) recurrent pancreatitis (n = 7328); and (4) chronic pancreatitis (n = 4546), We also identified those with associated diagnoses indicating gallbladder disease or alcoholism, The patients were followed up through record linkage to the nationwide Swedish Cancer Register, Death Register, and Migration Register, Results: After exclusion of cancers occurring in the first year, there were excess risks for pancreatic cancer in all subcohorts, However, the risks declined with time in all subcohorts, A persistent excess risk after 10 years was restricted to patients with associated alcohol abuse (standardized incidence ratio, 3.8; 95% confidence interval, 1.5-7.9). Conclusions: The findings are not consistent with reports that pancreatitis is causally associated with a long-term risk of pancreatic cancer, Selection bias, alcohol consumption, and smoking may contribute to some of the patterns of risk that have been observed. C1 UNIV UPPSALA HOSP,DEPT CANC EPIDEMIOL,UPPSALA,SWEDEN. HARVARD UNIV,SCH PUBL HLTH,DEPT EPIDEMIOL,BOSTON,MA 02115. INT EPIDEMIOL INST,ROCKVILLE,MD. NCI,DIV CANC EPIDEMIOL & GENET,BETHESDA,MD 20892. RP Karlson, BM (reprint author), UNIV UPPSALA HOSP,DEPT SURG,S-75185 UPPSALA,SWEDEN. NR 26 TC 113 Z9 122 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 AUG PY 1997 VL 113 IS 2 BP 587 EP 592 DI 10.1053/gast.1997.v113.pm9247480 PG 6 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA XQ410 UT WOS:A1997XQ41000041 PM 9247480 ER PT J AU Heselmeyer, K Macville, M Schrock, E Blegen, H Hellstrom, AC Shah, K Auer, G Ried, T AF Heselmeyer, K Macville, M Schrock, E Blegen, H Hellstrom, AC Shah, K Auer, G Ried, T TI Advanced-stage cervical carcinomas are defined by a recurrent pattern of chromosomal aberrations revealing high genetic instability and a consistent gain of chromosome arm 3q SO GENES CHROMOSOMES & CANCER LA English DT Article ID COMPARATIVE GENOMIC HYBRIDIZATION; MOLECULAR CYTOGENETIC ANALYSIS; HUMAN PAPILLOMAVIRUS; SOLID TUMORS; COPY NUMBER; CANCER; LOSSES; AMPLIFICATION; GENESIS; P53 AB We have analyzed 30 cases of advanced-stage cervical squamous cell carcinoma (stages Ilb-IV) by comparative genomic hybridization (CGH). The most consistent chromosomal gain in the aneuploid tumors was mapped to chromosome arm 3q in 77% of the cases. Acquisition of genetic material also occurred frequently on Iq (47%), 5p (30%), 6p (27%), and 20 (23%). Recurrent losses were mapped on 2q (33%), 3p (50%), 4 (33%), 8p (23%), and 13q (27%). High-level copy number increases were mapped to chromosome 8, chromosome arms 3q, 5p, 8q, 12p, 14q, 17q, 19q, 20p, and 20q, and chromosomal bands 3q26-27, 9p23-24, 11q22-23, and 12p13. In the majority of the cases, the presence of high-risk human papilloma virus genomes was detected. High proliferative activity was accompanied by crude aneuploidy. Increased p21/WAF-I activity, but low or undetectable expression of TP53 were representative for the immunophenotype. This study confirms the importance of a gain of chromosome arm 3q in cervical carcinogenesis and identifies additional, recurrent chromosomal aberrations that are required for progression from stage I tumors to advanced-stage carcinomas. (C) 1997 Wiley-Liss, Inc.dagger C1 NIH,NATL CTR HUMAN GENOME RES,DIAGNOST DEV BRANCH,BETHESDA,MD 20892. KAROLINSKA INST,DEPT TUMOR PATHOL,DIV CELL & MOL ANAL,STOCKHOLM,SWEDEN. KAROLINSKA HOSP & INST,RADIUMHEMMET,DEPT GYNAECOL & ONCOL,STOCKHOLM,SWEDEN. JOHNS HOPKINS UNIV,SCH HYG & PUBL HLTH,DEPT MOL MICROBIOL & IMMUNOL,BALTIMORE,MD. NR 29 TC 208 Z9 213 U1 0 U2 4 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 1045-2257 J9 GENE CHROMOSOME CANC JI Gene Chromosomes Cancer PD AUG PY 1997 VL 19 IS 4 BP 233 EP 240 DI 10.1002/(SICI)1098-2264(199708)19:4<233::AID-GCC5>3.0.CO;2-Y PG 8 WC Oncology; Genetics & Heredity SC Oncology; Genetics & Heredity GA XN873 UT WOS:A1997XN87300005 PM 9258658 ER PT J AU Barks, JH Thompson, FH Taetle, R Yang, JM Stone, JF Wymer, JA Khavari, R Guan, XY Trent, JM Pinkel, D Nelson, MA AF Barks, JH Thompson, FH Taetle, R Yang, JM Stone, JF Wymer, JA Khavari, R Guan, XY Trent, JM Pinkel, D Nelson, MA TI Increased chromosome 20 copy number detected by fluorescence in situ hybridization (FISH) in malignant melanoma SO GENES CHROMOSOMES & CANCER LA English DT Article ID BREAST-CANCER; AMPLIFICATION; REGION; MICRODISSECTION; GENES; CDK4; MDM2; DNA AB DNA amplification is an important mechanism of tumor progression that allows cancer cells to up-regulate the expression of critical genes such as oncogenes and genes conferring drug resistance. Recent studies using comparative genomic hybridization (CGH) revealed increased DNA copies of 20q sequences in 7 melanoma cell lines and 8 archival metastatic melanoma lesions. To evaluate chromosome 20 abnormalities in more detail and to resolve discrepancies between karyotype and CGH findings, we performed FISH analysis of metaphase cells in 13 melanoma cell lines (including the 7 lines used for CGH) and 9 primary melanoma specimens by using a whole chromosome paint specific for chromosome 20. All 13 cell lines (100%) and 8/9 primary tumors (89%) showed extra copies of chromosome 20 relative to tumor ploidy. Additionally, 6/14 cell lines (43%) and 2/8 primary tumors (25%) showed translocated chromosome 20 material previously undetected by standard cytogenetics. Cytologic evidence for gene amplification was also found in one cell line, which contained an add(20)(p13), with additional DNA being derived from 20q sequences. These data suggest that overrepresentation of a gene or genes important for melanoma pathogenesis resides on the long arm of chromosome 20. (C) 1997 Wiley-Liss, Inc. C1 UNIV ARIZONA,ARIZONA CANC CTR,MOL ONCOL LAB,TUCSON,AZ 85724. UNIV ARIZONA,GRAD INTERDISCIPLINARY PROGRAM GENET,TUCSON,AZ. NIH,NATL CTR HUMAN GENOME RES,BETHESDA,MD 20892. SW BIOMED RES INST & GENZYME GENET,SCOTTSDALE,AZ. UNIV CALIF SAN FRANCISCO,DEPT MOL CYTOMETRY,SAN FRANCISCO,CA 94143. RI Guan, Xin-Yuan/A-3639-2009 OI Guan, Xin-Yuan/0000-0002-4485-6017 FU NCI NIH HHS [1R29 CA70145-01, CA23074, CA27502] NR 16 TC 31 Z9 33 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 1045-2257 J9 GENE CHROMOSOME CANC JI Gene Chromosomes Cancer PD AUG PY 1997 VL 19 IS 4 BP 278 EP 285 DI 10.1002/(SICI)1098-2264(199708)19:4<278::AID-GCC11>3.0.CO;2-C PG 8 WC Oncology; Genetics & Heredity SC Oncology; Genetics & Heredity GA XN873 UT WOS:A1997XN87300011 PM 9258664 ER PT J AU Karhu, R Knuutila, S Kallioniemi, OP Siitonen, S Aine, R Vilpo, L AF Karhu, R Knuutila, S Kallioniemi, OP Siitonen, S Aine, R Vilpo, L TI Frequent loss of the 11q14-24 region in chronic lymphocytic leukemia: A study by comparative genomic hybridization SO GENES CHROMOSOMES & CANCER LA English DT Article ID MULTIVARIATE SURVIVAL ANALYSIS; SOLID TUMORS; COPY NUMBER; CLASSIFICATION; CELLS AB The genetic basis and molecular pathogenesis of chronic lymphocytic leukemia (CLL) and the molecular mechanisms responsible for its progression remain poorly understood, Hel-e, karyotyping techniques specifically optimized for CLL, comparative genomic hybridization (CGH), and fluorescence in situ hybridization were used to search for CLL-specific genetic abet-rations. CGH and karyotyping both revealed co py number changes in 12 of the 25 CLL cases (48%) analyzed, Loss at 11q emerged as the most common aberration (6 cases), followed by a gain of chromosome 12 (4) and loss at 13q (3), Concordance between CGH and C-banding was found in 23 of the 25 cases (92%), which is more than reported in a recent similar CGH study of CLL. Owing to the basic differences in G-banding and CGH, however, their simultaneous clinical application is recommended. The frequent loss of 11q14-24 suggests that this chromosomal region deserves further attention as a candidate locus involved in the pathogenesis of CLL. (C) 1997 Wiley-Liss, Inc. C1 UNIV TAMPERE,FIN-33101 TAMPERE,FINLAND. UNIV HELSINKI,HAARTMAN INST,DEPT MED GENET,HELSINKI,FINLAND. NIH,NATL CTR HUMAN GENOME RES,CANC GENET LAB,BETHESDA,MD 20892. TAMPERE UNIV HOSP,DEPT PATHOL,TAMPERE,FINLAND. RP Karhu, R (reprint author), TAMPERE UNIV HOSP,DEPT CLIN CHEM,POB 2000,FIN-33521 TAMPERE,FINLAND. RI Kallioniemi, Olli/H-5111-2011; Kallioniemi, Olli/H-4738-2012 OI Kallioniemi, Olli/0000-0002-3231-0332; Kallioniemi, Olli/0000-0002-3231-0332 NR 18 TC 53 Z9 53 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 1045-2257 J9 GENE CHROMOSOME CANC JI Gene Chromosomes Cancer PD AUG PY 1997 VL 19 IS 4 BP 286 EP 290 DI 10.1002/(SICI)1098-2264(199708)19:4<286::AID-GCC12>3.0.CO;2-E PG 5 WC Oncology; Genetics & Heredity SC Oncology; Genetics & Heredity GA XN873 UT WOS:A1997XN87300012 PM 9258665 ER PT J AU Grewal, SIS Klar, AJS AF Grewal, SIS Klar, AJS TI A recombinationally repressed region between mat2 and mat3 loci shares homology to centromeric repeats and regulates directionality of mating-type switching in fission yeast SO GENETICS LA English DT Article ID ORIGIN RECOGNITION COMPLEX; SCHIZOSACCHAROMYCES-POMBE; SACCHAROMYCES-CEREVISIAE; MEIOTIC RECOMBINATION; DNA-REPLICATION; S-POMBE; GENES; INTERCONVERSION; EXPRESSION; CASSETTES AB Cells of the fission yeast Schizosaccharomyces pombe switch mating type by replacing genetic information at the transcriptionally active mat1 locus with sequences copied from one of two closely Linked silent loci, mat2-P or mat3-M. By a process referred to as directionality of switching, cells predominantly sw itch to the opposite mat1 allele; the mat1-P allele preferentially recombines with mat3, while mat1-M selects the mat2. In contrast to efficient recombination at mat1, recombination within the adjoining mat2-mat3 interval is undetectable. We defined the role of sequences between mat2 and mat3, designated the K-region, in directionality as well as recombinational suppression. Cloning and sequencing analysis revealed that a part of the K-region is homologous to repeat sequences present at centromeres, which also display transcriptional and recombinational suppression. Replacement of 7.5 kb of the K-region with the ura4(+) gene affected directionality in a variegated manner. Analysis of the swi6-mod locus, which was previously shown to affect directionality, in K Delta::ura4(+) strains suggested the existence of at least two overlapping directionality mechanisms. Our work furthers the model that directionality is regulated by cell-type specific organization of the heterochromatin-like structure in the mating-type region and provides evidence that the K-region contributes to silencing of the mat2-mat3 interval. C1 NCI, GENE REGULAT & CHROMOSOME BIOL LAB,ABL, BASIC RES PROGRAM,FREDERICK CANC RES & DEV CTR, FREDERICK, MD 21702 USA. NR 61 TC 113 Z9 115 U1 0 U2 0 PU GENETICS SOCIETY AMERICA PI BETHESDA PA 9650 ROCKVILLE AVE, BETHESDA, MD 20814 USA SN 0016-6731 EI 1943-2631 J9 GENETICS JI Genetics PD AUG PY 1997 VL 146 IS 4 BP 1221 EP 1238 PG 18 WC Genetics & Heredity SC Genetics & Heredity GA XM833 UT WOS:A1997XM83300003 PM 9258669 ER PT J AU Mason, JM Champion, LE Hook, G AF Mason, JM Champion, LE Hook, G TI Germ-line effects of a mutator, mu2, in Drosophila melanogaster SO GENETICS LA English DT Article ID DOUBLE-STRAND BREAKS; CHROMATIN STRUCTURE; DNA-SEQUENCES; TERMINAL DELETIONS; IONIZING-RADIATION; MOLECULAR ANALYSIS; TELOMERIC REPEATS; ALPHA-THALASSEMIA; CHROMOSOME ENDS; MAMMALIAN-CELLS AB A mutator, mu2(a), in Drosophila melanogaster potentiates terminal deficiencies. In the female germ line the y mutant frequency induced by irradiation of mature oocytes with 5 Gy increases approximately twofold in heterozygotes and 20-fold in homozygotes compared with wild type. The recovery of terminal deficiencies is not limited to breaks close to chromosome ends; high frequencies of deficiencies can be recovered with breakpoints located in centric heterochromatin or near the middle of a chromosome arm. Lesions induced by gamma-rays are repaired slowly in mu2(a) oocytes, but become ''fixed'' as terminal deficiencies upon fertilization. A few lesions induced in wild-type females also produce terminal deficiencies. Mutator males do not exhibit an increase in terminal deletions, regardless of the germ cell stage irradiated. In addition, there is no increase in the mutant frequency when mature sperm are irradiated and fertilize eggs produced by mu2(a) females. The data are consistent with the hypothesis that lesions induced in sperm chromosomes are repaired after fertilization, while lesions induced in oocyte chromosomes are shunted instead to a mechanism that stabilizes broken chromosome ends. We propose that mu2 affects chromosomal structure during oogenesis, thereby modulating DNA repair. C1 NIEHS,CELLULAR & GENET TOXICOL BRANCH,RES TRIANGLE PK,NC 27709. RP Mason, JM (reprint author), NIEHS,MOL GENET LAB,RES TRIANGLE PK,NC 27709, USA. NR 73 TC 22 Z9 23 U1 0 U2 0 PU GENETICS PI BALTIMORE PA 428 EAST PRESTON ST, BALTIMORE, MD 21202 SN 0016-6731 J9 GENETICS JI Genetics PD AUG PY 1997 VL 146 IS 4 BP 1381 EP 1397 PG 17 WC Genetics & Heredity SC Genetics & Heredity GA XM833 UT WOS:A1997XM83300015 PM 9258681 ER PT J AU Oda, T Elkahloun, AG Meltzer, PS Chandrasekharappa, SC AF Oda, T Elkahloun, AG Meltzer, PS Chandrasekharappa, SC TI Identification and cloning of the human homolog (JAG1) of the rat Jagged1 gene from the Alagille syndrome critical region at 20p12 SO GENOMICS LA English DT Article ID ARTERIOHEPATIC DYSPLASIA; CONSTRUCTION; DELETION; FAMILY AB Notch proteins are a family of closely related transmembrane receptors proven to be instrumental in cell fate decisions. Recently, Notch ligands Delta and Jagged have been identified in Drosophila and fat, respectively. We have isolated the human homolog of the rat Jagged1 gene, JAG1, from a CpG island in a YAC clone covering the Alagille syndrome critical region at chromosome 20p12 (tel-SNAP-D20S186-cen). Alagille syndrome is an autosomal dominant disorder characterized by neonatal jaundice, paucity of intrahepatic bile ducts, and abnormalities of the heart, skeleton, and eyes. The human Jagged1 (JAG1), therefore, appears to be a strong candidate gene for this disease. Here we describe the identification, full-length cDNA cloning, expression patterns, and precise physical location of this gene within the Alagille syndrome critical region. (C) 1997 Academic Press. C1 NATL HUMAN GENOME RES INST, LAB GENE TRASFER, NIH, BETHESDA, MD 20892 USA. NATL HUMAN GENOME RES INST, CANC GENET LAB, NIH, BETHESDA, MD 20892 USA. NR 19 TC 45 Z9 48 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 0888-7543 EI 1089-8646 J9 GENOMICS JI Genomics PD AUG 1 PY 1997 VL 43 IS 3 BP 376 EP 379 DI 10.1006/geno.1997.4820 PG 4 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA XR734 UT WOS:A1997XR73400015 PM 9268641 ER PT J AU Butler, RN Kupfer, C Faye, EE Guazzo, E AF Butler, RN Kupfer, C Faye, EE Guazzo, E TI Keeping an eye on vision: Primary care of age-related ocular disease - A roundtable discussion .1. SO GERIATRICS LA English DT Editorial Material AB Normal changes in the lens, retina, and vitreous accompany aging, but loss of vision in late life is not an inevitable consequence of aging. Cataract, glaucoma, diabetic retinopathy, and age-related macular degeneration (ARMD) account for most vision loss in the older population. Visual impairment reduces older patients' ability to function independently and increases their risk of depression and of injury due to falls. When older persons have a visual complaint, they tend to blame it on being old and do not tell their physicians. In the primary care office, simple screening questions and examination of the dilated eye can often reveal a need for further examination and/or referral. C1 MT SINAI MED CTR, DEPT GERIATR & ADULT DEV, NEW YORK, NY 10029 USA. UNIV MARYLAND, SCH MED, BALTIMORE, MD 21201 USA. NEI, NIH, BETHESDA, MD 20892 USA. RP Butler, RN (reprint author), INT LONGEV CTR US, NEW YORK, NY USA. NR 0 TC 5 Z9 5 U1 1 U2 6 PU ADVANSTAR COMMUNICATIONS INC PI DULUTH PA 131 W 1ST STREET, DULUTH, MN 55802 USA SN 0016-867X EI 1936-5764 J9 GERIATRICS JI Geriatrics PD AUG PY 1997 VL 52 IS 8 BP 30 EP 41 PG 12 WC Geriatrics & Gerontology SC Geriatrics & Gerontology GA XP855 UT WOS:A1997XP85500018 PM 9261284 ER PT J AU Kalinec, F Kalinec, G Negrini, C Kachar, B AF Kalinec, F Kalinec, G Negrini, C Kachar, B TI Immunolocalization of anion exchanger 2 alpha in auditory sensory hair cells SO HEARING RESEARCH LA English DT Article DE hair cells; outer hair cells; anion exchanger proteins; auditory sensory transduction; organ of Corti ID HEREDITARY OVALOCYTOSIS; CYTOPLASMIC DOMAIN; SHAPE CHANGES; GUINEA-PIG; MEMBRANE; PROTEIN; BAND-3; TRANSDUCTION; CYTOSKELETON; GENERATION AB We have previously reported the isolation from a guinea pig organ of Corti cDNA library of a cDNA clone that encodes a novel isoform of the anion exchanger 2 (AE2) protein (Negrini, Rivolta, Kalinec and Kachar, 1995. Cloning of an organ of Corti anion exchanger 2 isoform with a truncated C-terminal domain. Biophys. Acta, 1236, 207-211). The deduced protein, named AE2 alpha, has a conserved cytoplasmic domain and a short membrane domain with only two membrane spanning regions, as opposed to the fourteen present in the conventional AE2. Now, we are showing the immunolocalization and preliminary characterization of this protein using an antipeptide antibody specific for this novel AE2 isoform. In Western blots, this antibody binds to an similar to 89 kDa polypeptide that corresponds to a phosphorylated protein with serines as main phosphate acceptor residues. In immunofluorescence experiments, the antibody labels the stereocilia and the lateral wall of the outer hair cells and the stereocilia of the inner hair cells. Our results suggest that AE2 alpha is a membrane-cytoskeletal linker in regions of the hair cell, where sensory transduction mechanisms take place. C1 NIH,NATL INST DEAFNESS & OTHER COMMUN DISORDERS,SECT STRUCT CELL BIOL,BETHESDA,MD 20850. NR 24 TC 13 Z9 13 U1 1 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0378-5955 J9 HEARING RES JI Hear. Res. PD AUG PY 1997 VL 110 IS 1-2 BP 141 EP 146 DI 10.1016/S0378-5955(97)00076-2 PG 6 WC Audiology & Speech-Language Pathology; Neurosciences; Otorhinolaryngology SC Audiology & Speech-Language Pathology; Neurosciences & Neurology; Otorhinolaryngology GA XR641 UT WOS:A1997XR64100013 PM 9282896 ER PT J AU Agnello, V Liang, TJ AF Agnello, V Liang, TJ TI Is hepatitis C virus a sialodacryoadenitis virus? SO HEPATOLOGY LA English DT Editorial Material ID MIXED CRYOGLOBULINEMIA; INFECTION C1 NIDDK,LIVER DIS SECT,NIH,BETHESDA,MD 20034. RP Agnello, V (reprint author), LAHEY HITCHCOCK CLIN,BURLINGTON,MA, USA. NR 9 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 0270-9139 J9 HEPATOLOGY JI Hepatology PD AUG PY 1997 VL 26 IS 2 BP 509 EP 510 DI 10.1002/hep.510260240 PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA XQ609 UT WOS:A1997XQ60900040 PM 9252169 ER PT J AU Senden, N Linnoila, I Timmer, E vandeVelde, H Roebroek, A VandeVen, W Broers, J Ramaekers, F AF Senden, N Linnoila, I Timmer, E vandeVelde, H Roebroek, A VandeVen, W Broers, J Ramaekers, F TI Neuroendocrine-specific protein (NSP)-reticulons as independent markers for non-small cell lung cancer with neuroendocrine differentiation - An in vitro histochemical study SO HISTOCHEMISTRY AND CELL BIOLOGY LA English DT Article ID NEURO-ENDOCRINE DIFFERENTIATION; ADHESION MOLECULE EXPRESSION; NSP-ENCODED RETICULONS; L-DOPA DECARBOXYLASE; MONOCLONAL-ANTIBODY; CHROMOGRANIN-A; ENDOPLASMIC-RETICULUM; INSITU HYBRIDIZATION; MESSENGER-RNA; LINES AB Neuroendocrine-specific protein (NSP)-reticulons have recently been discovered and were shown to exhibit a restricted, neuroendocrine/neural-specific expression pattern. These protein aggregates are anchored to the membranes of the endoplasmic reticulum and occur in small cell lung cancer (SCLC), but not in typical non-SCLC. In the current study we have examined the occurrence of NSP-reticulons in non-SCLC cell lines known to express neuroendocrine features (non-SCLC-NE). NSP-reticulon expression was observed in all three non-SCLC-NE cell lines studied, albeit with variable intensity and in varying numbers of cells. Western blot analysis confirmed the presence of NSP-reticulon expression in these non-SCLC-NE cell lines, and showed that they were predominantly of the NSP-A type. When compared to conventional neuroendocrine markers, NSP-reticulons revealed a distinct staining profile, showing only partial overlap with the other markers. The non-SCLC-NE cell lines combined these neuroendocrine characteristics with some features of non-SCLC. We conclude that NSP-reticulon expression is restricted to lung carcinoma cells with a neuroendocrine phenotype and predict that these constituents may become clinically relevant markers for the detection of neuroendocrine differentiation in solid rumours. C1 UNIV MAASTRICHT,DEPT MOL CELL BIOL & GENET,NL-6200 MD MAASTRICHT,NETHERLANDS. NCI,BIOMARKERS & PREVENT RES BRANCH,ROCKVILLE,MD. CATHOLIC UNIV LEUVEN,CTR HUMAN GENET,ONCOL MOL LAB,B-3000 LOUVAIN,BELGIUM. NR 51 TC 15 Z9 15 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0301-5564 J9 HISTOCHEM CELL BIOL JI Histochem. Cell Biol. PD AUG PY 1997 VL 108 IS 2 BP 155 EP 165 DI 10.1007/s004180050157 PG 11 WC Cell Biology; Microscopy SC Cell Biology; Microscopy GA XQ405 UT WOS:A1997XQ40500008 PM 9272435 ER PT J AU Avraham, KB Hasson, T Sobe, T Balsara, B Testa, JR Skvorak, AB Morton, CC Copeland, NG Jenkins, NA AF Avraham, KB Hasson, T Sobe, T Balsara, B Testa, JR Skvorak, AB Morton, CC Copeland, NG Jenkins, NA TI Characterization of unconventional MYO6, the human homologue of the gene responsible for deafness in Snell's waltzer mice SO HUMAN MOLECULAR GENETICS LA English DT Article ID HAIR-CELLS; MYOSIN; SEQUENCES; HEARING; MOUSE; PHOSPHORYLATION; LOCALIZATION; COCHLEA AB Deafness is the most common form of sensory impairment in humans, Mutations in unconventional myosins have been found to cause deafness in humans and mice. The mouse recessive deafness mutation, Snell's waltzer, contains an intragenic deletion in an unconventional myosin, myosin VI (focus designation, Myo6). The requirement for Myo6 for proper hearing in mice makes this gene an excellent candidate for a human deafness disorder. Here we report the cloning and characterization of the human unconventional myosin VI (locus designation, MYO6) cDNA. The MYO6 gene maps to human chromosome 6q13. The isolation of the human gene makes it now possible to determine if mutations in MYO6 contribute to the pathogenesis of deafness in the human population. C1 YALE UNIV,DEPT BIOL,NEW HAVEN,CT 06511. YALE UNIV,DEPT PATHOL,NEW HAVEN,CT 06511. FOX CHASE CANC CTR,DEPT MED ONCOL,PHILADELPHIA,PA 19111. BRIGHAM & WOMENS HOSP,DEPT PATHOL,BOSTON,MA 02115. BRIGHAM & WOMENS HOSP,DEPT OBSTET GYNECOL & REPROD BIOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,BOSTON,MA 02115. NCI,FREDERICK CANC RES & DEV CTR,ABL BASIC RES PROGRAM,MAMMALIAN GENET LAB,FREDERICK,MD 21702. RP Avraham, KB (reprint author), TEL AVIV UNIV,SACKLER SCH MED,DEPT HUMAN GENET,IL-69978 TEL AVIV,ISRAEL. FU NIDCD NIH HHS [DC00038-05, DC00871]; NIDDK NIH HHS [DK38979] NR 33 TC 67 Z9 69 U1 0 U2 2 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD, ENGLAND OX2 6DP SN 0964-6906 J9 HUM MOL GENET JI Hum. Mol. Genet. PD AUG PY 1997 VL 6 IS 8 BP 1225 EP 1231 DI 10.1093/hmg/6.8.1225 PG 7 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA XN408 UT WOS:A1997XN40800004 PM 9259267 ER PT J AU Ellison, JW Wardak, Z Young, MF Robey, PG LaigWebster, M Chiong, W AF Ellison, JW Wardak, Z Young, MF Robey, PG LaigWebster, M Chiong, W TI PHOG, a candidate gene for involvement in the short stature of Turner syndrome SO HUMAN MOLECULAR GENETICS LA English DT Article ID X-CHROMOSOME INACTIVATION; ALPHA-SUBUNIT GENE; PSEUDOAUTOSOMAL REGION; GROWTH GENE(S); SHORT ARM; MOUSE; ESCAPE; DISTAL; LOCALIZATION; DELETION AB The abnormalities seen in Turner syndrome (monosomy X) presumably result from haploinsufficiency of certain genes on the X chromosome, Gene dosage considerations lead to the prediction that the culpable genes escape X inactivation and have functional homologs on the Y chromosome, Among the genes with these characteristics are those residing in the pseudoautosomal regions (PAR) of the sex chromosomes, A pseudoautosomal location for a dosage-sensitive locus involved in stature has been suggested based on the analyses of patients with deletions of a specific segment of the short arm PAR; hemizygosity for this putative locus probably also contributes to the short stature in Turner individuals, We have isolated a gene from the critical deleted region that encodes a novel homeodomain-containing transcription factor and is expressed at highest levels in osteogenic cells, We have named the gene PHOG, for pseudoautosomal homeobox-containing osteogenic gene, Its deletion in patients with short stature, the predicted altered dosage in 45,X individuals, along with the nature of the encoded protein and its expression pattern, make PHOG an attractive candidate for involvement in the short stature of Turner syndrome. We have also found that the mouse homolog of PHOG is autosomal, which may help to explain the lack of a growth abnormality in mice with monosomy X. C1 UNIV CALIF SAN FRANCISCO,DEPT PEDIAT,SAN FRANCISCO,CA 94143. NIDR,CRANIOFACIAL & SKELETAL DIS BRANCH,NIH,BETHESDA,MD 20892. RI Robey, Pamela/H-1429-2011 OI Robey, Pamela/0000-0002-5316-5576 FU NICHD NIH HHS [HD28825] NR 37 TC 183 Z9 193 U1 0 U2 2 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD, ENGLAND OX2 6DP SN 0964-6906 J9 HUM MOL GENET JI Hum. Mol. Genet. PD AUG PY 1997 VL 6 IS 8 BP 1341 EP 1347 DI 10.1093/hmg/6.8.1341 PG 7 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA XN408 UT WOS:A1997XN40800019 PM 9259282 ER PT J AU Cahill, CM Holder, AT Lawton, TL Butcher, GW Taussig, MJ AF Cahill, CM Holder, AT Lawton, TL Butcher, GW Taussig, MJ TI Recognition of porcine growth hormone by a panel of monoclonal antibodies SO HYBRIDOMA LA English DT Article ID HOMOLOG-SCANNING MUTAGENESIS; MESSENGER-RNA; DWARF MICE; NUCLEOTIDE-SEQUENCE; ANTIGENIC STRUCTURE; DNA-SEQUENCE; PROLACTIN; BOVINE; LOCATION; ENHANCEMENT AB A panel of murine monoclonal antibodies (MAbs) against porcine growth hormone (pGH) has been raised from BALB/c mice. MAbs were characterized for binding to growth hormones (GH), prolactins (PRL), and placental lactogen (PL) from different species and to the N-terminal peptides of GH. From their patterns of cross-reactivity MAbs were assigned into nine specificity groups. The sharing of pGH epitopes among hormones of different species was related to the sequence similarity to pGH, i.e., overlap was greatest for equine, ruminant, and rodent GHs and least for human GH, ovine, and porcine PRLs, and human PL. Partial epitope mapping was carried out by relating hormone cross-reactivity patterns with amino acid sequences. Two epitopes were localized to interhelical loops, around valine-73 and glycine-130, respectively. Direct mapping with synthetic peptides localized other epitopes (Groups 7, 8, and 9) to the N-terminal region of the GH molecule. Selected MAbs were studied for the enhancement of the somatogenic activity of pGH in the dwarf mouse bioassay, measuring weight gain and sulphate incorporation into costal cartilage. Only those antibodies with specificities for GHs and not PRL or PL showed significant enhancement in this assay. C1 BABRAHAM INST,DEPT CELLULAR PHYSIOL,CAMBRIDGE CB2 4AT,ENGLAND. IDEXX INC,WESTBROOK,ME 04092. BABRAHAM INST,DEPT IMMUNOL,CAMBRIDGE CB2 4AT,ENGLAND. RP Cahill, CM (reprint author), NIA,GERONTOL RES CTR,CELLULAR & MOL BIOL LAB,NIH,4940 EASTERN AVE,BALTIMORE,MD 21224, USA. NR 33 TC 2 Z9 3 U1 0 U2 1 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 SN 0272-457X J9 HYBRIDOMA JI Hybridoma PD AUG PY 1997 VL 16 IS 4 BP 371 EP 379 DI 10.1089/hyb.1997.16.371 PG 9 WC Biochemical Research Methods; Biotechnology & Applied Microbiology; Immunology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Immunology GA XX228 UT WOS:A1997XX22800008 PM 9309428 ER EF