FN Thomson Reuters Web of Science™ VR 1.0 PT J AU Sweitzer, TD Bennett, DD Hanover, JA AF Sweitzer, TD Bennett, DD Hanover, JA TI Regulation of nuclear import by calcium: Measurement of free calcium within the endoplasmic reticulum with a targeted aequorin SO FASEB JOURNAL LA English DT Meeting Abstract C1 NIDDK, Lab Cell Biochem & Biol, NIH, Bethesda, MD 20892 USA. Mayo Med Sch, Rochester, MN 55905 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR 24 PY 1998 VL 12 IS 8 SU S MA 202 BP A1345 EP A1345 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 260QN UT WOS:000083961500356 ER PT J AU Torigoe, C Inman, JK Metzger, H AF Torigoe, C Inman, JK Metzger, H TI A molecular basis for ligand antagonism SO FASEB JOURNAL LA English DT Meeting Abstract C1 NIAMSD, ARB, NIH, Bethesda, MD 20892 USA. NIAID, LI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR 24 PY 1998 VL 12 IS 8 SU S MA 547 BP A1405 EP A1405 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 260QN UT WOS:000083961500701 ER PT J AU Trawick, ML Bowser, TE Folk, JE AF Trawick, ML Bowser, TE Folk, JE TI Specificity of gamma-glutamylamine cyclotransferase SO FASEB JOURNAL LA English DT Meeting Abstract C1 Baylor Univ, Dept Chem, Waco, TX 76798 USA. Baylor Univ, Inst Biomed Studies, Waco, TX 76798 USA. NIDR, OPPCB, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR 24 PY 1998 VL 12 IS 8 SU S MA 268 BP A1357 EP A1357 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 260QN UT WOS:000083961500422 ER PT J AU Tse, C Sera, T Wolffe, AP Hansen, JC AF Tse, C Sera, T Wolffe, AP Hansen, JC TI Hyperacetylation of the core histone N-termini induces decondensation of nucleosomal arrays and dramatically facilitates transcription SO FASEB JOURNAL LA English DT Meeting Abstract C1 Univ Texas, Hlth Sci Ctr, Dept Biochem, San Antonio, TX USA. NICHHD, Mol Embryol Lab, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR 24 PY 1998 VL 12 IS 8 SU S MA 42 BP A1314 EP A1314 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 260QN UT WOS:000083961500197 ER PT J AU Tully, DB Cox, VT Mumtaz, MM Davis, VL Chapin, RE AF Tully, DB Cox, VT Mumtaz, MM Davis, VL Chapin, RE TI Six high priority organochlorine pesticides singly or combined are not estrogenic in a HeLa transcriptional activation assay SO FASEB JOURNAL LA English DT Meeting Abstract C1 NIEHS, Res Triangle Pk, NC 27709 USA. Agcy Tox Subst & Dis Registry, Atlanta, GA 30333 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR 24 PY 1998 VL 12 IS 8 SU S MA 862 BP A1459 EP A1459 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 260QN UT WOS:000083961501015 ER PT J AU van Leeuwen, JEM Samelson, LE AF van Leeuwen, JEM Samelson, LE TI Increased basal and TCR-induced association of 70Z Cbl with Crk(L) and p85 PI3K in Jurkat T cells SO FASEB JOURNAL LA English DT Meeting Abstract C1 NICHHD, CBMB, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR 24 PY 1998 VL 12 IS 8 SU S MA 596 BP A1413 EP A1413 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 260QN UT WOS:000083961500751 ER PT J AU Virador, VM Matsunaga, N Sakai, C Hearing, VJ AF Virador, VM Matsunaga, N Sakai, C Hearing, VJ TI Characterization of expression patterns and the biofunctional domains of agouti signal protein SO FASEB JOURNAL LA English DT Meeting Abstract C1 NCI, Cell Biol Lab, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR 24 PY 1998 VL 12 IS 8 SU S MA 835 BP A1454 EP A1454 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 260QN UT WOS:000083961500989 ER PT J AU Vonakis, BM Haleem-Smith, H Benjamin, PS Metzger, H AF Vonakis, BM Haleem-Smith, H Benjamin, PS Metzger, H TI Structural basis for the interaction of Lyn kinase with the unphosphorylated high affinity receptor for IgE (Fc epsilon RI) SO FASEB JOURNAL LA English DT Meeting Abstract C1 NIAMSD, ARB, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR 24 PY 1998 VL 12 IS 8 SU S MA 779 BP A1445 EP A1445 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 260QN UT WOS:000083961500932 ER PT J AU Walker, H Ferretti, JA Stadtman, TC AF Walker, H Ferretti, JA Stadtman, TC TI Isotope exchange studies on the Escherichia coli selenophosphate synthetase mechanism SO FASEB JOURNAL LA English DT Meeting Abstract C1 NHLBI, Biochem Lab, NIH, Bethesda, MD 20892 USA. NHLBI, Biophys Chem Lab, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR 24 PY 1998 VL 12 IS 8 SU S MA 269 BP A1357 EP A1357 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 260QN UT WOS:000083961500425 ER PT J AU Wang, LH Kirken, RA Erwin, RA Taub, D Murphy, WJ Farrar, WL AF Wang, LH Kirken, RA Erwin, RA Taub, D Murphy, WJ Farrar, WL TI Tyrphostin AG-490 inhibits the JAK3/STAT5a/b signaling pathway and antigen-specific activation of human T cells SO FASEB JOURNAL LA English DT Meeting Abstract C1 NCI, FCRDC, Div Basic Sci, CMMS,Lab Mol Immunoregulat, Frederick, MD 21702 USA. NCI, FCRDC, SAIC Frederick, IRSP, Frederick, MD 21702 USA. NIA, Immunol Lab, Baltimore, MD 21224 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR 24 PY 1998 VL 12 IS 8 SU S MA 591 BP A1412 EP A1412 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 260QN UT WOS:000083961500743 ER PT J AU Wang, QJ Mushinski, JF AF Wang, QJ Mushinski, JF TI The V5 domain as the critical determinant of the isozyme-specific effects of protein kinase C-delta and -epsilon SO FASEB JOURNAL LA English DT Meeting Abstract C1 NCI, Genet Lab, Bethesda, MD 20892 USA. RI Wang, Qiming/B-6064-2012 NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR 24 PY 1998 VL 12 IS 8 SU S MA 589 BP A1412 EP A1412 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 260QN UT WOS:000083961500742 ER PT J AU Wang, SW Chae, HZ Seo, MS Kim, K Baines, IC Rhee, SG AF Wang, SW Chae, HZ Seo, MS Kim, K Baines, IC Rhee, SG TI Mammalian peroxiredoxin isoforms can reduce hydrogen peroxide generated in response to growth factors and tumor necrosis factor-alpha SO FASEB JOURNAL LA English DT Meeting Abstract C1 NHLBI, Lab Cell Signaling, NIH, Bethesda, MD 20892 USA. NHLBI, Cell Biol Lab, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR 24 PY 1998 VL 12 IS 8 SU S MA 895 BP A1465 EP A1465 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 260QN UT WOS:000083961501049 ER PT J AU Wang, W O'Connell, B Ambudkar, LS AF Wang, W O'Connell, B Ambudkar, LS TI Identification and cloning of TRP gene homologues in rat brain and salivary glands. SO FASEB JOURNAL LA English DT Meeting Abstract C1 NIDR, Secretory Physiol Sect, NIH, Bethesda, MD 20892 USA. NIDR, Gene Transfer Unit GGTB, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR 24 PY 1998 VL 12 IS 8 SU S MA 961 BP A1476 EP A1476 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 260QN UT WOS:000083961501115 ER PT J AU Warner, DR Weinstein, LS AF Warner, DR Weinstein, LS TI Intramolecular contact between Switch 3 and the alpha D-alpha E loop of Gs alpha is essential for high affinity guanine nucleotide binding SO FASEB JOURNAL LA English DT Meeting Abstract C1 NINDS, NIH, Bethesda, MD 20892 USA. NIDDK, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR 24 PY 1998 VL 12 IS 8 SU S MA 332 BP A1367 EP A1367 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 260QN UT WOS:000083961500486 ER PT J AU Wolff, EC Um, P Park, MH AF Wolff, EC Um, P Park, MH TI Identification of critical residues in the active site of human deoxyhypusine synthase SO FASEB JOURNAL LA English DT Meeting Abstract C1 NIDR, OPCB, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR 24 PY 1998 VL 12 IS 8 SU S MA 709 BP A1433 EP A1433 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 260QN UT WOS:000083961500865 ER PT J AU Wolfsberg, TG Thompson, W Lawrence, CE Landsman, D AF Wolfsberg, TG Thompson, W Lawrence, CE Landsman, D TI Sequence analysis of the gene regulatory regions of the yeast Saccharomyces cerevisiae. SO FASEB JOURNAL LA English DT Meeting Abstract C1 Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20894 USA. New York State Dept Hlth, Wadsworth Ctr, Biometr Lab, Albany, NY 12201 USA. RI Landsman, David/C-5923-2009 NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR 24 PY 1998 VL 12 IS 8 SU S MA 533 BP A1402 EP A1402 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 260QN UT WOS:000083961500685 ER PT J AU Wu, C AF Wu, C TI Chromatin remodeling and transcription SO FASEB JOURNAL LA English DT Meeting Abstract C1 NCI, Mol Cell Biol Lab, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR 24 PY 1998 VL 12 IS 8 SU S MA 40 BP A1314 EP A1314 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 260QN UT WOS:000083961500196 ER PT J AU Wu, HB Tsai, WC Rechler, MM AF Wu, HB Tsai, WC Rechler, MM TI IGFBP-3 mediates TGF-8-induced growth inhibition in mink lung epithelial cell SO FASEB JOURNAL LA English DT Meeting Abstract C1 NIDDK, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR 24 PY 1998 VL 12 IS 8 SU S MA 192 BP A1343 EP A1343 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 260QN UT WOS:000083961500345 ER PT J AU Wu, YL Kang, SW Levine, RL Bourdi, M Pohi, L Rhee, SG AF Wu, YL Kang, SW Levine, RL Bourdi, M Pohi, L Rhee, SG TI Oxidants generated during EGF signaling targeted multiple protein disulfide isomerases in human A-431 cells. SO FASEB JOURNAL LA English DT Meeting Abstract C1 NHLBI, Biochem Lab, NIH, Bethesda, MD 20892 USA. NHLBI, Lab Cell Signaling, NIH, Bethesda, MD 20892 USA. NHLBI, Lab Mol Immunol, NIH, Bethesda, MD 20892 USA. RI Levine, Rodney/D-9885-2011 NR 0 TC 1 Z9 1 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR 24 PY 1998 VL 12 IS 8 SU S MA 984 BP A1480 EP A1480 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 260QN UT WOS:000083961501137 ER PT J AU Xu, X Liu, C Liu, ZY Noguchi, CT AF Xu, X Liu, C Liu, ZY Noguchi, CT TI Activity of the erythropoietin receptor promoter in transgenic mice SO FASEB JOURNAL LA English DT Meeting Abstract C1 NIDDK, Biol Chem Lab, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR 24 PY 1998 VL 12 IS 8 SU S MA 904 BP A1466 EP A1466 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 260QN UT WOS:000083961501059 ER PT J AU Yan, S Rodrigues, RG Roberts, DD AF Yan, S Rodrigues, RG Roberts, DD TI Hemoglobin induces a common receptor on Candida albicans for several extracellular matrix proteins. SO FASEB JOURNAL LA English DT Meeting Abstract C1 NCI, Pathol Lab, NIH, Bethesda, MD 20892 USA. RI Roberts, David/A-9699-2008 OI Roberts, David/0000-0002-2481-2981 NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR 24 PY 1998 VL 12 IS 8 SU S MA 213 BP A1347 EP A1347 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 260QN UT WOS:000083961500369 ER PT J AU Yang, KS Kang, SO Chock, PB Yim, MB AF Yang, KS Kang, SO Chock, PB Yim, MB TI Activation of NF-kappa B by L-ascorbate in Jurkat cells SO FASEB JOURNAL LA English DT Meeting Abstract C1 Seoul Natl Univ, Dept Microbiol, Seoul, South Korea. NHLBI, Biochem Lab, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR 24 PY 1998 VL 12 IS 8 SU S MA 1009 BP A1484 EP A1484 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 260QN UT WOS:000083961501164 ER PT J AU Zeng, EY Soldner, A Schoneberg, T Wess, J AF Zeng, EY Soldner, A Schoneberg, T Wess, J TI Putative disulfide bond in the M3 muscarinic acetylcholine receptor is essential for proper cell surface localization of the receptor protein SO FASEB JOURNAL LA English DT Meeting Abstract C1 NIDDK, Bioorgan Chem Lab, NIH, Bethesda, MD 20892 USA. Free Univ Berlin, Inst Pharmakol, Fachberiech Human Med, D-1000 Berlin, Germany. NR 0 TC 0 Z9 0 U1 0 U2 1 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR 24 PY 1998 VL 12 IS 8 SU S MA 854 BP A1458 EP A1458 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 260QN UT WOS:000083961501008 ER PT J AU Zhao, X Greener, T Greene, LE Eisenberg, E AF Zhao, X Greener, T Greene, LE Eisenberg, E TI Expression of the clathrin assembly protein, auxilin, in tissue culture cells inhibits endocytosis. SO FASEB JOURNAL LA English DT Meeting Abstract C1 NHLBI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR 24 PY 1998 VL 12 IS 8 SU S MA 924 BP A1469 EP A1469 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 260QN UT WOS:000083961501078 ER PT J AU Zhou, X Park, SI Carlson, B Moustafa, M Crain, P Jung, JE Lee, BJ Diamond, A Hatfield, D AF Zhou, X Park, SI Carlson, B Moustafa, M Crain, P Jung, JE Lee, BJ Diamond, A Hatfield, D TI Characterization of selenocysteine (SEC) tRNA population in Drosophila SO FASEB JOURNAL LA English DT Meeting Abstract C1 NIH, Bethesda, MD 20892 USA. Univ Utah, Salt Lake City, UT USA. Univ Chicago, Chicago, IL 60637 USA. SNU, Seoul, South Korea. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR 24 PY 1998 VL 12 IS 8 SU S MA 951 BP A1474 EP A1474 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 260QN UT WOS:000083961501106 ER PT J AU Zhu, X Wess, J AF Zhu, X Wess, J TI N-terminal V2 vasopressin receptor fragments inhibit wild type receptor function via heterodimer formation SO FASEB JOURNAL LA English DT Meeting Abstract C1 NIDDK, Bioorgan Chem Lab, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR 24 PY 1998 VL 12 IS 8 SU S MA 853 BP A1457 EP A1457 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 260QN UT WOS:000083961501007 ER PT J AU Zimmerman, SB Murphy, LD Rosner, JL AF Zimmerman, SB Murphy, LD Rosner, JL TI Urea denaturation of isolated E-coli nucleoids. SO FASEB JOURNAL LA English DT Meeting Abstract C1 NIDDK, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR 24 PY 1998 VL 12 IS 8 SU S MA 760 BP A1442 EP A1442 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 260QN UT WOS:000083961500916 ER PT J AU Li, J Noguchi, CT Miller, W Hardison, R Schechter, AN AF Li, J Noguchi, CT Miller, W Hardison, R Schechter, AN TI Multiple regulatory elements in the 5 '-flanking sequence of the human epsilon-globin gene SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID TRANSGENIC MICE; BETA-GLOBIN; DEVELOPMENTAL REGULATION; FACTOR-BINDING; GAMMA-GLOBIN; SILENCER; REGION; EXPRESSION; ACTIVATION; PROMOTER AB We have previously reported, on the basis of transfection experiments, the existence of a silencer element in the 5'-flanking region of the human embryonic (epsilon) globin gene, located at -270 base pairs 5' to the cap site, which provides negative regulation for this gene. Experiments in transgenic mice suggest the physiological importance of this epsilon-globin silencer, but also suggest that downregulation of epsilon-globin gene expression may involve other negative elements flanking the epsilon-globin gene. We have now extended the analysis of epsilon-globin gene regulation to include the flanking region spanning up to 6 kilobase pairs 5' to the locus control region using reporter gene constructs with deletion mutations and transient transfection assays. We have identified and characterized other strong negative regulatory regions, as well as several positive regions that affect transcription activation. The negative regulatory regions at -3 kilobase pairs (epsilon NRA-I and epsilon NRA-II), flanked by a positive control element, has a strong effect on the epsilon-globin promoter both in erythroid K562 and nonerythroid HeLa cells and contains several binding sites for transcription factor GATA-1, as evidenced from DNA-protein binding assays. The GATA-1 sites within epsilon NRA-II are directly needed for negative control. Both epsilon NRA-I and epsilon NRA-II are active on a heterologous promoter and hence appear to act as transcription silencers. Another negative control region located at -1.7 kilobase pairs (epsilon NRB) does not exhibit general silencer activity as epsilon NRB does not affect transcription activity when used in conjunction with an epsilon-globin minimal promoter, The negative effect of epsilon NRB is erythroid specific, but not stage-specific as it can repress transcription activity in both K562 erythroid cells as well as in primary cultures of adult erythroid cells. Phylogenetic DNA sequence comparisons with other primate and other mammalian species show unusual degree of flanking sequence homology for the epsilon-globin gene, including in several of the regions identified in these functional and DNA-protein binding analyses, providing alternate evidence for their potential importance. We suggest that the down-regulation of epsilon-globin gene expression as development progresses involves complex, cooperative interactions of these negative regulatory elements, epsilon NRA-I/epsilon NRA-II, epsilon NRB, the epsilon-globin silencer and probably other negative and positive elements in the 5'-flanking region of the epsilon-globin gene. C1 NIDDK, Biol Chem Lab, NIH, Bethesda, MD 20892 USA. Penn State Univ, Ctr Gene Regulat, Dept Comp Sci & Engn, University Pk, PA 16802 USA. Penn State Univ, Ctr Gene Regulat, Dept Biochem & Mol Biol, University Pk, PA 16802 USA. RP Schechter, AN (reprint author), NIDDK, Biol Chem Lab, NIH, Bldg 10,Rm 9N-307,10 Ctr Dr,MSC 1822, Bethesda, MD 20892 USA. RI Hardison, Ross/G-1142-2010 OI Hardison, Ross/0000-0003-4084-7516 FU NIDDK NIH HHS [R01 DK27635]; NLM NIH HHS [R01 LM05110, R01 LM05773] NR 36 TC 19 Z9 20 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD APR 24 PY 1998 VL 273 IS 17 BP 10202 EP 10209 DI 10.1074/jbc.273.17.10202 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA ZJ519 UT WOS:000073224200019 PM 9553070 ER PT J AU Lee, SJ Ha, MJ Lee, J Nguyen, P Choi, YH Pirnia, F Kang, WK Wang, XF Kim, SJ Trepel, JB AF Lee, SJ Ha, MJ Lee, J Nguyen, P Choi, YH Pirnia, F Kang, WK Wang, XF Kim, SJ Trepel, JB TI Inhibition of the 3-hydroxy-3-methylglutaryl-coenzyme A reductase pathway induces p53-independent transcriptional regulation of p21(WAF1/CIP1) in human prostate carcinoma cells SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID RETINOBLASTOMA-SUSCEPTIBILITY GENE; CYCLIN-DEPENDENT KINASES; GROWTH-FACTOR-BETA; COMPETITIVE INHIBITOR; MEVALONATE PATHWAY; INDUCED APOPTOSIS; CDK INHIBITOR; CANCER-CELLS; G(1) ARREST; RB PROTEIN AB Progression through the cell cycle is controlled by the induction of cyclins and the activation of cognate cyclin-dependent kinases. The 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitor lovastatin induces growth arrest and cell death in certain cancer cell types. We have pursued the mechanism of growth arrest in PC-3-M cells, a p53-null human prostate carcinoma cell line. Lovastatin treatment increased protein and mRNA levels of the cyclin-dependent kinase inhibitor p21(WAF1/CIP1), increased binding of p21 with Cdk2, markedly inhibited cyclin E-and Cdk2-associated phosphorylation of histone H1 or GST-retinoblastoma protein, enhanced binding of the retinoblastoma protein to the transcription factor E2F-1 in vivo, and induced the activation of a p21 promoter reporter construct. By using p21 promoter deletion constructs, the lovastatin-responsive element was mapped to a region between -93 and -64 relative to the transcription start site. Promoter mutation analysis indicated that the lovastatin-responsive site coincided with the previously identified transforming growth factor-beta-responsive element. These data indicate that in human prostate carcinoma cells an inhibitor of the HMG-CoA reductase pathway can circumvent the loss of wild-type p53 function and induce critical downstream regulatory events leading to transcriptional activation of p21. C1 NCI, Med Branch, NIH, Div Clin Sci, Bethesda, MD 20892 USA. Duke Univ, Med Ctr, Dept Pharmacol, Durham, NC 27710 USA. NCI, Chemoprevent Lab, Div Basic Sci, NIH, Bethesda, MD 20892 USA. RP Trepel, JB (reprint author), NCI, Med Branch, NIH, Div Clin Sci, Bldg 10,Rm 12N226, Bethesda, MD 20892 USA. NR 57 TC 138 Z9 139 U1 0 U2 2 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD APR 24 PY 1998 VL 273 IS 17 BP 10618 EP 10623 DI 10.1074/jbc.273.17.10618 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA ZJ519 UT WOS:000073224200072 PM 9553123 ER PT J AU Zhu, MH Berry, JA Russell, SM Leonard, WJ AF Zhu, MH Berry, JA Russell, SM Leonard, WJ TI Delineation of the regions of interleukin-2 (IL-2) receptor beta chain important for association of Jak1 and Jak3 - Jak1-independent functional recruitment of Jak3 to IL-2R beta SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID GAMMA-CHAIN; SIGNAL-TRANSDUCTION; CYTOPLASMIC DOMAINS; MOLECULAR-CLONING; TYROSINE KINASE; JANUS KINASE; ACTIVATION; CELLS; PHOSPHORYLATION; PROLIFERATION AB Interleukin-2 (IL-2) induces heterodimerization of the IL-2 receptor beta (IL-2R beta) and gamma(c) chains of its receptor and activates the Janus family tyrosine kinases, Jak1 and Jak3, Whereas Jak1 associates with IL-2R beta, Jak3 associates primarily with gamma(c) but also with IL-2R beta. We analyzed four IL-2R beta mutations that diminish IL-2-induced proliferation and found that each also decreased IL-2-induced signal transducer and activator of transcription (STAT) activation. For this reason, and because the mutations were in the IL-2R beta membrane-proximal region, we investigated and found that each mutation diminished IL-2R beta association with both Jak1 and Jak3. This suggested that these Jaks might interact with the same region of IL-2R beta; however, certain IL-2R beta internal deletions and C-terminal truncations differentially affected the association of Jak1 and Jak3, Interestingly, just as Jak1-IL-2R beta association is Jak3-independent and functionally important, we show that Jak3-IL-2R beta association is Jak1-independent and implicate this association as being important for IL-2-induced Stat5 activation. Moreover, Jak1 and Jak3 could associate only in the presence of IL-2R beta, suggesting that these kinases can simultaneously bind to IL-2R beta, Thus, our data not only demonstrate that somewhat more distal as well as membrane-proximal cytoplasmic regions of a type I cytokine receptor are important for Jak kinase association but also suggest that two IL-2R beta-Jak kinase interactions are important for IL-2 signaling. C1 NHLBI, Lab Mol Immunol, NIH, Bethesda, MD 20892 USA. RP Leonard, WJ (reprint author), NHLBI, Lab Mol Immunol, NIH, 10 Ctr Dr, Bethesda, MD 20892 USA. RI Russell, Sarah/B-9341-2009 OI Russell, Sarah/0000-0001-5826-9641 NR 36 TC 52 Z9 52 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD APR 24 PY 1998 VL 273 IS 17 BP 10719 EP 10725 DI 10.1074/jbc.273.17.10719 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA ZJ519 UT WOS:000073224200085 PM 9553136 ER PT J AU Griffith, CE Zhang, WG Wange, RL AF Griffith, CE Zhang, WG Wange, RL TI ZAP-70-dependent and -independent activation of Erk in Jurkat T cells - Differences in signaling induced by H2O2 and CD3 cross-linking SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID PROTEIN-TYROSINE KINASE; ANTIGEN RECEPTOR-ZETA; HYDROGEN-PEROXIDE; LYMPHOCYTES-T; ZAP-70; PHOSPHORYLATION; TRANSDUCTION; EXPRESSION; SLP-76; PATHWAYS AB Oxidative stress in T cells induces signaling events similar to those initiated by T cell antigen receptor engagement, including tyrosine phosphorylation and activation of the critical protein-tyrosine kinase ZAP-70. Distal signaling events such as the activation of mitogen-activated protein kinases and downstream transcription factors are also initiated by oxidative stimuli. In this study Pile, a ZAP-70-negative Jurkat T cell line, was used to investigate the role of ZAP-70 in mediating activation of Erk in response to H2O2. Consistent with the hypothesis that ZAP-70 is required for activation of Erk in response to an oxidative stimulus, Erk1 and Erk2 could be rapidly activated in Jurkat cells but not in P116 cells upon addition of H2O2. P116 cells became competent for H2O2-induced Erk activation upon stable transfection with wild-type ZAP-70. An in vivo ZAP-70 substrate, SLP-76, implicated in Erk activation, also became rapidly tyrosine-phosphorylated in Jurkat cells, but not in P116 cells, upon treatment with H2O2. Surprisingly, although ZAP-70 was required for H2O2-mediated Erk activation, Erk activation in response to T cell antigen receptor engagement did not require ZAP-70. In addition to demonstrating a requirement for ZAP-70 in H2O2-stimulated Erk activation, these results provide the first evidence for the existence of a ZAP-70-independent pathway for Erk activation in T cells. C1 NIA, Biol Chem Lab, Gerontol Res Ctr, NIH, Baltimore, MD 21224 USA. NICHD, Cell Biol & Metab Branch, NIH, Bethesda, MD 20892 USA. RP Wange, RL (reprint author), NIA, Biol Chem Lab, Gerontol Res Ctr, NIH, MSC 12,5600 Nathan Shock Dr, Baltimore, MD 21224 USA. EM wanger@grc.nia.nih.gov NR 52 TC 69 Z9 69 U1 0 U2 1 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD APR 24 PY 1998 VL 273 IS 17 BP 10771 EP 10776 DI 10.1074/jbc.273.17.10771 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA ZJ519 UT WOS:000073224200092 PM 9553143 ER PT J AU Hsu, YT Youle, RJ AF Hsu, YT Youle, RJ TI Bax in murine thymus is a soluble monomeric protein that displays differential detergent-induced conformations SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID PROGRAMMED CELL-DEATH; ROD PHOTORECEPTOR CELLS; MITOCHONDRIAL-MEMBRANES; ENDOPLASMIC-RETICULUM; BCL-2; BCL-X(L); HETERODIMERIZATION; INHIBITION; APOPTOSIS; CHANNEL AB Bcl-2, Bcl-X-L, and Bax are members of the Bcl-2 family that play important roles in apoptosis regulation. These proteins are believed to be membrane-bound and to regulate apoptosis through formation of homo-and heterodimers. However, we recently found by subcellular fractionation that whereas Bcl-2 is predominantly a membrane protein as previously reported, Bax and a significant fraction of Bcl-X-L are soluble in thymocyte and splenocyte extracts. In addition, we have demonstrated that the ability of Bax to form dimers appears to be a detergent-induced phenomenon that coincides with a detergent-induced conformational change. We have further investigated the tertiary and quaternary states of Bax in the presence of various detergents. Detergents such as Triton X-100 and Triton X-114 readily enable Bax hetero-and homodimerization. However, other detergents such as polydocanol, W-l, octyl glucoside, dodecyl maltoside, Tween 20, and sodium cholate allow varying degrees of Bax hetero-and homodimerization. Detergents such as 3-[(3-cholamidopropyl)dimethylammonio]-1-propanesulfonic acid (Chaps) and Brij 35 allow neither hetero-nor homodimer formation. Immunoprecipitation analysis with the conformation-sensitive antibody uBax 6A7 revealed that whereas Triton X-100 readily exposes the N-terminal Bax epitope (amino acid 13-19), only limited exposure of the epitope occurs in Triton X-114, polydocanol, dodecyl maltoside, and sodium cholate, and no exposure of this epitope was observed in W-1, Chaps, octyl glucoside, between 20, and Brij 35. Moreover, we could not detect any proteins associated with the cytosolic form of Bax based on immunopurification of this protein. Sephacryl S-100 gel filtration chromatography analysis of the cytosolic Bax indicated that this protein is monomeric and displays an apparent molecular mass of 25 kDa. Induction of apoptosis which causes the insertion of the soluble form of Bax into membranes did not result in appreciable Bax/Bcl-X-L, Bax/Bcl-2 or Bax/Bax dimer formation as determined by cross-linking studies, Further analysis of Bax after apoptosis induction by immunoprecipitation in the presence of Chaps also revealed no significant heterodimer formation. In conclusion, Bax displays several distinct states in different detergents that expose defined regions of the protein. In addition, these results suggest that mechanisms other than the simple dimerization among members of the Bcl-2 family may be required for the regulation of apoptosis. C1 NINDS, Biochem Sect, Surg Neurol Branch, NIH, Bethesda, MD 20892 USA. RP Youle, RJ (reprint author), NINDS, Biochem Sect, Surg Neurol Branch, NIH, 10 Ctr Dr,Rm 5D-37, Bethesda, MD 20892 USA. EM youle@helix.nih.gov NR 49 TC 400 Z9 409 U1 0 U2 1 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD APR 24 PY 1998 VL 273 IS 17 BP 10777 EP 10783 DI 10.1074/jbc.273.17.10777 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA ZJ519 UT WOS:000073224200093 PM 9553144 ER PT J AU Lunn, G Phillips, LR Pacula-Cox, C AF Lunn, G Phillips, LR Pacula-Cox, C TI Reversed-phase high-performance liquid chromatography of 4-(2-pyridyl)-1-piperazinethiocarboxylic acid 2-[1-(pyridyl)ethylidene]hydrazide dihydrochloride (NSC 348977), a synthetic thiosemicarbazone with antitumor activity SO JOURNAL OF CHROMATOGRAPHY B LA English DT Article DE NSC 348977; thiosemicarbazone ID 2-ACETYLPYRIDINE THIOSEMICARBAZONES; DERIVATIVES; COMPLEXES; INVITRO; AGENTS AB Reversed-phase HPLC conditions for the separation of 4-(2-pyridyl)-1-piperazinethiocarboxylic acid 2-[1-(pyridyl)ethylidene]hydrazide dihydrochloride (NSC 348977, I), a synthetic thiosemicarbazone with antitumor activity, from mouse plasma have been investigated. Following denaturization and precipitation of the spiked plasma with acetonitrile, an aliquot of the supernatant was diluted with aqueous buffer and subjected to analysis on a Nova-Pak C-18 column (150x3.9 mm I.D.) by isocratic elution with 50 mM aqueous potassium phosphate buffer (pH 6.8, containing 1 mM EDTA)-acetonitrile (60:40, v/v). The column effluent was monitored for UV absorption at 310 nm. Problems identified in the sample preparation and separation of I include sensitivity to oxygen, light, non-neutral pH and the presence of metal ions. These factors were seen to adversely influence sample recovery, and attempts were made to find conditions which minimize their effects. (C) 1998 Elsevier Science B.V. C1 NCI, Frederick Canc Res & Dev Ctr, Program Resources Inc Dyncorp, Lab Pharmaceut Chem, Frederick, MD 21702 USA. NCI, Lab Pharmaceut Chem, Dev Therapeut Program, Div Canc Treatment, Frederick, MD 21702 USA. RP Lunn, G (reprint author), US FDA, HFD-530,5600 Fishers Lane, Rockville, MD 20857 USA. FU NCI NIH HHS [N01- CO-74102] NR 20 TC 2 Z9 2 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 APR 24 PY 1998 VL 708 IS 1-2 BP 217 EP 222 DI 10.1016/S0378-4347(97)00637-3 PG 6 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA ZR377 UT WOS:000073968600025 PM 9653965 ER PT J AU Kroutil, LC Frey, MW Kaboord, BF Kunkel, TA Benkovic, SJ AF Kroutil, LC Frey, MW Kaboord, BF Kunkel, TA Benkovic, SJ TI Effect of accessory proteins on T4 DNA polymerase replication fidelity SO JOURNAL OF MOLECULAR BIOLOGY LA English DT Article DE DNA replication; fidelity; accessory proteins; sliding clamp; processivity ID HIV-1 REVERSE-TRANSCRIPTASE; ERROR-PRONE REPLICATION; I KLENOW FRAGMENT; KINETIC-ANALYSIS; BACTERIOPHAGE-T4; EXONUCLEASE; HOLOENZYME; PROCESSIVITY; INVITRO; MISALIGNMENT AB The influence of replication accessory proteins on the fidelity of T4 DNA polymerase has been examined. Steady-state kinetic measurements showed that exonuclease-deficient T4 DNA polymerase, alone or with clamp loaders gp44/gp62 and polymerase clamp gp45, displays decreased binding affinity for incorrect as compared to correct dNTPs and a deceased k(cat) for misinsertion as compared to correct insertion. Kinetic constants were similar with and without accessory proteins, indicating that accessory proteins had little effect on misinsertion. They also had little effect on the K-m value for extension of a T.T mismatch. However, the k(cat), value for T.T mismatch extension was fivefold higher in the presence of the clamp loader and clamp proteins. Thus, in the absence of proofreading, these accessory proteins may promote stable misincorporation. The kinetic analysis is supported by error rate determinations during gap-filling synthesis, which require both misinsertion and mispair extension. For some mispairs, the accuracy of exonuclease-deficient polymerase alone is similar to that in the presence of clamp loader, clamp and single-stranded DNA binding protein (gpp32). However, exonuclease-deficient holoenzyme complex is actually less accurate than the polymerase alone for some base substitutions. We suggest that gp45 promotes extension of mismatches by tethering the polymerase to DNA, a process that may be relevant to replication past lesions or other blocks to DNA synthesis. The error rate for one-nucleotide deletions in homopolymeric runs was similar for the polymerase with or without its accessory proteins. This implies that strand misalignment errors arise during highly processive replication. Thus, either unpaired bases can migrate through the run while the DNA polymerase is bound to the template-primer, or the DNA polymerase dissociates from the DNA to allow misalignment but remains tethered to the template through interactions with the clamp. Finally, the T4 replication accessory proteins reduced by greater than or equal to 10-fold the rate at which exonuclease-deficient T4 DNA polymerase generated deletions of larger numbers of nucleotides, indicating that these proteins influence replication fidelity for other than single base mutations. C1 NIEHS, Mol Genet Lab, Res Triangle Pk, NC 27709 USA. Penn State Univ, Dept Chem, Davey Lab 152, University Pk, PA 16802 USA. RP Kunkel, TA (reprint author), NIEHS, Mol Genet Lab, Res Triangle Pk, NC 27709 USA. FU NIGMS NIH HHS [GM13306] NR 49 TC 33 Z9 33 U1 0 U2 2 PU ACADEMIC PRESS LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0022-2836 J9 J MOL BIOL JI J. Mol. Biol. PD APR 24 PY 1998 VL 278 IS 1 BP 135 EP 146 DI 10.1006/jmbi.1998.1676 PG 12 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA ZM059 UT WOS:000073500600011 PM 9571039 ER PT J AU Horita, DA Baldisseri, DM Zhang, WX Altieri, AS Smithgall, TE Gmeiner, WH Byrd, RA AF Horita, DA Baldisseri, DM Zhang, WX Altieri, AS Smithgall, TE Gmeiner, WH Byrd, RA TI Solution structure of the human Hck SH3 domain and identification of its ligand binding site SO JOURNAL OF MOLECULAR BIOLOGY LA English DT Article DE Hck; SH3; NMR; protein tyrosine kinase; signal transduction ID TRIPLE-RESONANCE NMR; PROTEIN-STRUCTURE DETERMINATION; QUANTITATIVE J-CORRELATION; SIDE-CHAIN RESONANCES; PROLINE-RICH PEPTIDES; CHEMICAL-SHIFT INDEX; TYROSINE KINASE; SECONDARY STRUCTURE; LARGER PROTEINS; C-13 MAGNETIZATION AB SH3 domains are protein binding domains that occur widely among signal transduction proteins. Here, we present the NMR-determined solution structure of the SH3 domain from the cytoplasmic protein tyrosine kinase, Hck. Hck is involved in a number of cell signal transduction pathways, frequently in pathways associated with immune response. SH3 domains bind proteins via a left-handed polyproline type II helix on the target protein. We have assessed the structural impact of binding to a ligand through addition of a peptide corresponding to a proline-rich region of a Hck target, the GTPase activating protein of the Ras pathway. Ligand binding effects small structural changes and stabilizes the SH3 domain structure. Also, we have compared the solution structure of the Hck SH3 domain to the crystal structure of Hck, in which the SH3 domain exhibits an intramolecular binding to an interdomain linker region. These structures are interpreted as the apo-and holo-forms of the Hck SH3 domain. (C) 1998 Academic Press Limited. C1 NCI, Frederick Canc Res & Dev Ctr, ABL Basic Res Program, Frederick, MD 21702 USA. Univ Nebraska, Med Ctr, Eppley Inst Res Canc & Allied Dis, Omaha, NE 68198 USA. RP Byrd, RA (reprint author), NCI, Frederick Canc Res & Dev Ctr, ABL Basic Res Program, Frederick, MD 21702 USA. RI Byrd, R. Andrew/F-8042-2015; OI Byrd, R. Andrew/0000-0003-3625-4232; Horita, David/0000-0002-9563-107X FU NCRR NIH HHS [P41 RR002301] NR 81 TC 27 Z9 30 U1 0 U2 4 PU ACADEMIC PRESS LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0022-2836 J9 J MOL BIOL JI J. Mol. Biol. PD APR 24 PY 1998 VL 278 IS 1 BP 253 EP 265 DI 10.1006/jmbi.1998.1690 PG 13 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA ZM059 UT WOS:000073500600020 PM 9571048 ER PT J AU Dobbins, DE Premen, AJ AF Dobbins, DE Premen, AJ TI Receptor mechanisms of bradykinin-mediated activation of prenodal lymphatic smooth muscle SO REGULATORY PEPTIDES LA English DT Article DE lymphatic contractility; lymph vessel; lymphatic smooth muscle contraction; lymphatic pumping; edema; kinins; adrenergic receptors; bradykinin receptors ID BOVINE MESENTERIC LYMPHATICS; CONSTRICTION; PROSTAGLANDINS; CONTRACTILITY; ANTAGONISTS; HISTAMINE AB We have previously shown that several endogenous vasoactive agents constrict prenodal lymph vessels in the canine forelimb. In this study, we assessed the receptor mechanisms by which bradykinin activates lymphatic smooth muscle. Intralymphatic (i.l.) infusion of bradykinin at concentrations of 3.82 x 10(-6), 3.82 x 10(-5) and 3.82 x 10(-4) molar significantly increased lymphatic perfusion pressure. To determine the potential role of lymphatic alpha-receptors in this response, we infused bradykinin at a concentration of 3.82 x 10(-4) molar i.l. before and during intra-arterial (i.a.) phentolamine administration. Prior to phentolamine, bradykinin resulted in a doubling of the lymphatic perfusion pressure. Phentolamine alone had no effect on the resting lymphatic pressure, but significantly reduced forelimb arterial pressures. When the infusion of bradykinin was repeated during phentolamine administration, there was no significant change in the lymphatic perfusion pressure. To determine the subclass of alpha-adrenergic receptors involved in this response, we infused bradykinin and the alpha(1)-receptor agonist phenylephrine i.l. before and during administration of i.a. prazosin, a specific alpha(1)-receptor antagonist, i.a. Prior to prazosin, both phenylephrine and bradykinin significantly increased lymphatic perfusion pressure. During prazosin administration, neither phenylephrine nor bradykinin significantly altered the lymphatic perfusion pressure. These data indicate that bradykinin-mediated increases in prenodal lymphatic smooth muscle tone are mediated by lymphatic alpha(1)-adrenergic receptors. (C) 1998 Elsevier Science B.V. C1 Uniformed Serv Univ Hlth Sci, Dept Physiol, Bethesda, MD 20814 USA. NIA, Geriat Program, NIH, Bethesda, MD 20892 USA. RP Dobbins, DE (reprint author), Uniformed Serv Univ Hlth Sci, Dept Physiol, 4301 Jones Bridge Rd, Bethesda, MD 20814 USA. NR 19 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0167-0115 J9 REGUL PEPTIDES JI Regul. Pept. PD APR 24 PY 1998 VL 74 IS 1 BP 47 EP 51 DI 10.1016/S0167-0115(98)00017-2 PG 5 WC Endocrinology & Metabolism; Physiology SC Endocrinology & Metabolism; Physiology GA ZR667 UT WOS:000074001700008 PM 9657359 ER PT J AU van Turennout, M Hagoort, P Brown, CM AF van Turennout, M Hagoort, P Brown, CM TI Brain activity during speaking: From syntax to phonology in 40 milliseconds SO SCIENCE LA English DT Article ID PARTIAL INFORMATION; LEXICAL ACCESS; POTENTIALS AB In normal conversation, speakers translate thoughts into words at high speed. To enable this speed, the retrieval of distinct types of linguistic knowledge has to be orchestrated with millisecond precision. The nature of this orchestration is still largely unknown. This report presents dynamic measures of the real-time activation of two basic types of linguistic knowledge, syntax and phonology. Electrophysiological data demonstrate that during noun-phrase production speakers retrieve the syntactic gender of a noun before its abstract phonological properties. This two-step process operates at high speed: the data show that phonological information is already available 40 milliseconds after syntactic properties have been retrieved. C1 Max Planck Inst Psycholinguist, NL-6525 XD Nijmegen, Netherlands. RP van Turennout, M (reprint author), NIMH, Lab Brain & Cognit, Bldg 10,Room 4C104,10 Ctr Dr,MSC 1366, Bethesda, MD 20892 USA. RI Hagoort, Peter/B-7417-2012 NR 13 TC 133 Z9 133 U1 2 U2 17 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA SN 0036-8075 J9 SCIENCE JI Science PD APR 24 PY 1998 VL 280 IS 5363 BP 572 EP 574 PG 3 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA ZJ684 UT WOS:000073242100042 ER PT J AU Hoeg, JM AF Hoeg, JM TI Guidelines for trials of gene therapy and somatic gene therapy in cardiovascular disease SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article; Proceedings Paper CT VIth World Conference on Clinical Pharmacology and Therapeutics CY AUG, 1996 CL BUENOS AIRES, ARGENTINA SP Int Union Pharm C1 NHLBI, Mol Dis Branch, NIH, Bethesda, MD 20892 USA. RP Hoeg, JM (reprint author), Care of Dujovne CA, Kansas Fdn Clin Pharmacol, 10550 Quivira Rd,Suite 240, Overland Pk, KS 66215 USA. NR 7 TC 0 Z9 0 U1 0 U2 0 PU EXCERPTA MEDICA INC PI NEW YORK PA 245 WEST 17TH STREET, NEW YORK, NY 10011 USA SN 0002-9149 J9 AM J CARDIOL JI Am. J. Cardiol. PD APR 23 PY 1998 VL 81 IS 8A SI SI BP 60F EP 63F DI 10.1016/S0002-9149(98)00266-5 PG 4 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA ZN749 UT WOS:000073678300030 PM 9604912 ER PT J AU Vermaak, D Steinbach, OC Dimitrov, S Rupp, RAW Wolffe, AP AF Vermaak, D Steinbach, OC Dimitrov, S Rupp, RAW Wolffe, AP TI The globular domain of histone H1 is sufficient to direct specific gene repression in early Xenopus embryos SO CURRENT BIOLOGY LA English DT Article ID LINKER HISTONES; BINDING-SITE; IN-VIVO; CHROMATIN; NUCLEOSOME; H-1; TRANSCRIPTION; LOCATION; DNA AB One molecule of a linker histone such as histone H1 is incorporated into every metazoan nucleosome [1]. Histone H1 has three distinct structural domains: the positively charged amino-terminal and carboxy-terminal tails are separated by a globular domain that is similar to the winged-helix motif found in sequence-specific DNA-binding proteins [2], The globular domain interacts with DNA immediately contiguous to that wrapped around the core histones [3,4], whereas the tail domains are important for the compaction of nucleosomal arrays [5], Experiments in vivo indicate that histone H1 does not function as a global transcriptional repressor, but instead has more specific regulatory roles [6-9], In Xenopus, maternal stores of the B4 linker histone that are assembled into chromatin during the early cleavage divisions are replaced by somatic histone H1 during gastrulation [10], This transition in chromatin composition causes the repression of genes encoding oocyte-type 5S rRNAs, and restricts the competence of ectodermal cells to differentiate into mesoderm [6,9-11], Here, we demonstrate that the globular domain of histone H1 is sufficient for di recti ng gene-specific transcriptional repression and for restricting the mesodermal competence of embryonic ectoderm, We discuss our results in the context of specific structural roles for this domain in the nucleosome. C1 NICHHD, Mol Embryol Lab, NIH, Bethesda, MD 20892 USA. Max Planck Gesell, Friedrich Miescher Lab, D-72076 Tubingen, Germany. RP Wolffe, AP (reprint author), NICHHD, Mol Embryol Lab, NIH, 18T,Room 106, Bethesda, MD 20892 USA. EM awlme@helix.nih.gov RI dimitrov, stefan/M-7697-2013 NR 19 TC 46 Z9 48 U1 0 U2 2 PU CURRENT BIOLOGY LTD PI LONDON PA 34-42 CLEVELAND STREET, LONDON W1P 6LB, ENGLAND SN 0960-9822 J9 CURR BIOL JI Curr. Biol. PD APR 23 PY 1998 VL 8 IS 9 BP 533 EP 536 DI 10.1016/S0960-9822(98)70206-4 PG 4 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA ZK617 UT WOS:000073343100022 PM 9560345 ER PT J AU Huang, MJ Maynard, A Turpin, JA Graham, L Janini, GM Covell, DG Rice, WG AF Huang, MJ Maynard, A Turpin, JA Graham, L Janini, GM Covell, DG Rice, WG TI Anti-HIV agents that selectively target retroviral nucleocapsid protein zinc fingers without affecting cellular zinc finger proteins SO JOURNAL OF MEDICINAL CHEMISTRY LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; ACID-BINDING-PROTEINS; DNA-BINDING; POLY(ADP-RIBOSE) POLYMERASE; NONINFECTIOUS VIRUS; REPAIR; INHIBITORS; APOPTOSIS; ENZYME; AIDS AB Agents that target the two highly conserved Zn fingers of the human immunodeficiency virus (HIV) nucleocapsid p7 (NCp7) protein are under development as antivirals. These agents covalently modify Zn-coordinating cysteine thiolates of the fingers, causing Zn ejection, loss of native protein structure and nucleic acid binding capacity, and disruption of virus replication. Concentrations of three antiviral agents that promoted in vitro Zn ejection from NCp7 and inhibited HIV replication did not impact the functions of cellular Zn finger proteins, including poly(ADP-ribose) polymerase and the Spl and GATA-1 transcription factors, nor did the compounds inhibit HeLa nuclear extract mediated transcription. Selectivity of interactions of these agents with NCp7 was supported by molecular modeling analysis which (1) identified a common saddle-shaped nucleophilic region on the surfaces of both NCp7 Zn fingers, (2) indicated a strong correspondence between computationally docked positions for the agents tested and overlap of frontier orbitals within the nucleophilic loci of the NCp7 Zn fingers, and (3) revealed selective steric exclusion of the agents from the core of the GATA-1 Zn finger. Further modeling analysis suggests that the thiolate of Cys49 in the carboxy-terminal finger is the site most susceptible to electrophilic attack. These data provide the first experimental evidence and rationale for antiviral agents that selectively target retroviral nucleocapsid protein Zn fingers. C1 NCI, Frederick Canc Res & Dev Ctr, Lab Antiviral Drug Mechanisms, SAIC Frederick, Frederick, MD 21702 USA. NCI, Frederick Canc Res & Dev Ctr, Lab Expt & Computat Biol, SAIC Frederick, Frederick, MD 21702 USA. NCI, Frederick Canc Res & Dev Ctr, Chem Synth & Anal Lab, SAIC Frederick, Frederick, MD 21702 USA. RP Rice, WG (reprint author), NCI, Frederick Canc Res & Dev Ctr, Lab Antiviral Drug Mechanisms, SAIC Frederick, Bldg 431T-B,POB B, Frederick, MD 21702 USA. FU NCI NIH HHS [N01-CO-56000] NR 65 TC 112 Z9 118 U1 1 U2 8 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 APR 23 PY 1998 VL 41 IS 9 BP 1371 EP 1381 DI 10.1021/jm9708543 PG 11 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA ZK644 UT WOS:000073346000004 PM 9554870 ER PT J AU Moro, S Guo, DP Camaioni, E Boyer, JL Harden, TK Jacobson, KA AF Moro, S Guo, DP Camaioni, E Boyer, JL Harden, TK Jacobson, KA TI Human P2Y(1) receptor: Molecular modeling and site-directed mutagenesis as tools to identify agonist and antagonist recognition sites SO JOURNAL OF MEDICINAL CHEMISTRY LA English DT Article ID PURINOCEPTORS; EXPRESSION; PROTEIN; SPECIFICITY; HYDROLYSIS; CLONING; ACIDS AB The molecular basis for recognition by human P2Y(1) receptors of the novel, competitive antagonist 2'-deoxy-N-6-methyladenosine 3',5'-bisphosphate (MRS 2179) was probed using site-directed mutagenesis and molecular modeling. The potency of this antagonist was measured in mutant receptors in which key residues in the transmembrane helical domains (TMs) 3, 5, 6, and 7 were replaced by Ala or other amino acids. The capacity of MRS 2179 to block stimulation of phospholipase C promoted by 2-methylthioadenosine 5'-diphosphate (2-MeSADP) was lost in P2Y(1) receptors having F226A, K280A, or Q307A mutations, indicating that these residues are critical for the binding of the antagonist molecule. Mutation of the residues His132, Thr222, and Tyr136 had an intermediate effect on the capacity of MRS 2179 to block the P2Y(1) receptor. These positions therefore appear to have a modulatory role in recognition of this antagonist. F131A, H277A, T221A, R310K, or S317A mutant receptors exhibited an apparent affinity for PARS 2179 that was similar to that observed with the wild-type receptor. Thus, Phe131, Thr221, His277, and Ser317 are not essential for antagonist recognition. A computer-generated model of the human P2Y(1) receptor was built and analyzed to help interpret these results. The model was derived through primary sequence comparison, secondary structure prediction, and three-dimensional homology building, using rhodopsin as a template, and was consistent with data obtained from mutagenesis studies. We have introduced a "cross-docking" procedure to obtain energetically refined 3D structures of the Ligand-receptor complexes. Cross-docking simulates the reorganization of the native receptor structure induced by a ligand. A putative nucleotide binding site was localized and used to predict which residues are likely to be in proximity to agonists and antagonists. According to our model TM6 and TM7 are close to the adenine ring, TM3 and TM6 are close to the ribose moiety, and TM3, TM6, and TM7 are near the triphosphate chain. C1 NIDDK, Mol Recognit Sect, NIH, LBC, Bethesda, MD 20892 USA. Univ N Carolina, Sch Med, Dept Pharmacol, Chapel Hill, NC 27599 USA. RP Jacobson, KA (reprint author), NIDDK, Mol Recognit Sect, NIH, LBC, Bldg 8A,Rm B1A-19, Bethesda, MD 20892 USA. RI Moro, Stefano/A-2979-2012; Jacobson, Kenneth/A-1530-2009; OI Moro, Stefano/0000-0002-7514-3802; Jacobson, Kenneth/0000-0001-8104-1493; Camaioni, Emidio/0000-0002-8529-0849 FU Intramural NIH HHS [Z99 DK999999, Z01 DK031116-20] NR 29 TC 132 Z9 134 U1 0 U2 1 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 APR 23 PY 1998 VL 41 IS 9 BP 1456 EP 1466 DI 10.1021/jm970684u PG 11 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA ZK644 UT WOS:000073346000013 PM 9554879 ER PT J AU Xiao, W Li, GY Player, MR Maitra, RK Waller, CF Silverman, RH Torrence, PF AF Xiao, W Li, GY Player, MR Maitra, RK Waller, CF Silverman, RH Torrence, PF TI Nuclease-resistant composite 2 ',5 '-oligoadenylate-3 ',5 '-oligonucleotides for the targeted destruction of RNA: 2-5A-iso-antisense SO JOURNAL OF MEDICINAL CHEMISTRY LA English DT Article ID THERAPEUTIC AGENTS; ANTISENSE CHIMERAS; 2-5A ANTISENSE; RIBONUCLEASE; INTERFERON; INHIBITION; CLEAVAGE AB A new modification of 2-5A-antisense, 2-5A-iso-antisense, has been developed based on a reversal of the direction of the polarity of the antisense domain of a 2-5A-antisense composite nucleic acid. This modification was able to anneal with its target RNA as well as the parental 2-5A-antisense chimera. The 2-5A-iso-antisense oligonucleotide displayed enhanced resistance to degradation by 3'-exonuclease enzyme activity such as that represented by snake venom phosphodiesterase and by that found in human serum. 2-5A-Iso-antisense was able to effect the degradation of a synthetic nontargeted substrate, [5'-P-32]pC(11)U(2)C(7), and two targeted RNAs, PKR and BCR mRNAs, in a cell-free system containing purified recombinant human 2-5A-dependent RNase L. These results demonstrated that the novel structural modification represented by 2-5A-iso-antisense provided a stabilized biologically active formulation of the 2-5A-antisense strategy. C1 NIDDKD, Sect Biomed Chem, Med Chem Lab, NIH, Bethesda, MD 20892 USA. Cleveland Clin Fdn, Lerner Res Inst, Dept Canc Biol, Cleveland, OH 44195 USA. RP Torrence, PF (reprint author), NIDDKD, Sect Biomed Chem, Med Chem Lab, NIH, Bldg 8,Rm B2A02, Bethesda, MD 20892 USA. FU NCI NIH HHS [1 PO1 CA 62220] NR 27 TC 19 Z9 20 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 APR 23 PY 1998 VL 41 IS 9 BP 1531 EP 1539 DI 10.1021/jm970841p PG 9 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA ZK644 UT WOS:000073346000020 PM 9554886 ER PT J AU Race, R Chesebro, B AF Race, R Chesebro, B TI Scrapie infectivity found in resistant species SO NATURE LA English DT Letter ID MICE C1 NIAID, Rocky Mt Labs, Persistent Viral Dis Lab, Hamilton, MT 59840 USA. RP Race, R (reprint author), NIAID, Rocky Mt Labs, Persistent Viral Dis Lab, Hamilton, MT 59840 USA. NR 7 TC 90 Z9 94 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 APR 23 PY 1998 VL 392 IS 6678 BP 770 EP 770 DI 10.1038/33834 PG 1 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA ZJ679 UT WOS:000073241200035 PM 9572135 ER PT J AU Albrecht, JH Poon, RYC Ahonen, CL Rieland, BM Deng, CX Crary, GS AF Albrecht, JH Poon, RYC Ahonen, CL Rieland, BM Deng, CX Crary, GS TI Involvement of p21 and p27 in the regulation of CDK activity and cell cycle progression in the regenerating liver SO ONCOGENE LA English DT Article DE cyclins; cyclin-dependent kinases; liver regeneration; G1 phase ID GROWTH-FACTOR-BETA; KINASE INHIBITOR P21; DEPENDENT KINASES; MICE LACKING; RESTRICTION POINT; GENE-EXPRESSION; MESSENGER-RNA; DNA-SYNTHESIS; TGF-BETA; P27(KIP1) AB In tissue culture systems, p21 and p27 inhibit cyclin-dependent kinase (CDK) activity and cell cycle progression in response to numerous stimuli, but little is known about their involvement in cell growth in vivo. We examined the modulation of CDK activity by these proteins after 70% partial hepatectomy (PH), an in vivo model of synchronous hepatocyte cell cycle progression, After PH In BALB/c mice, p21 was induced during the prereplicative (G1) phase and was maximally expressed after peak hepatocyte DNA synthesis. p27 was present in quiescent liver and was minimally induced after PH. p21 and p27 immunoprecipitated with CDK2, CDK4, and cyclin D1 in the regenerating liver. The activity of CDK2-, CDK4- and cyclin D1-associated kinases was upregulated after PH, and maximal activity of these enzyme complexes corresponded to peak DNA synthesis. Immunodepletion experiments suggested that p27 plays a role in downregulating CDK2 activity before and after peak DNA synthesis. Compared to cogenic wild-type mice, p21-/-mice demonstrated evidence of markedly accelerated hepatocyte progression through G1 phase after PH: DNA synthesis, upregulation of cyclin A and PCNA, induction of cyclin D1- and CDK2-associated kinase activity, and appearance of a phosphorylated retinoblastoma protein (Rh) species occurred earlier in the p21-/-mice. These results suggest that p21 and p27 modulate CDK activity in the regenerating liver, and that p21 regulates the rate of progression through G1 phase of the cell cycle in vivo. C1 Hennepin Cty Med Ctr, Dept Med 865B, Minneapolis, MN 55415 USA. Hennepin Cty Med Ctr, Dept Pathol, Minneapolis, MN 55415 USA. Minneapolis Med Res Fdn, Minneapolis, MN 55404 USA. Hong Kong Univ Sci & Technol, Dept Biochem, Kowloon, Hong Kong. NIDDKD, Biochem & Metab Lab, NIH, Bethesda, MD 20892 USA. RP Albrecht, JH (reprint author), Hennepin Cty Med Ctr, Dept Med 865B, 701 Park Ave, Minneapolis, MN 55415 USA. RI deng, chuxia/N-6713-2016; OI Poon, Randy/0000-0001-5571-6231 NR 65 TC 145 Z9 149 U1 0 U2 6 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE RG21 6XS, HAMPSHIRE, ENGLAND SN 0950-9232 J9 ONCOGENE JI Oncogene PD APR 23 PY 1998 VL 16 IS 16 BP 2141 EP 2150 DI 10.1038/sj.onc.1201728 PG 10 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA ZJ077 UT WOS:000073177200012 PM 9572495 ER PT J AU Hou, W Tsuda, T Jensen, RT AF Hou, W Tsuda, T Jensen, RT TI Neuromedin B activates phospholipase D through both PKC-dependent and PKC-independent mechanisms SO BIOCHIMICA ET BIOPHYSICA ACTA-LIPIDS AND LIPID METABOLISM LA English DT Article DE neuromedin B; phospholipase D; phospholipase C; protein kinase C; receptor; calcium ID SWISS 3T3 CELLS; INOSITOL-LIPID HYDROLYSIS; ADP-RIBOSYLATION FACTOR; PROTEIN-KINASE-C; BOMBESIN RECEPTORS; RAT-BRAIN; CAMP ACCUMULATION; STABLE EXPRESSION; CA2+ MOBILIZATION; PHORBOL ESTER AB The actions of neuromedin B (NMB), a recently discovered mammalian bombesin-related peptide, are mediated by interacting with a distinct receptor; however, little is known about its cellular basis of action. Recent studies show activation of phospholipase D (PLD) is an important transduction cascade for a number of GI hormones, especially for stimulation of growth and protein sorting. The purpose of the present study was to determine whether activation of the NMB receptor causes activation of PLD and to explore whether this activation was coupled to PLC activation. Rat C6 glioblastoma cells (C6 cells), which contain a low density of native NMB receptors and BALE 3T3 cells stably transfected with rat NMB receptors, were used. NMB caused a 3-fold increase in C6 cells and an Ii-fold increase in rNMB-R transfected cells in PLD activity. Increases in PLD activity were rapid and NMB was 100-fold more potent than gastrin-releasing peptide (GRP). NMB caused a half-maximal increase in [Ca2+](i) at 0.2 nM, in [H-3]IP and PLD at 1 nM, and half-maximal receptor occupation at 1.2 nM. TPA increased PLD dose-dependently with a half-maximal effect at 60 nM. The calcium ionophore A23187 (1 mu M) alone did not increase PLD activity but potentiated the effect of TPA. The Ca2+-ATPase inhibitor, thapsigargin, did not affect NMB- or TPA-stimulated PLD activities, although it blocked completely the NMB-induced increase in [Ca2+](i), The PKC inhibitor GF109203X completely abolished TPA-induced PLD activity, however, it only inhibited NMB-induced PLD activity by 20%. The combination of thapsigargin and GF109203X had the same effect as GF109203X alone. These data indicate that NMB receptor activation is coupled to both PLC and PLD. In contrast to a number of other phospholipase C-coupled receptors, NMB receptor stimulated changes in [Ca2+](i) do not contribute to PLD activation. Both PKC-dependent and PKC-independent mechanisms are involved in the NMB-stimulated PLD activation with the PKC-independent pathway predominating. Published by Elsevier Science B.V. C1 DDB, NIH, NIDDK, Bethesda, MD 20892 USA. RP Jensen, RT (reprint author), DDB, NIH, NIDDK, Bldg 10,Rm 9C-103,10 Ctr DR MSC 1804, Bethesda, MD 20892 USA. EM robertj@bdg10.niddk.nih.gov NR 59 TC 7 Z9 7 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 APR 22 PY 1998 VL 1391 IS 3 BP 337 EP 350 DI 10.1016/S0005-2760(98)00014-9 PG 14 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA ZK553 UT WOS:000073336400005 PM 9555086 ER PT J AU Kornyshev, AA Leikin, S AF Kornyshev, AA Leikin, S TI Theory of interaction between helical molecules (vol 107, pg 3656, 1997) SO JOURNAL OF CHEMICAL PHYSICS LA English DT Correction C1 Forschungszentrum Julich, Inst Energieverfahrenstech, D-52425 Julich, Germany. NICHHD, Lab Phys & Struct Biol, NIH, Bethesda, MD 20892 USA. RP Kornyshev, AA (reprint author), Forschungszentrum Julich, Inst Energieverfahrenstech, Postfach 1913, D-52425 Julich, Germany. RI Kornyshev, Alexei/C-3404-2008 NR 1 TC 21 Z9 21 U1 0 U2 1 PU AMER INST PHYSICS PI MELVILLE PA CIRCULATION & FULFILLMENT DIV, 2 HUNTINGTON QUADRANGLE, STE 1 N O 1, MELVILLE, NY 11747-4501 USA SN 0021-9606 J9 J CHEM PHYS JI J. Chem. Phys. PD APR 22 PY 1998 VL 108 IS 16 BP 7035 EP 7035 DI 10.1063/1.476117 PG 1 WC Chemistry, Physical; Physics, Atomic, Molecular & Chemical SC Chemistry; Physics GA ZJ230 UT WOS:000073192500056 ER PT J AU Romanova, LY Alexandrov, IA Nordan, RP Blagosklonny, MV Mushinski, JF AF Romanova, LY Alexandrov, IA Nordan, RP Blagosklonny, MV Mushinski, JF TI Cross-talk between protein kinase C-alpha (PKC-alpha) and -delta (PKC-delta): PKC-alpha elevates the PKC-delta protein level, altering its mRNA transcription and degradation SO BIOCHEMISTRY LA English DT Article ID DOWN-REGULATION; PHORBOL ESTER; MESSENGER-RNA; ENDOPLASMIC-RETICULUM; UP-REGULATION; BINDING SITE; CELLS; ISOZYMES; EXPRESSION; PHOSPHORYLATION AB Studies utilizing the overexpression of individual isoforms indicated that both PKC-alpha and -delta promote a number of biological effects, including inhibition of DNA synthesis associated with rearrangements of the actin cytoskeleton in the murine B-cell lymphoma (Baf3), differentiation of the murine promyelocyte line 32D, and activation of MAP kinase in CHO fibroblasts. We postulated that these results reflect some form of cross-regulation between PKC-alpha and -delta rather than their functional redundancy. In this report, we show that overexpression of PKC-alpha in Baf3 and 32D leads to an elevation of the endogenous PKC-delta mRNA and protein levels. The elevated steady-state PKC-delta mRNA level results from a combination of increased PKC-delta transcription and mRNA stability. Upregulation of PKC-delta mRNA by PKC-alpha occurs even after a selective depletion of the PKC-delta protein. In addition, phorbol ester-induced elevation of PKC-delta mRNA and protein levels can be prevented by the PKC inhibitor GF109203X, an indication of the requirement for PKC kinase activity. Inhibition of new protein synthesis by cycloheximide showed that upregulation of PKC-delta mRNA, as opposed to delayed downregulation of the PKC-delta protein, is primarily responsible for the accumulation of this isoform by PKC-alpha. In parental Baf3 and 32D cells and PKC-alpha overexpressers, PKC-alpha and PKC-delta are uniquely involved in cross-regulation, while PKC-epsilon, PKC-eta, and PKC-mu are not. C1 NIH, Natl Canc Inst, Genet Lab, Bethesda, MD 20892 USA. NIH, Natl Canc Inst, Med Branch, Bethesda, MD 20892 USA. US FDA, Ctr Biol Evaluat & Res, Div Monoclonal Antibodies, Bethesda, MD 20892 USA. RP Mushinski, JF (reprint author), NIH, Natl Canc Inst, Genet Lab, Bldg 37,Rm 2B23,37 Convent Dr,MSC 4255, Bethesda, MD 20892 USA. NR 33 TC 44 Z9 45 U1 0 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD APR 21 PY 1998 VL 37 IS 16 BP 5558 EP 5565 DI 10.1021/bi9731807 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA ZM208 UT WOS:000073515500027 PM 9548940 ER PT J AU Lee, RE Brennan, PJ Besra, GS AF Lee, RE Brennan, PJ Besra, GS TI Synthesis of beta-D-arabinofuranosyl-1-monophosphoryl polyprenols: Examination of their function as mycobacterial arabinosyl transferase donors SO BIOORGANIC & MEDICINAL CHEMISTRY LETTERS LA English DT Article ID SALMONELLA-ANATUM; BIOSYNTHESIS; ETHAMBUTOL AB A convenient synthetic strategy has been developed to produce libraries of beta-D-arabinofuranosyl-monophosphorylpolyprenol. Those containing C-50 and C-55 polyprenols were the most active as donors for the cell-free synthesis of the arabinans of mycobacterial cell walls. (C) 1998 Elsevier Science Ltd. All rights reserved. C1 Colorado State Univ, Dept Microbiol, Ft Collins, CO 80523 USA. RP Lee, RE (reprint author), NIAID, Rocky Mt Labs, Lab Intracellular Pathogens, TB Res Unit, Hamilton, MT 59840 USA. RI Lee, Richard/J-4997-2013 OI Lee, Richard/0000-0002-2397-0443 NR 10 TC 29 Z9 29 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0960-894X J9 BIOORG MED CHEM LETT JI Bioorg. Med. Chem. Lett. PD APR 21 PY 1998 VL 8 IS 8 BP 951 EP 954 DI 10.1016/S0960-894X(98)00147-4 PG 4 WC Chemistry, Medicinal; Chemistry, Organic SC Pharmacology & Pharmacy; Chemistry GA ZL750 UT WOS:000073467100013 PM 9871518 ER PT J AU Ziegelstein, RC Blank, PS Cheng, L Capogrossi, MC AF Ziegelstein, RC Blank, PS Cheng, L Capogrossi, MC TI Cytosolic alkalinization of vascular endothelial cells produced by an abrupt reduction in fluid shear stress SO CIRCULATION RESEARCH LA English DT Article DE endothelium; cytosolic pH; shear stress; carboxy-seminaphthorhodafluor-1; DIDS ID MESSENGER-RNA LEVELS; NA+-H+ ANTIPORT; GROWTH-FACTOR; CAROTID BIFURCATION; CL-/HCO3 EXCHANGE; INTRACELLULAR PH; SMOOTH-MUSCLE; BLOOD-FLOW; CALCIUM; ATHEROSCLEROSIS AB Reductions in fluid shear stress produce endothelium-dependent vasoconstriction and promote neointimal hyperplasia, but the intracellular signaling mechanisms involved in these processes are poorly understood. To examine whether decreases in fluid shear stress affect endothelial cytosolic pH, carboxy-seminaphthorhodafluor-1-loaded rat aortic endothelial cells were cultured in glass microcapillary tubes and examined during abrupt reductions in laminar flow. After a 30-minute exposure to a shear stress of 2.7 dyne/cm(2) in bicarbonate buffer, the acute reduction of fluid shear stress from 2.7 to 0.3 dyne/cm(2) transiently increased cytosolic pH from 7.20+/-0.02 to 7.47+/-0.07 (mean+/-SEM, P<.05 versus control). This was not affected by prior inhibition of the Na+-H+ exchanger with 10 mu mol/L ethylisopropylamiloride but was abolished in bicarbonate-free buffer. Recovery from an ammonium chloride prepulse-induced acid load occurred more rapidly when fluid shear stress was abruptly reduced from 2.7 to 0.3 dyne/cm(2) after maximal acidification (+0.04+/-0.02 pH unit at 2 minutes) than when shear stress was maintained at 2.7 dyne/cm(2) continuously (0.00+/-0.00 pH unit at 2 minutes, P<.05). This accelerated cytosolic pH recovery was dependent on the presence of bicarbonate ion and was blocked by the addition of the exchange inhibitors DIDS (100 mu mol/L) and ethylisopropylamiloride or by removal of buffer Na+, indicating that the acute reduction in fluid shear stress activates the extracellular Na+-dependent Cl--HCO3-exchanger and the Na+-H+ exchanger and increases cytosolic pH in vascular endothelial cells. C1 Johns Hopkins Univ, Sch Med, Johns Hopkins Bayview Med Ctr, Dept Med,Div Cardiol, Baltimore, MD 21224 USA. NIA, Cardiovasc Sci Lab, Gerontol Res Ctr, NIH, Baltimore, MD 21224 USA. Ist Dermopatico Immacolata, Lab Patol Vascolare, Rome, Italy. RP Ziegelstein, RC (reprint author), Johns Hopkins Univ, Sch Med, Johns Hopkins Bayview Med Ctr, Dept Med,Div Cardiol, 4940 Eastern Ave, Baltimore, MD 21224 USA. EM rziegels@welchlink.welch.jhu.edu FU NHLBI NIH HHS [HL-03102] NR 39 TC 12 Z9 13 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0009-7330 J9 CIRC RES JI Circ.Res. PD APR 20 PY 1998 VL 82 IS 7 BP 803 EP 809 PG 7 WC Cardiac & Cardiovascular Systems; Hematology; Peripheral Vascular Disease SC Cardiovascular System & Cardiology; Hematology GA ZK048 UT WOS:000073279700008 PM 9562440 ER PT J AU Gindhart, JG Desai, CJ Beushausen, S Zinn, K Goldstein, LSB AF Gindhart, JG Desai, CJ Beushausen, S Zinn, K Goldstein, LSB TI Kinesin light chains are essential for axonal transport in Drosophila SO JOURNAL OF CELL BIOLOGY LA English DT Review ID BOVINE BRAIN KINESIN; MEMBRANOUS ORGANELLES INVIVO; MOTOR-NEURON-DISEASE; HEAVY-CHAIN; CYTOPLASMIC DYNEIN; MONOCLONAL-ANTIBODIES; CONVENTIONAL KINESIN; SYNAPTIC VESICLES; BINDING PROTEIN; ATPASE ACTIVITY AB Kinesin is a heterotetramer composed of two 115-kD heavy chains and two 58-kD light chains. The microtubule motor activity of kinesin is performed by the heavy chains, but the functions of the light chains are poorly understood. Mutations were generated in the Drosophila gene Kinesin light chain (Klc), and the phenotypic consequences of loss of Klc function were analyzed at the behavioral and cellular levels. Loss of Klc function results in progressive lethargy, crawling defects, and paralysis followed by death at the end of the second larval instar. Klc mutant axons contain large aggregates of membranous organelles in segmental nerve axons. These aggregates, or organelle jams (Hurd, D.D., and W.M. Saxton, 1996. Genetics. 144: 1075-1085), contain synaptic vesicle precursors as well as organelles that may be transported by kinesin? kinesin-like protein 68D, and cytoplasmic dynein, thus providing evidence that the loss of Klc function blocks multiple pathways of axonal transport. The similarity of the Klc and Khc (Saxton et al. 1991. Cell 64:1093-1102: Hurd, D.D., and W.M. Saxton. 1996. Genetics 144: 1075-1085) mutant phenotypes indicates that KLC is essential for kinesin function, perhaps by tethering KHC to intracellular cargos or by activating the kinesin motor. C1 Univ Calif San Diego, Dept Pharmacol, Div Mol & Cellular Med, Howard Hughes Med Inst, La Jolla, CA 92093 USA. CALTECH, Div Biol, Pasadena, CA 91125 USA. NINDS, Neurobiol Lab, NIH, Bethesda, MD 20892 USA. RP Goldstein, LSB (reprint author), Univ Calif San Diego, Dept Pharmacol, Div Mol & Cellular Med, Howard Hughes Med Inst, La Jolla, CA 92093 USA. NR 100 TC 124 Z9 125 U1 0 U2 4 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0021-9525 J9 J CELL BIOL JI J. Cell Biol. PD APR 20 PY 1998 VL 141 IS 2 BP 443 EP 454 DI 10.1083/jcb.141.2.443 PG 12 WC Cell Biology SC Cell Biology GA ZK156 UT WOS:000073291000012 PM 9548722 ER PT J AU Huang, H Paul, WE AF Huang, H Paul, WE TI Impaired interleukin 4 signaling in T helper type 1 cells SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article ID RECEPTOR-GAMMA-CHAIN; JAK-3 JANUS KINASE; MICE LACKING JAK3; IL-2 RECEPTOR; FUNCTIONAL COMPONENT; GENE-EXPRESSION; MYELOID CELLS; LYMPHOCYTES-T; BETA-CHAIN; STAT6 AB Cluster of differentation (CD)4(+) T helper cells (Th)1s fail to produce interleukin (IL)-4. Even if restimulated in the presence of IL-4, a condition that induces IL-4-producing capacity in naive CD4(+) T cells, This fail to become IL-4 producers. We report that Th1 cells have a major impairment in IL-4 signaling. When compared to both Th2s and naive T cells, they display a striking diminution in phosphorylation of Stat6. They also show reduced phosphorylation of Janus kinase (JAK)-3 and insulin receptor substrate (IRS)-2 when compared to Th2s. Stat6 and JAK-3 are present in equivalent amounts in Th1s and Th2s, but IRS-2 protein levels are much lower in Th1s than in Th2s. Altered sensitivity to IL-4, the major inducer of the Th2 phenotype,may explain the stability of the Th1 state. C1 NIAID, Immunol Lab, NIH, Bethesda, MD 20892 USA. RP Paul, WE (reprint author), NIAID, Immunol Lab, NIH, Bldg 10,Rm 11N311,10 Ctr Dr,MSC 1892, Bethesda, MD 20892 USA. NR 58 TC 79 Z9 80 U1 0 U2 0 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0022-1007 J9 J EXP MED JI J. Exp. Med. PD APR 20 PY 1998 VL 187 IS 8 BP 1305 EP 1313 DI 10.1084/jem.187.8.1305 PG 9 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA ZK126 UT WOS:000073287900014 PM 9547341 ER PT J AU Zhou, P Seder, RA AF Zhou, P Seder, RA TI CD40 ligand is not essential for induction of type 1 cytokine responses or protective immunity after primary or secondary infection with Histoplasma capsulatum SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article ID EXPERIMENTAL ALLERGIC ENCEPHALOMYELITIS; CELL-MEDIATED-IMMUNITY; CD4(+) T-CELLS; IFN-GAMMA; COSTIMULATORY ACTIVITY; MONOCLONAL-ANTIBODIES; LEISHMANIA-MAJOR; INTERFERON-GAMMA; DENDRITIC CELLS; DEFICIENT MICE AB The induction of type 1 immune responses (interleukin [IL]-12, interferon [IFN]-gamma) has been shown to be important in mediating protection against many intracellular infections including Histoplasma capsulatum. Costimulatory molecules such as CD40 ligand (CD40L) have been shown to be a central regulator of type 1 responses in vivo. To study the role of CD40L in mediating protection against infection with H. capsulatum, CD40L-deficient (CD40L(-/-)) and CD40L(+/+) mice were infected with H. capsulatum and assessed for various parameters. After a lethal challenge of H. capsulatum, CD40L(-/-) mice were not substantially different from CD40L(+/+) mice in terms of mortality, fungal burden, or production of IFN-gamma, IL-12, nitric oxide, or tumor necrosis factor alpha. Moreover, CD40L(-/-) mice treated with anti-IFN-gamma or anti-IL-12 at the time of infection had accelerated mortality, providing further evidence that IL-12 and IFN-gamma are produced in vivo in the absence of CD40L. In addition, CD40L(-/-) mice infected with a sublethal dose of H. capsulatum survived infection, whereas all mice infected with the same dose and treated with anti-IFN-gamma had accelerated mortality, demonstrating that IFN-gamma but not CD40L was essential for primary immunity to H, capsulatum infection. Interestingly, depletion of either CD4(+) or CD8(+) T cells resulted in accelerated mortality in CD40L(-/-) mice, suggesting a critical role for these cells in response to infection. Finally, CD40L(-/-) mice initially infected with a sublethal dose of H. capsulatum were protected from secondary infection with a lethal dose of H. capsulatum, demonstrating that CD40L is not required for the maintenance of memory immunity. C1 NIAID, Clin Immunol Sect, Clin Invest Lab, NIH, Bethesda, MD 20892 USA. RP Seder, RA (reprint author), NIAID, Clin Immunol Sect, Clin Invest Lab, NIH, Bldg 10,Rm 11C215,9000 Rockville Pike, Bethesda, MD 20892 USA. EM rseder@nih.gov NR 60 TC 55 Z9 56 U1 0 U2 0 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0022-1007 J9 J EXP MED JI J. Exp. Med. PD APR 20 PY 1998 VL 187 IS 8 BP 1315 EP 1324 DI 10.1084/jem.187.8.1315 PG 10 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA ZK126 UT WOS:000073287900015 PM 9547342 ER PT J AU Grewal, RP Cantor, R Turner, G Grewal, RK Detera-Wadleigh, SD AF Grewal, RP Cantor, R Turner, G Grewal, RK Detera-Wadleigh, SD TI Genetic mapping and haplotype analysis of oculopharyngeal muscular dystrophy SO NEUROREPORT LA English DT Article DE chromosome 14q11.2-q13; genetics; haplotype analysis; Hispanic Americans; linkage analysis; oculopharyngeal muscular dystrophy ID CHROMOSOME 14Q11.2-Q13; LINKAGE; LOCUS; MAPS AB OCULOPHARYNGEAL muscular dystrophy (OPMD) is an autosomal dominant muscular dystrophy characterized by late onset ptosis, proximal muscle weakness and swallowing difficulties. This disease has been recently linked to chromosome 14q11.2-q13 in French-Canadian pedigrees. We studied three unrelated American families with OPMD of Hispanic descent and our results indicate that in this ethnic group, this disease also maps to chromosome 14q11.2-q13 (marker MYH7.24; Z(max) = 3.98; theta(max) = 0). These results represent an independent demonstration of disease linkage in a second distinct ethnic group. Furthermore, our analysis demonstrates a unique haplotype that is shared by affected individuals from all three families suggesting a founder effect for OPMD in this population. Meiotic recombinants and radiation hybrid mapping permit the narrowing of the critical region to 1 Mb which will facilitate positional cloning of the OPMD disease gene. (C) 1998 Rapid Science Ltd. C1 Univ So Calif, Sch Med, Dept Neurol, Los Angeles, CA 90089 USA. Cedars Sinai Med Ctr, Div Med Genet, Los Angeles, CA 90048 USA. NIMH, Unit Gene Mapping & Express, Clin Neurogenet Branch, NIH, Bethesda, MD 20892 USA. Kaiser Permanente, Dept Ophthalmol, W Los Angeles, CA USA. RP Grewal, RP (reprint author), Univ So Calif, Sch Med, Dept Neurol, SHS 172, Los Angeles, CA 90089 USA. FU NIA NIH HHS [K12AG00521] NR 12 TC 6 Z9 6 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0959-4965 J9 NEUROREPORT JI Neuroreport PD APR 20 PY 1998 VL 9 IS 6 BP 961 EP 965 DI 10.1097/00001756-199804200-00002 PG 5 WC Neurosciences SC Neurosciences & Neurology GA ZM026 UT WOS:000073497300003 PM 9601650 ER PT J AU Brown, P AF Brown, P TI BSE: the final resting place SO LANCET LA English DT Editorial Material ID SURVIVAL; VARIANT C1 NINDS, Cent Nervous Syst Studies Lab, Bethesda, MD 20892 USA. RP Brown, P (reprint author), NINDS, Cent Nervous Syst Studies Lab, Bethesda, MD 20892 USA. NR 10 TC 17 Z9 18 U1 0 U2 1 PU LANCET LTD PI LONDON PA 42 BEDFORD SQUARE, LONDON WC1B 3SL, ENGLAND SN 0140-6736 J9 LANCET JI Lancet PD APR 18 PY 1998 VL 351 IS 9110 BP 1146 EP 1147 DI 10.1016/S0140-6736(05)79115-7 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA ZJ483 UT WOS:000073220200003 PM 9643681 ER PT J AU Hibbeln, JR AF Hibbeln, JR TI Fish consumption and major depression SO LANCET LA English DT Letter C1 NIAAA, Outpatient Clin, Rockville, MD 20852 USA. RP Hibbeln, JR (reprint author), NIAAA, Outpatient Clin, Rockville, MD 20852 USA. NR 5 TC 459 Z9 475 U1 2 U2 26 PU LANCET LTD PI LONDON PA 42 BEDFORD SQUARE, LONDON WC1B 3SL, ENGLAND SN 0140-6736 J9 LANCET JI Lancet PD APR 18 PY 1998 VL 351 IS 9110 BP 1213 EP 1213 DI 10.1016/S0140-6736(05)79168-6 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA ZJ483 UT WOS:000073220200069 PM 9643729 ER PT J AU Evans, RL Turner, RJ AF Evans, RL Turner, RJ TI Evidence for a physiological role of NH4+ transport on the secretory Na+-K+-2Cl-cotransporter SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article DE salivary fluid secretion; Na+-K+-2Cl(-) cotransport; exocrine glands; NH4+ transport; stimulus-secretion coupling ID PAROTID ACINAR-CELLS; FLUID SECRETION; NA+/H+ EXCHANGE; RAT; COTRANSPORTER; LOCALIZATION; MECHANISMS AB The secretory Na+-K+-2Cl(-) cotransporter in salivary acinar cells is responsible for driving the transepithelial Cl- fluxes that give rise to fluid secretion. We demonstrate that the application of the muscarinic agonist carbachol to rat parotid acini results in an intracellular acid load that can be blocked by bumetanide, a specific inhibitor of the cotransporter. One component of this bumetanide-sensitive acid load is ouabain-sensitive while a second is dependent on the presence of sub-millimolar concentrations of NH4+ in our media. Our data indicate that this latter effect arises from NH4+ entry on the cotransporter operating in a Na+-NH4+-2Cl(-) cotransport mode and that at physiological NH4+ levels in the rat (similar to 0.1 mM), 10-15% of the acinar Cl- entry occurs via this route. We suggest that Na+-NH4+-2Cl(-) cotransport may also play a significant physiological role in other cell types and that this mode of operation of the secretory Na+-K+-2Cl(-) cotransporter could account for the currently unexplained presence of this protein in a number of tissues. (C) 1998 Academic Press. C1 NIDR, Membrane Biol Sect, Gene Therapy & Therapeut Branch, NIH, Bethesda, MD 20892 USA. Univ Rochester, Sch Med & Dent, Dept Dent Res, Rochester, NY 14642 USA. RP Evans, RL (reprint author), NIDR, Membrane Biol Sect, Gene Therapy & Therapeut Branch, NIH, Bethesda, MD 20892 USA. NR 30 TC 13 Z9 14 U1 0 U2 0 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD APR 17 PY 1998 VL 245 IS 2 BP 301 EP 306 DI 10.1006/bbrc.1998.8428 PG 6 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA ZK046 UT WOS:000073279500003 PM 9571145 ER PT J AU Player, MR Kalinichenko, EN Podkopaeva, TL Mikhailopulo, IA Seela, F Torrence, PF AF Player, MR Kalinichenko, EN Podkopaeva, TL Mikhailopulo, IA Seela, F Torrence, PF TI Dissection of the roles of adenine ring nitrogen (N-1) and exocyclic amino (N-6) moieties in the interaction of 2-5A with RNase L SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article ID BIOLOGICAL-ACTIVITY; RIBONUCLEASE-L; ANALOGS; BINDING; ACTIVATION; BASE AB To elucidate further the roles played by the adenine bases in the interaction of RNase L (EC 3.1.2.6) with the 2',5'-oligoadenylate 2-5A, p5'A2'(p5'A2')(n)p5' A, a series of sequence-specific 1-deazaadenosine (c(1)A)-substituted analogues were synthesized and evaluated for their ability to bind to and activate human RNase L in comparison to earlier reported inosine-substituted congeners of 2-5A. Substitution of only the 5'-terminal adenosine of p5'A2'p5'A2 p5 A with c(1)A afforded an analogue with strongly diminished RNase L binding and activation ability, While replacement of the second or middle adenosine of p5 A2' p5'A2'p5' A had only a modest effect. In distinct contrast to p5'A2'p5'A2'p5'I, the c(1)A analogue with the third or 2'-terminal adenosine replacement approached parent p5' A2'p5'A2'p5' A in RNase L activation ability. These results permitted a further dissection of the role of various nucleotidic functional groups in the interaction of 2-5A with RNase L: specifically, that the 5'-terminal adenosine purine N-1 moiety is key for binding to RNase L, while the 2'-terminal adenosine N-6 exocyclic amino group is critical for RNase L activation. (C) 1998 Academic Press. C1 NIDDKD, Sect Biomed Chem, Med Chem Lab, NIH, Bethesda, MD 20892 USA. Byelarussian Acad Sci, Inst Bioorgan Chem, Minsk 220141, Byelarus. Univ Osnabruck, Inst Chem, Organ & Bioorgan Chem Lab, D-49076 Osnabruck, Germany. RP Torrence, PF (reprint author), NIDDKD, Sect Biomed Chem, Med Chem Lab, NIH, Bethesda, MD 20892 USA. NR 26 TC 4 Z9 4 U1 0 U2 0 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD APR 17 PY 1998 VL 245 IS 2 BP 430 EP 434 DI 10.1006/bbrc.1998.8451 PG 5 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA ZK046 UT WOS:000073279500027 PM 9571169 ER PT J AU Lin, SH Cheng, HW Earley, K Luo, WP Chou, J AF Lin, SH Cheng, HW Earley, K Luo, WP Chou, J TI Demonstration of adhesion activity of the soluble Ig-domain protein C-CAM4 by attachment to the plasma membrane SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article ID CELL-CELL ADHESION; PREGNANCY-SPECIFIC BETA-1-GLYCOPROTEIN; CARCINOEMBRYONIC ANTIGEN FAMILY; INTERCELLULAR-ADHESION; BILIARY GLYCOPROTEIN; MOLECULAR-BIOLOGY; ECTO-ATPASE; C-CAM; SURFACE; EXPRESSION AB The carcinoembryonic antigen (CEA) family is a large group of proteins with immunoglobulin (Ig)-like structures. The membrane-associated CEA-family proteins have been shown to mediate intercellular adhesion. In addition to these membrane-associated proteins, several secreted CELL-like proteins, such as C-CAM4, PSG1b, and PSG11s, have also been identified. The functions of these soluble proteins are not clear because they cannot support intercellular adhesion like the membrane-associated proteins can. A fundamental question important for understanding the functions of these soluble proteins is whether they can interact in a homophilic fashion as do many of their membrane-associated homologues. We found that the homophilic interactions between these soluble proteins were too weak to be detected by solution binding assays, This is not unexpected because interactions between adhesion molecules are usually transient and weak to allow for control of association and dissociation. By expressing these soluble CEA-family proteins, C-CAM4, PSG1b, and PSG11s, as membrane-anchored forms, we showed that C-CAM4 could mediate intercellular adhesion, whereas PSG1b and PSG11s, despite their 52 % identity to C-CAM4, could not. These results suggest that C-CAM4, but not PSG1b and PSG11s, can probably form homodimers. Thus, these secretory CEA-family members most likely have different interaction mechanisms, i.e., C-CAM4 might function as dimers, while PSGs might function as monomers. (C) 1998 Academic Press. C1 Univ Texas, Md Anderson Canc Ctr, Dept Mol Pathol, Houston, TX 77030 USA. NIH, Sect Cell Differentiat, Bethesda, MD 20892 USA. RP Lin, SH (reprint author), Univ Texas, Md Anderson Canc Ctr, Dept Mol Pathol, Box 89,1515 Holcombe Blvd, Houston, TX 77030 USA. FU NCI NIH HHS [CA64856] NR 24 TC 6 Z9 6 U1 0 U2 0 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD APR 17 PY 1998 VL 245 IS 2 BP 472 EP 477 DI 10.1006/bbrc.1998.8381 PG 6 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA ZK046 UT WOS:000073279500035 PM 9571177 ER PT J AU Crespo, P de Mora, JF Aaronson, DS Santos, E Gutkind, JS AF Crespo, P de Mora, JF Aaronson, DS Santos, E Gutkind, JS TI Transforming G protein-coupled receptors block insulin and ras-induced adipocytic differentiation in 3T3-L1 cells: Evidence for a PKC and MAP kinase independent pathway SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article ID GROWTH-FACTOR; INDUCED PHOSPHORYLATION; GENE-EXPRESSION; TUMOR PROMOTERS; ACTIVATION; FIBROBLASTS; INHIBITION; STIMULATION; SHC; PROSTACYCLIN AB We have used the expression of muscarinic m1 receptors in the preadipocytic 3T3-L1 cell line for dissecting the nature of the G protein-linked pathways governing adipocytic differentiation, a complex process controlled by many stimuli and their downstream targets. 3T3-L1 cells can be differentiated by insulin or by ras oncogenes, and MAP kinase has been implicated in this process. However, mi stimulation failed to induce differentiation of 3T3-L1 cells. Furthermore, it prevented insulin or v-ras-induced adipocytic differentiation, utilizing a protein kinase C-independent pathway. mi stimulation did not alter the phosphorylation state of the insulin receptor substrates IRS-1 and SHC, nor the recruitment of Grb-S. Interestingly, whereas mi receptors potently activated MAP kinase, another differentiation-inhibitor, TNF alpha, did not affect it. These results suggest that the control of adipocytic differentiation can occur utilizing a biochemical route independent of protein kinase C, and acting downstream, or independently from the Ras-MAP kinase pathway. (C) 1998 Academic Press. C1 NIDR, Mol Signalling Unit, Cellular Dev & Oncol Lab, NIH, Bethesda, MD 20892 USA. NCI, Cellular & Mol Biol Lab, NIH, Bethesda, MD 20892 USA. RP Crespo, P (reprint author), Univ Cantabria, Fac Med, Dept Biol Mol, Cardenal Herrera Oria SN, E-39011 Santander, Spain. EM crespop@medi.unican.es RI Gutkind, J. Silvio/A-1053-2009; Crespo, Piero/M-3273-2014; Font de Mora, Jaime/H-6304-2015 OI Crespo, Piero/0000-0003-2825-7783; Font de Mora, Jaime/0000-0002-6816-2095 NR 40 TC 5 Z9 5 U1 0 U2 1 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD APR 17 PY 1998 VL 245 IS 2 BP 554 EP 561 DI 10.1006/bbrc.1998.8480 PG 8 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA ZK046 UT WOS:000073279500052 PM 9571194 ER PT J AU Mertani, HC Garcia-Caballero, T Lambert, A Gerard, F Palayer, C Boutin, JM Vonderhaar, BK Waters, MJ Lobie, PE Morel, G AF Mertani, HC Garcia-Caballero, T Lambert, A Gerard, F Palayer, C Boutin, JM Vonderhaar, BK Waters, MJ Lobie, PE Morel, G TI Cellular expression of growth hormone and prolactin receptors in human breast disorders SO INTERNATIONAL JOURNAL OF CANCER LA English DT Article ID POLYMERASE CHAIN-REACTION; HUMAN DIGESTIVE TISSUES; MAMMARY-GLAND; MESSENGER-RNA; GENE-EXPRESSION; CANCER CELLS; FACTOR-I; CARCINOMA; IDENTIFICATION; LOCALIZATION AB Growth hormone (GH) and prolactin (PRL) exert their regulatory functions in the mammary gland by acting on specific receptors, Using isotopic in situ hybridization and immunohistochemistry, we have localized the expression of hGH receptor (hGHR) and hPRL receptor (hPRLR) in a panel of human breast disorders. Surgical specimens from adult females included normal breast, inflamatory lesions (mastitis) benign proliferative breast disease (fibroadenoma, papilloma, adenosis, epitheliosis), intraductal carcinoma or lobular carcinoma in situ, and invasive ductal, lobular or medullary carcinoma. Cases of male breast enlargement (gynecomastia) were also studied. In site hybridization analysis demonstrated the co-expression of hGHR and hPRLR mRNA in all samples tested, Epithelial cells of both normal and tumor tissues were labelled. Quantitative estimation of receptor mRNA levels was regionally measured in areas corresponding to tumor cells and adipose cells from the same section. It demonstrated large individual variation and no correlation emerged according to the histological type of lesion. Receptor immunoreactivity was detected both in the cytoplasm and nuclei or in the cytoplasm alone, Scattered stromal cells were found positive in some cases, but the labeling intensity was always weaker than for neoplastic epithelial cells. Our results demonstrate the expression of the hGHR and hPRLR genes and their translation in epithelial cells of normal, proliferative and neoplastic lesions of the breast, They also demonstrate that stromal components express GHR and PRLR genes. Thus the putative role of hGH or hPRL in the progression of proliferative mammary disorders is not due to grossly altered levels of receptor expression. (C) 1998 Wiley-Liss, Inc. C1 Natl Univ Singapore, Inst Mol & Cell Biol, Singapore 117609, Singapore. Univ Lyon 1, CNRS, UMR 5578, F-69622 Villeurbanne, France. Univ Santiago, Hosp Gen Galicia, Fac Med, Dept Ciencias Morfol, Santiago De Compostela, Spain. Lab Marcel Merieux, Lyon, France. NCI, Mol & Cellular Endocrinol Sect, Lab Tumor Immunol & biol, NIH, Bethesda, MD USA. Univ Queensland, Dept Physiol & Pharmacol, Brisbane, Qld 4072, Australia. RP Mertani, HC (reprint author), Natl Univ Singapore, Inst Mol & Cell Biol, 30 Med Dr, Singapore 117609, Singapore. RI ASTAR, IMCB/E-2320-2012; Garcia-Caballero, Tomas/H-7213-2015 NR 53 TC 122 Z9 123 U1 0 U2 2 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0020-7136 J9 INT J CANCER JI Int. J. Cancer PD APR 17 PY 1998 VL 79 IS 2 BP 202 EP 211 PG 10 WC Oncology SC Oncology GA ZL132 UT WOS:000073402000017 PM 9583737 ER PT J AU Vestner, B Bustin, M Gruss, C AF Vestner, B Bustin, M Gruss, C TI Stimulation of replication efficiency of a chromatin template by chromosomal protein HMG-17 SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID SIMIAN VIRUS-40 DNA; HISTONE ACETYLATION; T-ANTIGEN; MULTIPLE FUNCTIONS; NUCLEOSOMAL DNA; XENOPUS EGGS; TRANSCRIPTION; COMPLEX; INVITRO; CELLS AB The effect of chromosomal protein HMG-17 on the replication of a chromatin template was studied with minichromosomes containing the SV40 origin of replication. The minichromosomes were assembled from M13 DNA in Xenopus egg extracts in either the absence or presence of HMG-17. Structural data show that HMG-17 was efficiently incorporated into the chromatin and induced an extended chromatin structure. Using an in vitro SV40 replication system, we find that minichromosomes containing HMG-17 replicate with higher efficiency than minichromosomes deficient of HMG-17. The replicational potential of chromatin was enhanced only when HMG-17 was incorporated into the template during, but not after, chromatin assembly. HMG-17 stimulated replication only from a chromatin template, but not from protein-free DNA. Thus, HMG-17 protein enhances the rate of replication of a chromatin template by unfolding the higher order chromatin structure and increasing the accessibility of target sequences to components of the replication machinery. C1 Univ Konstanz, Div Biol, D-78457 Konstanz, Germany. NCI, Mol Carcinogenesis Lab, NIH, Bethesda, MD 20892 USA. RP Gruss, C (reprint author), Univ Konstanz, Div Biol, Univ Str 10, D-78457 Konstanz, Germany. RI Bustin, Michael/G-6155-2015 NR 57 TC 44 Z9 53 U1 0 U2 2 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD APR 17 PY 1998 VL 273 IS 16 BP 9409 EP 9414 DI 10.1074/jbc.273.16.9409 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA ZH610 UT WOS:000073128800011 PM 9545265 ER PT J AU Feng, JQ Luan, XH Wallace, J Jing, D Ohshima, T Kulkarni, AB D'Souza, RN Kozak, CA MacDougall, M AF Feng, JQ Luan, XH Wallace, J Jing, D Ohshima, T Kulkarni, AB D'Souza, RN Kozak, CA MacDougall, M TI Genomic organization, chromosomal mapping, and promoter analysis of the mouse dentin sialophosphoprotein (Dspp) gene, which codes for both dentin sialoprotein and dentin phosphoprotein SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID RAT INCISOR; SEQUENCE DETERMINATION; PHOSPHOPHORYN; BIOSYNTHESIS; PROTEINS; RECEPTOR AB Our laboratory has reported that two major noncollagenous dentin proteins, dentin sialoprotein and dentin phosphoprotein, are specific cleavage products of a larger precursor protein termed dentin sialophosphoprotein (MacDougall, M., Simmons, D., Luan, X., Nydegger, J., Feng, J. Q., and Gu, T. T. (1997) J. Biol. Chem. 272:835-842). To confirm our single gene hypothesis and initiate in vitro promoter studies, we have characterized the structural organization of the mouse dentin sialophosphoprotein gene. This gene has a transcription unit of similar to 9.4 kilobase pairs and is organized into 5 exons and 4 introns. Exon 1 contains a noncoding 5' sequence, and exon 2 contains the transcriptional start site, signal peptide, and first two amino acids of the NH2 terminus. Exons 3 and 4 contain coding information for 29 and 314 amino acids, respectively. The remainder of the coding information and the untranslated 3' region are contained in exon 5. Chromosomal mapping localized the gene to mouse chromosome 5q21 in close proximity to other dentin/bone matrix genes. Computer analysis of the promoter proximal 1.6-kilobase pair sequence revealed a number of potentially important cis-regulatory sequences; these include the recognition elements of AP-1, AP-2, Msx-1, serum response elements, SP-1, and TCF-1. In vitro studies showed that the DSPP promoter is active in an odontoblast cell line, MO6-G3, with basal activity mapped to -95 bp. Two potential enhancer and suppresser elements were identified in the regions between -1447 and -791 bp and -791 and -95 bp, respectively. The structural organization of the dentin sialophosphoprotein gene confirms our finding that both dentin sialoprotein and dentin phosphoprotein are encoded by a single gene with a continuous open reading frame. C1 Univ Texas, Hlth Sci Ctr, Sch Dent, Dept Pediat Dent, San Antonio, TX 78284 USA. NIDR, Gene Targeting Res & Core Facil, NIH, Bethesda, MD 20892 USA. Univ Texas, Hlth Sci Ctr, Dent Branch, San Antonio, TX 78284 USA. NIAID, NIH, Bethesda, MD 20892 USA. RP MacDougall, M (reprint author), Univ Texas, Hlth Sci Ctr, Sch Dent, Dept Pediat Dent, 7703 Floyd Curl Dr, San Antonio, TX 78284 USA. OI D'Souza, Rena/0000-0002-1505-5173 FU NIDCR NIH HHS [DE 09875, DE 11685] NR 39 TC 151 Z9 167 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD APR 17 PY 1998 VL 273 IS 16 BP 9457 EP 9464 DI 10.1074/jbc.273.16.9457 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA ZH610 UT WOS:000073128800018 PM 9545272 ER PT J AU Edwards, GM Wilford, FH Liu, XW Hennighausen, L Djiane, J Streuli, CH AF Edwards, GM Wilford, FH Liu, XW Hennighausen, L Djiane, J Streuli, CH TI Regulation of mammary differentiation by extracellular matrix involves protein-tyrosine phosphatases SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID CELL-CYCLE PROGRESSION; EPITHELIAL-CELLS; GENE-EXPRESSION; DNA-BINDING; SIGNAL-TRANSDUCTION; BASEMENT-MEMBRANE; KINASE JAK2; ACTIVATION; PROLACTIN; PHOSPHORYLATION AB Extracellular matrix and growth factors cooperate to regulate signaling pathways and gene transcription in adherent cells. However, the mechanism of extracellular matrix signaling is poorly defined. In mammary gland, the expression of milk protein genes is controlled by cross-talk between signals derived from the basement membrane protein, laminin, and the lactogenic hormone, prolactin. Signals from basement membrane are transduced by beta(1) integrins and are required for prolactin to activate DNA binding of the milk protein gene transcription factor, Stat5. Here we show that basement membrane is necessary for tyrosine phosphorylation of the prolactin receptor and thus directly affects cytokine signaling and differentiation at the level of the plasma membrane. Prolactin does not induce tyrosine phosphorylation of its receptor, Jak2, or Stat5 in nondifferentiated breast epithelia cultured on collagen I, and we show that this is due to a vanadate-sensitive activity that inhibits the prolactin pathway. We suggest that protein-tyrosine phosphatases are novel targets for regulation by extracellular matrix and in mammary cells represent an additional control to the requirement of integrins for milk protein production. C1 Univ Manchester, Sch Biol Sci, Manchester M13 9PT, Lancs, England. INRA, Unite Endocrinol Mol, F-78352 Jouy En Josas, France. NIDDK, Biochem & Metab Lab, NIH, Bethesda, MD 20892 USA. RP Streuli, CH (reprint author), Univ Manchester, Sch Biol Sci, 3-239 Stopford Bldg,Oxford Rd, Manchester M13 9PT, Lancs, England. FU Wellcome Trust NR 54 TC 73 Z9 74 U1 1 U2 1 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD APR 17 PY 1998 VL 273 IS 16 BP 9495 EP 9500 DI 10.1074/jbc.273.16.9495 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA ZH610 UT WOS:000073128800023 PM 9545277 ER PT J AU Bodor, J Habener, JF AF Bodor, J Habener, JF TI Role of transcriptional repressor ICER in cyclic AMP-mediated attenuation of cytokine gene expression in human thymocytes SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID ACTIVATED T-CELLS; RESPONSE ELEMENT-BINDING; ACCESSORY MOLECULE CD28; INTERLEUKIN-2 PROMOTER; CAMP INHIBITION; PROTEIN-KINASE; NUCLEAR FACTOR; IL-2; CREB; LYMPHOCYTES AB Proliferating human medullary thymocytes can exhibit characteristic T helper cell type 1 cytokine responses exemplified by the immediate early expression of interleukin-2, interferon-gamma, tumor necrosis factor-alpha, and lymphotoxin-beta. Here we report that cAMP-mediated attenuation of the transcription of T helper-1-specific cytokine genes in human medullary thymocytes correlates with the induction of the cAMP-mediated transcriptional repressor ICER (inducible cAMP early repressor). We show that ICER binds specifically to several NFAT/AP-1 (nuclear factor of activated T cells/activating protein-1) composite DNA sites essential for the activation of the interleukin (IL)-2 promoter as well as to a homologous DNA motif present in the proximal segment of the interferon-gamma promoter, In the presence of the minimal NFAT DNA-binding domain, which is sufficient for both DNA binding and AP-1 complex formation, ICER and NFAT form NFAT/ICER ternary complexes on several NFAT/AP-1 DNA composite sites previously identified as essential for the expression of the immunoregulatory cytokines such as IL-2, IL-4, granulocyte-macrophage colony-stimulating factor, and tumor necrosis factor-alpha. In extracts prepared from human medullary thymocytes treated with forskolin and ionomycin, these composite sites bind endogenously expressed ICER either singly or in complexes. Moreover, in Jurkat cells, ectopically expressed ICER represses transcription from NFAT-mediated, phorbol ester/ionophore-activated IL-2, granulocyte-macrophage colony-stimulating factor, and tumor necrosis factor-alpha promoters. We present evidence that ICER interactions with NFAT/AP-1 composite DNA sites correlate with its ability to repress transcription. These findings provide further insight into the mechanisms involved in cAMP-mediated transcriptional attenuation of cytokine expression. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Mol Endocrinol Lab,Howard Hughes Med Inst, Boston, MA 02114 USA. RP Bodor, J (reprint author), NCI, Expt Immunol Branch, Div Basic Sci, NIH, Bldg 10,R4B14,10 Ctr Dr, Bethesda, MD 20892 USA. EM Bodorj@exchange.nih.gov FU NIDDK NIH HHS [DK 25532] NR 46 TC 94 Z9 97 U1 0 U2 2 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD APR 17 PY 1998 VL 273 IS 16 BP 9544 EP 9551 DI 10.1074/jbc.273.16.9544 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA ZH610 UT WOS:000073128800030 PM 9545284 ER PT J AU Lincoln, AJ Monczak, Y Williams, SC Johnson, PF AF Lincoln, AJ Monczak, Y Williams, SC Johnson, PF TI Inhibition of CCAAT/enhancer-binding protein alpha and beta translation by upstream open reading frames SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID TRANSCRIPTIONAL ACTIVATOR PROTEIN; DECARBOXYLASE MESSENGER-RNA; ACUTE-PHASE RESPONSE; C/EBP-ALPHA; ADIPOCYTE DIFFERENTIATION; 3T3-L1 PREADIPOCYTES; MYELOMONOCYTIC CELLS; EUKARYOTIC RIBOSOMES; GENE-EXPRESSION; FAMILY AB CCAAT/enhancer-binding protein (C/EBP) alpha is a bZIP transcription factor whose expression is restricted to specific cell types. Analysis of C/EBP alpha mRNA and protein levels in various mammalian cells indicates that expression of this gene is controlled both transcriptionally and post-transcriptionally. We report here that C/EBP alpha translation is repressed in several cell lines by an evolutionarily conserved upstream open reading frame (uORF), which acts in cis to inhibit C/EBP alpha translation. Mutations that disrupt the uORF completely abolished translational repression of C/EBP alpha. The related c/ebp beta gene also contains an uORF that suppresses translation. The length of the spacer sequence between the uORF terminator and the ORF initiator codon (7 bases in all c/ebp alpha genes and 4 bases in c/ebp beta homologs) is precisely conserved. The effects of insertions, deletions, and base substitutions in the C/EBP alpha spacer showed that both the length and nucleotide sequence of the spacer are important for efficient translational repression. Our data indicate that the uORFs regulate translation of full-length C/EBP alpha and C/EBP beta and do not play a role in generating truncated forms of these proteins, as has been suggested by start site multiplicity models. C1 NCI, Frederick Canc Res & Dev Ctr, Adv Biosci Labs, Basic Res Program,NIH, Frederick, MD 21702 USA. RP Johnson, PF (reprint author), NCI, Frederick Canc Res & Dev Ctr, Adv Biosci Labs, Basic Res Program,NIH, POB B, Frederick, MD 21702 USA. EM johnsopf@fcrfv1.ncifcrf.gov RI Johnson, Peter/A-1940-2012 OI Johnson, Peter/0000-0002-4145-4725 NR 63 TC 73 Z9 74 U1 1 U2 1 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD APR 17 PY 1998 VL 273 IS 16 BP 9552 EP 9560 DI 10.1074/jbc.273.16.9552 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA ZH610 UT WOS:000073128800031 PM 9545285 ER PT J AU Pohl, M Wank, SA AF Pohl, M Wank, SA TI Molecular cloning of the helodermin and exendin-4 cDNAs in the lizard - Relationship to vasoactive intestinal polypeptide/pituitary adenylate cyclase activating polypeptide and glucagon-like peptide 1 and evidence against the existence of mammalian homologues SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID GASTRIN-RELEASING PEPTIDE; GILA MONSTER VENOM; AMINO-ACID-SEQUENCES; GUINEA-PIG PANCREAS; THYROID C-CELLS; PROLINE ENDOPEPTIDASE; AMPHIBIAN BOMBESIN; DISPERSED ACINI; NEUROMEDIN-B; RAT AB Helodermin and exendin-4, two peptides isolated from the salivary gland of the Gila monster, Heloderma suspectum, are approximately 50% homologous to vasoactive intestinal peptide (VIP) and glucagon-like peptide-1 (GLP-1), respectively, and interact with the mammalian receptors for VIP and GLP-1 with equal or higher affinity and efficacy, Immunohistochemical studies suggested the presence of helodermin-like peptides in mammals. To determine whether helodermin and exendin-4 are present in mammals and their evolutionary relationship to VIP and GLP-1, their cDNAs were first cloned from Gila monster salivary gland. Northern blots and reverse transcription-polymerase chain reaction of multiple Gila monster tissues identified similar to 500-base pair transcripts only from salivary gland. Both helodermin and exendin-4 full-length cDNAs were similar to 500 base pairs long, and they encoded precursor proteins containing the entire amino acid sequence of helodermin and exendin-4, as well as a 44- or 45-amino acid N-terminal extension peptide, respectively, having similar to 60% homology, The size and structural organization of these cDNAs indicated that they were closely related to one another but markedly different from known cDNAs for the VIP/GLP-1 peptide family previously identified in both lower and higher evolved species. Cloning of the Gila monster VIP/peptide histidine isoleucine, pituitary adenylate cyclase activating polypeptide, and glucagon/GLP-1 cDNAs and Southern blotting of Gila monster DNA demonstrate the coexistence of separate genes for these peptides and suggests, along with the restricted salivary gland expression, that helodermin and exendin-4 coevolved to serve a separate specialized function. Probing of a variety of rat and human tissues on Northern blots, human and rat Southern blots, and genomic and cDNA libraries with either helodermin-or exendin-4-specific cDNAs failed to identify evidence for mammalian homologues, These data indicate that helodermin and exendin-4 are not the precursors to VIP and GLP-1 and that they belong to a separate peptide family encoded by separate genes. Furthermore, the existence of as yet undiscovered mammalian homologues to helodermin and exendin-4 seems unlikely. C1 NIDDK, Digest Dis Branch, NIH, Bethesda, MD 20892 USA. RP NIDDK, Digest Dis Branch, NIH, Bldg 10,Rm 9C-103, Bethesda, MD 20892 USA. NR 45 TC 50 Z9 60 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 APR 17 PY 1998 VL 273 IS 16 BP 9778 EP 9784 DI 10.1074/jbc.273.16.9778 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA ZH610 UT WOS:000073128800061 PM 9545315 ER PT J AU Bai, RL Choe, K Ewell, JB Nguyen, NY Hamel, E AF Bai, RL Choe, K Ewell, JB Nguyen, NY Hamel, E TI Direct photoaffinity labeling of cysteine-295 of alpha-tubulin by guanosine 5 '-triphosphate bound in the nonexchangeable site SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID EXCHANGEABLE NUCLEOTIDE SITE; AMINO-ACID-SEQUENCE; DIMER DISSOCIATION; BETA-TUBULIN; FLUORESCENCE ANISOTROPY; PORCINE BRAIN; BINDING SITE; GTP; MICROTUBULES; POLYMERIZATION AB The alpha beta-tubulin heterodimer has two high affinity guanosine 5'-triphosphate binding sites, so that purified tubulin usually contains two molecules of bound guanosine nucleotide. Half this nucleotide is freely exchangeable with exogenous guanine nucleotide, and its binding site has been readily localized to the beta-subunit, The remaining nonexchangeable guanosine 5'-triphosphate can only be released from tubulin by denaturing the protein. We replaced the exchangeable site nucleotide of tubulin with 2'-deoxyguanosine 5'-diphosphate, exposed the resulting tubulin to ultraviolet light, degraded the protein, and isolated ribose-containing peptide derived from the nonexchangeable site. A large cyanogen bromide peptide was recovered, and its further degradation with endoproteinase Glu-C established that cysteine-295 of alpha-tubulin was the major reactive amino acid cross-linked to guanosine by ultraviolet irradiation. C1 NIH, Frederick Canc Res & Dev Ctr, Div Canc Treatment & Diag,Dev Therapeut Program, Lab Drug Discovery Res & Dev, Frederick, MD 21702 USA. NIH, Frederick Canc Res & Dev Ctr, Sci Applicat Int Corp, Frederick, MD 21702 USA. US FDA, Ctr Biol Evaluat & Res, Facil Biotechnol Resources, Bethesda, MD 20892 USA. RP Hamel, E (reprint author), NIH, Bldg 37,Rm 5D02, Bethesda, MD 20892 USA. NR 28 TC 9 Z9 9 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD APR 17 PY 1998 VL 273 IS 16 BP 9894 EP 9897 DI 10.1074/jbc.273.16.9894 PG 4 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA ZH610 UT WOS:000073128800077 PM 9545331 ER PT J AU Fitzgerald, DJ Fryling, CM McKee, ML Vennari, JC Wrin, T Cromwell, MEM Daugherty, AL Mrsny, RJ AF Fitzgerald, DJ Fryling, CM McKee, ML Vennari, JC Wrin, T Cromwell, MEM Daugherty, AL Mrsny, RJ TI Characterization of V3 loop-Pseudomonas exotoxin chimeras - Candidate vaccines for human immunodeficiency virus-1 SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID PRINCIPAL NEUTRALIZING DOMAIN; HIV-SERONEGATIVE VOLUNTEERS; RECEPTOR-RELATED PROTEIN; ANTIBODY-RESPONSES; MONOCLONAL-ANTIBODIES; RECOMBINANT GP160; PEPTIDE VACCINE; PRIMARY ISOLATE; T-CELLS; INFECTION AB To develop a candidate vaccine for human immunodeficiency virus, type 1 (HIV-1), chimeric proteins were constructed by inserting sequences derived from the V3 loop of gp120 into a nontoxic form of Pseudomonas exotoxin (PE). Inserts of 14 or 26 amino acids, constrained by a disulfide bond, were introduced between domains II and III of PE. V3 loop-toxin proteins expressed in Escherichia coli and corresponding to either MN (subtype B) or Thai (subtype E) strains, were recognized by strain-specific monoclonal anti-gp120 antibodies. When loop sequences were introduced into an enzymatically active form of the toxin, there was no loss of toxin-mediated cell killing, suggesting that these sequences were co-transported to the cytosol. Sera from rabbits injected with nontoxic PE-V3 loop chimeras were reactive for strain-specific gp120s in Western blots, immunocapture assays, enzyme-linked immunosorbent assays, and neutralized HIV-1 infectivity. Since toxin vectors were designed to receive oligonucleotide duplexes encoding any V3 loop sequence, this approach should allow for the production of V3 loop-toxin chimeras corresponding to multiple HIV isolates. C1 NCI, NIH, Biotherapy Sect, Mol Biol Lab,Div Basic Sci, Bethesda, MD 20892 USA. Genentech Inc, Pharmaceut Res & Dev, Cell Banking, S San Francisco, CA 94080 USA. Genentech Inc, Pharmaceut Res & Dev, Drug Delivery Biol, S San Francisco, CA 94080 USA. RP Fitzgerald, DJ (reprint author), Bldg 37,Rm 4B03,37 Convent Dr,MSC 4255, Bethesda, MD 20892 USA. NR 52 TC 13 Z9 13 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD APR 17 PY 1998 VL 273 IS 16 BP 9951 EP 9958 DI 10.1074/jbc.273.16.9951 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA ZH610 UT WOS:000073128800085 PM 9545339 ER PT J AU Yang, FQ Quan, J Zhang, TY Ito, Y AF Yang, FQ Quan, J Zhang, TY Ito, Y TI Multidimensional counter-current chromatographic system and its application SO JOURNAL OF CHROMATOGRAPHY A LA English DT Article DE counter-current chromatography; multidimensional separation; Ginkgo biloba; Hippophae rhamnoides; isorhamnetin; kaempferol; quercetin; flavone aglycones; aglycones ID SEPARATION; FLAVONOIDS AB A multidimensional counter-current chromatographic system was set up for the first time with two sets of high-speed counter-current chromatography instruments. This system was successfully applied to the preparative separation of isorhamnetin, kaempferol and quercetin from crude flavone aglycones of Ginkgo biloba L. and Hippophae rhamnoides L. with a two-phase solvent system composed of chloroform-methanol-water (4:3:2, v/v/v). (C) 1998 Elsevier Science B.V. C1 NHLBI, Biophys Chem Lab, NIH, Bethesda, MD 20892 USA. Beijing Inst New Technol Applicat, Beijing 100035, Peoples R China. RP Ito, Y (reprint author), NHLBI, Biophys Chem Lab, NIH, Bldg 10, Bethesda, MD 20892 USA. NR 6 TC 52 Z9 60 U1 2 U2 10 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0021-9673 J9 J CHROMATOGR A JI J. Chromatogr. A PD APR 17 PY 1998 VL 803 IS 1-2 BP 298 EP 301 DI 10.1016/S0021-9673(97)01273-9 PG 4 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA ZK989 UT WOS:000073387800030 PM 9604337 ER PT J AU Dorgai, L Sloan, S Weisberg, RA AF Dorgai, L Sloan, S Weisberg, RA TI Recognition of core binding sites by bacteriophage integrases SO JOURNAL OF MOLECULAR BIOLOGY LA English DT Article DE site-specific recombination; lysogeny; DNA-protein interaction; specificity determinants; evolution ID PROTEIN-DNA COMPLEX; PHAGE-LAMBDA; INT PROTEIN; RECOMBINATION SPECIFICITY; IDENTIFYING DETERMINANTS; ATTACHMENT SITES; STRAND EXCHANGE; SEQUENCE; CONSTRUCTION; MUTANTS AB Bacteriophage integrases promote recombination between DNA molecules that carry attachment sites. They are members of a large and widely distributed family of site-specific recombinases with diverse biological roles. The integrases of phages lambda and HK022 are closely related members' of this family, but neither protein efficiently recombines the attachment sites of the other phage. The nucleotides responsible for this specificity difference are located close to the points of recombinational strand exchange, within an integrase binding motif called the extended core binding site. There are four imperfectly repeated copies of this motif in each set of phage attachment sites, but only two, B' and C, contain major specificity determinants. When these specificity determinants were replaced by the corresponding nucleotides from a site with the alternative specificity, the resulting mutant was recombined by both integrases. Thus, the determinants act by impeding recombination promoted by the non-cognate integrase. We found that identical nucleotide substitutions within different core site copies had different effects on recombination, suggesting that integrase does not recognize each of the extended core binding sites in the same way. Finally, substitution at several positions in lambda integrase with the corresponding HK022-specific amino acids prevents recombination of lambda attachment sites, and this defect can be suppressed in an allele-specific manner by appropriate substitutions of HK022-specific nucleotides in the extended core binding sites. (C) 1998 Academic Press Limited. C1 NICHHD, Sect Microbial Genet, Genet Mol Lab, NIH, Bethesda, MD 20892 USA. Zoltan Bay Inst Biotechnol, Szeged, Hungary. RP Weisberg, RA (reprint author), NICHHD, Sect Microbial Genet, Genet Mol Lab, NIH, Bethesda, MD 20892 USA. NR 36 TC 26 Z9 27 U1 0 U2 0 PU ACADEMIC PRESS LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0022-2836 J9 J MOL BIOL JI J. Mol. Biol. PD APR 17 PY 1998 VL 277 IS 5 BP 1059 EP 1070 DI 10.1006/jmbi.1998.1642 PG 12 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA ZL475 UT WOS:000073436600006 PM 9571022 ER PT J AU Mandel-Gutfreund, Y Margalit, H Jernigan, RL Zhurkin, VB AF Mandel-Gutfreund, Y Margalit, H Jernigan, RL Zhurkin, VB TI A role for CH center dot center dot center dot O interactions in protein-DNA recognition SO JOURNAL OF MOLECULAR BIOLOGY LA English DT Article DE protein-DNA recognition; hydrogen bonds; CH center dot center dot center dot O interactions; electrostatics ID REPRESSOR-OPERATOR COMPLEX; CRYSTAL-STRUCTURE; HYDROGEN-BONDS; NUCLEIC-ACIDS; 2.5-ANGSTROM RESOLUTION; BINDING DOMAIN; MINOR-GROOVE; CRYSTALLOGRAPHIC EVIDENCE; B/HLH/Z DOMAIN; ATOMIC CHARGES AB The concept of CH ... O hydrogen bonds has recently gained much interest, with a number of reports indicating the significance of these non-classical hydrogen bonds in stabilizing nucleic acid and protein structures. Here, we analyze the CH ... O interactions in the protein-DNA interface, based on 43 crystal structures of protein-DNA complexes. Surprisingly, we find that the number of close intermolecular CH ... O contacts involving the thymine methyl group and position C5 of cytosine is comparable to the number of protein-DNA hydrogen bonds involving nitrogen and oxygen atoms as donors and acceptors. A comprehensive analysis of the geometries of these close contacts shows that they are similar to other CH ... O interactions found in proteins and small molecules, as well as to classical NH ... O hydrogen bonds. Thus, we suggest that C5 of cytosine and C5-Met of thymine form relatively weak CH ... O hydrogen bonds with Asp, Asn, Glu, Gin, Ser, and Thr, contributing to the specificity of recognition. Including these interactions, in addition to the classical protein-DNA hydrogen bonds, enables the extraction of simple structural principles for amino acid-base recognition consistent with electrostatic considerations. (C) 1998 Academic Press Limited. C1 Hebrew Univ Jerusalem, Hadassah Med Sch, Dept Mol Genet & Biotechnol, IL-91120 Jerusalem, Israel. RP Margalit, H (reprint author), NCI, Lab Expt & Computat Biol, NIH, Bldg 12B,Rm B116,MSC 5677,12 South Dr, Bethesda, MD 20892 USA. RI Jernigan, Robert/A-5421-2012; Margalit, Hanah/H-1651-2013 NR 70 TC 127 Z9 130 U1 0 U2 2 PU ACADEMIC PRESS LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0022-2836 J9 J MOL BIOL JI J. Mol. Biol. PD APR 17 PY 1998 VL 277 IS 5 BP 1129 EP 1140 DI 10.1006/jmbi.1998.1660 PG 12 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA ZL475 UT WOS:000073436600011 PM 9571027 ER PT J AU Dell'Angelica, EC Klumperman, J Stoorvogel, W Bonifacino, JS AF Dell'Angelica, EC Klumperman, J Stoorvogel, W Bonifacino, JS TI Association of the AP-3 adaptor complex with clathrin SO SCIENCE LA English DT Article ID PROTEIN; VESICLES; MEMBRANE; SUBUNITS; BINDING; GOLGI AB A heterotetrameric complex termed AP-3 is involved in signal-mediated protein sorting to endosomal-lysosomal organelles. AP-3 has been proposed to be a component of a nonclathrin coat. In vitro binding assays showed that mammalian AP-3 did associate with clathrin by interaction of the appendage domain of its beta 3 subunit with the amino-terminal domain of the clathrin heavy chain. The beta 3 appendage domain contained a conserved consensus motif for clathrin binding. AP-3 colocalized with clathrin in cells as observed by immunofluorescence and immunoelectron microscopy. Thus, AP-3 function in protein sorting may depend on clathrin. C1 NICHHD, Cell Biol & Metab Branch, NIH, Bethesda, MD 20892 USA. Univ Utrecht, Sch Med, Dept Cell Biol, Inst Biomembranes, NL-3584 CX Utrecht, Netherlands. RP Bonifacino, JS (reprint author), NICHHD, Cell Biol & Metab Branch, NIH, Bethesda, MD 20892 USA. EM juan@helix.nih.gov OI Bonifacino, Juan S./0000-0002-5673-6370 NR 27 TC 275 Z9 278 U1 1 U2 6 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA SN 0036-8075 J9 SCIENCE JI Science PD APR 17 PY 1998 VL 280 IS 5362 BP 431 EP 434 DI 10.1126/science.280.5362.431 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA ZH907 UT WOS:000073159600046 PM 9545220 ER PT J AU Peters, R Sikorski, R AF Peters, R Sikorski, R TI Beauty in simplicity SO SCIENCE LA English DT Article C1 Harvard Univ, Sch Med, Boston, MA 02115 USA. NCI, Bethesda, MD 20892 USA. RP Peters, R (reprint author), Harvard Univ, Sch Med, Boston, MA 02115 USA. NR 3 TC 0 Z9 0 U1 0 U2 1 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA SN 0036-8075 J9 SCIENCE JI Science PD APR 17 PY 1998 VL 280 IS 5362 BP 456 EP 457 PG 2 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA ZH907 UT WOS:000073159600055 PM 9575088 ER PT J AU Peters, R Sikorski, R AF Peters, R Sikorski, R TI Showing off your lab SO SCIENCE LA English DT Article C1 Harvard Univ, Sch Med, Boston, MA 02115 USA. NCI, Bethesda, MD 20892 USA. RP Peters, R (reprint author), Harvard Univ, Sch Med, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA SN 0036-8075 J9 SCIENCE JI Science PD APR 17 PY 1998 VL 280 IS 5362 BP 457 EP 457 PG 1 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA ZH907 UT WOS:000073159600056 ER PT J AU Papile, LA Tyson, JE Stoll, BJ Wright, LL Donovan, EF Bauer, CR Krause-Steinrauf, H Verter, J Korones, SB Lemons, JA Fanaroff, AA Stevenson, DK AF Papile, LA Tyson, JE Stoll, BJ Wright, LL Donovan, EF Bauer, CR Krause-Steinrauf, H Verter, J Korones, SB Lemons, JA Fanaroff, AA Stevenson, DK TI A multicenter trial of two dexamethasone regimens in ventilator-dependent premature infants SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID CHRONIC LUNG-DISEASE; EARLY POSTNATAL DEXAMETHASONE; RESPIRATORY-DISTRESS SYNDROME; BIRTH-WEIGHT INFANTS; BRONCHOPULMONARY DYSPLASIA; FOLLOW-UP; PRETERM INFANTS; CLINICAL-TRIALS; THERAPY AB Background Ventilator-dependent premature infants are often treated with dexamethasone. However, the optimal timing of therapy is unknown. Methods We compared the benefits and hazards of initiating dexamethasone therapy at two weeks of age and at four weeks of age in 371 ventilator-dependent very-low-birth-weight infants (501 to 1500 g) who had respiratory-index scores (mean airway pressure x the fraction of inspired oxygen) of greater than or equal to 2.4 at two weeks of age. One hundred eighty-two infants received dexamethasone for two weeks followed by placebo for two weeks, and 189 infants received placebo for two weeks followed by either dexamethasone (those with a respiratory-index score of greater than or equal to 2.4 on treatment day 14) or additional placebo for two weeks. Dexamethasone was given at a dose of 0.25 mg per kilogram of body weight twice daily intravenously or orally for five days, and the dose was then tapered. Results The median time to ventilator independence was 36 days in the dexamethasone-placebo group and 37 days in the placebo-dexamethasone group. The incidences of chronic lung disease (defined as the need for oxygen supplementation at 36 weeks' postconceptional age) were 66 percent and 67 percent, respectively. Dexamethasone was associated with an increased incidence of nosocomial bacteremia (relative risk, 1.5; 95 percent confidence interval, 1.1 to 2.1) and hyperglycemia (relative risk, 1.9; 95 percent confidence interval, 1.2 to 3.0) in the dexamethasone-placebo group, elevated blood pressure (relative risk, 2.9; 95 percent confidence interval, 1.2 to 6.9) in the placebo-dexamethasone group, and diminished weight gain and head growth (P<0.001) in both groups. Conclusions Treatment of ventilator-dependent premature infants with dexamethasone at two weeks of age is more hazardous and no more beneficial than treatment at four weeks of age. (C) 1998, Massachusetts Medical Society. C1 Univ New Mexico, Hlth Sci Ctr, Dept Pediat, Albuquerque, NM 87131 USA. Univ Texas, SW Med Ctr, Dallas, TX USA. Emory Univ, Atlanta, GA 30322 USA. NICHHD, Bethesda, MD 20892 USA. Univ Cincinnati, Cincinnati, OH 45221 USA. Univ Miami, Miami, FL 33152 USA. George Washington Univ, Ctr Biostat, Rockville, MD USA. Univ Tennessee, Memphis, TN USA. Indiana Univ, Indianapolis, IN 46204 USA. Case Western Reserve Univ, Cleveland, OH 44106 USA. Stanford Univ, Stanford, CA 94305 USA. Brown Univ, Women & Infants Hosp, Providence, RI USA. Yale Univ, New Haven, CT USA. Wayne State Univ, Detroit, MI USA. RP Papile, LA (reprint author), Univ New Mexico, Hlth Sci Ctr, Dept Pediat, UNMH ACC 3 W, Albuquerque, NM 87131 USA. FU NICHD NIH HHS [U10 HD27851, U10 HD21373, U10 HD27881] NR 30 TC 105 Z9 108 U1 0 U2 0 PU MASS MEDICAL SOC PI BOSTON PA 10 SHATTUCK, BOSTON, MA 02115 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD APR 16 PY 1998 VL 338 IS 16 BP 1112 EP 1118 DI 10.1056/NEJM199804163381604 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA ZH080 UT WOS:000073070100004 PM 9545359 ER PT J AU Wise, SC Burmeister, LA Zhou, XF Bubulya, A Oberfield, JL Birrer, MJ Shemshedini, L AF Wise, SC Burmeister, LA Zhou, XF Bubulya, A Oberfield, JL Birrer, MJ Shemshedini, L TI Identification of domains of c-Jun mediating androgen receptor transactivation SO ONCOGENE LA English DT Article DE c-Jun; androgen receptor; transactivation ID ACTIVATED PROTEIN-KINASES; MAMMARY-TUMOR VIRUS; NUCLEAR RECEPTORS; TRANSCRIPTIONAL ACTIVATION; GLUCOCORTICOID RECEPTOR; ESTROGEN-RECEPTOR; RESPONSE ELEMENT; AP-1 ACTIVITY; FUNCTION AF-2; IN-VITRO AB The proto-oncoprotein c-Jun, when complexed with c-Fos, forms the climeric complex identified as AP-1 which regulates transcription directly by binding to AP-1-responsive genes. We have previously reported an indirect mechanism by which c-Jun is able to regulate transcription by stimulating androgen receptor transactivation in the absence of c-Fos or any apparent DNA binding. A series of c-Jun mutants were tested in order to characterize the domains of c-Jun responsible for this effect. The studies reported here indicate that functional bZIP region and a portion of the N-terminal activation functions is necessary for c-Jun stimulation of androgen receptor transactivation. Testing c-Jun/v-Jun chimeras, we show that v-Jun is unable to stimulate androgen receptor transactivation and the effect is dependent on the c-Jun activation functions, c-Jun exhibits a bell-shaped activity on androgen receptor-mediated transactivation which appears to be distinct from c-Jun's transactivation ability. A c-Jun mutant deficient in transactivation is able to stimulate androgen receptor activity. These results indicate that c-Jun's transactivation ability can be separated from c-Jun's ability to stimulate the androgen receptor transactivation. C1 Univ Toledo, Dept Biol, Toledo, OH 43606 USA. NCI, Dept Cell & Canc Biol, Div Clin Sci, Rockville, MD 20850 USA. RP Shemshedini, L (reprint author), Univ Toledo, Dept Biol, Toledo, OH 43606 USA. NR 55 TC 28 Z9 30 U1 1 U2 1 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE RG21 6XS, HAMPSHIRE, ENGLAND SN 0950-9232 J9 ONCOGENE JI Oncogene PD APR 16 PY 1998 VL 16 IS 15 BP 2001 EP 2009 DI 10.1038/sj.onc.1201697 PG 9 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA ZH166 UT WOS:000073079400012 PM 9591784 ER PT J AU Penninx, BWJH Guralnik, JM de Leon, CFM Pahor, M Visser, M Corti, MC Wallace, RB AF Penninx, BWJH Guralnik, JM de Leon, CFM Pahor, M Visser, M Corti, MC Wallace, RB TI Cardiovascular events and mortality in newly and chronically depressed persons > 70 years of age SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article ID CORONARY HEART-DISEASE; MYOCARDIAL-INFARCTION; SEX-DIFFERENCES; ARTERY DISEASE; RISK; SYMPTOMS; POPULATIONS; ASSOCIATION; STRESS AB The role of duration of depressed mood in the prediction of cardiovascular disease (CVD) requires further study, as it has been suggested that emerging depressive symptoms may be a better predictor than persistent depressive symptoms. This prospective cohort study of 3,701 men and women aged >70 years uses 3 measurement occasions of depressive symptomatology (Center for Epidemiologic Studies-Depression Scale) during a 6-year period to distinguish persons who were newly (depressed at baseline but not at 3 and 6 years before baseline) and chronically depressed (depressed at baseline and at 3 or 6 years before baseline). Their risk of subsequent CVD events and all-cause mortality was compared with that of subjects who were never depressed during the 6-year period. Outcome events were based on death certificates and Medicare hospitalization records. During a median follow-up of 4.0 years, there were 732 deaths (46.2/1,000 person-years) and 933 new CVD events (64.7/1,000 person-years). In men, but not in women, newly depressed mood was associated with an increased risk of CVD mortality (relative risk 1.75, 95% confidence interval [CI] 1.00 to 3.05), new CVD events (relative risk 2.07, 95% CI 1.44 to 2.96), and new coronary heart disease events (relative risk 2.03, 95% CI 1.28 to 3.24) after adjustment for traditional CVD risk factors. The association between newly depressed mood and all-cause mortality was smaller (relative risk 1.40, 95% CI 0.95 to 2.07). Chronic depressed mood was not associated with new CVD events or all-cause mortality. Our findings suggest that newly depressed older men, but not women, were approximately twice as likely to have a CVD event than those who were never depressed. In men, recent onset of depressed mood is a better predictor of CVD than long-term depressed mood. (C) 1998 by Excerpta Medica, Inc. C1 NIA, Epidemiol Demog & Biometry Program, Bethesda, MD 20892 USA. Rush Presbyterian St Lukes Med Ctr, Rush Inst Healthy Aging, Chicago, IL 60612 USA. Univ Tennessee, Dept Prevent Med, Memphis, TN USA. Univ Padua, Dept Internal Med, I-35100 Padua, Italy. Univ Iowa, Dept Prevent Med & Environm Hlth, Iowa City, IA 52242 USA. RP Penninx, BWJH (reprint author), NIA, Epidemiol Demog & Biometry Program, 7201 Wisconsin Ave,Gateway Bldg,Suite 3C-309, Bethesda, MD 20892 USA. FU NIA NIH HHS [N01-AG-02107, N01-AG-02106, N01-AG-0215] NR 30 TC 146 Z9 150 U1 2 U2 2 PU EXCERPTA MEDICA INC PI NEW YORK PA 245 WEST 17TH STREET, NEW YORK, NY 10011 USA SN 0002-9149 J9 AM J CARDIOL JI Am. J. Cardiol. PD APR 15 PY 1998 VL 81 IS 8 BP 988 EP 994 DI 10.1016/S0002-9149(98)00077-0 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA ZK092 UT WOS:000073284100009 PM 9576158 ER PT J AU Petrovitch, H White, L Masaki, KH Ross, GW Abbott, RD Rodriguez, BL Lu, GQ Burchfiel, CM Blanchette, PL Curb, JD AF Petrovitch, H White, L Masaki, KH Ross, GW Abbott, RD Rodriguez, BL Lu, GQ Burchfiel, CM Blanchette, PL Curb, JD TI Influence of myocardial infarction, coronary artery bypass surgery, and stroke on cognitive impairment in late life SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article ID MINI-MENTAL STATE; ALZHEIMERS-DISEASE; COMMUNITY POPULATION; VASCULAR DEMENTIA; ASSOCIATION AB Relations between cognitive test scores in later life and prior myocardial infarction (MI), coronary artery bypass graft surgery (CABG), and stroke were examined for this study. Subjects were 3,734 Japanese-American men (80% of surviving Honolulu Heart Program cohort) aged 71 to 93 years at the time of cognitive testing. Impairment was defined as scoring below the 16th percentile on a validated cognitive assessment scale. Prior MI, stroke, and CABG were established using hospital surveillance, history, and record review. After adjustment for age, years of education, and years of childhood spent in Japans men with prior stroke were significantly more likely than others to have poor cognitive performance (odds ratio 4.4, 95% confidence limits 3.0 to 6.7). History of >1 stroke was associated with an odds ratio of 50 (95% confidence limits 10.5 to 238.3). There was no significant association between cognitive performance and greater than or equal to 1 prior MI or history of CABG. Time between events and cognitive function testing did not affect results. Analyses support a significant association between clinical stroke and persistent cognitive impairment, but fail to implicate CABG or MI. (C) 1998 by Excerpta Medica, Inc. C1 Hawaii Ctr Hlth Res, Homolulu Asia Aging Study, Honolulu, HI 96813 USA. Kuakini Med Ctr, Honolulu Heart Program, Honolulu, HI USA. NIA, NIH, Bethesda, MD 20892 USA. Dept Vet Affairs, Honolulu, HI USA. Univ Hawaii, John A Burns Sch Med, Dept Med, Honolulu, HI 96822 USA. Univ Virginia, Div Biostat, Charlottesville, VA USA. NHLBI, Epidemiol & Biometry Program, Div Epidemiol & Clin Applicat, Bethesda, MD 20892 USA. RP Petrovitch, H (reprint author), Hawaii Ctr Hlth Res, Homolulu Asia Aging Study, 846 S Hotel St, Honolulu, HI 96813 USA. FU NHLBI NIH HHS [1-HC-05102]; NIA NIH HHS [1-AG-4-2149] NR 29 TC 34 Z9 34 U1 0 U2 1 PU EXCERPTA MEDICA INC PI NEW YORK PA 245 WEST 17TH STREET, NEW YORK, NY 10011 USA SN 0002-9149 J9 AM J CARDIOL JI Am. J. Cardiol. PD APR 15 PY 1998 VL 81 IS 8 BP 1017 EP 1021 DI 10.1016/S0002-9149(98)00082-4 PG 5 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA ZK092 UT WOS:000073284100014 PM 9576163 ER PT J AU Chu, KC AF Chu, KC TI Re: "Temporal trends in diabetes mortality among American Indians and hispanics in New Mexico: Birth cohort and period effects" SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Letter ID RATES C1 NCI, Off Special Populat, Bethesda, MD 20892 USA. RP Chu, KC (reprint author), NCI, Off Special Populat, Execut Plaza N, Bethesda, MD 20892 USA. NR 4 TC 4 Z9 4 U1 0 U2 0 PU JOHNS HOPKINS UNIV SCHOOL HYGIENE PUB HEALTH PI BALTIMORE PA 111 MARKET PLACE, STE 840, BALTIMORE, MD 21202-6709 USA SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD APR 15 PY 1998 VL 147 IS 8 BP 796 EP 797 PG 2 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA ZH296 UT WOS:000073093100013 PM 9554422 ER PT J AU Miller, JH Fedoronko, DA Hass, BD Myint, M Kempner, ES AF Miller, JH Fedoronko, DA Hass, BD Myint, M Kempner, ES TI Radiation effects on the native structure of proteins: Fragmentation without dissociation SO ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS LA English DT Article DE radiation fragmentation; proteins; dissociation ID MOLECULAR-WEIGHT; ENERGY-TRANSFER; TARGET ANALYSIS; INACTIVATION; SIZE AB Several proteins (avidin, carboxypeptidase B, glucose-8-phosphate dehydrogenase, glutamate dehydrogenase, maltase, and peroxidase) composed of one to six subunits were irradiated in the frozen state. Each irradiated protein was examined by size-exclusion chromatography (SEC) and by denaturing gel electrophoresis (SDS-PAGE). All these proteins eluted from SEC as a single peak even though SDS-PAGE showed cleavage of the polypeptide backbone of the monomers. Thus, fragmentation of the subunits did not result in dissociation of the oligomeric structure. C1 NIAMSD, Phys Biol Lab, NIH, Bethesda, MD 20892 USA. RP Kempner, ES (reprint author), NIAMSD, Phys Biol Lab, NIH, Bldg 6,Room 140, Bethesda, MD 20892 USA. NR 18 TC 13 Z9 13 U1 0 U2 1 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0003-9861 J9 ARCH BIOCHEM BIOPHYS JI Arch. Biochem. Biophys. PD APR 15 PY 1998 VL 352 IS 2 BP 281 EP 287 DI 10.1006/abbi.1998.0604 PG 7 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA ZL906 UT WOS:000073485400016 PM 9587417 ER PT J AU Lee-Kwon, W Park, D Bernier, M AF Lee-Kwon, W Park, D Bernier, M TI Involvement of the Ras extracellular signal-regulated kinase signalling pathway in the regulation of ERCC-1 mRNA levels by insulin SO BIOCHEMICAL JOURNAL LA English DT Article ID GROWTH-FACTOR-I; PROTEIN TRANSFERASE INHIBITOR; REPAIR EXCISION NUCLEASE; PEPCK GENE-EXPRESSION; PP70 S6 KINASE; PHOSPHATIDYLINOSITOL 3-KINASE; PHOSPHOENOLPYRUVATE CARBOXYKINASE; GLUCOSE-TRANSPORT; GLYCOGEN-SYNTHASE; OXIDATIVE DAMAGE AB Expression of DNA repair enzymes, which includes ERCC-1, might be under the control of hormonal and growth factor stimulation. In the present study it was observed that insulin increased ERCC-1 mRNA levels both in Chinese hamster ovary cells overexpressing human insulin receptors (HIRc cells) and in fully differentiated 3T3-L1 adipocytes, To investigate the mechanisms underlying the increase in ERCC-1 gene expression in HIRc cells, we used a variety of pharmacological tools known to inhibit distinct signalling pathways. None of these inhibitors affected the amount of ERCC-1 mRNA in unstimulated cells. The pretreatment of cells with two chemically unrelated phosphatidylinositol 3'-kinase inhibitors, wortmannin and LY294002, failed to block the doubling of ERCC-1 mRNA content by insulin. Similarly, inhibition of pp70 S6 kinase by rapamycin had no apparent effects on this insulin response. In contrast, altering the p21(ras)-dependent pathway with either manumycin, an inhibitor of Ras farnesylation, or PD98059, an inhibitor of the mitogen-activated protein kinase/extracellular signal-regulated protein kinase (ERK) kinase, suppressed the induction of ERCC-1 mRNA by insulin (P < 0.001), Furthermore inhibition of RNA and protein synthesis negatively regulated the expression of this insulin-regulated gene (P < 0.005). These results suggest that insulin enhances ERCC-1 mRNA levels by the activation of the Ras-ERK-dependent pathway without the involvement of the phosphatidylinositol 3'-kinase/pp70 S6 kinase. C1 NIA, Diabet Sect, Clin Invest Lab, NIH, Baltimore, MD 21224 USA. RP Bernier, M (reprint author), NIA, Diabet Sect, Clin Invest Lab, NIH, 5600 Nathan Shock Dr, Baltimore, MD 21224 USA. OI Bernier, Michel/0000-0002-5948-368X NR 59 TC 23 Z9 24 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 APR 15 PY 1998 VL 331 BP 591 EP 597 PN 2 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA ZK562 UT WOS:000073337500034 PM 9531502 ER PT J AU Nabiev, I Fleury, F Kudelina, I Pommier, Y Charton, F Riou, JF Alix, AJP Manfait, M AF Nabiev, I Fleury, F Kudelina, I Pommier, Y Charton, F Riou, JF Alix, AJP Manfait, M TI Spectroscopic and biochemical characterisation of self-aggregates formed by antitumor drugs of the camptothecin family - Their possible role in the unique mode of drug action SO BIOCHEMICAL PHARMACOLOGY LA English DT Article DE camptothecin; topoisomerase I; J-aggregates; circular dichroism; fluorescence; antitumour effects ID DNA TOPOISOMERASE-I; INTOPLICINE; DERIVATIVES; RESISTANCE; HYDROLYSIS; STABILITY; BINDING AB We describe the effect strongly influencing the biological activity of some camptothecin (CPT) drugs, the inhibitors of DNA topoisomerase I (topo I), namely, the formation of J-type aggregates in an aqueous buffer solution. These aggregates were built up under certain dilution conditions of the stock DMSO solutions of 20-S-camptothecin (20(S)CPT), 10,11-methylenedioxy-CPT (10,11-CPT) and 7-ethyl-10-hydroxy-CPT (SN38). The aggregates were found to be stereospecific, not being detectable for the 20(R)-stereoisomer of CPT. They were formed by the stacking interaction between quinoline rings of CPT chromophores with the inverse position of the nitrogen atoms. The aggregates were stable at acidic and neutral pHs, but dissociated at basic pHs. Self-aggregation prevented hydrolysis of the lactone ring at neutral pHs, thus preserving the drugs in a biologically active form. Addition of BSA did not induce either disaggregation or hydrolysis of the lactone ring, whereas the monomeric form of the drugs was shown to undergo rapid conversion to an inactive carboxylate form in the presence of human serum albumin [5]. The drugs did not form the aggregates in the presence of topo I. Moreover, rapid dissociation of the aggregates was observed if a self-aggregated drug solution was added to topo I alone or to the DNA-topo I cleavage assay. Neither DNA alone nor oligonucleotides derived from the sequences of the CPT enhanced or topo I-induced cleavage sites in SV40 plasmid DNA induces changes in the aggregation state of the drugs. These observations are indicative of interaction between the aggregates and topo I. The aggregates were found to penetrate within the cells with much higher efficiency than a monomeric form of the drugs. Cellular uptake of aggregated and nonaggregated species correlated well with cytotoxic effects produced by the drug. In this manner, CPT's self-aggregation should be regarded as a favourable phenomenon producing species with a more stable biologically active structure of the lactone ring and exhibiting enhanced cellular uptake levels relative to the monomeric forms of medications. (C) 1998 Elsevier Science Inc. C1 Univ Reims Champagne Ardenne, Lab Spect Biomol, UFR Pharm, F-51096 Reims, France. Russian Acad Sci, Shemyakin & Ovchinnikov Inst Bioorgan Chem, Opt Spect Div, Moscow 117871, Russia. NCI, Mol Pharmacol Lab, Dev Therapeut Program, Div Canc Treatment,NIH, Bethesda, MD 20892 USA. Univ Reims Champagne Ardenne, Lab Spect & Struct Biomol, INSERM, U314, F-51092 Reims, France. Rhone Poulenc Rorer SA, Dept Biol, F-94403 Vitry, France. RP Nabiev, I (reprint author), Univ Reims Champagne Ardenne, Lab Spect Biomol, UFR Pharm, 51 Rue Cognacq Jay, F-51096 Reims, France. RI Nabiev, Igor/A-5077-2014 OI Nabiev, Igor/0000-0002-8391-040X NR 26 TC 47 Z9 48 U1 0 U2 8 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0006-2952 J9 BIOCHEM PHARMACOL JI Biochem. Pharmacol. PD APR 15 PY 1998 VL 55 IS 8 BP 1163 EP 1174 DI 10.1016/S0006-2952(97)00508-X PG 12 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA ZH978 UT WOS:000073167400004 PM 9719470 ER PT J AU Weinberger, D AF Weinberger, D TI Animal models of schizophrenia and the plausibility of clinical hypotheses SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract C1 NIMH, Neurosci Ctr St Elizabeths, Washington, DC 20032 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 1998 VL 43 SU 8 MA 5 BP 2S EP 2S DI 10.1016/S0006-3223(98)90453-X PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA ZJ674 UT WOS:000073240700007 ER PT J AU Volavka, J Coccaro, E Higley, JD Linnoila, M AF Volavka, J Coccaro, E Higley, JD Linnoila, M TI Gene expression, impulse control, and aggression SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract C1 Nathan S Kline Inst Psychiat Res, Orangeburg, NY 10962 USA. Eastern PA Psychiat Inst, Philadelphia, PA 19129 USA. NIAAA, Poolesville, MD 20837 USA. NIAAA, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 1998 VL 43 SU 8 MA 7 BP 3S EP 3S DI 10.1016/S0006-3223(98)90455-3 PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA ZJ674 UT WOS:000073240700009 ER PT J AU Weinberger, DR Bertolino, A Callicott, JH Lenkinski, RE Poland, R AF Weinberger, DR Bertolino, A Callicott, JH Lenkinski, RE Poland, R TI New insights in the neurobiology and clinical implications of N-acetyl-aspartate SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract C1 NIMH, Intramural Res Program, Clin Brain Disorders Branch, Washington, DC 20032 USA. RI Lenkinski, Robert/F-9045-2014 NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 1998 VL 43 SU 8 MA 9 BP 3S EP 3S DI 10.1016/S0006-3223(98)90457-7 PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA ZJ674 UT WOS:000073240700011 ER PT J AU Roca, C Altemus, M Galliven, E Schmidt, P Deuster, P Gold, P Murphy, D Rubinow, D AF Roca, C Altemus, M Galliven, E Schmidt, P Deuster, P Gold, P Murphy, D Rubinow, D TI Effect of reproductive hormones on the hypothalamic-pituitary axis response to stress SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract C1 NIMH, Behav Endocrinol Branch, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 1998 VL 43 SU 8 MA 17 BP 6S EP 6S DI 10.1016/S0006-3223(98)90465-6 PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA ZJ674 UT WOS:000073240700019 ER PT J AU Kumra, S Giedd, JN Hamburger, S Rapoport, JL AF Kumra, S Giedd, JN Hamburger, S Rapoport, JL TI Brain anatomic magnetic resonance imaging in pediatric patients with "multidimensionally impaired syndrome" SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract C1 NIMH, Child Psychiat Branch, Bethesda, MD 20892 USA. RI Giedd, Jay/A-3080-2008; Giedd, Jay/B-7302-2012; Giedd, Jay/J-9644-2015 OI Giedd, Jay/0000-0003-0827-3460; Giedd, Jay/0000-0003-2002-8978 NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 1998 VL 43 SU 8 MA 39 BP 12S EP 12S DI 10.1016/S0006-3223(98)90487-5 PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA ZJ674 UT WOS:000073240700041 ER PT J AU De Bellis, MD Casey, BJ Clark, DB Giedd, J Boring, A Kersh, A Frustaci, K AF De Bellis, MD Casey, BJ Clark, DB Giedd, J Boring, A Kersh, A Frustaci, K TI Anatomical MRI in maltreated children with PTSD SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract C1 Univ Pittsburgh, Western Psychiat Inst & Clin, Med Ctr, Pittsburgh, PA 15213 USA. NIH, Bethesda, MD 20892 USA. RI Giedd, Jay/A-3080-2008; Giedd, Jay/B-7302-2012; Giedd, Jay/J-9644-2015 OI Giedd, Jay/0000-0003-0827-3460; Giedd, Jay/0000-0003-2002-8978 NR 0 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 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 1998 VL 43 SU 8 MA 53 BP 16S EP 16S DI 10.1016/S0006-3223(98)90501-7 PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA ZJ674 UT WOS:000073240700055 ER PT J AU Nahas, Z Stallings, LE Speer, AM Teneback, C Vincent, DJ Bohning, DE Spicer, KM Cheng, KT Molloy, M Risch, SC George, MS AF Nahas, Z Stallings, LE Speer, AM Teneback, C Vincent, DJ Bohning, DE Spicer, KM Cheng, KT Molloy, M Risch, SC George, MS TI Perfusion SPECT studies of rTMS effects on blood flow in health and depression SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract C1 Med Univ S Carolina, Charleston, SC 29425 USA. NIMH, Dept Psychiat, Bethesda, MD 20892 USA. NIMH, Dept Radiol, Bethesda, MD 20892 USA. NIMH, Dept Neurol, Bethesda, MD 20892 USA. NIMH, Biol Psychiat Branch, Bethesda, MD 20892 USA. Ralph H Johnson Vet Affairs Hosp, Charleston, SC USA. NR 0 TC 4 Z9 4 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 1998 VL 43 SU 8 MA 63 BP 19S EP 20S DI 10.1016/S0006-3223(98)90511-X PG 2 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA ZJ674 UT WOS:000073240700065 ER PT J AU Lorberbaum, JP Newman, JD Horwitz, AR Dubno, JR Nahas, Z Teneback, C Johnson, MR Lydiard, RB Ballenger, JC MacLean, PD George, MS AF Lorberbaum, JP Newman, JD Horwitz, AR Dubno, JR Nahas, Z Teneback, C Johnson, MR Lydiard, RB Ballenger, JC MacLean, PD George, MS TI Functional MRI of mothers responding to infant cries SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract C1 Med Univ S Carolina, Charleston, SC 29425 USA. NICHHD, NIH, Bethesda, MD 20892 USA. Ctr St Elizabeths, Natl Inst Mental Hlth Neurosci, Washington, DC USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 1998 VL 43 SU 8 MA 80 BP 25S EP 25S DI 10.1016/S0006-3223(98)90528-5 PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA ZJ674 UT WOS:000073240700082 ER PT J AU Benson, BE Carson, RE Sandoval, W Linthicum, WL Kimbrell, TA Kieswetter, DO Herscovitch, P Eckelman, WC McCann, UD Weiss, SRB Post, RM Ketter, TA AF Benson, BE Carson, RE Sandoval, W Linthicum, WL Kimbrell, TA Kieswetter, DO Herscovitch, P Eckelman, WC McCann, UD Weiss, SRB Post, RM Ketter, TA TI A potential cholinergic mechanism of procaine's limbic activation SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract C1 NIMH, Biol Psychiat Branch, NIH, Bethesda, MD 20892 USA. Stanford Univ, Sch Med, Stanford, CA 94305 USA. RI Carson, Richard/H-3250-2011 OI Carson, Richard/0000-0002-9338-7966 NR 0 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 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 1998 VL 43 SU 8 MA 89 BP 27S EP 28S DI 10.1016/S0006-3223(98)90537-6 PG 2 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA ZJ674 UT WOS:000073240700091 ER PT J AU Pietrini, P Guazzelli, M Jaffe, K Sandhu, N Schlaifer, JD Grafman, J AF Pietrini, P Guazzelli, M Jaffe, K Sandhu, N Schlaifer, JD Grafman, J TI Brain activation during imagined aggressive behavior in humans SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract C1 NINCDS, Cognit Neurosci Sect, NIH, Bethesda, MD 20892 USA. Univ Pisa, Dept Psychiat, I-56100 Pisa, Italy. Univ Pisa, Dept Human & Environm Sci, I-56100 Pisa, Italy. NR 0 TC 0 Z9 0 U1 1 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 1998 VL 43 SU 8 MA 92 BP 28S EP 28S DI 10.1016/S0006-3223(98)90540-6 PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA ZJ674 UT WOS:000073240700094 ER PT J AU Hamid, EH Baca, SM Meredith, GE Hyde, TM Egan, MF AF Hamid, EH Baca, SM Meredith, GE Hyde, TM Egan, MF TI Neuroleptic drug effects on synaptophysin gene expression levels SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract C1 NIMH, Neuropsychiat Res Hosp, IRP, Washington, DC 20032 USA. Emory Univ, Dept Neurosci, Atlanta, GA 30322 USA. Royal Coll Surg Ireland, Dept Neurol, Dublin 2, Ireland. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 1998 VL 43 SU 8 MA 113 BP 34S EP 34S DI 10.1016/S0006-3223(98)90561-3 PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA ZJ674 UT WOS:000073240700115 ER PT J AU Bachus, SE Hyde, TM Rubinstein, SL Herman, MM Kleinman, JE AF Bachus, SE Hyde, TM Rubinstein, SL Herman, MM Kleinman, JE TI Entorhinal cortical preprosomatostatin mRNA in psychiatric disorders SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract ID CEREBROSPINAL-FLUID; IMMUNOREACTIVITY C1 NIMH, Ctr Neurosci St Elizabeths, Clin Brain Disorders Branch, Washington, DC 20032 USA. NR 4 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 1998 VL 43 SU 8 MA 127 BP 38S EP 39S DI 10.1016/S0006-3223(98)90575-3 PG 2 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA ZJ674 UT WOS:000073240700129 ER PT J AU Roca, CA Altemus, M Schmidt, PJ Deuster, PD Gold, P Murphy, DL Rubinow, DR AF Roca, CA Altemus, M Schmidt, PJ Deuster, PD Gold, P Murphy, DL Rubinow, DR TI Effect of gonadal steroids on hypothalamic-pituitary-adrenal (HPA) axis function SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract C1 NIMH, Behav Endocrinol Branch, Bethesda, MD 20892 USA. Cornell Univ, Dept Psychiat, New York, NY 10021 USA. Uniformed Serv Univ Hlth Sci, Bethesda, MD 20814 USA. NIMH, Clin Endocrinol Branch, Bethesda, MD 20892 USA. NIMH, Clin Sci Lab, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 1998 VL 43 SU 8 MA 160 BP 48S EP 48S DI 10.1016/S0006-3223(98)90608-4 PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA ZJ674 UT WOS:000073240700162 ER PT J AU Dukoff, R Molchan, S Putnam, K Lai, J Sunderland, T AF Dukoff, R Molchan, S Putnam, K Lai, J Sunderland, T TI Dehydroepiandrosterone administration in demented patients and nondemented elderly volunteers SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract C1 NIMH, Geriatr Psychiat Branch, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 1998 VL 43 SU 8 MA 185 BP 54S EP 55S DI 10.1016/S0006-3223(98)90633-3 PG 2 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA ZJ674 UT WOS:000073240700187 ER PT J AU Bedwell, J Kumra, S Rapoport, JL Asarnow, R AF Bedwell, J Kumra, S Rapoport, JL Asarnow, R TI Comparison of neuropsychological deficits in pediatric patients with childhood-onset schizophrenia and "multidimensionally impaired syndrome" SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract C1 NIMH, Child Psychiat Branch, Bethesda, MD USA. Univ Calif Los Angeles, Inst Neuropsychiat, Los Angeles, CA 90024 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 1998 VL 43 SU 8 MA 186 BP 55S EP 55S DI 10.1016/S0006-3223(98)90634-5 PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA ZJ674 UT WOS:000073240700188 ER PT J AU Mirsky, AF Levav, M Herault, J Xiong, L Seni, MH Andermann, E AF Mirsky, AF Levav, M Herault, J Xiong, L Seni, MH Andermann, E TI Neuropsychological, risk indicators in relatives of generalized seizure disorder patients SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract C1 NIMH, Psychol & Psychopathol Lab, Bethesda, MD 20892 USA. McGill Univ, Montreal Neurol Inst, Montreal, PQ, Canada. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 1998 VL 43 SU 8 MA 198 BP 58S EP 58S DI 10.1016/S0006-3223(98)90646-1 PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA ZJ674 UT WOS:000073240700200 ER PT J AU Ketter, TA Kennedy, SH Kimbrell, TA Wu, JC Sackeim, HA George, MS AF Ketter, TA Kennedy, SH Kimbrell, TA Wu, JC Sackeim, HA George, MS TI Brain imaging studies of treatments in mood disorders SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract C1 Stanford Univ, Stanford, CA 94305 USA. Clarke Inst Psychiat, Toronto, ON M5T 1R8, Canada. NIMH, Bethesda, MD 20892 USA. Univ Calif Irvine, Irvine, CA 92717 USA. New York State Psychiat Inst, New York, NY 10032 USA. Med Univ S Carolina, Charleston, SC 29425 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 1998 VL 43 SU 8 MA 206 BP 61S EP 61S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA ZJ674 UT WOS:000073240700208 ER PT J AU Callicott, JH Bertolino, A Mattay, VS Ellmore, TE Jones, KM Coppola, RC Goldberg, TE Frank, JA Weinberger, DR AF Callicott, JH Bertolino, A Mattay, VS Ellmore, TE Jones, KM Coppola, RC Goldberg, TE Frank, JA Weinberger, DR TI Novel approaches to the study of schizophrenia using fMRI SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract C1 Sensor Syst Inc, Sterling, VA USA. NIH, OIR, Lab Diagnost Radiol Res, Bethesda, MD USA. NIMH, Clin Brain Disorders Branch, IRP, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 1998 VL 43 SU 8 MA 211 BP 62S EP 62S DI 10.1016/S0006-3223(98)90659-X PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA ZJ674 UT WOS:000073240700213 ER PT J AU Bertolino, A Esposito, G Callicott, JH Mattay, VS Van Horn, JD Frank, JA Berman, KF Weinberger, DR AF Bertolino, A Esposito, G Callicott, JH Mattay, VS Van Horn, JD Frank, JA Berman, KF Weinberger, DR TI Neurophysiological correlates of H-1-magnetic resonance spectroscopic imaging SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract C1 NIMH, Clin Brain Disorders Branch, NIH, Bethesda, MD USA. NR 0 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 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 1998 VL 43 SU 8 MA 212 BP 63S EP 63S DI 10.1016/S0006-3223(98)90660-6 PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA ZJ674 UT WOS:000073240700214 ER PT J AU Breiter, H Gollub, R Edmister, W Talavage, T Makris, N Kennedy, D Melcher, J Kantor, H Elman, I Gastfriend, D Riorden, J Campbell, T Foley, M Hyman, S Weisskoff, R Rosen, B AF Breiter, H Gollub, R Edmister, W Talavage, T Makris, N Kennedy, D Melcher, J Kantor, H Elman, I Gastfriend, D Riorden, J Campbell, T Foley, M Hyman, S Weisskoff, R Rosen, B TI fMRI of cocaine effects on brainstem and reward circuitry SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract C1 MGH, NMR Ctr, Charlestown, MA USA. MGH, Dept Psychiat, Boston, MA USA. NIMH, Off Director, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 1998 VL 43 SU 8 MA 214 BP 63S EP 63S DI 10.1016/S0006-3223(98)90662-X PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA ZJ674 UT WOS:000073240700216 ER PT J AU Mirsky, AF Levav, M Herault, J Xiong, L Seni, MH Andermann, E AF Mirsky, AF Levav, M Herault, J Xiong, L Seni, MH Andermann, E TI Neuropsychological risk indicators in relatives of generalized seizure disorder patients SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract C1 NIMH, Psychol & Psychopathol Lab, NIH, Bethesda, MD 20892 USA. McGill Univ, Montreal Neurol Inst, Montreal, PQ, Canada. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 1998 VL 43 SU 8 MA 218 BP 64S EP 65S DI 10.1016/S0006-3223(98)90666-7 PG 2 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA ZJ674 UT WOS:000073240700220 ER PT J AU Bermann, KF Holt, JL Esposito, G Callicott, JL Egan, MF Van Horn, JD Bertolino, A Weinberger, DR AF Bermann, KF Holt, JL Esposito, G Callicott, JL Egan, MF Van Horn, JD Bertolino, A Weinberger, DR TI Beyond hypofrontality in functional brain imaging of schizophrenia SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract C1 NIMH, Clin Brain Disorders Branch, IRP, Bethesda, MD 20892 USA. NR 0 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 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 1998 VL 43 SU 8 MA 226 BP 67S EP 67S DI 10.1016/S0006-3223(98)90674-6 PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA ZJ674 UT WOS:000073240700228 ER PT J AU Kumra, S Bedwell, J Hommer, D Rapoport, J AF Kumra, S Bedwell, J Hommer, D Rapoport, J TI Comparison of smooth pursuit eye movements in pediatric patients with childhood-onset schizophrenia and "multidimensionally impaired syndrome" SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract C1 NIMH, Child Psychiat Branch, Bethesda, MD USA. NIAAA, Clin Studies Lab, Rockville, MD USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 1998 VL 43 SU 8 MA 230 BP 68S EP 68S DI 10.1016/S0006-3223(98)90678-3 PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA ZJ674 UT WOS:000073240700232 ER PT J AU D'Souza, DC Deadwyler, SA Heishman, SJ Menard, JF Mathew, RJ AF D'Souza, DC Deadwyler, SA Heishman, SJ Menard, JF Mathew, RJ TI New perspectives in the basic and clinical pharmacology of cannabinoidergic systems SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract C1 Yale Univ, Sch Med, Dept Psychiat, New Haven, CT 06520 USA. Wake Forest Univ, Bowman Gray Sch Med, Winston Salem, NC 27109 USA. NIDA, Addict Res Ctr, Clin Pharmacol Branch, Lexington, KY USA. Sanofi Pharmaceut, Sanofi Res, Brussels, Belgium. Duke Univ, Med Ctr, Dept Psychiat, Durham, NC 27706 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 1998 VL 43 SU 8 MA 251 BP 75S EP 75S DI 10.1016/S0006-3223(98)90699-0 PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA ZJ674 UT WOS:000073240700253 ER PT J AU George, MS Nahas, Z Speer, AM Avery, D Molloy, M Risch, SC Lorberbaum, JP Bohning, DE Post, RM AF George, MS Nahas, Z Speer, AM Avery, D Molloy, M Risch, SC Lorberbaum, JP Bohning, DE Post, RM TI How does TMS improve depression? Current hints about the role of intensity, frequency, location and dose SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract C1 Med Univ S Carolina, Charleston, SC 29425 USA. NIMH, Dept Psychiat, Bethesda, MD 20892 USA. NIMH, Dept Radiol, Bethesda, MD 20892 USA. NIMH, Dept Neurol, Bethesda, MD 20892 USA. NIMH, Biol Psychiat Branch, Bethesda, MD 20892 USA. Ralph H Johnson Vet Affairs Hosp, Charleston, SC USA. Univ Washington, Seattle, WA 98195 USA. NR 0 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 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 1998 VL 43 SU 8 MA 253 BP 76S EP 76S DI 10.1016/S0006-3223(98)90701-6 PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA ZJ674 UT WOS:000073240700255 ER PT J AU Cora-Locatelli, G Greenberg, BD Harmon, A Martin, J Ziemann, U Wasserman, E Leong, YM Murphy, DL AF Cora-Locatelli, G Greenberg, BD Harmon, A Martin, J Ziemann, U Wasserman, E Leong, YM Murphy, DL TI Cortical excitability and augmentation strategies in OCD SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract C1 NIMH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 1998 VL 43 SU 8 MA 258 BP 77S EP 78S DI 10.1016/S0006-3223(98)90706-5 PG 2 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA ZJ674 UT WOS:000073240700260 ER PT J AU Kaye, W Halmi, K Berrettini, W Goldman, D Fichter, M Strober, M Kaplan, A Woodside, B Treasure, J Magistretti, P Leibowitz, S Plotnikov, K Pollice, C Lilenfeld, L AF Kaye, W Halmi, K Berrettini, W Goldman, D Fichter, M Strober, M Kaplan, A Woodside, B Treasure, J Magistretti, P Leibowitz, S Plotnikov, K Pollice, C Lilenfeld, L TI Genes in anorexia nervosa: Clinical characteristics of SIB pairs SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract C1 Univ Pittsburgh, Med Ctr, Pittsburgh, PA 15213 USA. Cornell Univ, Med Ctr, White Plains, NY 10605 USA. Univ Penn, Philadelphia, PA 19104 USA. NIH, Rockville, MD 20852 USA. Klin Roseneck, D-83209 Prien Am Chiemsee, Germany. Univ Calif Los Angeles, Los Angeles, CA 90024 USA. Toronto Gen Hosp, Toronto, ON M5S 2C4, Canada. Toronto Hosp, Toronto, ON M5G 2C4, Canada. Inst Psychiat, London SE5 8AF, England. Univ Lausanne, CH-1005 Lausanne, Switzerland. Rockefeller Univ, New York, NY 10021 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 1998 VL 43 SU 8 MA 270 BP 81S EP 81S DI 10.1016/S0006-3223(98)90718-1 PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA ZJ674 UT WOS:000073240700272 ER PT J AU Adler, CM Malhotra, AK Goldberg, T Elman, I Pickar, D Breier, A AF Adler, CM Malhotra, AK Goldberg, T Elman, I Pickar, D Breier, A TI Comparison of ketamine-induced and schizophrenic thought disorder SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract C1 NIMH, Expt Therapeut Branch, Bethesda, MD 20892 USA. Clin Brain Disorders Branch, Washington, DC USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 1998 VL 43 SU 8 MA 278 BP 83S EP 84S DI 10.1016/S0006-3223(98)90726-0 PG 2 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA ZJ674 UT WOS:000073240700280 ER PT J AU Neumeister, A Turner, EH Matthews, JR Postolache, TT Barnett, RL Rauh, M Vetticad, RG Kasper, S Rosenthal, NE AF Neumeister, A Turner, EH Matthews, JR Postolache, TT Barnett, RL Rauh, M Vetticad, RG Kasper, S Rosenthal, NE TI Tryptophan depletion versus catecholamine depletion in SAD SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract C1 Dept Gen Psychiat, A-1090 Vienna, Austria. NIMH, Clin Psychobiol Branch, Bethesda, MD 20892 USA. RI Turner, Erick/A-4848-2008 OI Turner, Erick/0000-0002-3522-3357 NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 1998 VL 43 SU 8 MA 285 BP 86S EP 86S DI 10.1016/S0006-3223(98)90733-8 PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA ZJ674 UT WOS:000073240700287 ER PT J AU Nahas, Z Speer, A Molloy, M Arana, GW Risch, SC George, MS AF Nahas, Z Speer, A Molloy, M Arana, GW Risch, SC George, MS TI Frequency and intensity in the antidepressant effect of left prefrontal rTMS SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract C1 Med Univ S Carolina, Charleston, SC 29425 USA. NIMH, Dept Psychiat, Bethesda, MD 20892 USA. NIMH, Dept Radiol, Bethesda, MD 20892 USA. NIMH, Dept Neurol, Bethesda, MD 20892 USA. NIMH, Biol Psychiat Branch, Bethesda, MD 20892 USA. Ralph H Johnson Vet Affairs Hosp, Charleston, SC USA. NR 1 TC 6 Z9 7 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 1998 VL 43 SU 8 MA 315 BP 94S EP 95S DI 10.1016/S0006-3223(98)90763-6 PG 2 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA ZJ674 UT WOS:000073240700317 ER PT J AU Nahas, Z Speer, A Lorberbaum, J Molloy, M Liberatos, C Risch, SC George, MS AF Nahas, Z Speer, A Lorberbaum, J Molloy, M Liberatos, C Risch, SC George, MS TI Safety of rTMS: MRI scans before and after 2 weeks of daily left prefrontal rTMS for depression SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract ID STIMULATION C1 Med Univ S Carolina, Charleston, SC 29425 USA. NIMH, Dept Psychiat, Bethesda, MD 20892 USA. NIMH, Dept Radiol, Bethesda, MD 20892 USA. NIMH, Dept Neurol, Bethesda, MD 20892 USA. NIMH, Biol Psychiat Branch, Bethesda, MD 20892 USA. NR 2 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 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 1998 VL 43 SU 8 MA 316 BP 95S EP 95S DI 10.1016/S0006-3223(98)90764-8 PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA ZJ674 UT WOS:000073240700318 ER PT J AU Postolache, TT Doty, RL Wehr, TA Han, L Turner, EH Matthews, JR Neumeister, A Kroger, H Rosenthal, NE AF Postolache, TT Doty, RL Wehr, TA Han, L Turner, EH Matthews, JR Neumeister, A Kroger, H Rosenthal, NE TI Unirhinal olfactory identification in seasonal affective disorder SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract C1 NIMH, Clin Psychobiol Branch, Bethesda, MD 20892 USA. Univ Penn, Med Ctr, Ctr Smell & Taste, Philadelphia, PA 19104 USA. RI Doty, Richard/B-7623-2012; Turner, Erick/A-4848-2008; Doty, Richard/G-1602-2013 OI Turner, Erick/0000-0002-3522-3357; NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 1998 VL 43 SU 8 MA 338 BP 101S EP 102S DI 10.1016/S0006-3223(98)90786-7 PG 2 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA ZJ674 UT WOS:000073240700340 ER PT J AU Osuch, EA Frye, MA Little, JT Kimbrell, TA Huggins, T Dunn, R Speer, A Cora-Locatelli, G Vanderham, L Post, RM Mathe, AA AF Osuch, EA Frye, MA Little, JT Kimbrell, TA Huggins, T Dunn, R Speer, A Cora-Locatelli, G Vanderham, L Post, RM Mathe, AA TI CSF neuropeptide Y correlates with anxiety in patients with affective disorders SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract C1 NIMH, Biol Psychiat Branch, Bethesda, MD 20892 USA. Univ Pittsburgh, Western Psychiat Inst, Pittsburgh, PA 15213 USA. NIMH, Clin Sci Lab, Bethesda, MD 20892 USA. Karolinska Inst, Stockholm, Sweden. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 1998 VL 43 SU 8 MA 339 BP 102S EP 102S DI 10.1016/S0006-3223(98)90787-9 PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA ZJ674 UT WOS:000073240700341 ER PT J AU Elman, I Gastfriend, DR Adler, CM Malhotra, AK Bir, C Pickar, D Breier, A AF Elman, I Gastfriend, DR Adler, CM Malhotra, AK Bir, C Pickar, D Breier, A TI Effects of acute metabolic stress on pituitary-adrenal axis activation in patients with schizophrenia SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. NIMH, Expt Therapeut Branch, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 1998 VL 43 SU 8 MA 415 BP 124S EP 125S DI 10.1016/S0006-3223(98)90863-0 PG 2 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA ZJ674 UT WOS:000073240700417 ER PT J AU Nicolson, R Kumra, S Giedd, J Fernandez, T Bedwell, J Lenane, M Rapoport, JL AF Nicolson, R Kumra, S Giedd, J Fernandez, T Bedwell, J Lenane, M Rapoport, JL TI Clinical and biological correlates of cytogenetic abnormalities in childhood-onset psychosis SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract C1 NIMH, Child Psychiat Branch, Bethesda, MD 20892 USA. RI Giedd, Jay/A-3080-2008; Fernandez, Thomas/D-4295-2009; Nicolson, Robert/E-4797-2011; Giedd, Jay/B-7302-2012; Giedd, Jay/J-9644-2015 OI Fernandez, Thomas/0000-0003-0830-022X; Giedd, Jay/0000-0003-0827-3460; Giedd, Jay/0000-0003-2002-8978 NR 0 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 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 1998 VL 43 SU 8 MA 425 BP 127S EP 128S DI 10.1016/S0006-3223(98)90873-3 PG 2 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA ZJ674 UT WOS:000073240700427 ER PT J AU Garver, D Filbey, F Vawter, M Holcomb, J Nair, R Tekell, J Kingsbury, S Christensen, J AF Garver, D Filbey, F Vawter, M Holcomb, J Nair, R Tekell, J Kingsbury, S Christensen, J TI Schizophrenia: Multiple disease processes and clinical differences SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract C1 Vet Adm Med Ctr, Dallas, TX 75216 USA. Univ Texas, SW Med Ctr, Austin, TX USA. NIMH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 1998 VL 43 SU 8 MA 430 BP 129S EP 129S DI 10.1016/S0006-3223(98)90878-2 PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA ZJ674 UT WOS:000073240700432 ER PT J AU Su, TP Pickar, D Breier, A AF Su, TP Pickar, D Breier, A TI Dextroamphetamine-induced neurochemical effects in chronic schizophrenics and healthy volunteers SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract C1 NIMH, Expt Therapeut Branch, Bethesda, MD 20892 USA. Cheng Hsi Med Ctr, Taipei 112, Taiwan. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 1998 VL 43 SU 8 MA 443 BP 133S EP 133S DI 10.1016/S0006-3223(98)90891-5 PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA ZJ674 UT WOS:000073240700445 ER PT J AU Krasnewich, D Dietrich, K Bauer, L Ginns, EI Sidransky, E AF Krasnewich, D Dietrich, K Bauer, L Ginns, EI Sidransky, E TI Splenectomy in Gaucher disease: New management dilemmas SO BLOOD LA English DT Letter C1 NIMH, Clin Neurosci Branch, NIH, Bethesda, MD 20892 USA. NIH, Warren Grant Magnuson Clin Ctr, Dept Diagnost Radiol, Bethesda, MD 20892 USA. RP Krasnewich, D (reprint author), NIMH, Clin Neurosci Branch, NIH, Bethesda, MD 20892 USA. NR 5 TC 11 Z9 11 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0006-4971 J9 BLOOD JI Blood PD APR 15 PY 1998 VL 91 IS 8 BP 3085 EP 3087 PG 3 WC Hematology SC Hematology GA ZG521 UT WOS:000073012000057 PM 9531624 ER PT J AU Sheikh, MS Burns, TF Huang, Y Wu, GS Amundson, S Brooks, KS Fornace, AJ El-Deiry, WS AF Sheikh, MS Burns, TF Huang, Y Wu, GS Amundson, S Brooks, KS Fornace, AJ El-Deiry, WS TI p53-dependent and -independent regulation of the death receptor KILLER/DR5 gene expression in response to genotoxic stress and tumor necrosis factor alpha SO CANCER RESEARCH LA English DT Article ID FACTOR-INDUCED APOPTOSIS; CELL-DEATH; P53; BAX; FAS/APO-1; INDUCTION AB The death receptor (DR) KILLER/DR5 gene has recently been identified as a doxorubicin-regulated transcript that was also induced by exogenous wild-type p53 in p53-negative cells. KILLER/DR5 gene encodes a DR containing cell surface protein that is highly homologous to DR4, another DR of the tumor necrosis factor (TNF) receptor family, Both DR4 and KILLER/DR5 independently bind to their specific Ligand TRAIL and engage the caspase cascade to induce apoptosis. TRID (also known as TRAIL-R3) is an antiapoptotic decoy receptor that lacks the cytoplasmic death domain and competes with KILLER/DR5 and DR4 for binding to TRAIL. In this study, we demonstrate that the DR KILLER/DR5 gene is regulated in a p53-dependent and -independent manner during genotoxic and nongenotoxic stress-induced apoptosis. Just like other p53-regulated genes, ionizing radiation induction of KILLER/DR5 occurs in p53 wild-type cells, whereas methyl methanesulfonate regulation of KILLER/DR5 occurs in a p53-dependent and -independent manner. However, unlike other p53-regulated genes, KILLER/DR5 is not regulated following UV irradiation, TNF-alpha, a nongenotoxic cytokine, also induced the expression of KILLER/DR5 in a number of cancer cell lines, irrespective of p53 status. TNF-alpha did not alter the KILLER/DR5 mRNA stability, suggesting that the TNF-alpha regulation of KILLER/DR5 expression appears transcriptional. We also provide evidence that KILLER/DR5 is regulated in a trigger and cell type-specific manner and that its induction by TNF-alpha, p53, or DNA damage is not the consequence of apoptosis induced by these agents. Unlike KILLER/DR5, none of the other KILLER/DR5 family members, including DR4, TRID, or the ligand TRAIL, displayed genotoxic stress or TNF-alpha regulation in a p53 transcription-dependent manner. Thus, KILLER/DR5 appears a bona fide downstream target of p53 that is also regulated in a cell type-specific, trigger-dependent, and p53-independent manner. C1 NCI, Div Basic Sci, Basic Res Lab, NIH, Bethesda, MD 20892 USA. NIA, Gene Express & Aging Sect, Biol Chem Lab, NIH, Baltimore, MD 21224 USA. Univ Penn, Sch Med, Howard Hughes Med Inst, Lab Mol Oncol & Cell Cycle Regulat, Philadelphia, PA 19104 USA. RP Sheikh, MS (reprint author), NCI, Div Basic Sci, Basic Res Lab, NIH, Room 5 C09,Bldg 37, Bethesda, MD 20892 USA. RI Fornace, Albert/A-7407-2008 OI Fornace, Albert/0000-0001-9695-085X NR 27 TC 331 Z9 337 U1 0 U2 11 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD APR 15 PY 1998 VL 58 IS 8 BP 1593 EP 1598 PG 6 WC Oncology SC Oncology GA ZH644 UT WOS:000073132600004 PM 9563466 ER PT J AU Felix, K Kelliher, K Bornkamm, GW Janz, S AF Felix, K Kelliher, K Bornkamm, GW Janz, S TI Association of elevated mutagenesis in the spleen with genetic susceptibility to induced plasmacytoma development in mice SO CANCER RESEARCH LA English DT Article ID TRANSGENIC MICE; MUTATION; INDUCTION; ASSAY AB Using the phage lambda LIZ-based transgenic in vivo mutagenesis assay, mean mutant rates were determined in the spleen of mice exposed to sustained oxidative stress and were found to be increased approximately 3-fold in plasmacytoma-susceptible BALB/c and C.D2-Idh1-Pep3 mice, but not in plasmacytoma-resistant DBA/2N mice. This finding suggests a correlation between the genetic susceptibility to inflammation-induced peritoneal plasmacytomagenesis and the phenotype of increased mutagenesis in lymphoid tissues, raising the possibility that plasmacytoma resistance genes may inhibit tumor development by minimizing oxidative mutagenesis in B cells. C1 NCI, Genet Lab, DBS, NIH, Bethesda, MD 20892 USA. GSF, Inst Klin Mol Biol & Tumorgenet, Munich, Germany. RP Felix, K (reprint author), NCI, Genet Lab, DBS, NIH, Bldg 37,Room 2B03, Bethesda, MD 20892 USA. EM felixk@dc37a.nci.nih.gov NR 21 TC 4 Z9 4 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD APR 15 PY 1998 VL 58 IS 8 BP 1616 EP 1619 PG 4 WC Oncology SC Oncology GA ZH644 UT WOS:000073132600008 PM 9563470 ER PT J AU Schmidt, L Junker, K Weirich, G Glenn, G Choyke, P Lubensky, I Zhuang, ZP Jeffers, M Woude, GV Neumann, H McClellan, W Linehan, WM Zbar, B AF Schmidt, L Junker, K Weirich, G Glenn, G Choyke, P Lubensky, I Zhuang, ZP Jeffers, M Woude, GV Neumann, H McClellan, W Linehan, WM Zbar, B TI Two North American families with hereditary papillary renal carcinoma and identical novel mutations in the MET proto-oncogene SO CANCER RESEARCH LA English DT Article ID CELL CARCINOMA AB Hereditary papillary renal carcinoma (HPRC) is a newly recognized inherited disorder characterized by a predisposition to develop multiple bilateral papillary renal carcinomas. Individuals affected with HPRC have been shown to have germ-line mutations in the tyrosine kinase domain of the MET proto-oncogene. We identified a novel mutation in exon 16 of the MET gene in two large North American HPRC families. The H1112R MET mutation segregated with the disease, was not present in 320 normal chromosomes, and caused malignant transformation of NIH 3T3 cells. By examining individuals with the H1112R mutation, we determined the age-dependent penetrance of this mutation and identified additional nonrenal malignancies that occurred in mutation carriers. Affected members of the two families shared the same haplotype within and immediately distal to the MET gene, suggesting a founder effect. The identification of the H1112R mutation will facilitate predictive testing in HPRC and guide future studies of the MET gene in human neoplasia. C1 NCI, Frederick Canc Res & Dev Ctr, Immunobiol Lab, Frederick, MD 21702 USA. NCI, Frederick Canc Res & Dev Ctr, Adv Biosci Labs, Basic Res Program, Frederick, MD 21702 USA. NCI, Frederick Canc Res & Dev Ctr, Intramural Res Support Program, Sci Applicat Int Corp Frederick, Frederick, MD 21702 USA. NCI, Urol Oncol Branch, NIH, Bethesda, MD 20892 USA. NCI, Genet Epidemiol Branch, NIH, Bethesda, MD 20892 USA. NCI, Pathol Lab, NIH, Bethesda, MD 20892 USA. NIH, Dept Diagnost Radiol, Bethesda, MD 20892 USA. Univ Freiburg, D-79106 Freiburg, Germany. RP Zbar, B (reprint author), NCI, Frederick Canc Res & Dev Ctr, Immunobiol Lab, Bldg 560 Room 12-71, Frederick, MD 21702 USA. NR 13 TC 137 Z9 140 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD APR 15 PY 1998 VL 58 IS 8 BP 1719 EP 1722 PG 4 WC Oncology SC Oncology GA ZH644 UT WOS:000073132600027 PM 9563489 ER PT J AU Bordi, C Ferraro, G Azzoni, C Corleto, V Gibril, F Delle Fave, G Jensen, RT AF Bordi, C Ferraro, G Azzoni, C Corleto, V Gibril, F Delle Fave, G Jensen, RT TI Topographic distribution of ECL cell changes in the oxyntic mucosa of ZES patients. SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 NIH, Digest Dis Branch, Bethesda, MD 20892 USA. Univ La Sapienza, Gastroenterol Sect, Rome, Italy. Univ Parma, Dept Pathol, I-43100 Parma, Italy. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR 15 PY 1998 VL 114 IS 4 SU S MA G0318 BP A78 EP A78 DI 10.1016/S0016-5085(98)80316-8 PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA ZH263 UT WOS:000073089600316 ER PT J AU Cai, T Yu, P Monga, SPS Mishra, B Mishra, L AF Cai, T Yu, P Monga, SPS Mishra, B Mishra, L TI Molecular cloning and expression of mouse itih-4: Encodes a scaffolding protein in liver formation. SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 VA Med Ctr, Lab Dev Mol Biol, Washington, DC USA. Temple Univ, Fels Inst Canc Res & Mol Biol, Philadelphia, PA 19122 USA. Natl Human Genome Res Inst, Clin Gene Therapy Branch, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR 15 PY 1998 VL 114 IS 4 SU S MA L0079 BP A1218 EP A1218 DI 10.1016/S0016-5085(98)84941-X PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA ZH263 UT WOS:000073089604941 ER PT J AU Cai, T Yu, P Monga, SPS Mishra, B Mishra, L AF Cai, T Yu, P Monga, SPS Mishra, B Mishra, L TI elf3, a novel beta-spectrin gene in liver and bile duct development. SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 VA Med Ctr, Lab Dev Mol Biol, Washington, DC USA. Temple Univ, Fels Inst Canc Res & Mol Biol, Philadelphia, PA 19122 USA. Natl Human Genome Res Inst, Clin Gene Therapy Branch, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR 15 PY 1998 VL 114 IS 4 SU S MA G2103 BP A516 EP A516 DI 10.1016/S0016-5085(98)82092-1 PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA ZH263 UT WOS:000073089602092 ER PT J AU Carroll, J Tio, L Thomas, G Yancey, K AF Carroll, J Tio, L Thomas, G Yancey, K TI Epidermolysis Bullosa Acquisita associated with a severe hypopharyngeal and esophageal stricture. SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 Georgetown Univ, Washington, DC USA. NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR 15 PY 1998 VL 114 IS 4 SU S MA G0344 BP A84 EP A85 DI 10.1016/S0016-5085(98)80341-7 PN 2 PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA ZH263 UT WOS:000073089600341 ER PT J AU Choi, JK Linehan, C Perin, N Pohl, M Wank, SA AF Choi, JK Linehan, C Perin, N Pohl, M Wank, SA TI Internalization is not important for desensitization or resensitization of the cholecystokinin type B receptor (CCKBR). SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 NIDDK, DDB, NIH, Bethesda, MD USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR 15 PY 1998 VL 114 IS 4 SU S MA G4649 BP A1136 EP A1136 DI 10.1016/S0016-5085(98)84619-2 PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA ZH263 UT WOS:000073089604619 ER PT J AU Chung, DC Brown, SB Graeme-Cook, F Warshaw, AL Seto, M Jensen, RT Arnold, A AF Chung, DC Brown, SB Graeme-Cook, F Warshaw, AL Seto, M Jensen, RT Arnold, A TI Overexpression of cyclin D1 protein in pancreatic endocrine tumors. SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. Univ Connecticut, Ctr Hlth, Ctr Mol Med, Farmington, CT USA. Aichi Canc Ctr, Lab Chemotherapy, Nagoya, Aichi 464, Japan. NIH, Digest Dis Branch, Bethesda, MD 20892 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR 15 PY 1998 VL 114 IS 4 SU S MA G1821 BP A448 EP A448 DI 10.1016/S0016-5085(98)81810-6 PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA ZH263 UT WOS:000073089601810 ER PT J AU Corleto, VD Romano, G Severi, C Capurso, G Strom, R Weber, HC Jensen, RT Delle Fave, G AF Corleto, VD Romano, G Severi, C Capurso, G Strom, R Weber, HC Jensen, RT Delle Fave, G TI Somatostatin mediates contractility of the human circular colonic smooth muscle cells (SMC) through a receptor subtype 2 (SST2). SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 Univ La Sapienza, Gastroenterol Unit, Dept Cellular Biotechnol & Haematol, Rome, Italy. NIH, Digest Dis Branch, Bethesda, MD 20892 USA. Boston Univ, Sch Med, Boston, MA 02215 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR 15 PY 1998 VL 114 IS 4 SU S MA G3043 BP A737 EP A737 DI 10.1016/S0016-5085(98)83019-9 PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA ZH263 UT WOS:000073089603019 ER PT J AU Eissele, R Anlauf, M Schafer, MKH Eiden, LE Frank, M Arnold, R Weihe, E AF Eissele, R Anlauf, M Schafer, MKH Eiden, LE Frank, M Arnold, R Weihe, E TI Expression of the vesicular monoamine transporters I and II in gastric endocrine cell hyperplasia and gastric carcinoids. SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 Univ Marburg, Dept Gastroenterol, Marburg, Germany. Univ Marburg, Dept Anat, Marburg, Germany. NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR 15 PY 1998 VL 114 IS 4 SU S MA G4666 BP A1140 EP A1140 DI 10.1016/S0016-5085(98)84636-2 PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA ZH263 UT WOS:000073089604636 ER PT J AU Ferris, HA Tapia, JA Jensen, RT Garcia, LJ AF Ferris, HA Tapia, JA Jensen, RT Garcia, LJ TI Stimulation of translocation and tyrosine phosphorylation of p130(Cas) in rat pancreatic acinar cells by cholecystokinin (CCK). SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 Univ Extremadura, Caceres, Spain. NIH, Bethesda, MD 20892 USA. RI Tapia, Jose/C-5181-2008 OI Tapia, Jose/0000-0002-3614-6867 NR 0 TC 0 Z9 0 U1 0 U2 3 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR 15 PY 1998 VL 114 IS 4 SU S MA G1858 BP A457 EP A457 DI 10.1016/S0016-5085(98)81847-7 PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA ZH263 UT WOS:000073089601847 ER PT J AU Frucht, H Wank, SA Tarasova, N Xiao, Y AF Frucht, H Wank, SA Tarasova, N Xiao, Y TI Uncoupling of the expression and function of CCK-B/gastrin receptors on human colon cancer cell lines. SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 Fox Chase Canc Ctr, Div Gastroenterol, Philadelphia, PA 19111 USA. NIH, Digest Dis Branch, Bethesda, MD 20892 USA. ABL Basic Res Program, Frederick, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR 15 PY 1998 VL 114 IS 4 SU S MA G2459 BP A598 EP A599 PN 2 PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA ZH263 UT WOS:000073089602441 ER PT J AU Frucht, H Jensen, RT Dexter, D Xiao, Y AF Frucht, H Jensen, RT Dexter, D Xiao, Y TI Functional expression of m3 muscarinic cholinergic receptors on human colon cancer cell lines. SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 Fox Chase Canc Ctr, Div Gastroenterol, Philadelphia, PA 19111 USA. NIH, Digest Dis Branch, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR 15 PY 1998 VL 114 IS 4 SU S MA G2458 BP A598 EP A598 PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA ZH263 UT WOS:000073089602440 ER PT J AU Fuss, IJ Boirivant, M Chu, AC Strober, W AF Fuss, IJ Boirivant, M Chu, AC Strober, W TI Oxazolone-induced colitis: An animal model of ulcerative colitis treatable with antibodies to IL-4. SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 ISS, Dept Immunol, Rome, Italy. NIH, Mucosal Immun Sect, Bethesda, MD 20892 USA. RI BOIRIVANT, MONICA/B-9977-2016 NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR 15 PY 1998 VL 114 IS 4 SU S MA G4020 BP A980 EP A981 DI 10.1016/S0016-5085(98)83994-2 PN 2 PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA ZH263 UT WOS:000073089603993 ER PT J AU Gibril, F Serrano, J Yu, F Goebel, SU Jensen, RT AF Gibril, F Serrano, J Yu, F Goebel, SU Jensen, RT TI An aggressive and nonaggressive form of disease exists in patients with multiple endocrine neoplasia type 1 and Zollinger-Ellison syndrome (ZES). SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 NIH, Bethesda, MD 20892 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR 15 PY 1998 VL 114 IS 4 SU S MA G4684 BP A1144 EP A1144 PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA ZH263 UT WOS:000073089604654 ER PT J AU Gibril, F Reynolds, JC Chen, CC Serrano, J Goebel, SU Yu, F Lubensky, IA Norton, JA Jensen, RT AF Gibril, F Reynolds, JC Chen, CC Serrano, J Goebel, SU Yu, F Lubensky, IA Norton, JA Jensen, RT TI A prospective study of gastric localization in patients with Zollinger-Ellison syndrome (ZES) with somatostatin receptor scintigraphy (SRS) and its association with the presence of gastric carcinoid tumors. SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 NIH, Bethesda, MD 20892 USA. Univ Calif San Francisco, Med Ctr, San Francisco, CA 94143 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR 15 PY 1998 VL 114 IS 4 SU S MA G4683 BP A1144 EP A1144 PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA ZH263 UT WOS:000073089604653 ER PT J AU Goebel, SU Gibril, F Yu, F Serrano, J Jensen, RT AF Goebel, SU Gibril, F Yu, F Serrano, J Jensen, RT TI Serum chromogranin A as a marker of disease presence extent or activity in patients with gastrinoma. SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR 15 PY 1998 VL 114 IS 4 SU S MA G4689 BP A1145 EP A1145 DI 10.1016/S0016-5085(98)84659-3 PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA ZH263 UT WOS:000073089604659 ER PT J AU Gonsky, R Deem, RL Young, HA Targan, SR AF Gonsky, R Deem, RL Young, HA Targan, SR TI Identification of both CD2 enhancer and repressor elements within the interferon-gamma promoter which regulate cytokine secretion in lamina propria T-cells. SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 NCI, Frederick Canc Res & Dev Ctr, Expt Immunol Lab, Frederick, MD 21702 USA. Cedars Sinai Med Ctr, Ctr Inflammatory Bowel Dis, Los Angeles, CA 90048 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR 15 PY 1998 VL 114 IS 4 SU S MA G4043 BP A986 EP A987 DI 10.1016/S0016-5085(98)84017-1 PN 2 PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA ZH263 UT WOS:000073089604016 ER PT J AU Hou, W Ryan, RR Coy, DH Jensen, RT AF Hou, W Ryan, RR Coy, DH Jensen, RT TI The orphan receptor, BRS-3, causes tyrosine phosphorylation (TYR-P) of focal adhesion kinase (p125(FAK)). SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 Univ Pecs, H-7643 Pecs, Hungary. NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR 15 PY 1998 VL 114 IS 4 SU S MA G4707 BP A1150 EP A1150 DI 10.1016/S0016-5085(98)84677-5 PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA ZH263 UT WOS:000073089604677 ER PT J AU Hunyady, B Young, WS Mezey, E AF Hunyady, B Young, WS Mezey, E TI Distribution of dopamine receptor subtypes in the upper GI tract of the rat. SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 Med Univ Pecs, H-7643 Pecs, Hungary. NIH, Bethesda, MD 20892 USA. RI Young, W Scott/A-9333-2009 OI Young, W Scott/0000-0001-6614-5112 NR 0 TC 1 Z9 1 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR 15 PY 1998 VL 114 IS 4 SU S MA G4708 BP A1150 EP A1150 PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA ZH263 UT WOS:000073089604679 ER PT J AU Hunyady, B Mezey, E AF Hunyady, B Mezey, E TI Histaminergic properties of gastrin-producing endocrine cells of the rat stomach. SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 Univ Pecs, H-7643 Pecs, Hungary. NIH, Bethesda, MD 20892 USA. RI Young, W Scott/A-9333-2009 OI Young, W Scott/0000-0001-6614-5112 NR 0 TC 1 Z9 1 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR 15 PY 1998 VL 114 IS 4 SU S MA G4709 BP A1150 EP A1150 PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA ZH263 UT WOS:000073089604676 ER PT J AU Ito, T Mantey, SA Coy, DH Jiang, NY Fuselier, J Jensen, RT AF Ito, T Mantey, SA Coy, DH Jiang, NY Fuselier, J Jensen, RT TI Vasoactive intestinal peptide (VIP) structural requirements for high affinity interaction with the VIP receptor in pancreatic acini. SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 Tulane Univ, New Orleans, LA 70118 USA. NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR 15 PY 1998 VL 114 IS 4 SU S MA G1914 BP A470 EP A470 DI 10.1016/S0016-5085(98)81903-3 PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA ZH263 UT WOS:000073089601903 ER PT J AU Katsuno, T Pradhan, TK Mantey, SA Donohue, PJ Battey, JF Coy, DH Jensen, RT AF Katsuno, T Pradhan, TK Mantey, SA Donohue, PJ Battey, JF Coy, DH Jensen, RT TI Elucidation of receptor domains of gastrin-releasing peptide receptor (GRPR) determining high selectivity for peptide antagonists. SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 Tulane Univ, New Orleans, LA 70118 USA. NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR 15 PY 1998 VL 114 IS 4 SU S MA G4719 BP A1153 EP A1153 DI 10.1016/S0016-5085(98)84689-1 PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA ZH263 UT WOS:000073089604691 ER PT J AU Lau, DTY Kleiner, DE Ghany, MG Schmid, P Hoofnagle, JH AF Lau, DTY Kleiner, DE Ghany, MG Schmid, P Hoofnagle, JH TI Sustained virologic response to interferon alpha (IFN-alpha) in chronic hepatitis C is associated with long-term histologic improvement and lack of hepatic HCV RNA SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 NIDDK, Liver Dis Sect, Bethesda, MD USA. NCI, Pathol Lab, NIH, Bethesda, MD 20892 USA. Natl Inst Genet, Los Angeles, CA USA. NR 0 TC 5 Z9 5 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR 15 PY 1998 VL 114 IS 4 SU S MA L0353 BP A1284 EP A1284 DI 10.1016/S0016-5085(98)85211-6 PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA ZH263 UT WOS:000073089605211 ER PT J AU Mantey, SA Ryan, RR Weber, HC Pradhan, T Coy, DH Jensen, RT AF Mantey, SA Ryan, RR Weber, HC Pradhan, T Coy, DH Jensen, RT TI Native human bombesin receptor subtype 3 has a unique pharmacology. SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 Tulane Univ, New Orleans, LA 70118 USA. NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR 15 PY 1998 VL 114 IS 4 SU S MA G4754 BP A1162 EP A1162 DI 10.1016/S0016-5085(98)84724-0 PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA ZH263 UT WOS:000073089604727 ER PT J AU Marth, T Kelsall, B Strober, W Zeitz, M AF Marth, T Kelsall, B Strober, W Zeitz, M TI Mucosal immune responses to fed soluble protein antigen in T cell receptor (TCR) transgenic mice. SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 NIH, Mucosal Immun Sect, Bethesda, MD 20892 USA. Univ Saarland, D-6650 Homburg, Germany. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR 15 PY 1998 VL 114 IS 4 SU S MA G4229 BP A1033 EP A1033 DI 10.1016/S0016-5085(98)84202-9 PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA ZH263 UT WOS:000073089604202 ER PT J AU Nozu, T Chrousos, GP Webster, EL Rice, KC Tache, Y AF Nozu, T Chrousos, GP Webster, EL Rice, KC Tache, Y TI Stress-induced inhibition of gastric and stimulation of colonic motor function involved CRF interaction with different receptor subtypes in rats. SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 VA Med Ctr, CURE Dig Dis Res Ctr, Dept Med, Los Angeles, CA USA. Univ Calif Los Angeles, Inst Brain Res, Los Angeles, CA 90024 USA. NIH, Pediat Endocrinol Sect, Bethesda, MD 20892 USA. NIH, Med Chem Branch, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR 15 PY 1998 VL 114 IS 4 SU S MA G4786 BP A1170 EP A1170 DI 10.1016/S0016-5085(98)84756-2 PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA ZH263 UT WOS:000073089604757 ER PT J AU Pisegna, JR Lew, EA Tarasova, NI Kopp, JA Michejda, CJ Walsh, JH Wank, SA AF Pisegna, JR Lew, EA Tarasova, NI Kopp, JA Michejda, CJ Walsh, JH Wank, SA TI The cholecystokinin type b receptor (CCKBR) in the human kidney mediates gastrin-stimulated urinary sodium excretion. SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 Univ Calif Los Angeles, CURE VA, DDRC, Los Angeles, CA USA. NCI, Frederick Canc Res & Dev Ctr, ABL Basic Res Program, Bethesda, MD 20892 USA. NIDDK, Digest Dis Branch, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR 15 PY 1998 VL 114 IS 4 SU S MA G4797 BP A1172 EP A1173 DI 10.1016/S0016-5085(98)84767-7 PN 2 PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA ZH263 UT WOS:000073089604765 ER PT J AU Pradhan, TK Katsuno, T Ryan, RR Mantey, SA Akeson, MA Donohue, PJ Battey, JF Spindel, ER Jensen, RT AF Pradhan, TK Katsuno, T Ryan, RR Mantey, SA Akeson, MA Donohue, PJ Battey, JF Spindel, ER Jensen, RT TI The Bombesin Receptor Subtype 4 is coupled to phospholipase C and has a unique pharmacology. SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 NIH, Bethesda, MD 20892 USA. Oregon Reg Primate Res Ctr, Beaverton, OR 97006 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR 15 PY 1998 VL 114 IS 4 SU S MA G4798 BP A1173 EP A1173 DI 10.1016/S0016-5085(98)84768-9 PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA ZH263 UT WOS:000073089604770 ER PT J AU Quezado, MM Makhlouf, HR Sanjuan, X Bryant, B Merino, MJ Sobin, LH Duray, PH AF Quezado, MM Makhlouf, HR Sanjuan, X Bryant, B Merino, MJ Sobin, LH Duray, PH TI Microdissection detects multiple chromosomal abnormalities in gastrointestinal stromal tumors. SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 NCI, Bethesda, MD 20892 USA. Armed Forces Inst Pathol, Washington, DC 20306 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR 15 PY 1998 VL 114 IS 4 SU S MA G2745 BP A665 EP A665 DI 10.1016/S0016-5085(98)82725-X PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA ZH263 UT WOS:000073089602725 ER PT J AU Ryan, RR Weber, HC Mantey, SA Pradhan, TK Hou, W Coy, DH Jensen, RT AF Ryan, RR Weber, HC Mantey, SA Pradhan, TK Hou, W Coy, DH Jensen, RT TI Pharmacology and intracellular signaling of the human Bombesin Receptor Subtype 3. SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 NIH, Bethesda, MD 20892 USA. Tulane Univ, New Orleans, LA 70118 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR 15 PY 1998 VL 114 IS 4 SU S MA G4812 BP A1176 EP A1177 DI 10.1016/S0016-5085(98)84782-3 PN 2 PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA ZH263 UT WOS:000073089604780 ER PT J AU Schoen, RE Kuller, LK Tangen, C Burke, G Tracy, R Dobs, A Savage, P AF Schoen, RE Kuller, LK Tangen, C Burke, G Tracy, R Dobs, A Savage, P TI Body size, increased blood glucose and insulin, and colorectal cancer (CRC). SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 NHLBI, Bethesda, MD USA. Univ Pittsburgh, Pittsburgh, PA 15260 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR 15 PY 1998 VL 114 IS 4 SU S MA G2784 BP A674 EP A674 PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA ZH263 UT WOS:000073089602764 ER PT J AU Serrano, J Goebel, SU Heppner, C Burns, AL Marx, SJ Gibril, F Jensen, RT AF Serrano, J Goebel, SU Heppner, C Burns, AL Marx, SJ Gibril, F Jensen, RT TI Occurrence of multiple endocrine neoplasia type 1 (MEN-1) gene mutations in patients with Zollinger-Ellison syndrome (ZES). SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 NIH, Bethesda, MD 20892 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR 15 PY 1998 VL 114 IS 4 SU S MA G2022 BP A496 EP A496 DI 10.1016/S0016-5085(98)82011-8 PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA ZH263 UT WOS:000073089602011 ER PT J AU Serrano, J Gibril, F Yu, F Goebel, SU Jensen, RT AF Serrano, J Gibril, F Yu, F Goebel, SU Jensen, RT TI Gastric antisecretory drug-induced achlorhydria causes decreases in serum vitamin B-12 levels in patients with Zollinger-Ellison syndrome (ZES): A prospective study. SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 NIH, Bethesda, MD 20892 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR 15 PY 1998 VL 114 IS 4 SU S MA G1156 BP A282 EP A282 DI 10.1016/S0016-5085(98)81146-3 PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA ZH263 UT WOS:000073089601146 ER PT J AU Tan, D Matsumoto, A Conry-Cantilena, C Melpolder, JC Hess, G Leuther, M Shih, JWK Alter, HJ AF Tan, D Matsumoto, A Conry-Cantilena, C Melpolder, JC Hess, G Leuther, M Shih, JWK Alter, HJ TI Hepatitis G virus infection in blood donors with positive screening test for hepatitis C virus antibody. SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 NIH, Dept Transfus Med, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR 15 PY 1998 VL 114 IS 4 SU S MA L0630 BP A1352 EP A1352 DI 10.1016/S0016-5085(98)85488-7 PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA ZH263 UT WOS:000073089605488 ER PT J AU Tomizawa, M Xanthopoulos, K AF Tomizawa, M Xanthopoulos, K TI Primary of hepatocytes deficient in CCAAT/enhancer binding protein alpha exhibit increased proliferative activity and biliary epithelium character. SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 Natl Human Genome Res Inst, Clin Gene Therapy Branch, NIH, Bethesda, MD USA. Aurora Biosci Corp, Mol Biol & Genomics, San Diego, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR 15 PY 1998 VL 114 IS 4 SU S MA L0643 BP A1355 EP A1355 PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA ZH263 UT WOS:000073089605501 ER PT J AU van Stolk, R Budd, GT Kresty, R Ganapathi, R Elson, P Church, J Piazza, G Fryer, B Provencher, K Pamukcu, R Hawk, E Kelloff, G Stoner, G AF van Stolk, R Budd, GT Kresty, R Ganapathi, R Elson, P Church, J Piazza, G Fryer, B Provencher, K Pamukcu, R Hawk, E Kelloff, G Stoner, G TI Effect of sulindac sulfone on proliferation, apoptosis, and polyps in a clinical trial in familial adenomatous polyposis (FAP) with rectal polyps. SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 Ohio State Univ, Columbus, OH 43210 USA. Cleveland Clin Fdn, Cleveland, OH 44195 USA. Cell Pathways Inc, Horsham, PA USA. NCI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR 15 PY 1998 VL 114 IS 4 SU S MA G2881 BP A696 EP A696 DI 10.1016/S0016-5085(98)82860-6 PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA ZH263 UT WOS:000073089602860 ER PT J AU Weber, HC Marsh, D Lubensky, I Lin, A Eng, C AF Weber, HC Marsh, D Lubensky, I Lin, A Eng, C TI Germline PTEN/MMAC1/TEP1 mutations and association with gastrointestinal manifestations in Cowden disease. SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 Boston Univ, Sch Med, Boston, MA 02118 USA. Dana Farber Canc Inst, Human Canc Genet Unit, Boston, MA 02115 USA. NCI, Bethesda, MD 20892 USA. NR 0 TC 3 Z9 3 U1 0 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR 15 PY 1998 VL 114 IS 4 SU S MA G2902 BP A702 EP A702 DI 10.1016/S0016-5085(98)82880-1 PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA ZH263 UT WOS:000073089602880 ER PT J AU Xiao, ZL Chen, Q Amaral, J Biancani, P Jensen, RT Behar, J AF Xiao, ZL Chen, Q Amaral, J Biancani, P Jensen, RT Behar, J TI Excess membrane cholesterol alters CCK receptor binding affinity and capacity of human gallbladder muscle. SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 Rhode Isl Hosp, Dept Med, Providence, RI 02903 USA. Brown Univ, Providence, RI 02912 USA. NIDDK, Digest Dis Branch, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR 15 PY 1998 VL 114 IS 4 SU S MA G3531 BP A861 EP A861 PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA ZH263 UT WOS:000073089603509 ER PT J AU Yu, F Zheng, YL Jensen, RT Lubensky, IA Ferrin, LJ AF Yu, F Zheng, YL Jensen, RT Lubensky, IA Ferrin, LJ TI High resolution scan of genome rearrangements in gastrinomas. SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 NCI, Pathol Lab, NIH, Bethesda, MD 20892 USA. NIDDK, Genet & Biochem Branch, Digest Dis Branch, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR 15 PY 1998 VL 114 IS 4 SU S MA G2084 BP A511 EP A511 DI 10.1016/S0016-5085(98)82073-8 PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA ZH263 UT WOS:000073089602073 ER PT J AU Yu, P Cai, T Monga, SPS Mishra, B Mishra, L AF Yu, P Cai, T Monga, SPS Mishra, B Mishra, L TI Structure and expression of Cded, a novel gene encoding a PH domain, maps to the distal portion of mouse chromosome 2. SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 VA Med Ctr, Lab Dev Mol Biol, Washington, DC USA. Temple Univ, Fels Inst Canc Res & Mol Biol, Philadelphia, PA 19122 USA. Natl Human Genome Res Inst, Clin Gene Therapy Branch, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR 15 PY 1998 VL 114 IS 4 SU S MA L0706 BP A1370 EP A1371 DI 10.1016/S0016-5085(98)85564-9 PN 2 PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA ZH263 UT WOS:000073089605564 ER PT J AU Zheng, YL Herr, A Ferrin, LJ AF Zheng, YL Herr, A Ferrin, LJ TI Detailed genome anatomy of the commonly studied gastric adenocarcinoma cell lines. SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 NIDDK, Genet & Biochem Branch, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR 15 PY 1998 VL 114 IS 4 SU S MA G2934 BP A709 EP A709 DI 10.1016/S0016-5085(98)82911-9 PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA ZH263 UT WOS:000073089602911 ER PT J AU Stumpo, DJ Eddy, RL Haley, LL Sait, S Shows, TB Lai, WS Young, WS Speer, MC Dehejia, A Polymeropoulos, M Blackshear, PJ AF Stumpo, DJ Eddy, RL Haley, LL Sait, S Shows, TB Lai, WS Young, WS Speer, MC Dehejia, A Polymeropoulos, M Blackshear, PJ TI Promoter sequence, expression, and fine chromosomal mapping of the human gene (MLP) encoding the MARCKS-like protein: Identification of neighboring and linked polymorphic loci for MLP and MACS and use in the evaluation of human neural tube defects SO GENOMICS LA English DT Article ID C-KINASE SUBSTRATE; ABNORMAL BRAIN-DEVELOPMENT; HUMAN GENOME; LINKAGE DISEQUILIBRIUM; FAMILY; MICE; PHOSPHORYLATION; DEFICIENCY; MACMARCKS; BINDING AB The MARCKS-like protein (MLP), also known as F52, MacMARCKS, or MARCKS-related protein, is a widely distributed substrate for protein kinase C (PKC), Recent studies using gene disruption in vivo have demonstrated the importance of both MARCKS and MLP to the development of the central nervous system; specifically, mice lacking either protein exhibit a high frequency of neural tube defects. We isolated a genomic clone for human MLP and discovered a directly linked polymorphism (MLP1) useful for genetic linkage analysis. The MLP promoter was 71% identical over 433 bp to that of the corresponding mouse gene, Mlp, with conservation of many putative transcription factor-binding sites; it was only 36% identical over 433 bp to the promoter of the human gene, MACS, which encodes the MLP homologue MARCKS. This 433-bp fragment drove expression of an MLP-beta-galactosidase transgene in a tissue-specific and developmental expression pattern that was similar to that observed for the endogenous gene, as shown by in situ hybridization histochemistry, In contrast to MACS, the MLP and Mlp promoters contain a TATA box approximately 40 bp 5' of the presumed transcription initiation site. MLP was localized to chromosome 1p34 --> 1pter by analysis of human-mouse somatic cell hybrid DNA and to 1p34 by fluorescence in situ hybridization, Radiation hybrid mapping of MLP placed it between genetic markers D1S511 (LOD > 3.0) and WI9232. MACS was localized to 6q21 between D6S266 (LOD > 3.0) and AFM268vh5 by the same technique. We tested the novel MLP1 polymorphism and the MACS flanking markers in a series of 43 Caucasian simplex families in which the affected child had a lumbosacral myelomeningocele. We found no evidence of linkage disequilibrium, suggesting that these loci were not major genes for spina bifida in these families, Nonetheless, the identification of linked and neighboring polymorphisms for MACS and MLP should permit similar genetic studies in other groups of patients with neural tube defects and other neurodevelopmental abnormalities. (C) 1998 Academic Press. C1 NIEHS, Off Clin Res, Res Triangle Pk, NC 27709 USA. NIEHS, Lab Signal Transduct, Res Triangle Pk, NC 27709 USA. Duke Univ, Med Ctr, Dept Biochem, Durham, NC 27710 USA. Duke Univ, Med Ctr, Dept Med, Durham, NC 27710 USA. Roswell Pk Canc Inst, Dept Human Genet, Buffalo, NY 14263 USA. NIH, Natl Ctr Human Genome Res, Bethesda, MD 20892 USA. NIMH, Sect Neural Gene Express, Bethesda, MD 20892 USA. RP Blackshear, PJ (reprint author), NIEHS, Off Clin Res, A2-05,111 Alexander Dr, Res Triangle Pk, NC 27709 USA. RI Young, W Scott/A-9333-2009 OI Young, W Scott/0000-0001-6614-5112 FU NHGRI NIH HHS [HG00333]; NICHD NIH HHS [HD33400]; NINDS NIH HHS [NS26630] NR 40 TC 23 Z9 24 U1 0 U2 1 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0888-7543 J9 GENOMICS JI Genomics PD APR 15 PY 1998 VL 49 IS 2 BP 253 EP 264 DI 10.1006/geno.1998.5247 PG 12 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA ZN543 UT WOS:000073656400011 PM 9598313 ER PT J AU Stanley, E Gilbert, DG Jenkins, NA Copeland, NG Harvey, RP AF Stanley, E Gilbert, DG Jenkins, NA Copeland, NG Harvey, RP TI Murine cerberus homologue Cer1 maps to chromosome 4 SO GENOMICS LA English DT Article ID GENETIC-LINKAGE MAP C1 Royal Melbourne Hosp, Walter & Eliza Hall Inst Med Res, Parkville, Vic 3050, Australia. NCI, Frederick Canc Res & Dev Ctr, Mammalian Genet Lab, ABL Basic Res Program, Frederick, MD 21702 USA. RP Harvey, RP (reprint author), Royal Melbourne Hosp, Walter & Eliza Hall Inst Med Res, Parkville, Vic 3050, Australia. RI Stanley, Ed/A-2985-2013 OI Stanley, Ed/0000-0002-6389-3665 NR 7 TC 5 Z9 5 U1 0 U2 0 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0888-7543 J9 GENOMICS JI Genomics PD APR 15 PY 1998 VL 49 IS 2 BP 337 EP 338 DI 10.1006/geno.1997.5249 PG 2 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA ZN543 UT WOS:000073656400026 PM 9598328 ER PT J AU Kastner, DL AF Kastner, DL TI Familial Mediterranean fever: The genetics of inflammation SO HOSPITAL PRACTICE LA English DT Article AB When a patient complains of episodic fever accompanied by unexplained arthritis, peritonitis, pleurisy, or skin rash, this disorder should be considered. The disease-related gene codes for a protein that guides a neutrophil's participation in inflammation; the protein's existence implies an entire regulatory pathway hitherto unknown. At least two other mendelian periodic fever syndromes have also been described. C1 NIAMSD, Genet Sect, Arthrit & Rheumatism Branch, Bethesda, MD 20892 USA. RP Kastner, DL (reprint author), NIAMSD, Genet Sect, Arthrit & Rheumatism Branch, Bethesda, MD 20892 USA. NR 12 TC 47 Z9 49 U1 0 U2 1 PU MCGRAW HILL HEALTHCARE PUBLICATIONS PI MINNEAPOLIS PA 4530 WEST 77TH ST, MINNEAPOLIS, MN 55435-5000 USA SN 8750-2836 J9 HOSP PRACT JI Hosp. Pract. PD APR 15 PY 1998 VL 33 IS 4 BP 131 EP + PG 14 WC Medicine, General & Internal SC General & Internal Medicine GA ZH329 UT WOS:000073097100012 PM 9562837 ER PT J AU Hisada, M Garber, JE Fung, CY Fraumeni, JF Li, FP AF Hisada, M Garber, JE Fung, CY Fraumeni, JF Li, FP TI Multiple primary cancers in families with Li-Fraumeni syndrome SO JNCI-JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID ADRENAL-CORTICAL CARCINOMA; 2ND MALIGNANT NEOPLASMS; TUMOR-SUPPRESSOR GENE; LONG-TERM SURVIVORS; BREAST-CANCER; P53 GENE; GERMLINE MUTATIONS; HODGKINS-DISEASE; OVARIAN-CANCER; MORTALITY AB Background: Li-Fraumeni syndrome is a dominantly inherited disorder characterized by early-onset breast cancer, sarcomas, and other cancers in children and young adults, Members of families with this syndrome also develop multiple primary cancers, but the frequency is unknown. To approach this issue, we quantified the incidence of second and third primary cancers in individuals from 24 Li-Fraumeni kindreds originally diagnosed with cancer during the period from 1968 through 1986, Methods: The relative risk (RR) of subsequent cancers and 95% confidence intervals (CIs) were calculated by use of population-based incidence data from the Connecticut Cancer Registry. Kaplan-Meier analysis was used to determine the cumulative probability (+/- standard error) of subsequent cancers. Results: Among 200 Li-Fraumeni syndrome family members diagnosed with cancer, 30 (15%) developed a second cancer. Eight individuals (4%) had a third cancer, while four (2%) eventually developed a fourth cancer. Overall, the RR of occurrence of a second cancer was 5.3 (95% CI = 2.8-7.8), with a cumulative probability of second cancer occurrence of 57% (+/-10%) at 30 years after diagnosis of a first cancer. RRs of second cancers occurring in families with this syndrome were 83.0 (95% CI = 36.9-187.6), 9.7 (95% CI = 4.9-19.2), and 1.5 (95% CI = 0.5-4.2) for individuals with a first cancer at ages 0-19 years, 20-44 years, and 45 years or more, respectively. Thirty (71%) of 42 subsequent cancers in this group were component cancers of Li-Fraumeni syndrome. Conclusions: Compared with the general population, members of Li-Fraumeni syndrome families have an exceptionally high risk of developing multiple primary cancers. The excess risk of additional primary cancers is mainly for cancers that are characteristic of Li-Fraumeni syndrome, with the highest risk observed for survivors of childhood cancers. Cancer survivors in these families should be closely monitored for early manifestations of new cancers. C1 Harvard Univ, Sch Publ Hlth, Dana Farber Canc Inst, Div Canc Epidemiol & Control, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiat Oncol, Boston, MA USA. NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. RP Harvard Univ, Sch Publ Hlth, Dana Farber Canc Inst, Div Canc Epidemiol & Control, 44 Binney St,SM202, Boston, MA 02115 USA. FU NHGRI NIH HHS [5RO1HG00725] NR 53 TC 264 Z9 271 U1 0 U2 4 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0027-8874 EI 1460-2105 J9 JNCI-J NATL CANCER I JI JNCI-J. Natl. Cancer Inst. PD APR 15 PY 1998 VL 90 IS 8 BP 606 EP 611 DI 10.1093/jnci/90.8.606 PG 6 WC Oncology SC Oncology GA ZH325 UT WOS:000073096700012 PM 9554443 ER PT J AU Bianco, P Kuznetsov, SA Riminucci, M Fisher, LW Spiegel, AM Robey, PG AF Bianco, P Kuznetsov, SA Riminucci, M Fisher, LW Spiegel, AM Robey, PG TI Reproduction of human fibrous dysplasia of bone in immunocompromised mice by transplanted mosaics of normal and Gs alpha-mutated skeletal progenitor cells SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article DE McCune-Albright Syndrome; G protein; marrow stromal cells; transplantation; somatic mosaicism ID MCCUNE-ALBRIGHT SYNDROME; STIMULATORY G-PROTEIN; ACTIVATING MUTATIONS; STEM-CELLS; MARROW; SUBUNIT; G(S); EXPRESSION; ADIPOCYTES AB We have isolated progenitor cells from the stromal system of the fibrous dysplastic marrow of patients with McCune-Albright Syndrome. Analysis of the Gs alpha gene from individual colonies provided direct evidence for the presence of two different genotypes within single fibrous dysplastic lesions: marrow stromal cells containing two normal Gs alpha alleles, and those containing one normal allele and an allele with an activating mutation. Transplantation of clonal populations of normal cells into the subcutis of immunocompromised mice resulted in normal ossicle formation. in contrast, transplantation of clonal populations of mutant cells always led to the loss of transplanted cells from the transplantation site and no ossicle formation. However, transplantation of a mixture of normal and mutant cells reproduced an abnormal ectopic ossicle recapitulating human fibrous dysplasia and providing an in vivo cellular model of this disease. These results provide experimental evidence for the necessity of both normal and mutant cells in the development of McCune-Albright Syndrome fibrous dysplastic lesions in bone. C1 NIDR, Craniofacial & Skeletal Dis Branch, NIH, Bethesda, MD 20892 USA. NIDDKD, Metab Dis Branch, NIH, Bethesda, MD 20892 USA. Univ Aquila, Dept Expt Med, I-67100 Laquila, Italy. Univ Rome La Sapienza, I-00161 Rome, Italy. RP Robey, PG (reprint author), NIDR, Craniofacial & Skeletal Dis Branch, NIH, 30 Convent Dr,MSC 4320, Bethesda, MD 20892 USA. EM probey@yoda.nidr.nih.gov RI Robey, Pamela/H-1429-2011 OI Robey, Pamela/0000-0002-5316-5576 FU Telethon [E.0519] NR 32 TC 140 Z9 142 U1 1 U2 2 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD APR 15 PY 1998 VL 101 IS 8 BP 1737 EP 1744 DI 10.1172/JCI2361 PG 8 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA ZJ234 UT WOS:000073193000025 PM 9541505 ER PT J AU Pratley, RE Thompson, DB Prochazka, M Baier, L Mott, D Ravussin, E Sakul, H Ehm, MG Burns, DK Foroud, T Garvey, WT Hanson, RL Knowler, WC Bennett, PH Bogardus, C AF Pratley, RE Thompson, DB Prochazka, M Baier, L Mott, D Ravussin, E Sakul, H Ehm, MG Burns, DK Foroud, T Garvey, WT Hanson, RL Knowler, WC Bennett, PH Bogardus, C TI An autosomal genomic scan for loci linked to prediabetic phenotypes in Pima Indians SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article DE type 2 diabetes mellitus; glucose tolerance; insulin secretion; insulin action; genetics ID DEPENDENT DIABETES-MELLITUS; SUSCEPTIBILITY LOCUS; QUANTITATIVE TRAITS; VARIANCE-COMPONENTS; INSULIN-RESISTANCE; GENETIC-LINKAGE; WIDE SEARCH; MUTATIONS; OBESITY; NIDDM AB Type 2 diabetes mellitus is a common chronic disease that is thought to have a substantial genetic basis. Identification of the genes responsible has been hampered by the complex nature of the syndrome. Abnormalities in insulin secretion and insulin action predict the development of type 2 diabetes and are, themselves, highly heritable traits. Since fewer genes may contribute to these precursors of type 2 diabetes than to the overall syndrome, such genes may be easier to identify. We, therefore, undertook an autosomal genomic scan to identify loci linked to prediabetic traits in Pima Indians, a population with a high prevalence of type 2 diabetes. 363 nondiabetic Pima Indians were genotyped at 516 polymorphic microsatellite markers on all 22 autosomes, Linkage analyses were performed using three methods (single-marker, nonparametric multipoint [MAPMAKER/SIBS], and variance components multipoint). These analyses provided evidence for linkage at several chromosomal regions, including 3q21-24 linked to fasting plasma insulin concentration and in vivo insulin action, 4p15-q12 linked to fasting plasma insulin concentration, 9q21 linked to 2-h insulin concentration during oral glucose tolerance testing, and 22q12-13 linked to fasting plasma glucose concentration. These results suggest loci that may harbor genes contributing to type 2 diabetes in Pima Indians. None of the linkages exceeded a LOD score of 3.6 (a 5% probability of occurring in a genome-wide scan). These findings must, therefore, be considered tentative until extended in this population or replicated in others. C1 NIDDKD, Clin Diabet & Nutr Sect, NIH, Phoenix, AZ 85016 USA. NIDDKD, Phoenix Epidemiol & Clin Res Branch, NIH, Phoenix, AZ 85016 USA. Sequana Therapeut Inc, Dept Stat Genet, La Jolla, CA 92037 USA. Glaxo Wellcome Inc, Res Triangle Pk, NC 27709 USA. Indiana Univ, Sch Med, Dept Med Genet, Indianapolis, IN 46202 USA. Med Univ S Carolina, Ralph H Johnson Vet Affairs Med Ctr, Dept Med, Charleston, SC 29425 USA. RP Pratley, RE (reprint author), NIDDKD, Clin Diabet & Nutr Sect, NIH, 4212 N 16Th St, Phoenix, AZ 85016 USA. RI Hanson, Robert/O-3238-2015 OI Hanson, Robert/0000-0002-4252-7068 FU NCRR NIH HHS [1P41-RR-03655]; NIDDK NIH HHS [DK-47461] NR 43 TC 173 Z9 183 U1 0 U2 1 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD APR 15 PY 1998 VL 101 IS 8 BP 1757 EP 1764 DI 10.1172/JCI1850 PG 8 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA ZJ234 UT WOS:000073193000027 PM 9541507 ER PT J AU Kim, MG Chen, C Flomerfelt, FA Germain, RN Schwartz, RH AF Kim, MG Chen, C Flomerfelt, FA Germain, RN Schwartz, RH TI A subtractive PCR-based cDNA library made from fetal thymic stromal cells SO JOURNAL OF IMMUNOLOGICAL METHODS LA English DT Article DE cDNA library; fetal thymic organ culture; polymerase chain reaction; thymic stromal cells; subtractive hybridization ID THYMOCYTES IN-VITRO; POSITIVE SELECTION; NEGATIVE SELECTION; T-CELLS; EPITHELIUM; MOUSE; DIFFERENTIATION; LYMPHOCYTES; LINE; MHC AB We describe our initial approach to clone and characterize genes expressed preferentially in thymic stromal cells, in an attempt to generate molecular reagents to study the role of these cells in thymopoiesis and rhymic function. Thymic stromal cells were prepared from fetal thymic organ cultures by treating them with 2-deoxyguanosine and depleting the remaining hematopoietic cells with anti-CD45 antibody. A cDNA library was then prepared after subtraction and amplification by PCR. The cloned inserts were sequenced and compared for homology with known genes in the data base. Unidentified cDNAs were then examined for expression in normal and SCID thymus and in a set of SV40-transformed rhymic epithelial cell lines, by Northern blotting and a dot blot assay. In this report we describe the development of the library and present a general description of the genes identified from the initial 249 cDNAs sequenced. Among these, a relatively high percentage (55%) do not show any homology to previously identified genes. Several genes with a limited expression pattern were selected for further study. (C) 1998 Published by Elsevier Science B.V. All rights reserved. C1 NIAID, Cellular & Mol Immunol Lab, NIH, Bethesda, MD 20892 USA. NIAID, Immunol Lab, NIH, Bethesda, MD 20892 USA. RP Schwartz, RH (reprint author), NIAID, Cellular & Mol Immunol Lab, NIH, Bldg 4,Rm 111, Bethesda, MD 20892 USA. EM rs34r@nih.gov NR 40 TC 19 Z9 21 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0022-1759 J9 J IMMUNOL METHODS JI J. Immunol. Methods PD APR 15 PY 1998 VL 213 IS 2 BP 169 EP 182 DI 10.1016/S0022-1759(98)00031-3 PG 14 WC Biochemical Research Methods; Immunology SC Biochemistry & Molecular Biology; Immunology GA 104DD UT WOS:000074996800005 PM 9692849 ER PT J AU Hemmer, B Vergelli, M Gran, B Ling, N Conlon, P Pinilla, C Houghten, R McFarland, HF Martin, R AF Hemmer, B Vergelli, M Gran, B Ling, N Conlon, P Pinilla, C Houghten, R McFarland, HF Martin, R TI Cutting edge: Predictable TCR antigen recognition based on peptide scans leads to the identification of agonist ligands with no sequence homology SO JOURNAL OF IMMUNOLOGY LA English DT Article ID T-CELL RECEPTOR; MYELIN BASIC-PROTEIN; ALPHA-BETA; AUTOIMMUNITY; ACTIVATION; COMPLEX; BINDING; CLONES; HLA-A2; VIRUS AB The potential of CD4+ T cells for cross-recognition of self and foreign Ags has important implications for the understanding of thymic selection, lymphocyte survival, and the occurrence of autoimmune diseases. Here, we define the extensive flexibility of Ag recognition for three human CD4+ autoreactive T cell clones (TCC) by using ligands with single and multiple amino acid (aa) substitutions. Our results demonstrate that the spectrum of tolerated ligands and the resulting stimulatory potency of peptides for a TCC can be predicted by the relative influence of each aa, Using this approach, me have identified stimulatory Ligands not sharing a single aa in corresponding positions with the Ag used to establish the TCC. These results argue for an independent contribution of each aa in the peptide sequence to the affinity of the MHC/peptide complex to the TCR. C1 NINDS, Cellular Immunol Sect, Neuroimmunol Branch, NIH, Bethesda, MD 20892 USA. Neurocrine Biosci Inc, San Diego, CA 92121 USA. Torrey Pines Inst Mol Studies, San Diego, CA 92121 USA. Multiple Peptide Syst, San Diego, CA 92121 USA. Univ Maryland, Sch Med, Dept Neurol, Baltimore, MD 21201 USA. RP Martin, R (reprint author), NINDS, Cellular Immunol Sect, Neuroimmunol Branch, NIH, Bldg 10 Room 5B16,10 Ctr Dr MSC 1400, Bethesda, MD 20892 USA. RI Gran, Bruno/A-2288-2013 OI Gran, Bruno/0000-0001-6384-2342 NR 30 TC 121 Z9 122 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD APR 15 PY 1998 VL 160 IS 8 BP 3631 EP 3636 PG 6 WC Immunology SC Immunology GA ZG143 UT WOS:000072970400002 PM 9558061 ER PT J AU Kwak, LW Pennington, R Boni, L Ochoa, AC Robb, RJ Popescu, MC AF Kwak, LW Pennington, R Boni, L Ochoa, AC Robb, RJ Popescu, MC TI Cutting edge: Liposomal formulation of a self lymphoma antigen induces potent protective antitumor immunity SO JOURNAL OF IMMUNOLOGY LA English DT Article ID B-CELL LYMPHOMA; IDIOTYPE VACCINATION; TUMOR-IMMUNITY; INDUCTION; IMMUNIZATION; RESISTANCE; PROTEINS; SURFACE; LINE AB We developed a liposome carrier for a model nonimmunogenic, self Ag. This carrier reproducibly converted lymphoma Ig into a potent tumor rejection Ag in mice, A single immunization induced protection against challenges representing 20 to 100 times the minimum lethal dose of parental tumor, This protective effect required minimal amounts of incorporated Ag and IL-2 and elicited specific Abs (compared with free Ag or liposomal control Ig which did not elicit any specific Abs); depletion experiments demonstrated a requirement for effector CD4(+) and CD8(+) T cells, Head-to-head comparisons, indicating superior potency and induction of specific T cell activation, distinguished liposomal from prototype, carrier-conjugated Ag. These results provide a strategy for formulating weak tumor or other clinically important Ags into vaccines. C1 NCI, Frederick Canc Res & Dev Ctr, Dept Expt Transplantat & Immunol, Med Branch,Div Clin Sci, Frederick, MD 21702 USA. Biomira USA, Cranbury, NJ 08512 USA. SAIC Frederick, Frederick, MD 21702 USA. RP Kwak, LW (reprint author), NCI, Frederick Canc Res & Dev Ctr, Dept Expt Transplantat & Immunol, Med Branch,Div Clin Sci, Bldg 567,Rm 205, Frederick, MD 21702 USA. NR 27 TC 43 Z9 43 U1 3 U2 3 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD APR 15 PY 1998 VL 160 IS 8 BP 3637 EP 3641 PG 5 WC Immunology SC Immunology GA ZG143 UT WOS:000072970400003 PM 9558062 ER PT J AU Ochoa-Garay, J Kaye, J Coligan, JE AF Ochoa-Garay, J Kaye, J Coligan, JE TI Nuclear factor kappa B Is required for peptide antigen-induced differentiation of a CD4(+)CD8(+) thymocyte line SO JOURNAL OF IMMUNOLOGY LA English DT Article ID T-CELL DEVELOPMENT; CLASS-I; TNF-ALPHA; PROTEOLYTIC DEGRADATION; TARGETED DISRUPTION; POSITIVE SELECTION; INDUCED APOPTOSIS; MICE LACKING; P50 SUBUNIT; ACTIVATION AB NF-kappa B transcription factors are known to regulate the expression of a number of genes involved in T cell activation and function, Some evidence has suggested that they also play a role in T cell development. However, the role of NF-kappa B in Ag-induced thymocyte differentiation has not been directly addressed to date. Here we critically examine this role by employing DPK, a CD4(+)CD8(+) thymocyte line that undergoes differentiation upon TCR engagement in a process that closely mimics positive selection, Expression of a degradation-resistant form of I kappa B alpha in DPK cells results in constitutive inhibition of NF-kappa B activity, We find that in the absence of NF-kappa B activity, MHC-peptide-induced differentiation of DPK is blocked. Furthermore, differentiation induced by a nonphysiologic stimulus, anti-TCR Ab, is greatly reduced, Altogether, our data indicate a requirement for NF-kappa B in the developmental changes associated with positive selection. C1 NIAID, Mol Struct Lab, Rockville, MD 20852 USA. Scripps Res Inst, Dept Immunol, La Jolla, CA 92037 USA. RP Coligan, JE (reprint author), NIAID, Mol Struct Lab, Twinbrook 2,Room 103,12441 Parklawn Dr, Rockville, MD 20852 USA. NR 63 TC 11 Z9 11 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD APR 15 PY 1998 VL 160 IS 8 BP 3835 EP 3843 PG 9 WC Immunology SC Immunology GA ZG143 UT WOS:000072970400029 PM 9558088 ER PT J AU Lai, L Alaverdi, N Maltais, L Morse, HC AF Lai, L Alaverdi, N Maltais, L Morse, HC TI Mouse cell surface antigens: Nomenclature and immunophenotyping SO JOURNAL OF IMMUNOLOGY LA English DT Review ID HEMATOPOIETIC STEM-CELLS; DENDRITIC CELLS; T-CELLS; MONOCLONAL-ANTIBODIES; MOLECULAR-CLONING; MURINE HOMOLOG; DIFFERENTIATION ANTIGEN; ADHESION MOLECULE; BONE-MARROW; B-CELLS AB This paper reviews cell surface Ags expressed on mouse hemopoietic and nonhemopoietic cells, The review will cover molecules included in the cluster of differentiation (CD) from CD1 to CD166 and lymphocyte Ag (Ly) series from Ly-1 to Ly-81 as well as some new Ags without current CD or Ly assignments. In addition to an update on mouse nomenclature, there will be a discussion of some known functions of the molecules and brief comments on the use of particular Ags for immunophenotyping of cell subsets. Several novel markers mentioned may prove useful in mouse immunology research. C1 NIAID, Immunopathol Lab, NIH, Bethesda, MD 20892 USA. PharMingen, San Diego, CA 92121 USA. Jackson Lab, Bar Harbor, ME 04609 USA. RP Morse, HC (reprint author), NIAID, Immunopathol Lab, NIH, Bldg 7,Room 304, Bethesda, MD 20892 USA. OI Morse, Herbert/0000-0002-9331-3705 FU NHGRI NIH HHS [HG00330] NR 57 TC 59 Z9 63 U1 2 U2 9 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD APR 15 PY 1998 VL 160 IS 8 BP 3861 EP 3868 PG 8 WC Immunology SC Immunology GA ZG143 UT WOS:000072970400032 PM 9558091 ER PT J AU Rubbert, A Combadiere, C Ostrowski, M Arthos, J Dybul, M Machado, E Cohn, MA Hoxie, JA Murphy, PM Fauci, AS Weissman, D AF Rubbert, A Combadiere, C Ostrowski, M Arthos, J Dybul, M Machado, E Cohn, MA Hoxie, JA Murphy, PM Fauci, AS Weissman, D TI Dendritic cells express multiple chemokine receptors used as coreceptors for HIV entry SO JOURNAL OF IMMUNOLOGY LA English DT Article ID EOSINOPHIL EOTAXIN RECEPTOR; EPIDERMAL LANGERHANS CELLS; IMMUNODEFICIENCY-VIRUS; FUNCTIONAL EXPRESSION; CC-CHEMOKINE; MOLECULAR-CLONING; BLOOD MONOCYTES; T-CELLS; INFECTION; RANTES AB Cells of the dendritic lineage are thought to be among the first cells infected after mucosal exposure to HIV, Zn this study, we have identified the presence of multiple chemokine receptors on dendritic cells (DC) that may function as coreceptors for HIV entry, DC effectively used CCR5 far entry of macrophage (M)-tropic isolates. CCR3, the eotaxin receptor, initially identified on eosinophils, is expressed on DC and may be used as an entry coreceptor by certain dual-tropic strains, CXCR4 was not expressed on DC, although SDF-1 induced a calcium flux and DC could be infected by T cell line (T)-tropic HIV. Our findings pro,ide evidence for the presence of a non-CXCR4 SDF-1 receptor on DC that is used mainly by T-tropic strains of HIV. DC from individuals homozygous for a 32-bp deletion of the CCR5 gene are also infectable with M-tropic strains of HIV-1, and this infection is inhibited by stromal cell-derived factor (SDF)1, suggesting that this receptor can also be used by hi-tropic HIV for entry, Delineation of the spectrum of coreceptor usage on DC may offer new approaches to interfere with the initiation and propagation of HIV infection. C1 NIAID, Immunoregulat Lab, NIH, Bethesda, MD 20892 USA. NIAID, Host Def Lab, NIH, Bethesda, MD 20892 USA. Univ Penn, Dept Pathol & Lab Med, Philadelphia, PA 19104 USA. RP Rubbert, A (reprint author), NIAID, Immunoregulat Lab, NIH, Bldg 10,Room 6A02,10 Ctr Dr,MSC-1576, Bethesda, MD 20892 USA. RI Combadiere, Christophe/I-5639-2013 OI Combadiere, Christophe/0000-0002-1755-4531 NR 65 TC 116 Z9 117 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD APR 15 PY 1998 VL 160 IS 8 BP 3933 EP 3941 PG 9 WC Immunology SC Immunology GA ZG143 UT WOS:000072970400041 PM 9558100 ER PT J AU Inamura, N Mekori, YA Bhattacharyya, SP Bianchine, PJ Metcalfe, DD AF Inamura, N Mekori, YA Bhattacharyya, SP Bianchine, PJ Metcalfe, DD TI Induction and enhancement of Fc epsilon RI-dependent mast cell degranulation following coculture with activated T cells: Dependency on ICAM-1- and leukocyte function-associated antigen (LFA)-1-mediated heterotypic aggregation SO JOURNAL OF IMMUNOLOGY LA English DT Article ID DELAYED-TYPE HYPERSENSITIVITY; ADHESION MOLECULE-1; DE-GRANULATION; LYMPHOCYTES-T; LFA-1; STIMULATION; FIBRONECTIN; HISTAMINE; RECEPTORS; PROLIFERATION AB Activated mast cells are known to reside in close apposition to T cells in various inflammatory processes, In this regard, we have reported that activated mast cells form heterotypic aggregates with activated lymphocytes. To determine whether this interaction would result in mast cell degranulation, we examined the effect of EL-4, 2B4, or freshly isolated T cells, activated by PMA or immobilized anti-CD3 mAb, on histamine release from murine hone marrow-derived cultured mast cells (BMCMC). Coculturing BMCMC with activated hut not with resting T cells resulted in significant histamine release, Also, Fc epsilon RI cross-linking-induced degranulation was augmented when BMCMC were cocultured with activated T cells, Supernatants of activated T cells failed to exert the stimulatory effect, Separation of the two cell populations with a porous membrane prevented degranulation, indicating that BMCMC activation was adhesion dependent, Indeed, the kinetics of histamine release paralleled the kinetics of the formation of heterotypic aggregates, which peaked after 12 h of coculture, Introduction of anti-LFA-l and anti-intercellular adhesion molecule-1 mAb inhibited the adhesion-induced mast cell degranulation, These data suggest a heretofore unrecognized mast cell activation pathway induced by LFA-1/intercellular adhesion molecule-1-mediated heterotypic aggregation with activated T cells. C1 NIAID, LAD, NIH, Bethesda, MD 20892 USA. Fujisawa Pharmaceut Co Ltd, Ibaraki, Osaka, Japan. Meir Gen Hosp, Dept Med, Kfar Saba, Israel. Tel Aviv Univ, Sackler Sch Med, IL-69978 Tel Aviv, Israel. RP Metcalfe, DD (reprint author), NIAID, LAD, NIH, Bldg 10,Room 11C205,10 Ctr Dr,MSC 1881, Bethesda, MD 20892 USA. NR 52 TC 91 Z9 91 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD APR 15 PY 1998 VL 160 IS 8 BP 4026 EP 4033 PG 8 WC Immunology SC Immunology GA ZG143 UT WOS:000072970400053 PM 9558112 ER PT J AU Jakob, T Udey, MC AF Jakob, T Udey, MC TI Regulation of E-cadherin-mediated adhesion in Langerhans cell-like dendritic cells by inflammatory mediators that mobilize Langerhans cells in vivo SO JOURNAL OF IMMUNOLOGY LA English DT Article ID TUMOR-NECROSIS-FACTOR; DRAINING LYMPH-NODES; FACTOR-ALPHA; CONTACT SENSITIZATION; EPITHELIAL-CELLS; GENE-EXPRESSION; PROTEIN CAUSES; INTERLEUKIN-1; ANTIGEN; CYTOKINES AB Adhesion of Langerhans cells (LC) to keratinocytes is mediated by E-cadherin, IL-1, TNF-alpha, and LPS mobilize LC from epidermis and presumably attenuate LC-keratinocyte adhesion, To determine whether these mediators modulated LC E-cadherin-dependent adhesion directly, we characterized their effects on LC-like dendritic cells expanded from marine fetal skin (FSDDC), FSDDC were propagated from day 16 C57BL/6 fetal skin and isolated as aggregates (FSDDC-A) in which homophilic adhesion was mediated by E-cadherin, IL-1, TNF-alpha, and LPS induced dissociation of FSDDC-A that began within 4 to 8 h and was complete within 20 h, Anti-IL-1RI mAb inhibited disaggregation caused by IL-1 alpha and IL-1 beta, but not that induced by TNF-alpha or LPS, Anti-TNF-alpha mAb inhibited the effect of TNF-alpha and LPS, but not that caused by IL-1 alpha or IL-1 beta, Flow cytometry of FSDDC-A revealed that IL-1, TNF-alpha, and LPS induced increased expression of MHC class II, CD40, and CD86 and decreased E-cadherin expression that was temporally related to dissociation of aggregates, IL-1 and TNF-alpha caused a rapid reduction in FSDDC E-cadherin mRNA levels that preceded the decrease in E-cadherin surface expression, These results demonstrate that cytokines that induce LC emigration in vivo act directly on LC-like cells in vitro, reduce E-cadherin mRNA levels, down-regulate E-cadherin surface expression, and induce a loss of E-cadherin-mediated adhesion. C1 NCI, Dermatol Branch, NIH, Bethesda, MD 20892 USA. RP Udey, MC (reprint author), NCI, Dermatol Branch, NIH, Bldg 10,Room 12N238, Bethesda, MD 20892 USA. RI Jakob, Thilo/J-1621-2012 NR 43 TC 112 Z9 117 U1 0 U2 2 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD APR 15 PY 1998 VL 160 IS 8 BP 4067 EP 4073 PG 7 WC Immunology SC Immunology GA ZG143 UT WOS:000072970400058 PM 9558117 ER PT J AU Trotter, JL Pelfrey, CM Trotter, AL Selvidge, JA Gushleff, KC Mohanakumar, T McFarland, HF AF Trotter, JL Pelfrey, CM Trotter, AL Selvidge, JA Gushleff, KC Mohanakumar, T McFarland, HF TI T cell recognition of myelin proteolipid protein and myelin proteolipid protein peptides in the peripheral blood of multiple sclerosis and control subjects SO JOURNAL OF NEUROIMMUNOLOGY LA English DT Article DE multiple sclerosis; T cells; myelin proteolipid protein ID EXPERIMENTAL ALLERGIC ENCEPHALOMYELITIS; EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS; CENTRAL-NERVOUS-SYSTEM; LYMPH-NODE CELLS; BASIC-PROTEIN; ENCEPHALITOGENIC EPITOPE; CEREBROSPINAL-FLUID; ADOPTIVE TRANSFER; MICE; IDENTIFICATION AB Myelin proteolipid protein (PLP) is a prime candidate autoantigen for multiple sclerosis. In order to define potential immunodominant epitopes, T cell lines (TCL) from the peripheral blood of HLA-DR 15(2) MS patients were established which responded to the intact molecule of PLP. These TCL were then tested in individual proliferation assays with a variety of PLP peptides spanning most of the PLP molecule. Multiple peptides were recognized by TCL from the RIS population, with more than one peptide often recognized by lines from the same individual. Three immunodominant peptides were identified which were recognized by the majority of MS patients. Estimated frequency analyses were then performed on the peripheral blood of HLA-DR15(2)-positive MS and control subjects using TCL initiated by the three immunodominant peptides, 40-60, 95-117, and 185-206. TCL from HLA-DRIS MS subjects recognized peptide 95-117 significantly mon often than TCL from control subjects. (C) 1998 Elsevier Science B.V. C1 Washington Univ, Sch Med, Dept Neurol & Neurol Surg, St Louis, MO 63110 USA. Washington Univ, Sch Med, Dept Pathol, St Louis, MO 63110 USA. NINDS, Neuroimmunol Branch, NIH, Bethesda, MD 20892 USA. RP Trotter, JL (reprint author), Washington Univ, Sch Med, Dept Neurol & Neurol Surg, Box 8111,660 S Euclid, St Louis, MO 63110 USA. OI Pelfrey, Clara/0000-0002-6108-7555 FU NINDS NIH HHS [R01NS29851] NR 58 TC 49 Z9 50 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-5728 J9 J NEUROIMMUNOL JI J. Neuroimmunol. PD APR 15 PY 1998 VL 84 IS 2 BP 172 EP 178 DI 10.1016/S0165-5728(97)00260-9 PG 7 WC Immunology; Neurosciences SC Immunology; Neurosciences & Neurology GA ZR735 UT WOS:000074008500010 PM 9628460 ER PT J AU Simpson, PB Russell, JT AF Simpson, PB Russell, JT TI Mitochondrial Ca2+ uptake and release influence metabotropic and ionotropic cytosolic Ca2+ responses in rat oligodendrocyte progenitors SO JOURNAL OF PHYSIOLOGY-LONDON LA English DT Article ID PERMEABILITY TRANSITION; HEART-MITOCHONDRIA; CALCIUM WAVES; ASTROCYTES; NEURONS; CELLS; DEPOLARIZATION; REMYELINATION; PROLIFERATION; OSCILLATIONS AB 1. Many physiologically important activities of oligodendrocyte progenitor cells (0-2A cells), including proliferation, migration and differentiation, are regulated by cytosolic Ca2+ signals. However, little is known concerning the mechanisms of Ca2+ signalling in this cell type. We have studied the interactions between Ca2+ entry, Ca2+ release from endoplasmic reticulum and Ca2+ regulation by mitochondria in influencing cytosolic Ca2+ responses in 0-2A cells. 2. Methacholine (MCh; 100 mu M) activated Ca2+ waves that propagated from several initiation sites along 0-2A processes. 3. During a Ca2+ wave evoked by MCh, mitochondrial membrane potential was often either depolarized (21% of mitochondria) or hyperpolarized (20% of mitochondria), as measured by changes in the fluorescence of 5,5',6,6'-tetrachloro-1,1',3,3'-tetraethylbenzimidazole carbocyanine iodide(JC-1). 4. Stimulation with kainate (100 mu M) evoked a slowly rising, sustained cytosolic Ca2+ elevation in 0-2A cells. This also, in some cases, resulted in either a depolarization (15% of mitochondria) or hyperpolarization (12% of mitochondria) of mitochondrial membrane potential. 5. Simultaneous measurement of cytosolic (fluo-3 AM) and mitochondrial (rhod-2 AM) Ca2+ responses revealed that Ca2+ elevations in the cytosol evoked by either MCh or kainate were translated into long-lasting Ca2+ elevations in subpopulations of mitochondria. In some mitochondria, Ca2+ signals appeared to activate Ca2+ release into the cytosol. 6. Inhibition of the mitochondrial Na+-Ca2(+) exchanger by CGP-37157 (25 mu M) decreased kainate Ca2+ response amplitude and increased the rate of return of the response to basal Ca2+ levels. 7. Thus, both ionotropic and metabotropic stimulation evoke changes in mitochondrial membrane potential and Ca2+ levels in 0-2A cells. Ca2+ uptake into some mitochondria is activated by Ca2+ entry into cells or release from stores. Mitochondrial Ca2+ release appears to play a key role in shaping kainate-evoked Ca2+ responses. C1 NICHHD, Lab Cellular & Mol Neurophysiol, NIH, Bethesda, MD 20892 USA. RP Russell, JT (reprint author), NICHHD, Lab Cellular & Mol Neurophysiol, NIH, Bethesda, MD 20892 USA. EM james@helix.nih.gov NR 41 TC 51 Z9 51 U1 0 U2 0 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 40 WEST 20TH STREET, NEW YORK, NY 10011-4211 USA SN 0022-3751 J9 J PHYSIOL-LONDON JI J. Physiol.-London PD APR 15 PY 1998 VL 508 IS 2 BP 413 EP 426 DI 10.1111/j.1469-7793.1998.413bq.x PG 14 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA ZM054 UT WOS:000073500100009 PM 9508806 ER PT J AU Pilcher, AS Yagi, H Jerina, DM AF Pilcher, AS Yagi, H Jerina, DM TI A novel synthetic method for cis-opened benzo[a]pyrene 7,8-diol 9,10-epoxide adducts at the exocyclic N-6-amino group of deoxyadenosine SO JOURNAL OF THE AMERICAN CHEMICAL SOCIETY LA English DT Article ID CARCINOGEN BENZOPYRENE; TRANS ADDITION; DUPLEX; OLIGODEOXYNUCLEOTIDES; NONANUCLEOTIDE; OPPOSITE C1 NIDDKD, Bioorgan Chem Lab, NIH, Bethesda, MD 20892 USA. RP Jerina, DM (reprint author), NIDDKD, Bioorgan Chem Lab, NIH, Bethesda, MD 20892 USA. NR 19 TC 23 Z9 23 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0002-7863 J9 J AM CHEM SOC JI J. Am. Chem. Soc. PD APR 15 PY 1998 VL 120 IS 14 BP 3520 EP 3521 DI 10.1021/ja980176p PG 2 WC Chemistry, Multidisciplinary SC Chemistry GA ZJ097 UT WOS:000073179200037 ER PT J AU Sabichi, AL Hendricks, DT Bober, MA Birrer, MJ AF Sabichi, AL Hendricks, DT Bober, MA Birrer, MJ TI Retinoic acid receptor beta expression and growth inhibition of gynecologic cancer cells by the synthetic retinoid N-(4-hydroxyphenyl) retinamide SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID FENRETINIDE; CARCINOMA; LINES; DIFFERENTIATION; APOPTOSIS; HEAD; NECK; ISOTRETINOIN; PREVENTION; MODULATION AB Background: The synthetic retinoid N-(4-hydroxyphenyl) retinamide (4HPR) can inhibit the growth of tumor cells. Preliminary results from a clinical trial suggest that 4HPR may reduce ovarian cancer incidence. We examined the growth-inhibitory effects of 4HPR on gynecologic cancer cell lines in vitro and the role of retinoid receptors in modulating this effect. Methods: Twelve human gynecologic cancer cell lines (the ovarian cell lines-A224, AD10, UCI 101, UCI 107, SKOV3, 222, CP70, ML3B, and ML5; the cervical cell lines-HT3 and ME180; and the endometrial cell line-Hec 1A were tested for sensitivity to 4HPR (by assaying cell proliferation rates). Cel electrophoretic analysis of DNA fragmentation was used to measure programmed cell death (apoptosis), Specific retinoid receptor (retinoic acid receptor [RAR] and retinoid X receptor) messenger RNA (mRNA) levels were measured by northern blot hybridization, AD10 cells were stably transfected with human RAR beta complementary DNA, and the effect of 4HPR on cell proliferation was examined, Results: 4HPR inhibited the growth of all 12 cell lines, but to varying degrees; IC50 values (i.e., concentrations that inhibit proliferation by 50%) ranged from 0.3 to 9 mu M. Following 4HPR treatment, ovarian cancer cells that were sensitive to 4HPR (222, CP70, and UCI 101; IC50 <3 mu M) contained higher levels of RAR beta transcripts than more resistant cells (AD10, ME180, Hec 1A, and A224; IC50 greater than or equal to 3 mu M) (2.8-fold; two-sided P = .006), Anchorage-independent growth of transfected AD10 cells expressing high levels of RAR beta was totally abolished, even in the absence of 4HPR; transfectants expressing low levels of RAR beta exhibited lower levels of anchorage-independent growth and grew more slowly in the presence of 4HPR than control untransfected AD10 cells. Conclusion: 4HPR inhibited the proliferation of ovarian cancer cells lit vitro; RAR beta expression appeared to be associated with this effect. C1 NCI, Med Branch, Div Clin Sci, Bethesda, MD 20892 USA. RP Birrer, MJ (reprint author), 9610 Med Ctr Dr, Rockville, MD 20850 USA. EM birrerm@bprb.nci.nih.gov NR 32 TC 100 Z9 101 U1 0 U2 1 PU NATL CANCER INSTITUTE PI BETHESDA PA 9030 OLD GEORGETOWN RD, BETHESDA, MD 20814 USA SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD APR 15 PY 1998 VL 90 IS 8 BP 597 EP 605 DI 10.1093/jnci/90.8.597 PG 9 WC Oncology SC Oncology GA ZH325 UT WOS:000073096700011 PM 9554442 ER PT J AU Manns, A Hanchard, B Morgan, OS Wilks, R Cranston, B Nam, J Blank, M Kuwayama, M Yashiki, S Fujiyoshi, T Blattner, W Sonoda, S AF Manns, A Hanchard, B Morgan, OS Wilks, R Cranston, B Nam, J Blank, M Kuwayama, M Yashiki, S Fujiyoshi, T Blattner, W Sonoda, S TI Human leukocyte antigen class II alleles associated with human T-cell lymphotropic virus type I infection and adult T-cell leukemia/lymphoma in a black population SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID TROPICAL SPASTIC PARAPARESIS; HTLV-I; MYELOPATHY; LEUKEMIA; JAMAICA; HLA; ANTIBODIES; LYMPHOMA; PATTERNS; DISEASE AB Background: Human T-cell lymphotropic virus type I(HTLV-T) is linked to adult T-cell leukemia/lymphoma (ATL) and HTLV-I-associated myelopathy (HAM; also known as tropical spastic paraparesis [TSP]), a chronic neurodegenerative disorder. Worldwide, several million HTLV-I carriers are at risk for disease, with an estimated lifetime cumulative risk of 1%-5%. However, the determinants of disease progression are relatively unknown. We studied human leukocyte antigens (HLA class II) that have been implicated in the pathogenesis of HTLV-I-related diseases. Methods: We analyzed HLA class II alleles among asymptomatic HTLV-I carriers (n = 45), patients with ATL (n = 49) or HAM/TSP (n = 54), and HTLV-I seronegative control subjects (n = 51), All participants were of African descent and were enrolled in epidemiologic studies conducted at the University of the West Indies, Kingston, Jamaica. We used standard microlymphocytotoxicity assays for HLA antigen serotyping and polymerase chain reaction-based methods to examine HLA class II DRB1 and DQB1 alleles, Results: Two antigens determined by serotyping, DR15 and DQ1, occurred at significantly increased frequency among HTLV-I carriers compared with seronegative control subjects (42% versus 22% for DR15 [odds ratio (OR)= 2.7; 95% confidence interval (CI) = 1.0-7.2] and 78% versus 53% for DQ1 [OR = 3.1; 95% CI = 1.2-8.5]). Asymptomatic carriers were shown to have an HLA class II allele distribution similar to that of patients with ATL, and the frequencies of the alleles DRB1*1501, DRB1*1101, and DQB1*0602 were significantly greater in patients with ATL and asymptomatic carriers than in patients with HAM/TSP, In addition, haplotypes DRB1*1101-DQB1*0301 and DRB1*1501-DQB1*0602 were significantly increased among patients with ATL compared with patients with HAM/TSP. Conclusions: These data suggest that host genetic background is an important factor in determining whether HTLV-I carriers develop either ATL or HAM/TSP. C1 NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA. Univ W Indies, Dept Pathol, Med & Trop Metab Res Unit, Kingston 7, Jamaica. Kagoshima Univ, Fac Med, Dept Virol, Kagoshima 890, Japan. RP Manns, A (reprint author), NCI, Div Canc Epidemiol & Genet, NIH, Execut Plaza N,Rm 434, Bethesda, MD 20892 USA. FU NCI NIH HHS [N01-CP40548] NR 41 TC 27 Z9 28 U1 0 U2 0 PU NATL CANCER INSTITUTE PI BETHESDA PA 9030 OLD GEORGETOWN RD, BETHESDA, MD 20814 USA SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD APR 15 PY 1998 VL 90 IS 8 BP 617 EP 622 DI 10.1093/jnci/90.8.617 PG 6 WC Oncology SC Oncology GA ZH325 UT WOS:000073096700014 PM 9554445 ER PT J AU Okada, T Ramsey, WJ Munir, J Wildner, O Blaese, RM AF Okada, T Ramsey, WJ Munir, J Wildner, O Blaese, RM TI Efficient directional cloning of recombinant adenovirus vectors using DNA-protein complex SO NUCLEIC ACIDS RESEARCH LA English DT Article ID GENERATION; TYPE-5 AB We describe an efficient cloning system utilizing adenoviral DNA-protein complexes which allows the directional cloning of genes into adenoviral expression vectors in a single step, DNA-protein complexes derived from a recombinant adenovirus (AVC2.null) were isolated by sequential use of CsCl step gradients followed by isopycnic centrifugation in a mixture of CsCl and guanidine HCl. AVC2.null is an adenoviral expression vector containing unique restriction sites between the human CMV-IE promoter and the SV40 intron/polyadenylation site. Transgenes were prepared for cloning into this vector by introduction of compatible restriction sites by PCR. A vector expressing rat granulocyte-macrophage colony-stimulating factor (GM-CSF) was constructed using DNA-protein complex as well as by traditional recombination techniques. The efficacy of our adenoviral cloning system utilizing DNA-protein complex was two logs higher than that seen using homologous recombination. All viruses generated by directional ligation of the insert into the vector DNA-protein complexes contained the desired transgene in the correct orientation. This technique greatly simplifies and accelerates the generation of recombinant adenoviral vectors. C1 NHGRI, Clin Gene Therapy Branch, NIH, Bethesda, MD 20892 USA. RP Ramsey, WJ (reprint author), NHGRI, Clin Gene Therapy Branch, NIH, Bldg 10,Room 10C103,MSC 1851, Bethesda, MD 20892 USA. NR 18 TC 24 Z9 26 U1 0 U2 2 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-1048 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD APR 15 PY 1998 VL 26 IS 8 BP 1947 EP 1950 DI 10.1093/nar/26.8.1947 PG 4 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA ZJ569 UT WOS:000073229900012 PM 9518487 ER PT J AU Chen, KH Yakes, FM Srivastava, DK Singhal, RK Sobol, RW Horton, JK Van Houten, B Wilson, SH AF Chen, KH Yakes, FM Srivastava, DK Singhal, RK Sobol, RW Horton, JK Van Houten, B Wilson, SH TI Up-regulation of base excision repair correlates with enhanced protection against a DNA damaging agent in mouse cell lines SO NUCLEIC ACIDS RESEARCH LA English DT Article ID EXTRACELLULAR-SUPEROXIDE-DISMUTASE; TUMOR-NECROSIS-FACTOR; OXIDE SYNTHASE GENE; POLYMERASE-BETA; INTERFERON-GAMMA; OXIDATIVE STRESS; LIPOPOLYSACCHARIDE; MACROPHAGES; FIBROBLASTS; EXPRESSION AB DNA polymerase beta is required in mammalian cells for the predominant pathway of base excision repair involving single nucleotide gap filling DNA synthesis. Here we examine the relationship between oxidative stress, cellular levels of DNA polymerase beta and base excision repair capacity in vitro, using mouse monocytes and either wild-type mouse fibroblasts or those deleted of the DNA polymerase beta gene. Treatment with an oxidative stress-inducing agent such as hydrogen peroxide, 3-morpholinosydnonimine, xanthine/xanthine oxidase or lipopolysaccharide was found to increase the level of DNA polymerase beta in both monocytes and fibroblasts, Base excision repair capacity in vitro, as measured in crude cell extracts, was also increased by lipopolysaccharide treatment in both cell types. In monocytes lipopolysaccharide-mediated up-regulation of the base excision repair system correlated with increased resistance to the monofunctional DNA alkylating agent methyl methanesulfonate. By making use of a quantitative PCR assay to detect lesions in genomic DNA we show that lipopolysaccharide treatment of fibroblast cells reduces the incidence of spontaneous DNA lesions. This effect may be due to the enhanced DNA polymerase beta-dependent base excision repair capacity of the cells, because a similar decrease in DNA lesions was not observed in cells deficient in base excision repair by virtue of DNA polymerase beta gene deletion. Similarly, fibroblasts treated with lipopolysaccharide were more resistant to methyl methanesulfonate than untreated cells. This effect was not observed in cells deleted of the DNA polymerase beta gene. These results suggest that the DNA polymerase beta-dependent base excision repair pathway can be up-regulated by oxidative stress-inducing agents in mouse cell lines. C1 Univ Texas, Med Branch, Sealy Ctr Mol Sci, Galveston, TX 77555 USA. RP Wilson, SH (reprint author), NIEHS, Struct Biol Lab, POB 12233, Res Triangle Pk, NC 27709 USA. EM wilson@niehs.nih.gov RI Sobol, Robert/E-4125-2013 OI Sobol, Robert/0000-0001-7385-3563 FU NIEHS NIH HHS [ES06492, ES06676, ES06839] NR 38 TC 77 Z9 77 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-1048 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD APR 15 PY 1998 VL 26 IS 8 BP 2001 EP 2007 DI 10.1093/nar/26.8.2001 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA ZJ569 UT WOS:000073229900021 PM 9518496 ER PT J AU Newton, DL Boque, L Wlodawer, A Huang, CY Rybak, SM AF Newton, DL Boque, L Wlodawer, A Huang, CY Rybak, SM TI Single amino acid substitutions at the N-terminus of a recombinant cytotoxic ribonuclease markedly influence biochemical and biological properties SO BIOCHEMISTRY LA English DT Article ID FREE PROTEIN-SYNTHESIS; P-30 PROTEIN; ANTITUMOR RIBONUCLEASE; GOLGI PROTEINS; BREFELDIN-A; ANGIOGENIN; INHIBITOR; ONCONASE(R); MECHANISM; TAMOXIFEN AB Onconase is a cytotoxic ribonuclease with antitumor properties. A semisynthetic gene encoding the entire protein sequence was constructed by fusing oligonucleotides coding for the first 15 and the last 6 of the 104 amino acids to a genomic clone that encoded the remaining amino acid residues [Newton, D. L., et al. (1997) Protein Eng. 10, 463-470]. The resulting protein product expressed in Escherichia coli exhibited little enzymatic or cytotoxic activity due to the unprocessed N-terminal Met amino acid residue. In this study, we demonstrate that modification of the 5'-region of the gene to encode [Met(-1)]Ser or [Met-(-1)]Tyr instead of the native pyroglutamate results in recombinant onconase derivatives with restored activities. [Met-(-1)]rOnc(E1Y) was more active than [Met-(-1)]rOnc(E1Y) in all assays tested. Consistent with the action of native onconase, [Met-(-1)]rOnc(E1S) was a potent inhibitor of protein synthesis in the cell-free rabbit reticulocyte lysate assay, degrading tRNA at concentrations that correlated with inhibition of protein synthesis. An interesting difference between the recombinant onconase derivatives and the native protein was their susceptibility to inhibition by the major intracellular RNase inhibitor, PRI (onconase is refractory to PRI inhibition). [Met-(-1)]rOnc(E1S) and [Met-(-1)]rOnc(E1Y) inhibited protein synthesis in intact SF539 neuroblastoma cells with IC50's very similar to that of onconase (IC50 3.5, 10, and 10 mu g/mL after 1 day and 0.16, 0.35, and 2.5 mu g/mL after 5 days for onconase, [Met-(-1)]rOnc(E1S), and [Met-(-1)]rOnc(E1Y), respectively). Similar to that of onconase, cytotoxic activity of the recombinant derivatives was potentiated by monensin, N(H)4Cl, and retinoic acid. Brefeldin A completely blocked the enhancement of cytotoxicity caused by retinoic acid with all three proteins. Thus, drug-induced alterations of the intracellular trafficking of the recombinant derivatives also resembles that of onconase. Stability studies as assessed in serum-containing medium in the presence or absence of cells at 37 degrees C showed that the recombinant proteins were as stable to temperature and cell culture conditions as the native protein. Therefore, exchanging the Glu amino acid residue at the amino terminus of onconase with an amino acid residue containing a hydroxyl group produces recombinant proteins with ribonuclease and cytotoxic properties similar to native onconase. C1 NCI, Frederick Canc Res & Dev Ctr, Lab Biochem Physiol, Div Basic Sci, Frederick, MD 21702 USA. NCI, Frederick Canc Res & Dev Ctr, Intramural Res Support Program,Basic Res Program, SAIC Frederick,Macromol Struct Lab,ABL, Frederick, MD 21702 USA. NHLBI, Biochem Lab, Bethesda, MD 20892 USA. RP Rybak, SM (reprint author), NCI, Frederick Canc Res & Dev Ctr, Lab Biochem Physiol, Div Basic Sci, Bldg 567,Room 152, Frederick, MD 21702 USA. NR 44 TC 40 Z9 41 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD APR 14 PY 1998 VL 37 IS 15 BP 5173 EP 5183 DI 10.1021/bi972147h PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA ZK043 UT WOS:000073279200015 PM 9548748 ER PT J AU Ohno, H Poy, G Bonifacino, JS AF Ohno, H Poy, G Bonifacino, JS TI Cloning of the gene encoding the murine clathrin-associated adaptor medium chain mu 2: gene organization, alternative splicing and chromosomal assignment SO GENE LA English DT Article DE murine; clathrin; mu 2; gene organization; adaptation ID INSITU HYBRIDIZATION; SORTING SIGNALS; AP-2 COMPLEXES; LOCALIZATION; PROTEINS; EXPRESSION AB The mu 2 chain of the clathrin-associated adaptor complex AP-2 is a member of the adaptor medium chain family, a group of proteins involved in the sorting of integral membrane proteins in endocytic/exocytic pathways. Here, we report the cloning of the (MMU)CLAPM1 gene encoding the murine mu 2 chain, the first member of the family for which this information has become available. The mu 2 gene is approximately 8.5 kb long and is organized into 12 exons and 11 introns. Two transcripts are generated by alternative splicing of exon 5, a mini-exon of only six nucleotides. Proteins encoded by both transcripts are capable of interacting with tyrosine-based sorting signals, suggesting that they are functionally equivalent. The mu 2 gene is localized to the proximal region of mouse chromosome 16, which is syntenic to the proximal region of human chromosome 3. The isolation and characterization of the mu 2 gene should be instrumental for future studies of the genetics and physiological role of the adaptor medium chains in mammals. (C) 1998 Elsevier Science B.V. C1 NICHHD, Cell Biol & Metab Branch, NIH, Bethesda, MD 20892 USA. NIDDKD, Genet & Biochem Branch, Bethesda, MD 20892 USA. RP Bonifacino, JS (reprint author), NICHHD, Cell Biol & Metab Branch, NIH, Bldg 18T Room 101,18 Lib Dr,MSC 5430, Bethesda, MD 20892 USA. RI Ohno, Hiroshi/L-7899-2014 OI Ohno, Hiroshi/0000-0001-8776-9661 NR 20 TC 7 Z9 8 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 APR 14 PY 1998 VL 210 IS 2 BP 187 EP 193 DI 10.1016/S0378-1119(97)00649-5 PG 7 WC Genetics & Heredity SC Genetics & Heredity GA ZJ790 UT WOS:000073253500002 PM 9573360 ER PT J AU Hamasaki-Katagiri, N Katagiri, Y Tabor, CW Tabor, H AF Hamasaki-Katagiri, N Katagiri, Y Tabor, CW Tabor, H TI Spermine is not essential for growth of Saccharomyces cerevisiae: identification of the SPE4 gene (spermine synthase) and characterization of a spe4 deletion mutant SO GENE LA English DT Article DE polyamine; spermidine; spermidine synthase; spermine; yeast ID S-ADENOSYLMETHIONINE DECARBOXYLASE; YEAST; CELLS; TRANSFORMATION; INHIBITORS; POLYAMINES; BINDING; VECTORS; CLONING AB Spermine, ubiquitously present in most organisms, is the final product of the biosynthetic pathway for polyamines and is synthesized from spermidine. In order to investigate the physiological roles of spermine, we identified the SPE4 gene, which codes for spermine synthase, on the right arm of chromosome XII of Saccharomyces cerevisiae and prepared a deletion mutant in this gene. This mutant has neither spermine nor spermine synthase activity. Using the spe4 deletion mutant, we show that S. cerevisiae does not require spermine for growth, even though spermine is normally present in the wild-type organism. This is in striking contrast to the absolute requirement of S. cerevisiae for spermidine for growth, which we had previously reported using a mutant lacking the SPE3 gene (spermidine synthase). (C) 1998 Elsevier Science B.V. C1 NIDDKD, Biochem Pharmacol Lab, NIH, Bethesda, MD 20892 USA. NICHHD, Growth Factors Sect, NIH, Bethesda, MD 20892 USA. RP NIDDKD, Biochem Pharmacol Lab, NIH, Bethesda, MD 20892 USA. EM tabor@helix.nih.gov NR 27 TC 43 Z9 44 U1 1 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0378-1119 EI 1879-0038 J9 GENE JI Gene PD APR 14 PY 1998 VL 210 IS 2 BP 195 EP 201 DI 10.1016/S0378-1119(98)00027-4 PG 7 WC Genetics & Heredity SC Genetics & Heredity GA ZJ790 UT WOS:000073253500003 PM 9573363 ER PT J AU Topol, IA Burt, SK Toscano, M Russo, N AF Topol, IA Burt, SK Toscano, M Russo, N TI Protonation of glycine and alanine: proton affinities, intrinsic basicities and proton transfer path SO JOURNAL OF MOLECULAR STRUCTURE-THEOCHEM LA English DT Article DE density functional theory; G2; proton affinity; basicity; amino acids; gas phase ID GAS-PHASE BASICITIES; DENSITY FUNCTIONAL CALCULATIONS; GASEOUS ALPHA-ALANINE; AMINO-ACIDS; INDUCED FRAGMENTATION; ELECTRON-DIFFRACTION; MOLECULAR-ENERGIES; 2ND-ROW COMPOUNDS; KINETIC APPROACH; EXCHANGE-ENERGY AB Proton affinities and intrinsic basicities for nitrogen and oxygen protonation in the gas phase of the amino acids glycine and alanine were calculated using density functional theory (DFT) and ab initio methods at different levels of theory from Hartree-Fock (HF) to G2 approximations. All methods gave good agreement for proton affinities for nitrogen protonation for both amino acids. However, dramatic differences were found between DFT, MP4/MP2, and G2 results on one hand, and MP4//HF results on the other to the calculation of structural and energetic characteristics of oxygen protonation in glycine and alanine. An investigation into the source of these differences revealed that electron correlation effects are chiefly responsible for the differences in calculated oxygen proton affinities between the various methods. It has been found that proton transfer between nitrogen and oxygen protonation sites in both amino acids occurs without a transfer path barrier when correlated methods were used to calculate the path energetics. (C) 1998 Elsevier Science B.V. C1 NCI, Frederick Canc Res & Dev Ctr, Frederick Biomed Supercomp Ctr, SAIC Frederick, Frederick, MD 21702 USA. Univ Calabria, Dipartimento Chim, I-87030 Arcavacata Di Rende, Italy. RP Topol, IA (reprint author), NCI, Frederick Canc Res & Dev Ctr, Frederick Biomed Supercomp Ctr, SAIC Frederick, Frederick, MD 21702 USA. OI Nino, Russo/0000-0003-3826-3386 NR 60 TC 18 Z9 18 U1 1 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0166-1280 J9 J MOL STRUC-THEOCHEM JI Theochem-J. Mol. Struct. PD APR 14 PY 1998 VL 430 BP 41 EP 49 PG 9 WC Chemistry, Physical SC Chemistry GA ZE981 UT WOS:000072850900006 ER PT J AU Szczepanowska, J Ramachadran, U Herring, CJ Gruschus, JM Qin, J Korn, ED Brzeska, H AF Szczepanowska, J Ramachadran, U Herring, CJ Gruschus, JM Qin, J Korn, ED Brzeska, H TI Effect of mutating the regulatory phosphoserine and conserved threonine on the activity of the expressed catalytic domain of Acanthamoeba myosin I heavy chain kinase SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID DEPENDENT PROTEIN-KINASE; CRYSTAL-STRUCTURES; PHOSPHORYLATION; ACTIVATION; AUTOPHOSPHORYLATION; SUBUNIT; SEQUENCE; COMPLEX; FAMILY AB Phosphorylation of Ser-627 is both necessary and sufficient for full activity of the expressed 35-kDa catalytic domain of myosin I heavy chain kinase (MIHCK). Ser-627 lies in the variable loop between highly conserved residues DFG and APE at a position at which a phosphorylated Ser/Thr also occurs in many other Ser/Thr protein kinases, The variable loop of MIHCK contains two other hydroxyamino acids: Thr-631, which is conserved in almost all Ser/Thr kinases, and Thr-632, which is not conserved. We determined the effects on the kinase activity of the expressed catalytic domain of mutating Ser-627, Thr-631, and Thr-632 individually to Ala, Asp, and Glu, The S627A mutant was substantially less active than wild type (wt), with a lower k(cat) and higher K-m for both peptide substrate and ATP, but was more active than unphosphorylated wt. The S627D and S627E mutants were also less active than phosphorylated wt, i.e., acidic amino acids cannot substitute for phospho-Ser-627. The activity of the T631A mutant was as low as that of the S627A mutant, whereas the T632A mutant was as active as phosphorylated wt, indicating that highly conserved Thr-631, although not phosphorylated, is essential for catalytic activity. Asp and Glu substitutions for Thr-631 and Thr-632 were inhibitory to various degrees. Molecular modeling indicated that Thr-631 can hydrogen bond with conserved residue Asp-591 in the catalytic loop and that similar interactions are possible for other kinases whose activities also are regulated by phosphorylation in the variable loop. Thus, this conserved Thr residue may be essential for the activities of other Ser/Thr protein kinases as well as for the activity of MIHCK. C1 NHLBI, Cell Biol Lab, NIH, Bethesda, MD 20892 USA. NHLBI, Biophys Chem Lab, NIH, Bethesda, MD 20892 USA. RP Korn, ED (reprint author), NHLBI, Cell Biol Lab, NIH, Bldg 3,Room B1-22, Bethesda, MD 20892 USA. EM edk@nih.gov RI Korn, Edward/F-9929-2012 NR 41 TC 11 Z9 12 U1 0 U2 1 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 APR 14 PY 1998 VL 95 IS 8 BP 4146 EP 4151 DI 10.1073/pnas.95.8.4146 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA ZH535 UT WOS:000073120800016 PM 9539704 ER PT J AU Dever, TE Sripriya, R McLachlin, JR Lu, JF Fabian, JR Kimball, SR Miller, LK AF Dever, TE Sripriya, R McLachlin, JR Lu, JF Fabian, JR Kimball, SR Miller, LK TI Disruption of cellular translational control by a viral truncated eukaryotic translation initiation factor 2 alpha kinase homolog SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID DEPENDENT PROTEIN-KINASE; NUCLEAR POLYHEDROSIS-VIRUS; SACCHAROMYCES-CEREVISIAE; CATALYTIC SUBUNIT; SHUTTLE VECTORS; FACTOR-II; YEAST; GENE; GCN2; EXPRESSION AB Phosphorylation of eukaryotic translation initiation factor 2 alpha (eIF2 alpha) is a common cellular mechanism to limit protein synthesis in stress conditions. Baculovirus PK2, which resembles the C-terminal half of a protein kinase domain, was found to inhibit both human and yeast eIF2 alpha kinases. Insect cells infected with wild-type, but not pk2-deleted, baculovirus exhibited reduced eIF2 alpha phosphorylation and increased translational activity. The negative regulatory effect of human protein kinase RNA-regulated (PKR), an eIF2 alpha kinase, on virus production was counteracted by PK2, indicating that baculoviruses have evolved a unique strategy for disrupting a host stress response. PK2 was found in complex with PKR and blocked kinase autophosphorylation in vivo, suggesting a mechanism of kinase inhibition mediated by interaction between truncated and intact kinase domains. C1 NICHHD, Lab Eukaryot Gene Regulat, NIH, Bethesda, MD 20892 USA. Univ Georgia, Dept Entomol, Athens, GA 30602 USA. Penn State Univ, Coll Med, Dept Cellular & Mol Physiol, Hershey, PA 17033 USA. RP Dever, TE (reprint author), NICHHD, Lab Eukaryot Gene Regulat, NIH, Bldg 6A,Room B1A-02,6 Ctr Dr, Bethesda, MD 20892 USA. FU NIAID NIH HHS [AI23719]; NIDDK NIH HHS [DK13499, R01 DK013499] NR 42 TC 49 Z9 52 U1 0 U2 2 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 APR 14 PY 1998 VL 95 IS 8 BP 4164 EP 4169 DI 10.1073/pnas.95.8.4164 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA ZH535 UT WOS:000073120800019 PM 9539707 ER PT J AU Drake, RR Neamati, N Hong, HX Pilon, AA Sunthankar, P Hume, SD Milne, GWA Pommier, Y AF Drake, RR Neamati, N Hong, HX Pilon, AA Sunthankar, P Hume, SD Milne, GWA Pommier, Y TI Identification of a nucleotide binding site in HTV-1 integrase SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article; Proceedings Paper CT 10th International Meeting of the Society-for-Antiviral-Research CY APR 06-11, 1997 CL ATLANTA, GEORGIA SP Soc Antiviral Res ID IMMUNODEFICIENCY-VIRUS TYPE-1; VIRAL-DNA; RETROVIRAL INTEGRATION; CRYSTAL-STRUCTURE; CATALYTIC DOMAIN; HIV-1 INTEGRASE; ACTIVE-SITE; PROTEIN; REPLICATION; MUTATIONS AB HIV-1 integrase is essential for viral replication and can be inhibited by antiviral nucleotides. Photoaffinity labeling with the 3'-azido-3'-deoxythymidine (AZT) analog 3',5-diazido-2',3'-dideoxyuridine 5'-monophosphate (5N(3)-AZTMP) and proteolytic mapping identified the amino acid 153-167 region of integrase as the site of photocrosslinking. Docking of 5N(3)-AZTMP revealed the possibility for strong hydrogen bonds between the inhibitor and lysines 156, 159, and 160 of the enzyme. Mutation of these residues reduced photocrosslinking selectively. This report elucidates the binding site of a nucleotide inhibitor of HIV-1 integrase, and possibly a component of the enzyme polynucleotide binding site. C1 Univ Arkansas Med Sci, Dept Biochem & Mol Biol, Little Rock, AR 72205 USA. NCI, Div Basic Sci, Mol Pharmacol Lab, NIH, Bethesda, MD 20892 USA. NCI, Div Basic Sci, Med Chem Lab, NIH, Bethesda, MD 20892 USA. RP Drake, RR (reprint author), Univ Arkansas Med Sci, Dept Biochem & Mol Biol, Slot 516,4301 W Markham, Little Rock, AR 72205 USA. EM drakerichardr@exchange.uams.edu; pommier@nih.gov NR 36 TC 54 Z9 54 U1 0 U2 3 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 APR 14 PY 1998 VL 95 IS 8 BP 4170 EP 4175 DI 10.1073/pnas.95.8.4170 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA ZH535 UT WOS:000073120800020 PM 9539708 ER PT J AU Sata, M Donaldson, JG Moss, J Vaughan, M AF Sata, M Donaldson, JG Moss, J Vaughan, M TI Brefeldin A-inhibited guanine nucleotide-exchange activity of Sec7 domain from yeast Sec7 with yeast and mammalian ADP ribosylation factors SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID GOLGI-APPARATUS; PHOSPHOLIPASE-D; SACCHAROMYCES-CEREVISIAE; PROTEIN-TRANSPORT; BINDING PROTEINS; CHOLERA-TOXIN; ARF; MEMBRANE; CELLS; IDENTIFICATION AB The Saccharomyces cerevisiae Sec7 protein (ySec7p), which is an important component of the yeast secretory pathway, contains a sequence of approximate to 200 amino acids referred to as a Sec7 domain. Similar Sec7 domain sequences have been recognized in several guanine nucleotide-exchange proteins (GEPs) for ADP ribosylation factors (ARFs). ARFs are approximate to 20-kDa GTPases that regulate intracellular vesicular membrane trafficking and activate phospholipase D. GEPs activate ARFs by catalyzing the replacement of bound GDP with GTP. We, therefore, undertook to determine whether a Sec7 domain itself could catalyze nucleotide exchange on ARF and found that it exhibited brefeldin A (BFA)-inhibitable ARF GEP activity. BFA is known to inhibit ARF GEP activity in Golgi membranes, thereby causing reversible apparent dissolution of the Golgi complex in many cells. The His(6)-tagged Sec7 domain from ySec7p (rySec7d) synthesized in Escherichia coli enhanced binding of guanosine 5'-[gamma-[S-35]thio]triphosphate by recombinant yeast ARF1 (ryARF1) and ryARF2 but not by ryARF3. The effects of rySec7d on ryARF2 were inhibited by BFA in a concentration-dependent manner but not by inactive analogues of BFA (B-17, B-27, and B-36). rySec7d also promoted BFA-sensitive guanosine 5'-[gamma-thio]triphosphate binding by nonmyristoylated recombinant human, ARF1 (rh-ARF1), rhARF5, and rhARF6, although the effect on rhARF6 was very small. These results are consistent with the conclusion that the yeast Sec7 domain itself contains the elements necessary for ARF GEP activity and its inhibition by BFA. C1 NHLBI, Pulm Crit Care Med Branch, NIH, Bethesda, MD 20892 USA. NHLBI, Cell Biol Lab, NIH, Bethesda, MD 20892 USA. RP Sata, M (reprint author), NHLBI, Pulm Crit Care Med Branch, NIH, Room 5N-307,Bldg 10,10 Ctr Dr,MSC 1590, Bethesda, MD 20892 USA. NR 38 TC 68 Z9 70 U1 1 U2 2 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 APR 14 PY 1998 VL 95 IS 8 BP 4204 EP 4208 DI 10.1073/pnas.95.8.4204 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA ZH535 UT WOS:000073120800026 PM 9539714 ER PT J AU Rai, SS Wolff, J AF Rai, SS Wolff, J TI The C terminus of beta-tubulin regulates vinblastine-induced tubulin polymerization SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID COLCHICINE-BINDING SITE; LOCALIZATION; SUBTILISIN; BRAIN; PROTEOLYSIS; INVITRO; SUBUNIT; DOMAIN; AGENTS; COMMON AB Oligoanions such as sodium triphosphate or GTP prevent and/or reverse vinblastine-induced polymerization of tubulin. We now show that the anions of glutamate-rich extreme C termini of tubulin are similarly involved in the regulation of the vinblastine effect. Cleavage of the C termini by limited proteolysis with subtilisin enhances, vinblastine-induced tubulin polymerization and abolishes the anion effect. Only the beta-tubulin C terminus needs to be removed to achieve these changes and the later cleavage of the alpha-tubulin C terminus has little additional effect. In fact, vinblastine concentrations >20 mu M block cleavage of the alpha-tubulin C terminus in the polymer, whereas cleavage of the beta-tubulin C terminus proceeds unimpeded over the time used. The vinblastine effect on tubulin polymerization is also highly pH-dependent between pH 6.5 and 7.5; this is less marked, but not absent, after subtilisin treatment. A working model is proposed wherein an anionic domain proximal to the extreme C terminus must interact with a cationic domain to permit vinblastine to promote polymerization. Both exogenous and extreme C-terminal anions compete for the cationic domain with the proximal anionic domain to prevent vinblastine-induced polymerization. We conclude that the electrostatic regulation of tubulin polymerization induced by vinblastine resides primarily in the beta-tubulin C terminus but that additional regulation proximal in the tubulin molecule also plays a role. C1 NIDDKD, Lab Biochem & Genet, NIH, Bethesda, MD 20892 USA. RP Wolff, J (reprint author), NIDDKD, Lab Biochem & Genet, NIH, Bldg 8,Room 2A23, Bethesda, MD 20892 USA. NR 32 TC 21 Z9 22 U1 0 U2 3 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 APR 14 PY 1998 VL 95 IS 8 BP 4253 EP 4257 DI 10.1073/pnas.95.8.4253 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA ZH535 UT WOS:000073120800035 PM 9539723 ER PT J AU Kouprina, N Annab, L Graves, J Afshari, C Barrett, JC Resnick, MA Larionov, V AF Kouprina, N Annab, L Graves, J Afshari, C Barrett, JC Resnick, MA Larionov, V TI Functional copies of a human gene can be directly isolated by transformation-associated recombination cloning with a small 3 ' end target sequence SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE gene isolation; yeast artificial chromosome ID YEAST ARTIFICIAL-CHROMOSOME; HUMAN HPRT LOCUS; EFFICIENT MANIPULATION; DNA-SEQUENCES; CELLS; VECTORS; BREAKS AB Unique, small sequences (sequence tag sites) have been identified at the 3' ends of most human genes that serve as landmarks in genome mapping. We investigated whether a single copy gene could be isolated directly from total human DNA by transformation-associated recombination (TAR) cloning in yeast using a short, 3' unique target. A TAR cloning vector was constructed that, when linearized, contained a small amount (381 bp) of 3' hypoxanthine phosphoribosyltransferase (HPRT) sequence at one end and an 189-bp Alu repeat at the other end. Transformation with this vector along with human DNA led to selective isolations of the entire HPRT gene as yeast artificial chromosomes (YACs) that extended from the 3' end sequence to various Alu positions as much as 600 kb upstream, These YACs were retrofitted with a Neo(R) and a bacterial artificial chromosome (BAC) sequence to transfer the YACs to bacteria and subsequently the BACs to mouse cells by using a Neo selection. Most of the HPRT isolates were functional, demonstrating that TAR cloning retains the functional integrity of the isolated material. Thus, this modified version of TAR cloning, which we refer to as radial TAR cloning, can be used to isolate large segments of the human genome accurately and directly with only a small amount of sequence information. C1 NIEHS, Mol Genet Lab, NIH, Res Triangle Pk, NC 27709 USA. NIEHS, Mol Carcinogenesis Lab, NIH, Res Triangle Pk, NC 27709 USA. RP Kouprina, N (reprint author), NIEHS, Mol Genet Lab, NIH, Box 12233, Res Triangle Pk, NC 27709 USA. FU NHGRI NIH HHS [1-YO2-HG-60021-01] NR 21 TC 40 Z9 42 U1 0 U2 5 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD APR 14 PY 1998 VL 95 IS 8 BP 4469 EP 4474 DI 10.1073/pnas.95.8.4469 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA ZH535 UT WOS:000073120800073 PM 9539761 ER PT J AU Li, GF Chandler, SP Wolffe, AP Hall, TC AF Li, GF Chandler, SP Wolffe, AP Hall, TC TI Architectural specificity in chromatin structure at the TATA box in vivo: Nucleosome displacement upon beta-phaseolin gene activation SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID MAJOR LATE PROMOTER; RNA POLYMERASE-II; TRANSCRIPTION FACTOR; ATTACHMENT REGIONS; HIGHER-PLANTS; DNA; HISTONES; PROTEIN; CORE; ORGANIZATION AB Extensive studies of the beta-phaseolin (phas) gene in transgenic tobacco have shown that it is highly active during seed embryogenesis but is completely silent in leaf and other vegetative tissues, In vivo footprinting revealed that the lack of even basal transcriptional activity in vegetative tissues is associated with the presence of a nucleosome that is rotationally positioned with base pair precision over three phased TATA boxes present in the phas promoter. Positioning is sequence-dependent because an identical rotational setting is obtained upon nucleosome reconstitution in vitro, A comparison of DNase I and dimethyl sulfate footprints in vivo and in vitro strongly suggests that this repressive chromatin architecture is remodeled concomitant with gene activation in the developing seed. This leads to the disruption of histonemediated DNA wrapping and the assembly of the TATA boxes into a transcriptionally competent nucleoprotein complex. C1 Texas A&M Univ, Inst Dev & Mol Biol, College Stn, TX 77843 USA. Texas A&M Univ, Dept Biol, College Stn, TX 77843 USA. NICHHD, Mol Embryol Lab, NIH, Bethesda, MD 20892 USA. RP Hall, TC (reprint author), Texas A&M Univ, Inst Dev & Mol Biol, College Stn, TX 77843 USA. EM tim@bio.tamu.edu NR 50 TC 56 Z9 58 U1 0 U2 0 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD APR 14 PY 1998 VL 95 IS 8 BP 4772 EP 4777 DI 10.1073/pnas.95.8.4772 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA ZH535 UT WOS:000073120800126 PM 9539814 ER PT J AU Savage, PJ Pressel, SL Curb, JD Schron, EB Applegate, WB Black, HR Cohen, J Davis, BR Frost, P Smith, W Gonzalez, N Guthrie, GP Oberman, A Rutan, G Probstfield, JL Stamler, J AF Savage, PJ Pressel, SL Curb, JD Schron, EB Applegate, WB Black, HR Cohen, J Davis, BR Frost, P Smith, W Gonzalez, N Guthrie, GP Oberman, A Rutan, G Probstfield, JL Stamler, J CA Cooperative Res Grp TI Influence of long-term, low-dose, diuretic-based, antihypertensive therapy on glucose, lipid, uric acid, and potassium levels in older men and women with isolated systolic hypertension - The systolic hypertension in the elderly program SO ARCHIVES OF INTERNAL MEDICINE LA English DT Article ID CORONARY HEART-DISEASE; BLOOD-PRESSURE; DIABETES-MELLITUS; RISK-FACTORS; INTOLERANCE; DRUGS; DISTURBANCES; METABOLISM; FRAMINGHAM; TOLERANCE AB Background: Previous studies often of short duration have raised concerns that antihypertensive therapy with diuretics and beta-blockers adversely alters levels of other cardiovascular disease risk factors. Methods: The Systolic Hypertension in the Elderly Program was a community-based, multicenter, randomized, double-blind, placebo-controlled clinical trial of treatment of isolated systolic hypertension in men and women aged 60 years and older. This retrospective analysis evaluated development of diabetes mellitus in all 4736 participants in the Systolic Hypertension in the Elderly Program, including changes in serum chemistry test results in a subgroup for 3 years. Patients were randomized to receive placebo or treatment with active drugs, with the dose increased in stepwise fashion if blood pressure control goals were not attained: step 1, 12.5 mg of chlorthalidone or 25.0 mg of chlorthalidone; and step 2, the addition of 25 mg of atenolol or 50 mg of atenolol or reserpine or matching placebo. Results: After 3 years, the active treatment group had a 13/4 mm Hg greater reduction in systolic and diastolic blood pressure than the placebo group (both groups, P < .001). New cases of diabetes were reported by 8.6% of the participants in the active treatment group and 7.5% of the participants in the placebo group (P = .25). Small effects of active treatment compared with placebo were observed with fasting levels of glucose (+0.20 mmol/L [+3.6 mg/dL]; P < .01), total cholesterol (+0.09 mmol/L [+3.5 mg/dL]; P < .01), high-density lipoprotein cholesterol (-0.02 mmol/L [-0.77 mg/dL]; P < .01) and creatinine (+2.8 mu mol/L [+0.03 mg/dL]; P < .001). Larger effects were seen with fasting levels of triglycerides (+0.9 mmol/L [+17 mg/dL]; P < .001), uric acid (+35 mu mol/L [+.06 mg/dL]; P < .001), and potassium (-0.3 mmol/L; P < .001). No evidence was found for a subgroup at higher risk of risk factor changes with active treatment. Conclusions: Antihypertensive therapy with low-dose chlorthalidone (supplemented if necessary) for isolated systolic hypertension lowers blood pressure and its cardiovascular disease complications and has relatively mild effects on other cardiovascular disease risk factor levels. C1 Univ Texas, Hlth Sci Ctr, Sch Publ Hlth, SHEP Coordinating Ctr, Houston, TX 77030 USA. NHLBI, Div Clin Applicat, NIH, Bethesda, MD 20892 USA. Univ Hawaii, John A Burns Sch Med, Honolulu, HI 96822 USA. Univ Tennessee, Memphis, TN USA. Vet Affairs Med Ctr, Memphis, TN USA. Rush Presbyterian St Lukes Med Ctr, Chicago, IL 60612 USA. Northwestern Univ, Sch Med, Chicago, IL USA. Washington Univ, Sch Med, St Louis, MO USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. Univ Minnesota, Minneapolis, MN USA. Univ Kentucky, Lexington, KY USA. Univ Alabama, Birmingham, AL USA. Univ Washington, Seattle, WA 98195 USA. RP Savage, PJ (reprint author), Univ Texas, Hlth Sci Ctr, Sch Publ Hlth, SHEP Coordinating Ctr, 1200 Herman Pressler St,Suite 801, Houston, TX 77030 USA. NR 39 TC 158 Z9 170 U1 1 U2 4 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0003-9926 J9 ARCH INTERN MED JI Arch. Intern. Med. PD APR 13 PY 1998 VL 158 IS 7 BP 741 EP 751 DI 10.1001/archinte.158.7.741 PG 11 WC Medicine, General & Internal SC General & Internal Medicine GA ZH209 UT WOS:000073083800008 PM 9554680 ER PT J AU Kalebic, T Blakesley, V Slade, C Plasschaert, S Leroith, D Helman, LJ AF Kalebic, T Blakesley, V Slade, C Plasschaert, S Leroith, D Helman, LJ TI Expression of a kinase-deficient IGF-I-R suppresses tumorigenicity of rhabdomyosarcoma cells constitutively expressing a wild type IGF-I-R SO INTERNATIONAL JOURNAL OF CANCER LA English DT Article ID GROWTH; RECEPTOR; APOPTOSIS; CANCER; TUMOR; VIVO; ANTIBODY; MUTANT AB Previous results have shown that the insulin-like growth factor type I receptor (IGF-I-R) plays a critical role in the control of rhabdomyosarcoma (RMS) growth. The purpose of this study was to investigate whether a mutated IGF-I-R, when expressed in RMS cells, may interfere with the function of the endogenous wild-type IGF-I-R. We also examined whether the expression of a mutated IGF-I-R may induce phenotypic changes in RMS cells. We used here the mutated IGF-I-R with a lysine to arginine residue 1003 substitution, called IGF-I-KR, which carries a mutation in the ATP-binding domain of the intracellular beta subunit, while the extracellular, ligand binding alpha subunit remains unchanged. We observed that the expression of this mutated IGF-I-KR markedly decreased the response of RMS cells to stimulation with IGF-I. White stimulation with IGF-I increases the autophosphorylation of IGF-I-R in the parent cells, stimulation with IGF-I failed to produce a comparable increase in autophosphorylation in the cells expressing the mutated IGF-I-KR. We also observed a decreased plating efficiency of cells expressing the mutated IGF-I-KR. Consistently, a decrease of RMS growth in vivo was observed in an animal model. Our data suggest that the IGF/IGF-I-R signaling pathway may be inhibited by expressing a mutated ICF-I-KR and that such a mutant gene could be utilized in developing novel therapeutic strategies to suppress RMS growth. (C) 1998 Wiley-Liss, Inc.dagger C1 NCI, Mol Oncol Sect, Pediat Branch, Bethesda, MD 20892 USA. Sect Mol & Cellular Physiol, Diabet Branch, Bethesda, MD USA. RP Kalebic, T (reprint author), NCI, Mol Oncol Sect, Pediat Branch, Bld 10 Rm 13N240,9000 Rockville Pike, Bethesda, MD 20892 USA. NR 21 TC 39 Z9 42 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0020-7136 J9 INT J CANCER JI Int. J. Cancer PD APR 13 PY 1998 VL 76 IS 2 BP 223 EP 227 DI 10.1002/(SICI)1097-0215(19980413)76:2<223::AID-IJC9>3.0.CO;2-Z PG 5 WC Oncology SC Oncology GA ZF037 UT WOS:000072856400009 PM 9537584 ER PT J AU Zeidler, M Brown, P AF Zeidler, M Brown, P TI More patients should be excluded from being tissue donors SO BRITISH MEDICAL JOURNAL LA English DT Letter C1 Western Gen Hosp, Edinburgh EH4 2XU, Midlothian, Scotland. NINDS, Cent Nervous Syst Studies Lab, NIH, Bethesda, MD 20892 USA. RP Zeidler, M (reprint author), Western Gen Hosp, Edinburgh EH4 2XU, Midlothian, Scotland. NR 1 TC 2 Z9 2 U1 0 U2 0 PU BRITISH MED JOURNAL PUBL GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0959-8138 J9 BRIT MED J JI Br. Med. J. PD APR 11 PY 1998 VL 316 IS 7138 BP 1170 EP 1171 PG 4 WC Medicine, General & Internal SC General & Internal Medicine GA ZH054 UT WOS:000073067500065 PM 9552975 ER PT J AU Baron, JA Gridley, G Weiderpass, E Nyren, O Linet, M AF Baron, JA Gridley, G Weiderpass, E Nyren, O Linet, M TI Venous thromboembolism and cancer SO LANCET LA English DT Article ID PULMONARY-EMBOLISM; ORAL-CONTRACEPTIVES; OVARIAN-CANCER; THROMBOSIS; RISK; MALIGNANCY AB Background Although cancer has been clearly associated with venous thromboembolism (VTE), many aspects of this relation are poorly understood, including the cancer sites most affected and the cancer risk during long-term follow-up. To clarify these relations, we carried out a large, population-based analysis of VTE and cancer risk. Methods Using the Swedish Inpatient Register and linkage to the nationwide Cancer Registry, we assessed cancer incidence during 1989 among 61 998 patients without a previous cancer diagnosis admitted to hospital between 1965 and 1983 for VTE. To measure possible increases in cancer risk, we computed standardised incidence ratios (SIRs) using Swedish national cancer rates for the period of the study. Findings At the time of thromboembolic admission or during the first year of follow-up, 2509 cancers were diagnosed (SIR 3.2, 95% CI 3.1-3.4). The SIR for polycythaemia vera was 12.9 (8.6-18.7), and the SIRs for cancers of the liver, pancreas, ovary, and brain, and for Hodgkin lymphoma also exceeded 5.0. Patients aged less than 65 years had higher SIRs than those who were older. In subsequent years, 6081 cancers were diagnosed (1.3, 1.3-1.3). Even 10 years or more after admission to hospital with VTE, cancer incidence had increased (1.3, 1.3-1.4). Interpretation At the time of VTE or in the first year afterwards, we found a large increase in the risk for diagnosis of virtually all cancers. In subsequent years, a persistent 30% increase in risk remains. Either premalignant change promotes thrombosis, or cancer and thrombosis share common risk factors. C1 Dartmouth Coll, Hitchcock Med Ctr, Dartmouth Med Sch, Dept Med, Hanover, NH 03756 USA. Dartmouth Coll, Hitchcock Med Ctr, Dartmouth Med Sch, Dept Community & Family Med, Hanover, NH 03756 USA. Karolinska Inst, Dept Med Epidemiol, Stockholm, Sweden. NCI, Div Canc Etiol, Epidemiol & Biostat Program, Bethesda, MD 20892 USA. RP Baron, JA (reprint author), DHMC, 7927 Rubin Bldg,1 Med Ctr Dr, Lebanon, NH 03756 USA. EM John.Baron@Dartmouth.edu RI Weiderpass, Elisabete/M-4029-2016 OI Weiderpass, Elisabete/0000-0003-2237-0128 FU NCI NIH HHS [N01-CP-60538] NR 27 TC 304 Z9 324 U1 0 U2 5 PU LANCET LTD PI LONDON PA 42 BEDFORD SQUARE, LONDON WC1B 3SL, ENGLAND SN 0140-6736 J9 LANCET JI Lancet PD APR 11 PY 1998 VL 351 IS 9109 BP 1077 EP 1080 DI 10.1016/S0140-6736(97)10018-6 PG 4 WC Medicine, General & Internal SC General & Internal Medicine GA ZH269 UT WOS:000073090200007 PM 9660575 ER PT J AU Gubin, AN Kincaid, RL AF Gubin, AN Kincaid, RL TI A pressure-extrusion method for DNA extraction from agarose gels SO ANALYTICAL BIOCHEMISTRY LA English DT Article ID SPIN-COLUMN CHROMATOGRAPHY; RAPID METHOD; RECOVERY; CENTRIFUGATION; PURIFICATION C1 Veritas Inc, Rockville, MD 20850 USA. RP Gubin, AN (reprint author), NIH, Biol Chem Lab, Bldg 10,Room 9N308, Bethesda, MD 20892 USA. NR 10 TC 4 Z9 4 U1 0 U2 1 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0003-2697 J9 ANAL BIOCHEM JI Anal. Biochem. PD APR 10 PY 1998 VL 258 IS 1 BP 150 EP 152 DI 10.1006/abio.1998.2581 PG 3 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA ZF409 UT WOS:000072894600024 PM 9527865 ER PT J AU Izenwasser, S Thompson-Montgomery, D Deben, SE Chowdhury, IN Werling, LL AF Izenwasser, S Thompson-Montgomery, D Deben, SE Chowdhury, IN Werling, LL TI Modulation of amphetamine-stimulated (transporter mediated) dopamine release in vitro by sigma(2) receptor agonists and antagonists SO EUROPEAN JOURNAL OF PHARMACOLOGY LA English DT Article DE caudate putamen; cocaine; dopamine transporter; dopamine uptake ID GUINEA-PIG BRAIN; RAT HIPPOCAMPAL SLICES; BINDING-SITES; H-3 DOPAMINE; NOREPINEPHRINE RELEASE; SUBNANOMOLAR AFFINITY; REVERSE TRANSPORT; PC12 CELLS; IN-VIVO; LIGAND AB Some sigma receptor ligands have been shown to bind with low affinity to the dopamine transporter and to inhibit [H-3]dopamine uptake. It has not previously been shown whether any of these compounds influence release of dopamine via facilitated exchange diffusion. To further examine the nature of the interaction between sigma receptor ligands and the dopamine transporter, the effects of sigma receptor ligands on amphetamine-stimulated [H-3]dopamine release were examined in slices prepared from rat caudate putamen. In the absence of exogenous Ca2+, both (+)-pentazocine and (-)-pentazocine potentiated amphetamine-stimulated [H-3]dopamine release at concentrations consistent with their affinities for sigma(2) receptors. In contrast, BD737 (1S,2R-(-)-cis-N-{2-(3,4-dichlorophenyl)ethyl}-N-methyl-2-(1-pyrrolidinyl)cyclohexylamine), a sigma(1) receptor agonist, had no effect on amphetamine-stimulated release. Neither isomer of pentazocine alone had any effect on basal [H-3]dopamine release under these conditions. Three antagonists at sigma receptors, one of which is non-selective for subtypes, and two of which are sigma(2)-selective, ail blocked the enhancement of stimulated release produced by (+)-pentazocine. Enhancement of stimulated release by (-)-pentazocine was similarly blocked by sigma(2) receptor antagonists. Our data support the contention that it is possible to regulate transporter-mediated events with drugs that act at a subpopulation of a receptors pharmacologically identified as the sigma(2) subtype. (C) 1998 Elsevier Science B.V. C1 NIDA, Psychobiol Sect, Intramural Res Program, NIH, Baltimore, MD 21224 USA. George Washington Univ, Med Ctr, Dept Pharmacol, Washington, DC 20037 USA. RP Izenwasser, S (reprint author), Univ Miami, Sch Med, Dept Neurol, 1501 NW 9th Ave,Room 4061, Miami, FL 33136 USA. RI Izenwasser, Sari/G-9193-2012 NR 39 TC 20 Z9 21 U1 3 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0014-2999 J9 EUR J PHARMACOL JI Eur. J. Pharmacol. PD APR 10 PY 1998 VL 346 IS 2-3 BP 189 EP 196 DI 10.1016/S0014-2999(98)00063-6 PG 8 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA ZQ278 UT WOS:000073841300009 PM 9652359 ER PT J AU Liu, YS Gorospe, M Kokkonen, GC Boluyt, MO Younes, A Mock, YD Wang, XT Roth, GS Holbrook, NJ AF Liu, YS Gorospe, M Kokkonen, GC Boluyt, MO Younes, A Mock, YD Wang, XT Roth, GS Holbrook, NJ TI Impairments in both p70 S6 kinase and extracellular signal-regulated kinase signaling pathways contribute to the decline in proliferative capacity of aged hepatocytes SO EXPERIMENTAL CELL RESEARCH LA English DT Article ID CELL-CYCLE REGULATION; INITIATION-FACTOR 4E; PROTEIN-KINASE; RAT HEPATOCYTES; DNA-SYNTHESIS; TRANSLATION INITIATION; MESSENGER-RNA; E GENE; RAPAMYCIN; ACTIVATION AB Treatment of primary cultured hepatocytes from adult (6-month-old) rats with epidermal growth factor (EGF) results in at marked elevation in DNA synthesis, a response that is markedly attenuated in cells of aged (24-month-old) animals. Recently we demonstrated that this age-related attenuation is associated with reduced activation of extracellular signal-regulated kinase (ERK) in response to EGF treatment, in order to gain further insight into the mechanisms responsible for the age-related decline in this proliferative response, we investigated the expression and/or activities of several other regulatory molecules important for G1 to S phase progression in EGF-stimulated young and aged hepatocytes. Induction of cyclin D1 and activation of cyclin-dependent kinase 2 (CDK2) by EGF were found to be diminished in the aged cells. In young cells, prior to treatment with rapamycin inhibited the induction of DNA synthesis and activation of CDK2 to levels similar to those seen in aged cells without inhibiting ERK activity and cyclin D1 expression. This suggested that a distinct, ERK-independent, rapamycin-sensitive pathway might also contribute to the proliferative response in hepatocytes and be subject to age-related alterations. Further studies demonstrated that activation of p70 S6 kinase (p70(S6k)), a rapamycin-sensitive event, following EGF treatment was 40% lower in aged hepatocytes relative to young cells, although the kinetics of activation did not differ in the two age groups. Western blot analysis for p70(S6k) expression revealed similar levels of proteins in young and aged cells. From these findings, we conclude that deficiencies in both the ERK and p70(S6k) signaling pathways contribute to the age-related decline in the proliferative response of hepatocytes. (C) 1998 Academic Press. C1 NIA, Gene Express & Aging Sect, Biol Chem Lab, Gerontol Res Ctr, Baltimore, MD 21224 USA. NIA, Cellular & Mol Biol Lab, Baltimore, MD 21224 USA. NIA, Cardiovasc Sci Lab, Baltimore, MD 21224 USA. RP Holbrook, NJ (reprint author), NIA, Gene Express & Aging Sect, Biol Chem Lab, Gerontol Res Ctr, Box 12,5600 Nathan Shock Dr, Baltimore, MD 21224 USA. RI Liu, Yusen/E-3527-2011 NR 46 TC 15 Z9 15 U1 0 U2 0 PU ACADEMIC PRESS INC 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 APR 10 PY 1998 VL 240 IS 1 BP 40 EP 48 DI 10.1006/excr.1997.3931 PG 9 WC Oncology; Cell Biology SC Oncology; Cell Biology GA ZK186 UT WOS:000073294000005 PM 9570919 ER PT J AU Zolkiewska, A Thompson, WC Moss, J AF Zolkiewska, A Thompson, WC Moss, J TI Interaction of integrin alpha 7 beta 1 in C2C12 myotubes and in solution with laminin SO EXPERIMENTAL CELL RESEARCH LA English DT Article ID SKELETAL-MUSCLE CELLS; ADP-RIBOSYLTRANSFERASE; MONOCLONAL-ANTIBODIES; EXTRACELLULAR-MATRIX; CYTOPLASMIC DOMAINS; BASEMENT-MEMBRANES; IV COLLAGEN; S-LAMININ; EXPRESSION; MYOGENESIS AB The dimer of integrin alpha 7 and beta 1 is a major laminin-binding receptor in skeletal. muscle. We studied interactions of integrity alpha 7 beta 1 with the extracellular matrix protein laminin in solution and in intact cells. Integrin alpha 7 beta 1 bound to EHS laminin (laminin-1, composed of alpha 1, beta 1, and gamma 1 chains), but not to endogenous laminin expressed in C2C12 myotubes. Northern blot analysis demonstrated that C2C12 myotubes synthesized laminin-1 alpha, beta, and gamma subunits mRNAs, C2C12 laminin was, however, immunologically distinct from EHS laminin; it was not recognized by 5D3 anti-laminin-1 monoclonal. antibody, whereas 5A2 and LT3 antibodies reacted equally swell with C2C12 and EHS laminins, Following deglycosylation of ENS laminin, separation of the subunits by SDS-PAGE, Western blotting, and partial amino acid sequencing of the protein bands, the epitope recognized by 5D3 antibody was localized to the gamma 1 laminin chain. Following binding in vitro the complex of EHS laminin and integrin alpha 7 beta 1 was subject to chemical cross-linking. The two proteins did not undergo cross-linking at the cell surface, consistent with the fact that in intact, resting myotubes integrin alpha 7 beta 1 interacted poorly with EHS laminin, which may reflect a limited accessibility of integrin alpha 7 beta 1 in the membrane to laminin or an inactive state of the integrin. (C) 1998 Academic Press. C1 NHLBI, Pulm Crit Care Med Branch, NIH, Bethesda, MD 20892 USA. RP Moss, J (reprint author), NHLBI, Pulm Crit Care Med Branch, NIH, Bldg 10, Bethesda, MD 20892 USA. EM mossj@fido.nhlbi.nih.gov NR 42 TC 4 Z9 5 U1 0 U2 0 PU ACADEMIC PRESS INC 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 APR 10 PY 1998 VL 240 IS 1 BP 86 EP 94 DI 10.1006/excr.1998.4002 PG 9 WC Oncology; Cell Biology SC Oncology; Cell Biology GA ZK186 UT WOS:000073294000010 PM 9570924 ER PT J AU Talts, JF Mann, K Yamada, Y Timpl, R AF Talts, JF Mann, K Yamada, Y Timpl, R TI Structural analysis and proteolytic processing of recombinant G domain of mouse laminin alpha 2 chain SO FEBS LETTERS LA English DT Article DE basement membrane; recombinant protein; protein module; proteolysis; splicing ID A-CHAIN; HEPARIN-BINDING; MUSCULAR-DYSTROPHY; GLOBULAR DOMAIN; HUMAN PLACENTA; HIGH-AFFINITY; CELL-SURFACE; PROTEIN; ISOFORMS; MEROSIN AB Four individual LG modules from the C-terminus of the laminin alpha 2 chain (LG1, LG2, LG4 and LG5) and combinations of these modules were prepared as recombinant products from transfected mammalian cells. This demonstrated that LG modules represent autonomously folding protein domains. Successful production depended on proper alignment of module borders and required a sequence correction at the C-terminus which added an extra cysteine. The LG modules were glycosylated and shown by electron microscopy to have a globular shape, indicating proper folding. Evidence is provided for the splicing of a 12 bp exon in LG2, although this did not impair folding. Proteolytic cleavage at the C-terminus of a basic sequence was observed close to the N-terminus of LG3, A similar processing also occurs in tissue-derived laminin-2 and -4 which contain the alpha 2 chain. (C) 1998 Federation of European Biochemical Societies. C1 Max Planck Inst Biochem, D-82152 Martinsried, Germany. NIDR, NIH, Bethesda, MD 20892 USA. RP Timpl, R (reprint author), Max Planck Inst Biochem, D-82152 Martinsried, Germany. RI Mann, Karlheinz/C-4254-2008 NR 38 TC 61 Z9 61 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 APR 10 PY 1998 VL 426 IS 1 BP 71 EP 76 DI 10.1016/S0014-5793(98)00312-3 PG 6 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA ZJ758 UT WOS:000073250000015 PM 9598981 ER PT J AU Rhee, S Miles, EW Davies, DR AF Rhee, S Miles, EW Davies, DR TI Cryo-crystallography of a true substrate, indole-3-glycerol phosphate, bound to a mutant (alpha D60N) tryptophan synthase alpha(2)beta(2) complex reveals the correct orientation of active site alpha Glu49 SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID 3-DIMENSIONAL STRUCTURE; SALMONELLA-TYPHIMURIUM; CATALYTIC RESIDUE; SUBUNIT AB The reversible cleavage of indole-3-glycerol by the cy-subunit of tryptophan synthase has been proposed to be catalyzed by alpha Glu49 and alpha Asp60. Although previous x-ray crystallographic structures of the tryptophan synthase alpha(2) beta(2) complex showed an interaction between the carboxylate of alpha Asp60 and the bound inhibitor indole-3-propanol phosphate, the carboxylate of alpha Glu49 was too distant to play its proposed role, To clarify the structural and functional roles of alpha Glu49, we have determined crystal structures of a mutant (alpha D60N) alpha(2) beta(2) complex in the presence and absence of the true substrate, indole-3-glycerol phosphate. The enzyme in the crystal cleaves indole-3-glycerol phosphate very slowly at room temperature but not under cryo-conditions of 95 K. The structure of the complex with the true substrate obtained by cryo-crystallography reveals that indole-3-glycerol phosphate and indole-3-propanol phosphate have similar binding modes but different torsion angles. Most importantly, the side chain of alpha Glu49 interacts with S-hydroxyl group of indole-3-glycerol phosphate as proposed, The movement of the side chain of alpha Glu49 into an extended conformation upon binding the true substrate provides evidence for an induced fit mechanism. Our results demonstrate how cryo-crystallography and mutagenesis can provide insight into enzyme mechanism. C1 NIDDK, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. NIDDK, Lab Biochem & Genet, NIH, Bethesda, MD 20892 USA. RP Davies, DR (reprint author), NIDDK, Mol Biol Lab, NIH, Bldg 5,Rm 338, Bethesda, MD 20892 USA. NR 15 TC 42 Z9 44 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 EI 1083-351X J9 J BIOL CHEM JI J. Biol. Chem. PD APR 10 PY 1998 VL 273 IS 15 BP 8553 EP 8555 DI 10.1074/jbc.273.15.8553 PG 3 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA ZG331 UT WOS:000072990800003 PM 9535826 ER PT J AU Adachi, K Saito, H Tanaka, T Oka, T AF Adachi, K Saito, H Tanaka, T Oka, T TI Molecular cloning and characterization of the murine Staf cDNA encoding a transcription activating factor for the selenocysteine tRNA gene in mouse mammary gland SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID TRANSFER RNA(SER)SEC GENE; ZINC-FINGER PROTEIN; OPEN READING FRAME; TRANSFER-RNA GENE; MESSENGER-RNA; GLUTATHIONE-PEROXIDASE; EPITHELIAL-CELLS; ELEMENTS; TGA; TERMINATION AB We have isolated and characterized a cDNA encoding a transcription activating factor for the mouse selenocysteine tRNA (tRNA(sec)) gene from mouse mammary gland. The full-length cDNA, designated m-Staf, has a 1878-base pair open reading frame encoding 626 amino acids. The predicted amino acid sequence of m-Staf is highly homologous to that of Staf, another selenocysteine tRNA gene transcription activating factor of Xenopus laevis. Like Staf, m-Staf contains seven tandemly repeated zinc fingers and four repeated motifs. Gel shift assays indicated that the recombinant m-Staf specifically bound to the activator element region in the mouse tRNA(sec) gene. Transient co-transfection experiments in Drosophila Schneider cells, which lack endogenous Staf-like binding activity, showed that m-Staf increased the mouse tRNA(sec) gene transcription about 15-fold, whereas it stimulated Pol II-dependent thymidine kinase promoter only 2-fold. Northern blot analysis detected the presence of a 3.4-kilobase pair m-Staf transcript, which was widely but differentially expressed in various murine tissues. The binding activity of m-Staf in mouse mammary gland was undetectable during virgin and postlactating periods but increased markedly in parallel with the increase of tRNA(sec) transcript during the periods of pregnancy and lactation, when the gland undergoes growth and development. These results indicate that m-Staf is a transcriptional activator of the mouse tRNA(sec) gene and that its binding activity in the mammary gland undergoes developmental alterations. C1 NIDDK, Mol & Cellular Biol Lab, NIH, Bethesda, MD 20892 USA. RP Oka, T (reprint author), NIDDK, Mol & Cellular Biol Lab, NIH, Bldg 8,Rm 309, Bethesda, MD 20892 USA. NR 39 TC 15 Z9 16 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD APR 10 PY 1998 VL 273 IS 15 BP 8598 EP 8606 DI 10.1074/jbc.273.15.8598 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA ZG331 UT WOS:000072990800010 PM 9535833 ER PT J AU Shimizu, T Cao, CX Shao, RG Pommier, Y AF Shimizu, T Cao, CX Shao, RG Pommier, Y TI Lamin B phosphorylation by protein kinase C alpha and proteolysis during apoptosis in human leukemia HL60 cells SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID TOPOISOMERASE-II INHIBITORS; ISOLATED THYMOCYTE NUCLEI; DNA FRAGMENTATION; HL-60 CELLS; POLY(ADP-RIBOSE) POLYMERASE; ICE/CED-3 PROTEASE; ACTIVATION; DEGRADATION; INDUCTION; DEATH AB Protein phosphorylation plays an important role in signal transduction, but its involvement in apoptosis still remains unclear. In this report, the p53-null human leukemia HL60 cells were used to investigate phosphorylation and degradation of lamin B during apoptosis. We found that lamin B was phosphorylated within I h after addition of the DNA topoisomerase I inhibitor, camptothecin, and that lamin B phosphorylation preceded lamin B degradation and DNA fragmentation. Using a cell-free system we also found that cytosol from camptothecin-treated cells induced lamin B phosphorylation and degradation in isolated nuclei from untreated HL60 cells. Lamin B phosphorylation was prevented by the protein kinase C (PKC) inhibitor 7-hydroxystaurosporine (UCN-01) but not by the Cdc2 inhibitor, flavopiridol. Phosphorylation of lamin B was inhibited by immunodepletion of PKC alpha from activated cytosol and was restored by addition of purified PKC alpha. PKC alpha activity also increased rapidly as lamin B was phosphorylated after initiation of the apoptotic response in HL60 cells. These data suggest that lamin B is phosphorylated by PKC alpha and proteolyzed before DNA fragmentation in HL60 cells undergoing apoptosis. C1 NCI, Mol Pharmacol Lab, Div Basic Sci, NIH, Bethesda, MD 20892 USA. RP Pommier, Y (reprint author), NCI, Mol Pharmacol Lab, Div Basic Sci, NIH, Bldg 37,Rm 5D02, Bethesda, MD 20892 USA. NR 46 TC 71 Z9 71 U1 0 U2 1 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD APR 10 PY 1998 VL 273 IS 15 BP 8669 EP 8674 DI 10.1074/jbc.273.15.8669 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA ZG331 UT WOS:000072990800019 PM 9535842 ER PT J AU Goodwin, DC Gunther, MR Hsi, LC Crews, BC Eling, TE Mason, RP Marnett, LJ AF Goodwin, DC Gunther, MR Hsi, LC Crews, BC Eling, TE Mason, RP Marnett, LJ TI Nitric oxide trapping of tyrosyl radicals generated during prostaglandin endoperoxide synthase turnover - Detection of the radical derivative of tyrosine 385 SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID HIGHER OXIDATION-STATES; H SYNTHASE; RIBONUCLEOTIDE REDUCTASE; PEROXIDASE REACTION; VESICULAR GLAND; CATALYSIS; BIOSYNTHESIS; MACROPHAGES; ENZYME; HEME AB Tyrosyl radicals have been detected during turnover of prostaglandin endoperoxide H synthase (PGHS), and they are speculated to participate in cyclooxygenase catalysis, Spectroscopic approaches to elucidate the identity of the radicals have not been definitive, so we have attempted to trap the radical(s) with nitric oxide (NO), NO quenched the EPR signal generated by reaction of purified ram seminal vesicle PGHS with arachidonic acid, suggesting that NO coupled with a tyrosyl radical to form inter alia nitrosocyclohexadienone, Subsequent formation of nitrotyrosine was detected by Western blotting of PGHS incubated with NO and arachidonic acid or organic hydroperoxides using an antibody against nitrotyrosine. Both arachidonic acid and NO were required to form nitrotyrosine, and tyrosine nitration was blocked by the PGHS inhibitor indomethacin. The presence of superoxide dismutase had no effect on nitration, indicating that peroxynitrite was not the nitrating agent, To identify which tyrosines were nitrated, PGHS was digested with trypsin, and the resulting peptides were separated by high pressure liquid chromatography and monitored with a diode array detector, A single peptide was detected that exhibited a spectrum consistent with the presence of nitrotyrosine. Consistent with Western blotting results, both NO and arachidonic acid were required to observe nitration of this peptide, and its formation was blocked by the PGHS inhibitor indomethacin, Peptide sequencing indicated that the modified residue was tyrosine 385, the source of the putative catalytically active tyrosyl radical. C1 Vanderbilt Univ, Sch Med, AB Hancock Jr Mem Lab Canc Res, Dept Biochem, Nashville, TN 37232 USA. NIEHS, Lab Pharmacol & Chem, NIH, Res Triangle Pk, NC 27709 USA. RP Vanderbilt Univ, Sch Med, AB Hancock Jr Mem Lab Canc Res, Dept Biochem, Nashville, TN 37232 USA. EM marnett@toxicology.mc.vanderbilt.edu FU NCI NIH HHS [CA 47479]; NIEHS NIH HHS [ES 00267] NR 32 TC 110 Z9 110 U1 1 U2 2 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 EI 1083-351X J9 J BIOL CHEM JI J. Biol. Chem. PD APR 10 PY 1998 VL 273 IS 15 BP 8903 EP 8909 DI 10.1074/jbc.273.15.8903 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA ZG331 UT WOS:000072990800049 PM 9535872 ER PT J AU Gladyshev, VN Jeang, KT Wootton, JC Hatfield, DL AF Gladyshev, VN Jeang, KT Wootton, JC Hatfield, DL TI A new human selenium-containing protein - Purification, characterization, and cDNA sequence SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID THIOREDOXIN REDUCTASE; IODOTHYRONINE DEIODINASE; SELENOCYSTEINE; SELENOPROTEIN; GENE; CLONING; MAP AB Selenium which occurs in proteins as the amino acid, selenocysteine, is essential for numerous biological processes and for human health. A prominent Se-75-labeled protein detected in human T-cells migrated as a 15-kDa band by SDS-polyacrylamide gel electrophoresis. This protein subunit was purified and subjected to tryptic digestion and peptide sequence analyses. Sequences of tryptic peptides derived from the protein corresponded to a human placental gene sequence containing an open reading frame of 162 residues and a readthrough in-frame TGA codon. Three different peptide sequences of the 15-kDa protein corresponded to a nucleotide sequence located downstream of this codon, suggesting that the T-cell 15-kDa selenoprotein contains a selenocysteine residue encoded by TGA. Post-translational processing of the N-terminal portion of the predicted gene product to give the 15-kDa protein was suggested on the basis of molecular mass, amino acid analysis, and immunoblot assays of the purified protein. The 3'-untranslated region (UTR) of the gene encoding the 15-kDa protein contained a sequence that is very similar to the canonical selenocysteine-inserting sequence element. Computer analysis of transcript map data bases indicated that this gene was located on human chromosome 1. Its coding sequence showed no homology to known protein-encoding genes. The 15-kDa protein gene was expressed as mRNA in a wide range of tissues, with increased levels in the thyroid, parathyroid, and prostate-derived cells as evidenced by searches of partial cDNA sequences in public data bases. Genes corresponding to the 15-kDa selenocysteine containing protein were found in mice and rats, while the corresponding genes in Caenorhabditis elegans and Brugia malayi contained a cysteine codon in place of TGA The discovery of a new human selenoprotein provides an additional example of the role of selenium in mammalian systems. C1 NCI, Basic Res Lab, Sect Mol Biol Selenium, NIH, Bethesda, MD 20892 USA. NHLBI, Biochem Lab, NIH, Bethesda, MD 20892 USA. NIAID, Mol Microbiol Lab, NIH, Bethesda, MD 20892 USA. NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20892 USA. RP Hatfield, DL (reprint author), NCI, Basic Res Lab, Sect Mol Biol Selenium, NIH, Bldg 37,Rm 2D09,9000 Rockville Pike, Bethesda, MD 20892 USA. RI Jeang, Kuan-Teh/A-2424-2008; Gladyshev, Vadim/A-9894-2013 NR 30 TC 116 Z9 119 U1 1 U2 9 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD APR 10 PY 1998 VL 273 IS 15 BP 8910 EP 8915 DI 10.1074/jbc.273.15.8910 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA ZG331 UT WOS:000072990800050 PM 9535873 ER PT J AU Beohar, N Kawamoto, S AF Beohar, N Kawamoto, S TI Transcriptional regulation of the human nonmuscle myosin II heavy chain-A gene - Identification of three clustered cis-elements in intron-1 which modulate transcription in a cell type- and differentiation state-dependent manner SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID BOX-BINDING-PROTEINS; MESSENGER-RNA; ACTIVATION DOMAINS; MYOD FAMILY; SP1; DNA; CLONING; EXPRESSION; PROMOTER; SEQUENCE AB In an attempt to identify cis-acting elements for transcriptional regulation of the human nonmuscle myosin II heavy chain (MHC)-A gene, the region extending 20 kilobases (kb) upstream and 40 kb downstream from the transcription start sites, which includes the entire 37-kb intron 1, was examined. Using transient transfection analysis of luciferase reporter constructs, a 100-base pair (bp) region (N2d) in intron 1, located 23 kb downstream from the transcriptional start sites, has been found to activate transcription in a cell type-and differentiation state-dependent manner, Maximum activity (similar to 20-fold) is seen in NIH 3T3 fibroblasts and intermediate activity (7-fold) in proliferating and undifferentiated C2C12 myoblasts, In contrast, this region is almost inactive in terminally differentiated C2C12 myotubes, in which endogenous nonmuscle MHC-A expression is down-regulated, Gel mobility shift assays and methylation interference analyses were performed using NIH 3T3 nuclear extracts to determine the protein-binding elements for transcription factors, Three binding elements have been identified within the N2d region, Antibody-supershift experiments, as well as competition experiments using consensus binding sequences for specific transcription factors, revealed that the most 5'-element, C (GGGAGGGGCC) is recognized specifically and exclusively by Sp1 and Sp3 transcriptional factors, Element C is immediately followed by a novel element, A (GTGACCC), A third element, F (GTGTCAGGTG), which contains an E-box, is located 50 bp 3' to element A. Element F can be recognized partially by upstream stimulatory factors, USF1 and/or USF2, Transfection studies with luciferase reporter constructs which include mutations in all three elements in various combinations demonstrate that the A and C binding factors cooperatively activate transcriptional activity in NIH 3T3 cells, The F binding factor shows an additive effect on transcription. C1 NHLBI, Mol Cardiol Lab, NIH, Bethesda, MD 20892 USA. RP Kawamoto, S (reprint author), NHLBI, Mol Cardiol Lab, NIH, Bldg 10,Rm 8N202,10 Ctr Dr,MSC 1762, Bethesda, MD 20892 USA. NR 41 TC 25 Z9 25 U1 0 U2 2 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD APR 10 PY 1998 VL 273 IS 15 BP 9168 EP 9178 DI 10.1074/jbc.273.15.9168 PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA ZG331 UT WOS:000072990800084 PM 9535907 ER PT J AU Ribas, JC Wickner, RB AF Ribas, JC Wickner, RB TI The Gag domain of the Gag-Pol fusion protein directs incorporation into the L-A double-stranded RNA viral particles in Saccharomyces cerevisiae SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID IMMUNODEFICIENCY-VIRUS TYPE-1; N-ACETYLTRANSFERASE; REPLICATION; MAK3; ENCAPSIDATION; PR160GAG-POL; MUTAGENESIS; PROPAGATION; POLYMERASE; EXPRESSION AB The L-A double-stranded RNA virus of yeast encodes its major coat protein, Gag, and a Gag-Pol fusion protein made by a -1 ribosomal frameshift, a coding strategy used by many retroviruses. We find that cells expressing only Gag from one plasmid and only Gag-Pol (in frame) from a separate plasmid can support the propagation of M-1 double-stranded RNA, encoding the killer toxin. We use this system to separately investigate the functions of Gag and the Gag part of Gag-Pol. L-A contains two fusion protein molecules per particle, and although N-terminal acetylation of Gag is essential for viral assembly, it is completely dispensable for function of Gag-Pol. In general, the requirements on Gag for viral assembly and propagation are more stringent than on the Gag part of Gag-Pol. Finally, we directly show that it is Gag that instructs the incorporation of Gag-Pol into the viral particles. C1 NIDDK, Lab Biochem & Genet, NIH, Bethesda, MD 20892 USA. RP Wickner, RB (reprint author), NIDDK, Lab Biochem & Genet, NIH, Bldg 8,Rm 225,8 Ctr Dr MSC 0830, Bethesda, MD 20892 USA. RI Ribas, Juan/C-9864-2015 OI Ribas, Juan/0000-0001-6430-0895 NR 37 TC 17 Z9 18 U1 0 U2 2 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD APR 10 PY 1998 VL 273 IS 15 BP 9306 EP 9311 DI 10.1074/jbc.273.15.9306 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA ZG331 UT WOS:000072990800102 PM 9535925 ER PT J AU Ito, Y Matsuda, K Ma, Y Qi, L AF Ito, Y Matsuda, K Ma, Y Qi, L TI Toroidal coil counter-current chromatography study of the mass transfer rate of proteins in aqueous-aqueous polymer phase system SO JOURNAL OF CHROMATOGRAPHY A LA English DT Article DE counter-current chromatography; mass transfer; proteins ID FLOW-THROUGH CENTRIFUGE; ROTATING SEALS; SEPARATION AB The cause of excessive band broadening of protein samples in polymer phase partitioning by counter-current chromatography (CCC) was investigated. A simple rotary device was constructed to measure the mass transfer rates of five samples including potassium dichromate, methylene blue, lysozyme, ovalbumin and human serum albumin. The results indicated that the mass transfer rates of these samples are closely correlated with their molecular masses: the higher the molecular mass, the lower the mass transfer rate. These findings are also consistent with the partition efficiencies of these samples in the same solvent system by CCC. The beneficial effect of the Coriolis force demonstrated in protein separations by the toroidal coil centrifuge may be reasonably explained on the basis of the mass transfer resistance of protein molecules through the interface: we speculate that when the Coriolis force acts parallel to the effective coil segment it can produce large interfacial areas by dispersing the mobile phase into the stationary phase, thus accelerating the mass transfer rate of protein samples. (C) 1998 Elsevier Science B.V. C1 NHLBI, Biophys Chem Lab, NIH, Bethesda, MD 20892 USA. RP Ito, Y (reprint author), NHLBI, Biophys Chem Lab, NIH, Bldg 10,Room 7N-322, Bethesda, MD 20892 USA. NR 9 TC 19 Z9 19 U1 1 U2 5 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0021-9673 J9 J CHROMATOGR A JI J. Chromatogr. A PD APR 10 PY 1998 VL 802 IS 2 BP 277 EP 283 DI 10.1016/S0021-9673(97)01171-0 PG 7 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA ZJ550 UT WOS:000073228000003 PM 9595695 ER PT J AU Ward, H Baldwin, D Wang, T Warner, H Seymour, K Marquardt, C McFalls, E Foker, JE AF Ward, H Baldwin, D Wang, T Warner, H Seymour, K Marquardt, C McFalls, E Foker, JE TI Ion-exchange column chromatographic method for assaying purine metabolic pathway enzymes SO JOURNAL OF CHROMATOGRAPHY B LA English DT Article DE enzymes; purine; 5 '-nucleotidase; adenosine kinase; adenine phosphoribosyl transferase; hypoxanthine phosphoribosyl transferase ID PERFORMANCE LIQUID-CHROMATOGRAPHY; 5'-NUCLEOTIDASE ACTIVITY; MYOCARDIAL ISCHEMIA; ADENOSINE FORMATION; HEART; CATABOLISM; ADENINE AB High energy phosphate levels fall rapidly during cardiac ischemia and recover slowly (more than one week) during reperfusion. The slow recovery of ATP may reflect a lack of purine metabolic precursors and/or increased activity of purine catabolic enzymes such as 5'-nucleotidase (5'-NT, EC 3.1,3.5) and adenosine deaminase (ADA, EC 3.5.4.4). The activity of enzymes involved in both the catabolism of ATP precursors (5-NT and ADA) and the restoration of ATP from slow synthetic pathways [adenosine kinase (AR, EC 2.7.1.20), adenine phosphoribusyl transferase (APRT, EC 2.4.2.7) and hypoxanthine phosphoribosyl transferase (HPRT, EC 2.4.2.8)] may directly affect the rate of ATP recovery. Strategies to enhance recovery will depend on the relative activity of these enzymes following ischemia. Their activity in different species and their response to ischemia. are not well characterized. Hence, rapid assay methods for-these enzymes would facilitate detailed time course studies of their activities in postischemic myocardium. WE modified a single ion-exchange column chromatographic method using DEAE-Sephadex to determine the products of incubation of 5'-NT, AK, APRT and HPRT with their respective substrates. The uniformity of the final product measurement procedure for all assays permits the activities of the foul enzymes to be rapidly determined io a single tissue sample and facilitates the study of a large number of samples. This technique should also be useful fur enzymes of the pyrimidine metabolic pathway. (C) 1998 Elsevier Science B.V. C1 Univ Minnesota, Dept Surg, Minneapolis, MN 55417 USA. Vet Affairs Med Ctr, Minneapolis, MN 55417 USA. Univ Rochester, Rochester, NY 14642 USA. NIA, NIH, Bethesda, MD 20892 USA. Univ Minnesota, Dept Med, Minneapolis, MN 55417 USA. RP Ward, H (reprint author), Univ Minnesota, Dept Surg, Minneapolis, MN 55417 USA. FU NHLBI NIH HHS [HL 26640, HL 52157] NR 27 TC 4 Z9 4 U1 0 U2 1 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 APR 10 PY 1998 VL 707 IS 1-2 BP 295 EP 300 DI 10.1016/S0378-4347(97)00577-X PG 6 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA ZJ706 UT WOS:000073238700037 PM 9613962 ER PT J AU Jager, W Zembsch, B Wolschann, P Pittenauer, E Senderowicz, AM Sausville, EA Sedlacek, HH Graf, J Thalhammer, T AF Jager, W Zembsch, B Wolschann, P Pittenauer, E Senderowicz, AM Sausville, EA Sedlacek, HH Graf, J Thalhammer, T TI Metabolism of the anticancer drug flavopiridol, a new inhibitor of cyclin dependent kinases, in rat liver SO LIFE SCIENCES LA English DT Article DE flavopiridol; metabolism; glucuronides; rat liver ID BREAST-CARCINOMA CELLS; MORPHINE; FLAVONE; ARREST AB Flavopiridol (FLAP) is a promising novel chemotherapeutic agent currently undergoing clinical phase I trials. To examine hepatic metabolism and biliary disposition of FLAP we applied the isolated perfused rat liver system. Besides FLAP two metabolites were detected by high performance liquid chromatography in bile and perfusate. Twenty-five min after FLAP (30 mu M) addition to the perfusion medium, biliary secretion of metabolite 1 and 2 reached a maximum of 1.04 +/- 0.52 and 11.34 +/- 4.72 nmol/g.liver.min, respectively. Biliary excretion of parent FLAP, however, continuously increased for 60 min up to 406 +/- 134 pmol/g liver.min. In the perfusate, metabolite 1 was below detection limit and release of metabolite 2 was low (2.8 +/- 0.7 pmol/g liver.min after 60 min). Enzymatic hydrolysis with beta-glucuronidase, mass spectroscopy and electron absorption spectroscopy revealed that both metabolites are monoglucuronides with the glucuronide in position 5 and 7 of the flavonoid core, respectively. The amount of FLAP, metabolite 1 and metabolite 2 excreted into bile during the 60 min of perfusion was 1.94 +/- 0.91, 5.15 +/- 1.95 and 57.29 ? 23.60 % of FLAP cleared from the perfusate during 60 min, respectively. In contrast to the structurally similar flavonoids genistein and daidzein, no inhibition of UDP-glucuronyltransferase with methylumbelliferone as a substrate was observed indicating that different UDP-glucuronyltransferase isoforms are involved in FLAP metabolism. In conclusion, we find that glucuronidation is the major mechanism of hepatic FLAP biotransformation. Metabolites are mainly excreted into bile but also released into systemic circulation. The pharmacological and toxicological effects of these metabolites remain to be elucidated. C1 Univ Vienna, Inst Pharmaceut Chem, A-1090 Vienna, Austria. Univ Vienna, Inst Theoret Chem, A-1090 Vienna, Austria. Univ Vienna, Dept Gen & Expt Pathol, A-1090 Vienna, Austria. Inst Agr Ecol, Fed Off & Res Ctr Agr, Vienna, Austria. NCI, Bethesda, MD 20892 USA. Hoechst Marion Roussel, Marburg, Germany. RP Jager, W (reprint author), Univ Vienna, Inst Pharmaceut Chem, Althanstr 14, A-1090 Vienna, Austria. EM wjaeger@speedy.pch.univie.ac.at RI Jager, Walter/I-6242-2013 OI Jager, Walter/0000-0002-4970-8179 NR 26 TC 56 Z9 57 U1 0 U2 6 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0024-3205 J9 LIFE SCI JI Life Sci. PD APR 10 PY 1998 VL 62 IS 20 BP 1861 EP 1873 DI 10.1016/S0024-3205(98)00152-0 PG 13 WC Medicine, Research & Experimental; Pharmacology & Pharmacy SC Research & Experimental Medicine; Pharmacology & Pharmacy GA ZH990 UT WOS:000073168600006 PM 9600328 ER PT J AU Kremerskothen, J Zopf, D Walter, P Cheng, JG Nettermann, M Niewerth, U Maraia, RJ Brosius, J AF Kremerskothen, J Zopf, D Walter, P Cheng, JG Nettermann, M Niewerth, U Maraia, RJ Brosius, J TI Heterodimer SRP9/14 is an integral part of the neural BC200 RNP in primate brain SO NEUROSCIENCE LETTERS LA English DT Article DE BC200 ribonucleoprotein; exaptation; dendritic translation; SRP9/14; elongation arrest ID SIGNAL RECOGNITION PARTICLE; SECONDARY STRUCTURE; ALU; EVOLUTION; SUBUNIT; PROTEIN; FAMILY; RNAS; DNA; SRP AB BC200 RNA is a brain-specific, small non-messenger RNA with a somatodendritic localization in primate neurons and a constituent of a ribonucleoprotein (RNP) complex. The primary and secondary structure of the 5' domain of BC200 RNA resembles that of the Alu domain of 7SL RNA, which is an integral part of the signal recognition particle (SRP). This would predict that similar proteins bind to this defined domain of both RNA species in vitro and in vivo. The data presented in this paper reveal that a protein that binds BC200 RNA in vivo is immunoreactive with antibodies against SRP9. This further supports the notion that the 5' domain of the BC200 RNA can fold into structures similar to the SRP Alu domain and, as a result, bind identical or similar proteins in vivo. The SRP9 protein binds only as dimer with SRP14 protein to the Alu domain of 7SL RNA to form a subdomain that, in SRP, is functional in translation arrest. Therefore, our data also indicate that the neuronal BC200 RNP is a candidate for regulating decentralized protein biosynthesis in dendrites, possibly with a mechanism that resembles translation arrest of the SRP. (C) 1998 Elsevier Science Ireland Ltd. C1 Univ Munster, Ctr Mol Biol Inflammat, Inst Expt Pathol, D-48149 Munster, Germany. Univ Calif San Francisco, Dept Biochem, San Francisco, CA 94143 USA. NICHHD, Mol Growth Regulat Lab, Bethesda, MD 20892 USA. RP Brosius, J (reprint author), Univ Munster, Ctr Mol Biol Inflammat, Inst Expt Pathol, Von Esmarch Str 56, D-48149 Munster, Germany. RI Brosius, Jurgen/F-5029-2016 OI Brosius, Jurgen/0000-0003-1650-2059 FU NIMH NIH HHS [MH38819] NR 22 TC 25 Z9 26 U1 0 U2 1 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0304-3940 J9 NEUROSCI LETT JI Neurosci. Lett. PD APR 10 PY 1998 VL 245 IS 3 BP 123 EP 126 DI 10.1016/S0304-3940(98)00215-8 PG 4 WC Neurosciences SC Neurosciences & Neurology GA ZL011 UT WOS:000073389900001 PM 9605471 ER PT J AU Melek, M Gellert, M van Gent, DC AF Melek, M Gellert, M van Gent, DC TI Rejoining of DNA by the RAG1 and RAG2 proteins SO SCIENCE LA English DT Article ID V(D)J RECOMBINATION; INTEGRATION; GENE AB Assembly of immunoglobulin and T cell receptor genes from separate gene segments [V(D)J recombination] begins with DNA double-strand breakage by the RAG1 and RAG2 proteins, acting at a pair of recombination signal sequences (RSSs). Here, the RAG proteins are shown to reverse the cleavage reaction by joining an RSS to a broken coding sequence end. These "hybrid joints" have also been found in lymphoid cells, even when the normal pathway of DNA double-strand break repair is inactive, and can now be explained by this activity of the RAG proteins. C1 NIDDKD, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. Erasmus Univ, Dept Cell Biol & Genet, NL-3000 DR Rotterdam, Netherlands. RP Gellert, M (reprint author), NIDDKD, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. NR 19 TC 86 Z9 86 U1 0 U2 2 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA SN 0036-8075 J9 SCIENCE JI Science PD APR 10 PY 1998 VL 280 IS 5361 BP 301 EP 303 DI 10.1126/science.280.5361.301 PG 3 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA ZH195 UT WOS:000073082400056 PM 9535663 ER PT J AU Ott, DE Hewes, SM Alvord, WG Henderson, LE Arthur, LO AF Ott, DE Hewes, SM Alvord, WG Henderson, LE Arthur, LO TI Inhibition of friend virus replication by a compound that reacts with the nucleocapsid zinc finger: Anti-retroviral effect demonstrated in vivo SO VIROLOGY LA English DT Article ID MURINE LEUKEMIA-VIRUS; FOCUS-FORMING VIRUS; CYS-HIS BOX; IN-VIVO; NONINFECTIOUS VIRUS; NUCLEOTIDE-SEQUENCE; ENVELOPE GENE; GENOMIC RNA; PROTEIN; THERAPY AB The zinc finger structure that is found in the nucleocapsid protein of nearly all retroviruses has been proposed as a target for antiviral therapy. Since compounds that chemically attack the cysteines of the finger have been shown to inactivate both human immunodeficiency virus type 1 (HIV-I) and murine leukemia virus (MuLV) in vitro, 14 of these compounds were tested in an MuLV-induced Friend disease model to assess their ability to inhibit retroviral replication in vivo. Of the 14 compounds tested, only Aldrithiol-2 clearly exhibited anti-retroviral activity as measured indirectly by the delay of Friend disease onset (P < 0.05). These results were confirmed by quantitative competitive polymerase chain reaction studies which monitored viral spread by measuring the level of viral DNA in the peripheral blood mononuclear cells of treated mice. Comparison of treated mice with untreated mice revealed that Aldrithiol-2 produced a greater than 2-log reduction in virus levels. These results functionally demonstrate that a zinc finger-attacking compound can inhibit viral replication in vivo. Since only 1 of the 14 compounds studied was effective, this study also shows the importance of in vivo testing of these types of antiviral compounds in an animal model. Given the strict conservation of the metal-coordinating cysteine structure within HIV-I and MuLV zinc fingers, our results support the proposal that anti-retroviral drugs which target the nucleocapsid zinc finger may be clinically useful against HIV-1. C1 NCI, Frederick Canc Res & Dev Ctr, AIDS Vaccine Program, SAIC Frederick, Frederick, MD 21702 USA. NCI, Frederick Canc Res & Dev Ctr, Data Management Serv Inc, Frederick, MD 21702 USA. RP Ott, DE (reprint author), NCI, Frederick Canc Res & Dev Ctr, AIDS Vaccine Program, SAIC Frederick, Frederick, MD 21702 USA. EM ott@avpvx1.ncifcrf.gov NR 52 TC 13 Z9 14 U1 0 U2 1 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0042-6822 J9 VIROLOGY JI Virology PD APR 10 PY 1998 VL 243 IS 2 BP 283 EP 292 DI 10.1006/viro.1998.9062 PG 10 WC Virology SC Virology GA ZK860 UT WOS:000073371100004 PM 9568028 ER PT J AU Engleka, KA Lewis, EW Howard, BH AF Engleka, KA Lewis, EW Howard, BH TI Mechanisms of replication-deficient vaccinia virus T7 RNA polymerase hybrid expression: Effect of T7 RNA polymerase levels and alpha-amanitin SO VIROLOGY LA English DT Article ID TRANSIENT GENE-EXPRESSION; MAMMALIAN-CELLS; TRANSCRIPTIONAL INTERFERENCE; PROTEIN-SYNTHESIS; CYTOPLASMIC EXPRESSION; CATIONIC LIPOSOMES; ESCHERICHIA-COLI; CLONED GENES; PROMOTER; SYSTEM AB Components of the eukaryotic vaccinia virus/T7 RNA polymerase hybrid expression system were assessed using recombinant and nonrecombinant forms of modified vaccinia Ankara (MVA), a replication-deficient vaccinia virus strain. Recombinant MVA virus expressing T7 RNA polymerase (Wyatt, L. S., Moss, B., and Rozenblatt, S. (1995). Virology 210, 202-205) stimulated high levels of expression from a T7 promoter-chloramphenicol acetyltransferase (CAT) reporter. Most, but not all, of the virally induced expression was T7 RNA polymerase and T7 promoter dependent, with no viral enhancement of translation of T7 transcripts. The efficacy of supplying T7 RNA polymerase expression from nonviral sources was evaluated using a self-amplifying T7 RNA polymerase autogene or an inducible T7 RNA polymerase expression vector. The latter modes yielded CAT activity dependent on T7 RNA polymerase expression; however, expression required viral factors independent of T7 RNA polymerase and did not reach that attained using the recombinant virus. In further experiments, MVA-induced T7 RNA polymerase expression was upregulated by alpha-amanitin, an inhibitor of eukaryotic polymerases. This indicates that MVA/T7 RNA polymerase hybrid expression may be rendered still more efficient by ameliorating transcriptional interference due to an alpha-amanitin-sensitive eukaryotic factor(s). (C) 1998 Academic Press. C1 NICHHD, Lab Mol Growth Regulat, NIH, Bethesda, MD 20892 USA. RP Engleka, KA (reprint author), Thomas Jefferson Univ, Jefferson Med Coll, Dept Physiol, 1020 Locust St, Philadelphia, PA 19107 USA. EM engleka1@jeflin.tju.edu NR 48 TC 3 Z9 3 U1 1 U2 2 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0042-6822 J9 VIROLOGY JI Virology PD APR 10 PY 1998 VL 243 IS 2 BP 331 EP 339 DI 10.1006/viro.1998.9070 PG 9 WC Virology SC Virology GA ZK860 UT WOS:000073371100009 PM 9568032 ER PT J AU Koonin, EV Aravind, L AF Koonin, EV Aravind, L TI Genomics: Re-evaluation of translation machinery evolution SO CURRENT BIOLOGY LA English DT Article ID TRANSFER-RNA-SYNTHETASE; BACTERIA; SEQUENCE AB Experiments based on genome sequence analysis have revealed unexpected complexity in the evolution of the translation apparatus, including concerted evolution of Gln-tRNA synthetase and Glu-tRNA(Gln) amidotransferase, and a novel, class I Lys-tRNA synthetase shared by archaea and spirochaetes. (C) Current Biology Ltd ISSN 0960-9822. C1 NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20894 USA. Texas A&M Univ, Dept Biol, College Stn, TX 77843 USA. RP Koonin, EV (reprint author), NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20894 USA. NR 29 TC 9 Z9 9 U1 0 U2 1 PU CURRENT BIOLOGY LTD PI LONDON PA 34-42 CLEVELAND STREET, LONDON W1P 6LB, ENGLAND SN 0960-9822 J9 CURR BIOL JI Curr. Biol. PD APR 9 PY 1998 VL 8 IS 8 BP R266 EP R269 DI 10.1016/S0960-9822(98)70169-1 PG 4 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA ZH181 UT WOS:000073081000007 PM 9550696 ER PT J AU Nussbaum, RL AF Nussbaum, RL TI Human genetics - Putting the Parkin into Parkinson's SO NATURE LA English DT Article ID JUVENILE PARKINSONISM; DISEASE C1 Natl Human Genome Res Inst, Bethesda, MD 20892 USA. RP Nussbaum, RL (reprint author), Natl Human Genome Res Inst, 49 Convent Dr, Bethesda, MD 20892 USA. EM rlnuss@nhgri.nih.gov NR 9 TC 10 Z9 10 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 J9 NATURE JI Nature PD APR 9 PY 1998 VL 392 IS 6676 BP 544 EP 545 DI 10.1038/33271 PG 2 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA ZG300 UT WOS:000072987200026 PM 9560145 ER PT J AU Grimbacher, B Holland, SM Puck, JM AF Grimbacher, B Holland, SM Puck, JM TI The interleukin-4 receptor variant Q576R in hyper-IgE syndrome SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Letter C1 Natl Human Genome Res Inst, Bethesda, MD 20892 USA. NIAID, Bethesda, MD USA. RP Grimbacher, B (reprint author), Natl Human Genome Res Inst, Bethesda, MD 20892 USA. NR 5 TC 30 Z9 30 U1 0 U2 0 PU MASS MEDICAL SOC PI BOSTON PA 10 SHATTUCK, BOSTON, MA 02115 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD APR 9 PY 1998 VL 338 IS 15 BP 1073 EP 1074 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA ZG134 UT WOS:000072969500020 PM 9537881 ER PT J AU Ioannidis, JPA Cappelleri, JC Lau, J AF Ioannidis, JPA Cappelleri, JC Lau, J TI Issues in comparisons between meta-analyses and large trials SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID RANDOMIZED CONTROLLED TRIALS; ACUTE MYOCARDIAL-INFARCTION; CLINICAL-TRIALS; PUBLICATION BIAS; METAANALYSIS; MANAGEMENT; RATES; RISK AB Context.-The extent of concordance between meta-analyses and large trials on the same topic has been investigated with different protocols. Inconsistent conclusions created confusion regarding the validity of these major tools of clinical evidence. Objective.-To evaluate protocols comparing meta-analyses and large trials in order to understand if and why they disagree on the concordance of these 2 clinical research methods, Design.-Systematic comparison of protocol designs, study selection, definitions of agreement, analysis methods, and reported discrepancies between large trials and meta-analyses. Results.-More discrepancies were claimed when large trials were selected from influential journals (which may prefer trials disagreeing with prior evidence) than from already performed meta-analyses (which may target homogeneous trials) and when both primary and secondary (rather than only primary) end points were considered. Depending on how agreement was defined, kappa coefficients varied from 0.22 (low agreement) to 0.72 (excellent agreement), The correlation of treatment effects between large trials and meta-analyses varied from -0.12 to 0.76, but was more similar (0.50-0.76) when only primary end points were considered, When both the magnitude and uncertainty of treatment effects were considered, large trials disagreed with meta-analyses 10% to 23% of the time, Discrepancies were attributed to different disease risks, variable protocols, quality, and publication bias. Conclusions.-Comparisons of large trials with meta-analyses may reach different conclusions depending on how trials and meta-analyses are selected and how end points and agreement are defined. Scrutiny of these 2 major research methods can enhance our appreciation of both for guiding medical practice. C1 NIAID, Therapeut Res Program, Div Aids, NIH, Bethesda, MD 20852 USA. Pfizer Inc, Pfizer Cent Res, Dept Clin Res, Groton, CT 06340 USA. Tufts Univ, New England Med Ctr, Sch Med, Div Clin Care Res, Boston, MA 02111 USA. RP Ioannidis, JPA (reprint author), NIAID, Therapeut Res Program, Div Aids, NIH, Solar Bldg,Room 2C31,6003 Execut Blvd, Bethesda, MD 20852 USA. EM ji24m@nih.gov RI Ioannidis, John/G-9836-2011 NR 48 TC 165 Z9 167 U1 1 U2 6 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD APR 8 PY 1998 VL 279 IS 14 BP 1089 EP 1093 DI 10.1001/jama.279.14.1089 PG 5 WC Medicine, General & Internal SC General & Internal Medicine GA ZF216 UT WOS:000072875300033 PM 9546568 ER PT J AU Alford, PB Xue, Y Thai, SF Shackelford, RE AF Alford, PB Xue, Y Thai, SF Shackelford, RE TI Maleylated-BSA enhances production of nitric oxide from macrophages SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article ID MURINE PERITONEAL-MACROPHAGES; LOW-DENSITY-LIPOPROTEIN; TRANSCRIPTION; ACTIVATION; EXPRESSION; RECEPTORS; PROMOTER; SYNTHASE; ALBUMIN; INVITRO AB Maleylated-bovine serum albumin (maleyl-BSA) elicits transcription and secretion of a number of proinflammatory genes via ligation of the low-affinity scavenger receptor (SR) on macrophages. We now demonstrate that while neither maleyl-BSA, nor interferon-gamma (INF-gamma) alone induce nitric oxide (NO) production, when combined they promote release of NO from murine peritoneal macrophages. This effect was blocked by treatment with oxidized-low density lipoprotein. Maleyl-BSA activated NF-kappa B dimers capable of binding the NF-kappa Bd sequence unique to the iNOS promoter, but this failed to induce significant new transcription or accumulation of iNOS mRNA. The combination of maleyl-BSA and IFN-gamma failed to demonstrate synergy at the transcriptional or mRNA levels, as these levels were comparable to those elicited by IFN-gamma alone. These studies suggest that the synergy in NO production between maleyl-BSA and IFN-gamma occurs after the accumulation of iNOS-specific mRNA, possibly at the translational or post-translational level. (C) 1998 Academic Press. C1 Duke Univ, Med Ctr, Dept Pathol, Durham, NC 27708 USA. RP Shackelford, RE (reprint author), NIEHS, POB 12233,F1-05,111 Alexander Dr, Res Triangle Pk, NC 27709 USA. EM shackel1@niehs.nih.gov NR 20 TC 8 Z9 8 U1 0 U2 1 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD APR 7 PY 1998 VL 245 IS 1 BP 185 EP 189 DI 10.1006/bbrc.1998.8400 PG 5 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA ZK045 UT WOS:000073279400033 PM 9535805 ER PT J AU Sharma, P Barchi, JJ Huang, XL Amin, ND Jaffe, H Pant, HC AF Sharma, P Barchi, JJ Huang, XL Amin, ND Jaffe, H Pant, HC TI Site-specific phosphorylation of Lys-Ser-Pro repeat peptides from neurofilament H by cyclin-dependent kinase 5: Structural basis for substrate recognition SO BIOCHEMISTRY LA English DT Article ID PROTEIN-KINASE; CRYSTAL-STRUCTURE; CATALYTIC SUBUNIT; SEQUENCE; ACTIVATION; SPECTRA; MOTIFS; BRAIN AB Recent work has shown that high molecular weight neurofilament (NF) proteins are phosphorylated in their carboxy-terminal tail portion by the enzyme cyclin-dependent kinase 5 (CDK-5). The tail domain of neurofilaments contains 52 tripeptide repeats, viz. Lys-Ser-Pro, which mainly exist as KSPXK and KSPXXX motifs (X = amino acid). CDK-5 specifically phosphorylates the serine residues within the KSPXK sites. We probed the structural basis for this type of substrate selectivity by studying the conformation of synthetic peptides containing either KSPXK or KSPXXX repeats designed from native neurofilament sequences. Synthetic peptides with KSPXK repeats were phosphorylated on serine with a recombinant CDK-5/p25 complex whereas those with KSPXXX repeats were unreactive in this system. Circular dichroism (CD) studies in 50% TFE/H2O revealed a predominantly helical conformation for the KSPXXX-containing peptides, whereas the CD spectra for KSPXK-containing peptides indicated the presence of a high population of extended structures in water and 50% TFE solutions. However, detailed NMR analysis of one such peptide which included two such KSPXK repeats suggested a turn-like conformation encompassing the first KSPXK repeat. Restrained molecular dynamics calculations yielded an unusually stable, folded structure with a double "S"-like bend incorporating the central residues of the peptide. The data suggest that a transient reverse turn or loop-type structure may be a requirement for CDK-5-promoted phosphate transfer to neurofilament-specific peptide segments. C1 NINDS, Neurochem Lab, NIH, Bethesda, MD 20892 USA. NCI, Med Chem Lab, Div Basic Sci, NIH, Bethesda, MD 20892 USA. RP NINDS, Neurochem Lab, NIH, Bldg 36,Room 4D20, Bethesda, MD 20892 USA. EM hcp@codon.nih.gov RI Barchi Jr., Joseph/N-3784-2014 NR 41 TC 24 Z9 25 U1 0 U2 3 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD APR 7 PY 1998 VL 37 IS 14 BP 4759 EP 4766 DI 10.1021/bi972746o PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA ZK042 UT WOS:000073279100009 PM 9537991 ER PT J AU Ramachandra, M Ambudkar, SV Chen, D Hrycyna, CA Dey, S Gottesman, MM Pastan, I AF Ramachandra, M Ambudkar, SV Chen, D Hrycyna, CA Dey, S Gottesman, MM Pastan, I TI Human P-glycoprotein exhibits reduced affinity for substrates during a catalytic transition state SO BIOCHEMISTRY LA English DT Article ID HAMSTER OVARY CELLS; NUCLEOTIDE-BINDING SITES; MULTIDRUG-RESISTANCE; ATPASE ACTIVITY; DRUG TRANSPORT; RECONSTITUTION; PURIFICATION; EXPRESSION; HYDROLYSIS; VESICLES AB Human P-glycoprotein (Pgp), a plasma membrane protein that confers multidrug resistance, functions as an ATP-dependent drug efflux pump. Pgp contains two ATP binding/utilization sites and exhibits ATPase activity that is stimulated in the presence of substrates and modulating agents. The mechanism of coupling of ATP hydrolysis to drug transport is not known, To understand the role of ATP hydrolysis in drug binding, it is necessary to develop methods for purifying and reconstituting Pgp that retains properties including stimulation of ATPase activity by known substrates to an extent similar to that in the native membrane. In this study, (His)(6)-tagged Pgp was expressed in Trichoplusia ni (High Five) cells using the recombinant baculovirus system and purified by metal affinity chromatography, Upon reconstitution into phospholipid vesicles, purified Pgp exhibited specific binding to analogues of substrates and ATP in affinity labeling experiments and displayed a high level of drug-stimulated ATPase activity (specific activity ranging from 4.5 to 6.5 mu mol min(-1) mg(-1)). The ATPase activity was inhibited by ADP in a competitive manner, and by vanadate and N-ethylmaleimide at low concentrations. Vanadate which is known to inhibit ATPase activity by trapping MgADP at the catalytic site inhibited photoaffinity labeling of Pgp with substrate analogues, [I-125]iodoarylazidoprazosin and [H-3]azidopine, only under ATP hydrolysis conditions. Because vanadate-trapped Pgp is known to resemble the ADP and phosphate-bound catalytic transition state, our findings indicate that ATP hydrolysis results in a conformation with reduced affinity for substrates. A catalytic transition conformation with reduced affinity would essentially result in substrate dissociation and supports a model for drug transport in which an ATP hydrolysis-induced conformational change leads to drug release toward the extracellular medium. C1 NCI, Mol Biol Lab, Div Basic Sci, NIH, Bethesda, MD 20892 USA. NCI, Cell Biol Lab, Div Basic Sci, NIH, Bethesda, MD 20892 USA. RP Pastan, I (reprint author), NCI, Mol Biol Lab, Div Basic Sci, NIH, Bldg 37,Room 4E16,37 Convent Dr,MSC 4255, Bethesda, MD 20892 USA. RI Ambudkar, Suresh/B-5964-2008 NR 39 TC 199 Z9 204 U1 1 U2 9 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD APR 7 PY 1998 VL 37 IS 14 BP 5010 EP 5019 DI 10.1021/bi973045u PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA ZK042 UT WOS:000073279100038 PM 9538020 ER PT J AU Grobler, JA Hurley, JH AF Grobler, JA Hurley, JH TI Catalysis by phospholipase C delta(1) requires that Ca2+ bind to the catalytic domain, but not the C2 domain SO BIOCHEMISTRY LA English DT Article ID PROTEIN-KINASE-C; PLECKSTRIN HOMOLOGY DOMAIN; HIGH-AFFINITY; PHOSPHATIDYLINOSITOL 4,5-BISPHOSPHATE; CRYSTAL-STRUCTURE; C-DELTA(1); CALCIUM; SYNAPTOTAGMIN; ACTIVATION; HYDROLYSIS AB The hydrolysis of phosphatidylinositol 4,5-bisphosphate (PIP2) by phosphoinositide-specific phospholipase C (PLC) is absolutely dependent on Ca2+. The PH domain truncated catalytic core of rat phospholipase C delta(1) (PLC-delta(1)) has Ca2+ binding sites in its catalytic and C2 domains, and potential Ca2+ binding sites in two EF-hands. A catalytically inactive PLC-delta(1) catalytic core bound with low affinity to PIP2-containing vesicles in the presence of Ca2+. A mutant PLC-delta(1) has been engineered which lacks the C2 domain Ca2+ binding site and the surrounding loops known as the jaws. Isothermal calorimetric titration showed four Ca2+ ions bind to the wild-type PLC-delta(1) catalytic core in solution but only one binds to the C2 domain jaws deletion mutant. The activity and Ca2+ dependence of wild-type and mutant phospholipase Cs were determined using substrate incorporated in detergent micelles and in large unilamellar vesicles. The activities of wild-type and mutant were identical to each other in both assay systems. Wild-type and the C2 jaws deletion mutant of PLC have Hill coefficients of 1.12-1.16 with respect to [Ca2+]. We conclude that a single Ca2+ bound to the catalytic domain is entirely responsible for the Ca2+ dependence of the basal activity of PLC-delta(1). C1 NIDDKD, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. RP Hurley, JH (reprint author), NIDDKD, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. NR 58 TC 40 Z9 42 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD APR 7 PY 1998 VL 37 IS 14 BP 5020 EP 5028 DI 10.1021/bi972952w PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA ZK042 UT WOS:000073279100039 PM 9538021 ER PT J AU Kubota, H Rothman, RB Dersch, C McCullough, K Pinto, J Rice, KC AF Kubota, H Rothman, RB Dersch, C McCullough, K Pinto, J Rice, KC TI Synthesis and biological activity of 3-substituted 3-desoxynaltrindole derivatives SO BIOORGANIC & MEDICINAL CHEMISTRY LETTERS LA English DT Article ID OPIOID RECEPTOR ANTAGONISTS; MESSAGE ADDRESS CONCEPT; MORPHINE-TOLERANCE; BORONIC ACIDS; BINDING-SITES; ORGANOSTANNANES; SELECTIVITY; NALTRINDOLE; DEPENDENCE; NALTREXONE AB The 3-unsubstituted and substituted analogs of naltrindole (NTI) were synthesized using palladium-catalyzed transformations, and their binding affinity to opioid receptors was determined. Although the 3-desoxy analog showed comparable delta selectivity with that of NTI, all of the novel compounds possessed low affinity for delta receptors indicating the important role of the 3-oxygen atom of NTI for interaction with delta-opioid receptors. Published by Elsevier Science Ltd. C1 NIDDK, Med Chem Lab, NIH, Bethesda, MD 20892 USA. NIDA, Addict Res Ctr, Clin Psychopharmacol Sect, Baltimore, MD 21224 USA. RP Rice, KC (reprint author), NIDDK, Med Chem Lab, NIH, Bldg 8,Room B1-23, Bethesda, MD 20892 USA. NR 30 TC 26 Z9 26 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0960-894X J9 BIOORG MED CHEM LETT JI Bioorg. Med. Chem. Lett. PD APR 7 PY 1998 VL 8 IS 7 BP 799 EP 804 DI 10.1016/S0960-894X(98)00105-X PG 6 WC Chemistry, Medicinal; Chemistry, Organic SC Pharmacology & Pharmacy; Chemistry GA ZG515 UT WOS:000073011400019 PM 9871544 ER PT J AU Cushman, M Insaf, S Ruell, JA Schaeffer, CA Rice, WG AF Cushman, M Insaf, S Ruell, JA Schaeffer, CA Rice, WG TI Synthesis of a cosalane analog with an extended polyanionic pharmacophore conferring enhanced potency as an anti-HIV agent SO BIOORGANIC & MEDICINAL CHEMISTRY LETTERS LA English DT Article ID ANTIVIRAL ACTIVITY; HUMAN CD4; DESIGN; SERIES AB A novel cosalane analog having an extended polyanionic pharmacophore was synthesized in order to target specific cationic residues on the surface of CD4. The design rationale is based on a hypothetical binding model of cosalane to the surface of the protein. The new analog displayed an EC50 of 0.55 mu M as an inhibitor of the cytopathic effect of HIV-1(RF) in CEM-SS cells, which represents a significant increase in potency over cosalane itself (EC50 5.1 mu M) Both cosalane and the new analog are inhibitors of viral entry into target cells. (C) 1998 Elsevier Science Ltd. All rights reserved. C1 Purdue Univ, Sch Pharm & Pharmacal Sci, Dept Med Chem & Mol Pharamacol, W Lafayette, IN 47907 USA. NCI, Frederick Canc Res & Dev Ctr, SAIC Frederick, Lab Antiviral Drug Mechanisms, Frederick, MD 21702 USA. RP Cushman, M (reprint author), Purdue Univ, Sch Pharm & Pharmacal Sci, Dept Med Chem & Mol Pharamacol, W Lafayette, IN 47907 USA. FU NIAID NIH HHS [N01-AI-36624] NR 15 TC 15 Z9 16 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0960-894X J9 BIOORG MED CHEM LETT JI Bioorg. Med. Chem. Lett. PD APR 7 PY 1998 VL 8 IS 7 BP 833 EP 836 DI 10.1016/S0960-894X(98)00121-8 PG 4 WC Chemistry, Medicinal; Chemistry, Organic SC Pharmacology & Pharmacy; Chemistry GA ZG515 UT WOS:000073011400025 PM 9871550 ER PT J AU Kreitman, RJ Pastan, I AF Kreitman, RJ Pastan, I TI Immunotoxins for targeted cancer therapy SO ADVANCED DRUG DELIVERY REVIEWS LA English DT Review DE monoclonal antibody; immunoconjugates; interleukin; ricin; pseudomonas exotoxin; diphtheria toxin; saporin; gelonin; fusion protein; Fv ID RICIN-A-CHAIN; EPIDERMAL GROWTH-FACTOR; PSEUDOMONAS EXOTOXIN-A; T-CELL LEUKEMIA; CHRONIC LYMPHOCYTIC-LEUKEMIA; ACUTE LYMPHOBLASTIC-LEUKEMIA; VERSUS-HOST DISEASE; PHASE-I TRIAL; BONE-MARROW TRANSPLANTATION; SEVERE COMBINED IMMUNODEFICIENCY AB Immunotoxins constitute a new modality for the treatment of cancer, since they target cells displaying specific surface-receptors or antigens. Immunotoxins contain a ligand such as a growth factor, monoclonal antibody, or fragment of an antibody which is connected to a protein toxin. After the ligand subunit binds to the surface of the target cell, the molecule internalizes and the toxin kills the cell. Bacterial toxins which have been targeted to cancer cells include Pseudomonas exotoxin and diphtheria toxin, which are well suited to forming recombinant single-chain or double-chain fusion toxins. Plant toxins include ricin, abrin, pokeweed antiviral protein, saporin and gelonin, and have generally been connected to ligands by disulfide-bond chemistry. Immunotoxins have been produced to target hematologic malignancies and solid tumors via a wide variety of growth factor receptors and antigens. Challenges facing the clinical application of immunotoxins are discussed. (C) 1998 Elsevier Science B.V. C1 NCI, NIH, Mol Biol Lab, Div Canc Biol, Bethesda, MD 20892 USA. RP Kreitman, RJ (reprint author), NCI, NIH, Mol Biol Lab, Div Canc Biol, 3714E16,37 Convent Dr MSC 4255, Bethesda, MD 20892 USA. NR 431 TC 62 Z9 75 U1 2 U2 13 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0169-409X J9 ADV DRUG DELIVER REV JI Adv. Drug Deliv. Rev. PD APR 6 PY 1998 VL 31 IS 1-2 BP 53 EP 88 DI 10.1016/S0169-409X(97)00094-X PG 36 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA ZL317 UT WOS:000073420500005 ER PT J AU Meiri, N Rosenblum, K AF Meiri, N Rosenblum, K TI Lateral ventricle injection of the protein synthesis inhibitor anisomycin impairs long-term memory in a spatial memory task SO BRAIN RESEARCH LA English DT Article DE water maze; anisomycin; rat; learning; hippocampus ID HIPPOCAMPALLY APPLIED ANISOMYCIN; MORRIS WATER MAZE; FREELY-MOVING RAT; APLYSIA; DISCRIMINATION; LESIONS; NEURONS AB Although protein synthesis inhibition has been shown to affect long-term memory in a wide variety of animal species, cases have been reported in which protein synthesis inhibition failed to affect memory consolidation [S. Wittstock, R. Menzel, Color learning and memory in honey bees are not affected by protein synthesis inhibition, Behav. Neural Biol., 62 (1994) 224-229.]. Most findings argue that the critical time for protein synthesis is during or immediately after training. However, other reports show a second time window, hours after training, where protein synthesis inhibition can cause amnesia [F.M. Freeman, S.P.R, Rose, A.B. Scholey, Two time windows of anisomycin-induced amnesia for passive avoidance training in the day-old chick, Neurobiol. Learn.Mem., 63 (1995) 291-295.][G. Grecksch, H. Matthies, Two sensitive periods for the amnesic effect of anisomycin, Pharmacol. Biochem. Behav., 12 (1980) 663-665.]. In this study, we addressed two questions: (1) Is protein synthesis essential for spatial memory? and (2) At what injection time window(s) will protein synthesis inhibition cause spatial memory amnesia? We report that bilateral intraventricular microinjection of anisomycin (Ani) impairs consolidation of long-term memory, in the hippocampal-dependent Morris water maze spatial memory task. Memory was impaired in a dose-dependent manner without affecting short-term memory. Spatial memory was affected only if Ani was injected 20 min before performing the task and not in any other time window before or after the behavioral test. The inhibition did not affect pre-existing memories or the capability to memorize once the effect of the inhibition diminished. (C) 1998 Elsevier Science B.V. C1 NINDS, LAS, NIH, Bethesda, MD 20892 USA. Natl Inst Med Res, Div Neurophysiol & Neuropharmacol, London NW7 1AA, England. Weizmann Inst Sci, Dept Neurobiol, IL-76100 Rehovot, Israel. RP Meiri, N (reprint author), NINDS, LAS, NIH, 36 Convent Dr,MSC 4124, Bethesda, MD 20892 USA. NR 45 TC 71 Z9 74 U1 1 U2 5 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0006-8993 J9 BRAIN RES JI Brain Res. PD APR 6 PY 1998 VL 789 IS 1 BP 48 EP 55 DI 10.1016/S0006-8993(97)01528-X PG 8 WC Neurosciences SC Neurosciences & Neurology GA ZL056 UT WOS:000073394400006 PM 9602054 ER PT J AU Guidry, G Landis, SC Davis, BM Albers, KM AF Guidry, G Landis, SC Davis, BM Albers, KM TI Overexpression of nerve growth factor in epidermis disrupts the distribution and properties of sympathetic innervation in footpads SO JOURNAL OF COMPARATIVE NEUROLOGY LA English DT Article DE transmitter plasticity; development; synapse formation; sweat glands ID RAT SWEAT GLANDS; VESICULAR ACETYLCHOLINE TRANSPORTER; NEUROTRANSMITTER PLASTICITY INVIVO; SUPERIOR CERVICAL GANGLIA; PRIMARY SENSORY NEURONS; DORSAL-ROOT GANGLION; CHOLINERGIC DIFFERENTIATION; TYROSINE-HYDROXYLASE; MYELINATED NOCICEPTORS; AXON GUIDANCE AB Sympathetic and sensory neurons form distinct axonal arborizations in several peripheral targets. The developmental mechanisms responsible for partitioning sympathetic and sensory axons between potential target tissues are poorly understood. We have used rodent footpads to study this process because three populations of peripheral axons innervate topographically segregated targets in the footpad; cholinergic sympathetic axons innervate sweat glands, noradrenergic sympathetic axons innervate blood vessels, and sensory axons form a plexus at the epidermal/dermal junction. To examine how nerve growth factor (NGF), a trophic and survival factor for sympathetic and some sensory neurons, may contribute to the generation of the patterned distribution of axons among targets, we studied transgenic mice (K14-NGF mice) in which NGF expression was significantly increased in the epidermis. Whereas the temporal sequence in which sensory and sympathetic fibers arrived in the footpad was not affected, the normal partitioning of axons between target tissues was disrupted. The two sympathetic targets in footpads, sweat glands, and blood vessels lacked substantial innervation and instead a dense plexus of catecholaminergic sympathetic fibers was found commingled with sensory fibers in the dermis. Those sympathetic fibers present in sweat glands expressed an abnormal dual catecholaminergic/cholinergic phenotype. Our findings indicate that overexpression of NGF in skin interferes with the segregation of sensory and sympathetic axonal arbors and suggests a role for target-derived NGF in the establishment of distinct axonal territories. Our data also suggest that by determining where axon arbors form, NGF can indirectly influence the phenotypic properties of sympathetic neurons. (C) 1998 Wiley-Liss, Inc. C1 NINDS, Neural Dev Sect, NIH, Bethesda, MD 20892 USA. Case Western Reserve Univ, Dept Neurosci, Cleveland, OH 44106 USA. Univ Kentucky, Coll Med, Dept Anat & Neurobiol, Lexington, KY 40536 USA. Univ Kentucky, Coll Med, Dept Pathol & Lab Med, Lexington, KY 40536 USA. RP Landis, SC (reprint author), NINDS, Neural Dev Sect, NIH, Bethesda, MD 20892 USA. EM slandis@codon.nih.gov OI Albers, Kathryn/0000-0003-4597-9323; Davis, Brian/0000-0002-4646-0569 FU NINDS NIH HHS [NS33730, NS31826, NS023678] NR 81 TC 24 Z9 24 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0021-9967 J9 J COMP NEUROL JI J. Comp. Neurol. PD APR 6 PY 1998 VL 393 IS 2 BP 231 EP 243 DI 10.1002/(SICI)1096-9861(19980406)393:2<231::AID-CNE7>3.0.CO;2-3 PG 13 WC Neurosciences; Zoology SC Neurosciences & Neurology; Zoology GA ZC820 UT WOS:000072621400007 PM 9548699 ER PT J AU Shores, EW Ono, M Kawabe, T Sommers, CL Tran, T Lui, K Udey, MC Ravetch, J Love, PE AF Shores, EW Ono, M Kawabe, T Sommers, CL Tran, T Lui, K Udey, MC Ravetch, J Love, PE TI T cell development in mice lacking all T cell receptor zeta family members (zeta, eta, and Fc epsilon RI gamma) SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article ID ANTIGEN RECEPTOR; INTRAEPITHELIAL LYMPHOCYTES; MUTANT MICE; CHAIN; CD3-ZETA; SELECTION; SUBUNIT; GENE; DIFFERENTIATION; CD3-EPSILON AB The zeta family includes zeta, eta, and Fc epsilon RI gamma (Fc gamma). Dimers of the zeta family proteins function as signal transducing subunits of the T cell antigen receptor (TCR), the pre-TCR, and a subset of Fc receptors. In mice lacking zeta/eta chains, T cell development is impaired, yet low numbers of CD4(+) and CD8(+) T cells develop. This finding suggests either that pre-TCR and TCR complexes lacking a zeta family dimer can promote T cell maturation, or that in the absence of zeta/eta, Fc gamma serves as a subunit in TCR complexes. To elucidate the role of zeta family dimers in T cell development, we generated mice lacking expression of all of these proteins and compared their phenotype to mice lacking only zeta/eta or Fc gamma. The data reveal that surface complexes that are expressed in the absence of zeta family dimers are capable of transducing signals required for alpha/beta-T cell development. Strikingly, T cells generated in both zeta/eta(-/-) and zeta/eta(-/-)-Fc gamma(-/-) mice exhibit a memory phenotype and elaborate interferon gamma. Finally, examination of different T cell populations reveals that zeta/eta and Fc gamma have distinct expression patterns that correlate with their thymus dependency. A possible function for the differential expression of zeta family proteins may be to impart distinctive signaling properties to TCR complexes expressed on specific T cell populations. C1 US FDA, Div Hematol Prod, Ctr Biol Evaluat & Res, Rockville, MD 20852 USA. Rockefeller Univ, Lab Mol Genet & Immunol, New York, NY 10021 USA. NCI, Dermatol Branch, NIH, Bethesda, MD 20892 USA. NICHHD, Lab Mammalian Genes & Dev, NIH, Bethesda, MD 20892 USA. RP Shores, EW (reprint author), US FDA, Div Hematol Prod, Ctr Biol Evaluat & Res, 1401 Rockville Pike,HFM-538, Rockville, MD 20852 USA. EM shoresew@helix.nih.gov RI kawabe, tsutomu/I-6277-2014 OI kawabe, tsutomu/0000-0002-9319-9930 NR 37 TC 44 Z9 44 U1 0 U2 1 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0022-1007 J9 J EXP MED JI J. Exp. Med. PD APR 6 PY 1998 VL 187 IS 7 BP 1093 EP 1101 DI 10.1084/jem.187.7.1093 PG 9 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA ZH131 UT WOS:000073075900012 PM 9529325 ER PT J AU Gandhi, RT Chen, BK Straus, SE Dale, JK Lenardo, MJ Baltimore, D AF Gandhi, RT Chen, BK Straus, SE Dale, JK Lenardo, MJ Baltimore, D TI HIV-1 directly kills CD4(+) T cells by a Fas-independent mechanism SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; ACTIVATION-INDUCED APOPTOSIS; LYMPHOPROLIFERATIVE SYNDROME; NORMAL INDIVIDUALS; LIGAND EXPRESSION; LYMPH-NODES; IN-VIVO; LYMPHOCYTES; INFECTION; DEATH AB The mechanism by which HIV-1 induces CD4(+) T cell death is not known. A fundamental issue is whether HIV-1 primarily induces direct killing of infected cells or indirectly causes death of uninfected bystander cells. This question was studied using a reporter virus system in which infected cells are marked with the cell surface protein placental alkaline phosphatase (PLAP). Infection by HIV-PLAP of peripheral blood mononuclear cells (PBMCs) and T cell lines leads to rapid depletion of CD4(+) T cells and induction of apoptosis. The great majority of HIV-induced T cell death in vitro involves direct loss of infected cells rather than indirect effects on uninfected bystander cells. Because of its proposed role in HIV-induced cell death, we also examined die Fas (CD95/Apo1) pathway in killing of T cells by HIV-1. Infected PBMCs or CEM cells display no increase in surface Fas relative to uninfected cells. In addition, HIV-1 kills CEM and Jurkat T cells in the presence of a caspase inhibitor that completely blocks Fas-mediated apoptosis. HIV-1 also depletes CD4(+) T cells in PBMCs from patients who have a genetically defective Fas pathway. These results suggest that HIV-1 induces direct apoptosis of infected cells and kills T cells by a Fas-independent mechanism. C1 CALTECH, Pasadena, CA 91125 USA. MIT, Dept Biol, Cambridge, MA 02139 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Rockefeller Univ, New York, NY 10021 USA. NIAID, Clin Invest Lab, NIH, Bethesda, MD 20892 USA. NIAID, Immunol Lab, NIH, Bethesda, MD 20892 USA. RP Baltimore, D (reprint author), CALTECH, Pasadena, CA 91125 USA. FU NIAID NIH HHS [1 K08 AI-01443-01]; NIGMS NIH HHS [GM07739, T32 GM007739] NR 47 TC 138 Z9 142 U1 1 U2 8 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0022-1007 J9 J EXP MED JI J. Exp. Med. PD APR 6 PY 1998 VL 187 IS 7 BP 1113 EP 1122 DI 10.1084/jem.187.7.1113 PG 10 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA ZH131 UT WOS:000073075900014 PM 9529327 ER PT J AU Yang, LP Riley, JL Carroll, RG June, CH Hoxie, J Patterson, BK Ohshima, Y Hodes, RJ Delespesse, G AF Yang, LP Riley, JL Carroll, RG June, CH Hoxie, J Patterson, BK Ohshima, Y Hodes, RJ Delespesse, G TI Productive infection of neonatal CD8(+) T lymphocytes by HIV-1 SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; PERSISTENT EXPANSIONS; CELLS; PHENOTYPE; CD4 AB CD8(+) T lymphocytes confer significant but ultimately insufficient protection against HIV infection. Here were report that activated neonatal CD8(+) T cells can be productively infected in vitro by macrophage-tropic (M-tropic) HIV-1 isolates, which are responsible for disease transmission, whearas they are resistant to T cell-tropic (T-tropic) HIV strains. Physiological activation of CD8-alpha/beta(+) CD4(-) cell receptor-alpha/beta(+) neonatal T cells, including activation by allogeneic dendritic cells, induces the accumulation of CD4 messenger RNA and the expression of CD4 Ag on the cell surface. The large majority of anti-CD3/B7.1-activated cord blood CD8(+) T cells coexpress CD4. the primary HIV receptor, as well as CCR5 and CXCR4, the coreceptors used by M- and T-tropic HIV-1 strains, respectively, to enter target cells. These findings are relevant to the rapid progression of neonatal HIV infection. Infection of primary HIV-specific CD8(+) T cells may compromise their survival and thus significantly contribute to the failure of the immune system to control the infection. Furthermore, these results indicate a previously unsuspected level of plasticity in the neonatal immune system in the regulation of CD4 expression by costimulation. C1 Univ Montreal, Notre Dame Hosp, Ctr Rech Louis Charles Simard, Lab Rech Allergie M4211K, Montreal, PQ H2L 4M1, Canada. Henry M Jackson Fdn Advancement Mil Med, Bethesda, MD 20889 USA. Walter Reed Army Inst Res, Div Retrovirol, Rockville, MD 20850 USA. NIH, Expt Immunol Branch, Bethesda, MD 20892 USA. NIA, NIH, Bethesda, MD 20892 USA. Northwestern Univ, Sch Med, Dept Obstet Gynecol & Med, Div Infect Dis, Chicago, IL 60611 USA. Univ Penn, Div Hematol Oncol, Philadelphia, PA 19104 USA. RP Delespesse, G (reprint author), Univ Montreal, Notre Dame Hosp, Ctr Rech Louis Charles Simard, Lab Rech Allergie M4211K, 1560 Sherbrooke St E, Montreal, PQ H2L 4M1, Canada. EM delespeg@ere.umontreal.ca OI Riley, James/0000-0002-1057-576X NR 30 TC 59 Z9 61 U1 0 U2 0 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0022-1007 J9 J EXP MED JI J. Exp. Med. PD APR 6 PY 1998 VL 187 IS 7 BP 1139 EP 1144 DI 10.1084/jem.187.7.1139 PG 6 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA ZH131 UT WOS:000073075900017 PM 9529330 ER PT J AU Lau, J Ioannidis, JPA Schmid, CH AF Lau, J Ioannidis, JPA Schmid, CH TI Meta-analyses, multivariate analyses, and coping with the play of chance - Reply SO LANCET LA English DT Letter C1 Tufts Univ, New England Med Ctr, Div Clin Care Res, Boston, MA 02111 USA. NIAID, Bethesda, MD 20892 USA. RP Lau, J (reprint author), Tufts Univ, New England Med Ctr, Div Clin Care Res, Boston, MA 02111 USA. RI Ioannidis, John/G-9836-2011 NR 5 TC 0 Z9 0 U1 1 U2 2 PU LANCET LTD PI LONDON PA 42 BEDFORD SQUARE, LONDON WC1B 3SL, ENGLAND SN 0140-6736 J9 LANCET JI Lancet PD APR 4 PY 1998 VL 351 IS 9108 BP 1062 EP 1063 DI 10.1016/S0140-6736(05)79033-4 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA ZF730 UT WOS:000072927200059 ER PT J AU Jin, DY Spencer, F Jeang, KT AF Jin, DY Spencer, F Jeang, KT TI Human T cell leukemia virus type 1 oncoprotein tax targets the human mitotic checkpoint protein MAD1 SO CELL LA English DT Article ID SPINDLE ASSEMBLY CHECKPOINT; BUDDING YEAST; I TAX; ACTIVATION; EXPRESSION; HTLV; GENE; P53; MITOSIS; LINE AB In searching for cellular targets of the HTLV-I oncoprotein Tax, we identified TXBP181,which we characterized as the human homolog of yeast mitotic checkpoint MAD1 protein. Evidence supporting TXBP181 as HsMAD1 includes sequence conservation with yeast MAD1, hyperphosphorylation during S/G(2)/M phases and upon treatment of cells with nocodazole, and binding to HsMAD2. HsMAD1 functions as a homodimer. It localizes to the centrosome during metaphase and to the spindle midzone and the midbody during anaphase and telophase. Expression of either Tax or a transdominant-negative TXBP181 results in multinucleated cells, a phenotype consistent with a loss of HsMAD1 function. We propose a model of viral transformation in which Tax targets TXBP181, thereby abrogating a mitotic checkpoint. C1 NIAID, Mol Microbiol Lab, Bethesda, MD 20892 USA. Johns Hopkins Univ, Ctr Genet Med, Baltimore, MD 21205 USA. RP Jeang, KT (reprint author), NIAID, Mol Microbiol Lab, Bethesda, MD 20892 USA. RI Jeang, Kuan-Teh/A-2424-2008 NR 55 TC 408 Z9 424 U1 0 U2 5 PU CELL PRESS PI CAMBRIDGE PA 1050 MASSACHUSETTES AVE, CIRCULATION DEPT, CAMBRIDGE, MA 02138 USA SN 0092-8674 J9 CELL JI Cell PD APR 3 PY 1998 VL 93 IS 1 BP 81 EP 91 DI 10.1016/S0092-8674(00)81148-4 PG 11 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA ZF571 UT WOS:000072910800012 PM 9546394 ER PT J AU Yang, YL Ramaswamy, SG Jakoby, WB AF Yang, YL Ramaswamy, SG Jakoby, WB TI Enzymatic hydrolysis of organic cyclic carbonates SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID METABOLISM AB Ethylene carbonate, a cyclic organic carbonate widely used industrially, is toxic when metabolically converted to ethylene glyco. A rat liver enzyme active in catalyzing the ring opening has been purified to electrophoretic homogeneity and found to be active in the hydrolysis of ethylene, vinylene, and propylene carbonates to CO2 and the respective glycols. Neither thiocarbonates nor open chain carbonates served as substrate nor did a variety of esters, lactams, lactones, and related heterocycles. The enzyme was active, however, with imides and appears to be identical to rat liver imidase. The identification was confirmed by copurification of enzyme activities, by similarities in the pattern of inhibition, and by the reactivity with a polyclonal antibody directed against the enzyme purified here. C1 NIDDK, Biochem & Metab Lab, NIH, Bethesda, MD 20892 USA. RP Jakoby, WB (reprint author), NIDDK, Biochem & Metab Lab, NIH, Bldg 10,9N119, Bethesda, MD 20892 USA. NR 17 TC 17 Z9 19 U1 0 U2 8 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD APR 3 PY 1998 VL 273 IS 14 BP 7814 EP 7817 DI 10.1074/jbc.273.14.7814 PG 4 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA ZF226 UT WOS:000072876300007 PM 9525873 ER PT J AU Kajava, AV AF Kajava, AV TI Structural diversity of leucine-rich repeat proteins SO JOURNAL OF MOLECULAR BIOLOGY LA English DT Article DE atomic structure; classification; database; evolution; leucine-rich motifs ID PLANT-DISEASE RESISTANCE; SACCHAROMYCES-CEREVISIAE; RIBONUCLEASE INHIBITOR; GENE; BINDING; ENCODES; MOTIF; DOMAIN; REGION; YEAST AB The superfamily of leucine-rich repeat proteins can be subdivided into at least six subfamilies, characterised by different lengths and consensus sequences of the repeats. It was proposed that the repeats from different subfamilies retain a similar superhelical fold, but differ in the three-dimensional structures of individual repeats. The sequence-structure relationship of three new subfamilies was examined by molecular modelling; I provide structural models for the repeats of all subfamilies. The models enable me to explain residue conservations within each subfamily. Furthermore, the difference in the packing explains why the repeats from different subfamilies never occur simultaneously in the same protein. Finally, these studies suggest different evolutionary origins for the different subfamilies. The approach used for the prediction of the leucine-rich repeat protein structures can be applied to other proteins containing internal repeats of about 20 to SO residue in length. (C) 1998 Academic Press Limited. C1 Swiss Inst Expt Canc Res, CH-1066 Epalinges, Switzerland. RP Kajava, AV (reprint author), NIH, Ctr Mol Modeling, DCRT, Bldg 12A,Room 2011, Bethesda, MD 20892 USA. RI Kajava, Andrey/E-1107-2014 OI Kajava, Andrey/0000-0002-2342-6886 NR 38 TC 349 Z9 374 U1 1 U2 12 PU ACADEMIC PRESS LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0022-2836 J9 J MOL BIOL JI J. Mol. Biol. PD APR 3 PY 1998 VL 277 IS 3 BP 519 EP 527 DI 10.1006/jmbi.1998.1643 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA ZK501 UT WOS:000073328800003 PM 9533877 ER PT J AU Gao, HQ Boyer, PL Arnold, E Hughes, SH AF Gao, HQ Boyer, PL Arnold, E Hughes, SH TI Effects of mutations in the polymerase domain on the polymerase, RNase H and strand transfer activities of human immunodeficiency virus type 1 reverse transcriptase SO JOURNAL OF MOLECULAR BIOLOGY LA English DT Article DE HIV-1; reverse transcriptase; polypurine tract; RNase H; mutation ID MURINE LEUKEMIA-VIRUS; HIGH-LEVEL EXPRESSION; ESCHERICHIA-COLI; RIBONUCLEASE-H; ANGSTROM RESOLUTION; CRYSTAL-STRUCTURE; TEMPLATE BINDING; PRIMER-TEMPLATE; DNA-SYNTHESIS; HIV-1 RT AB Based on structural analyses and on the behavior of mutants, we suggest that the polymerase domain of HIV-1 reverse transcriptase (RT) plays a critical role in holding and appropriately positioning the template-primer both at the polymerase active site and at the RNase H active site. For RT to successfully copy the viral RNA genome, RNase H must cleave the RNA with absolute precision. We believe that a combination of the structure of the template-primer and its precise positioning are responsible for the specific cleavages RNase H makes. We have proposed that resistance of HIV-1 RT to nucleoside analogs involves a subtle repositioning of the template-primer. This hypothesis is based on both structural and biochemical analyses. Mutations that confer resistance to nucleoside analogs do not cluster at the polymerase active site; however, they are in pos itions where they could alter the interaction between RT and the template-primer. If, as we:have hypothesized, the polymerase domain is primarily responsible for positioning the template-primer and RNase H cleavage depends on this positioning, it should be possible to use RNase H cleavage to monitor at least some of the major changes in the position of the template-primer. We have used three assays (polymerase, RNase H, and strand transfer) to investigate the effects of mutations in the polymerase domain, including mutations that confer resistance to nucleotide analogs, on HIV-1 RT. All three assays involve RNA sequences derived from the viral genome. The data show that alterations in the polymerase domain, in particular, mutations that are in positions that would be expected to alter the interaction of RT with the template-primer, can alter both the efficiency and specificity of RNase H cleavage. These results are discussed in light of the structure of HIV-1 RT. (C) 1998 Academic Press Limited. C1 NCI, Frederick Canc Res & Dev Ctr, ABL Basic Res Program, Frederick, MD 21702 USA. Rutgers State Univ, Ctr Adv Biotechnol & Med, Piscataway, NJ 08854 USA. Rutgers State Univ, Dept Chem, Piscataway, NJ 08854 USA. RP Hughes, SH (reprint author), NCI, Frederick Canc Res & Dev Ctr, ABL Basic Res Program, POB B, Frederick, MD 21702 USA. NR 62 TC 65 Z9 66 U1 0 U2 1 PU ACADEMIC PRESS LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0022-2836 J9 J MOL BIOL JI J. Mol. Biol. PD APR 3 PY 1998 VL 277 IS 3 BP 559 EP 572 DI 10.1006/jmbi.1998.1624 PG 14 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA ZK501 UT WOS:000073328800006 PM 9533880 ER PT J AU Starich, MR Wikstrom, M Arst, HN Clore, GM Gronenborn, AM AF Starich, MR Wikstrom, M Arst, HN Clore, GM Gronenborn, AM TI The solution structure of a fungal AREA protein-DNA complex: An alternative binding mode for the basic carboxyl tail of GATA factors SO JOURNAL OF MOLECULAR BIOLOGY LA English DT Article DE AREA; GATA transcription factors; NMR structure; class IV zinc finger; cGATA-1 DBD ID NITROGEN METABOLITE REPRESSION; ASPERGILLUS-NIDULANS; 3-DIMENSIONAL STRUCTURES; TRANSCRIPTION FACTORS; DIRECT REFINEMENT; NUCLEIC-ACIDS; NMR; SPECTROSCOPY; SPECIFICITY; ACTIVATION AB The solution structure of a complex between the DNA binding domain of a fungal GATA factor and a 13 base-pair oligonucleotide containing its physiologically relevant CGATAG target sequence has been determined by multidimensional nuclear;magnetic resonance spectroscopy. The AREA DNA binding domain, from Aspergillus nidulans, possesses a single Cys(2)-Cys(2) zinc finger module smd a basic C-terminal tail, which recognize the CGATAG element via an extensive network of hydrophobic interactions with the bases in the major groove and numerous non-specific contacts along the sugar-phosphate backbone. The zinc finger core of the AREA DNA binding domain has the same global fold as that of the C-terminal DNA binding domain of chicken GATA-1. in contrast to the complex with the DNA binding domain of GATA-1 in which the basic C-terminal tail wraps around the DNA and lies in the minor groove, the structure of complex with the AREA DNA binding domain reveals that the C-terminal tail of the fungal domain runs parallel with the sugar phosphate backbone along the edge of the minor groove. This difference is principally attributed to amino acid substitutions at two positions of the AREA DNA binding domain (Val55, Asn62) relative to that of GATA-1 (Gly55, Lys62). The impact of the different C-terminal tail binding modes on the affinity and specificity of GATA factors is discussed. (C) 1998 Academic Press Limited. C1 NIDDK, Chem Phys Lab, NIH, Bethesda, MD 20892 USA. Hammersmith Hosp, Imperial Coll, Sch Med, Dept Infect Dis, London W12 0NN, England. RP Gronenborn, AM (reprint author), NIDDK, Chem Phys Lab, NIH, Bldg 5, Bethesda, MD 20892 USA. RI Clore, G. Marius/A-3511-2008 OI Clore, G. Marius/0000-0003-3809-1027 NR 50 TC 50 Z9 54 U1 0 U2 1 PU ACADEMIC PRESS LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0022-2836 J9 J MOL BIOL JI J. Mol. Biol. PD APR 3 PY 1998 VL 277 IS 3 BP 605 EP 620 DI 10.1006/jmbi.1998.1625 PG 16 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA ZK501 UT WOS:000073328800009 PM 9533883 ER PT J AU Starich, MR Wikstrom, M Schumacher, S Arst, HN Gronenborn, AM Clore, GM AF Starich, MR Wikstrom, M Schumacher, S Arst, HN Gronenborn, AM Clore, GM TI The solution structure of the Leu22 -> Val mutant AREA DNA binding domain complexed with a TGATAG core element defines a role for hydrophobic packing in the determination of specificity SO JOURNAL OF MOLECULAR BIOLOGY LA English DT Article DE AREA; GATA transcription factors; L22V mutant; NMR structure; zinc finger ID NITROGEN METABOLITE REPRESSION; INITIATOR CONSTITUTIVE MUTATION; ASPERGILLUS-NIDULANS; COMPUTER-ANALYSIS; TERMINAL REGION; GENE; NMR; SPECTROSCOPY; PROTEINS; PERMEASE AB The seemingly innocuous leucine-to-valine mutation at Position 22 of the AREA DNA binding domain results in dramatic changes in the in vivo expression Profile of genes controlled by this GATA transcription factor. This is associated with a Preference of the Leu22 --> Val mutant for TGATAG sites over (A/C)GATAG sites. Quantitative gel retardation assays confirm this observation and show that the Leu22 --> Val mutant AREA DNA binding domain has a similar to 30-fold lower affinity than the wild-type domain for a 13 base-pair oligonucleotide containing the wild-type CGATAG target. To gain insight into the measured affinity data and further explore sequence specificity of the AREA protein, the solution structure of a complex between the Leu22 --> Val mutant AREA DNA binding domain and a 13 base-pair oligonucleotide containing its physiologically relevant TGATAG target sequence has been determined by multidimensional nuclear magnetic resonance spectroscopy. Comparison of this structure with that of the wild-type AREA DNA binding domain complexed to its cognate CGATAG target site shows how subtle changes in amino acid side-chain length and hydrophobic packing car, affect affinity and specificity GATA-containing sequences, and how changes in DNA sequence be compensated for by changes in protein sequence. (C) 1998 Academic Press Limited. C1 NIDDK, Chem Phys Lab, NIH, Bethesda, MD 20892 USA. Hammersmith Hosp, Imperial Coll, Sch Med, Dept Infect Dis & Bacteriol, London W12 0NN, England. RP Gronenborn, AM (reprint author), NIDDK, Chem Phys Lab, NIH, Bldg 5, Bethesda, MD 20892 USA. RI Clore, G. Marius/A-3511-2008 OI Clore, G. Marius/0000-0003-3809-1027 NR 28 TC 32 Z9 33 U1 0 U2 0 PU ACADEMIC PRESS LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0022-2836 J9 J MOL BIOL JI J. Mol. Biol. PD APR 3 PY 1998 VL 277 IS 3 BP 621 EP 634 DI 10.1006/jmbi.1997.1626 PG 14 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA ZK501 UT WOS:000073328800010 PM 9533884 ER PT J AU Copie, V Tomita, Y Akiyama, SK Aota, S Yamada, KM Venable, RM Pastor, RW Krueger, S Torchia, DA AF Copie, V Tomita, Y Akiyama, SK Aota, S Yamada, KM Venable, RM Pastor, RW Krueger, S Torchia, DA TI Solution structure and dynamics of linked cell attachment modules of mouse fibronectin containing the RGD and synergy regions: Comparison with the human fibronectin crystal structure SO JOURNAL OF MOLECULAR BIOLOGY LA English DT Article DE fibronectin; cell adhesion; RGD region; NMR; protein flexibility ID ISOTOPICALLY ENRICHED PROTEINS; SIDE-CHAIN RESONANCES; N-15 NMR RELAXATION; CARBON-J-COUPLINGS; 3-DIMENSIONAL STRUCTURE; C-13-ENRICHED PROTEINS; ROTATIONAL DIFFUSION; C-13 MAGNETIZATION; ADHESIVE FUNCTION; LARGER PROTEINS AB We report the three-dimensional solution structure of the mouse fibronectin cell attachment domain consisting of the linked ninth and tenth type III modules, mFnFn3(9,10). Because the tenth module contains the RGD cell attachment sequence while the ninth contains the synergy region, mFnFn3(9,10) has the cell attachment activity of intact fibronectin. Essentially complete signal assignments and approximately 1800 distance and angle restraints were derived from multidimensional heteronuclear NMR spectra. These restraints were used with a hybrid distance geometry/simulated annealing protocol to generate an ensemble of 20 NMR structures having no distance or angle violations greater than 0.3 Angstrom or 3 degrees. Although the beta-sheet core domains of the individual modules are well-ordered structures, having backbone atom rmsd values from the mean structure of 0.51(+/-0.12) and 0.40(+/-0.07) Angstrom, respectively, the rmsd of the core atom coordinates increases to 3.63(+/-1.41) A when the core domains of both modules are used to align the coordinates. The latter result is a consequence of the fact that the relative orientation of the two modules is not highly constrained by the NMR restraints. Hence, while structures of the beta-sheet core domains of the NMR structures are very similar to the core domains of the crystal structure of hFnFn3(9,10), the ensemble of NMR structures suggests that the two modules form a less extended and more flexible structure than the fully extended rod-like crystal structure. The radius of gyration, R-g, of mFnFn3(9,10) derived from small-angle neutron scattering measurements, 20.5(+/-0.5) Angstrom, agrees with the average R-g calculated for the NMR structures, 20.4 Angstrom, and is ca 1 Angstrom less than the value of R-g calculated for the X-ray structure. The values of the rotational anisotropy, D-parallel to/D-perpendicular to, derived from an analysis of N-15 relaxation data, range from 1.7 to 2.1, and are significantly less than the anisotropy of 2.67 predicted by hydrodynamic modeling of the crystal coordinates. In contrast, hydrodynamic modeling of the NMR coordinates yields anisotropies in the range of 1.9 to 2.7 (average 2.4(+/-0.2)), with NMR structures bent by more than 20 degrees relative the crystal structure having calculated anisotropies in best agreement with experiment. In addition, the relaxation parameters indicate that several loops in mFnFn3(9,10), including the RGD loop, are flexible on the nanosecond to picosecond time-scale. Taken together, our results suggest that, in solution, the Limited set of interactions between the mFnFn3(9,10) modules position the RGD and synergy regions to interact specifically with tell surface integrins, and at the same time permit sufficient flexibility that allows mFnFn3(9,10) to adjust for some variation in integrin structure or environment. (C) 1998 Academic Press Limited. C1 NIDR, Struct Mol Biol Unit, NIH, Bethesda, MD 20892 USA. NIDR, Craniofacial Dev Biol & Regenerat Branch, NIH, Bethesda, MD 20892 USA. US FDA, Biophys Lab, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. NIST, Ctr Neutron Res, Gaithersburg, MD 20899 USA. RP Copie, V (reprint author), Montana State Univ, Dept Biochem & Chem, Bozeman, MT 59717 USA. OI Yamada, Kenneth/0000-0003-1512-6805 NR 59 TC 129 Z9 130 U1 0 U2 11 PU ACADEMIC PRESS LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0022-2836 J9 J MOL BIOL JI J. Mol. Biol. PD APR 3 PY 1998 VL 277 IS 3 BP 663 EP 682 PG 20 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA ZK501 UT WOS:000073328800013 PM 9533887 ER PT J AU Waalkes, MP Rehm, S AF Waalkes, MP Rehm, S TI Lack of carcinogenicity of cadmium chloride in female Syrian hamsters SO TOXICOLOGY LA English DT Article DE cadmium; necrosis induction; Syrian hamster; amyloidosis; testicular tumor ID TESTES; RATS AB Cadmium is very effective at inducing necrosis within the ovaries of rodents, and the Syrian hamster appears particularly sensitive. The extent of cadmium-induced necrosis depends on the stage of the estrous cycle and is most pronounced when injected on the day prior to ovulation (proestrous). In male rodents cadmium induces a similar necrosis within the testes, which given sufficient time can lead to the development of testicular tumors. In this study we tested the hypothesis that cadmium-induced ovarian necrosis could eventually lead to tumor formation. In sexually mature groups of female Syrian hamsters (> 8 weeks old; n = 50-59), the estrous cycle was determined by visual inspection of vaginal discharge for four consecutive cycles. The animals were then given cadmium (0, 30, 40 and 50 mu mol/kg) subcutaneously as a single injection in the dorsal thoracic midline on cycle day 4 (proestrous). Based on prior work, these doses are sufficient to induce extensive acute ovarian damage. Animals were then observed over the next 78 weeks. Although survival and body weight were reduced by cadmium, treatment with the metal did not result in an enhanced incidence of tumors at any site including the ovaries. Non-neoplastic lesions such as amyloidosis and pancreatic hepatocytes were linked to cadmium exposure. These results indicate that the association of cadmium-induced testicular necrosis with tumor development seen in males does not occur in the Syrian hamster ovaries. (C) 1998 Elsevier Science Ireland Ltd. All rights reserved. C1 NCI, Comparat Carcinogenesis Lab, Div Basic Sci, Frederick Canc Res & Dev Ctr, Frederick, MD 21702 USA. RP Waalkes, MP (reprint author), NIEHS, Inorgan Carcinogenesis Sect, Comparat Carcinogenesis Lab, NCI, 111 Alexander Dr,POB 12233,MD F0-09, Res Triangle Pk, NC 27709 USA. NR 15 TC 9 Z9 9 U1 1 U2 2 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0300-483X J9 TOXICOLOGY JI Toxicology PD APR 3 PY 1998 VL 126 IS 3 BP 173 EP 178 DI 10.1016/S0300-483X(98)00012-2 PG 6 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA ZU816 UT WOS:000074237900003 PM 9674965 ER PT J AU Agoston, GE Robarge, MJ Izenwasser, S Newman, AH AF Agoston, GE Robarge, MJ Izenwasser, S Newman, AH TI Novel N-substituted benztropine ligands selective for the dopamine transporter. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 NIDA, IRP, NIH, Baltimore, MD 21224 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD APR 2 PY 1998 VL 215 MA 155-MEDI BP U905 EP U905 PN 1 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA ZA911 UT WOS:000072414402930 ER PT J AU Ananthan, S Kezar, HS Carter, RL Porreca, F Davis, P Xu, H McCullough, K Dersch, CM Rothman, RB AF Ananthan, S Kezar, HS Carter, RL Porreca, F Davis, P Xu, H McCullough, K Dersch, CM Rothman, RB TI Synthesis and opioid receptor binding profiles of phenyl pyridomorphinans. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 So Res Inst, Birmingham, AL 35255 USA. Univ Arizona, Dept Pharmacol, Tucson, AZ 85724 USA. NIDA, Addict Res Ctr, Clin Psychopharmacol Sect, Baltimore, MD 21224 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD APR 2 PY 1998 VL 215 MA 150-MEDI BP U904 EP U904 PN 1 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA ZA911 UT WOS:000072414402925 ER PT J AU Boyd, MR AF Boyd, MR TI Discovery of naturally occurring inhibitors of human immunodeficiency virus (HIV). SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 NCI, Lab Drug Discovery Res & Dev, Dev Therapeut Program,Div Canc Treatment & Diag, Frederick Canc Res & Dev Ctr, Frederick, MD 21702 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD APR 2 PY 1998 VL 215 MA 131-ORGN BP U40 EP U40 PN 2 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA ZA912 UT WOS:000072414500132 ER PT J AU Brechbiel, MW Gansow, OA Wu, C Garmestani, K Yordanov, A Deal, K Chappell, L AF Brechbiel, MW Gansow, OA Wu, C Garmestani, K Yordanov, A Deal, K Chappell, L TI Chelated metal ions for therapeutic and diagnostic applications. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 NCI, Chem Sect, DCS, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD APR 2 PY 1998 VL 215 MA 106-NUCL BP U959 EP U959 PN 1 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA ZA911 UT WOS:000072414403094 ER PT J AU Cao, M Topol, IA Burt, SK Erickson, JW AF Cao, M Topol, IA Burt, SK Erickson, JW TI Quantum mechanical study of interactions between metal binding sites in zinc finger protein and disulfide compounds. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 NCI, Frederick Canc Res & Dev Ctr, FBSC, SBP,SAIC Frederick, Frederick, MD 21702 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD APR 2 PY 1998 VL 215 MA 124-COMP BP U539 EP U539 PN 1 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA ZA911 UT WOS:000072414401716 ER PT J AU Casimiro-Garcia, A Hejchman, E Ruell, JA Cushman, M Williamson, K Rice, WG AF Casimiro-Garcia, A Hejchman, E Ruell, JA Cushman, M Williamson, K Rice, WG TI Design, synthesis and biological evaluation of new alkenyldiarylmethanes (ADAMS) with enhanced potencies as anti-HIV-1 agents. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 Purdue Univ, Sch Pharm & Pharmacal Sci, Dept Med Chem & Mol Pharmacol, W Lafayette, IN 47907 USA. NCI, Frederick Canc Res & Dev Ctr, Lab Antiviral Drug Mechanisms, SAIC Frederick, Frederick, MD 21702 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD APR 2 PY 1998 VL 215 MA 029-MEDI BP U869 EP U869 PN 1 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA ZA911 UT WOS:000072414402806 ER PT J AU Contrera, J AF Contrera, J TI Monitoring licensees of PHS owned technology SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 NIH, Off Technol Transfer, Rockville, MD 20852 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD APR 2 PY 1998 VL 215 MA 020-CHAL BP U148 EP U148 PN 1 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA ZA911 UT WOS:000072414400471 ER PT J AU Eckelman, WC Lang, LX Jagoda, E Wu, CC Brechbiel, MW Gansow, A Pastan, I Paik, CH Carrasquillo, JA AF Eckelman, WC Lang, LX Jagoda, E Wu, CC Brechbiel, MW Gansow, A Pastan, I Paik, CH Carrasquillo, JA TI The role of kidney uptake in the choice of a therapeutic radionuclide. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 NIH, Bethesda, MD 20892 USA. RI Carrasquillo, Jorge/E-7120-2010 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD APR 2 PY 1998 VL 215 MA 055-NUCL BP U944 EP U944 PN 1 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA ZA911 UT WOS:000072414403044 ER PT J AU Guerra, MA AF Guerra, MA TI Balancing the needs of basic research and technology transfer SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 NCI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD APR 2 PY 1998 VL 215 MA 049-CHAL BP U155 EP U155 PN 1 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA ZA911 UT WOS:000072414400500 ER PT J AU Joslin-Akers, J Yagi, H Jerina, DM Cheh, AM AF Joslin-Akers, J Yagi, H Jerina, DM Cheh, AM TI Bacterial mutational spectra of dibenz[a,h]anthracene and benzo[c]chrysene diol epoxides. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 NIDDKD, Bioorgan Chem Lab, Bethesda, MD 20892 USA. American Univ, Dept Chem, Washington, DC 20016 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD APR 2 PY 1998 VL 215 MA 398-CHED BP U292 EP U292 PN 1 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA ZA911 UT WOS:000072414400912 ER PT J AU Keefer, LK AF Keefer, LK TI Nitric oxide (NO) and medicinal chemistry. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 NCI, Frederick Canc Res & Dev Ctr, Comparat Carcinogenesis Lab, Chem Sect, Frederick, MD 21702 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD APR 2 PY 1998 VL 215 MA 641-CHED BP U360 EP U360 PN 1 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA ZA911 UT WOS:000072414401158 ER PT J AU Kennel, SJ Boll, RA Mirzadeh, S AF Kennel, SJ Boll, RA Mirzadeh, S TI CHX-DTPA-antibody conjugates for vascular targeted radioimmunotherapy with Bi-213 and Y-90. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 Oak Ridge Natl Lab, Div Life Sci, Oak Ridge, TN 37831 USA. NCI, Radiat Oncol Branch, NIH, Rockville, MD 20892 USA. RI Boll, Rose/C-4138-2016 OI Boll, Rose/0000-0003-2507-4834 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD APR 2 PY 1998 VL 215 MA 089-NUCL BP U954 EP U954 PN 1 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA ZA911 UT WOS:000072414403078 ER PT J AU Lee, RE McNeil, MR Fleet, GWJ AF Lee, RE McNeil, MR Fleet, GWJ TI Synthesis of iminosugars possessing galactofuranosyl stereochemistry as potential inhibitors of mycobacterial cell wall biosynthesis. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 NIAID, Rocky Mt Lab, TB Res Unit, Hamilton, MT 59840 USA. Colorado State Univ, Dept Microbiol, Ft Collins, CO 80523 USA. Dyson Perrins Lab, Oxford OX1 3QY, England. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD APR 2 PY 1998 VL 215 MA 030-CARB BP U113 EP U113 PN 1 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA ZA911 UT WOS:000072414400358 ER PT J AU Samala, L Jagtap, PG Chaudhary, AG Chordia, MD Gharpure, M Gunathilaka, AAL Higgs, PI Rimoldi, JM Kingston, DGI Grover, S Lin, CM Hamel, E AF Samala, L Jagtap, PG Chaudhary, AG Chordia, MD Gharpure, M Gunathilaka, AAL Higgs, PI Rimoldi, JM Kingston, DGI Grover, S Lin, CM Hamel, E TI Synthesis and biological evaluation of 2-aroyl analogues of paclitaxels SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 Virginia Polytech Inst & State Univ, Dept Chem, Blacksburg, VA 24061 USA. NCI, Frederick Canc Res & Dev Ctr, Lab Drug Discovery R&D, DTP,DCTDC, Frederick, MD 21702 USA. RI Chordia, Mahendra/A-4706-2008 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD APR 2 PY 1998 VL 215 MA 176-MEDI BP U912 EP U912 PN 1 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA ZA911 UT WOS:000072414402950 ER PT J AU Scheinberg, DA Jurcic, J Finn, R Larson, S McDevitt, MR Geerlings, M Sgouros, G Brechbiel, M Gansow, OA AF Scheinberg, DA Jurcic, J Finn, R Larson, S McDevitt, MR Geerlings, M Sgouros, G Brechbiel, M Gansow, OA TI Clinical application of targeted alpha particles for cancer therapy SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. NCI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD APR 2 PY 1998 VL 215 MA 087-NUCL BP U953 EP U953 PN 1 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA ZA911 UT WOS:000072414403076 ER PT J AU Sokoloff, L AF Sokoloff, L TI Quantification and visualization of local metabolic and functional activities in brain in vivo. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 NIMH, Cerebral Metab Lab, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD APR 2 PY 1998 VL 215 MA 120-NUCL BP U963 EP U963 PN 1 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA ZA911 UT WOS:000072414403108 ER PT J AU Tomioka, K Adamczeski, M White, W AF Tomioka, K Adamczeski, M White, W TI Introducing two-dimensional NMR to sophomore organic chemistry students via an example of the sex and aggregation pheromone, (S)-cis-verbenol, a natural constituent in several species of bark beetles. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 American Univ, Dept Chem, Washington, DC 20016 USA. NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD APR 2 PY 1998 VL 215 MA 500-CHED BP U320 EP U320 PN 1 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA ZA911 UT WOS:000072414401013 ER PT J AU Waldmann, TA Brechbiel, M Garmestani, K Wu, C Schwarz, U Carrasquillo, J Eckelman, W Gansow, O AF Waldmann, TA Brechbiel, M Garmestani, K Wu, C Schwarz, U Carrasquillo, J Eckelman, W Gansow, O TI The IL-2/IL-15 receptor system: A target for immunotherapy of leukemia with humanized antibodies armed with beta and alpha emitting radionuclides. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 NIH, Bethesda, MD 20892 USA. RI Carrasquillo, Jorge/E-7120-2010 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD APR 2 PY 1998 VL 215 MA 076-NUCL BP U950 EP U950 PN 1 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA ZA911 UT WOS:000072414403065 ER PT J AU Wiener, EC Brechbiel, W Lauterbur, PC AF Wiener, EC Brechbiel, W Lauterbur, PC TI Factors influencing the design of dendrimer-based MRI contrast agents. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 Univ Illinois, Urbana, IL 61801 USA. NCI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD APR 2 PY 1998 VL 215 MA 088-NUCL BP U954 EP U954 PN 1 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA ZA911 UT WOS:000072414403077 ER PT J AU Wink, DA AF Wink, DA TI The chemical mechanisms in regulatory, cytotoxic, and cytoprotective roles of nitric oxide. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 NCI, Radiat Biol Branch, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD APR 2 PY 1998 VL 215 MA 640-CHED BP U360 EP U360 PN 1 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA ZA911 UT WOS:000072414401157 ER PT J AU Bulte, JWM Brooks, RA Moskowitz, BM Bryant, LH Frank, JA AF Bulte, JWM Brooks, RA Moskowitz, BM Bryant, LH Frank, JA TI T1 and T2 relaxometry of monocrystalline iron oxide nanoparticles (MION-46L): Theory and experiment SO ACADEMIC RADIOLOGY LA English DT Article; Proceedings Paper CT Symposium on Contrast Media Research CY MAY 18-22, 1997 CL KYOTO, JAPAN SP Bracco SpA, Milan, Italy, Bracco Res USA Inc, Princeton, NJ, Guerbet SA, Roissy, France, Mallinckrodt Med Inc, St Louis, MO, Nycomed Amersham AS, Olso, Norway, Schering AG, Berlin, Germany, Adv Magnet Inc, Princeton, NJ, ImaRx Pharm Corp, Tucson, AZ, DuPont Merck Pharm Co, N Billerica, Massachusetts, Alliance Pharm Corp, San Diego, Calif, Berlex Lab, Wayne, NJ, Bracco Res SA, Geneva, Switzerland, Ctr Invest Justesa Imagen SA, Madrid, Spain, EPIX Med Inc, Cambridge, Massachusetts, Molec Biosyst Inc, San Diego, Calif, Nycomed Amersham Imaging, Wayne, NJ ID MR RELAXATION-TIMES; FREQUENCY-DEPENDENCE; SPIN RELAXATION C1 NINDS, Lab Diagnost Radiol Res, NIH, Bethesda, MD 20892 USA. NINDS, Neuroimaging Branch, NIH, Bethesda, MD 20892 USA. Univ Minnesota, Dept Geol & Geophys, Minneapolis, MN 55455 USA. RP Bulte, JWM (reprint author), NINDS, Lab Diagnost Radiol Res, NIH, B10,B1N256,10 Ctr Dr MSC 1074, Bethesda, MD 20892 USA. RI Bulte, Jeff/A-3240-2008 OI Bulte, Jeff/0000-0003-1202-1610 NR 13 TC 19 Z9 19 U1 0 U2 2 PU ASSOC UNIV RADIOLOGISTS PI OAK BROOK PA 2021 SPRING RD, STE 600, OAK BROOK, IL 60521 USA SN 1076-6332 J9 ACAD RADIOL JI Acad. Radiol. PD APR PY 1998 VL 5 SU 1 BP S137 EP S140 DI 10.1016/S1076-6332(98)80084-6 PG 4 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA ZJ367 UT WOS:000073207400043 PM 9561064 ER PT J AU Wilbur, WJ AF Wilbur, WJ TI The knowledge in multiple human relevance judgments SO ACM TRANSACTIONS ON INFORMATION SYSTEMS LA English DT Article DE algorithms; experimentation; measurement; performance; document retrieval test set construction; human relevance judgments; inverse document frequency weights; log odds of relevance; minimal-length least-squares fit; vector model; word weights ID DOCUMENT-RETRIEVAL SYSTEM; PERFORMANCE AB We show first that the pooling of multiple human judgments of relevance provides a predictor of relevance that is Superior to that obtained from a single human's relevance judgments. A learning algorithm applied to a set of relevance judgments obtained from a single human would be expected to perform on new material at a level somewhat below that human. However, we examine two learning methods which when trained on the superior source of pooled human relevance judgments are able to perform at the level of a single human on new material. All performance comparisons are based on an independent human judge. Both algorithms function by producing term weights - one by a log odds calculation and the other by producing a least-squares fit to human relevance ratings. Some characteristics of the algorithms are examined. C1 Natl Ctr Biotechnol Informat, NIH, Bethesda, MD USA. RP Wilbur, WJ (reprint author), Natl Lib Med, Bldg 38A,Rm 8S806,8600 Rockville Pike, Bethesda, MD 20894 USA. NR 33 TC 6 Z9 6 U1 0 U2 0 PU ASSOC COMPUTING MACHINERY PI NEW YORK PA 1515 BROADWAY, NEW YORK, NY 10036 USA SN 1046-8188 J9 ACM T INFORM SYST JI ACM Trans. Inf. Syst. PD APR PY 1998 VL 16 IS 2 BP 101 EP 126 DI 10.1145/279339.279340 PG 26 WC Computer Science, Information Systems SC Computer Science GA 106GN UT WOS:000075121700001 ER PT J AU Teikari, JM Laatikainen, L Virtamo, J Haukka, J Rautalahti, M Liesto, K Albanes, D Taylor, P Heinonen, OP AF Teikari, JM Laatikainen, L Virtamo, J Haukka, J Rautalahti, M Liesto, K Albanes, D Taylor, P Heinonen, OP TI Six-year supplementation with alpha-tocopherol and beta-carotene and age-related maculopathy SO ACTA OPHTHALMOLOGICA SCANDINAVICA LA English DT Article DE alpha-tocopherol; beta-carotene; antioxidant; vitamin; ARM; macula; degeneration; visual acuity; AMD; maculopathy ID MACULAR DEGENERATION; VITAMIN-E; LENS OPACITIES; RAT RETINA; DAMAGE; LIGHT; ANTIOXIDANTS; PREVALENCE; BLINDNESS; ASCORBATE AB Purpose: Animal research and observational studies in man suggest a protective effect of antioxidant vitamins in the development of age-related maculopathy (ARM). Methods: The ATBC study a population-based, controlled clinical trial of alpha-tocopherol and beta carotene to prevent lung cancer, took place in Finland between 1983 and 1993, Over 29,000 smoking males aged 50 to 69 years were randomly assigned to alpha-tocopherol (AT; 50 mg/day), beta-carotene (BC; 20 mg/day), both of these, or placebo. We performed an end-of-trial ophthalmological examination on a random sample of 941 participants aged 65 years or more from two of the fourteen study areas, to discover if the five to eight-year intervention with alpha-tocopherol and/or beta-carotene had been associated with a difference in ARM prevalence. Age-related maculopathy was assessed using colour photographs of the macula. Results: Altogether, 269 cases of ARM were found; there were more cases in the AT group (32%; 75/237), BC group (29%; 68/234), and combined antioxidant group (28%; 73/257) than in the placebo group (25%; 53/213), However, neither substance was significantly associated with the risk of ARM in a logistic regression analysis controlling for possible risk factors. Conclusions: No beneficial effect of long-term supplementation,vith alpha-tocopherol or beta-carotene on the occurrence of ARM was detected among smoking males. C1 Univ Helsinki, Dept Ophthalmol, Helsinki, Finland. Univ Helsinki, Dept Publ Hlth, Helsinki, Finland. Natl Publ Hlth Inst, Helsinki, Finland. Laakso Hosp, Helsinki, Finland. NCI, NIH, Bethesda, MD 20892 USA. RP Teikari, JM (reprint author), Sepankatu 7 A 23, Helsinki 00150, Finland. EM teikari@pp.kolumbus.fi RI Albanes, Demetrius/B-9749-2015; Haukka, Jari/G-1484-2014 OI Haukka, Jari/0000-0003-1450-6208 FU NCI NIH HHS [N01-CN-45165] NR 41 TC 63 Z9 66 U1 0 U2 1 PU SCRIPTOR PUBLISHER PI HVIDOVRE PA SOVANGSVEJ 1-5, DK-2650 HVIDOVRE, DENMARK SN 1395-3907 J9 ACTA OPHTHALMOL SCAN JI Acta Ophthalmol. Scand. PD APR PY 1998 VL 76 IS 2 BP 224 EP 229 DI 10.1034/j.1600-0420.1998.760220.x PG 6 WC Ophthalmology SC Ophthalmology GA ZG777 UT WOS:000073038300020 PM 9591958 ER PT J AU Kuhlman, JJ Levine, B Johnson, RE Fudala, PJ Cone, EJ AF Kuhlman, JJ Levine, B Johnson, RE Fudala, PJ Cone, EJ TI Relationship of plasma buprenorphine and norbuprenorphine to withdrawal symptoms during dose induction, maintenance and withdrawal from sublingual buprenorphine SO ADDICTION LA English DT Article ID METHADONE-MAINTENANCE; OPIOID DEPENDENCE; OPIATE ADDICTION; CONTROLLED TRIAL; PHARMACOKINETICS AB Aims. Examine the relationship between buprenorphine and norbuprenorphine plasma concentrations with subject-reported withdrawal symptomatology during buprenorphine dose induction, maintenance treatment (daily and alternate-day dosing) and withdrawal. Design. Two groups of randomly assigned subjects inducted onto buprenorphine and maintained on 8 mg daily by the sublingual route for 18 days. Group 1 continued to receive daily buprenorphine to day 36. Group 2 subjects received alternate-day dosing of buprenorphine and placebo on days 19 to 36. Both groups received placebo on days 37 to 52. Setting. Inpatient facilities at the Addiction Research Center, Intramural Research Center, NIDA, Baltimore, MD. Participants. Eleven male, heroin-dependent volunteers participating in a research study. Intervention. Medications for treatment of withdrawal symptoms were prescribed as needed after day 39 (72 hours after the last dose of buprenorphine). Measurements. Plasma concentrations of buprenorphine and norbuprenorphine, withdrawal symptomatology and pupil diameter. Findings. The mean steady-state buprenorphine plasma concentration (24 hours) after daily administration a sublingual buprenorphine for study days 21-35 teas 0.80 ng/ml, and the mean alternate day steady-stare buprenorphine plasma concentration (24 hours) was 0.77 ng/ml. Daily and alternate day steady-state norbuprenorphine plasma concentrations were 1.10 and 0.90 ng/ml, respectively. Predicted alternate day steady-state buprenorphine and norbuprenorphine plasma concentrations at 48 hours were 0.49 ng/ml and 0.57 ng/ml, respectively. Withdrawal scores varied inversely with plasma concentration. There were no significant differences between Groups 1 and 2 during steady-state (days 21-35) with regard to withdrawal scale scores or pupillary diameter. The overall, mean terminal elimination half-lives for buprenorphine and norbuprenorphine were 42 and 57 hours, respectively. Conclusions. During daily buprenorphine maintenance, plasma concentrations greater than 0.7 ng/ml of buprenorphine and norbuprenorphine were associated with minimal withdrawal symptoms. The long elimination half-life of buprenorphine suggested that increasing the buprenorphine dose with alternate-day administration may provide an effective, flexible therapy regimen for the treatment of opioid dependence. C1 NIDA, Intramural Res Program, Addict Res Ctr, NIH, Baltimore, MD 21224 USA. Armed Forces Inst Pathol, Div Forens Toxicol, Washington, DC 20306 USA. Johns Hopkins Bayview Med Ctr, Dept Psychiat, Johns Hopkins Sch Med, Behav Pharmacol Res Units, Baltimore, MD USA. Univ Penn, Sch Med, Dept Psychiat, Philadelphia, PA 19104 USA. RP Cone, EJ (reprint author), NIDA, Intramural Res Program, Addict Res Ctr, NIH, POB 5180, Baltimore, MD 21224 USA. NR 39 TC 83 Z9 85 U1 0 U2 0 PU CARFAX PUBL CO PI ABINGDON PA PO BOX 25, ABINGDON, OXFORDSHIRE, ENGLAND OX14 3UE SN 0965-2140 J9 ADDICTION JI Addiction PD APR PY 1998 VL 93 IS 4 BP 549 EP 559 DI 10.1046/j.1360-0443.1998.93454910.x PG 11 WC Substance Abuse; Psychiatry SC Substance Abuse; Psychiatry GA ZJ556 UT WOS:000073228600010 PM 9684393 ER PT J AU Yim, MB Yim, HS Chock, PB Stadtman, ER AF Yim, MB Yim, HS Chock, PB Stadtman, ER TI Pro-oxidant activity of Cu,Zn-superoxide dismutase SO AGE LA English DT Article; Proceedings Paper CT Symposium on Oxygen Radicals and Aging CY MAY 01, 1997 CL PHILADELPHIA, PENNSYLVANIA SP Franklin Inst, Nathan Shock Ctr Excellence Basic Biol Aging, Natl Inst Aging, Johnson & Johnson, Amer Federat Aging Res ID AMYOTROPHIC-LATERAL-SCLEROSIS; CU,ZN SUPEROXIDE-DISMUTASE; HYDROGEN-PEROXIDE; TRANSGENIC MICE; K-M; MUTATIONS; GENE; COPPER; CELLS; SUPEROXIDE-DISMUTASE-1 C1 NHLBI, Biochem Lab, NIH, Bethesda, MD 20892 USA. RP Yim, MB (reprint author), NHLBI, Biochem Lab, NIH, Bldg 3,Room 202, Bethesda, MD 20892 USA. NR 27 TC 6 Z9 6 U1 0 U2 0 PU AMER AGING ASSOC PI MEDIA PA SALLY BALIN MEDICAL CENTER, 110 CHESLEY DR, MEDIA, PA 19063 USA SN 0161-9152 J9 AGE JI Age PD APR PY 1998 VL 21 IS 2 BP 91 EP 93 DI 10.1007/s11357-998-0013-9 PG 3 WC Geriatrics & Gerontology SC Geriatrics & Gerontology GA 160YZ UT WOS:000078262100008 PM 23604358 ER PT J AU Levine, RL AF Levine, RL TI Oxidative stress and aging SO AGING-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Article; Proceedings Paper CT International Conference on Biomedical Aspects of Aging Research CY DEC 10-13, 1997 CL FDN CINI SAN GIORGIO, VENICE, ITALY SP Amer Federat Aging Res, US, Univ Padova Italy, Natl Res Council, Ctr Study Aging, Nat Inst Aging, US, NIH, US, UN, Div Social Policies & Dev HO FDN CINI SAN GIORGIO C1 NHLBI, Biochem Lab, NIH, Bethesda, MD 20892 USA. RP Levine, RL (reprint author), NHLBI, Biochem Lab, NIH, Bldg 3, Bethesda, MD 20892 USA. RI Levine, Rodney/D-9885-2011 NR 0 TC 3 Z9 3 U1 0 U2 0 PU EDITRICE KURTIS S R L PI MILAN PA VIA LUIGI ZOJA 30, 20153 MILAN, ITALY SN 0394-9532 J9 AGING-CLIN EXP RES JI Aging-Clin. Exp. Res. PD APR PY 1998 VL 10 IS 2 BP 151 EP 151 PG 1 WC Geriatrics & Gerontology SC Geriatrics & Gerontology GA ZX376 UT WOS:000074509400018 PM 9666203 ER PT J AU McGowan, JA AF McGowan, JA TI NIH-supported intervention trials in osteoporosis SO AGING-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Article; Proceedings Paper CT International Conference on Biomedical Aspects of Aging Research CY DEC 10-13, 1997 CL FDN CINI SAN GIORGIO, VENICE, ITALY SP Amer Federat Aging Res, US, Univ Padova Italy, Natl Res Council, Ctr Study Aging, Nat Inst Aging, US, NIH, US, UN, Div Social Policies & Dev HO FDN CINI SAN GIORGIO C1 NIAMSD, NIH, Bethesda, MD 20892 USA. RP McGowan, JA (reprint author), NIAMSD, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU EDITRICE KURTIS S R L PI MILAN PA VIA LUIGI ZOJA 30, 20153 MILAN, ITALY SN 0394-9532 J9 AGING-CLIN EXP RES JI Aging-Clin. Exp. Res. PD APR PY 1998 VL 10 IS 2 BP 160 EP 160 PG 1 WC Geriatrics & Gerontology SC Geriatrics & Gerontology GA ZX376 UT WOS:000074509400031 PM 9666216 ER PT J AU Lakatta, EG AF Lakatta, EG TI Aging and cardiovascular structure and function in healthy sedentary humans SO AGING-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Article; Proceedings Paper CT International Conference on Biomedical Aspects of Aging Research CY DEC 10-13, 1997 CL FDN CINI SAN GIORGIO, VENICE, ITALY SP Amer Federat Aging Res, US, Univ Padova Italy, Natl Res Council, Ctr Study Aging, Nat Inst Aging, US, NIH, US, UN, Div Social Policies & Dev HO FDN CINI SAN GIORGIO C1 NIA, Gerontol Res Ctr, NIH, Baltimore, MD 21224 USA. RP Lakatta, EG (reprint author), NIA, Gerontol Res Ctr, NIH, 4940 Eastern Ave, Baltimore, MD 21224 USA. NR 3 TC 3 Z9 3 U1 0 U2 1 PU EDITRICE KURTIS S R L PI MILAN PA VIA LUIGI ZOJA 30, 20153 MILAN, ITALY SN 0394-9532 J9 AGING-CLIN EXP RES JI Aging-Clin. Exp. Res. PD APR PY 1998 VL 10 IS 2 BP 162 EP 164 PG 3 WC Geriatrics & Gerontology SC Geriatrics & Gerontology GA ZX376 UT WOS:000074509400034 PM 9666219 ER PT J AU Haseltine, FP AF Haseltine, FP TI HIV: A reproductive hazard - The biology of HIV transmission SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Editorial Material C1 NICHHD, Populat Res Ctr, Bethesda, MD 20892 USA. RP Haseltine, FP (reprint author), NICHHD, Populat Res Ctr, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA SN 0889-2229 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD APR PY 1998 VL 14 SU 1 BP S1 EP S2 PG 2 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA ZJ673 UT WOS:000073240600001 ER PT J AU Hild-Petito, S Veazey, RS Larner, JM Reel, JR Blye, RP AF Hild-Petito, S Veazey, RS Larner, JM Reel, JR Blye, RP TI Effects of two progestin-only contraceptives, Depo-Provera and Norplant-II, on the vaginal epithelium of rhesus monkeys SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Article; Proceedings Paper CT Conference on the Reproductive Tract and HIV-1 Transmission CY FEB 11-12, 1997 CL BETHESDA, MARYLAND SP Natl Inst Child Hlth & Human Dev, Off Res Womens Hlth, Natl Inst Allery & Infect Dis, Natl Inst Diabet & Digest & Kidney Dis, Off AIDS Res, Soc Adv Womens Hlth Res ID IMPLANTS AB The objective of this study was to determine whether progestin-only contraceptives induce thinning of the vaginal epithelium in nonhuman primates. Eight intact rhesus monkeys (four per group) mere treated with either a single intramuscular injection of 30 mg of Depo-Provera or a subcutaneous insertion of Norplant-II (2 x 75 mg rods; day 0). Norplant-II rods were removed 90 days after insertion. Vaginal biopsies were obtained during a pretreatment menstrual cycle and following treatment on days 10, 30, 60, 118, and 146. Formalin-fixed vaginal biopsies were evaluated for epithelial thickness and the degree of keratinization. The circulating levels of estradiol, progesterone, medroxyprogesterone acetate (MPA), or levonorgestrel (LNG) were monitored throughout the study by specific radioimmunoassays. Circulating levels of estradiol and progesterone confirmed the stage of the menstrual cycle in which pretreatment biopsies were obtained. Following treatment with Depo-Provera, serum levels of MPA increased to 2.3 +/- 0.6 ng/ml ((x) over bar +/- SE, n = 4) within 24 hr. Serum levels of MPA mere maximal on day 14 (5.5 +/- 0.9 ng/ml), dropped below 1 ng/ml by day 50, and were nondetectable by day 70. Circulating levels of LNG were elevated 24 hr after insertion of Norplant-II (5.8 +/- 3.0 ng/ml), peaked on day 2 (7.6 +/- 4.2 ng/ml), remained between 1.4 and 6.2 ng/ml from days 14 to 90, and were nondetectable by day 118, the first serum sample after removal of Norplant-II. There mere no significant differences (p > 0.05) in the epithelial thickness (mu m), number of epithelial cell layers, or type of epithelium present in vaginal biopsies obtained during the follicular or luteal phases of the pretreatment menstrual cycle. Conversely, a pronounced effect of progestin treatment was observed on the vaginal epithelium. There were no significant differences (p > 0.05) between the two progestin treatment groups, but a significant effect (p < 0.05) over time was observed (two-way ANOVA). Compared with pretreatment menstrual cycle controls, the vaginal epithelial thickness was decreased (p < 0.05) by day 30 or 60 following Norplant-II insertion or Depo-Provera injection, respectively. The number of epithelial cell layers was also decreased (p < 0.05) on days 30 and/or 60 in progestin-treated monkeys compared with pretreatment control cycles. Following removal of Norplant II or metabolic excretion of MPA, the vaginal epithellium regenerated and the thickness was no longer different (p > 0.05) from the pretreatment control cycle. These data demonstrate that progestin-only contraceptives induced thinning of the vaginal epithelium in rhesus monkeys, and this effect was rapidly reversible following physical or metabolic removal of the progestin. C1 BIOQUAL Inc, Rockville, MD 20850 USA. Harvard Univ, Sch Med, Southborough, MA 01772 USA. NICHHD, Contracept & Reprod Hlth Branch, Rockville, MD 20852 USA. RP Hild-Petito, S (reprint author), BIOQUAL Inc, 9600 Med Ctr Dr, Rockville, MD 20850 USA. FU NICHD NIH HHS [N01-HD-6-3259] NR 10 TC 46 Z9 46 U1 0 U2 3 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA SN 0889-2229 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD APR PY 1998 VL 14 SU 1 BP S125 EP S130 PG 6 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA ZJ673 UT WOS:000073240600024 PM 9581896 ER PT J AU Dawson, DA AF Dawson, DA TI Proceedings: International Workshop on Consumption Measures and Models for Use in Policy Development and Evaluation SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Article; Proceedings Paper CT International Workshop on Consumption Measures and Models for Use in Policy Development and Evaluation CY MAY 12-14, 1997 CL BETHESDA, MARYLAND AB The International Workshop on Consumption Measures and Models for Use in Policy Development and Evaluation was held in Bethesda, MD, on May 12-14, 1997. Participants included the following: Salme Ahlstrom, Finland; Time Alanko, Finland; Loran Archer, USA; Susan Bendy, Canada; Fe Caces, USA; Raul Caetano, USA; Deborah Dawson, USA; Kaye Fillmore, USA; Kathryn Graham, Canada; Thomas Greenfield, USA; Paul Gruenewald, USA; Thomas Harford, USA; Deborah Hasin, USA; Michael Hilton, USA; Harold Holder, USA; Bryan Johnstone, USA; Ronald Knibbe, Netherlands; Eckhart Kuhlhorn, Sweden; Paul Lemmens, Netherlands; Klaus Makela, Finland; Maria Elena Medina-Mora, Mexico; Lorraine Midanik, USA; M. W. Bud Perrine, USA; Jurgen Rehm, Canada; Anders Romelsjo, Sweden; Robin Room, Canada; Marcia Russell, USA; John Searles, USA; Eric Single, Canada; Linda Sobell, USA; Tim Stockwell, Australia; Gerald Williams, USA; Richard Wilsnack, USA. C1 NIAAA, DBE, NIH, Bethesda, MD 20892 USA. RP Dawson, DA (reprint author), NIAAA, DBE, NIH, Willco Bldg,Suite 514,6000 Execut Blvd,MSC 7003, Bethesda, MD 20892 USA. NR 0 TC 5 Z9 5 U1 1 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD APR PY 1998 VL 22 IS 2 SU S BP 1S EP 3S DI 10.1111/j.1530-0277.1998.tb04367.x PG 3 WC Substance Abuse SC Substance Abuse GA ZK324 UT WOS:000073307700001 ER PT J AU Robin, RW Long, JC Rasmussen, JK Albaugh, B Goldman, D AF Robin, RW Long, JC Rasmussen, JK Albaugh, B Goldman, D TI Relationship of binge drinking to alcohol dependence, other psychiatric disorders, and behavioral problems in an American Indian tribe SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Article DE alcoholism; binge drinking; American Indian ID DIAGNOSTIC INTERVIEW; SCHIZOPHRENIA; SCHEDULE AB The hypothesis that binge drinking is a benign behavior not associated with alcohol dependence, other psychiatric disorders, or problem areas, in American Indians, was tested in a sample of 582 adult Southwestern American Indian males and females in large multigenerational pedigrees. All information was obtained from semistructured psychiatric interviews that were independently blind-rated for DSM-III-R diagnoses, Three main outcome measures were used: the relationship between binge drinking and (1) alcohol dependence and other psychiatric disorders, (2) substance abuse treatment, and (3) four behavioral problem categories-violence/lawlessness, physical, social, and work. Binge drinking and alcohol dependence were strongly associated. Most hinge drinkers were diagnosed as alcohol dependent. However, when controlling far alcohol dependence and other covariates, binge drinking was independently associated with an increase in odds for positive diagnoses for multiple psychiatric disorders, and far social, work, physical, and violence/lawlessness behavioral problems. In sum, binge drinking was found to be a common and severe problem with deleterious consequences in multiple domains of functioning. Assessment instruments should be designed to elicit information on binge patterns of drinking and strategies devised to provide appropriate treatment. C1 NIAAA, Neurogenet Lab, NIH, Rockville, MD 20852 USA. Ctr Human Behav Studies Inc, Weatherford, OK USA. RP Robin, RW (reprint author), NIAAA, Neurogenet Lab, NIH, POB 617, Sitka, AK 99835 USA. RI Goldman, David/F-9772-2010 OI Goldman, David/0000-0002-1724-5405 NR 52 TC 94 Z9 94 U1 2 U2 9 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD APR PY 1998 VL 22 IS 2 BP 518 EP 523 DI 10.1111/j.1530-0277.1998.tb03682.x PG 6 WC Substance Abuse SC Substance Abuse GA ZJ534 UT WOS:000073226400033 PM 9581662 ER PT J AU Fruchart, JC Brewer, B Leitersdorf, E Brochier, M Brown, G Calvo, C Carmena, R Ceska, R Loy-Soong, WC Davignon, J Gotto, A Grundy, S Hamsten, A Keech, A Matsuzawa, Y Patch, JR Paoletti, R Raslova, K Smirnov, V Steiner, G Thompson, G Zhu, JR AF Fruchart, JC Brewer, B Leitersdorf, E Brochier, M Brown, G Calvo, C Carmena, R Ceska, R Loy-Soong, WC Davignon, J Gotto, A Grundy, S Hamsten, A Keech, A Matsuzawa, Y Patch, JR Paoletti, R Raslova, K Smirnov, V Steiner, G Thompson, G Zhu, JR TI Consensus for the use of fibrates in the treatment of dyslipoproteinemia and coronary heart disease SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Editorial Material ID LOW-DENSITY-LIPOPROTEIN; APOLIPOPROTEIN-C-III; DEPENDENT DIABETES-MELLITUS; PROLIFERATOR-ACTIVATED RECEPTOR; MIDDLE-AGED MEN; ARTERY DISEASE; MYOCARDIAL-INFARCTION; RISK-FACTORS; COMBINED HYPERLIPIDEMIA; CHOLESTEROL REDUCTION AB The hypolipidemic action of fibrates has recently been shown to involve the activation of peroxisome proliferator activated receptors establishing a molecular mechanism for this class of drugs. Increasing clinical trial evidence supports the efficacy of fibrates in the treatment of dyslipoproteinemias, particularly in patients with hypertriglyceridemia and low high-density lipoproteins. C1 Inst Pasteur, INSERM, U325, F-59019 Lille, France. NHLBI, NIH, Bethesda, MD 20892 USA. Hadassah Univ Hosp, Div Med, IL-91120 Jerusalem, Israel. RP Fruchart, JC (reprint author), Inst Pasteur, INSERM, U325, 1 Rue Prof Clamette, F-59019 Lille, France. RI Ceska, Richard/A-1840-2017 OI Ceska, Richard/0000-0002-2541-5179 NR 100 TC 144 Z9 145 U1 1 U2 6 PU EXCERPTA MEDICA INC PI NEW YORK PA 245 WEST 17TH STREET, NEW YORK, NY 10011 USA SN 0002-9149 J9 AM J CARDIOL JI Am. J. Cardiol. PD APR 1 PY 1998 VL 81 IS 7 BP 912 EP + PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA ZF712 UT WOS:000072924500016 PM 9555782 ER PT J AU Dwyer, JT Stone, EJ Yang, MH Feldman, H Webber, LS Must, A Perry, CL Nader, PR Parcel, GS AF Dwyer, JT Stone, EJ Yang, MH Feldman, H Webber, LS Must, A Perry, CL Nader, PR Parcel, GS CA Cardiovasc Hlth Collaborative Res Grp TI Predictors of overweight and overfatness in a multiethnic pediatric population SO AMERICAN JOURNAL OF CLINICAL NUTRITION LA English DT Article DE obesity; overweight; fatness; body mass index; triceps skinfold thickness; children; Child and Adolescent Trial for Cardiovascular Health; CATCH; African Americans ID CARDIOVASCULAR RISK-FACTORS; BODY-MASS INDEX; PHYSICAL-ACTIVITY; PRESCHOOL-CHILDREN; ADOLESCENT TRIAL; BLOOD-PRESSURE; BOGALUSA HEART; ENERGY-INTAKE; FOLLOW-UP; OBESITY AB The goal of the study was to determine whether overweight or overfatness were predicted from sex, race or ethnicity, school site, and intervention or control status for children who were 9 y old at the outset of the Child and Adolescent Trial for Cardiovascular Health (CATCH). In this ethnically and geographically diverse group of 5106 students, height, weight, and triceps skinfold thickness were measured at 9 (baseline) and 11 y (follow-up) of age. The strongest predictors of status at follow-up were baseline overweight (odds ratio: 69.0; 95% CI: 54.9, 96.3) and overfatness (odds ratio: 27.4; 95% CI: 22.4, 33.4); site, African American race or ethnicity, and male sex were also significant independent associations. Children in the overweight (>85th percentile for body mass index) group had significantly higher adjusted means for total blood cholesterol, higher apolipoprotein B concentrations, lower mean HDL-cholesterol concentrations, and lower performance on the 9-min run than those in other groups (<15th, 15-49th, or 50-85th body mass index percentiles). Similar results were found for these factors for those subjects with greater triceps skinfold-thickness measurements. Groups of children who were overweight and overfat at baseline were more likely to be overweight and overfat at follow-up and to have more cardiovascular risk factors than their peers. C1 New England Res Inst, Watertown, MA 02172 USA. New England Med Ctr, Frances Stern Nutr Ctr, Boston, MA 02111 USA. Tufts Univ, Sch Med, Boston, MA 02111 USA. Tufts Univ, Sch Nutr Sci & Policy, Boston, MA 02111 USA. Tufts Univ, Dept Family Med & Community Hlth, Boston, MA 02111 USA. NHLBI, NIH, Bethesda, MD 20892 USA. Tulane Univ, Sch Publ Hlth & Trop Med, Dept Epidemiol & Biostat, New Orleans, LA USA. Univ Minnesota, Sch Publ Hlth, Div Epidemiol, Minneapolis, MN 55455 USA. Univ Calif San Diego, Community Pediat Div, La Jolla, CA 92093 USA. Univ Texas, Houston Hlth Sci Ctr, Houston, TX USA. RP Dwyer, JT (reprint author), New England Res Inst, 9 Galen St, Watertown, MA 02172 USA. EM johanna.dwyer@es.nemc.org OI Dwyer, Johanna/0000-0002-0783-1769 FU NHLBI NIH HHS [U01-HL-39927, U01-HL-39880, U01-HL-39906] NR 54 TC 64 Z9 67 U1 0 U2 1 PU AMER SOC CLINICAL NUTRITION PI BETHESDA PA 9650 ROCKVILLE PIKE, SUBSCRIPTIONS, RM L-3300, BETHESDA, MD 20814-3998 USA SN 0002-9165 J9 AM J CLIN NUTR JI Am. J. Clin. Nutr. PD APR PY 1998 VL 67 IS 4 BP 602 EP 610 PG 9 WC Nutrition & Dietetics SC Nutrition & Dietetics GA ZE350 UT WOS:000072783800004 PM 9537606 ER PT J AU Fleming, DJ Jacques, PF Dallal, GE Tucker, KL Wilson, PWF Wood, RJ AF Fleming, DJ Jacques, PF Dallal, GE Tucker, KL Wilson, PWF Wood, RJ TI Dietary determinants of iron stores in a free-living elderly population: The Framingham Heart Study SO AMERICAN JOURNAL OF CLINICAL NUTRITION LA English DT Review DE serum ferritin; iron bioavailability; heme; meat intake; aging; iron absorption; dietary pattern; the elderly; vitamin C ID ASCORBIC-ACID SUPPLEMENTATION; NON-HEME IRON; SERUM FERRITIN; NONHEME-IRON; FOOD IRON; MENSTRUATING WOMEN; PLASMA FERRITIN; EXTRINSIC TAG; BIOCHEMICAL INDEXES; ALCOHOL-CONSUMPTION AB Epidemiologic studies have found a relation between body iron stores and risk of chronic disease. Iron-absorption studies from single meals have shown that many dietary factors can influence nonheme-iron bioavailability. However, little is known about the association of these dietary factors with iron stores in free-living elderly populations. To address this question, we investigated the consumption of various dietary components and iron stores in an elderly sample of The Framingham Heart Study participants. Serum ferritin was used as a measure of body iron stores in 634 free-living elderly (67-93 y of age), and dietary intake during the previous year was assessed by a food-frequency questionnaire. The relation between serum ferritin and various dietary factors was assessed by multiple regression analysis. Subjects whose ferritin concentrations might be pathologically elevated because of infection, inflammation, liver disease, or genetic hemochromatosis were excluded from the analysis. After we controlled for sex, age, body mass index, total energy intake, smoking, and use of aspirin and other medications known to affect blood loss, we found five significant dietary factors associated with iron stores. Heme iron, supplemental iron, dietary vitamin C, and alcohol were positively associated with serum ferritin, whereas coffee intake had a negative association. As expected, sex was a strong predictor of serum ferritin-women having significantly lower mean concentrations than men. However, age was not related to serum ferritin in our elderly population. Our results suggest that in typical Western-style diets, a small number of dietary factors probably modulate the bioavailability of dietary iron and influence the accumulation of iron stores. C1 Tufts Univ, Human Nutr Res Ctr Aging, Jean Mayer US Dept Agr, Mineral Bioavailabil Lab,Epidemiol Program, Boston, MA 02111 USA. Tufts Univ, Human Nutr Res Ctr Aging, Jean Mayer US Dept Agr, Div Biostat, Boston, MA 02111 USA. NHLBI, Framingham Heart Study, Framingham, MA USA. RP Wood, RJ (reprint author), Tufts Univ, Human Nutr Res Ctr Aging, Jean Mayer US Dept Agr, Mineral Bioavailabil Lab,Epidemiol Program, 711 Washington St, Boston, MA 02111 USA. EM wood_mb@hnrc.tufts.edu RI Tucker, Katherine/A-4545-2010; OI Tucker, Katherine/0000-0001-7640-662X FU NHLBI NIH HHS [N01-HC-38038, R01-HL-40423-05]; NINDS NIH HHS [2-R01-NS-17950-12] NR 144 TC 108 Z9 110 U1 0 U2 7 PU AMER SOC NUTRITION-ASN PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0002-9165 J9 AM J CLIN NUTR JI Am. J. Clin. Nutr. PD APR PY 1998 VL 67 IS 4 BP 722 EP 733 PG 12 WC Nutrition & Dietetics SC Nutrition & Dietetics GA ZE350 UT WOS:000072783800018 PM 9537620 ER PT J AU Montello, MJ Greenblatt, JJ Fallavollita, A Shoemaker, D AF Montello, MJ Greenblatt, JJ Fallavollita, A Shoemaker, D TI Accessing investigational anticancer agents outside of clinical trials SO AMERICAN JOURNAL OF HEALTH-SYSTEM PHARMACY LA English DT Letter ID PACLITAXEL; CANCER C1 NCI, Protocol & Informat Off, Canc Therapy Evaluat Program, Div Canc Treatment & Diag, Bethesda, MD 20892 USA. NCI, Regulatory Affairs Drug Sect, Canc Therapy Evaluat Program, Div Canc Treatment & Diag, Bethesda, MD 20892 USA. NCI, Pharmaceut Management Branch, Canc Therapy Evaluat Program, Div Canc Treatment & Diag, Bethesda, MD 20892 USA. NCI, Regulatory Affairs Branch, Canc Therapy Evaluat Program, Div Canc Treatment & Diag, Bethesda, MD 20892 USA. RP Montello, MJ (reprint author), NCI, Protocol & Informat Off, Canc Therapy Evaluat Program, Div Canc Treatment & Diag, Execut Plaza N,Room 707, Bethesda, MD 20892 USA. NR 5 TC 1 Z9 1 U1 0 U2 0 PU AMER SOC HEALTH-SYSTEM PHARMACISTS PI BETHESDA PA 7272 WISCONSIN AVE, BETHESDA, MD 20814 USA SN 1079-2082 J9 AM J HEALTH-SYST PH JI Am. J. Health-Syst. Pharm. PD APR 1 PY 1998 VL 55 IS 7 BP 651 EP + PG 3 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA ZF463 UT WOS:000072900000007 PM 9558419 ER PT J AU Griffith, AJ Sprunger, LK Sirko-Osadsa, DA Tiller, GE Meisler, MH Warman, ML AF Griffith, AJ Sprunger, LK Sirko-Osadsa, DA Tiller, GE Meisler, MH Warman, ML TI Marshall syndrome associated with a splicing defect at the COL11A1 locus SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Article ID COLLAGEN GENE COL11A1; ALPHA-1(XI) COLLAGEN; PRO-ALPHA-1(XI) COLLAGEN; STICKLER SYNDROME; MOLECULAR-BASIS; EXPRESSION; TISSUE; XI; MUTATION; LINKAGE AB Marshall syndrome is a rare, autosomal dominant skeletal dysplasia that is phenotypically similar to the more common disorder Stickler syndrome. For a large kindred with Marshall syndrome, we demonstrate a splice-donor-site mutation in the COL11A1 gene that cosegregates with the phenotype. The G(+1)-->A transition causes in-frame skipping of a 54-bp exon and deletes amino acids 726-743 from the major triple-helical domain of the alpha 1(XI) collagen polypeptide. The data support the hypothesis that the alpha 1(XI) collagen polypeptide has an important role in skeletal morphogenesis that extends beyond its contribution to structural integrity of the cartilage extracellular matrix. Our results also demonstrate allelism of Marshall syndrome with the subset of Stickler syndrome families associated with COL11A1 mutations. C1 Univ Michigan, Dept Human Genet, Ann Arbor, MI 48109 USA. Univ Michigan, Dept Otolaryngol Head & Neck Surg, Ann Arbor, MI 48109 USA. Case Western Reserve Univ, Sch Med, Dept Genet, Cleveland, OH 44106 USA. Case Western Reserve Univ, Sch Med, Dept Pediat, Cleveland, OH 44106 USA. Univ Hosp Cleveland, Ctr Human Genet, Cleveland, OH 44106 USA. Vanderbilt Univ, Sch Med, Dept Pediat, Nashville, TN 37212 USA. RP Griffith, AJ (reprint author), NIDCD, NIH, 5 Res Court,Room 2A01, Rockville, MD 20850 USA. RI Sprunger, Leslie/A-7840-2010 FU NHLBI NIH HHS [K08 HL02792]; NIAMS NIH HHS [AR01925]; NIGMS NIH HHS [GM24872] NR 43 TC 73 Z9 77 U1 0 U2 3 PU UNIV CHICAGO PRESS PI CHICAGO PA 5801 S ELLIS AVENUE, CHICAGO, IL 60637 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD APR PY 1998 VL 62 IS 4 BP 816 EP 823 DI 10.1086/301789 PG 8 WC Genetics & Heredity SC Genetics & Heredity GA ZM197 UT WOS:000073514400012 PM 9529347 ER PT J AU Liang, Y Wang, AH Probst, FJ Arhya, IN Barber, TD Chen, KS Deshmukh, D Dolan, DF Hinnant, JT Carter, LE Jain, PK Lalwani, AK Li, XYC Lupski, JR Moeljopawiro, S Morell, R Negrini, C Wilcox, ER Winata, S Camper, SA Friedman, TB AF Liang, Y Wang, AH Probst, FJ Arhya, IN Barber, TD Chen, KS Deshmukh, D Dolan, DF Hinnant, JT Carter, LE Jain, PK Lalwani, AK Li, XYC Lupski, JR Moeljopawiro, S Morell, R Negrini, C Wilcox, ER Winata, S Camper, SA Friedman, TB TI Genetic mapping refines DFNB3 to 17p11.2, suggests multiple alleles of DFNB3, and supports homology to the mouse model shaker-2 SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Article ID SMITH-MAGENIS SYNDROME; SOMATIC-CELL HYBRIDS; RECESSIVE DEAFNESS; LOCALIZATION; MUTATION; CHROMOSOME-17; CLONING; REGION; MAPS; DNA AB The nonsyndromic congenital recessive deafness gene, DFNB3, first identified in Bengkala, Bali, was mapped to a similar to 12-cM interval on chromosome 17. New short tandem repeats (STRs) and additional DNA samples were used to identify recombinants that constrain the DFNB3 interval to less than or similar to 6 cM on 17p11.2. Affected individuals from Bengkala and affected members of a family with hereditary deafness who were from Bila, a village neighboring Bengkala, were homozygous for the same alleles for six adjacent STRs in the DFNB3 region and were heterozygous for other distal markers, thus limiting DFNB3 to an similar to 3-cM interval. Nonsyndromic deafness segregating in two unrelated consanguineous Indian families, M21 and I-1924, were also linked to the DFNB3 region. Haplotype analysis indicates that the DFNB3 mutations in the three pedigrees most likely arose independently and suggests that DFNB3 makes a significant contribution to hereditary deafness worldwide. On the basis of conserved synteny, mouse deafness mutations shaker-2 (sh2) and sh2(J) are proposed as models of DFNB3. Genetic mapping has refined sh2 to a 0.6-cM interval of chromosome 11. Three homologous genes map within the sh2 and DFNB3 intervals, suggesting that sh2 is the homologue of DFNB3. C1 Natl Inst Deafness & Commun Disorders, Mol Genet Lab, NIH, Rockville, MD 20850 USA. Michigan State Univ, Dept Religious Studies, E Lansing, MI USA. Michigan State Univ, Grad Program Genet, E Lansing, MI USA. Univ Michigan, Dept Human Genet, Ann Arbor, MI 48109 USA. Univ Michigan, Kresge Hearing Res Inst, Ann Arbor, MI 48109 USA. Udayana Univ, Fac Med, Dept Biochem, Denpasar, Indonesia. Udayana Univ, Fac Med, Dept Microscop Anat, Denpasar, Indonesia. Baylor Coll Med, Dept Mol & Human Genet, Houston, TX 77030 USA. Rotary Deaf Sch, Ichalkaranji, India. Epstein Labs, Mol Oncol Lab, San Francisco, CA USA. Gadjah Mada Univ, Fac Biol, Biochem Lab, Yogyakarta, Indonesia. Gadjah Mada Univ, Interuniv Ctr Biotechnol, Yogyakarta, Indonesia. RP Friedman, TB (reprint author), Natl Inst Deafness & Commun Disorders, Mol Genet Lab, NIH, 5 Res Court,Room 2A01, Rockville, MD 20850 USA. RI Chen, Ken-Shiung/A-2204-2011; OI Morell, Robert/0000-0003-1537-7356; Camper, Sally/0000-0001-8556-3379 FU NIDCD NIH HHS [Z01 DC00035, Z01 DC00038, R01 DC02407] NR 47 TC 35 Z9 37 U1 0 U2 3 PU UNIV CHICAGO PRESS PI CHICAGO PA 5801 S ELLIS AVENUE, CHICAGO, IL 60637 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD APR PY 1998 VL 62 IS 4 BP 904 EP 915 DI 10.1086/301786 PG 12 WC Genetics & Heredity SC Genetics & Heredity GA ZM197 UT WOS:000073514400022 PM 9529344 ER PT J AU Weinberg, CR Wilcox, AJ Lie, RT AF Weinberg, CR Wilcox, AJ Lie, RT TI A log-linear approach to case-parent-triad data: Assessing effects of disease genes that act either directly or through maternal effects and that may be subject to parental imprinting SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Article ID HLA-ASSOCIATED RISKS; LINKAGE DISEQUILIBRIUM; FINNISH POPULATION; RELATIVE RISKS; TESTS AB We describe a log-linear method for analysis of case-parent-triad data, based on maximum likelihood with stratification on parental mating type. The method leads to estimates of association parameters, such as relative risks, for a single allele, and also to likelihood ratio chi(2) tests (LRTs) of linkage disequilibrium. Hardy-Weinberg equilibrium need not be assumed. Our simulations suggest that the LRT has power similar to that of the chi(2) "score" test proposed by Schaid and Sommer and that both can outperform the transmission/disequilibrium test (TDT), although the TDT can perform better under an additive model of inheritance. Because a restricted version of the LRT is asymptotically equivalent to the TDT, the proposed test can be regarded as a generalization of the TDT. The method that we describe generalizes easily to accommodate maternal effects on risk and, in fact, produces powerful and orthogonal tests of the contribution of fetal versus maternal genetic factors. We further generalize the model to allow for effects of parental imprinting. Imprinting effects can be fitted by a simple, iterative procedure that relies on the expectation-maximization algorithm and that uses standard statistical software for the maximization steps. Simulations reveal that LRT tests for detection of imprinting have very good operating characteristics. When a single allele is under study, the proposed method can yield powerful tests for detection of linkage disequilibrium and is applicable to a broader array of causal scenarios than is the TDT. C1 NIEHS, Biostat Branch, Res Triangle Pk, NC 27709 USA. NIEHS, Epidemiol Branch, Res Triangle Pk, NC 27709 USA. Univ Bergen, Sect Med Stat, Bergen, Norway. RP Weinberg, CR (reprint author), NIEHS, Biostat Branch, MD A3-03,POB 12233, Res Triangle Pk, NC 27709 USA. OI Wilcox, Allen/0000-0002-3376-1311 NR 14 TC 295 Z9 298 U1 0 U2 4 PU UNIV CHICAGO PRESS PI CHICAGO PA 5801 S ELLIS AVENUE, CHICAGO, IL 60637 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD APR PY 1998 VL 62 IS 4 BP 969 EP 978 DI 10.1086/301802 PG 10 WC Genetics & Heredity SC Genetics & Heredity GA ZM197 UT WOS:000073514400029 PM 9529360 ER PT J AU Becker, JA Vlach, J Raben, N Nagaraju, K Adams, EM Hermans, MM Reuser, AJJ Brooks, SS Tifft, CJ Hirschhorn, R Huie, ML Nicolino, M Plotz, PH AF Becker, JA Vlach, J Raben, N Nagaraju, K Adams, EM Hermans, MM Reuser, AJJ Brooks, SS Tifft, CJ Hirschhorn, R Huie, ML Nicolino, M Plotz, PH TI The African origin of the common mutation in African American patients with glycogen-storage disease type II SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Letter ID LYSOSOMAL ALPHA-GLUCOSIDASE; MISSENSE MUTATION; POMPE DISEASE; POINT MUTATION; MESSENGER-RNA; ONE ALLELE; IDENTIFICATION; EXPRESSION; DELETION; SUBSTITUTION C1 George Washington Univ, Childrens Natl Med Ctr, Washington, DC 20010 USA. George Washington Univ, Dept Amer Studies & Anthropol, Washington, DC 20010 USA. NIAMSD, Arthrit & Rheumatism Branch, NIH, Bethesda, MD 20892 USA. Erasmus Univ, Dept Clin Genet, NL-3000 DR Rotterdam, Netherlands. New York State Inst Basic Res Dev Disabil, Staten Isl, NY 10314 USA. NYU, Med Ctr, Div Med Genet, New York, NY 10016 USA. Hop Debrousse, Dept Endocrinol Pediat, Lyon, France. RP Plotz, PH (reprint author), NIAMSD, Arthrit & Rheumatism Branch, NIH, Bethesda, MD 20892 USA. NR 27 TC 23 Z9 28 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5801 S ELLIS AVENUE, CHICAGO, IL 60637 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD APR PY 1998 VL 62 IS 4 BP 991 EP 994 DI 10.1086/301788 PG 4 WC Genetics & Heredity SC Genetics & Heredity GA ZM197 UT WOS:000073514400034 PM 9529346 ER PT J AU Pinkerton, LE Biagini, RE Ward, EM Hull, RD Deddens, JA Boeniger, MF Schnorr, TM MacKenzie, BA Luster, MI AF Pinkerton, LE Biagini, RE Ward, EM Hull, RD Deddens, JA Boeniger, MF Schnorr, TM MacKenzie, BA Luster, MI TI Immunologic findings among lead-exposed workers SO AMERICAN JOURNAL OF INDUSTRIAL MEDICINE LA English DT Article DE lead; immune system; CD4+ T lymphocyte; immunoglobulins ID CELLULAR IMMUNE FUNCTION; MONOCLONAL-ANTIBODIES; IMMUNOGLOBULIN; HEALTH AB A comprehensive panel of immune parameters was evaluated among 145 lead-exposed workers with a median blood lead level (BLL) of 39 mu g/dL (range: 15-55 mu g/dL) and 84 unexposed workers. After adjusting for covariates, we found no major differences in the percentage of CD3+ cells, CD4+ T cells, CD8+ T cells, B cells, or NK cells between lead-exposed and unexposed workers, although the association between lead exposure and the number of CD4+ T cells was modified by age. We also found no differences between exposed and unexposed workers in serum immunoglobulin levels, salivary IgA, C3 complement levels, or lymphoproliferative responses. However among exposed workers, the percentage and number of B cells were positively associated with current BLL, serum IgG was negatively associated with cumulative lead exposure, and the percentage and number of CD4+/CD45RA+ cells were positively associated with cumulative lead exposure. We found no evidence of a marked immunotoxic effect of lead at the exposure levels studied, although some subtle differences in immunologic parameters were noted. (C) 1998 Wiley-Liss, Inc. C1 NIOSH, Cincinnati, OH 45226 USA. Univ Cincinnati, Dept Math Sci, Cincinnati, OH 45221 USA. Natl Inst Environm Hlth Sci, Res Triangle Pk, NC USA. RP Pinkerton, LE (reprint author), 4676 Columbia Pkwy,R-15, Cincinnati, OH 45226 USA. NR 25 TC 24 Z9 24 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0271-3586 J9 AM J IND MED JI Am. J. Ind. Med. PD APR PY 1998 VL 33 IS 4 BP 400 EP 408 DI 10.1002/(SICI)1097-0274(199804)33:4<400::AID-AJIM11>3.0.CO;2-2 PG 9 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA YZ546 UT WOS:000072264900011 PM 9513648 ER PT J AU Xu, S Jordan, EK Li, W Yang, YH Chesnick, SA Webster, HD Brocke, S Quigley, L McFarland, HF Frank, JA AF Xu, S Jordan, EK Li, W Yang, YH Chesnick, SA Webster, HD Brocke, S Quigley, L McFarland, HF Frank, JA TI In vivo three-dimensional MR microscopy of mice with chronic relapsing experimental autoimmune encephalomyelitis after treatment with insulin-like growth factor-I SO AMERICAN JOURNAL OF NEURORADIOLOGY LA English DT Article ID MAGNETIC-RESONANCE MICROSCOPY; EXPERIMENTAL ALLERGIC ENCEPHALOMYELITIS; MOUSE AB PURPOSE: The purpose of this study was to determine the ability of three-dimensional in vivo MR microscopy to depict the treatment effects of insulin-like growth factor-I (IGF-I) in SJL mice with chronic relapsing experimental autoimmune encephalomyelitis (crEAE). METHODS: The experiments were performed at 4.7-T on 10 crEAE mice and on one set of control animals. Five crEAE mice were treated with IGF-I and five were treated with a placebo. RESULTS: In the crEAE mice treated with the placebo, in vivo MR microscopy showed areas of abnormal signal throughout the cerebrum, brain stem, and cerebellum. These findings were not present in either the IGF-I-treated mice or the normal control animals. The diffuse alterations in signal intensity in the placebo-treated crEAE mice were not identified on histologic sections of the same areas. CONCLUSION: Differences between the IGF-I-and placebo-treated groups may reflect changes in stabilization or permeability of cell membranes and/or of the blood-brain barrier, although other alternative contrast mechanisms could be playing a role. In vivo MR microscopy depicted changes resulting from treatment of crEAE with IGF-I. C1 NIH, Lab Diagnost Radiol Res, Bethesda, MD 20892 USA. NIH, Expt Neuropathol Lab, Bethesda, MD 20892 USA. NIH, Cardiac Energet Lab, Bethesda, MD 20892 USA. NIH, Neuroimmunol Branch, Bethesda, MD 20892 USA. RP Frank, JA (reprint author), NIH, Lab Diagnost Radiol Res, Bldg 10,Room B1N-256, Bethesda, MD 20892 USA. NR 20 TC 9 Z9 9 U1 0 U2 0 PU AMER SOC NEURORADIOLOGY PI OAK BROOK PA 2210 MIDWEST RD, OAK BROOK, IL 60521 USA SN 0195-6108 J9 AM J NEURORADIOL JI Am. J. Neuroradiol. PD APR PY 1998 VL 19 IS 4 BP 653 EP 658 PG 6 WC Clinical Neurology; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA ZH516 UT WOS:000073118900011 PM 9576650 ER PT J AU Spong, CY Ghidini, A Ossandon, M Walker, CN Pezzullo, JC AF Spong, CY Ghidini, A Ossandon, M Walker, CN Pezzullo, JC TI Are the cytokines interleukin-6 and angiogenin stable in frozen amniotic fluid? SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Article DE cytokines; prolonged freezing; stability ID PRETERM LABOR; PREGNANCY; DIAGNOSIS; BLOOD AB OBJECTIVE: To determine the stability of cytokines in frozen stored amniotic fluid samples, we measured angiogenin, a potent inducer of neovascularization and interleukin-6, an inflammatory cytokine, in the same sample of midtrimester amniotic fluid 1 year apart. STUDY DESIGN: In this study paired aliquots of amniotic fluid kept at -70 degrees C were immunoassayed for angiogenin and interleukin-6 at two different time periods 1 year apart. Inclusion criteria were (1) samples with clearly identifiable numbers, (2) no evidence of breaks in sealing of samples, and (3) singleton gestation. Amniotic fluid was immunoassayed for angiogenin and interleukin-6 in July 1995 and 1996. Angiogenin sensitivities were 0.078 and 0.026 ng/ml, interassay coefficients of variation were 3.8% and 4.6%, and intraassay coefficients of variation were 2.7% and 2.9%, respectively, in 1995 and 1996. Interleukin-6 sensitivities were 1.74 and 2.37 pg/ml, interassay coefficients of variation were 8.9% and 2.6%, and intraassay coefficients of variation were 3.5% and 1.9%, respectively, in 1995 and 1996. Statistical analysis included paired t test, Wilcoxon signed-rank test, and regression with p < 0.05 significant. Angiogenin and interleukin-6 values were normalized with natural log transformation for statistical analysis. RESULTS: Paired amniotic fluid samples from 30 patients were immunoassayed from 1993 to 1995. The values of angiogenin were significantly lower in the 1996 assay compared with the 1995 assay (median 12.4 [range 5.6 to 61.3] vs 26.7 [range 13.6 to 159.2] ng/ml, p < 0.001). A significant correlation was found between the change in angiogenin levels and the year of the sample, with older samples having the greatest change in values (r = 0.5, p = 0.008). The values of interleukin-6 were significantly lower in the 1996 assay compared with the 1995 assay (median 230.8 [range 40.9 to 3711.3] vs 289.2 [range 53.7 to 19100.0] pg/ml, p < 0.001). CONCLUSIONS: Angiogenin and interleukin-6 values in amniotic fluid appear to decrease with time despite optimal freezing conditions. The year of sampling and length of storage should be taken into consideration when evaluating amniotic fluid cytokine levels from stored samples. C1 NICHHD, Dev Neurobiol Lab, NIH, Bethesda, MD USA. Georgetown Univ, Med Ctr, Dept Obstet & Gynecol, Washington, DC 20057 USA. Georgetown Univ, Med Ctr, Dept Biostat & Biomath, Washington, DC 20057 USA. RP Spong, CY (reprint author), NICHD, Dev Neurobiol Lab, NIH, Bldg 49,Room 5A-38,9000 Rockville Pike, Bethesda, MD 20892 USA. NR 11 TC 7 Z9 7 U1 0 U2 1 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD APR PY 1998 VL 178 IS 4 BP 783 EP 786 DI 10.1016/S0002-9378(98)70492-2 PG 4 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA ZK773 UT WOS:000073362100021 PM 9579444 ER PT J AU Wank, SA AF Wank, SA TI G protein-coupled receptors in gastrointestinal physiology I. CCK receptors: an exemplary family SO AMERICAN JOURNAL OF PHYSIOLOGY-GASTROINTESTINAL AND LIVER PHYSIOLOGY LA English DT Article DE cholecystokinin; gastrin; expression; cDNA; signal transduction ID CHOLECYSTOKININ RECEPTOR; GASTRIN RECEPTOR; FUNCTIONAL EXPRESSION; RAT PANCREAS; CELL; AFFINITY; CLONING; VIVO AB The CCK and gastrin families of peptides act as hormones and neuropeptides on central and peripheral receptors to mediate secretion and motility in the gastrointestinal tract in the physiological response to a normal meal. Thus far, two CCK receptors have been molecularly identified to mediate the actions of CCK and gastrin, CCK-A and CCK-B receptors (CCK-AR and CCK-BR, respectively). The regulation of CCK-AR and CCK-BR affinity by guanine nucleotides and the receptor activation of G protein-dependent stimulation of phospholipase C and adenylyl cyclase suggested that they were guanine nucleotide-binding protein-coupled receptors [G protein-coupled receptors (GPCRs)]; however, the eventual cloning of their cDNAs revealed their heptahelical structure and confirmed their membership in the GPCR superfamily. The gastrointestinal system is a rich source of neuroendocrine hormones that interact with a large number of GPCRs to regulate the complex tasks of digestion, absorption, and excretion of a meal. This article focuses on the CCK family of GPCRs, and its activities in the gastrointestinal system. C1 NIDDKD, Digest Dis Branch, NIH, Bethesda, MD 20892 USA. RP Wank, SA (reprint author), NIDDKD, Digest Dis Branch, NIH, Bldg 10,Rm 9C103, Bethesda, MD 20892 USA. NR 32 TC 175 Z9 178 U1 0 U2 2 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0193-1857 J9 AM J PHYSIOL-GASTR L JI Am. J. Physiol.-Gastroint. Liver Physiol. PD APR PY 1998 VL 274 IS 4 BP G607 EP G613 PG 7 WC Gastroenterology & Hepatology; Physiology SC Gastroenterology & Hepatology; Physiology GA ZG637 UT WOS:000073023800002 PM 9575840 ER PT J AU Gambassi, G Spurgeon, HA Ziman, BD Lakatta, EG Capogrossi, MC AF Gambassi, G Spurgeon, HA Ziman, BD Lakatta, EG Capogrossi, MC TI Opposing effects of alpha(1)-adrenergic receptor subtypes on Ca2+ and pH homeostasis in rat cardiac myocytes SO AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY LA English DT Article DE alpha-adrenoceptor subtypes; chloroethylclonidine; WB-4101; indo 1; cardiac inotropy; cytosolic pH ID RABBIT PAPILLARY-MUSCLE; CANINE PURKINJE-FIBERS; ALPHA-1-ADRENERGIC RECEPTOR; ALPHA-ADRENOCEPTORS; MOLECULAR-CLONING; BETA-ADRENOCEPTORS; INTRACELLULAR PH; CYTOSOLIC PH; HEART-CELLS; MYOFILAMENTS AB We examined the effect of alpha(1)-adrenergic receptor !AR) subtypes on contraction, cytosolic Ca2+ concentration ([Ca2+](i)), and cytosolic pH (pH(i)) of rat ventricular myocytes loaded with the Ca2+ indicator indo 1 or the pH indicator carboxy-seminaphthorhodafluor-1. Nonselective alpha(1)-AR stimulation was effected with phenylephrine plus nadolol. alpha(1)-AR subtype stimulation was achieved with alpha(1)-AR and chloroethylclonidine (CEC) or with alpha(1)-AR and WB-4101. Cells were in bicarbonate buffer with 0.5 mM Ca2+ and were electrically stimulated at 0.5 Hz. Results show that I) nonselective alpha(1)-AR stimulation increased twitch and [Ca2+](i) transient amplitudes, myofilament response to Ca2+, and pH(i); 2) alpha(1)-AR plus CEC increased twitch and [Ca2+](i) transient amplitudes and also enhanced myofilament response to Ca2+ via cytosolic alkalinization; 3) alpha(1)-AR plus WB-4101 decreased twitch and [Ca2+](i) transient amplitudes and also pH(i); and 4) cytosolic acidification due to alpha(1)-AR plus WB-4101 was abolished by protein kinase C inhibition (staurosporine pretreatment) or downregulation (prolonged exposure to phorbol esters). In summary, the net effects of alpha(1)-adrenergic stimulation on contraction, [Ca2+](i), and pH(i) are due to opposing WB-4101- and CEC-sensitive alpha(1)-AR subtype signaling pathways. C1 NIA, Cardiovasc Sci Lab, Gerontol Res Ctr, NIH, Baltimore, MD 21224 USA. RP Capogrossi, MC (reprint author), Ist Ricovero & Cura Carattere Sci, Ist Dermopat Immacolata, Lab Patol Vasc, Via Monti Creta 104, I-00167 Rome, Italy. NR 32 TC 28 Z9 28 U1 0 U2 1 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0363-6135 J9 AM J PHYSIOL-HEART C JI Am. J. Physiol.-Heart Circul. Physiol. PD APR PY 1998 VL 274 IS 4 BP H1152 EP H1162 PG 11 WC Cardiac & Cardiovascular Systems; Physiology; Peripheral Vascular Disease SC Cardiovascular System & Cardiology; Physiology GA ZE869 UT WOS:000072839800012 PM 9575918 ER PT J AU Burg, MB Peters, EM AF Burg, MB Peters, EM TI Effects of glycine betaine and glycerophosphocholine on thermal stability of ribonuclease SO AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY LA English DT Article DE counteracting osmolytes; kidney medulla; trimethylamine N-oxide; urea; inositol; taurine; sorbitol ID MEDULLARY ORGANIC OSMOLYTES; ELASMOBRANCH FISHES; UREA; PROTEIN; SOLUTES; RAT AB Urea in renal medullas is sufficiently high to perturb macromolecules, yet the cells survive and function. The counteracting osmolytes hypothesis holds that methylamines, such as glycine betaine (betaine) and glycerophosphocholine (GPC) in renal medullas, stabilize macromolecules and oppose the effects of urea. Although betaine counteracts effects of urea on macromolecules in vitro and protects renal cells from urea in tissue culture, renal cells accumulate GPC rather than betaine in response to high urea both in vivo and in tissue culture. A proposed explanation is that GPC counteracts urea more effectively than betaine. However, we previously found GPC slightly less effective than betaine in counteracting inhibition of pyruvate kinase activity by urea. To test another macromolecule, we now compare GPC and betaine in counteracting reduction of the thermal stability of RNase A by urea. We find that urea decreases the thermal transition temperature and that betaine and GPC increase it, counteracting urea approximately equally. Therefore, the preference for GPC in response to high urea presumably has some other basis, such as a lower metabolic cost of GPC accumulation. C1 NHLBI, Kidney & Electrolyte Metab Lab, Bethesda, MD 20892 USA. RP Burg, MB (reprint author), NIH, Bldg 10,Rm 6N260, Bethesda, MD 20892 USA. NR 16 TC 17 Z9 17 U1 0 U2 0 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 APR PY 1998 VL 274 IS 4 BP F762 EP F765 PG 4 WC Physiology; Urology & Nephrology SC Physiology; Urology & Nephrology GA ZG511 UT WOS:000073011000017 PM 9575901 ER PT J AU Schlaepfer, TE Strain, EC Greenberg, BD Preston, KL Lancaster, E Bigelow, GE Barta, PE Pearlson, GD AF Schlaepfer, TE Strain, EC Greenberg, BD Preston, KL Lancaster, E Bigelow, GE Barta, PE Pearlson, GD TI Site of opioid action in the human brain: Mu and kappa agonists' subjective and cerebral blood flow effects SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Article; Proceedings Paper CT Annual Meeting of the American-Psychiatric-Association CY MAY 20-25, 1995 CL MIAMI, FLORIDA SP Amer Psychiat Assoc ID PRECIPITATED WITHDRAWAL; DRUG DISCRIMINATION; ANTAGONIST OPIOIDS; OPIATE RECEPTOR; HYDROMORPHONE; MORPHINE; COCAINE; SPECT AB Objective: Humans experience the subjective effects of mu and kappa opioid agonists differently: mu agonists produce mainly euphoria, while kappa agonists are more likely to produce dysphoria. This study tested the hypothesis that these subjective effects would be associated with anatomically distinct changes in regional cerebral blood flow (CBF) relative to baseline as assessed with single photon emission computed tomography (SPECT). Method: Nine nondependent opioid abusers participated in the study. In the first phase of the study, the participants were acclimated to effects of the study drugs. In the second phase they underwent repeat challenges with the study drugs followed by an assessment of CBF with use of the SPECT tracer [99mTc]HMPAO. Medications tested were the prototypic mu agonist hydromorphone, the mixed agonist/antagonist butorphanol (which has a kappa agonist component of activity), and saline placebo. Results: Subjective effects of the drugs were distinctly different. Hydromorphone produced increased ratings of "good effects," while butorphanol led to more "bad effects." Hydromorphone significantly increased regional CBF in the anterior cingulate cortex, both amygdalae, and the thalamus-all structures belonging to the limbic system. Butorphanol caused a less distinct picture of regional CBF increases, mainly in the area of both temporal lobes. Conclusions: This study demonstrates that opioids with different subjective effects also produce statistically significant patterns of change in regional CBF from baseline, and the regions of statistical significance appear in different brain regions. In addition, these results demonstrate the applicability of SPECT functional neuroimaging in the study of medications with potential abuse liability. C1 Univ Hosp Bern, Dept Psychiat, Psychiat Neuroimaging Grp, CH-3010 Bern, Switzerland. Johns Hopkins Med Inst, Dept Psychiat, Div Psychiat Neuroimaging, Baltimore, MD 21205 USA. Johns Hopkins Med Inst, Dept Psychiat, Behav Pharmacol Res Unit, Baltimore, MD 21205 USA. NIMH, Clin Sci Lab, Bethesda, MD 20892 USA. NIDA, Addict Res Ctr, Baltimore, MD 21224 USA. RP Schlaepfer, TE (reprint author), Univ Hosp Bern, Dept Psychiat, Psychiat Neuroimaging Grp, Murtenstr 21, CH-3010 Bern, Switzerland. RI Preston, Kenzie/J-5830-2013; OI Preston, Kenzie/0000-0003-0603-2479; Schlaepfer, Thomas/0000-0003-0612-9692 FU NCRR NIH HHS [RR-00035] NR 25 TC 81 Z9 84 U1 0 U2 4 PU AMER PSYCHIATRIC ASSOCIATION PI WASHINGTON PA 1400 K ST NW, WASHINGTON, DC 20005 USA SN 0002-953X J9 AM J PSYCHIAT JI Am. J. Psychiat. PD APR PY 1998 VL 155 IS 4 BP 470 EP 473 PG 4 WC Psychiatry SC Psychiatry GA ZF739 UT WOS:000072928100005 PM 9545990 ER PT J AU Diehr, P Bild, DE Harris, TB Duxbury, A Siscovick, D Rossi, M AF Diehr, P Bild, DE Harris, TB Duxbury, A Siscovick, D Rossi, M TI Body mass index and mortality in nonsmoking older adults: The cardiovascular health study SO AMERICAN JOURNAL OF PUBLIC HEALTH LA English DT Article ID NUTRITIONAL-STATUS; NATIONAL-HEALTH; ELDERLY-MEN; WEIGHT-LOSS; WOMEN; AGE; ASSOCIATIONS; IMPACT AB Objectives. This study assesses the relationship of body mass index to 5-year mortality in a cohort of 4317 nonsmoking men and women aged 65 to 100 years. Methods. Logistic regression analyses were conducted to predict mortality as a function of baseline body mass index, adjusting for demographic, clinical, and laboratory covariates. Results. There was an inverse relationship between body mass index and mortality; death rates were higher for those who weighed the least. Inclusion of covariates had trivial effects on these results. People who had lost 10% or more of their body weight since age 50 had a relatively high death rate. When that group was excluded, there was no remaining relationship between body mass index and mortality. Conclusions. The association between higher body mass index and mortality often found in middle-aged populations was not observed in this large cohort of older adults. Overweight does not seem to be a risk factor for 5-year mortality in this age group. Rather, the risks associated with significant weight loss should be the primary concern. C1 Univ Washington, Dept Biostat, Seattle, WA 98195 USA. Univ Washington, Dept Hlth Serv, Seattle, WA 98195 USA. Univ Washington, Dept Med, Seattle, WA 98195 USA. Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA. NHLBI, Div Epidemiol & Clin Applicat, Bethesda, MD 20892 USA. NIA, Bethesda, MD 20892 USA. Univ Calif Davis, Sch Med, Sect Geriatr, Davis, CA USA. Univ Pittsburgh, Div Geriatr Med, Pittsburgh, PA USA. Univ Pittsburgh, Dept Epidemiol, Pittsburgh, PA USA. RP Diehr, P (reprint author), Univ Washington, Dept Biostat, Box 357232, Seattle, WA 98195 USA. FU NHLBI NIH HHS [N01-HC-85079, N01-HC-85080, N01-HC-85081] NR 27 TC 126 Z9 128 U1 0 U2 4 PU AMER PUBLIC HEALTH ASSOC INC PI WASHINGTON PA 800 I STREET, NW, WASHINGTON, DC 20001-3710 USA SN 0090-0036 EI 1541-0048 J9 AM J PUBLIC HEALTH JI Am. J. Public Health PD APR PY 1998 VL 88 IS 4 BP 623 EP 629 DI 10.2105/AJPH.88.4.623 PG 7 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA ZT681 UT WOS:000074113900018 PM 9551005 ER PT J AU Fintor, L Brown, M Fischer, R Suleiman, O Garlinghouse, C Camburn, J Frazier, E Houn, F AF Fintor, L Brown, M Fischer, R Suleiman, O Garlinghouse, C Camburn, J Frazier, E Houn, F TI The impact of mammography quality improvement legislation in Michigan: Implications for the national mammography quality standards act SO AMERICAN JOURNAL OF PUBLIC HEALTH LA English DT Article ID FACILITIES; ASSURANCE AB Objectives. This study examined the impact of state legislation on mammography quality and access in Michigan. Methods. The impact of state legislation was analyzed with respect to utilization, numbers of machines and facilities, and image quality. Results. The legislation had a positive effect on image quality improvement, had no impact on utilization by women aged 50 years and above, and resulted in few facility closures. Conclusions. Michigan's legislative intervention appears to have had a positive effect on efforts to improve mammography quality assurance with implications for other federal and state efforts to achieve quality assurance in health care delivery. C1 NCI, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA. US FDA, Div Mammog Qual & Radiat Programs, Rockville, MD 20857 USA. Michigan Dept Community Hlth, Ctr Chron Dis Prevent & Hlth Promot, Lansing, MI USA. Michigan Dept Consumer & Ind Serv, Bur Hlth Syst, Lansing, MI USA. Ctr Dis Control & Prevent, Natl Ctr Chron Dis Prevent & Hlth Promot, Atlanta, GA USA. RP Fintor, L (reprint author), Univ Michigan, Sch Med, Div Gen Med, Consortium Hlth Outcomes Innovat & Costeffectiven, 1904 Clin Fac Off Bldg,1414 Catherine St, Ann Arbor, MI 48109 USA. NR 17 TC 7 Z9 7 U1 0 U2 0 PU AMER PUBLIC HEALTH ASSOC INC PI WASHINGTON PA 1015 FIFTEENTH ST NW, WASHINGTON, DC 20005 USA SN 0090-0036 J9 AM J PUBLIC HEALTH JI Am. J. Public Health PD APR PY 1998 VL 88 IS 4 BP 667 EP 671 DI 10.2105/AJPH.88.4.667 PG 5 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA ZT681 UT WOS:000074113900029 PM 9551016 ER PT J AU Hurd, SS Lenfant, C AF Hurd, SS Lenfant, C TI NHLBI: Fifty years of achievement in pulmonary biology and medicine SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Article C1 NHLBI, Div Lung Dis, NIH, Bethesda, MD 20892 USA. RP Hurd, SS (reprint author), NHLBI, Div Lung Dis, NIH, 6701 Rockledge Dr,Suite 10018, Bethesda, MD 20892 USA. NR 1 TC 4 Z9 4 U1 0 U2 0 PU AMER LUNG ASSOC PI NEW YORK PA 1740 BROADWAY, NEW YORK, NY 10019 USA SN 1073-449X J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PD APR PY 1998 VL 157 IS 4 SU S BP S168 EP S171 PG 4 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA ZH251 UT WOS:000073088500017 PM 9563776 ER PT J AU Summers, RM Shaw, DJ Shelhamer, JH AF Summers, RM Shaw, DJ Shelhamer, JH TI CT virtual bronchoscopy of simulated endobronchial lesions: Effect of scanning, reconstruction, and display settings and potential pitfalls SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Article ID SPIRAL CT; PERSPECTIVE C1 NIH, Dept Diagnost Radiol, Warren Grant Magnuson Clin Ctr, Bethesda, MD 20892 USA. NIH, Crit Care Dept, Warren Grant Magnuson Clin Ctr, Bethesda, MD 20892 USA. RP Summers, RM (reprint author), NIH, Dept Diagnost Radiol, Warren Grant Magnuson Clin Ctr, Bldg 10,Rm 1C660,10 Ctr Dr MSC 1182, Bethesda, MD 20892 USA. NR 9 TC 54 Z9 66 U1 0 U2 0 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 USA SN 0361-803X J9 AM J ROENTGENOL JI Am. J. Roentgenol. PD APR PY 1998 VL 170 IS 4 BP 947 EP 950 PG 4 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA ZC706 UT WOS:000072608400023 PM 9530041 ER PT J AU Adams, CS Horton, WE AF Adams, CS Horton, WE TI Chondrocyte apoptosis increases with age in the articular cartilage of adult animals SO ANATOMICAL RECORD LA English DT Article ID GROWTH PLATE CARTILAGE; RETINOIC ACID; BONE-GROWTH; OSSEOUS JUNCTION; INDIAN HEDGEHOG; FRAGMENTED DNA; IN-VITRO; DIFFERENTIATION; OSTEOARTHRITIS; INDUCTION AB Background: Apoptosis in vivo has been identified in developing cartilage from embryonic chick sterna and avian and murine growth plates. To date, no evidence exists that chondrocytes in articular cartilage undergo apoptosis. Methods: We examined the distribution of cells demonstrating fragmented DNA in the articular knee cartilage of C57BL/6 mice (aged 11, 18, 24, and 30 months) and Wistar rats (aged 6, 12, and 24 months) using a DNA end-labeling technique. Results: Control experiments utilizing retinoic acid-induced apoptosis in a chondrocyte cell line, established that DNA end-labeling correlated with DNA ladder formation. In vivo, apoptotic cells were detected in articular cartilage tissue in both species examined. The percentage of apoptotic cells increased significantly (P < 0.05 with age) for all joint surfaces in both species, No significant difference was found between the medial and lateral or femoral and tibial joint surfaces of the knee, Apoptotic cells were observed in both the calcified and uncalcified regions of the articular cartilage of C57 mice. In the rat, only the calcified region of articular cartilage contained apoptotic cells. Conclusions: These results suggest that apoptosis plays a role in some aspect of maintenance, remodeling, or turnover of mature articular cartilage, In addition, the increase in apoptosis associated with aging could contribute to the greater risk for cartilage degeneration. (C) 1998 Wiley-Liss, Inc.(dagger) C1 NIA, Biol Chem Lab, Ctr Gerontol Res, NIH, Baltimore, MD 21224 USA. RP Adams, CS (reprint author), NIA, Biol Chem Lab, Ctr Gerontol Res, NIH, 4940 Eastern Ave, Baltimore, MD 21224 USA. OI Adams, Christopher/0000-0003-2100-4417 NR 41 TC 135 Z9 142 U1 3 U2 7 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0003-276X J9 ANAT REC JI Anat. Rec. PD APR PY 1998 VL 250 IS 4 BP 418 EP 425 PG 8 WC Anatomy & Morphology SC Anatomy & Morphology GA ZG316 UT WOS:000072989300005 PM 9566531 ER PT J AU Meigs, JB Nathan, DM Wilson, PWF Cupples, LA Singer, DE AF Meigs, JB Nathan, DM Wilson, PWF Cupples, LA Singer, DE TI Metabolic risk factors worsen continuously across the spectrum of nondiabetic glucose tolerance - The Framingham Offspring Study SO ANNALS OF INTERNAL MEDICINE LA English DT Article DE glucose intolerance; diabetes mellitus, non-insulin-dependent; cardiovascular diseases; risk factors; insulin resistance ID CORONARY HEART-DISEASE; UNITED-STATES POPULATION; DENSITY-LIPOPROTEIN CHOLESTEROL; CARDIOVASCULAR-DISEASE; INSULIN-RESISTANCE; PIMA-INDIANS; ASYMPTOMATIC HYPERGLYCEMIA; PRECIPITATION PROCEDURE; DIAGNOSTIC-CRITERIA; ORIGINAL COHORT AB Background: Categorical definitions for glucose intolerance imply that risk thresholds exist, but metabolic risk for type 2 diabetes mellitus or cardiovascular disease may increase continuously as glucose intolerance increases. Objective: To examine the distributions of the following meta belie risk factors across the spectrum of glucose tolerance: overall and central obesity, hypertension, low levels of high-density lipoprotein cholesterol, and increased triglyceride and insulin levels. Design: Cross-sectional analysis. Setting: The community-based Framingham Offspring Study. Participants: 2583 adults without previously diagnosed diabetes. Measurements: Clinical data; fasting glucose, insulin, and lipid levels; and glucose and insulin levels taken 2 hours after oral challenge were collected from 1991 to 1993. Glucose tolerance was determined by 1980 World Health Organization criteria. Patients with normal glucose tolerance were categorized into quintiles of fasting glucose. The distributions of each metabolic risk factor and the metabolic sum of the six risk factors were assessed across seven categories from the lowest quintile of normal fasting glucose level through impaired glucose tolerance and previously undiagnosed diabetes. Results: The mean age of patients was 54 years (range, 26 to 82 years); 52.7% of patients were women. Glucose tolerance testing found that 12.7% of patients had impaired glucose tolerance and 4.8% had previously undiagnosed diabetes. Multivariable-adjusted mean measures of risk factors and odds ratios for obesity, elevated waist-to-hip ratio, hypertension, low levels of high-density lipoprotein cholesterol, elevated triglyceride levels, and hyperinsulinemia showed continuous increases across the spectrum of nondiabetic glucose tolerance. Although a threshold effect near the upper range of nondiabetic glucose tolerance could not be ruled out for triglyceride levels in men and for insulin levels Z hours after oral challenge in men and women, no other metabolic risk factors showed clear evidence of thresholds for increased risk. Conclusions: Metabolic risk factors for type 2 diabetes mellitus and for cardiovascular disease worsen continuously across the spectrum of glucose tolerance categories, beginning in the lowest quintiles of normal fasting glucose level. C1 Massachusetts Gen Hosp, Div Gen Med, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. Boston Univ, Sch Publ Hlth, Dept Epidemiol & Biostat, Boston, MA 02118 USA. Massachusetts Gen Hosp, Diabet Unit, Boston, MA 02114 USA. Boston Univ, Sch Med, Boston, MA 02118 USA. NHLBI, Framingham, MA USA. RP Meigs, JB (reprint author), Massachusetts Gen Hosp, Div Gen Med, Staniford 50-9, Boston, MA 02114 USA. FU NHLBI NIH HHS [N01-HC-38083] NR 68 TC 136 Z9 141 U1 0 U2 1 PU AMER COLL PHYSICIANS PI PHILADELPHIA PA INDEPENDENCE MALL WEST 6TH AND RACE ST, PHILADELPHIA, PA 19106-1572 USA SN 0003-4819 J9 ANN INTERN MED JI Ann. Intern. Med. PD APR 1 PY 1998 VL 128 IS 7 BP 524 EP + PG 11 WC Medicine, General & Internal SC General & Internal Medicine GA ZE539 UT WOS:000072803500002 PM 9518396 ER PT J AU Schlessinger, D Nagaraja, R AF Schlessinger, D Nagaraja, R TI Impact and implications of yeast and human artificial chromosomes SO ANNALS OF MEDICINE LA English DT Article DE centromere; chromosome; genep gene therapy ID HUMAN GENOME; NUCLEOTIDE-SEQUENCE; DNA; MAP; CLONING; INSERTS AB Artificial chromosomes have been developed in the last 10 years to sustain genome mapping and, more recently, to begin initiating functional studies and some approaches to gene therapy. The use of yeast artificial chromosomes (YACs) in mapping the human X chromosome is reported as an example. The requirements which have postponed the development of human artificial chromosomes have now been relatively met, and some prospects are previewed here. C1 NIA, IRP, GRC, Genet Lab, Baltimore, MD 21224 USA. Washington Univ, Sch Med, Ctr Genet Med, St Louis, MO 63110 USA. RP Schlessinger, D (reprint author), NIA, IRP, GRC, Genet Lab, Box 31,5600 Nathan Shock Dr, Baltimore, MD 21224 USA. EM schlessingerd@grc.nia.nih.gov NR 29 TC 1 Z9 1 U1 0 U2 0 PU BLACKWELL SCIENCE LTD PI OXFORD PA P O BOX 88, OSNEY MEAD, OXFORD OX2 0NE, OXON, ENGLAND SN 0785-3890 J9 ANN MED JI Ann. Med. PD APR PY 1998 VL 30 IS 2 BP 186 EP 191 DI 10.3109/07853899808999402 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA ZN640 UT WOS:000073666600008 PM 9667797 ER PT J AU Filippi, M Horsfield, MA Ader, HJ Barkhof, F Bruzzi, P Evans, A Frank, JA Grossman, RI McFarland, HF Molyneux, P Paty, DW Simon, J Tofts, PS Wolinsky, JS Miller, DH AF Filippi, M Horsfield, MA Ader, HJ Barkhof, F Bruzzi, P Evans, A Frank, JA Grossman, RI McFarland, HF Molyneux, P Paty, DW Simon, J Tofts, PS Wolinsky, JS Miller, DH TI Guidelines for using quantitative measures of brain magnetic resonance imaging abnormalities in monitoring the treatment of multiple sclerosis SO ANNALS OF NEUROLOGY LA English DT Article ID CONVENTIONAL SPIN-ECHO; APPEARING WHITE-MATTER; MRI LESION LOAD; HYPOINTENSE LESIONS; DISEASE PROGRESSION; DISABILITY; PATHOLOGY; IMAGES; BENIGN; TIME AB The change of brain lesion load, measured on T-2-weighted magnetic resonance imaging (MRI) using computer-assisted techniques, is a widely used secondary endpoint for phase III clinical trials in multiple sclerosis (MS). Collection, transfer, and analysis of the electronic data across multiple centers have all proved challenging and give rise to potential errors. However, many new acquisition schemes and postprocessing techniques have been developed; these may reduce scan times and result in better lesion conspicuity or lessen the human interaction needed for data analysis. This review considers many aspects of the use of MRI in clinical trials for MS and provides international consensus guidelines, derived from a task force of the European Magnetic Resonance Networks in Multiple Sclerosis (MAGNIMS) together with a group of North American experts. The main points considered are the organization of correctly powered trials and selection of participating sites; the appropriate choice of pulse sequences and image acquisition protocol given the current state of technology; quality assurance for data acquisition and analysis; accuracy and reproducibility of lesion load assessments; and the potential for the application of quantitative methods to other MRI-derived measures of disease burden. C1 Univ Milan, Inst Sci, Dept Neurol, MS Biosignal Anal Ctr,Osped San Raffaele, I-20132 Milan, Italy. Univ Leicester, Div Med Phys, Leicester, Leics, England. Free Univ Amsterdam Hosp, Dept Biostat & Epidemiol, Amsterdam, Netherlands. Free Univ Amsterdam Hosp, Dept Radiol, Dutch MR Ctr MS, NL-1081 HV Amsterdam, Netherlands. Natl Inst Canc Res, Unit Clin Epidemiol & Trials, Genoa, Italy. Montreal Neurol Inst, McConnell Brain Imaging Ctr, Montreal, PQ, Canada. NIH, Lab Diagnost Radiol Res, Bethesda, MD 20892 USA. NIH, Neuroimmunol Branch, Bethesda, MD 20892 USA. Univ Penn, Dept Radiol, Philadelphia, PA 19104 USA. Inst Neurol, NMR Res Unit, London WC1N 3BG, England. Univ British Columbia, Dept Med, Div Neurol, Vancouver, BC V6T 1W5, Canada. Univ Colorado, Hlth Sci Ctr, Dept Radiol, Denver, CO 80262 USA. Univ Texas, Hlth Sci Ctr, Dept Neurol, Houston, TX 77225 USA. RP Filippi, M (reprint author), Univ Milan, Inst Sci, Dept Neurol, MS Biosignal Anal Ctr,Osped San Raffaele, Via Olgettina 60, I-20132 Milan, Italy. RI Tofts, Paul/C-8517-2009; Horsfield, Mark/C-6569-2013; OI Tofts, Paul/0000-0002-8552-2419; Horsfield, Mark/0000-0002-0815-6697; Bruzzi, Paolo/0000-0002-7874-2077 NR 64 TC 126 Z9 128 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0364-5134 J9 ANN NEUROL JI Ann. Neurol. PD APR PY 1998 VL 43 IS 4 BP 499 EP 506 DI 10.1002/ana.410430414 PG 8 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA ZF997 UT WOS:000072954400013 PM 9546332 ER PT J AU Cho-Chung, YS Beaucage, S Bergan, R Marquez, V Neckers, L Torrence, PF AF Cho-Chung, YS Beaucage, S Bergan, R Marquez, V Neckers, L Torrence, PF TI Presentations from the second NIH symposium on therapeutic oligonucleotides - Introduction SO ANTISENSE & NUCLEIC ACID DRUG DEVELOPMENT LA English DT Editorial Material C1 NCI, Cellular Biochem Sect, Tumor Immunol & Biol Lab, DBS, Bethesda, MD 20892 USA. US FDA, Ctr Biol Evaluat & Res, Div Hematol Prod, Bethesda, MD 20892 USA. NCI, Tumor Cell Biol Sect, Med Branch, DCS, Bethesda, MD 20892 USA. NIDDK, Biomed Chem Sect, Med Chem Lab, Bethesda, MD 20892 USA. RP Cho-Chung, YS (reprint author), NCI, Cellular Biochem Sect, Tumor Immunol & Biol Lab, DBS, Bldg 10,Room 5B05, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA SN 1087-2906 J9 ANTISENSE NUCLEIC A JI Antisense Nucleic Acid Drug Dev. PD APR PY 1998 VL 8 IS 2 BP 113 EP 114 PG 2 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Research & Experimental Medicine GA ZK996 UT WOS:000073388500005 ER PT J AU Cho-Chung, YS AF Cho-Chung, YS TI CRE-palindrome oligonucleotide as a transcription factor decoy and an inhibitor of tumor growth SO ANTISENSE & NUCLEIC ACID DRUG DEVELOPMENT LA English DT Article; Proceedings Paper CT 2nd NIH Symposium on Therapeutic Oligonucleotides - Targeting Transcription Factors and Signaling Pathways CY DEC 05, 1997 CL NIH, MASUR AUDITORIUM, BETHESDA, MARYLAND SP NIH, Interinst Therapeut Oligonucleotide Interest Grp HO NIH, MASUR AUDITORIUM ID ENKEPHALIN ENHANCER REGION; HAIRPIN FORMATION; GENE-TRANSCRIPTION; CYCLIC-AMP; EXPRESSION; CAMP; DNA; ACTIVATION; REPRESSOR; INDUCTION C1 NCI, Cellular Biochem Sect, Tumor Immunol & Biol Lab, Bethesda, MD 20892 USA. RP Cho-Chung, YS (reprint author), NCI, Cellular Biochem Sect, Tumor Immunol & Biol Lab, Bldg 10,Room 5B05, Bethesda, MD 20892 USA. NR 24 TC 11 Z9 11 U1 0 U2 0 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA SN 1087-2906 J9 ANTISENSE NUCLEIC A JI Antisense Nucleic Acid Drug Dev. PD APR PY 1998 VL 8 IS 2 BP 167 EP 170 DI 10.1089/oli.1.1998.8.167 PG 4 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Research & Experimental Medicine GA ZK996 UT WOS:000073388500015 PM 9593058 ER PT J AU Neckers, LM Kanekal, M Connell, Y AF Neckers, LM Kanekal, M Connell, Y TI Non-antisense oligonucleotide approaches for experimental treatment of glioblastoma SO ANTISENSE & NUCLEIC ACID DRUG DEVELOPMENT LA English DT Article; Proceedings Paper CT 2nd NIH Symposium on Therapeutic Oligonucleotides - Targeting Transcription Factors and Signaling Pathways CY DEC 05, 1997 CL NIH, MASUR AUDITORIUM, BETHESDA, MARYLAND SP NIH, Interinst Therapeut Oligonucleotide Interest Grp HO NIH, MASUR AUDITORIUM ID BACTERIAL-DNA; INTERFERON-GAMMA; CPG MOTIFS; OLIGODEOXYNUCLEOTIDES; INTERLEUKIN-12 C1 NCI, Med Branch, NIH, Key W Facil, Rockville, MD 20850 USA. RP Neckers, LM (reprint author), NCI, Med Branch, NIH, Key W Facil, 9610 Ctr Dr,Suite 300, Rockville, MD 20850 USA. NR 8 TC 6 Z9 6 U1 0 U2 0 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA SN 1087-2906 J9 ANTISENSE NUCLEIC A JI Antisense Nucleic Acid Drug Dev. PD APR PY 1998 VL 8 IS 2 BP 177 EP 179 DI 10.1089/oli.1.1998.8.177 PG 3 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Research & Experimental Medicine GA ZK996 UT WOS:000073388500017 PM 9593060 ER PT J AU Gandjbakhche, AH Chernomordik, V Hebden, JC Nossal, R AF Gandjbakhche, AH Chernomordik, V Hebden, JC Nossal, R TI Time-dependent contrast functions for quantitative imaging in time-resolved transillumination experiments SO APPLIED OPTICS LA English DT Article ID DOMAIN; MEDIA AB We have developed a methodology that can be used in reconstruction algorithms to quantify the optical coefficients and the geometrical cross section of a weakly abnormal optical target embedded in an otherwise homogeneous medium. This novel procedure uses different time-dependent point-spread functions to analyze the diffusive and absorptive contrasts obtained from time-of-flight measurements. Data obtained from time-resolved transillumination of a tissue like phantom are used to test the accuracy of this new deconvolution methodology. C1 NICHHD, Lab Integrat & Med Biophys, NIH, Bethesda, MD 20892 USA. UCL, Dept Phys Med, London WC1E 6JA, England. RP Gandjbakhche, AH (reprint author), NICHHD, Lab Integrat & Med Biophys, NIH, Bethesda, MD 20892 USA. NR 18 TC 62 Z9 62 U1 0 U2 0 PU OPTICAL SOC AMER PI WASHINGTON PA 2010 MASSACHUSETTS AVE NW, WASHINGTON, DC 20036 USA SN 0003-6935 J9 APPL OPTICS JI Appl. Optics PD APR 1 PY 1998 VL 37 IS 10 BP 1973 EP 1981 DI 10.1364/AO.37.001973 PG 9 WC Optics SC Optics GA ZD695 UT WOS:000072713700040 PM 18273117 ER PT J AU Zelko, I Kobayashi, R Honkakoski, P Negishi, M AF Zelko, I Kobayashi, R Honkakoski, P Negishi, M TI Molecular cloning and characterization of a novel nuclear protein kinase in mice SO ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS LA English DT Article ID TRANSCRIPTION; GENE; PROMOTER; DNA AB We cloned cDNAs which encode a mouse liver nuclear protein with an apparent molecular mass of 51 kDa, using sequences derived from a purified protein as the basis for designing specific primers, The deduced amino acid sequences revealed that the 51-kDa protein contains characteristic subdomain structures of a protein kinase, The bacterially expressed recombinant 51-kDa protein catalyzed phosphorylation of general substrates such as casein and was autophosphorylated at serine residue(s), This 51-kDa protein kinase, designated 51PK, is 40% identical to the 34-kDa protein kinase encoded by the vaccinia virus B1 gene and 25% identical 60 the casein kinase I isoforms, including yeast HRR25, The 51PK mRNA was expressed as two splice variants and the 51PK protein was exclusively localized in nuclei, Northern hybridization showed that 51PK mRNA was expressed in various tissues, with highest levels in testis, spleen, lung, and liver, These results, therefore, indicate that 51PK is a nuclear serine/threonine kinase and a novel distinct member of the protein kinase superfamily. (C) 1998 Academic Press. C1 NIEHS, Reprod & Dev Toxicol Lab, Pharmacogenet Sect, NIH, Res Triangle Pk, NC 27709 USA. Cold Spring Harbor Lab, Cold Spring Harbor, NY 11724 USA. RP Negishi, M (reprint author), NIEHS, Reprod & Dev Toxicol Lab, Pharmacogenet Sect, NIH, Res Triangle Pk, NC 27709 USA. RI Zelko, Igor/L-2673-2013; OI Zelko, Igor/0000-0003-3976-3884; Honkakoski, Paavo/0000-0002-4332-3577 NR 16 TC 14 Z9 15 U1 0 U2 0 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0003-9861 J9 ARCH BIOCHEM BIOPHYS JI Arch. Biochem. Biophys. PD APR 1 PY 1998 VL 352 IS 1 BP 31 EP 36 DI 10.1006/abbi.1998.0582 PG 6 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA ZF421 UT WOS:000072895800004 PM 9521809 ER PT J AU La Grenade, L Manns, A Fletcher, V Carberry, C Hanchard, B Maloney, EM Cranston, B Williams, NP Wilks, R Kang, EC Blattner, WA AF La Grenade, L Manns, A Fletcher, V Carberry, C Hanchard, B Maloney, EM Cranston, B Williams, NP Wilks, R Kang, EC Blattner, WA TI Clinical, pathologic, and immunologic features of human T-lymphotrophic virus type I-associated infective dermatitis in children SO ARCHIVES OF DERMATOLOGY LA English DT Article ID CELL LEUKEMIA LYMPHOMA; HTLV-I; CARRIERS; JAPANESE; SUBSETS; ATL AB Objectives: To define the clinical and laboratory features associated with infective dermatitis (ID) and confirm its association with human T-lymphotrophic virus type I(HTLV-I), Design: A case series of patients with ID were compared with patients with atopic dermatitis (AD), which is an important disease in the differential diagnosis of ID. Setting: Patients were recruited from dermatology and pediatric clinics at the University Hospital of the West Indies and the Bustamante Children's Hospital, Kingston, Jamaica. Main Outcome Measures: Clinical and laboratory features of patients with AD were compared with those of patients with ID. Patients: Consecutive patients older than 1 1/2 years diagnosed as having ID (n=50) and AD (n=35) were enrolled based on clinical findings. Results: The mean ages of patients with ID and AD were 6.9 and 7.8 years, respectively. Histologically, both diseases were predominantly chronic dermatitis with propensity for skin colonization with Staphylococcus aureus and beta-hemolytic streptococci; however, the distribution of sites of skin involvement differed. Infection with HTLV-I was the most distinguishing feature among patients with ID, with seropositive results in 100%; only 5 (14%) of the 35 patients with AD had results seropositive for HTLV-I. Infective dermatitis was further characterized by dermatopathic lymphadenitis in 16 (67%) of 24 patients with Palpable nodes. Anemia, lymphocytosis, and low albumin and elevated serum globulin levels were more prevalent among patients with ID. Significant elevations of IgA, IgD, and IgG levels were observed among patients with ID compared with those with AD. However, both patients with AD and those with ID had levels of IgD and IgE elevated above the normal range. T-cell subsets among patients with ID revealed T-cell activation with a high percentage of HLA-DR antigen positivity, elevated CD4 (2.4 x 10(9)/L) and CD8 (1.4 x 10(9)/L) cell counts, with an increased CD4/CD8 ratio of 1:73. Conclusion: Infective dermatitis is a distinct clinical entity associated with HTLV-I, which plays a role in the pathogenesis and immune perturbations observed. C1 NCI, Viral Epidemiol Branch, NIH, Bethesda, MD 20892 USA. Univ W Indies, Dept Med, Kingston 7, Jamaica. Univ W Indies, Dept Pathol, Kingston 7, Jamaica. Univ W Indies, Trop Med & Metab Unit, Kingston 7, Jamaica. RP Manns, A (reprint author), NCI, Viral Epidemiol Branch, NIH, 6130 Execut Blvd,Suite 434, Bethesda, MD 20892 USA. FU NCI NIH HHS [N01-CP-40548, N01-CP-31006] NR 22 TC 65 Z9 70 U1 0 U2 1 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0003-987X J9 ARCH DERMATOL JI Arch. Dermatol. PD APR PY 1998 VL 134 IS 4 BP 439 EP 444 DI 10.1001/archderm.134.4.439 PG 6 WC Dermatology SC Dermatology GA ZG877 UT WOS:000073049000005 PM 9554295 ER PT J AU Nagler, RM Baum, BJ Miller, G Fox, PC AF Nagler, RM Baum, BJ Miller, G Fox, PC TI Long-term salivary effects of single-dose head and neck irradiation in the rat SO ARCHIVES OF ORAL BIOLOGY LA English DT Article DE salivary glands; irradiation; long-term; xerostomia ID PAROTID-GLAND; X-IRRADIATION; ACINAR-CELLS; FLOW-RATES; RADIOTHERAPY; CANCER; INJURY AB The effect of a single dose of X-irradiation (either 2.5, 5, 7.5, 10 or 15 Gy) to the head and neck region oil parotid and submandibular gland function in rats was evaluated for up to 1 year. No animal receiving 15 Gy survived the entire study. Animals receiving greater than or equal to 7.5 Gy showed significantly less increase in body weight over time. Average wet weights of both gland types were reduced with as little as 2.5 Gy. Pilocarpine-stimulated parotid salivary flow was diminished significantly at 12 months for each radiation;dose group. Significant salivary flow reductions from submandibular glands were seen at greater than or equal to 7.5 Gy at this same time-point. These results show that a single radiation exposure of as low as 2.5 Gy to the head and neck region of rats can cause significant long-term alterations in salivary gland function. (C) 1998 Elsevier Science Ltd. All rights reserved. C1 NIDR, NIH, Gene Therapy & Therapeut Branch, Bethesda, MD 20892 USA. NIH, Pathol Unit, Vet Resource Program, Natl Ctr Res Resources, Bethesda, MD 20892 USA. RP Fox, PC (reprint author), NIDR, NIH, Gene Therapy & Therapeut Branch, Bethesda, MD 20892 USA. NR 24 TC 34 Z9 36 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0003-9969 J9 ARCH ORAL BIOL JI Arch. Oral Biol. PD APR PY 1998 VL 43 IS 4 BP 297 EP 303 DI 10.1016/S0003-9969(97)00120-9 PG 7 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA ZT626 UT WOS:000074106700006 PM 9839705 ER PT J AU Lee, J Lewin, NE Blumberg, PM Marquez, VE AF Lee, J Lewin, NE Blumberg, PM Marquez, VE TI Conformationally constrained analogues of diacylglycerol having a perhydrofuro[3,4-c]furan-1,4-dione bis-gamma-butyrolactone skeleton SO ARCHIVES OF PHARMACAL RESEARCH LA English DT Article DE protein kinase C; ligand; diacylglycerol; phorbol ester; bis-gamma-butyrolactone ID PROTEIN-KINASE-C AB Bis-gamma-lactones (1, 2) having a perhydrofuro[3,4-c]furan-1,4-dione skeleton were designed as conformationally constrained diacylglycerol analogues. They were synthesized from D-apiose in 11 steps, and evaluated as PKC-alpha ligands by measuring their ability to displace bound [H-3]-PDBU from the enzyme. The compounds showed moderate binding affinities with K-i values of 13.89 (+/-5.67) mu M and 11.47 (+/-0.89) mu M, respectively. Their similar binding affinities indicate that these two bicyclic compounds were not effectively discriminated by PKC-alpha in terms of the direction of the side chain as other ligands built on similar bis-gamma-lactones. C1 Seoul Natl Univ, Coll Pharm, Kwanak Ku, Seoul 151742, South Korea. NCI, Cellular Carcinogenesis & Tumor Promot Lab, Div Basic Sci, NIH, Bethesda, MD 20892 USA. NCI, Med Chem Lab, Div Basic Sci, NIH, Bethesda, MD 20892 USA. RP Lee, J (reprint author), Seoul Natl Univ, Coll Pharm, Kwanak Ku, Seoul 151742, South Korea. NR 13 TC 2 Z9 2 U1 0 U2 0 PU PHARMACEUTICAL SOCIETY KOREA PI SEOUL PA 1489-3 SUHCHO-DONG, SUHCHO-KU, SEOUL 137-071, SOUTH KOREA SN 0253-6269 J9 ARCH PHARM RES JI Arch. Pharm. Res. PD APR PY 1998 VL 21 IS 2 BP 164 EP 167 PG 4 WC Chemistry, Medicinal; Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA ZH385 UT WOS:000073103200011 PM 9875425 ER PT J AU Rider, LG Gurley, RC Pandey, JP Garcia-de la Torre, I Kalovidouris, AE O'Hanlon, TP Love, LA Hennekam, RCM Baumbach, LL Neville, HE Garcia, CA Klingman, J Gibbs, M Weisman, MH Targoff, IN Miller, FW AF Rider, LG Gurley, RC Pandey, JP Garcia-de la Torre, I Kalovidouris, AE O'Hanlon, TP Love, LA Hennekam, RCM Baumbach, LL Neville, HE Garcia, CA Klingman, J Gibbs, M Weisman, MH Targoff, IN Miller, FW TI Clinical, serologic, and immunogenetic features of familial idiopathic inflammatory myopathy SO ARTHRITIS AND RHEUMATISM LA English DT Article ID INCLUSION-BODY MYOSITIS; SYSTEMIC LUPUS-ERYTHEMATOSUS; DEPENDENT DIABETES-MELLITUS; SIGNAL RECOGNITION PARTICLE; RHEUMATOID-ARTHRITIS; GENETIC SUSCEPTIBILITY; OLIGONUCLEOTIDE PROBES; IRANIAN JEWS; DISEASE; HLA AB Objective. To describe the clinical, serologic, and immunogenetic features of familial idiopathic inflammatory myopathy (IIM) and to compare these with the features of sporadic IIM. Methods. Clinical signs and symptoms, autoantibodies, HLA-DRB1 and DQA1 alleles, and GM/KM phenotypes were compared among 36 affected and 28 unaffected members of 16 unrelated families in which 2 or more blood relatives developed an IIM. In addition, findings in patients with familiar IIM were compared with those in 181 patients with sporadic IIM, The families included 3 pairs of monozygotic twins with juvenile dermatomyositis, 11 families with other siblings or relatives with polymyositis or dermatomyositis, and 3 families with inclusion body myositis. Results, The clinical features of familial IIM were similar to those of sporadic IIM, although the frequency of myositis-specific autoantibodies tvas lon cr in familial than in sporadic IIM. DRB1*0301 mas a common genetic risk factor for familial and sporadic IIM, but contributed less to the genetic risk of familial IIM (etiologic fraction 0.35 versus 0.51 in sporadic IIM), Homozygosity at the HLA-DQA1 locus was found to be a genetic risk factor unique to familial IIM (57% versus 24% of controls; odds ratio 4.2, corrected P = 0.002), Conclusion. These findings emphasize that 1) familial muscle weakness is not always due to inherited metabolic defects or dystrophies, but may be the result of the development of IIM in several members of the same family, and 2) multiple genetic factors are likely important in the etiology and disease expression of familial IIM, as is also the case for sporadic myositis, but DQA1 homozygosity is a distinct risk factor for familial IIM. C1 US FDA, Ctr Biol Evaluat & Res, Div Monoclonal Antibodies, NIH, Bethesda, MD 20892 USA. NIAMSD, NIH, Bethesda, MD 20892 USA. Med Univ S Carolina, Charleston, SC 29425 USA. Univ Guadalajara, Guadalajara 44430, Jalisco, Mexico. Hosp Gen Occidente SS, Guadalajara, Jalisco, Mexico. US FDA, Ctr Food & Special Nutr, Washington, DC 20204 USA. Amsterdam Med Coll, Dept Pediat, Amsterdam, Netherlands. Amsterdam Med Coll, Inst Human Genet, Amsterdam, Netherlands. Univ Miami, Sch Med, Miami, FL 33152 USA. Univ Colorado, Sch Med, Denver, CO 80202 USA. Denver VA Med Ctr, Denver, CO USA. Louisiana State Univ, Sch Med, New Orleans, LA USA. So Calif Permanente Med Grp, Walnut Creek, CA USA. Univ Calif San Diego, Med Ctr, San Diego, CA 92103 USA. Univ Oklahoma, Med Sci Ctr, VA Med Ctr, Oklahoma City, OK USA. Oklahoma Med Res Fdn, Oklahoma City, OK 73104 USA. Indiana Univ, VA Med Ctr, Indianapolis, IN 46204 USA. RP Rider, LG (reprint author), US FDA, Ctr Biol Evaluat & Res, Div Monoclonal Antibodies, NIH, Bldg 29B,Room 2G11,HFM-561,8800 Rockville Pike, Bethesda, MD 20892 USA. OI Rider, Lisa/0000-0002-6912-2458; Miller, Frederick/0000-0003-2831-9593 NR 58 TC 35 Z9 36 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD APR PY 1998 VL 41 IS 4 BP 710 EP 719 DI 10.1002/1529-0131(199804)41:4<710::AID-ART19>3.0.CO;2-K PG 10 WC Rheumatology SC Rheumatology GA ZG163 UT WOS:000072972800018 PM 9550481 ER PT J AU Konitsiotis, S Kafetzopoulos, E Anastasopoulos, D Blanchet, PJ AF Konitsiotis, S Kafetzopoulos, E Anastasopoulos, D Blanchet, PJ TI Opposite rotation induced by dopamine agonists in rats with unilateral lesions of the globus pallidus or substantia nigra SO BEHAVIOURAL BRAIN RESEARCH LA English DT Article DE Substantia nigra; Globus pallidus; apomorphine; amphetamine; rotational behavior; dopamine ID BASAL GANGLIA; SUBTHALAMIC NUCLEUS; EXPERIMENTAL PARKINSONISM; FUNCTIONAL-ANATOMY; EXTERNAL PALLIDUM; SQUIRREL-MONKEY; MOTOR-ACTIVITY; RECEPTORS; NEURONS; PROJECTIONS AB Normal rats with a unilateral ibotenic acid lesion of substantia nigra pars reticulata (SNR, n = 12) or globus pallidus (GP, n=12) were challenged systemically with the mixed dopaminergic agonist apomorphine (0.5 and 1.5 mg/kg) and the indirect acting d-amphetamine (1.5 mg/kg). The low dose of apomorphine produced a weak contralateral rotation only in the SNR-lesioned group, which showed an intense ipsilateral rotation following the administration of the higher dose. GP-lesioned rats also showed ipsilateral rotation after the high dose of apomorphine. d-Amphetamine produced ipsilateral rotation in GP-lesioned rats, contrasting with a vigorous contralateral rotation in SNR-lesioned rats. The unexpected opposite rotation after apomorphine and d-amphetamine, observed only in SNR-lesioned animals, indicates that the role of SNR in basal ganglia functions is less clear and more complex than what is expected from our current model of basal ganglia circuitry and functions. On the other hand, the GP lesion resulted in a consistent and predictable ipsilateral rotation after both apomorphine and d-amphetamine, indicating a more determinant effect on the output of the basal ganglia than heretofore believed. Our results may contribute to the recently expressed views challenging the established model of basal ganglia organisation. (C) 1998 Elsevier Science B.V. All rights reserved. C1 NINDS, Expt Therapeut Branch, NIH, Bethesda, MD 20892 USA. Univ Ioannina, Dept Pharmacol, GR-45110 Ioannina, Greece. Univ Ioannina, Dept Neurol, GR-45110 Ioannina, Greece. RP Konitsiotis, S (reprint author), NINDS, Expt Therapeut Branch, NIH, Bldg 10,Room 5C103, Bethesda, MD 20892 USA. NR 35 TC 18 Z9 18 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0166-4328 J9 BEHAV BRAIN RES JI Behav. Brain Res. PD APR PY 1998 VL 92 IS 1 BP 77 EP 83 DI 10.1016/S0166-4328(97)00127-7 PG 7 WC Behavioral Sciences; Neurosciences SC Behavioral Sciences; Neurosciences & Neurology GA ZK015 UT WOS:000073276400008 PM 9588687 ER PT J AU Saito, K Yoshioka, H Kazama, S Cutler, RG AF Saito, K Yoshioka, H Kazama, S Cutler, RG TI Release of nitric oxide from a spin trap, N-tert-butyl-alpha-phenylnitrone, under various oxidative conditions SO BIOLOGICAL & PHARMACEUTICAL BULLETIN LA English DT Article DE N-tert-butyl-alpha-phenylnitrone; oxidative stress; nitric oxide; hydroxyl radical ID NITRONE PBN; BUTYLNITRONE; PROTECTION; DAMAGE; INJURY; BRAIN; HEART AB Nitric oxide (NO) generation from a spin trap, N-tert-butyl-alpha-phenylnitrone (PBN) under various oxidative conditions was examined. The absorbance of PBN at 295 nm decreased with time of UV-irradiation, showing that PBN was decomposed by UV irradiation. The hydroxyl radical formed from a Fenton reagent also decomposed PBN, but there was little effect by a peroxyl radical and a superoxide. Nitrite, an oxidative product of NO, in PBN solution was determined using, a NOx analyzer based on Griess reaction. UV-irradiation and the hydroxyl radical also formed nitrite. Direct detection of NO from the sample on reaction with hydroxyl radical was successful using a GC/MS/SIM on the UV-irradiated sample. NO generated in PBN solutions activated guanylate cyclase. From these results, PBN is viewed as a new kind of medicine which acts as an antioxidant and as an NO donor in vivo. C1 NIA, Gerontol Res Ctr, NIH, Baltimore, MD 21224 USA. Univ Shizuoka, Sch Pharmaceut Sci, Shizuoka 422, Japan. Univ Shizuoka, Inst Environm Sci, Shizuoka 422, Japan. RP Saito, K (reprint author), NIA, Gerontol Res Ctr, NIH, 4940 Eastern Ave, Baltimore, MD 21224 USA. NR 19 TC 13 Z9 13 U1 0 U2 1 PU PHARMACEUTICAL SOC JAPAN PI TOKYO PA 2-12-15 SHIBUYA, SHIBUYA-KU, TOKYO, 150-0002, JAPAN SN 0918-6158 J9 BIOL PHARM BULL JI Biol. Pharm. Bull. PD APR PY 1998 VL 21 IS 4 BP 401 EP 404 PG 4 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA ZH605 UT WOS:000073128300019 PM 9586581 ER PT J AU Saito, K Yoshioka, H Cutler, RG AF Saito, K Yoshioka, H Cutler, RG TI A spin trap, N-tert-butyl-alpha-phenylnitrone extends the life span of mice SO BIOSCIENCE BIOTECHNOLOGY AND BIOCHEMISTRY LA English DT Article DE N-tert-butyl-alpha-phenylnitrone (PBN); oxidative stress; life span; reactive oxygen species; nitric oxide ID REQUIRING PROLONGED OBSERVATION; NITRONE PBN; OXIDATIVE DAMAGE; FREE-RADICALS; GERBIL BRAIN; RAT-HEART; INJURY; PROTECTION; SENESCENCE; AGE AB To characterize the pharmacological effects of N-tert-butyl-alpha-phenylnirone (PBN) on Life span, we administered PEN in drinking mater to 24.5-month-old mice, and the survivors were counted, Their mater consumption and body weights were measured as biological markers. PEN-treated animals as compared with control animals had prolonged mean and maximum life spans. Their water consumption decreased but no significant change was found in their body weights, indicating that the metabolism was improved. Results showed that PEN indeed affects physiological functions and extends life span, We propose that nitric oxide release from PEN may be involved in altering the aging process. C1 Univ Shizuoka, Inst Environm Sci, Shizuoka 422, Japan. NIA, Gerontol Res Ctr, NIH, Baltimore, MD 21224 USA. RP Saito, K (reprint author), Univ Shizuoka, Inst Environm Sci, 52-1 Yada, Shizuoka 422, Japan. NR 25 TC 49 Z9 50 U1 0 U2 0 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 0916-8451 EI 1347-6947 J9 BIOSCI BIOTECH BIOCH JI Biosci. Biotechnol. Biochem. PD APR PY 1998 VL 62 IS 4 BP 792 EP 794 DI 10.1271/bbb.62.792 PG 3 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Chemistry, Applied; Food Science & Technology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Chemistry; Food Science & Technology GA ZM212 UT WOS:000073515900032 PM 9614711 ER PT J AU Loimas, S Wahlfors, J Janne, J AF Loimas, S Wahlfors, J Janne, J TI Herpes simplex virus thymidine kinase green fluorescent protein fusion gene: New tool for gene transfer studies and gene therapy SO BIOTECHNIQUES LA English DT Article ID MAMMALIAN-CELLS; EXPRESSION; DNA AB Green fluorescent protein (GFP) and herpes simplex virus type-1 thymidine kinase (TK) are commonly used markers in gene transfer studies. The latter gene has also proven to be an effective tool in cancer "suicide" gene therapy. To facilitate rapid and reliable selection of cells expressing TK, we constructed a plasmid expressing a TK-green fluorescent protein fusion gene (TK-GFP). In this fusion gene, the expression of each component is coupled to one another, permitting accurate determination of the percentage of cells expressing TK by detecting the green fluorescence produced by GFP. Transfection of the fusion plasmid to mammalian cells revealed that the construct is fully functional, making the cells both fluorescent and sensitive to ganciclovir. C1 Univ Kuopio, AI Virtanen Inst, FIN-70211 Kuopio, Finland. Natl Human Genome Res Inst, NIH, Bethesda, MD USA. RP Loimas, S (reprint author), Univ Kuopio, AI Virtanen Inst, POB 1627, FIN-70211 Kuopio, Finland. EM loimas@messi.uku.fi NR 17 TC 53 Z9 56 U1 0 U2 0 PU EATON PUBLISHING CO PI NATICK PA 154 E. CENTRAL ST, NATICK, MA 01760 USA SN 0736-6205 J9 BIOTECHNIQUES JI Biotechniques PD APR PY 1998 VL 24 IS 4 BP 614 EP 618 PG 5 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA ZH111 UT WOS:000073073300022 PM 9564534 ER PT J AU Arguello, F Alexander, M Sterry, JA Tudor, G Smith, EM Kalavar, NT Greene, JF Koss, W Morgan, CD Stinson, SF Siford, TJ Alvord, WG Klabansky, RL Sausville, EA AF Arguello, F Alexander, M Sterry, JA Tudor, G Smith, EM Kalavar, NT Greene, JF Koss, W Morgan, CD Stinson, SF Siford, TJ Alvord, WG Klabansky, RL Sausville, EA TI Flavopiridol induces apoptosis of normal lymphoid cells, causes immunosuppression, and has potent antitumor activity in vivo against human leukemia and lymphoma xenografts SO BLOOD LA English DT Article ID CYCLIN-DEPENDENT KINASES; BREAST-CARCINOMA CELLS; ESTROGEN-BINDING-SITES; BONE-MARROW; HOST-DISEASE; GROWTH; FLAVONE; INHIBITION; PROGENITORS; ACTIVATION AB Flavopiridol is a novel semisynthetic flavone derivative of the alkaloid rohitukine. Flavopiridol is known to inhibit potently the activity of multiple cyclin-dependent kinases. We have assessed its effects on normal and malignant cells in preclinical animal models of localized and disseminated human hematopoietic neoplasms. Flavopiridol, when administered as daily bolus intravenous (IV) injections, produced selective apoptosis of cells in the thymus, spleen, and lymph nodes, resulting in atrophy of these organs. With the exception of the intestinal crypts, apoptosis or tissue damage was absent in all other organs investigated (kidneys, liver, lungs, bone/bone marrow, muscle, and heart). Flavopiridol had a marked apoptotic effect documented by DNA nick-end labeling, or DNA agarose gels in xenografts of human hematopoietic tumors HL-60, SUDHL-4, and Nalm/6. After treatment with 7.5 mg/kg flavopiridol bolus IV or intraperitoneal on each of 5 consecutive days, 11 out of 12 advanced stage subcutaneous (s.c.) human HL-60 xenografts underwent complete regressions, and animals remained disease-free several months after one course of flavopiridol treatment. SUDHL-4 s.c. lymphomas treated with flavopiridol at 7.5 mg/kg bolus IV for 5 days underwent either major (two out of eight mice) or complete (four out of eight mice) regression, with two animals remaining disease-free for more than 60 days. The overall growth delay was 73.2%. The acquired immunodeficiency syndrome-associated lymphoma AS283 showed no significant response when flavopiridol was used in advanced s.c. tumors, but when treatment was initiated in early stages, there was a complete regression of the early tumors, and a significant overall growth delay (>84%). When flavopiridol was used in severe combined immunodeficient mice bearing disseminated human acute lymphoblastic leukemia Nalm/6 cells, there was 15-day prolongation in survival (P = .0089). We conclude that flavopiridol greatly influences apoptosis in both normal and malignant hematopoietic tissues. This activity was manifested in our study as a potent antileukemia or antilymphoma effect in human tumor xenografts, which was dose and schedule dependent. These findings provide compelling evidence for the use of flavopiridol in human hematologic malignancies. This is a US government work, There are no restrictions on its use. C1 NCI, Frederick Canc Res & Dev Ctr, Lab Drug Discovery Res & Dev, Dev Therapeut Program,Div Canc Treatment & Diag, Frederick, MD USA. NCI, Frederick Canc Res & Dev Ctr, Sci Applicat Int Corp, Frederick, MD USA. NCI, Frederick Canc Res & Dev Ctr, Data Management Serv Inc, Frederick, MD USA. Univ Rochester, Strong Mem Hosp, Div Clin Labs, Rochester, NY 14642 USA. Scott & White Clin, Dept Pathol, Temple, TX USA. Scott & White Clin, Immunol Sect, Temple, TX USA. RP Sausville, EA (reprint author), NCI, Dev Therapeut Program, Div Canc Treatment & Diag, EPN-843 MSC 7458,6130 Execut Blvd, Rockville, MD 20852 USA. NR 38 TC 193 Z9 198 U1 0 U2 4 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0006-4971 J9 BLOOD JI Blood PD APR 1 PY 1998 VL 91 IS 7 BP 2482 EP 2490 PG 9 WC Hematology SC Hematology GA ZD305 UT WOS:000072671900032 PM 9516149 ER PT J AU Held, TK Mielke, MEA Chedid, M Unger, M Trautmann, M Huhn, D Cross, AS AF Held, TK Mielke, MEA Chedid, M Unger, M Trautmann, M Huhn, D Cross, AS TI Granulocyte colony-stimulating factor worsens the outcome of experimental Klebsiella pneumoniae pneumonia through direct interaction with the bacteria SO BLOOD LA English DT Article; Proceedings Paper CT 96th Annual General Meeting of the American-Society-for-Microbiology CY MAY 19-24, 1996 CL NEW ORLEANS, LOUISIANA SP Amer Soc Microbiol ID HUMAN-NEUTROPHILS; CAPSULAR POLYSACCHARIDE; ESCHERICHIA-COLI; MONOCLONAL-ANTIBODY; MYCOBACTERIUM-AVIUM; GROWTH; MICE; INFECTIONS; VIRULENCE; SEPSIS AB Besides its well-established effects on granulocytopoiesis, granulocyte colony-stimulating factor (G-CSF) has been shown to have direct effects on the recruitment and bactericidal ability of neutrophils, resulting in improved survival of experimentally infected animals. We studied the effect of G-CSF on the course of experimental pneumonia induced by Klebsiella pneumoniae, an important gram-negative bacillary pulmonary pathogen. Using a highly reproducible murine model, we here show the paradoxical finding that mortality from infection was significantly increased when animals received G-CSF before induction of pneumonia. Administration of G-CSF promoted replication of bacteria in the river and spleen, thus indicating an impairment rather than an enhancement of antibacterial mechanisms. By contrast, a monoclonal antibody against Klebsiella K2 capsule significantly reduced bacterial multiplication in the lung, liver, and spleen, and abrogated the increased mortality caused by G-CSF. In vitro studies showed a direct effect of G-CSF on K pneumoniae resulting in increased capsular polysaccharide (CPS) production. When bacteria were coincubated with therapeutically achievable concentrations of G-CSF, phagocytic uptake and killing by neutrophils was impaired. Western blot analysis showed three binding sites of G-CSF to K pneumoniae. Binding of I-125-G-CSF to K pneumoniae was displaced by an excess of unlabeled G-CSF, whereas an unrelated cytokine, interleukin-1 alpha, did not compete with G-CSF binding to the bacteria. Thus, in this model, the direct effect of G-CSF on a bacterial virulence factor, CPS production, outweighed any beneficial effect of G-CSF on recruitment and stimulation of leukocytes. (C) 1998 by The American Society of Hematology. C1 Humboldt Univ, Virchow Klinikum, Dept Hematol & Oncol, Abt Innere Med MS Hamatol & Onkol, D-13353 Berlin, Germany. Humboldt Univ, Virchow Klinikum, Dept Paidopathol & Placentol, D-13353 Berlin, Germany. Free Univ Berlin, Inst Infect Dis, Dept Med Microbiol & Infect Dis Immunol, D-1000 Berlin, Germany. NCI, Cellular & Mol Biol Lab, NIH, Bethesda, MD 20892 USA. Univ Ulm, Dept Microbiol, D-89069 Ulm, Germany. Univ Maryland, Sch Med, Div Infect Dis, Baltimore, MD 21201 USA. Univ Maryland, Sch Med, Program Oncol, Baltimore, MD 21201 USA. RP Held, TK (reprint author), Humboldt Univ, Virchow Klinikum, Dept Hematol & Oncol, Abt Innere Med MS Hamatol & Onkol, Augustenburger Pl 1, D-13353 Berlin, Germany. NR 52 TC 41 Z9 41 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0006-4971 J9 BLOOD JI Blood PD APR 1 PY 1998 VL 91 IS 7 BP 2525 EP 2535 PG 11 WC Hematology SC Hematology GA ZD305 UT WOS:000072671900037 PM 9516154 ER PT J AU Rao, GN Ney, E Herbert, RA AF Rao, GN Ney, E Herbert, RA TI Effect of retinoid analogues on mammary cancer in transgenic mice with c-neu breast cancer oncogene SO BREAST CANCER RESEARCH AND TREATMENT LA English DT Article DE breast cancer; c-neu transgenic mice; N-(4-hydroxyphenyl) retinamide; arotinoid Ro 40-8757; retinoid analogues ID MOUSE; BEARING; MODELS; FIBER AB Breast cancer is one of the most common cancers and is a leading cause of mortality in women. The TG.NK transgenic mouse line expresses the c-neu breast cancer oncogene under the control of an MMTV promoter and appears to be a useful animal model for evaluation of intervention strategies to delay/prevent breast cancer. Fiber-rich nonpurified diet (NTP-2000), as compared to a purified diet (AIN-76A), has previously been shown to significantly delay the development of mammary cancer in the TG,NK model. Four-week old hemizygous TG,NK female mice with MMTV/c-neu oncogene were fed NTP-2000 diet containing the retinoid analogue 4-hydroxyphenyl retinamide (4-HPR) at 5 mM/kg or an arotinoid Ro 40-8757 at 2 and 3 mmol/kg for 26 weeks. The 4-HPR at 5 mmol/kg diet delayed the development of palpable tumors up to 24 weeks, but by 26 weeks, the incidence was not significantly different from the NTP-2000 diet control group, However, the 4-HPR diet markedly decreased the average weight of the tumors at 26 weeks, The 4-HPR diet also caused a significant increase in body weight without an increase ill food consumption. Arotinoid Re-40-8757 at both doses inhibited the development of mammary tumors for the duration of the study. However, the Ro 40-8757 at 3 mmol/kg appeared to be toxic as indicated by a significant depression of the average body weight with alopecia and skin scaling in some mice. Our observations with TG.NK transgenic mouse and fiber-rich diet (NTP-2000) indicate that the arotinoid Ro 40-8757 has a markedly higher inhibitory effect on the development of mammary cancer than 4-HPR, Studies to evaluate genetic changes and expression of hormonal receptors and growth factors associated with the inhibition of mammary cancer development by the retinoid analogues are in progress. C1 NIEHS, Environm Toxicol Program, NIH, Res Triangle Pk, NC 27709 USA. RP Rao, GN (reprint author), NIEHS, Environm Toxicol Program, NIH, MD B3-08,POB 12233, Res Triangle Pk, NC 27709 USA. NR 24 TC 20 Z9 20 U1 0 U2 0 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA SPUIBOULEVARD 50, PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS SN 0167-6806 J9 BREAST CANCER RES TR JI Breast Cancer Res. Treat. PD APR PY 1998 VL 48 IS 3 BP 265 EP 271 DI 10.1023/A:1005957620881 PG 7 WC Oncology SC Oncology GA ZL054 UT WOS:000073394200008 PM 9598873 ER PT J AU Hamburger, AW Fernandes, A Murakami, M Gerwin, BI AF Hamburger, AW Fernandes, A Murakami, M Gerwin, BI TI The role of transforming growth factor alpha production and ErbB-2 overexpression in induction of tumorigenicity of lung epithelial cells SO BRITISH JOURNAL OF CANCER LA English DT Article DE lung cancer; ErbB-2 receptors; transforming growth factor ID SYNERGISTIC INTERACTION; SHORTENED SURVIVAL; TRANSGENIC MICE; EXPRESSION; C-ERBB-2; GENES; DIFFERENTIATION; ADENOCARCINOMAS; PHOSPHORYLATION; PROTEIN AB Over-expression of erbB-2 is associated with shortened survival of patients with lung adenocarcinomas, We demonstrated that human lung epithelial cells, overexpressing erbB-2, formed tumours in nude mice only when high levels of transforming growth factor (TGF)-alpha were produced (E6T cells). To define the role that TGF-alpha production played in induction of tumorigenicity, a non-tumorigenic TGF-alpha-negative clone of ErbB-2 overexpressing cells (E2 cells) was transfected with an expression vector for TGF-alpha (E2 alpha cells). Transfected clones produced TGF-alpha at 11-25% of the level produced by the E6T cell line. Tumorigenic E6T cells transfected with a TGF-alpha antisense vector (EGTA cells) expressed only 6% of the TGF-alpha level of the parental cells. Clones of E6T, EGTA, E2 and E2 alpha were inoculated into athymic nude mice to measure tumorigenic potential. E6T cells formed tumours with a 70% efficiency. E2, EGTA and E2 alpha cells failed to form tumours, The levels of EGFR were similar in non-tumorigenic E2 and tumorigenic E6T cells but higher in E2 alpha and EGTA cells, and ErbB-2 were greatly overexpressed in an E2 alpha clone, In vitro, ErbB-2 co-immunoprecipitated with EGFR in lysates of unstimulated E6T and E2 alpha TGF-alpha-producing cells, indicating that the lower TGF-alpha levels were sufficient to induce in vitro heterodimerization. These studies suggest that induction of the tumorigenic phenotype depends on achieving a threshold level of TGF-alpha sufficient to activate downstream signalling by ErbB-2 containing active heterodimers. C1 Univ Maryland, Marlene & Stewart Greenebaum Canc Ctr, Baltimore, MD 21201 USA. Univ Maryland, Dept Pathol, Baltimore, MD 21201 USA. NCI, Human Carcinogenesis Lab, NIH, Bethesda, MD 20892 USA. RP Hamburger, AW (reprint author), Univ Maryland, Marlene & Stewart Greenebaum Canc Ctr, 655 W Baltimore St,Room 9-051 BRB, Baltimore, MD 21201 USA. FU NCI NIH HHS [F33CA63763] NR 29 TC 5 Z9 5 U1 0 U2 1 PU CHURCHILL LIVINGSTONE PI EDINBURGH PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE, LEITH WALK, EDINBURGH EH1 3AF, MIDLOTHIAN, SCOTLAND SN 0007-0920 J9 BRIT J CANCER JI Br. J. Cancer PD APR PY 1998 VL 77 IS 7 BP 1066 EP 1071 DI 10.1038/bjc.1998.178 PG 6 WC Oncology SC Oncology GA ZD877 UT WOS:000072733400008 PM 9569041 ER PT J AU Colaianni, LA AF Colaianni, LA TI Hospital librarians and the Medical Library Association SO BULLETIN OF THE MEDICAL LIBRARY ASSOCIATION LA English DT Article ID INFORMATION; CARE AB Hospital librarians have been active participants in and contributors to the Medical Library Association since it was founded. This article reviews the history of the Hospital Libraries Section and provides some personal observations on the contributions the association has made to hospital librarians and their growing influence on the association. C1 Natl Lib Med, Bethesda, MD 20894 USA. RP Colaianni, LA (reprint author), Natl Lib Med, 8600 Rockville Pike, Bethesda, MD 20894 USA. NR 17 TC 1 Z9 1 U1 0 U2 0 PU MEDICAL LIBRARY ASSOC PI CHICAGO PA 65 EAST WACKER PLACE, STE 1900, CHICAGO, IL 60601-7298 USA SN 0025-7338 J9 B MED LIBR ASSOC JI Bull. Med. Libr. Assoc. PD APR PY 1998 VL 86 IS 2 BP 217 EP 222 PG 6 WC Information Science & Library Science SC Information Science & Library Science GA ZJ545 UT WOS:000073227500010 PM 9578942 ER PT J AU Kenney, LB Miller, BA Ries, LAG Nicholson, HS Byrne, J Reaman, GH AF Kenney, LB Miller, BA Ries, LAG Nicholson, HS Byrne, J Reaman, GH TI Increased incidence of cancer in infants in the US: 1980-1990 SO CANCER LA English DT Article; Proceedings Paper CT 64th Annual Meeting of the Society-for-Pediatric-Research CY MAY 05-11, 1995 CL SAN DIEGO, CALIFORNIA SP Soc Pediat Res DE childhood cancer; infants; incidence; central nervous system tumors; neuroblastoma; acute lymphoblastic leukemia ID ACUTE LYMPHOBLASTIC-LEUKEMIA; UNITED-STATES; EXPERIENCE; MORTALITY; AGE AB BACKGROUND. During the decade between 1980-1990, the rate of cancer in children in the U.S. increased. It is unknown whether cancer in infancy, which is biologically and clinically different from cancer in older children, also increased. METHODS. To evaluate changes in cancer incidence in infants in the U.S. age < 1 year, data from the Surveillance, Epidemiology, and End Results (SEER) program and the U.S. Bureau of the Census were used to construct age specific, population-based cancer incidence rates. RESULTS. Overall, the annual cancer rate in infants increased from 189 cases per million infants: between 1979-1981 to 220 between 1989-1991. At both timepoints, female infants had higher cancer rates than male infants. Although the rates for female infants remained stable at 223 between 1979-1981 versus 236 between 1989-1991, rates for male infants increased from 158 to 205 during the same timepoints. Male infants had increased rates of central nervous system (CNS) tumors (P < 0.05), neuroblastoma, and retinoblastoma; female infants had increased rates of teratomas (P < 0.01) and hepatoblastomas. Between 1979-1981, the three most common types of cancer in infants were neuroblastoma. leukemia, and renal tumors (27%, 15%, and 14%, respectively), and were neuroblastoma, CNS tumors, and leukemia between 1989-1991 (27%, 15%, and 13%, respectively). CONCLUSIONS. This study shows chat the rate of certain types of cancer in infants in the U.S. is increasing. Studies of both genetic and environmental factors are needed to explain these increased rates and the changing distribution of cancer in the first year of life. (C) 1998 American Cancer Society. C1 Univ Massachusetts, Med Ctr, Dept Pediat, Div Hematol Oncol, Worcester, MA 01655 USA. NCI, Div Canc Prevent & Control, NIH, Bethesda, MD 20892 USA. Oregon Hlth Sci Univ, Dept Pediat, Div Hematol Oncol, Portland, OR 97201 USA. Childrens Natl Med Ctr, Dept Hematol Oncol, Washington, DC 20010 USA. RP Kenney, LB (reprint author), Univ Massachusetts, Med Ctr, Dept Pediat, Div Hematol Oncol, 55 Lake Ave N, Worcester, MA 01655 USA. NR 14 TC 32 Z9 32 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0008-543X J9 CANCER JI Cancer PD APR 1 PY 1998 VL 82 IS 7 BP 1396 EP 1400 DI 10.1002/(SICI)1097-0142(19980401)82:7<1396::AID-CNCR25>3.0.CO;2-0 PG 5 WC Oncology SC Oncology GA ZC962 UT WOS:000072636700025 PM 9529034 ER PT J AU Hiraiwa, H Hamazaki, M AF Hiraiwa, H Hamazaki, M TI A neuroblastoma cell line derived from a case detected through a mass screening system in Japan: A case report including the biologic and phenotypic characteristics of the cell line - Author reply SO CANCER LA English DT Letter ID N-MYC; AMPLIFICATION C1 NICHD, Sect Cellular Differentiat, Heritable Disorders Branch, NIH, Bethesda, MD USA. Shizuoka Childrens Hosp, Dept Pathol, Shizuoka, Japan. RP Hiraiwa, H (reprint author), NICHD, Sect Cellular Differentiat, Heritable Disorders Branch, NIH, Bethesda, MD USA. NR 7 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0008-543X J9 CANCER JI Cancer PD APR 1 PY 1998 VL 82 IS 7 BP 1418 EP 1418 DI 10.1002/(SICI)1097-0142(19980401)82:7<1418::AID-CNCR37>3.0.CO;2-7 PG 1 WC Oncology SC Oncology GA ZC962 UT WOS:000072636700037 ER PT J AU Wingo, PA Ries, LAG Parker, SL Heath, CW AF Wingo, PA Ries, LAG Parker, SL Heath, CW TI Long-term cancer patient survival in the United States SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID BREAST-CANCER; PROGNOSTIC FACTOR; PROSTATE-CANCER; AGE; CARCINOMA; DETERMINANTS; RACE AB Although survival rates are useful for monitoring progress in the early detection and treatment of cancer and are of particular interest to patients with new diagnoses, there are limited population-based estimates of long-term survival rates, We used data collected by the Surveillance, Epidemiology, and End Results Program for cases diagnosed during 1974-1991 and followed through 1992 to estimate relative survival at 5, 10, and 15 years after diagnosis of cancer of the breast, prostate, colon and rectum, and lung, Relative survival after diagnosis of breast and prostate cancer continued to decline up through 15 years after diagnosis, whereas survival after diagnosis of lung and colon or rectal cancer remained approximately constant after 5 and 10 years, respectively, Age-specific patterns of survival varied by site, stage, and demographics, Among patients with localized breast and prostate cancer, women who were younger than age 45 at breast cancer diagnosis and men who were 75 years and older at prostate cancer diagnosis had the poorest relative survival, Relative survival among lung cancer patients decreased with age at diagnosis, regardless of stage or demographics, and age-specific patterns of relative survival for patients with cancer of the colon and rectum differed according to race, Among white patients diagnosed with cancers of the colon and rectum, relative survival did not vary by age at diagnosis; among black patients older than 45 at diagnosis, relative survival decreased with age, This study provides population-based estimates of long-term survival and confirms black/white, male/female, and stage-and age-specific differences for the major cancers. C1 Amer Canc Soc, Epidemiol & Surveillance Res Dept, Atlanta, GA 30329 USA. NCI, Div Canc Prevent & Control, Bethesda, MD 20892 USA. RP Wingo, PA (reprint author), Amer Canc Soc, Epidemiol & Surveillance Res Dept, 1599 Clifton Rd NE, Atlanta, GA 30329 USA. NR 30 TC 112 Z9 113 U1 2 U2 3 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD APR PY 1998 VL 7 IS 4 BP 271 EP 282 PG 12 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA ZG556 UT WOS:000073015500002 PM 9568781 ER PT J AU Michaud, DS Giovannucci, EL Ascherio, A Rimm, EB Forman, MR Sampson, L Willett, WC AF Michaud, DS Giovannucci, EL Ascherio, A Rimm, EB Forman, MR Sampson, L Willett, WC TI Associations of plasma carotenoid concentrations and dietary intake of specific carotenoids in samples of two prospective cohort studies using a new carotenoid database SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID FOOD-FREQUENCY QUESTIONNAIRE; BETA-CAROTENE; VITAMIN-A; CARDIOVASCULAR-DISEASE; ALCOHOL-CONSUMPTION; HEART-DISEASE; CANCER; MEN; VEGETABLES; WOMEN AB Diet-plasma carotenoid associations were examined in samples of women and men from each cohort in the Nurses' Health Study and the Health Professionals Follow-Up Study, In each sample, participants completed two self-administered food frequency questionnaires with at least a 1-year interval and provided a blood specimen preceding the second food frequency questionnaire. Carotenoid intakes were estimated from values for the five major carotenoids found in human plasma, specifically, alpha- and beta-carotene, beta-cryptoxanthin, lutein, and lycopene, using the United States Department of Agriculture-National Cancer Institute Carotenoid Database, as well as updated values for tomato products, Pearson correlation coefficients were calculated to compare diet-plasma correlations over time by sex after adjustment for recognized covariates, Among nonsmoking women (n = 162), the adjusted diet-plasma carotenoid associations were 0.48 for alpha-carotene, 0.27 for beta-carotene and lutein, 0.32 for beta-cryptoxanthin, and 0.21 for lycopene, Among nonsmoking men (ii = 110), diet-plasma correlations were 0.47 for alpha-carotene and lycopene, 0.35 for beta-carotene, 0.43 for beta-cryptoxanthin, and 0.40 for lutein, Correlations between total fruit or vegetable intake and each plasma carotenoid level were not as high as any of the calculated carotenoid intake using the new database values, The correlations observed in this study indicate that the new carotenoid database provides valuable information on specific carotenoid intake and may be useful in epidemiological studies that attempt to account for associations between fruit or vegetable intake and disease. C1 Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Channing Lab, Boston, MA 02115 USA. NCI, Div Canc Prevent & Control, NIH, Bethesda, MD 20892 USA. RP Michaud, DS (reprint author), Harvard Univ, Sch Publ Hlth, Dept Nutr, 665 Huntington Ave, Boston, MA 02115 USA. RI Michaud, Dominique/I-5231-2014 FU NCI NIH HHS [CA-40356, CA-55075]; NHLBI NIH HHS [HL-35464] NR 46 TC 170 Z9 171 U1 0 U2 8 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD APR PY 1998 VL 7 IS 4 BP 283 EP 290 PG 8 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA ZG556 UT WOS:000073015500003 PM 9568782 ER PT J AU Li, Y Millikan, RC Carozza, S Newman, B Liu, E Davis, R Miike, R Wrensch, M AF Li, Y Millikan, RC Carozza, S Newman, B Liu, E Davis, R Miike, R Wrensch, M TI p53 mutations in malignant gliomas SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID TUMOR-SUPPRESSOR GENE; STRAND CONFORMATION POLYMORPHISM; HUMAN BRAIN-TUMORS; HUMAN CANCERS; ASTROCYTOMAS; PROGRESSION; ETIOLOGY; GRADE; MODEL; CELLS AB A population-based series of incident cases of malignant glioma were analyzed for mutations in the tumor suppressor gene p53, Exons 4-8 were screened using PCR-single-strand conformation analysis and confirmed through direct sequencing, Of 62 tumors analyzed, 12 (19%) contained mutations in p53: one 18-bp duplication in exon 5, five point mutations in exon 4, three point mutations in exon 7, two point mutations in exon 8, and a splice-site mutation at the exon 6/intron 7 boundary, In contrast to previous studies of malignant glioma, the prevalence of transversion mutations (56%) was higher than transition mutations (33%), A large proportion of transversion mutations occurred in exon 4, a region that is not routinely screened in gliomas. We present here an improved method for screening exon 4 (and other GC-rich regions) of p53 using PCR-single-strand conformation analysis, The high frequency of transversion mutations suggests a role for exogenous carcinogens in the etiology of malignant glioma. C1 Univ Calif San Francisco, Dept Epidemiol & Biostat, Sch Med, San Francisco, CA 94143 USA. Univ Calif San Francisco, Dept Neuropathol, Sch Med, San Francisco, CA 94143 USA. Univ N Carolina, Sch Publ Hlth, Dept Epidemiol, Chapel Hill, NC 27599 USA. Texas Dept Hlth, Canc Registry Div, Austin, TX 78756 USA. NCI, Div Clin Sci, Bethesda, MD 20892 USA. RP Wrensch, M (reprint author), Univ Calif San Francisco, Dept Epidemiol & Biostat, Sch Med, San Francisco, CA 94143 USA. RI Liu, Edison/C-4141-2008 FU NCI NIH HHS [CA 52689] NR 44 TC 12 Z9 15 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD APR PY 1998 VL 7 IS 4 BP 303 EP 308 PG 6 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA ZG556 UT WOS:000073015500006 PM 9568785 ER PT J AU Hartman, TJ Albanes, D Pietinen, P Hartman, AM Rautalahti, M Tangrea, JA Taylor, PR AF Hartman, TJ Albanes, D Pietinen, P Hartman, AM Rautalahti, M Tangrea, JA Taylor, PR TI The association between baseline vitamin E, selenium, and prostate cancer in the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID SERUM SELENIUM; RISK; CARCINOGENESIS; INVITRO; TUMORS; MEN AB The association between prostate cancer and baseline vitamin E and selenium was evaluated in the trial-based cohort of the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study (n = 29,133), During up to 9 years of follow-up, 317 men developed incident prostate cancer, Multivariate Cox proportional hazards models that adjusted for intervention group, benign prostatic hyperplasia, age, smoking, and urban residence were used to evaluate associations between prostate cancer and exposures of interest. There were no significant associations between baseline serum alpha-tocopherol, dietary vitamin E, or selenium and prostate cancer overall, The associations between prostate cancer and vitamin E and some of the baseline dietary tocopherols differed significantly by alpha-tocopherol intervention status, with the suggestion of a protective effect for total vitamin E among those who received the alpha-tocopherol intervention (relative risk was 1.00, 0.68, 0.80, and 0.52 for increasing quartiles; P = 0.07). C1 NCI, Div Canc Prevent & Control, Bethesda, MD 20892 USA. Natl Publ Hlth Inst, SF-00300 Helsinki, Finland. RP Hartman, TJ (reprint author), NCI, Div Canc Prevent & Control, Execut Plaza N,Suite 211,6130 Execut Blvd,MSC 732, Bethesda, MD 20892 USA. RI Albanes, Demetrius/B-9749-2015 FU NCI NIH HHS [N01 CN 45165] NR 34 TC 109 Z9 112 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD APR PY 1998 VL 7 IS 4 BP 335 EP 340 PG 6 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA ZG556 UT WOS:000073015500011 PM 9568790 ER PT J AU Cullinane, C Bohr, VA AF Cullinane, C Bohr, VA TI DNA interstrand cross-links induced by psoralen are not repaired in mammalian mitochondria SO CANCER RESEARCH LA English DT Article ID HAMSTER OVARY CELLS; GENE-SPECIFIC REPAIR; MISMATCH-REPAIR; RINR-38 CELLS; DAMAGE; CISPLATIN; ADDUCTS; MONOADDUCTS; ACID AB Although it is generally known that mitochondria are defective in DNA damage processing, little is known about the DNA repair pathways and mechanisms that exist in these vital organelles. Certain lesions that are removed by base excision repair are efficiently removed in mitochondria, whereas some bulky lesions that are removed by nucleotide excision repair are not repaired in these organelles. There has been much interest in whether mitochondria possess activities for recombination repair, and some previous studies have reported such activities, whereas others have not. We have taken the approach of studying the formation and removal of interstrand cross-links (ICLs) in DNA. These lesions are thought to be repaired by a repair mechanism that involves nucleotide excision and recombinational repair. The formation and repair of DNA ICLs by 4'-hydroxymethyl-4,5',8-trimethylpsoralen was investigated in bath the nuclear and mitochondrial genomes in hamster cells. Seven-fold-higher levels of ICLs were generated in mtDNA than in the dihydrofolate reductase gene, clearly indicating that the mitochondrial gnome is a preferential target of 4'-hydroxymethyl-4,5',8-trimethylpsoralen damage. ICLs were removed efficiently from the dihydrofolate reductase gene, but no repair was observed in mtDNA. Our observations support previous work showing efficient gene-specific repair of these lesions in the nucleus but suggest that repair of this type of ICL does not exist in the mitochondria. The preferential damage of mtDNA and the absence of cross-link repair further suggests that mtDNA may be a biologically important target for psoralen. C1 NIA, Mol Genet Lab, Baltimore, MD 21224 USA. La Trobe Univ, Dept Biochem, Bundoora, Vic 3083, Australia. RP Bohr, VA (reprint author), NIA, Mol Genet Lab, 5600 Nathan Shock Dr, Baltimore, MD 21224 USA. NR 31 TC 29 Z9 31 U1 1 U2 2 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD APR 1 PY 1998 VL 58 IS 7 BP 1400 EP 1404 PG 5 WC Oncology SC Oncology GA ZE314 UT WOS:000072780200018 PM 9537239 ER PT J AU Bogi, K Lorenzo, PS Szallasi, Z Acs, P Wagner, GS Blumberg, PM AF Bogi, K Lorenzo, PS Szallasi, Z Acs, P Wagner, GS Blumberg, PM TI Differential selectivity of ligands for the C1A and C1b phorbol ester binding domains of protein kinase C delta: Possible correlation with tumor-promoting activity SO CANCER RESEARCH LA English DT Article ID CD-1 MOUSE SKIN; NONPROMOTING 12-DEOXYPHORBOL 13-ESTERS; CYSTEINE-RICH DOMAIN; 12-MYRISTATE 13-ACETATE; INDUCED TRANSLOCATION; BIOLOGICAL RESPONSES; IN-VIVO; BRYOSTATIN-1; ACTIVATOR; ALPHA AB Protein kinase C (PKC) represents the major, high-affinity receptor for the phorbol esters as well as for a series of structurally diverse natural products, The phorbol esters function by binding to the tandem C1a and C1b domains in PKC, leading to enzyme activation. Although the typical phorbol esters represent the paradigm for tumor promoters in mouse skin, it is now clear that different high affinity ligands for PKC have distinct biological effects. Thus, the daphnane analogue mezerein is a second-stage promoter, the macrolide bryostatin 1 is a partial antagonist, and certain 12-deoxyphorbol 13-monoesters also function as partial antagonists but with a different pattern of activity, The biochemical basis for these differences is an area of active investigation, In this report, we have examined the relative interaction of ligands differing in structure and pattern of biological response with the Cia and C1b domains of PKC delta. We mutated either or both of the C1 domains of PKC delta, expressed the constructs in NM 3T3 cells, and monitored the interaction of the ligands by their ability to induce translocation of the mutated PKC delta from the cytosol to the particulate fraction, We found that different ligands showed different dependence on the C1a and C1b domains for translocation, Whereas phorbol 12-myristate 13-acetate and the indole alkaloids indolactam and octylindolactam were selectively dependent on the C1b domain, selectivity was not observed for mezerein, for the 12-deoxyphorbol 13-monoesters prostratin or 12-deoxyphorbol 13-phenylacetate, or for the macrocyclic lactone bryostatin 1, Provocatively, the pattern of response corresponds with the activity of the compounds as complete tumor promoters. C1 NCI, Mol Mechanisms Tumor Promot Sect, Cellular Carcinogenesis & Tumor Promot Lab, Bethesda, MD 20892 USA. Uniformed Serv Univ Hlth Sci, Dept Pharmacol, Bethesda, MD 20814 USA. RP Blumberg, PM (reprint author), NCI, Mol Mechanisms Tumor Promot Sect, Cellular Carcinogenesis & Tumor Promot Lab, Bldg 37-3A01,37 Convent Dr,MSC 4255, Bethesda, MD 20892 USA. EM blumberp@dc37a.nci.nih.gov NR 48 TC 63 Z9 63 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD APR 1 PY 1998 VL 58 IS 7 BP 1423 EP 1428 PG 6 WC Oncology SC Oncology GA ZE314 UT WOS:000072780200022 PM 9537243 ER PT J AU Tennenbaum, T Lowry, D Darwiche, N Morgan, DL Gartsbein, M Hansen, L De Luca, LM Hennings, H Yuspa, SH AF Tennenbaum, T Lowry, D Darwiche, N Morgan, DL Gartsbein, M Hansen, L De Luca, LM Hennings, H Yuspa, SH TI Topical retinoic acid reduces skin papilloma formation but resistant papillomas are at high risk for malignant conversion SO CANCER RESEARCH LA English DT Article ID SQUAMOUS-CELL CARCINOMA; FEMALE SENCAR MICE; MOUSE EPIDERMAL-CELLS; GROWTH-FACTOR-BETA; TUMOR PROGRESSION; CARCINOGENESIS PROTOCOL; 2-STAGE CARCINOGENESIS; ACTINIC KERATOSIS; HL-60 CELLS; RAS GENE AB Retinoic acid (RA) was topically applied to the skin of Sencar mice during the promotion phase of specific tumor induction protocols that produce papillomas at low (12-O-tetradecanoylphorhol-13-acetate promoted, TPA) or high (mezerein-promoted) risk for premalignant progression and malignant conversion, RA consistently reduced the yield of papillomas and carcinomas in both protocols, but the frequency of malignant conversion in papillomas that emerged during RA treatment was not reduced, When TPA was reapplied after cessation of RA treatment, the number of papillomas increased 2-fold, suggesting that RA had not eliminated initiated cells. In vitro, RA prevented the emergence of transformed keratinocytes in an assay that mimics malignant conversion, suggesting that RA can suppress conversion if applied during the stage of premalignant progression, Examination of tumor markers at weeks 14 and 22 of the tumor-induction experiments in vivo indicated that papillomas evolving during RA treatment exhibited a phenotype of high progression risk, even in the TPA-promoted groups. In the majority of these tumors, the alpha 6 beta 4 integrin and retinoid X receptor alpha transcripts were detected suprabasally, indicating an advanced state of premalignant progression. RA-treated tumors also expressed higher levels of transcripts for transforming growth factor (TGF)-beta 1 and localized TGF-beta 1 peptide in the basal portions of the tumor fronds. Because up-regulated expression of TGF-beta 1 suppresses papilloma formation, these studies suggest a mechanism whereby RA can prevent papilloma eruption via a TGF-beta intermediate, but papillomas resistant to RA may have altered TGF-beta signaling and progress to carcinomas at an increased frequency. C1 NCI, Cellular Carcinogenesis & Tumor Promot Lab, Div Basic Sci, NIH, Bethesda, MD 20892 USA. Bar Ilan Univ, Dept Life Sci, IL-52900 Ramat Gan, Israel. RP Yuspa, SH (reprint author), NCI, Cellular Carcinogenesis & Tumor Promot Lab, Div Basic Sci, NIH, Bldg 37,Room 3B25,37 Convent Dr MSC 4255, Bethesda, MD 20892 USA. OI Darwiche, Nadine/0000-0002-1862-5426 NR 57 TC 17 Z9 17 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD APR 1 PY 1998 VL 58 IS 7 BP 1435 EP 1443 PG 9 WC Oncology SC Oncology GA ZE314 UT WOS:000072780200024 PM 9537245 ER PT J AU Kuppusamy, P Afeworki, M Shankar, RA Coffin, D Krishna, MC Hahn, SM Mitchell, JB Zweier, JL AF Kuppusamy, P Afeworki, M Shankar, RA Coffin, D Krishna, MC Hahn, SM Mitchell, JB Zweier, JL TI In vivo electron paramagnetic resonance imaging of tumor heterogeneity and oxygenation in a murine model SO CANCER RESEARCH LA English DT Article ID FREE-RADICALS; NITROXIDE RADICALS; RAT-HEART; METABOLISM; SUPEROXIDE; RADIATION; OXIMETRY; TISSUES; CHEMOTHERAPY; MIMICS AB Nitroxides are redox-sensitive probes, which are useful in noninvasively delineating tissue heterogeneity especially with respect to metabolic activity and tissue oxygenation. Recent studies have shown that nitroxides are in vitro and in vivo radioprotectors and selectively protect normal tissue compared to tumor tissue, It has been postulated that the basis for selective radioprotection of normal tissues is greater bioreduction of nitroxides in tumor tissue compared to normal tissue, The aim of the present study mas to investigate the distribution and lifetime of nitroxides in tumor and normal tissues, Mice were implanted with tumor cells (RIF-1) in the thigh, and the tumor was allowed to grow to about 10-15 mm in diameter. After i.v. infusion of nitroxides, in vitro electron paramagnetic resonance spectroscopy and imaging of the tumor were performed using a specially built bridged-loop surface resonator. The pharmacokinetic and spatial distribution of the nitroxides in tumor tissue were followed and compared with those in normal tissue, Three-dimensional spatial images showed significant heterogeneity in the nitroxide distribution as well as reduction rates, The nitroxide reduction rates were significantly higher in tumors than in the normal tissue, Measurements using spin label oximetry showed a substantial difference in the level of oxygenation between normal tissue (muscle) and tumor tissue, Average pO(2) levels in tumor tissue were found to be 3-fold lower than in a corresponding volume of normal tissue, The lower pO(2) levels in tumor compared to normal tissue may explain the more rapid reduction of nitroxides in these tissues, This study demonstrates that electron paramagnetic resonance imaging can perform noninvasive anatomical as well as functional imaging and provide in vivo physiological information regarding cellular metabolism in tumor and normal tissues. C1 Johns Hopkins Univ, Sch Med, Electron Paramagnet Resonance Ctr, Baltimore, MD 21224 USA. Johns Hopkins Univ, Sch Med, Dept Med, Mol & Cellular Biophys Labs, Baltimore, MD 21224 USA. NCI, Radiat Biol Branch, NIH, Bethesda, MD 20892 USA. Hosp Univ Penn, Dept Radiat Oncol, Philadelphia, PA 19104 USA. RP Kuppusamy, P (reprint author), Johns Hopkins Univ, Sch Med, Electron Paramagnet Resonance Ctr, 5501 Hopkins Bayview Circle, Baltimore, MD 21224 USA. EM kuppu@welchlink.welch.jbu.edu FU NHLBI NIH HHS [HL-38324] NR 54 TC 129 Z9 133 U1 2 U2 13 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD APR 1 PY 1998 VL 58 IS 7 BP 1562 EP 1568 PG 7 WC Oncology SC Oncology GA ZE314 UT WOS:000072780200044 PM 9537265 ER PT J AU Rhim, JS Tsai, WP Chen, ZQ Chen, Z Van Waes, C Burger, AM Lautenberger, JA AF Rhim, JS Tsai, WP Chen, ZQ Chen, Z Van Waes, C Burger, AM Lautenberger, JA TI A human vascular endothelial cell model to study angiogenesis and tumorigenesis SO CARCINOGENESIS LA English DT Article ID HUMAN PAPILLOMAVIRUS TYPE-16; MAMMARY EPITHELIAL-CELLS; FIBROBLAST GROWTH-FACTOR; INTEGRIN ALPHA(V)BETA(3); TELOMERASE ACTIVITY; SQUAMOUS CARCINOMA; GENE-TRANSFER; IMMORTALIZATION; TUMOR; EXPRESSION AB Endothelial cell biology has recently been the subject of considerable interest in thrombosis and cancer research. However, the successful establishment of immortalized human endothelial cells which retain differentiated cell characteristics has been rare. We have successfully established immortalized human umbilical vein endothelial cells (HUVECs) by human papilloma virus (HPV)-16 E6-E7, HPV-16 E6, E7 and E6-E7 were successfully introduced into HUVEC cells. Both E6 and E7 cultures had an extended lifespan but eventually underwent senescence. E6-E7 cultures 4-5-2G, however, acquired an indefinite lifespan in culture but did not undergo malignant conversion. Telomerase activity was not detected in either E6 or E7 cultures; however, telomerase was detected in E6-E7 4-5-2G cells. The cells exhibited a 'cobblestone' morphology and developed a capillary-like tube structure upon reaching confluence. The 4-5-2G line expressed Factor VIII related antigen and took up DiI-Ac-LDL as markers of endothelial origin. The line expressed integrin subunits (alpha v beta 3, alpha v beta 5,beta 1, alpha 2, alpha 3, beta 4 and alpha 6) consistent with an endothelial origin. The higher passage of 4-5-2G line showed a similar intensity of integrin immunostaining to that of primary HUVECS. Subsequent infection of these immortal cells with the Kirsten murine sarcoma virus which contains an activated K-ras oncogene induced morphological transformation that led to the acquisition of invasion capability and neoplastic properties. Telomerase was also detected in the tumorigenic v-Ki-ras transformed cell line. These cell lines should be useful for studies of the molecular mechanisms underlying normal and neoplastic endothelial cell proliferation and migration, and might also provide an in vitro model for development of pharmacologic and gene therapy for cardiovascular thrombosis and cancer. C1 NCI, Lab Biochem Physiol, Frederick, MD 21702 USA. SAIC, IRSP, Lab Cellular Biol, Frederick, MD 21702 USA. NIDOCD, Head & Neck Surg Branch, Bethesda, MD 20892 USA. Univ Freiburg, Tumor Biol Ctr, Freiburg, Germany. NCI, Lab Genom Divers, Frederick, MD 21702 USA. RP NCI, Lab Biochem Physiol, Frederick, MD 21702 USA. EM rhimi@fcrfv1.ncifcrf.gov NR 60 TC 36 Z9 40 U1 1 U2 2 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0143-3334 EI 1460-2180 J9 CARCINOGENESIS JI Carcinogenesis PD APR PY 1998 VL 19 IS 4 BP 673 EP 681 DI 10.1093/carcin/19.4.673 PG 9 WC Oncology SC Oncology GA ZL464 UT WOS:000073435500020 PM 9600354 ER PT J AU Fournier, JG Escaig-Haye, F de Villemeur, TB Robain, O Lasmezas, CI Deslys, JP Dormont, D Brown, P AF Fournier, JG Escaig-Haye, F de Villemeur, TB Robain, O Lasmezas, CI Deslys, JP Dormont, D Brown, P TI Distribution and submicroscopic immunogold localization of cellular prion protein (PrPc) in extracerebral tissues SO CELL AND TISSUE RESEARCH LA English DT Article DE prion protein (PrPc); electron microscopy; secretory granules; membrane; extracerebral tissues; hamster; human ID ULTRASTRUCTURAL-LOCALIZATION; INSITU HYBRIDIZATION; SCRAPIE; FORM; CELLS; PRECURSOR; DISEASES; BIOLOGY; RNA AB In transmissible spongiform encephalopathies such as scrapie in animals and Creutzfeldt-Jakob disease in humans, the central event is the conversion of a host-encoded amyloidogenic protein (PrPc) into an abnormal isoform (PrPsc) that accumulates as amyloid in TSE brain. PrPc is a membrane sialoglycoprotein synthesized in the central nervous system and elsewhere. We have examined the ultrastructural localization of PrPc in numerous hamster and some human extracerebral tissues, by means of a post-embedding electron-microscopic method combined with immunogold labeling. In stomach, intestine, lung, and kidney from hamsters, and in stomach, kidney, and spleen from humans, immunogold labeling specific for PrPc is observed on various cellular substructures related to secretory pathways: Golgi apparatus, secretory globules, and plasma membrane. In mucous epithelial cells of stomach and intestine, PrPc appears to be concentrated in secretory globules, suggesting a role for PrPc in the secretory function of the digestive tract. The secretory aspect of PrPc may be a key to understanding the physiopathological mechanisms underlying TSE. C1 Hop La Pitie Salpetriere, Inst Mycol, INSERM, U153, F-75651 Paris 13, France. Hop Trousseau, Serv Neuropediat, F-75571 Paris, France. Hop St Vincent de Paul, INSERM, U29, F-75674 Paris 14, France. CEA, Lab Neurovirol, Fontenay Aux Roses, France. NINDS, Cent Nervous Syst Studies Lab, NIH, Bethesda, MD 20892 USA. RP Fournier, JG (reprint author), Hop La Pitie Salpetriere, Inst Mycol, INSERM, U153, 47 Bd Hop, F-75651 Paris 13, France. NR 28 TC 56 Z9 58 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0302-766X J9 CELL TISSUE RES JI Cell Tissue Res. PD APR PY 1998 VL 292 IS 1 BP 77 EP 84 DI 10.1007/s004410051036 PG 8 WC Cell Biology SC Cell Biology GA ZF545 UT WOS:000072908200009 PM 9506914 ER PT J AU Becker, EL Forouhar, FA Grunnet, ML Boulay, F Tardif, M Bormann, BJ Sodja, D Ye, RD Woska, JR Murphy, PM AF Becker, EL Forouhar, FA Grunnet, ML Boulay, F Tardif, M Bormann, BJ Sodja, D Ye, RD Woska, JR Murphy, PM TI Broad immunocytochemical localization of the formylpeptide receptor in human organs, tissues, and cells SO CELL AND TISSUE RESEARCH LA English DT Article DE neurons; brain; chemotaxis; endothelial cells; human ID FORMYL PEPTIDE RECEPTOR; N-FORMYLPEPTIDE; CHEMOTACTIC FACTORS; HUMAN-SPERMATOZOA; LIGAND-BINDING; CDNA; NEUTROPHILS; IDENTIFICATION AB The formylpeptide receptor (FPR), previously found only on polymorphonuclear leukocytes and monocytes/macrophages, responds to both synthetic N-formyl oligopeptides and those produced by bacteria. The cDNA for human FPR has been cloned and a rabbit polyclonal antiserum directed against a synthetic 11-amino-acid peptide corresponding to the deduced carboxy-terminus has been produced. We have now extensively characterized and used the antibody to detect FPR on normal human tissues and cell types. The receptor antigen is present on some epithelial cells, especially those with a secretory function, and on some endocrine cells, e,g., follicular cells of the thyroid and cortical cells of the adrenal. Liver hepatocytes and Kupffer cells are positive. Smooth muscle and endothelial cells are also generally positive. In the brain and spinal cord, the neurons of the motor, sensory, and cerebellar systems, and those of the parasympathetic and sympathetic systems stain positively. These data suggest that the putative endogenous agonist for FPR or an antigenically similar receptor reacts with cellular targets in the neuromuscular, vascular, endocrine, and immune systems. C1 Univ Connecticut, Ctr Hlth, Dept Pathol, Farmington, CT 06030 USA. CEA, Biochim Lab, CNRS, URA 1130,DBMS, F-38054 Grenoble 9, France. Pfizer Inc, Cent Res, Res & Dev, Groton, CT 06340 USA. Scripps Res Inst, Dept Immunol, La Jolla, CA 92037 USA. Boehringer Ingelheim Pharmaceut Inc, Dept Immunol, Ridgefield, CT 06877 USA. NIAID, Host Def Lab, NIH, Bethesda, MD 20892 USA. RP Becker, EL (reprint author), Univ Connecticut, Ctr Hlth, Dept Pathol, 263 Farmington Ave, Farmington, CT 06030 USA. RI Ye, Richard/O-5223-2016 OI Ye, Richard/0000-0002-2164-5620 NR 26 TC 61 Z9 63 U1 1 U2 4 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0302-766X J9 CELL TISSUE RES JI Cell Tissue Res. PD APR PY 1998 VL 292 IS 1 BP 129 EP 135 DI 10.1007/s004410051042 PG 7 WC Cell Biology SC Cell Biology GA ZF545 UT WOS:000072908200015 PM 9506920 ER PT J AU Rasper, DM Vaillancourt, JP Hadano, S Houtzager, VM Seiden, I Keen, SLC Tawa, P Xanthoudakis, S Nasir, J Martindale, D Koop, BF Peterson, EP Thornberry, NA Huang, JQ MacPherson, DP Black, SC Hornung, F Lenardo, MJ Hayden, MR Roy, S Nicholson, DW AF Rasper, DM Vaillancourt, JP Hadano, S Houtzager, VM Seiden, I Keen, SLC Tawa, P Xanthoudakis, S Nasir, J Martindale, D Koop, BF Peterson, EP Thornberry, NA Huang, JQ MacPherson, DP Black, SC Hornung, F Lenardo, MJ Hayden, MR Roy, S Nicholson, DW TI Cell death attenuation by 'Usurpin', a mammalian DED-caspase homologue that precludes caspase-8 recruitment and activation by the CD-95 (Fas, APO-1) receptor complex SO CELL DEATH AND DIFFERENTIATION LA English DT Article DE apoptosis; caspase; CD95 (Fas, APO-1); ischemia/reperfusion injury ID INTERLEUKIN-1-BETA-CONVERTING ENZYME; ICE/CED-3 PROTEASE; APOPTOSIS; INHIBITION; MECHANISMS; INTERACTS; DOMAIN; FAMILY; BRAIN; GENES AB Apoptotic cell suicide initiated by ligation of CD95 (Fas/APO-1) occurs through recruitment, oligomerization and autocatalytic activation of the cysteine protease, caspase-8 (MACH, FLICE, Mch5). An endogenous mammalian regulator of this process, named Usurpin, has been identified (aliases for Usurpin include CASH, Gasper, CLARP, FLAME-1, FLIP, I-FLICE and MRIT). This protein is ubiquitously expressed and exists as at least three isoforms arising by alternative mRNA splicing. The Usurpin gene is comprised of 13 exons and is clustered within approximately 200 Kb with the caspase-8 and -10 genes on human chromosome 2q33-34. The Usurpin polypeptide has features in common with pro-caspase-8 and -10, including tandem 'death effector domains' on the N-terminus of a large subunit/small subunit caspase-like domain, but it lacks key residues that are necessary for caspase proteolytic activity, including the His and Cys which form the catalytic substrates diad, and residues that stabilize the P-1 aspartic acid in substrates. Retro-mutation of these residues to functional caspase counterparts failed to restore proteolytic activity, indicating that other determinants also ensure the absence of catalytic potential. Usurpin heterodimerized with pro-caspase-8 in vitro and precluded pro-caspase-8 recruitment by the FADD/MORT1 adapter protein. Cell death induced by CD95 (Fas/APO-1) ligation was attenuated in cells transfected with Usurpin. In vivo, a Usurpin deficit was found in cardiac infarcts where TUNEL-positive myocytes and active caspase-3 expression were prominent following ischemia/reperfusion injury. In contrast, abundant Usurpin expression (and a caspase-3 deficit) occurred in surrounding unaffected cardiac tissue, suggesting reciprocal regulation of these pro-and anti-apoptotic molecules in vivo. Usurpin thus appears to be an endogenous modulator of apoptosis sensitivity in mammalian cells, including the susceptibility of cardiac myocytes to apoptotic death following ischemia/reperfusion injury. C1 Merck Frosst Ctr Therapeut Res, Dept Biochem & Mol Biol, Pointe Claire, PQ H9R 4P8, Canada. Merck Frosst Ctr Therapeut Res, Dept Pharmacol, Pointe Claire, PQ H9R 4P8, Canada. Merck Res Labs, Dept Enzymol, Rahway, NJ 07065 USA. NIAID, Immunol Lab, NIH, Bethesda, MD 20892 USA. Univ British Columbia, Dept Med Genet, Canadian Genet Dis Network, Ctr Mol Med & Therapeut, Vancouver, BC V6T 1Z4, Canada. Tokai Univ, Sch Med, Japan Sci & Technol Corp, Int Cooperat Res Project, Kanagawa 25911, Japan. Univ Victoria, Dept Biol, Ctr Environm Hlth, Victoria, BC V8W 3N5, Canada. RP Nicholson, DW (reprint author), Merck Frosst Ctr Therapeut Res, Dept Biochem & Mol Biol, POB 1005, Pointe Claire, PQ H9R 4P8, Canada. RI Koop, Ben/A-8151-2008; Hayden, Michael/D-8581-2011 OI Koop, Ben/0000-0003-0045-5200; Hayden, Michael/0000-0001-5159-1419 NR 50 TC 259 Z9 267 U1 0 U2 5 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE RG21 6XS, HAMPSHIRE, ENGLAND SN 1350-9047 J9 CELL DEATH DIFFER JI Cell Death Differ. PD APR PY 1998 VL 5 IS 4 BP 271 EP 288 DI 10.1038/sj.cdd.4400370 PG 18 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA ZF385 UT WOS:000072892200003 PM 10200473 ER PT J AU Castelli, JC Hassel, BA Maran, A Paranjape, J Hewitt, JA Li, XL Hsu, YT Silverman, RH Youle, RJ AF Castelli, JC Hassel, BA Maran, A Paranjape, J Hewitt, JA Li, XL Hsu, YT Silverman, RH Youle, RJ TI The role of 2 '-5 ' oligoadenylate-activated ribonuclease L in apoptosis SO CELL DEATH AND DIFFERENTIATION LA English DT Article DE programmed cell death; interferon; viruses; staurosporine; diethylmaleate ID PROGRAMMED CELL-DEATH; 28S RIBOSOMAL-RNA; 2-5A-DEPENDENT RNASE; DNA FRAGMENTATION; IN-VIVO; BCL-2; PREVENTION; PROTEIN; GENE; DEGRADATION AB Apoptosis of viral infected cells appears to be one defense strategy to limit viral infection. Interferon can also confer viral resistance by the induction of the 2-5A system com prised of 2'-5' oligoadenylate synthetase (GAS), and RNase L., Since rRNA is degraded upon activation of RNase L and during apoptosis and since both of these processes serve antiviral functions, we examined the role RNase L may play in cell death. Inhibition of RNase L activity, by transfection with a dominant negative mutant, blocked staurosporine-induced apoptosis of NIH3T3 cells and SV40-transformed BALB/c cells, In addition, K562 cell lines expressing inactive RNase L were more resistant to apoptosis induced by decreased glutathione levels. Hydrogen peroxide-induced death of NIH3T3 cells did not occur by apoptosis and was not dependent upon active RNAse L. Apoptosis regulatory proteins of the Bcl-2 family did not exhibit altered expression levels in the absence of RNase L activity, RNase L is required for certain pathways of cell death and may help mediate viral-induced apoptosis. C1 NINDS, Biochem Sect, Surg Neurol Branch, NIH, Bethesda, MD 20892 USA. Cleveland Clin Fdn, Res Inst, Dept Canc Biol, Cleveland, OH 44195 USA. Univ Maryland, Baltimore Canc Ctr, Dept Immunol & Microbiol, Baltimore, MD 21201 USA. RP Youle, RJ (reprint author), NINDS, Biochem Sect, Surg Neurol Branch, NIH, Bethesda, MD 20892 USA. NR 39 TC 122 Z9 124 U1 0 U2 1 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE RG21 6XS, HAMPSHIRE, ENGLAND SN 1350-9047 J9 CELL DEATH DIFFER JI Cell Death Differ. PD APR PY 1998 VL 5 IS 4 BP 313 EP 320 DI 10.1038/sj.cdd.4400352 PG 8 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA ZF385 UT WOS:000072892200007 PM 10200477 ER PT J AU Thaloor, D Singh, AK Sidhu, GS Prasad, PV Kleinman, HK Maheshwari, RK AF Thaloor, D Singh, AK Sidhu, GS Prasad, PV Kleinman, HK Maheshwari, RK TI Inhibition of angiogenic differentiation of human umbilical vein endothelial cells by curcumin SO CELL GROWTH & DIFFERENTIATION LA English DT Article ID FIBROBLAST GROWTH-FACTOR; CAPILLARY-LIKE STRUCTURES; NECROSIS-FACTOR-ALPHA; BASEMENT-MEMBRANE; EXPRESSION; MATRIX; KINASE; PROLIFERATION; BIOSYNTHESIS; STROMELYSIN AB Angiogenesis is a crucial step in the growth and metastasis of cancers, Curcumin inhibits tumor initiation and growth. We analyzed the effect of curcumin on endothelial cell migration, attachment, and tube formation on Matrigel. Curcumin had no effect on endothelial cell migration or attachment to either plastic or Matrigel. Curcumin treatment resulted in a dose-dependent inhibition of tube formation when the cells were treated before plating or at the time of plating on Matrigel. Curcumin treatment also caused the preformed tubes to break down. Curcumin inhibited angiogenesis in a s.c. Matrigel plug model in mice, The role of metalloproteinases has been shown to be important in angiogenesis; therefore, zymography was performed to determine whether curcumin affected protease activity. Zymographs of curcumin-treated culture supernatants showed a decrease in the gelatinolytic activities of secreted 53- and 72-kDa metalloproteinases. Western and Northern analysis showed a dose-dependent decrease in the protein expression and transcript of 72 kDa, indicating that curcumin may be exerting its inhibitory effect at both the transcriptional and posttranscriptional level. These findings suggest that curcumin acts as an angiogenesis inhibitor by modulating protease activity during endothelial morphogenesis. Curcumin could be developed as an antiangiogenic drug. C1 Uniformed Serv Univ Hlth Sci, Dept Pathol, Ctr Combat Casualty & Life Sustainment Res, Bethesda, MD 20814 USA. Birla Inst Technol & Sci, Pilani 333031, Rajasthan, India. NIDR, NIH, Bethesda, MD 20892 USA. RP Maheshwari, RK (reprint author), Uniformed Serv Univ Hlth Sci, Dept Pathol, Ctr Combat Casualty & Life Sustainment Res, 4301 Jones Bridge Rd, Bethesda, MD 20814 USA. NR 35 TC 116 Z9 134 U1 0 U2 3 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 1044-9523 J9 CELL GROWTH DIFFER JI Cell Growth Differ. PD APR PY 1998 VL 9 IS 4 BP 305 EP 312 PG 8 WC Cell Biology SC Cell Biology GA ZG202 UT WOS:000072977400003 PM 9563850 ER PT J AU Gainer, H Chin, H AF Gainer, H Chin, H TI Molecular diversity in neurosecretion: Reflections on the hypothalamo-neurohypophysial system SO CELLULAR AND MOLECULAR NEUROBIOLOGY LA English DT Review DE oxytocin; vasopressin; prohormone convertase; axonal transport; kinesin; calcium channels; SNARE hypothesis; exocytosis; synaptotagmin ID DENSE-CORE VESICLES; PEPTIDERGIC NERVE-TERMINALS; PROHORMONE CONVERTASE PC2; CALCIUM-CHANNEL SUBTYPES; BOVINE CHROMAFFIN CELLS; RAT-BRAIN; AXONAL-TRANSPORT; CA2+-DEPENDENT EXOCYTOSIS; NEUROENDOCRINE CHAPERONE; UNCONVENTIONAL MYOSINS AB 1. The diversity of molecules involved in various aspects of neurosecretion, such as proprotein processing, axonal transport of large dense core vesicles (LDCVs), and regulated secretion, is discussed in the context of the hypothalamo-neurohypophysial system (HNS). 2. Recent studies have uncovered a family of at least seven processing enzymes known as proprotein convertases (PCs) which are involved in proteolytically cleaving protein precursors at paired basic amino acid motifs to yield biologically active peptides. Three of these, PC1(3), 2, and 5, are found in neurons and are involved in producing regulated secretory peptide products. 3. The axonal transport of LDCVs occurs on microtubule tracks by still unknown mechanisms. There are over 11 distinct kinesin-related molecules that have now been identified as possible microtubule motor candidates. 4. Calcium channels in the nervous system are known to be derived from at least five alpha-subunit and four beta-subunit genes with multiple alternatively spliced isoforms in each case. These could account, in part, for the varied calcium currents found in the HNS. 5. The large number of proteins and isoforms now demonstrated to be involved in regulated secretion are discussed, with a focus on LDCV compositions and the synaptotagmin gene family. C1 NINDS, Neurochem Lab, NIH, Bethesda, MD 20892 USA. RP Gainer, H (reprint author), NINDS, Neurochem Lab, NIH, Bldg 36,Rm 4D20,9000 Rockville Pike, Bethesda, MD 20892 USA. NR 129 TC 24 Z9 24 U1 0 U2 1 PU PLENUM PUBL CORP PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0272-4340 J9 CELL MOL NEUROBIOL JI Cell. Mol. Neurobiol. PD APR PY 1998 VL 18 IS 2 BP 211 EP 230 DI 10.1023/A:1022568904002 PG 20 WC Cell Biology; Neurosciences SC Cell Biology; Neurosciences & Neurology GA ZA834 UT WOS:000072406700005 PM 9535291 ER PT J AU Yang, DJ Kuan, CT Payne, J Kihara, A Murray, A Wang, LM Alimandi, M Pierce, JH Pastan, I Lippman, ME AF Yang, DJ Kuan, CT Payne, J Kihara, A Murray, A Wang, LM Alimandi, M Pierce, JH Pastan, I Lippman, ME TI Recombinant heregulin Pseudomonas exotoxin fusion proteins: Interactions with the heregulin receptors and antitumor activity in vivo SO CLINICAL CANCER RESEARCH LA English DT Article ID EPIDERMAL GROWTH-FACTOR; HUMAN-BREAST-CANCER; ERBB3 GENE-PRODUCT; TUMOR-CELL GROWTH; CHIMERIC TOXINS; FACTOR-ALPHA; CYTOTOXIC ACTIVITY; NEU-ONCOGENE; EGF RECEPTOR; EXPRESSION AB Growth factor receptors provide unique opportunities for development of targeted anticancer therapy, Members of the type I receptor tyrosine kinase family, including epidermal growth factor (EGF) receptor (EGFR) and ErbB-2/neu, are often overexpressed in various human cancer cells, including breast, Recently, it has been shown that both ErbB-3 and ErbB-4 are receptors for heregulin (HRG)/Neu differentiation factor, Eight chimeric toxins composed of the extracellular and EGF-like domains of four different HRG isoforms and truncated Pseudomonas exotoxin (PE38KDEL) were constructed, The fusion proteins exhibited activity similar to the native HRG in inducing ErbB receptors phosphorylation, The EGF-like domain of HRG beta 1 and HRG beta 2 fused to PE38KDEL showed the highest cytotoxic activity, with a IC50 of less than or equal to 0.001 ng/ml, The alpha isoforms that were fused to PE38KDEL were 100-fold less active than the beta isoforms, The HRG-Pseudomonas exotoxin (PE) toxins show extremely high activity against cells expressing ErbB-4 receptor, alone or together with other members of the ErbB receptor family, Cells that do not express ErbB-4 but express ErbB-3 receptor, together with the ErbB-2 or EGFR, exhibited moderate sensitivity to HRG-PE toxins, HRG-PE toxins have little or no activity against cells expressing EGFR, ErbB-2, or ErbB-3 alone, More than an 80% tumor regression was achieved by intratumor injection of 1 mu g of fusion proteins per day for 5 days, Continuous i,p, administration of EGF-like domain of HRG beta 1-PE38KDEL for 7 days via a miniosmotic pump at a dose of 40 mu g/kg/day inhibited the growth of ErbB-4 receptor positive but not ErbB-4 receptor negative cell lines in athymic nude mice, We conclude that there is therapeutic potential of HRG-PE toxins in the therapy of cancers overexpressing the ErbB-4 or ErbB-2 plus ErbB-3 receptors. C1 Georgetown Univ, Med Ctr, Vincent T Lombardi Canc Res Ctr, Washington, DC 20007 USA. Georgetown Univ, Med Ctr, Dept Biochem & Mol Biol, Washington, DC 20007 USA. Georgetown Univ, Med Ctr, Dept Med & Pharmacol, Washington, DC 20007 USA. NCI, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. NCI, Mol & Cellular Biol Lab, NIH, Bethesda, MD 20892 USA. RP Yang, DJ (reprint author), Georgetown Univ, Med Ctr, Vincent T Lombardi Canc Res Ctr, Washington, DC 20007 USA. FU NCI NIH HHS [CA51008, 1P50CA58185] NR 57 TC 22 Z9 27 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD APR PY 1998 VL 4 IS 4 BP 993 EP 1004 PG 12 WC Oncology SC Oncology GA ZG200 UT WOS:000072977200022 PM 9563895 ER PT J AU Fan, SJ Cherney, B Reinhold, W Rucker, K O'Connor, PM AF Fan, SJ Cherney, B Reinhold, W Rucker, K O'Connor, PM TI Disruption of p53 function in immortalized human cells does not affect survival or apoptosis after taxol or vincristine treatment SO CLINICAL CANCER RESEARCH LA English DT Article ID TUMOR-SUPPRESSOR GENE; DNA-DAMAGE; WILD-TYPE; LINES; MUTATIONS; AGENTS; RADIOSENSITIVITY; SENSITIVITY; CARCINOMA; CANCER AB In the present study, we report our findings on the impact of p53 disruption on the sensitivity of human cell lines to the antimitotic agents Taxol and vincristine. Comparisons of cell survival and apoptosis were made with gamma-irradiation and, in some cases, several other DNA-damaging chemotherapeutic agents, Studies in eight Burkitt's lymphoma and lymphoblastoid cell lines (four wild-type p53 and four mutant p53 cell lines) revealed that the DNA-damaging agents assayed tended to exhibit less growth inhibition in the mutant p53 cell lines compared to the wildtype p53 cell lines, In contrast, no significant correlation was apparent between p53 gene status and the growth-inhibitory potency of Taxol or vincristine in these eight cell lines, We also found that contrary to gamma-irradiation, Taxol and vincristine could induce apoptosis in lymphoma cell lines harboring p53 mutations, These observations were explored further in lymphoblastoid VDSO cells (wild-type p53) from a normal individual and stably transfected VDSO derivatives lacking p53 function due to expression of the human papillomavirus type-16 E6 gene, We found that p53 disruption in VDSO/E6 cells blocked gamma-ray-induced apoptosis and afforded a survival advantage to VDSO/E6 cells compared to control-transfected cells, In contrast, p53 disruption did not affect Taxol-or vincristine-induced apoptosis or survival in VDSO cells, The effect of p53 disruption on Taxol sensitivity was explored further in the breast carcinoma MCF-7 and colon carcinoma HCT-116 cell lines that had been stably transfected with either the human papillomavirus type-16 Ed gene or a dominant-negative mutant p53 gene, Again, in these cell model systems, we found that p53 disruption did not affect the growth-inhibitory potency of Taxol, Taken together, our results suggest that p53 status is not a dominant factor in the mechanism by which antimitotic agents induce apoptosis and reduce survival in immortalized human cell lines. C1 US FDA, Immunol Lab, Bethesda, MD 20892 USA. NCI, Mol Pharmacol Lab, Div Basic Sci, NIH, Bethesda, MD 20892 USA. RP O'Connor, PM (reprint author), Agouron Pharmaceut Inc, Oncol Res Div, 3565 Gen Atom Ct, San Diego, CA 92121 USA. EM poconnor@agouron.com RI Ain, Kenneth/A-5179-2012 OI Ain, Kenneth/0000-0002-2668-934X NR 32 TC 77 Z9 78 U1 1 U2 3 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD APR PY 1998 VL 4 IS 4 BP 1047 EP 1054 PG 8 WC Oncology SC Oncology GA ZG200 UT WOS:000072977200028 PM 9563901 ER PT J AU Magone, MT Chan, CC Rizzo, LV Kozhich, AT Whitcup, SM AF Magone, MT Chan, CC Rizzo, LV Kozhich, AT Whitcup, SM TI A novel murine model of allergic conjunctivitis SO CLINICAL IMMUNOLOGY AND IMMUNOPATHOLOGY LA English DT Article DE allergy; animal model; conjunctivitis; cytokines; mouse ID T-CELL CLONES; CYTOKINE PRODUCTION; ANTIBODY-RESPONSES; ADHESION MOLECULE; EPITHELIAL-CELLS; IGE PRODUCTION; MAST-CELLS; ANTIGEN-E; B-CELLS; RAGWEED AB Allergic conjunctivitis affects over 40 million patients per year in the United States. Here we present the first murine model that incorporates the clinical, cellular, and humoral parameters of allergic conjunctivitis, including a ragweed-induced Th2-type cytokine production by lymphocytes. SWR/J mice were immunized with short ragweed pollen in aluminum hydroxide. Ten days after immunization, allergic conjunctivitis was induced by one topical application of ragweed pollen onto the eye. Immediate response was characterized by chemosis, redness of the conjunctiva, and lid edema, Histopathology and immunohistochemistry showed dense conjunctival infiltration with polymorphonuclear leukocytes, macrophages, and CD4+ T lymphocytes. In addition, ragweed-specific IgG1 and IgE serum levels were significantly higher in immunized animals, and high levels of IL-4 and IL-5 were detected in supernatants from ragweed-activated lymphocytes. This reproducible model is a well-suited instrument for testing the pathophysiology and future therapies of allergic conjunctivitis. C1 NEI, NIH, Bethesda, MD 20892 USA. RP Magone, MT (reprint author), NEI, NIH, Bldg 10,Rm 10B22, Bethesda, MD 20892 USA. EM tmagone@box-t.nih.gov RI Rizzo, Luiz Vicente/B-4458-2009 NR 40 TC 64 Z9 67 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 0090-1229 J9 CLIN IMMUNOL IMMUNOP JI Clin. Immunol. Immunopathol. PD APR PY 1998 VL 87 IS 1 BP 75 EP 84 DI 10.1006/clin.1997.4507 PG 10 WC Immunology; Pathology SC Immunology; Pathology GA ZM248 UT WOS:000073519500010 PM 9576013 ER PT J AU Dorman, SE Gill, VJ Gallin, JI Holland, SM AF Dorman, SE Gill, VJ Gallin, JI Holland, SM TI Burkholderia pseudomallei infection in a puerto rican patient with chronic granulomatous disease: Case report and review of occurrences in the Americas SO CLINICAL INFECTIOUS DISEASES LA English DT Article ID PSEUDOMONAS-PSEUDOMALLEI; SEVERE MELIOIDOSIS; CEPACIA; CEFTAZIDIME; GLADIOLI; THAILAND; SURVIVAL AB Burkholderia species, notably Burkholderia cepacia and Burkholderia gladioli, are important pathogens in patients with chronic granulomatous disease (CGD), Burkholderia pseudomallei, the causative agent of melioidosis, is endemic in Southeast Asia and northern Australia but is a rare pathogen in other parts of the world. We describe the occurrence of B. pseudomallei infection in a Puerto Rican patient with CGD, This is one of only a small number of documented cases of melioidosis autochthonous to the Americas and is the first reported case of B. pseudomallei infection in a CGD patient from the Americas. We conclude that B. pseudomallei, like B. cepacia and B. gladioli, should be considered a potential pathogen in patients with CGD and that melioidosis should be considered in the differential diagnosis for ill residents of or travelers to Puerto Rico. C1 NIH, Microbiol Serv, Dept Clin Pathol, Warren Grant Magnuson Clin Ctr, Bethesda, MD 20892 USA. NIAID, Host Def Lab, Bethesda, MD 20892 USA. RP Dorman, SE (reprint author), NIH, Microbiol Serv, Dept Clin Pathol, Warren Grant Magnuson Clin Ctr, Bldg 10,Room 11N103,10 Ctr Dr,MSC 1886, Bethesda, MD 20892 USA. NR 43 TC 47 Z9 48 U1 0 U2 1 PU UNIV CHICAGO PRESS PI CHICAGO PA 5801 S ELLIS AVENUE, CHICAGO, IL 60637 USA SN 1058-4838 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD APR PY 1998 VL 26 IS 4 BP 889 EP 894 DI 10.1086/513928 PG 6 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA ZH279 UT WOS:000073091300016 PM 9564470 ER PT J AU Silva, AE McMahon, BJ Parkinson, AJ Sjogren, MH Hoofnagle, JH Di Bisceglie, AM AF Silva, AE McMahon, BJ Parkinson, AJ Sjogren, MH Hoofnagle, JH Di Bisceglie, AM TI Hepatitis B virus DNA in persons with isolated antibody to hepatitis B core antigen who subsequently received hepatitis B vaccine SO CLINICAL INFECTIOUS DISEASES LA English DT Article ID POLYMERASE CHAIN-REACTION; ENZYME-IMMUNOASSAY; SERUM; POPULATION AB Serum samples from 133 persons who were positive only for antibody to hepatitis B core antigen (anti-HBc) by enzyme immunoassay (EIA) were retested for seromarkers of hepatitis B virus (HBV) by radioimmunoassay and for HBV DNA by polymerase chain reaction analysis. All persons were subsequently vaccinated with hepatitis B vaccine. HBV DNA was found in only five persons, four of whom remained positive during retesting. Most persons had a primary antibody response with three doses of hepatitis B vaccine. Evidence of HBV DNA was not detected in 96% of persons with isolated anti-HBc by EIA. C1 Ctr Dis Control & Prevent, Arctic Invest Program, Natl Ctr Infect Dis, Anchorage, AK 99508 USA. NIH, Hepatitis Studies Sect, Bethesda, MD 20892 USA. USA, Med Res Inst Infect Dis, Frederick, MD USA. Ctr Dis Control & Prevent, Alaska Nat Med Ctr, Anchorage, AK 99508 USA. RP McMahon, BJ (reprint author), Ctr Dis Control & Prevent, Arctic Invest Program, Natl Ctr Infect Dis, 4055 Tudor Ctr Dr, Anchorage, AK 99508 USA. NR 10 TC 49 Z9 53 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5801 S ELLIS AVENUE, CHICAGO, IL 60637 USA SN 1058-4838 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD APR PY 1998 VL 26 IS 4 BP 895 EP 897 DI 10.1086/513918 PG 3 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA ZH279 UT WOS:000073091300017 PM 9564471 ER PT J AU Groll, AH Keul, HG Brodt, R Schneider, M AF Groll, AH Keul, HG Brodt, R Schneider, M TI AIDS-associated atypical Pneumocystis carinii pneumonia revisited SO CLINICAL INFECTIOUS DISEASES LA English DT Article ID CHANGING PATTERNS; INFECTIONS C1 Univ Frankfurt Hosp, Dept Internal Med, Frankfurt, Germany. Univ Frankfurt Hosp, Dept Pathol, Frankfurt, Germany. RP Groll, AH (reprint author), NCI, Immunocompromised Host Sect, Pediat Oncol Branch, Bldg 10,Room 13N240,10 Ctr Dr, Bethesda, MD 20892 USA. NR 5 TC 2 Z9 2 U1 1 U2 1 PU UNIV CHICAGO PRESS PI CHICAGO PA 5801 S ELLIS AVENUE, CHICAGO, IL 60637 USA SN 1058-4838 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD APR PY 1998 VL 26 IS 4 BP 1005 EP 1006 DI 10.1086/517633 PG 2 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA ZH279 UT WOS:000073091300046 PM 9564499 ER PT J AU Horton, ND Kaftani, DJ Bruce, DS Bailey, EC Krober, AS Jones, JR Turker, M Khattar, N Su, TP Bolling, SF Oeltgen, PR AF Horton, ND Kaftani, DJ Bruce, DS Bailey, EC Krober, AS Jones, JR Turker, M Khattar, N Su, TP Bolling, SF Oeltgen, PR TI Isolation and partial characterization of an opioid-like 88 kDa hibernation-related protein SO COMPARATIVE BIOCHEMISTRY AND PHYSIOLOGY B-BIOCHEMISTRY & MOLECULAR BIOLOGY LA English DT Article DE hibernation; opioid; HIT; opiate antagonist; glycoprotein; delta opiate receptor; woodchuck; RT-PCR ID GUINEA-PIG ILEUM; INTRAVENTRICULAR BETA-ENDORPHIN; IMMUNOREACTIVE MET-ENKEPHALIN; DELTA-RECEPTOR SUBTYPES; DOG PLASMA-ALBUMIN; INDUCTION TRIGGER; MAMMALIAN HIBERNATION; INDUCED CONTRACTILITY; ANESTHETIZED RATS; GROUND-SQUIRRELS AB Previous studies show that infusion of hibernating woodchuck albumin (HWA) induces hibernation in summer-active ground squirrels and results in profound behavioral and physiological depression in primates. These effects are reversed by the administration of opiate antagonists, suggesting that the putative hibernation induction trigger (HIT) may act through opioid receptors. We have demonstrated that both HIT-containing plasma and the synthetic alpha opioid D-Ala(2)-D-Leu(5)-enkephalin (DADLE), which mimics the activity of HIT in hibernators, extend tissue survival time of a multi-organ autoperfusion system by 3-fold. In this study we present the first data showing biological activity with a much more highly purified plasma fraction from hibernating woodchucks, identified as the hibernation-related factor (HRF). Both the HRF and DADLE show opiate-like contractile inhibition in the mouse vas deferens (Mvd) bioassay. We also have preliminary evidence in an isolated rabbit heart preparation indicating that the HRF and DADLE act similarly to restore left ventricular function following global myocardial ischemia. Furthermore, we have partially sequenced an alpha 1-glycoprotein-like 88 kDa hibernation-related protein (p88 HRP) present in this fraction, which may prove to be the blood-borne HIT molecule. (C) 1998 Elsevier Science Inc. All rights reserved. C1 Univ Kentucky, Med Ctr, Dept Pathol, Lexington, KY 40536 USA. Univ Texas, Coll Pharm, Div Pharmacol & Toxicol, Austin, TX USA. Wheaton Coll, Dept Biol, Wheaton, IL USA. NIDA, Portland, OR USA. Univ Michigan, Dept Surg, Ann Arbor, MI 48109 USA. Vet Adm Med Ctr, Lexington, KY 40511 USA. RP Univ Kentucky, Med Ctr, Dept Pathol, MS117 UK,800 Rose St, Lexington, KY 40536 USA. OI Jones, Jeffrey/0000-0002-7570-2571 NR 71 TC 40 Z9 40 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1096-4959 EI 1879-1107 J9 COMP BIOCHEM PHYS B JI Comp. Biochem. Physiol. B-Biochem. Mol. Biol. PD APR PY 1998 VL 119 IS 4 BP 787 EP 805 DI 10.1016/S0305-0491(98)00056-X PG 19 WC Biochemistry & Molecular Biology; Zoology SC Biochemistry & Molecular Biology; Zoology GA 118FT UT WOS:000075828300021 PM 9787770 ER PT J AU Lamb, ME AF Lamb, ME TI Fathers as primary caregivers SO CONTEMPORARY PSYCHOLOGY LA English DT Book Review C1 NICHHD, Sect Social & Emot Dev, Bethesda, MD 20892 USA. RP Lamb, ME (reprint author), NICHHD, Sect Social & Emot Dev, Bethesda, MD 20892 USA. NR 1 TC 0 Z9 0 U1 1 U2 2 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 0010-7549 J9 CONTEMP PSYCHOL JI Comtemp. Psychol. PD APR PY 1998 VL 43 IS 4 BP 271 EP 272 PG 2 WC Psychology, Multidisciplinary SC Psychology GA ZE606 UT WOS:000072811400018 ER PT J AU Esposito, C Banks, SM Eichacker, PQ AF Esposito, C Banks, SM Eichacker, PQ TI Prophylactic granulocyte colony-stimulating factor in critically ill patients: Not time yet SO CRITICAL CARE MEDICINE LA English DT Editorial Material DE granulocyte colony-stimulating factor; infection, nosocomial; mechanical ventilation; brain injury, acute; bacteremia ID SURGICAL PATIENTS; SEPSIS; INJURY; MECHANISMS; INFECTION; RATS; CSF C1 NIH, Dept Crit Care Med, Crit Care Med Sect, Bethesda, MD 20892 USA. RP Esposito, C (reprint author), NIH, Dept Crit Care Med, Crit Care Med Sect, Bldg 10,Rm 7D-43,9000 Rockville Pike, Bethesda, MD 20892 USA. NR 28 TC 9 Z9 9 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0090-3493 J9 CRIT CARE MED JI Crit. Care Med. PD APR PY 1998 VL 26 IS 4 BP 636 EP 637 DI 10.1097/00003246-199804000-00005 PG 2 WC Critical Care Medicine SC General & Internal Medicine GA ZH472 UT WOS:000073113900005 PM 9559595 ER PT J AU Walker, R Kaner, RJ AF Walker, R Kaner, RJ TI Pneumocystis pneumonia in the intensive care unit: Location, location, location? SO CRITICAL CARE MEDICINE LA English DT Editorial Material DE Pneumocystis carinii pneumonia; human immunodeficiency virus; acquired immunodeficiency syndrome; intensive care unit; resource allocation ID CARINII PNEUMONIA C1 NIAID, Bethesda, MD 20892 USA. Cornell Univ Med Coll, New York, NY USA. RP Walker, R (reprint author), NIH, Bldg 10,Room 11C103,10 Ctr Dr,MSC 1880, Bethesda, MD 20892 USA. RI Andrade, Hugo/M-6631-2013 OI Andrade, Hugo/0000-0001-6781-6125 NR 8 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0090-3493 J9 CRIT CARE MED JI Crit. Care Med. PD APR PY 1998 VL 26 IS 4 BP 640 EP 641 DI 10.1097/00003246-199804000-00007 PG 2 WC Critical Care Medicine SC General & Internal Medicine GA ZH472 UT WOS:000073113900007 PM 9559597 ER PT J AU Lamb, ME AF Lamb, ME TI Assessments of children's credibility in forensic contexts SO CURRENT DIRECTIONS IN PSYCHOLOGICAL SCIENCE LA English DT Article ID SEXUAL ABUSE C1 NICHHD, Sect Social & Emot Dev, Bethesda, MD 20814 USA. RP Lamb, ME (reprint author), NICHHD, Sect Social & Emot Dev, 9190 Rockville Pike, Bethesda, MD 20814 USA. NR 15 TC 6 Z9 6 U1 0 U2 0 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 APR PY 1998 VL 7 IS 2 BP 43 EP 46 DI 10.1111/1467-8721.ep13175602 PG 4 WC Psychology, Multidisciplinary SC Psychology GA 131QU UT WOS:000076587400002 ER PT J AU Finkel, T AF Finkel, T TI Oxygen radicals and signaling SO CURRENT OPINION IN CELL BIOLOGY LA English DT Article ID NF-KAPPA-B; HYPOXIA-INDUCIBLE FACTOR-1; ACTIVATED PROTEIN-KINASE; PROGRAMMED CELL-DEATH; SMOOTH-MUSCLE CELLS; TRANSCRIPTION FACTOR; NADPH OXIDASE; SUPEROXIDE-DISMUTASE; HYDROGEN-PEROXIDE; HUMAN-FIBROBLASTS AB Recent evidence suggests that reactive oxygen species, such as superoxide anions and hydrogen peroxide, function as intracellular second messengers. This review will discuss the progress in understanding the intracellular pathways leading from ligand stimulation to the generation of oxidants, as well as some of the increasing number of cellular processes that appear to be subject to redox regulation. (C) Current Biology Ltd ISSN 0955-0674. C1 NIH, Cardiol Branch, Bethesda, MD 20892 USA. RP Finkel, T (reprint author), NIH, Cardiol Branch, Bldg 10,Room 7B15,10 Ctr Dr, Bethesda, MD 20892 USA. NR 55 TC 815 Z9 838 U1 5 U2 35 PU CURRENT BIOLOGY LTD PI LONDON PA 34-42 CLEVELAND STREET, LONDON W1P 6LB, ENGLAND SN 0955-0674 J9 CURR OPIN CELL BIOL JI Curr. Opin. Cell Biol. PD APR PY 1998 VL 10 IS 2 BP 248 EP 253 DI 10.1016/S0955-0674(98)80147-6 PG 6 WC Cell Biology SC Cell Biology GA ZG821 UT WOS:000073043200012 PM 9561849 ER PT J AU Robey, E Fowlkes, BJ AF Robey, E Fowlkes, BJ TI The alpha beta versus gamma delta T-cell lineage choice SO CURRENT OPINION IN IMMUNOLOGY LA English DT Review ID RAG-1-DEFICIENT MICE; TRANSGENIC MICE; NOTCH PROTEINS; C-ELEGANS; RECEPTOR; GENE; THYMOCYTES; REARRANGEMENT; DROSOPHILA; LIN-12 AB During thymic development, immature T cells rearrange and express the genes encoding the T-cell antigen receptor and mature as either alpha beta or gamma delta lineage T cells. In the past year, advances have been made in understanding the role of individual components of the T-cell antigen receptor complex in the development of alpha beta and gamma delta lineage T cells. In addition, the transmembrane receptor Notch has recently been implicated as a new player in alpha beta versus gamma delta lineage determination. (C) Current Biology Ltd ISSN 0952-7915. C1 Univ Calif Berkeley, Dept Mol & Cell Biol, Berkeley, CA 94720 USA. NIAID, LCMI, NIH, Bethesda, MD 20892 USA. RP Robey, E (reprint author), Univ Calif Berkeley, Dept Mol & Cell Biol, 471 Life Sci Addit, Berkeley, CA 94720 USA. EM erobey@uclink4.berkeley.edu; bfowlkes@nih.gov NR 60 TC 48 Z9 49 U1 0 U2 0 PU CURRENT BIOLOGY LTD PI LONDON PA 34-42 CLEVELAND STREET, LONDON W1P 6LB, ENGLAND SN 0952-7915 J9 CURR OPIN IMMUNOL JI Curr. Opin. Immunol. PD APR PY 1998 VL 10 IS 2 BP 181 EP 187 DI 10.1016/S0952-7915(98)80247-1 PG 7 WC Immunology SC Immunology GA ZL135 UT WOS:000073402300010 PM 9602307 ER PT J AU Posner, MI Desimone, R AF Posner, MI Desimone, R TI Cognitive neuroscience - Overview: Beyond images SO CURRENT OPINION IN NEUROBIOLOGY LA English DT Editorial Material ID HUMAN BRAIN C1 Univ Oregon, Dept Psychol, Eugene, OR 97403 USA. NIMH, Neuropsychol Lab, NIH, Bethesda, MD 20892 USA. RP Posner, MI (reprint author), Univ Oregon, Dept Psychol, Straub Hall,15th & Onyx, Eugene, OR 97403 USA. NR 3 TC 2 Z9 2 U1 0 U2 1 PU CURRENT BIOLOGY LTD PI LONDON PA 34-42 CLEVELAND STREET, LONDON W1P 6LB, ENGLAND SN 0959-4388 J9 CURR OPIN NEUROBIOL JI Curr. Opin. Neurobiol. PD APR PY 1998 VL 8 IS 2 BP 175 EP 177 DI 10.1016/S0959-4388(98)80137-2 PG 3 WC Neurosciences SC Neurosciences & Neurology GA ZT400 UT WOS:000074081700001 PM 9635199 ER PT J AU Wiggs, CL Martin, A AF Wiggs, CL Martin, A TI Properties and mechanisms of perceptual priming SO CURRENT OPINION IN NEUROBIOLOGY LA English DT Article ID INFERIOR TEMPORAL CORTEX; SHORT-TERM-MEMORY; IMPLICIT MEMORY; RECOGNITION MEMORY; HIPPOCAMPAL-FORMATION; NEURAL MECHANISMS; PREFRONTAL CORTEX; EXPLICIT MEMORY; NEURONS; REPETITION AB Recent evidence suggests that the behavioral phenomenon of perceptual priming and the physiological finding of decreased neural responses with item repetition have similar properties. Both the behavioral and neurophysiological effects show graded changes with multiple repetitions, are resistant to manipulations of particular stimulus attributes (e.g. size and location), and occur independently of awareness. These and other recent findings (e.g. from functional brain imaging in humans) suggest that perceptual priming may be mediated by decreased neural responses associated with perceptual learning. C1 NIMH, Lab Brain & Cognit, Bethesda, MD 20892 USA. RP Wiggs, CL (reprint author), NIMH, Lab Brain & Cognit, Bldg 10,Room 4C-104,10 Ctr Dr,MSC 1366, Bethesda, MD 20892 USA. EM alex@codon.nih.gov RI martin, alex/B-6176-2009 NR 76 TC 516 Z9 522 U1 3 U2 26 PU CURRENT BIOLOGY LTD PI LONDON PA 34-42 CLEVELAND STREET, LONDON W1P 6LB, ENGLAND SN 0959-4388 J9 CURR OPIN NEUROBIOL JI Curr. Opin. Neurobiol. PD APR PY 1998 VL 8 IS 2 BP 227 EP 233 DI 10.1016/S0959-4388(98)80144-X PG 7 WC Neurosciences SC Neurosciences & Neurology GA ZT400 UT WOS:000074081700008 PM 9635206 ER PT J AU Swanson, J Castellanos, FX Murias, M LaHoste, G Kennedy, J AF Swanson, J Castellanos, FX Murias, M LaHoste, G Kennedy, J TI Cognitive neuroscience of attention deficit hyperactivity disorder and hyperkinetic disorder SO CURRENT OPINION IN NEUROBIOLOGY LA English DT Article ID DOPAMINE TRANSPORTER; BASAL GANGLIA; RECEPTOR GENE; MICE LACKING; HUMAN BRAIN; ADHD; ASSOCIATION; EXPRESSION; STIMULANTS; CHILDREN AB Currently, diagnoses of attention deficit hyperactivity disorder (ADHD) and hyperkinetic disorder (HKD) are made on the basis of phenomenology, but information is accumulating from the neurosciences about the biological bases of these disorders. Recent studies addressing the neuropsychology, neuroanatomy, neurochemistry, and molecular biology of ADHD/HKD document abnormalities in well-defined neuroanatomical networks and neurochemical pathways. Magnetic resonance imaging (MRI) studies have shown that some regions of the frontal lobes (anterior superior and inferior) and basal ganglia (caudate nucleus and globus pallidus) are about 10% smatter in ADHD groups than in control groups of children, and molecular genetic studies have shown that diagnosis of ADHD is associated with polymorphisms in some dopamine genes (the dopamine D4 receptor gene and the dopamine transporter gene). C1 Univ Calif Irvine, Child Dev Ctr, Irvine, CA 92612 USA. NIMH, Child Psychiat Branch, Bethesda, MD 20892 USA. Univ Toronto, Clarke Inst Psychiat, Toronto, ON M5T 1R8, Canada. RP Swanson, J (reprint author), Univ Calif Irvine, Child Dev Ctr, 19722 MacArthur Blvd, Irvine, CA 92612 USA. EM jswanson@uci.edu; fxc@helix.nih.gov; mmurias@uci.edu; glahoste@uci.edu; kennedyj@cs.clarke-inst.on.ca NR 50 TC 185 Z9 188 U1 4 U2 8 PU CURRENT BIOLOGY LTD PI LONDON PA 34-42 CLEVELAND STREET, LONDON W1P 6LB, ENGLAND SN 0959-4388 J9 CURR OPIN NEUROBIOL JI Curr. Opin. Neurobiol. PD APR PY 1998 VL 8 IS 2 BP 263 EP 271 DI 10.1016/S0959-4388(98)80150-5 PG 9 WC Neurosciences SC Neurosciences & Neurology GA ZT400 UT WOS:000074081700014 PM 9635212 ER PT J AU Ellis, TM Schatz, DA Ottendorfer, EW Lan, MS Wasserfall, C Salisbury, PJ She, JX Notkins, AL Maclaren, NK Atkinson, MA AF Ellis, TM Schatz, DA Ottendorfer, EW Lan, MS Wasserfall, C Salisbury, PJ She, JX Notkins, AL Maclaren, NK Atkinson, MA TI The relationship between humoral and cellular immunity to IA-2 in IDDM SO DIABETES LA English DT Article ID DEPENDENT DIABETES-MELLITUS; PROTEIN-TYROSINE-PHOSPHATASE; T-CELL; INSULIN; AUTOANTIGEN; RESPONSIVENESS; REACTIVITY; CHILDREN; ANTIGENS; RISK AB Autoantibodies to the neuroendocrine protein insulinoma-associated protein 2 (IA-2), a member of the tyrosine phosphatase family, have been observed in individuals with or at increased risk for IDDM. Because this disease is thought to result from a T-cell-mediated autoimmune destruction of the insulin-producing pancreatic beta-cells, we analyzed humoral and cellular immune reactivity to this autoantigen to further define its role in the pathogenesis of IDDM. Peripheral blood mononuclear cells (PBMC) from individuals with newly diagnosed IDDM or at varying levels of risk for the disease were stimulated in vitro with the entire 42-kDa internal domain of IA-2 (amino acids 603-979), a series of control antigens (glutathionine-S-transferase, tetanus toroid, Candida albicans, mumps, bovine serum albumin), and a mitogen (phytohemagglutinin). The frequency and mean stimulation index of PBMC proliferation against IA-2 was significantly higher in newly diagnosed IDDM subjects (14 of 33 [42%]; 3.8 +/- 4.5 at 10 mu g/ml) and autoantibody-positive relatives at increased risk for IDDM (6 of 9 [66%]; 3.9 +/- 3.2) compared with autoantibody-negative relatives (1 of 15 [7%]; 1.8 +/- 1.0) or healthy control subjects (1 of 12 [8%]; 1.5 +/- 1.0). The frequencies of cellular immune reactivities to all other antigens were remarkably similar between each subject group. Sera from 58% of the newly diagnosed IDDM patients tested mere IA-2 autoantibody positive. Despite investigations suggesting an inverse association between humoral and cellular immune reactivities against islet-cell-associated autoantigens, no such relationship was observed (r(s) = 0.18, P = 0.39) with respect to IA-2. These studies support the autoantigenic nature of IA-2 in IDDM and suggest the inclusion of cellular immune responses as an adjunct marker for the disease. C1 Univ Florida, Coll Med, Dept Pathol, Gainesville, FL 32610 USA. Univ Florida, Coll Med, Dept Pediat, Gainesville, FL USA. NIDR, Oral Med Lab, NIH, Bethesda, MD USA. RP Atkinson, MA (reprint author), Univ Florida, Coll Med, Dept Pathol, Box 100275, Gainesville, FL 32610 USA. EM atkinson@ufl.edu RI wasserfall, clive/J-9078-2012 OI wasserfall, clive/0000-0002-3522-8932 FU NIAID NIH HHS [R01AI/DK39250, P01 AI42288]; NIDDK NIH HHS [R29DK45342] NR 22 TC 37 Z9 38 U1 1 U2 2 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1660 DUKE ST, ALEXANDRIA, VA 22314 USA SN 0012-1797 J9 DIABETES JI Diabetes PD APR PY 1998 VL 47 IS 4 BP 566 EP 569 DI 10.2337/diabetes.47.4.566 PG 4 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA ZD577 UT WOS:000072700500009 PM 9568688 ER PT J AU Jun, HS Kang, Y Yoon, HS Kim, KH Notkins, AL Yoon, JW AF Jun, HS Kang, Y Yoon, HS Kim, KH Notkins, AL Yoon, JW TI Determination of encephalomyocarditis viral diabetogenicity by a putative binding site of the viral capsid protein SO DIABETES LA English DT Article ID INDUCED DIABETES-MELLITUS; SINGLE AMINO-ACID; PANCREATIC BETA-CELLS; NONDIABETOGENIC VARIANTS; VIRUS; RNA; IDENTIFICATION; MICE; SUSCEPTIBILITY; REPLICATION AB The molecular mechanism by which some, but not all, variants of encephalomyocarditis (EMC) virus selectively infect pancreatic beta-cells in mice and induce IDDM has been an enigma for more than a decade. We report here that the binding site of the EMC viral capsid protein VP1 determines viral diabetogenicity. Recombinant chimeric EMC viruses containing threonine, serine, proline, aspartic acid, or valine at position 152 of the major capsid protein VP1 bind poorly to beta-cells. In contrast, recombinant chimeric EMC viruses containing alanine or glycine at position 152 of the VP1 bind efficiently to and infect beta-cells, resulting in the development of diabetes. Three-dimensional molecular modeling reveals that the van der Waals interactions are greater and the residues surrounding position 152 of the VP1 are more closely packed in recombinant chimeric viruses containing threonine, serine, proline, aspartic acid, or valine at position 152 than in recombinant chimeric viruses containing alanine or glycine at the same position. Our studies reveal that the surface areas surrounding alanine or glycine at position 152 of the VP1 are more accessible, thus increasing the availability of the binding sites for attachment to beta-cell receptors and resulting in viral infection and the development of diabetes. C1 Univ Calgary, Fac Med,Dept Microbiol & Infect Dis, Julia McFarlane Diabet Res Ctr, Lab Viral Immunopathogenesis Diabet, Calgary, AB T2N 4N1, Canada. Ajou Univ, Sch Med, Dept Endocrinol & Metab, Inst Med Sci,Lab Endocrinol, Suwon 441749, South Korea. Abbott Labs, Div Pharmaceut Discovery, Abbott Pk, IL 60064 USA. NIDR, Oral Infect & Immun Branch, Expt Med Sect, NIH, Bethesda, MD USA. RP Yoon, JW (reprint author), Univ Calgary, Fac Med,Dept Microbiol & Infect Dis, Julia McFarlane Diabet Res Ctr, Lab Viral Immunopathogenesis Diabet, 3330 Hosp Dr NW, Calgary, AB T2N 4N1, Canada. RI Yoon, Ho Sup/A-2193-2011 NR 28 TC 12 Z9 13 U1 0 U2 0 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1660 DUKE ST, ALEXANDRIA, VA 22314 USA SN 0012-1797 J9 DIABETES JI Diabetes PD APR PY 1998 VL 47 IS 4 BP 576 EP 582 DI 10.2337/diabetes.47.4.576 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA ZD577 UT WOS:000072700500011 PM 9568690 ER PT J AU Harris, MI Flegal, KM Cowie, CC Eberhardt, MS Goldstein, DE Little, RR Wiedmeyer, HM Byrd-Holt, DD AF Harris, MI Flegal, KM Cowie, CC Eberhardt, MS Goldstein, DE Little, RR Wiedmeyer, HM Byrd-Holt, DD TI Prevalence of diabetes, impaired fasting glucose, and impaired glucose tolerance in US adults - The Third National Health and Nutrition Examination Survey, 1988-1994 SO DIABETES CARE LA English DT Article ID CARDIOVASCULAR-DISEASE; POPULATION; MORTALITY; TRENDS; NIDDM AB OBJECTIVE - To evaluate the prevalence and time trends for diagnosed and undiagnosed diabetes, impaired fasting glucose, and impaired glucose tolerance in U.S. adults by age, sex, and race or ethnic group, based on data from the Third National Health and Nutrition Examination Survey, 1988-1994 (NHANES III) and prior Health and Nutrition Examination Surveys (HANESs). RESEARCH DESIGN AND METHODS - NHANES III contained a probability sample of 18,825 U.S. adults greater than or equal to 20 years of age who were interviewed to ascertain a medical history of diagnosed diabetes, a subsample of 6,587 adults for whom fasting plasma glucose values were obtained, and a subsample of 2,844 adults between 40 and 74 years of age who received an oral glucose tolerance test. The Second National Health and Nutrition Examination Survey, 1976-1980, and Hispanic HANES used similar procedures to ascertain diabetes. Prevalence was calculated using the 1997 American Diabetes Association fasting plasma glucose criteria and the 1980-1985 World Health Organization (WHO) oral glucose tolerance test criteria. RESULTS - Prevalence of diagnosed diabetes in 1988-1994 was estimated to be 5.1% for U.S. adults greater than or equal to 20 years of age (10.2 million people when extrapolated to the 1997 U.S. population). Using American Diabetes Association criteria, the prevalence of undiagnosed diabetes (fasting plasma glucose greater than or equal to 126 mg/dl) was 2.7% (5.4 million), and the prevalence of impaired fasting glucose (110 to <126 mg/dl) was 6.9% (13.4 million). There were similar rates of diabetes for men and women, but the rates for non-Hispanic blacks and Mexican-Americans were 1.6 and 1.9 times the rate for non-Hispanic whites. Based on American Diabetes Association criteria, prevalence of diabetes (diagnosed plus undiagnosed) in the total population of people who were 40-74 years of age increased from 8.9% in the period 1976-1980 to 12.3% by 1988-1994. A similar increase was found when WHO criteria were applied (11.4 and 14.3%). CONCLUSIONS - The high rates of abnormal fasting and postchallenge glucose found in NHANES III, together with the increasing frequency of obesity and sedentary lifestyles in the population, make it likely that diabetes will continue to be a major health problem in the U.S. C1 NIDDK, NIH, Bethesda, MD 20892 USA. Social & Sci Syst, Bethesda, MD USA. Ctr Dis Control & Prevent, Natl Ctr Hlth Stat, Hyattsville, MD 20782 USA. Univ Missouri, Sch Med, Columbia, MO 65211 USA. RP Harris, MI (reprint author), NIDDK, NIH, Bldg 45,Room 5AN24, Bethesda, MD 20892 USA. EM harrism@ep.niddk.nih.gov RI Flegal, Katherine/A-4608-2013; OI Flegal, Katherine/0000-0002-0838-469X; Little, Randie/0000-0001-6450-8012 NR 27 TC 1840 Z9 1891 U1 7 U2 38 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1660 DUKE ST, ALEXANDRIA, VA 22314 USA SN 0149-5992 J9 DIABETES CARE JI Diabetes Care PD APR PY 1998 VL 21 IS 4 BP 518 EP 524 DI 10.2337/diacare.21.4.518 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA ZD293 UT WOS:000072670700010 PM 9571335 ER PT J AU Ustun, B Compton, W Mager, D Babor, T Baiyewu, O Chatterji, S Cottler, L Gogus, A Mavreas, V Peters, L Pull, C Saunders, J Smeets, R Stipec, MR Vrasti, MRS Hasin, D Room, R Van den Brink, W Regier, D Blaine, J Grant, BF Sartorius, N AF Ustun, B Compton, W Mager, D Babor, T Baiyewu, O Chatterji, S Cottler, L Gogus, A Mavreas, V Peters, L Pull, C Saunders, J Smeets, R Stipec, MR Vrasti, MRS Hasin, D Room, R Van den Brink, W Regier, D Blaine, J Grant, BF Sartorius, N TI WHO Study on the reliability and validity of the alcohol and drug use disorder instruments: Overview of methods and results (vol 47, pg 161, 1997) SO DRUG AND ALCOHOL DEPENDENCE LA English DT Correction C1 WHO, Div Mental Hlth & Prevent Substance Abuse, Unit Epidemiol Classificat & Assessment, CH-1211 Geneva 27, Switzerland. Washington Univ, Sch Med, Dept Psychiat, St Louis, MO 63110 USA. Univ Connecticut, Ctr Hlth, Dept Psychiat, Farmington, CT 06032 USA. Univ Coll Ibadan Hosp, Dept Psychiat, Ibadan, Nigeria. Hacettepe Univ, Dept Psychiat, Ankara, Turkey. Univ Athens, Dept Psychiat, Athens, Greece. St Vincents Hosp, Clin Res Unit Anxiety Disorders, Darlinghurst, NSW 2010, Australia. Ctr Hosp, Serv Neuropsychiat, Luxembourg, Luxembourg. Royal Prince Alfred Hosp, Dept Psychiat, Camperdown, NSW, Australia. Minist Hlth Welf & Sports, Inspectorate Hlth Care, Rijswijk, Netherlands. Behav Sci Res Inst, Off Dean Acad Affairs, San Juan, PR USA. Hosp Psychiat, Trimis, Romania. Columbia Univ, Coll Phys & Surg, Dept Psychiat, New York, NY 10021 USA. Addict Res Fdn, Toronto, ON M5S 2S1, Canada. Univ Amsterdam, Amsterdam Inst Addict Res, Amsterdam, Netherlands. NIMH, Div Epidemiol & Serv Res, Rockville, MD 20857 USA. NIDA, Div Clin Res, Rockville, MD 20852 USA. NIAAA, Div Biometry & Epidemiol, Rockville, MD 20852 USA. Univ Geneva, Dept Psychiat, Geneva, Switzerland. RP Ustun, B (reprint author), WHO, Div Mental Hlth & Prevent Substance Abuse, Unit Epidemiol Classificat & Assessment, CH-1211 Geneva 27, Switzerland. NR 1 TC 8 Z9 8 U1 0 U2 2 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0376-8716 J9 DRUG ALCOHOL DEPEN JI Drug Alcohol Depend. PD APR 1 PY 1998 VL 50 IS 2 BP 185 EP 186 PG 2 WC Substance Abuse; Psychiatry SC Substance Abuse; Psychiatry GA ZU348 UT WOS:000074188100011 ER PT J AU Pietrini, P Teipel, SJ Bartenstein, P Rapoport, SI Moller, HJ Hampel, H AF Pietrini, P Teipel, SJ Bartenstein, P Rapoport, SI Moller, HJ Hampel, H TI PET and the effects of aging and neurodegeneration on brain function: Basic principles SO DRUG NEWS & PERSPECTIVES LA English DT Article ID CEREBRAL BLOOD-FLOW; POSITRON EMISSION TOMOGRAPHY; GLUCOSE; (H2O)-O-15; DISEASE; VOLUME; AGE AB In the first pari of a three-part series on the role of positron emission tomography (PET) in the study of neurodegeneration and aging in the human brain, the authors review the historical development of the in vivo measurement of brain function resulting in recent advances in PET technology. An overview is presented of the physical principles of PET scanning and the inherent limitations of this technology to set the basis for the critical interpretation of PET data presented in the second and third parts and in the ever-increasing number of PET studies on the brain in different physiological and pathological conditions. Finally, the authors describe the ability to measure in vivo regional cerebral glucose metabolism with [F-18]-FDG PET, regional cerebral blood flow and the distribution and binding capacity of neuroreceptors. They conclude with future perspectives of PET technology and its relevance, especially for neuropsychiatric research. (C) 1988 Prous Science. All rights reserved. C1 Univ Munich, Dept Psychiat, Geriatr Res Branch, Alzheimer Res Grp, Munich, Germany. Tech Univ Munich, Dept Nucl Med, D-8000 Munich, Germany. Univ Munich, Dept Psychiat, D-8000 Munich, Germany. NIA, Neurosci Lab, NIH, Bethesda, MD 20892 USA. NR 32 TC 1 Z9 2 U1 0 U2 0 PU PROUS SCIENCE, SA PI BARCELONA PA PO BOX 540, PROVENZA 388, 08025 BARCELONA, SPAIN SN 0214-0934 J9 DRUG NEWS PERSPECT JI Drug News Perspect. PD APR PY 1998 VL 11 IS 3 BP 161 EP 165 DI 10.1358/dnp.1998.11.3.863652 PG 5 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA ZX986 UT WOS:000074575300004 PM 15616616 ER PT J AU Matsumoto, K Wassarman, KM Wolffe, AP AF Matsumoto, K Wassarman, KM Wolffe, AP TI Nuclear history of a pre-mRNA determines the translational activity of cytoplasmic mRNA SO EMBO JOURNAL LA English DT Article DE nuclear compartments; ribonuclear protein; splicing control; transcriptional control; translational control ID MATERNAL MESSENGER-RNA; PREMESSENGER RIBONUCLEOPROTEIN PARTICLE; SPLICING IN-VIVO; XENOPUS-LAEVIS; BINDING-PROTEINS; GENE-EXPRESSION; C-MOS; HISTONE-H4 ACETYLATION; SEQUENCE ELEMENT; SR PROTEINS AB The pathways of synthesis and maturation of premessenger RNA in the nucleus have a direct effect on the translational efficiency of mRNA in the cytoplasm. The transcription of intron-less mRNA in vivo directs this mRNA towards translational silencing. The presence of an intron at the 5' end of the transcript relieves this silencing, whereas an intron at the 3' end further represses translation. These regulatory events are strongly dependent on the transcription of pre-mRNA in the nucleus. The impact of nuclear history on regulatory events in the cytoplasm provides a novel mechanism for the control of gene expression. C1 NICHHD, Mol Embryol Lab, NIH, Bethesda, MD 20892 USA. RIKEN, Inst Phys & Chem Res, Bioorgan Chem Lab, Wako, Saitama 35101, Japan. RP Wolffe, AP (reprint author), NICHHD, Mol Embryol Lab, NIH, Bldg 18T,Room 106, Bethesda, MD 20892 USA. EM awlme@helix.nih.gov RI Matsumoto, Ken/F-9083-2013 OI Matsumoto, Ken/0000-0002-7864-3394 NR 95 TC 162 Z9 164 U1 0 U2 5 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0261-4189 EI 1460-2075 J9 EMBO J JI Embo J. PD APR 1 PY 1998 VL 17 IS 7 BP 2107 EP 2121 DI 10.1093/emboj/17.7.2107 PG 15 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA ZH034 UT WOS:000073065500024 PM 9524132 ER PT J AU Ehrhart-Bornstein, M Hinson, JP Bornstein, SR Scherbaum, WA Vinson, GP AF Ehrhart-Bornstein, M Hinson, JP Bornstein, SR Scherbaum, WA Vinson, GP TI Intraadrenal interactions in the regulation of adrenocortical steroidogenesis SO ENDOCRINE REVIEWS LA English DT Review ID RAT ADRENAL-GLAND; FIBROBLAST-GROWTH-FACTOR; CORTICOTROPIN-RELEASING-FACTOR; VASOACTIVE-INTESTINAL-PEPTIDE; RENIN-ANGIOTENSIN SYSTEM; ZONA-GLOMERULOSA CELLS; TUMOR-NECROSIS-FACTOR; SPLANCHNIC NERVE-STIMULATION; CYCLASE-ACTIVATING POLYPEPTIDE; MESSENGER-RIBONUCLEIC-ACID C1 Univ Leipzig, Dept Internal Med 3, D-04103 Leipzig, Germany. Queen Mary Univ London, Dept Biochem, London E1 4NS, England. NICHHD, NIH, Bethesda, MD 20892 USA. Univ Dusseldorf, Diabet Res Inst, D-40225 Dusseldorf, Germany. RP NIMH, NIH, Bldg 10,Room 2D46,10 Ctr Dr,MSC 1284, Bethesda, MD 20892 USA. NR 672 TC 409 Z9 421 U1 0 U2 5 PU ENDOCRINE SOC PI WASHINGTON PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA SN 0163-769X EI 1945-7189 J9 ENDOCR REV JI Endocr. Rev. PD APR PY 1998 VL 19 IS 2 BP 101 EP 143 DI 10.1210/er.19.2.101 PG 43 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA ZG219 UT WOS:000072979100001 PM 9570034 ER PT J AU Bornstein, SR Webster, EL Torpy, DJ Richman, SJ Mitsiades, N Igel, M Lewis, DB Rice, KC Joost, HG Tsokos, M Chrousos, GP AF Bornstein, SR Webster, EL Torpy, DJ Richman, SJ Mitsiades, N Igel, M Lewis, DB Rice, KC Joost, HG Tsokos, M Chrousos, GP TI Chronic effects of a nonpeptide corticotropin-releasing hormone type I receptor antagonist on pituitary-adrenal function, body weight, and metabolic regulation SO ENDOCRINOLOGY LA English DT Article ID SPLANCHNIC NERVE-STIMULATION; HYPOPHYSECTOMIZED RATS; INSULIN-RESISTANCE; ENERGY-BALANCE; LEPTIN LEVELS; ACTH RELEASE; GLAND; ADRENOCORTICOTROPIN; SECRETION; GLUCOCORTICOIDS AB CRH, the principal regulator of the hypothalamic-pituitary-adrenal axis and modulator of autonomic nervous system activity, also participates in the regulation of appetite and energy expenditure. Antalarmin, a pyrrolopyrimidine compound, antagonizes CRH type 1 receptor-mediated effects of CRH, including pituitary ACTH: release, stress behaviors, and acute inflammation. We administered antalarmin chronically to evaluate its effects on hypothalamic-pituitary-adrenal axis function and metabolic status. Adult male rats were treated twice daily with 20 mg/kg of ip antalarmin or placebo over 11 days. The animals were weighed; plasma ACTH, corticosterone, leptin, and blood glucose levels were determined; and morphometric analyses were performed to determine adrenal size and structure, including sizing, histochemistry, immunohistochemistry, and electron microscopy. Leptin messenger RNA expression in peripheral fat was analyzed by Northern blot. Antalarmin decreased plasma ACTH (mean +/- SD, 2.62 +/- 0.063 pg/ml) and corticosterone concentrations (10.21 +/- 1.80 mu g/dl) compared with those in vehicle-treated rats [respectively, 5.3 +/- 2.0 (P < 0.05) and 57.02 +/- 8.86 (P < 0.01)]. Antalarmin had no significant effect on body weight, plasma leptin, or blood glucose concentrations or fat cell leptin messenger RNA levels. The width of the adrenal cortex of animals treated with antalarmin was reduced by 31% compared with that in controls without atrophy of the gland. On the ultrastructural level, adrenocortical cells were in a hypofunctional state characterized by reduced vascularization, increased content of lipid droplets, and tubulovesicular mitochondria with fewer inner membranes. The apoptotic rate was increased in the outer zona fasciculata of animals treated with the antagonist (26.6 +/- 3.58%) compared with that in placebo-treated controls (6.8 +/- 0.91%). We conclude that chronic administration of antalarmin does not affect body weight, carbohydrate metabolism, or leptin expression, whereas it reduces adrenocortical function mildly, without anatomical, clinical, or biochemical evidence of causing adrenal atrophy. These results are promising for future uses of such an antagonist in the clinic. C1 NICHHD, Ctr Clin, Dev Neurobiol Branch, NIH, Bethesda, MD 20892 USA. NICHHD, Med Chem Branch, NIH, Bethesda, MD 20892 USA. NCI, Dept Pathol, NIH, Bethesda, MD 20892 USA. Univ Leipzig, Dept Internal Med 3, D-04103 Leipzig, Germany. Rhein Westfal TH Aachen, Inst Pharmacol & Toxicol, Aachen, Germany. RP Bornstein, SR (reprint author), NICHHD, Ctr Clin, Dev Neurobiol Branch, NIH, Bldg 10,Room 10N262, Bethesda, MD 20892 USA. RI Joost, Hans-Georg/J-4462-2013 OI Joost, Hans-Georg/0000-0002-5860-606X NR 60 TC 81 Z9 85 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 APR PY 1998 VL 139 IS 4 BP 1546 EP 1555 DI 10.1210/en.139.4.1546 PG 10 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA ZD282 UT WOS:000072669600012 PM 9528933 ER PT J AU Haft, CR Sierra, NDL Hamer, I Carpentier, JL Taylor, I AF Haft, CR Sierra, NDL Hamer, I Carpentier, JL Taylor, I TI Analysis of the juxtamembrane dileucine motif in the insulin receptor SO ENDOCRINOLOGY LA English DT Article ID GROWTH-FACTOR-I; STRUCTURAL DETERMINANTS; ENDOPLASMIC-RETICULUM; MEDIATED ENDOCYTOSIS; CYTOPLASMIC TAIL; SORTING SIGNALS; KINASE FAMILY; INTERNALIZATION; MEMBRANE; PROTEIN AB Dileucine-containing motifs are involved in trans-Golgi sorting, lysosomal targeting, and internalization. Previously, we have shown that the dileucine motif (EKITLL, residues 982-987) in the juxtamembrane region of the insulin receptor is involved in receptor internalization. Substitution of alanine residues for Leu(986) and Leu(987) led to a 3- to 5-fold decrease in the ability of the receptors to mediate insulin uptake. In the current study, we show that mutation of the same motif to Met(986)Ser(987), the sequence found in the homologous position in the type I insulin-like growth factor receptor, did not affect insulin uptake. Therefore, we inquired whether the sequence EKITMS as an isolated motif could mediate the targeting of a reporter molecule to endosomes and then lysosomes, as was shown previously with the EKITLL motif of the normal receptor. Chimeric molecules containing Tac antigen fused to different hexapeptide sequences showed distinct patterns of subcellular localization by immunofluorescence microscopy. Tac-EKITLL and Tac-EKITAA were found predominantly in lysosomes and the plasma membrane, respectively. In contrast, Tac-EKITMS was found at the plasma membrane, in the trans-Golgi network, and in endosomes, but only small amounts were found in lysosomes. Thus, the dileucine motif (EKITLL) plays an important role in directing endocytosis of the intact insulin receptor and in mediating efficient endocytosis and lysosomal targeting as an isolated motif. Substitution of AA for LL inhibits endocytosis and lysosomal targeting in both systems. In contrast, substitution of MS for LL permits rapid endocytosis in the intact receptor, but mediates modest endocytosis and very little targeting to lysosomes as an isolated motif. Our observations support the idea that sorting signals are recognized at multiple steps in the cell, and that specific amino acid substitutions may differentially affect each of these sorting steps. C1 NIDDKD, Diabet Branch, NIH, Bethesda, MD 20892 USA. Univ Geneva, Dept Morphol, Geneva, Switzerland. RP Taylor, I (reprint author), NIDDKD, Diabet Branch, NIH, Bldg 10,Room 9S-213,10 Ctr Dr,MSC-1829, Bethesda, MD 20892 USA. NR 54 TC 11 Z9 11 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 APR PY 1998 VL 139 IS 4 BP 1618 EP 1629 DI 10.1210/en.139.4.1618 PG 12 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA ZD282 UT WOS:000072669600021 PM 9528942 ER PT J AU Tian, Y Smith, RD Balla, T Catt, KJ AF Tian, Y Smith, RD Balla, T Catt, KJ TI Angiotensin II activates mitogen-activated protein kinase via protein kinase C and ras/raf-1 kinase in bovine adrenal glomerulosa cells SO ENDOCRINOLOGY LA English DT Article ID SMOOTH-MUSCLE-CELLS; SIGNAL-REGULATED KINASE-2; EPIDERMAL-GROWTH-FACTOR; TYROSINE-KINASE; CARDIAC MYOCYTES; ADRENOCORTICAL-CELLS; RECEPTOR SUBTYPE; RAF-1 KINASE; MAP KINASES; RAS AB Aneiotensin II (Ang II) stimulates growth and mitogenesis in bovine adrenal glomerulosa cells, but little is known about the signaling pathways that mediate these responses. An analysis of the growth-promoting pathways in cultured bovine adrenal glomerulosa cells revealed that Ang II, acting via the AT, receptor, caused rapid but transient activation of mitogen-activated protein kinase (MAPK), with an ED50 of 10-50 pM. Although neither Ca2+ influx nor Ca2+ release, from intracellular stores was sufficient to activate MAPK, Ca2+ appeared to play a permissive role in this response. A major component of Ang II-induced MAPK activation was insensitive to pertussis toxin (PTX), although a minor PTX-sensitive component could not be excluded. Ang II also induced the rapid activation of ras and raf-l kinase with time-courses that correlated with that of MAPK. Activation of protein kinase C (PKC) by phorbol 12-myristate 13-acetate was sufficient to activate both MAPK and raf-l kinase. However, whereas PKC depletion had no effect on Ang II-induced raf-l kinase activation, it attenuated Ang II-induced MAPK activation. Ang II also stimulated a mobility shift of raf-l, reflecting hyperphosphorylation of the kinase. However, unlike its activation, raf-l hyperphosphorylation was dependent on PKC and its time-course correlated not with activation, but rather with deactivation of the kinase. Taken together, these findings indicate that Ang II stimulates multiple pathways to MAPK activation via PKC and ras/raf-1 kinase in bovine adrenal glomerulosa cells. C1 NICHD, ERRB, NIH, Bethesda, MD 20892 USA. RP Catt, KJ (reprint author), NICHD, ERRB, NIH, Bldg 49,Room 6A-36,9000,Rockville Pike, Bethesda, MD 20892 USA. EM catt@helix.nih.gov OI Balla, Tamas/0000-0002-9077-3335 NR 50 TC 71 Z9 72 U1 0 U2 1 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 APR PY 1998 VL 139 IS 4 BP 1801 EP 1809 DI 10.1210/en.139.4.1801 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA ZD282 UT WOS:000072669600044 PM 9528965 ER PT J AU Kikuoka, S Shimojo, N Yamaguchi, K Watanabe, Y Hoshioka, A Hirai, A Saito, Y Tahara, K Kohn, LD Maruyama, N Kohno, Y Niimi, H AF Kikuoka, S Shimojo, N Yamaguchi, K Watanabe, Y Hoshioka, A Hirai, A Saito, Y Tahara, K Kohn, LD Maruyama, N Kohno, Y Niimi, H TI The formation of thyrotropin receptor (TSHR) antibodies in a Graves' animal model requires the N-terminal segment of the TSHR extracellular domain SO ENDOCRINOLOGY LA English DT Article ID THYROID-STIMULATING ANTIBODIES; MONOCLONAL-ANTIBODIES; GONADOTROPIN RECEPTORS; IDIOPATHIC MYXEDEMA; BLOCKING ANTIBODIES; DISEASE PATIENTS; IMMUNOGLOBULIN-G; BINDING; MICE; AUTOANTIBODIES AB Immunization of AKR/N mice with murine fibroblasts, transfected with the TSH receptor (TSHR) and a murine major histocompatibility complex class II molecule having the same H-2(k) haplotype (but not either alone), induces immune thyroid disease with the humoral and histological features of human Graves', including the presence of two different TSHR antibodies (TSHRAbs): stimulating TSHRAbs, which cause hyperthyroidism; and TSH-binding-inhibiting immunoglobulins. The primary functional epitope for both types of antibodies in Graves' patients is on the N-terminal portion of the extracellular domain of the TSHR, residues 25 to 165; most require residues 90-165 to express TSHRAb activity, as evidenced in studies using chimeras of the TSHR and lutropin-choriogonadotropin receptor (LH-CGR). To evaluate the role of this region of the TSHR in the formation of Graves' TSHRAbs, we immunized AKR/N mice with fibroblasts transfected with three human TSHR chimeras with residues 9-165 (Mc1+2), 90-165 (Mc2), or 261-370 (Mc4) substituted by equivalent residues of the rat LH-CGR. Mice immunized with the Mc1+2 and Mc2 chimeras, with the N-terminal portion of the extracellular domain of the TSHR substituted by LH-CGR residues, did not develop TSHRAbs. Mice immunized with the Mc4 chimera, having a major portion of the C-terminal portion of the extracellular domain of the TSHR replaced by comparable LH-CGR residues, can develop TSHRAbs. The results suggest that the N-terminal segment of the TSHR extracellular domain is not only a critical functional epitope for Graves' TSHRAbs, but it is important also in their formation in a mouse model of Graves' disease. C1 Chiba Univ, Sch Med, Dept Internal Med 2, Chuo Ku, Chiba 260, Japan. Chiba Univ, Sch Med, Dept Pediat, Chiba 260, Japan. SRL Inc, Hachioji, Tokyo 192, Japan. NIDDK, Cell Regulat Sect, Metab Dis Branch, NIH, Bethesda, MD 20892 USA. Tokyo Metropolitan Inst Gerontol, Dept Mol Biol, Tokyo 173, Japan. RP Shimojo, N (reprint author), Natl Shimoshizu Hosp, Dept Pediat & Clin Hlth, Chiba 284, Japan. NR 40 TC 25 Z9 25 U1 0 U2 0 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0013-7227 EI 1945-7170 J9 ENDOCRINOLOGY JI Endocrinology PD APR PY 1998 VL 139 IS 4 BP 1891 EP 1898 DI 10.1210/en.139.4.1891 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA ZD282 UT WOS:000072669600054 PM 9528975 ER PT J AU Sugino, N Zilberstein, M Srivastava, RK Telleria, CM Nelson, SE Risk, M Chou, JY Gibori, G AF Sugino, N Zilberstein, M Srivastava, RK Telleria, CM Nelson, SE Risk, M Chou, JY Gibori, G TI Establishment and characterization of a simian virus 40-transformed temperature-sensitive rat luteal cell line SO ENDOCRINOLOGY LA English DT Article ID OVARIAN GRANULOSA-CELLS; PROGESTERONE-RECEPTOR GENE; ESTROGEN-RECEPTOR; HYDROXYSTEROID DEHYDROGENASE; MOLECULAR-CLONING; CORPUS-LUTEUM; 20-ALPHA-HYDROXYSTEROID DEHYDROGENASE; GLUCOCORTICOID-RECEPTOR; INDEPENDENT REGULATION; NUCLEAR RECEPTORS AB The primary culture of rat luteal cells and their long-term maintenance have been difficult. Low cellular yields have limited the possibility for the study of gene regulation in luteal cells. The goal of this study was to develop a cell Line to serve as a model by which to study the expression and regulation of various genes specific to luteal cells. We attempted to develop a luteal cell line by transformation of large luteal cells through infection with a temperature-sensitive simian virus (SV-40 tsA209) mutant that has a temperature-sensitive mutation required for the maintenance of cell transformation. We report here the successful establishment of such a cell line, designated GG-CL cells. Large luteal cells were purified to homogeneity by flow cytometry from corpora lutea of day 14 pregnant rats, cultured for 24 h, and then infected with the SV-40 tsA209 mutant virus. Transformed cells were maintained at the permissive temperature (33 C) until colonies were identified. Several colonies of transformed cells were isolated and passaged. They multiplied at 33 C and formed multilayers. At the nonpermissive temperature (40 C), cells reverted to the normal differentiated phenotype similar to the primary luteal cells in culture. To determine whether GG-CL cells express the genes found in normal luteal cells, messenger RNA (mRNA) expression was examined by either Northern analysis or RT-PCR with primers specific to each mRNA. GG-CL cells were found to express receptors for interleukin-li and glucocorticoid, as well as the newly discovered estrogen receptor-beta (ER-beta) and the orphan nuclear receptor nur 77. No receptors for ER-alpha, progesterone, LH, or PRL could be detected. This cell line also expressed 20 alpha-hydroxysteroid dehydrogenase (20 alpha-HSD), but not cholesterol side-chain cleavage cytochrome P450 (P450scc), 3 beta-hydroxysteroid dehydrogenase, or aromatase cytochrome P450 (P450arom). Although the cells did not express the PRL receptor, they did express Janus kinase (JAK2) and signal transducers and activators of transcription (Stat5b), and, when transfected with the PRL receptor, they responded to PRL with a marked inhibition in 20 alpha-HSD mRNA expression. In addition, estradiol enhanced ER-beta expression in a dose-dependent manner whereas cAMP stimulation caused a marked and rapid increase in the expression of the orphan receptor nur 77. In summary, a temperature-sensitive cell, line was successfully established from the large luteal cells of rat corpora lutea. These cells express key genes encoding enzymes and receptors inherent to this defined luteal cell population and respond to stimulation by PRL, estradiol, and cAMP. C1 Univ Illinois, Dept Physiol & Biophys MC 901, Chicago, IL 60612 USA. Faulkner Ctr Reprod Med, Boston, MA 02130 USA. NICHHD, Heritable Disorders Branch, Bethesda, MD 20892 USA. RP Gibori, G (reprint author), Univ Illinois, Dept Physiol & Biophys MC 901, 901 S Wolcott Ave, Chicago, IL 60612 USA. FU FIC NIH HHS [FIC1F05TW205241]; NICHD NIH HHS [HD-11119] NR 44 TC 41 Z9 41 U1 0 U2 3 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 APR PY 1998 VL 139 IS 4 BP 1936 EP 1942 DI 10.1210/en.139.4.1936 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA ZD282 UT WOS:000072669600059 PM 9528980 ER PT J AU Oguchi, H Kimura, S AF Oguchi, H Kimura, S TI Multiple transcripts encoded by the thyroid-specific enhancer-binding protein (T/EBP) thyroid-specific transcription factor-1 (TTF-1) gene: Evidence of autoregulation SO ENDOCRINOLOGY LA English DT Article ID HEPATOCYTE NUCLEAR FACTOR-3; THYROTROPIN RECEPTOR GENE; THYROPEROXIDASE PROMOTER; EXPRESSION PATTERNS; DEFINITIVE ENDODERM; MAMMALIAN-CELLS; PEROXIDASE GENE; B GENE; LUNG; MOUSE AB Multiple transcripts derived from the gene encoding rat thyroid-specific enhancer-binding protein (T/EBP)/thyroid-specific transcription factor-1 (TTIF-1) were identified by complementary DNA cloning and sequencing, and Northern blotting analyses. Six different types of complementary DNAs were identified that differ at their 5' non-coding regions; four contain an intron of different lengths, whereas the other two possess no intron. Ribonuclease protection analyses revealed that multiple promoters are scattered throughout the upstream region, and the usage of these different promoters together with alternative splicing leads to a family of T/EBP messenger RNA (mRNA) species. A similar pattern of expression was also found in the human T/EBP gene expressed in a lung carcinoma cell line. Longer T/EBP mRNAs are more abundant in rat FRTL-5 thyroid cells maintained in the absence of TSH (-TSH) than in cells maintained in the presence of TSH (+TSH). Transfection analyses using the rat T/EBP gene DNA upstream of the ATG initiation codon connected to the luciferase reporter plasmid showed a similar relative activity profile between -TSH and +TSH culture conditions, suggesting that the abundance of longer mRNAs in -TSH conditions may not directly correlate with differences in promoter activities. Rather, TSH status might have a role in maintaining the physiological state of the cells. The upstream DNA of the rat and human T/EBP genes share a cluster of high and low sequence similarities, and both possess respectively 24 and 18 putative T/EBP-binding sites throughout. Cotransfection analyses of the T/EBP promoter-reporter constructs with a T/EBP expression vector into human HepG2 cells, which do not express T/EBP, suggested that autoregulation may be involved in controlling both rat and human T/EBP gene expression. C1 NCI, Lab Metab, NIH, Bethesda, MD 20892 USA. RP Kimura, S (reprint author), NCI, Lab Metab, NIH, Bldg 37,Room 3E-24,9000 Rockville Pike, Bethesda, MD 20892 USA. EM shioko@helix.nih.gov NR 43 TC 38 Z9 39 U1 1 U2 3 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 APR PY 1998 VL 139 IS 4 BP 1999 EP 2006 DI 10.1210/en.139.4.1999 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA ZD282 UT WOS:000072669600066 PM 9528987 ER PT J AU Normant, E Loh, YP AF Normant, E Loh, YP TI Depletion of carboxypeptidase E, a regulated secretory pathway sorting receptor, causes misrouting and constitutive secretion of proinsulin and proenkephalin, but not chromogranin A SO ENDOCRINOLOGY LA English DT Article ID TRANS-GOLGI NETWORK; PROHORMONE CONVERTASE PC2; PH-DEPENDENT AGGREGATION; CPE(FAT)/CPE(FAT) MICE; VESICLE BIOGENESIS; MAMMALIAN-CELLS; SECRETOGRANIN-I; GROWTH-HORMONE; DISULFIDE BOND; CPE(FAT) MICE AB Previous studies have shown that the prohormone POMC is sorted to the regulated secretory pathway (RSP), at the trans-Golgi network, by binding of a conformation-dependent sorting signal to a sorting receptor, identified as membrane-bound carboxypeptidase E (CPE) (Cool et al., 1997, Cell, 88:73-83). In this study, the role of CPE as a sorting receptor for other RSP proteins that contain sorting signals (proinsulin, proenkephalin, and chromogranin A) was investigated in neuroendocrine cells (Neuro-2a) stably expressing CPE antisense RNA. Whereas these cells were depleted of CPE by greater than 85%, electron microscopy showed that they contain dense core secretory granules identical to wild-type Neuro-2a cells, indicating that CPE is not essential for granulogenesis. Secretion and immunocytochemical studies showed that, in wild-type Neuro-2a cells, endogenous proenkephalin and transfected proinsulin/insulin were localized to punctate secretory granules and were released via the RSP. However, in CPE-depleted cells, these two prohormones were released constitutively and had a Golgi-like distribution but were not localized to punctate secretory granules. In contrast, chromogranin A was present in punctate secretory granules and released via the RSP, in wild-type and CPE-depleted Neuro-2a cells. Thus, the sorting of proinsulin and proenkephalin to the RSP, like POMC, necessitates binding to CPE, and hence, CPE acts as a common sorting receptor for targeting these prohormones to the RSP. In contrast, the sorting signal of chromogranin A does not use CPE as a sorting receptor, suggesting the existence of other sorting receptors for the RSP. C1 NICHD, Dev Neurobiol Lab, Cellular Neurobiol Sect, NIH, Bethesda, MD 20892 USA. RP Loh, YP (reprint author), NICHD, Dev Neurobiol Lab, Cellular Neurobiol Sect, NIH, Bldg 49,Room 5A38, Bethesda, MD 20892 USA. EM ypl@codon.nih.gov NR 39 TC 65 Z9 66 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 APR PY 1998 VL 139 IS 4 BP 2137 EP 2145 DI 10.1210/en.139.4.2137 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA ZD282 UT WOS:000072669600082 PM 9529003 ER PT J AU Spangelo, BL Farrimond, DD Thapa, M Bulathsinghala, CM Bowman, KL Sareh, A Hughes, FM Goldstein, AL Badamchian, M AF Spangelo, BL Farrimond, DD Thapa, M Bulathsinghala, CM Bowman, KL Sareh, A Hughes, FM Goldstein, AL Badamchian, M TI Thymosin fraction 5 inhibits the proliferation of the rat neuroendocrine MMQ pituitary adenoma and C6 glioma cell lines in vitro SO ENDOCRINOLOGY LA English DT Article ID HORMONE-RELEASE; GROWTH REGULATION; ALPHA-1; PROLACTIN; CYTOKINES; PEPTIDES; THYMUS; BRAIN; INVOLVEMENT; CONNECTION AB Cytokines such as interleukin-1 (IL-1) and IL-6 stimulate the hypothalamic-pituitary-adrenal (HPA) axis. In addition, these proteins affect pituitary cell proliferation in vitro. Thymosin fraction 5 (TF5) is a partially purified preparation of the bovine thymus that enhances immune system functioning. Because TF5 similarly stimulates the HPA axis, we examined the effects of this preparation on neuroendocrine tumor cell proliferation. Cells of the PRL-secreting rat anterior pituitary adenoma, MMQ (5-50 x 10(3) cells/well), were exposed to vehicle (RPMI-1640 containing 2.5% FCS, 7.5% horse serum, and antibiotics) or TF5 (100-500 mu g/ml) for up to 96 h and the proliferation of MMQ cells monitored using the MTT assay (3-(4, 5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide). TF5-mediated inhibition of cell proliferation was dependent on both TF5 concentration and the initial MMQ cell number. Minimal reductions in optical densities resulted from exposure to 100 mu g/ml TF5, whereas the highest concentration of this preparation (i.e. 500 mu g/ml) completely blocked MMQ cell division. The concentration-dependent effects of TF5 were particularly striking at initial plating densities of 25 and 50 x 10(3) MMQ cells/well; in contrast, all concentrations of TF5 completely inhibited MMQ cell growth at 5 and 10 x 10(3) cells/well. The antiproliferative actions of TF5 on MMQ cells were demonstrable within 24 h and remained for up to 96 h as determined by the MTT assay and actual cell counts. Because the highest densities of MMQ cells were partially refractive to the antiproliferative effects of TF5, we examined the effects of PRL (1-1000 nM) and MMQ cell conditioned medium (50%) on TF5 inhibition of MMQ adenoma proliferation. The TF5 concentration-dependent inhibition of MMQ cell growth was largely reversed by the 50% conditioned medium, whereas PRL slightly potentiated the antiproliferative actions of TF5. The proliferation of the rat C6 glioma cell line (10-30 x 10(3) cells/well) demonstrated greater sensitivity to TF5: concentrations as low as 10 mu g/ml TF5 inhibited C6 cell proliferation (P < 0.01), and near-maximal inhibition was noted at 200 mu g/ml TF5. Significant reductions in MMQ and C6 cell viabilities accompanied decreases in cell number and morphological analysis indicated these cells were dying by apoptosis. The peptides thymosin alpha(1) (T alpha(1)), thymosin beta(4) (T beta(4)), MB35, and MB40 had no effect on either MMQ or C6 cell proliferation, indicating that these TF5 components are not the principle active peptides. Therefore, TF5 was further separated into 60 fractions by preparative reverse phase HPLC. HPLC fractions 17, 25, 26, and 27 significantly suppressed MMQ cell proliferation (P < 0.01) to the same extent as TF5; other HPLC fractions had no effect. These data demonstrate a new biological property of TF5: the inhibition of cell proliferation and the induction of apoptosis in neuroendocrine tumor cells. The proliferation effects were time and concentration dependent and could be partially reversed by an activity present in the MMQ cell conditioned medium. Thus, TF5 and cytokines have opposite effects on adenoma cells because IL-2 and IL-6 stimulate GH(3) cell proliferation. We propose that circulating thymic peptides may act to prevent pituitary adenoma and glioma tumor formation, an action opposed by autocrine growth factors secreted by these tumors. C1 Univ Nevada, Dept Chem, Las Vegas, NV 89154 USA. NIEHS, Lab Signal Transduct, NIH, Res Triangle Pk, NC 27709 USA. George Washington Univ, Med Ctr, Dept Biochem & Mol Biol, Washington, DC 20037 USA. RP Spangelo, BL (reprint author), Univ Nevada, Dept Chem, 4505 Maryland Pkwy, Las Vegas, NV 89154 USA. EM spangelb@nevada.edu FU NIDDK NIH HHS [DK-42059] NR 35 TC 8 Z9 12 U1 0 U2 0 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0013-7227 EI 1945-7170 J9 ENDOCRINOLOGY JI Endocrinology PD APR PY 1998 VL 139 IS 4 BP 2155 EP 2162 DI 10.1210/en.139.4.2155 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA ZD282 UT WOS:000072669600084 PM 9529005 ER PT J AU Alexander, BH Checkoway, H Costa-Mallen, P Faustman, EM Woods, JS Kelsey, KT van Netten, C Costa, LG AF Alexander, BH Checkoway, H Costa-Mallen, P Faustman, EM Woods, JS Kelsey, KT van Netten, C Costa, LG TI Interaction of blood lead and delta-aminolevulinic acid dehydratase genotype on markers of heme synthesis and sperm production in lead smelter workers SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Article DE delta-aminolevulinic acid dehydratase; coproporphyrin; genotype; lead; semen; smelters; zinc protoporphyrin ID GENETIC-POLYMORPHISM; ZINC PROTOPORPHYRIN; EXPOSED WORKERS; METAL EXPOSURE; TOXICITY; ASSOCIATIONS; ISOZYMES AB 'The gene that encodes delta-aminolevulinic acid dehydratase (ALAD) has a polymorphism that may modify lead toxicokinetics and ultimately influence individual susceptibility to lead poisoning. To evaluate the effect of the ALAD polymorphism on lead-mediated outcomes, a cross-sectional study of male employees from a lead-zinc smelter compared associations between blood lead concentration and markers of heme synthesis and semen quality with respect to ALAD genotype. Mate employees were recruited via postal questionnaire to donate blood and urine for analysis of blood lead, zinc protoporphyrin (ZPP), urinary coproporphyrin (I,PU), and ALAD genotype, and semen samples for semen analysis. Of the 134 workers who had ALAD genotypes completed, 114 (85%) were ALAD1-1 (ALPLD1) and 20 (15%) were ALAD1-2 (ALAD2). The mean blood lead concentrations for ALAD1 and ALAD2 were 23.1 and 28.4 mu g/dl (p = 0.08), respectively. ZPP/heme ratios were higher in ALAD1 workers (68.6 vs. 57.8 mu mol/mol; p = 0.14), and the slope of the blood lead ZPP linear relationship was greater for ALAD1 (2.83 vs. 1.50, P = 0.06). No linear relationship between CPU and blood lead concentration was observed for either ALAD1 or ALAD2. The associations of blood lead concentration with ZPP, CPU, sperm count, and sperm concentration were more evident in workers with the ALAD1 genotype and blood lead concentrations greater than or equal to 40 mu g/dl. The ALAD genetic polymorphism appears to modify the association between blood lead concentration and ZPP. However, consistent modification of effects were not found for CPU, sperm count, or sperm concentration. C1 Univ Washington, Dept Environm Hlth, Seattle, WA 98195 USA. Univ Washington, NIEHS, Ctr Ecogenet & Environm Hlth, Seattle, WA 98195 USA. Univ Washington, Inst Risk Anal & Risk Commun, Seattle, WA 98195 USA. Univ Washington, Sch Publ Hlth & Community Med, Ctr Human Dev & Disabil, Seattle, WA 98195 USA. Harvard Univ, Sch Publ Hlth, Occupat Hlth Program, Dept Environm Hlth, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Canc Biol, Boston, MA 02115 USA. Univ British Columbia, Dept Hlth Care & Epidemiol, Vancouver, BC V6T 123, Canada. RP Alexander, BH (reprint author), Univ Washington, Dept Environm Hlth, Box 358772, Seattle, WA 98195 USA. RI Kelsey, Karl/I-1252-2014 FU NIEHS NIH HHS [ES07033, ES00002, ES04696] NR 26 TC 48 Z9 52 U1 1 U2 9 PU US DEPT HEALTH HUMAN SERVICES PUBLIC HEALTH SERVICE PI RES TRIANGLE PK PA NATL INST HEALTH, NATL INST ENVIRONMENTAL HEALTH SERVICES, PO BOX 12233, RES TRIANGLE PK, NC 27709-2233 USA SN 0091-6765 J9 ENVIRON HEALTH PERSP JI Environ. Health Perspect. PD APR PY 1998 VL 106 IS 4 BP 213 EP 216 DI 10.1289/ehp.98106213 PG 4 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA 110JZ UT WOS:000075378800020 PM 9495797 ER PT J AU Stokes, WS Marafante, E AF Stokes, WS Marafante, E TI Introduction and summary of the 13th meeting of the Scientific Group on Methodologies for the Safety Evaluation of Chemicals (SGOMSEC): Alternative testing methodologies SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Editorial Material DE risk assessment; alternative methods; toxicology; ecotoxicology; in vitro methods; reduction; refinement; replacement; testing AB A workshop on alternative toxicological testing methodologies was convened by the Scientific Group on Methodologies for the Safety Evaluation of Chemicals (SGOMSEC) 26-31 January 1997 in Ispra, Italy, at the European Centre for the Validation of Alternative Methods. The purpose of the workshop was to assess the current status of alternative testing methodologies available to evaluate adverse human health and environmental effects of chemicals. Another objective of the workshop was to identify and recommend research needed to fill knowledge gaps that would lead to new test methodologies. Four work groups were established to address conceptual issues, acute toxicity, organ toxicity, and ecotoxicology. A joint workshop report was prepared for each topic and included recommendations for the development and use of alternative methods. Participants concluded that alternative methods and approaches are available that can be incorporated into tiered strategies for toxicological assessments. Use of these methods will reduce the numbers of animals required, and in some instances reduce animal pain and distress. It was recommended that future efforts to develop test methods should emphasize mechanism-based methods that can provide improved predictions of toxicity. Continued international cooperation was encouraged to facilitate future progress in the development of alternative toxicological testing methods. These methods will provide for improvements in human health protection, environmental protection, and animal welfare. C1 NIEHS, Environm Toxicol Program, Res Triangle Pk, NC 27709 USA. European Ctr Validat Alternat Methods, Inst Environm, Ispra, Italy. RP Stokes, WS (reprint author), NIEHS, Environm Toxicol Program, POB 12233,EC-17, Res Triangle Pk, NC 27709 USA. NR 8 TC 9 Z9 9 U1 0 U2 0 PU US DEPT HEALTH HUMAN SERVICES PUBLIC HEALTH SERVICE PI RES TRIANGLE PK PA NATL INST HEALTH, NATL INST ENVIRONMENTAL HEALTH SERVICES, PO BOX 12233, RES TRIANGLE PK, NC 27709-2233 USA SN 0091-6765 J9 ENVIRON HEALTH PERSP JI Environ. Health Perspect. PD APR PY 1998 VL 106 SU 2 BP 405 EP 412 PG 8 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA 110WD UT WOS:000075403800002 PM 9599686 ER PT J AU Blaauboer, BJ Balls, M Barratt, M Casati, S Coecke, S Mohamed, MK Moore, J Rall, D Smith, KR Tennant, R Schwetz, BA Stokes, WS Younes, M AF Blaauboer, BJ Balls, M Barratt, M Casati, S Coecke, S Mohamed, MK Moore, J Rall, D Smith, KR Tennant, R Schwetz, BA Stokes, WS Younes, M TI 13th meeting of the Scientific Group on Methodologies for the Safety Evaluation of Chemicals (SGOMSEC): Alternative testing methodologies and conceptuals issues SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Article; Proceedings Paper CT 13th Meeting of the Scientific-Group-on-Methodologies-for-the-Safety-Evaluation-of-Chemicals on Alternative Testing Methodologies CY JAN 26-31, 1997 CL JOINT RES CTR, ISPRA, ITALY SP Sci Grp Methodol Safety Evaluat Chem, European Ctr Validat Alternat Methods, US Natl Inst Environm Hlth Sci, Commiss European Communities, Intl Program Chem Safety, US EPA, US FDA HO JOINT RES CTR DE risk assessment; alternative methods; toxicology; in vitro methods; reduction; refinement; replacement; testing; QSAR; PBBK modeling; transgenic models ID TOXICOLOGY; VALIDATION AB Substantial world-wide resources are being committed to develop improved toxicological testing methods that will contribute to better protection of human health and the environment. The development of new methods is intrinsically driven by new knowledge emanating from fundamental research in toxicology, carcinogenesis, molecular biology, biochemistry, computer sciences, and a host of other disciplines. Critical evaluations and strong scientific consensus are essential to facilitate adoption of alternative methods for use in the safety assessment of drugs, chemicals, and other environmental factors. Recommendations to hasten the development of new alternative methods included increasing emphasis on the development of mechanism-based methods, increasing fundamental toxicological research, increasing training on the use of alternative methods, integrating accepted alternative methods into toxicity assessment, internationally harmonizating chemical toxicity classification schemes, and increasing international cooperation to develop, validate, and gain acceptance of alternative methods. C1 Univ Utrecht, RITOX, NL-3508 TD Utrecht, Netherlands. Commiss European Communities, ECVAM, Ispra, Italy. Unilever Environm Safety Lab, Bedford, England. Ain Shams Univ, Dept Community Med, Cairo, Egypt. Inst Evaluating Hlth Risks, Washington, DC 20002 USA. NIEHS, Washington, DC 20002 USA. Univ Calif Berkeley, Sch Publ Hlth, Berkeley, CA 94720 USA. NIEHS, Res Triangle Pk, NC 27709 USA. Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. WHO, Int Programme Chem Safety, CH-1211 Geneva, Switzerland. RP Blaauboer, BJ (reprint author), Univ Utrecht, RITOX, POB 80-176, NL-3508 TD Utrecht, Netherlands. NR 11 TC 20 Z9 20 U1 1 U2 3 PU US DEPT HEALTH HUMAN SERVICES PUBLIC HEALTH SERVICE PI RES TRIANGLE PK PA NATL INST HEALTH, NATL INST ENVIRONMENTAL HEALTH SERVICES, PO BOX 12233, RES TRIANGLE PK, NC 27709-2233 USA SN 0091-6765 J9 ENVIRON HEALTH PERSP JI Environ. Health Perspect. PD APR PY 1998 VL 106 SU 2 BP 413 EP 418 DI 10.2307/3433790 PG 6 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA 110WD UT WOS:000075403800003 PM 9599687 ER PT J AU Spielmann, H Bochkov, NP Costa, L Gribaldo, L Guillouzo, A Heindel, JJ Karol, M Parchment, R Pfaller, W Peraita, PP Zacharewski, T AF Spielmann, H Bochkov, NP Costa, L Gribaldo, L Guillouzo, A Heindel, JJ Karol, M Parchment, R Pfaller, W Peraita, PP Zacharewski, T TI Alternative testing methodologies for organ toxicity SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Article; Proceedings Paper CT 13th Meeting of the Scientific-Group-on-Methodologies-for-the-Safety-Evaluation-of-Chemicals on Alternative Testing Methodologies CY JAN 26-31, 1997 CL JOINT RES CTR, ISPRA, ITALY SP Sci Grp Methodol Safety Evaluat Chem, European Ctr Validat Alternat Methods, US Natl Inst Environm Hlth Sci, Commiss European Communities, Intl Program Chem Safety, US EPA, US FDA HO JOINT RES CTR DE alternative methods; toxicology; in vitro methods; reduction; refinement; replacement; testing; hepatotoxicity; nephrotoxicity; immunotoxicity; neurotoxicity; hematotoxicity; reproductive toxicity; endocrine disruptors ID HUMAN HEPATOCYTE CULTURES; VITRO LIVER PREPARATIONS; IN-VITRO; INTERNATIONAL WORKSHOP; DRUG DEVELOPMENT; CELL-CULTURES; INVITRO; MODEL; RAT; VALIDATION AB in the past decade in vitro tests have been developed that represent a range of anatomic structure from perfused whole organs to subcellular fractions. To assess the use of in vitro tests for toxicity testing, we describe and evaluate the current status of organotypic cultures for the major target organs of toxic agents. This includes liver, kidney, neural tissue, the hematopoietic system, the immune system, reproductive organs, and the endocrine system. The second part of this report reviews the application of in vitro culture systems to organ specific toxicity and evaluates the application of these systems both in industry for safety assessment and in government for regulatory purposes. Members of the working group (WG) felt that access to high-quality human material is essential for better use of in vitro organ and tissue cultures in the risk assessment process. Therefore, research should focus on improving culture techniques that will allow better preservation of human material. The WG felt that it is also important to develop and make available relevant reference compounds for toxicity assessment in each organ system, to organize and make available via the internet complete in vivo toxicity data, including human data, containing dose, end points, and toxicokinetics. The WG also recommended that research should be supported to identify and to validate biological end points for target organ toxicity to be used in alternative toxicity testing strategies. C1 Bundesinst Gesundheitlichen Verbraucherschutz & V, D-12277 Berlin, Germany. Russian Acad Med Sci, Moscow, Russia. Univ Washington, Seattle, WA 98195 USA. Commiss European Communities, Joint Res Ctr, ECVAM, I-21020 Ispra, Italy. INSERM, Unite Detoxicat & Reparat, Rennes, France. NIEHS, Res Triangle Pk, NC 27709 USA. Univ Pittsburgh, Pittsburgh, PA USA. Wayne State Univ, Detroit, MI USA. Univ Innsbruck, A-6020 Innsbruck, Austria. Univ Western Ontario, London, ON, Canada. RP Spielmann, H (reprint author), Bundesinst Gesundheitlichen Verbraucherschutz & V, Dieodersdorfer Weg 1, D-12277 Berlin, Germany. EM zebet@bgw.de RI pfaller, walter/A-8803-2010 NR 69 TC 13 Z9 15 U1 0 U2 2 PU US DEPT HEALTH HUMAN SCIENCES PUBLIC HEALTH SCIENCE PI RES TRIANGLE PK PA NATL INST HEALTH, NATL INST ENVIRONMENTAL HEALTH SCIENCES, PO BOX 12233, RES TRIANGLE PK, NC 27709-2233 USA SN 0091-6765 J9 ENVIRON HEALTH PERSP JI Environ. Health Perspect. PD APR PY 1998 VL 106 SU 2 BP 427 EP 439 DI 10.2307/3433792 PG 13 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA 110WD UT WOS:000075403800005 PM 9599689 ER PT J AU Tennant, RW AF Tennant, RW TI Evaluation and validation issues in the development of transgenic mouse carcinogenicity bioassays SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Article; Proceedings Paper CT 13th Meeting of the Scientific-Group-on-Methodologies-for-the-Safety-Evaluation-of-Chemicals on Alternative Testing Methodologies CY JAN 26-31, 1997 CL JOINT RES CTR, ISPRA, ITALY SP Sci Grp Methodol Safety Evaluat Chem, European Ctr Validat Alternat Methods, US Natl Inst Environm Hlth Sci, Commiss European Communities, Intl Program Chem Safety, US EPA, US FDA HO JOINT RES CTR DE carcinogenicity bioassays; transgenic mouse models; carcinogen assay validation; chemical carcinogens; environmental carcinogens; cancer models ID GENETIC TOXICITY ASSAYS; RODENT CARCINOGENICITY; RAS GENE; MICE; IDENTIFICATION; TUMORIGENESIS; TOXICOLOGY; DEFICIENT; TUMORS; P53 AB Transgenic mouse models have emerged as plausible alternatives to long-term bioassays for carcinogenicity. Three transgenic lines evaluated to date have shown a clear capability to discriminate between carcinogens and noncarcinogens, using long-term bioassay results as the standard. The data also suggest that the transgenic lines will not fully duplicate long-term bioassay results. It is proposed that these models do not respond to chemicals that have induced highly restricted species or strain-specific tumor responses in mice or rats. Rather, the value of the transgenic models is predicated on a preferential response to transspecies carcinogens (i.e., those positive in both rats and mice, often including tumors in the same tissues). Thus, although results in transgenic models may not be completely concordant with long-term bioassays, the data can be used effectively in chemical and drug safety assessments. Further, it is proposed that validation of the models is readily achievable via ongoing studies. Validation of any alternative model is best achieved by sufficient mechanistic understanding of the model to reasonably predict the outcome of bioassays conducted in the models and use all available information on the drug or chemical. C1 NIEHS, Lab Environm Carcinogenesis & Mutagenesis, Res Triangle Pk, NC 27709 USA. RP Tennant, RW (reprint author), NIEHS, Lab Environm Carcinogenesis & Mutagenesis, POB 12233,MD B3-09, Res Triangle Pk, NC 27709 USA. EM tennant@niehs.nih.gov NR 21 TC 12 Z9 12 U1 0 U2 0 PU US DEPT HEALTH HUMAN SERVICES PUBLIC HEALTH SERVICE PI RES TRIANGLE PK PA NATL INST HEALTH, NATL INST ENVIRONMENTAL HEALTH SERVICES, PO BOX 12233, RES TRIANGLE PK, NC 27709-2233 USA SN 0091-6765 J9 ENVIRON HEALTH PERSP JI Environ. Health Perspect. PD APR PY 1998 VL 106 SU 2 BP 473 EP 476 PG 4 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA 110WD UT WOS:000075403800010 PM 9599694 ER PT J AU Jung, D Berg, PA Edler, L Ehrenthal, W Fenner, D Flesch-Janys, D Huber, C Klein, R Koitka, C Lucier, G Manz, A Muttray, A Needham, L Papke, O Pietsch, M Portier, C Patterson, D Prellwitz, W Rose, DM Thews, A Konietzko, J AF Jung, D Berg, PA Edler, L Ehrenthal, W Fenner, D Flesch-Janys, D Huber, C Klein, R Koitka, C Lucier, G Manz, A Muttray, A Needham, L Papke, O Pietsch, M Portier, C Patterson, D Prellwitz, W Rose, DM Thews, A Konietzko, J TI Immunologic findings in workers formerly exposed to 2,3,7,8-tetrachlorodibenzo-p-dioxin and its congeners SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Article; Proceedings Paper CT International Symposium on Dioxins and Furans - Epidemiological Assessment of Cancer Risks and Other Human Health Effects CY NOV 07-08, 1996 CL HEIDELBERG, GERMANY DE 2,3,7,8-tetrachlorodibenzo-p-dioxin; TCDD; immunology; human; epidemiology; proliferation; surface markers; autoantibodies; vaccination ID LONG-TERM EXPOSURE; IMMUNE-SYSTEM; FOLLOW-UP; IN-VITRO; TCDD; LYMPHOCYTES; BLOOD; DIOXINS; DIBENZOFURANS; INHIBITION AB One hundred ninety-two workers in a German pesticide factory who were exposed to polychlorinated dibenzodioxins and -furans (PCDD/PCDF) were investigated for former and present diseases and laboratory changes of the immune system. Moreover, in a subgroup of 29 highly exposed and 28 control persons, proliferation studies were performed. in addition to assays such as blood count, immunoglobulins, serum electrophoresis, monoclonal bands, surface markers, autoantibodies, and lymphocyte proliferation, two new methods, the rise of tetanus antibody concentration after vaccination and the in vitro resistance of lymphocytes to chromate, were used to diagnose the morphologic and functional stale of the immune system. There was no stringent correlation of actual PCDD/PCDF concentrations with the occurrence of infections or with one of the immune parameters. In addition, outcomes of the tetanus vaccination and the chromate resistance test were not correlated with PCDD/PCDF. However, the chromate resistance of lymphocytes stimulated by phytohemagglutinin of highly exposed persons was significantly lower than that for the control group. These findings indicate that the function of lymphocytes can be stressed and possibly impaired by high exposure to PCDD/PCDF. C1 Univ Mainz, Inst Arbeits Sozial & Umweltmed, D-55131 Mainz, Germany. Univ Tubingen, Clin Internal Med, Tubingen, Germany. German Canc Res Ctr, D-6900 Heidelberg, Germany. Univ Mainz, Inst Lab Med, D-6500 Mainz, Germany. Fenner & Colleagues, Hamburg, Germany. Med Ctr Chem Workers Hlth, Hamburg, Germany. Univ Mainz, Clin Internal Med, D-6500 Mainz, Germany. NIEHS, Res Triangle Pk, NC 27709 USA. Ctr Dis Control & Prevent, Atlanta, GA USA. ERGO Forsch Gesell mbH, Hamburg, Germany. Univ Mainz, Inst Microbiol, D-6500 Mainz, Germany. RP Jung, D (reprint author), Univ Mainz, Inst Arbeits Sozial & Umweltmed, Obere Zahlbacher Str 67, D-55131 Mainz, Germany. RI Portier, Christopher/A-3160-2010; Needham, Larry/E-4930-2011 OI Portier, Christopher/0000-0002-0954-0279; FU NIEHS NIH HHS [Y1-ES-0072] NR 33 TC 16 Z9 17 U1 1 U2 3 PU US DEPT HEALTH HUMAN SERVICES PUBLIC HEALTH SERVICE PI RES TRIANGLE PK PA NATL INST HEALTH, NATL INST ENVIRONMENTAL HEALTH SERVICES, PO BOX 12233, RES TRIANGLE PK, NC 27709-2233 USA SN 0091-6765 J9 ENVIRON HEALTH PERSP JI Environ. Health Perspect. PD APR PY 1998 VL 106 SU 2 BP 689 EP 695 DI 10.2307/3433821 PG 7 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA 110WD UT WOS:000075403800034 PM 9599718 ER PT J AU Schecter, A AF Schecter, A TI A selective historical review of congener-specific human tissue measurements as sensitive and specific biomarkers of exposure to dioxins and related compounds SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Article; Proceedings Paper CT International Symposium on Dioxins and Furans - Epidemiological Assessment of Cancer Risks and Other Human Health Effects CY NOV 07-08, 1996 CL HEIDELBERG, GERMANY DE exposure assessment; dioxins; dibenzofurans; PCBs; biomarkers of exposure; high resolution gas chromatography mass spectrometry ID AMERICAN VIETNAM VETERANS; OPERATION RANCH HAND; DIBENZO-PARA-DIOXIN; ADIPOSE-TISSUE; AGENT-ORANGE; MALE-RATS; POLYCHLORINATED-BIPHENYLS; LACTATIONAL EXPOSURE; CANCER MORTALITY; CHLORINATED DIOXINS AB Estimating internal exposure or dose of dioxins and related chemicals such as dibenzofurans and dioxinlike polychlorinated biphenyls is relatively straightforward in laboratory animals because a known dose is given and the amount absorbed can be measured. In wildlife, direct tissue measurement and measurement of environmental samples have both recently been used to estimate exposure. Until recently, human studies used only indirect indicators such as skin lesions to qualitatively estimate exposure to these chlorinated organic compounds. Environmental measurements have also sometimes been used to estimate human exposure. Dioxins in human tissue were not measured until the 1970s, when 2,3,7,8-tetrachlorodibenzo-p-dioxin was measured in mothers' milk, congener-specific measurement of dioxins and dibenzofurans in tissues (blood, milk, and adipose tissue) of the general population and exposed workers was first performed in the United Stales in the 1980s. Measurement in a sensitive and specific fashion of the 17 toxic dioxin and dibenzofuran congeners currently found in human tissue from industrial countries began in the 1980s. The use of known chemical standards, capillary columns, high resolution gas chromatography and mass spectrometry (GC-MS) has now become relatively common. GC-MS analysis of blood is currently accepted as the gold standard for estimating human exposure to dioxins. However, analyses are still costly and time consuming, and worldwide there are few qualified laboratories. There is currently a lack of knowledge concerning kinetics at higher and lower exposure levels for most of the toxic dioxin congeners and of levels in target tissues of concern. C1 SUNY Hlth Sci Ctr, Dept Prevent Med, Binghamton, NY USA. RP Schecter, A (reprint author), NIEHS, POB 12233,MD A3-02, Res Triangle Pk, NC 27709 USA. EM schecter@niehs.nih.gov NR 78 TC 24 Z9 26 U1 3 U2 4 PU US DEPT HEALTH HUMAN SERVICES PUBLIC HEALTH SERVICE PI RES TRIANGLE PK PA NATL INST HEALTH, NATL INST ENVIRONMENTAL HEALTH SERVICES, PO BOX 12233, RES TRIANGLE PK, NC 27709-2233 USA SN 0091-6765 J9 ENVIRON HEALTH PERSP JI Environ. Health Perspect. PD APR PY 1998 VL 106 SU 2 BP 737 EP 742 DI 10.2307/3433828 PG 6 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA 110WD UT WOS:000075403800041 PM 9599725 ER PT J AU Grassman, JA Masten, SA Walker, NJ Lucier, GW AF Grassman, JA Masten, SA Walker, NJ Lucier, GW TI Animal models of human response to dioxins SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Article; Proceedings Paper CT International Symposium on Dioxins and Furans - Epidemiological Assessment of Cancer Risks and Other Human Health Effects CY NOV 07-08, 1996 CL HEIDELBERG, GERMANY DE animal models; cancer; cytochrome P450; dioxin; dosimetry; gene expression; interspecies comparisons; human health effects; TCDD ID EPIDERMAL GROWTH-FACTOR; DIBENZO-P-DIOXINS; ARYL-HYDROCARBON HYDROXYLASE; HUMAN AH RECEPTOR; POLYMERASE CHAIN-REACTION; POLYCHLORINATED-BIPHENYLS PCBS; CYTOCHROMES P450 1A1; MESSENGER-RNA LEVELS; SPRAGUE-DAWLEY RATS; DOSE-RESPONSE AB 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is the most potent member of a class bf chlorinated hydrocarbons that interact with the aryl hydrocarbon receptor (AhR). TCDD and dioxinlike compounds are environmentally and biologically stable and as a result, human exposure is chronic and widespread. Studies of highly exposed human populations show that dioxins produce developmental effects, chloracne, and an increase in ail cancers and suggest that they may also alter immune and endocrine function. In contrast, the health effects of low-level environmental exposure have not been established. Experimental animal models can enhance the understanding of the effects of low-level dioxin exposure, particularly when there is evidence that humans respond similarly to the animal models. Although there are species differences in pharmacokinetics, experimental animal models demonstrate AhR-dependent health effects that are similar to those found in exposed human populations. Comparisons of biochemical changes show that humans and animal models have similar degrees of sensitivity to dioxin-induced effects. The information gained from animal models is important for developing mechanistic models of dioxin toxicity and critical for assessing the risks to human populations under different circumstances of exposure. C1 NIEHS, Lab Computat Biol & Risk Anal, Res Triangle Pk, NC 27709 USA. RP Grassman, JA (reprint author), NIEHS, Lab Computat Biol & Risk Anal, POB 12233,MD C4-05, Res Triangle Pk, NC 27709 USA. EM grassman@niehs.nih.gov RI Walker, Nigel/D-6583-2012; masten, scott/R-1403-2016 OI Walker, Nigel/0000-0002-9111-6855; masten, scott/0000-0002-7847-181X NR 185 TC 66 Z9 69 U1 3 U2 4 PU US DEPT HEALTH HUMAN SCIENCES PUBLIC HEALTH SCIENCE PI RES TRIANGLE PK PA NATL INST HEALTH, NATL INST ENVIRONMENTAL HEALTH SCIENCES, PO BOX 12233, RES TRIANGLE PK, NC 27709-2233 USA SN 0091-6765 EI 1552-9924 J9 ENVIRON HEALTH PERSP JI Environ. Health Perspect. PD APR PY 1998 VL 106 SU 2 BP 761 EP 775 DI 10.2307/3433831 PG 15 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA 110WD UT WOS:000075403800044 PM 9599728 ER PT J AU Huff, J Chan, P Waalkes, M AF Huff, J Chan, P Waalkes, M TI Arsenic carcinogenicity testing SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Letter ID NATIONAL TOXICOLOGY PROGRAM C1 Natl Inst Environm Hlth Sci, Res Triangle Pk, NC 27709 USA. NCI, Res Triangle Pk, NC USA. RP Huff, J (reprint author), Natl Inst Environm Hlth Sci, Res Triangle Pk, NC 27709 USA. NR 7 TC 7 Z9 7 U1 0 U2 0 PU US DEPT HEALTH HUMAN SERVICES PUBLIC HEALTH SERVICE PI RES TRIANGLE PK PA NATL INST HEALTH, NATL INST ENVIRONMENTAL HEALTH SERVICES, PO BOX 12233, RES TRIANGLE PK, NC 27709-2233 USA SN 0091-6765 J9 ENVIRON HEALTH PERSP JI Environ. Health Perspect. PD APR PY 1998 VL 106 IS 4 BP A170 EP A170 DI 10.2307/3433948 PG 1 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA 110JZ UT WOS:000075378800002 PM 9625616 ER PT J AU Roth, MJ Strickland, KL Wang, GQ Rothman, N Greenberg, A Dawsey, SM AF Roth, MJ Strickland, KL Wang, GQ Rothman, N Greenberg, A Dawsey, SM TI High levels of carcinogenic polycyclic aromatic hydrocarbons present within food from Linxian, China may contribute to that region's high incidence of oesophageal cancer SO EUROPEAN JOURNAL OF CANCER LA English DT Letter ID ESOPHAGEAL CANCER C1 NCI, Canc Prevent Studies Branch, Div Canc Prevent & Control, Bethesda, MD 20892 USA. Univ N Carolina, Dept Chem, Charlotte, NC 28223 USA. Chinese Acad Med Sci, Inst Canc, Dept Endoscopy, Beijing 100021, Peoples R China. NCI, Occupat Epidemiol Branch, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. RP Roth, MJ (reprint author), NCI, Canc Prevent Studies Branch, Div Canc Prevent & Control, Bethesda, MD 20892 USA. NR 11 TC 50 Z9 54 U1 0 U2 3 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0959-8049 J9 EUR J CANCER JI Eur. J. Cancer PD APR PY 1998 VL 34 IS 5 BP 757 EP 758 PG 2 WC Oncology SC Oncology GA ZP718 UT WOS:000073781500032 PM 9713287 ER PT J AU Snyder, HL Bacik, I Yewdell, JW Behrens, TW Bennink, JR AF Snyder, HL Bacik, I Yewdell, JW Behrens, TW Bennink, JR TI Promiscuous liberation of MHC-class I-binding peptides from the C termini of membrane and soluble proteins in the secretory pathway SO EUROPEAN JOURNAL OF IMMUNOLOGY LA English DT Article DE antigen processing; endoplasmic reticulum; MHC class I; peptide; protease ID MAJOR HISTOCOMPATIBILITY COMPLEX; ENDOGENOUSLY SYNTHESIZED PEPTIDE; TOXIC LYMPHOCYTES-T; ENDOPLASMIC-RETICULUM; ANTIGEN PRESENTATION; SIGNAL SEQUENCE; MOLECULES; TRANSPORTER; EXPRESSION; CELLS AB TAP can efficiently transport peptides up to twice as long as those bound to MHC class I molecules, suggesting a role for endoplasmic reticulum (ER) proteases in the trimming of TAP-transported peptides. To better define ER processing of antigenic peptides, we examined the capacity of TAP-deficient cells to present determinants derived from ER-targeted proteins encoded by recombinant vaccinia viruses. TAP-deficient cells failed to present antigenic peptides from internal locations in secreted proteins to MHC class I-restricted T lymphocytes. The same peptides were liberated from the C termini of a secreted protein and the lumenal domains of two membrane proteins delivered to the ER via different routes. These findings suggest that proteases in the secretory compartment can liberate C-terminal antigenic peptides from virtually any context. We propose that this activity often participates in the removal of N-terminal extensions from TAP-transported peptides, thereby creating optimally sized products for MHC class I binding. We further demonstrate that ER trimming of C termini can occur if we express an appropriate carboxypeptidase in the secretory pathway. The absence of such trimming under normal circumstances suggests that carboxypeptidase activity is generally deficient in the ER, consistent with the concordance between the specificity of TAP and MHC class I molecules for the same types of C-terminal residues. C1 NIAID, Viral Dis Lab, NIH, Bethesda, MD 20892 USA. Univ Minnesota, Sch Med, Dept Med, Minneapolis, MN 55455 USA. RP Yewdell, JW (reprint author), NIAID, Viral Dis Lab, NIH, Room 213,Bldg 4, Bethesda, MD 20892 USA. RI yewdell, jyewdell@nih.gov/A-1702-2012 NR 37 TC 45 Z9 45 U1 0 U2 1 PU WILEY-V C H VERLAG GMBH PI BERLIN PA MUHLENSTRASSE 33-34, D-13187 BERLIN, GERMANY SN 0014-2980 J9 EUR J IMMUNOL JI Eur. J. Immunol. PD APR PY 1998 VL 28 IS 4 BP 1339 EP 1346 PG 8 WC Immunology SC Immunology GA ZH354 UT WOS:000073099900024 PM 9565374 ER PT J AU Belkaid, Y Butcher, B Sacks, DL AF Belkaid, Y Butcher, B Sacks, DL TI Analysis of cytokine production by inflammatory mouse macrophages at the single-cell level: selective impairment of IL-12 induction in Leishmania-infected cells SO EUROPEAN JOURNAL OF IMMUNOLOGY LA English DT Article DE IL-12; Leishmania; macrophage; flow cytometry ID HUMAN-IMMUNODEFICIENCY-VIRUS; PROTEIN-KINASE-C; CUTANEOUS LEISHMANIASIS; INTERLEUKIN-12 PRODUCTION; DONOVANI INFECTION; IMMUNE-RESPONSE; RESISTANT MICE; SCID MICE; IN-VIVO; PROMASTIGOTES AB Intracellular staining for cytokines and parasites, combined with two-color flow cytometric analyses, were used to examine the frequencies of IL-12-, TNF-alpha- and IL-6-producing macrophages in response to Leishmania major infection and/or activation with IFN-gamma/lipopolysaccharide (LPS). Inflammatory macrophages were obtained from nonimmune granulomas, initiated by the injection of polyacrylamide microbeads (Bio-gel P-100) into subcutaneous pouches of different mouse strains. Infection of inflammatory macrophages in vitro using metacyclic promastigotes produced identical effects on cytokine responses regardless of whether cells from genetically resistant or susceptible mouse strains were used: IL-12 was not produced in response to infection itself, virtually every infected cell lost its ability to produce IL-12 in response to IFN-gamma/LPS, and the IL-6 response was partially inhibited, while the TNF-alpha response of infected cells was unimpaired. Low-multiplicity infection of inflammatory macrophages in vivo using either metacyclic promastigotes or tissue amastigotes also resulted in the complete and selective inhibition of IL-12 responses in infected cells. These data establish the physiologic relevance of prior observations regarding the selective impairment of IL-12 induction pathways in infected macrophages, and suggest a mechanisms for the delayed onset of cell-mediated control mechanisms that is typical of even self-limiting forms of leishmanial disease. C1 NIAID, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA. RP Sacks, DL (reprint author), NIAID, Parasit Dis Lab, NIH, Bldg 4,Rm 126,9000 Rockville Pk, Bethesda, MD 20892 USA. EM dsacks@nih.gov NR 41 TC 102 Z9 104 U1 0 U2 1 PU WILEY-V C H VERLAG GMBH PI BERLIN PA MUHLENSTRASSE 33-34, D-13187 BERLIN, GERMANY SN 0014-2980 J9 EUR J IMMUNOL JI Eur. J. Immunol. PD APR PY 1998 VL 28 IS 4 BP 1389 EP 1400 DI 10.1002/(SICI)1521-4141(199804)28:04<1389::AID-IMMU1389>3.0.CO;2-1 PG 12 WC Immunology SC Immunology GA ZH354 UT WOS:000073099900029 PM 9565379 ER PT J AU Sedmera, D Pexieder, T Hu, N Clark, EB AF Sedmera, D Pexieder, T Hu, N Clark, EB TI A quantitative study of the ventricular myoarchitecture in the stage 21-29 chick embryo following decreased loading SO EUROPEAN JOURNAL OF MORPHOLOGY LA English DT Article DE compact myocardium; image analysis; perfusion-fixation; trabecular orientation; chronic verapamil suffusion ID SCANNING LASER MICROSCOPY; MYOCARDIAL-CELLS; CANCELLOUS BONE; HUMAN HEART; RXR-ALPHA; MICE; MORPHOGENESIS; ORIENTATION; VERAPAMIL; PATTERNS AB During the early developmental period, ventricular myoarchitecture undergoes a transition from a smooth-walled cardiac tube, to left and right ventricular chambers filled with a sponge-like network of trabecular struts. We measured the quantitative changes of ventricular myocardium properties in normal stage 21-29 chick embryos and after chronic verapamil suffusion, which is known to decrease work load and decelerate ventricular growth. The morphologic parametres (compact layer thickness, ventricular wall composition, porosity of different layers and trabecular orientation) were determined from scanning electron micrographs of transversely dissected perfusion-fixed hearts. A vascular bed of stage 21 chick embryos was suffused with 1 ng of verapamil at 1 mu l per hour up to stages 24, 27 and 29 via a miniosmotic pump. From stage 24, the thickness of the compact myocardium in the left ventricle was greater than that of the right. The increase in thickness was minimal between stages 24 and 27, while the predominantly radially arranged trabeculae comprised up to 75% of total myocardial mass. The ratio of intertrabecular spaces to trabeculae (local porosity) decreased from the ventricular center (70%) towards the compact myocardium (0%). In verapamil-treated embryos, the hearts were smaller and showed delayed development. The compact myocardium was thinner than normal, and the proportion of trabeculae was higher than in controls. The local porosity values were similar in control and experimental groups. Decreased load resulted in delayed growth and morphogenesis, expressed as a persistence of trabeculae and a thinner compact myocardium. Embryonic heart pumping function is largely based on extensively developed trabeculation with regionally different properties. C1 Univ Lausanne, Inst Histol & Embryol, Lausanne, Switzerland. Univ Rochester, Sch Med & Dent, Specialized Ctr Res Pediat Cardiovasc Dis, Dept Pediat,Strong Childrens Res Ctr,NIH, Rochester, NY 14642 USA. RP Sedmera, D (reprint author), Univ Lausanne, Inst Physiol, Rue Bugnon 7, CH-1005 Lausanne, Switzerland. RI Sedmera, David/C-2146-2012 OI Sedmera, David/0000-0002-6828-3671 FU NHLBI NIH HHS [HL51498] NR 52 TC 32 Z9 32 U1 0 U2 2 PU SWETS ZEITLINGER PUBLISHERS PI LISSE PA P O BOX 825, 2160 SZ LISSE, NETHERLANDS SN 0924-3860 J9 EUR J MORPHOL JI Eur. J. Morphol. PD APR PY 1998 VL 36 IS 2 BP 105 EP 119 DI 10.1076/ejom.36.2.105.4775 PG 15 WC Anatomy & Morphology SC Anatomy & Morphology GA ZV768 UT WOS:000074339200005 PM 9651744 ER PT J AU Connaughton, VP Maguire, G AF Connaughton, VP Maguire, G TI Differential expression of voltage-gated K+ and Ca2+ currents in bipolar cells in the zebrafish retinal slice SO EUROPEAN JOURNAL OF NEUROSCIENCE LA English DT Article DE bipolar cells; Danio rerio; electrophysiology; retina; zebrafish ID TIGER SALAMANDER RETINA; INWARD ANOMALOUS RECTIFICATION; MEMBRANE CURRENTS; CALCIUM CURRENT; RAT RETINA; SYNAPTIC TERMINALS; GLUTAMATE RECEPTOR; BRACHYDANIO-RERIO; GOLDFISH RETINA; CLAMP ANALYSIS AB Whole-cell voltage-gated currents were recorded from bipolar cells in the zebrafish retinal slice. Two physiological populations of bipolar cells were identified. In the first, depolarizing voltage steps elicited a rapidly activating A-current that reached peak amplitude less than or equal to 5 ms of step onset. I-A was antagonized by external tetraethylammonium or 4-aminopyridine, and by intracellular caesium. The second population expressed a delayed rectifying potassium current (I-K) that reached peak amplitude greater than or equal to 10 ms after step onset and did not inactivate. I-K was antagonized by internal caesium and external tetraethylammonium. Bipolar cells expressing I-K also expressed a time-dependent h-current at membrane potentials <-50 mV. I-h was sensitive to external caesium and barium, and was also reduced by Na+-free Ringer, In both groups, a calcium current (I-Ca) and a calcium-dependent potassium current (I-K(Ca)) were identified. Depolarizing voltage steps >-50 mV activated I-Ca, which reached peak amplitude between -20 and -10 mV, I-Ca was eliminated in Ca2+-free Ringer and blocked by cadmium and cobalt, but not tetrodotoxin. In most cells, I-Ca was transient, activating rapidly at -50 mV, This current was antagonized by nickel, The remaining bipolar cells expressed a nifedipine-sensitive sustained current that activated between -40 and -30 mV, with both slower kinetics and smaller amplitude than transient I-Ca. I-K(Ca) was elicited by membrane depolarizations >-20 mV. Bipolar cells in the zebrafish retinal slice preparation express an array of voltage-gated currents which contribute to non-linear I-V characteristics. The zebrafish retinal slice preparation is well-suited to patch clamp analyses of membrane mechanisms and provides a suitable model for studying genetic defects in visual system development. C1 National Institute Neurological Diseases & Stroke, Neurophysiol Lab, NIH, Bethesda, MD 20892 USA. Univ Texas, Sch Med, Dept Neurobiol & Anat, Houston, TX 77030 USA. Univ Calif San Diego, Shiley Eye Ctr, Dept Ophthalmol, La Jolla, CA 92093 USA. RP Connaughton, VP (reprint author), National Institute Neurological Diseases & Stroke, Neurophysiol Lab, NIH, Bldg 36,Room 2C02,36 Convent Dr MSC 4066, Bethesda, MD 20892 USA. EM vikki@codon.nih.gov FU NEI NIH HHS [EY09133, EY06640] NR 53 TC 42 Z9 42 U1 1 U2 3 PU BLACKWELL SCIENCE LTD PI OXFORD PA P O BOX 88, OSNEY MEAD, OXFORD OX2 0NE, OXON, ENGLAND SN 0953-816X J9 EUR J NEUROSCI JI Eur. J. Neurosci. PD APR PY 1998 VL 10 IS 4 BP 1350 EP 1362 PG 13 WC Neurosciences SC Neurosciences & Neurology GA ZF095 UT WOS:000072862100014 PM 9749789 ER PT J AU Widenfalk, J Tomac, A Lindqvist, E Hoffer, B Olson, L AF Widenfalk, J Tomac, A Lindqvist, E Hoffer, B Olson, L TI GFR alpha-3, a protein related to GFR alpha-1, is expressed in developing peripheral neurons and ensheathing cells SO EUROPEAN JOURNAL OF NEUROSCIENCE LA English DT Article DE ganglia; GDNF receptors; in situ hybridization; mouse; Schwann cells ID NEUROTROPHIC FACTOR; MESSENGER-RNA; IN-VIVO; GDNF; RAT; MUTATIONS; SYSTEM; RET AB We report here the identification of a gene, termed GFR alpha-3 (glial cell line-derived neurotrophic factor family receptor alpha-3), related to GFR alpha-1 and GFR alpha-3 (also known as GDNFR-alpha and GDNFR-beta), and describe distribution of GDNF alpha-3 in the nervous system and other parts of the mouse body duping development and in the adult. GFR alpha-3 in situ hybridization signals were found mainly in the peripheral nervous system, with prominent signals in developing dorsal root and trigeminal ganglia. Sympathetic ganglia were also positive. Developing nerves manifested strong GFR alpha-3 mRNA signals, presumably generated by the Schwann cells. Olfactory ensheathing cells were also positive. Other non-neuronal cells appearing positive during development included chromaffin cells in the adrenal gland and small clusters of cells in the intestinal epithelium. In the central nervous system no robust signals could be detected at any stage investigated with the present probes. Compared with the previously described GFR alpha-1 and GFR alpha-2 mRNAs, which are widely distributed in the central nervous system and peripheral organs, the expression of GFR alpha-3 mRNA is much more restricted. The prominent expression in Schwann cells during development suggests a key role for GFR alpha-3 in the development of the peripheral nervous system. As Schwann cells are known to lack expression of the transducing RET receptor, we propose that a possible function of GFR alpha-3 during development could be to bind Schwann cell-derived GDNF-like ligands, thus presenting such molecules to growing axons. C1 Karolinska Inst, Dept Neurosci, S-17177 Stockholm, Sweden. NIDA, NIH, Baltimore, MD 21224 USA. NICHHD, Bethesda, MD 20892 USA. RP Widenfalk, J (reprint author), Karolinska Inst, Dept Neurosci, S-17177 Stockholm, Sweden. EM Johan.Widenfalk@neuro.ki.se NR 23 TC 47 Z9 49 U1 0 U2 0 PU BLACKWELL SCIENCE LTD PI OXFORD PA P O BOX 88, OSNEY MEAD, OXFORD OX2 0NE, OXON, ENGLAND SN 0953-816X J9 EUR J NEUROSCI JI Eur. J. Neurosci. PD APR PY 1998 VL 10 IS 4 BP 1508 EP 1517 DI 10.1046/j.1460-9568.1998.00192.x PG 10 WC Neurosciences SC Neurosciences & Neurology GA ZF095 UT WOS:000072862100029 PM 9749804 ER PT J AU Orwin, RG Sonnefeld, LJ Cordray, DS Pion, GM Perl, HI AF Orwin, RG Sonnefeld, LJ Cordray, DS Pion, GM Perl, HI TI Constructing quantitative implementation scales from categorical services data - Examples from a multisite evaluation SO EVALUATION REVIEW LA English DT Article AB Like measures of outcome, measures of implementation are most useful and analytically powerful when measured at client-level and are quantitative. However high-quality, individual-level, quantitative service utilization data can be expensive, intrusive, or otherwise impractical to obtain. Cruder data-for example, presence versus absence of a given service-are often more feasible to collect, as well as more likely to be available. Consequently, evaluators can benefit by finding ways to better exploit such data at the analysis phase to compensate for shortcomings at the collection phase. This article documents one such instance in which this was done. Specifically it describes how quantitative, client-level implementation scales were derived from qualitative (categorical) data and used to support a cross-site synthesis of implementation and outcome analyses in a multisite evaluation. It also suggests additional scenarios in which quantitative implementation scales might be derived form qualitative services data. C1 ROW Sci Inc, Rockville, MD 20850 USA. Vanderbilt Univ, Vanderbilt Inst Publ Policy Studies, Nashville, TN USA. NIAAA, Hlth Serv Res Program, NIH, Rockville, MD USA. RP Orwin, RG (reprint author), ROW Sci Inc, Rockville, MD 20850 USA. NR 18 TC 8 Z9 8 U1 0 U2 0 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0193-841X J9 EVALUATION REV JI Eval. Rev. PD APR PY 1998 VL 22 IS 2 BP 245 EP 288 DI 10.1177/0193841X9802200204 PG 44 WC Social Sciences, Interdisciplinary SC Social Sciences - Other Topics GA ZG978 UT WOS:000073059300004 PM 10183306 ER PT J AU Tang, FI Tien, LT Zhou, FC Hoffer, BJ Wang, Y AF Tang, FI Tien, LT Zhou, FC Hoffer, BJ Wang, Y TI Intranigral ventral mesencephalic grafts and nigrostriatal injections of glial cell line-derived neurotrophic factor restore dopamine release in the striatum of 6-hydroxydopamine-lesioned rats SO EXPERIMENTAL BRAIN RESEARCH LA English DT Article DE glial cell line-derived neurotrophic factor; dopamine; Parkinson's disease; substantia nigra grafts; voltammetry; rat ID NEURONS IN-VIVO; SUBSTANTIA-NIGRA; PARKINSONS-DISEASE; MESSENGER-RNA; BRAIN; GDNF; SYSTEM; BDNF; ADULT; PATHWAY AB We have previously reported that grafting of fetal ventral mesencephalic (VM) tissue to the nigral region of unilaterally 6-hydroxydopamine (6-OHDA)-lesioned rats, in conjunction with glial cell line-derived neurotrophic factor (GDNF) injection between nigra and striatum, restores nigrostriatal tyrosine hydroxylase (TH) immunoreactivity. In this study, we investigated the electrochemical indices of dopamine (DA) release in these grafted animals in the striatum and nigra. Adult Sprague-Dawley rats were anesthetized and unilaterally injected with 6-OHDA into the medial forebrain bundle. The completeness of lesions was tested by measuring methamphetamine-induced rotations. One to two months after 6-OHDA administration, fetal VM tissues were grafted in the lesioned nigral area followed by injection of GDNF, brain-derived neurotrophic factor (BDNF), or phosphate-buffered saline (PBS), along a tract from nigra to striatum. Animals receiving transplantation and GDNF, but not BDNF or PBS, injection showed a significant decrease in rotation 1-3 months after grafting. High-speed chronoamperometric recording techniques, using Nafion-coated carbon fiber electrodes, were used to evaluate DA overflow in the striatum. We found that 6-OHDA lesions resulted in a loss of KCl-induced DA overflow in the urethane-anesthetized rats. Three months after GDNF-bridged grafting, application of KCl elicited DA release both in nigra and striatum. The KCl-evoked DA release area was limited to the GDNF-bridging tract in the striatum, On the other hand, KCl did not induce DA release in the BDNF- or PBS-bridged grafts. Immunocytochemical studies indicated that TH-positive neurons and fibers were found in the nigra and striatum after GDNF-bridged grafting. Taken together, our data suggest that fetal nigral transplantation and GDNF injection may restore the nigrostriatal DA pathway and DA release in these hemiparkinsonian animals and support the hypothesis of trophic activity of GDNF on fiber outgrowth from midbrain DA neurons. C1 Natl Def Med Ctr, Dept Pharmacol, Taipei, Taiwan. Natl Yang Ming Univ, Dept Physiol, Taipei 112, Taiwan. Indiana Univ, Sch Med, Dept Anat, Indianapolis, IN USA. Univ Colorado, Hlth Sci Ctr, Dept Pharmacol, Denver, CO USA. RP Hoffer, BJ (reprint author), NIDA, POB 5180, Baltimore, MD 21224 USA. NR 57 TC 28 Z9 29 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0014-4819 J9 EXP BRAIN RES JI Exp. Brain Res. PD APR PY 1998 VL 119 IS 3 BP 287 EP 296 DI 10.1007/s002210050344 PG 10 WC Neurosciences SC Neurosciences & Neurology GA ZD097 UT WOS:000072651100003 PM 9551829 ER PT J AU Hasegawa, S Rodgers, GP Dwyer, N Noguchi, CT Blanchette-Mackie, EJ Uyesaka, N Schechter, AN Fibach, E AF Hasegawa, S Rodgers, GP Dwyer, N Noguchi, CT Blanchette-Mackie, EJ Uyesaka, N Schechter, AN Fibach, E TI Sickling of nucleated erythroid precursors from patients with sickle cell anemia SO EXPERIMENTAL HEMATOLOGY LA English DT Article DE butyrate; hydroxyurea; sickle cell anemia; sickle hemoglobin ID DISEASE PATHOPHYSIOLOGY; FETAL HEMOGLOBIN; BETA-THALASSEMIA; RED-CELLS; HYDROXYUREA; DEOXYGENATION; GELATION; MEMBRANE; SKELETON; DENSITY AB The pathophysiology of sickle cell anemia is primarily explained in terms of the oxygen-dependent polymerization of sickle hemoglobin (HbS) followed by sickling of erythrocytes. Since the rate and extent of HbS polymerization depend on its intracellular concentration, it has been generally assumed that sickling occurs primarily in mature erythrocytes with their high intracellular hemoglobin concentration. In the present study, we investigated the propensity of nucleated erythroid precursors to undergo sickling; both cultured and fresh marrow-derived erythroid precursors from patients with homozygous sickle cell anemia were studied. The results revealed that upon deoxygenation cultured erythroblasts underwent characteristic morphological deformation in the form of fine, fragile, elongated spicules. Ultrastructural analysis demonstrated highly organized and tightly aligned hemoglobin fibers in the protruded regions. Bone marrow cells examined under partial or complete deoxygenated conditions displayed similar morphological changes. When cultured SS erythroid precursors were exposed to hydroxyurea or butyrate, drugs that may increase fetal hemoglobin (HbF) and inhibit intracellular polymerization, a significant decrease was observed in the propensity of these precursors to undergo sickling, accompanied by a three-to fivefold increase in HbF. These results suggest that, in addition to mature erythrocytes, nucleated erythroid precursors in the bone marrow have the capacity to undergo characteristic sickling as a result of HbS polymerization and may be involved in several aspects of the pathophysiology of sickle cell anemia. Treatment with HbF-stimulating drugs may benefit patients with this disease by inhibiting polymerization-induced sickling of erythroid precursors in the marrow as well as mature erythrocytes in the peripheral blood. C1 NIDDK, Biol Chem Lab, NIH, Bethesda, MD 20892 USA. NIDDK, Cellular & Dev Biol Lab, NIH, Bethesda, MD 20892 USA. Nippon Med Sch, Dept Physiol, Tokyo 113, Japan. Hadassah Univ Hosp, Dept Hematol, IL-91120 Jerusalem, Israel. RP Rodgers, GP (reprint author), NIDDK, Biol Chem Lab, NIH, Bethesda, MD 20892 USA. OI Schechter, Alan N/0000-0002-5235-9408 NR 27 TC 6 Z9 6 U1 1 U2 2 PU CARDEN JENNINGS PUBL CO LTD PI CHARLOTTESVILLE PA BLAKE CTR, STE 200, 1224 W MAIN ST, CHARLOTTESVILLE, VA 22903 USA SN 0301-472X J9 EXP HEMATOL JI Exp. Hematol. PD APR PY 1998 VL 26 IS 4 BP 314 EP 319 PG 6 WC Hematology; Medicine, Research & Experimental SC Hematology; Research & Experimental Medicine GA ZG067 UT WOS:000072962300007 PM 9546314 ER PT J AU Sinha, R Rothman, N Salmon, CP Knize, MG Brown, ED Swanson, CA Rhodes, D Rossi, S Felton, JS Levander, OA AF Sinha, R Rothman, N Salmon, CP Knize, MG Brown, ED Swanson, CA Rhodes, D Rossi, S Felton, JS Levander, OA TI Heterocyclic amine content in beef cooked by different methods to varying degrees of doneness and gravy made from meat drippings SO FOOD AND CHEMICAL TOXICOLOGY LA English DT Article DE heterocyclic amines; beef; cooking method; MeIQx; PhIP; DiMeIQx ID COLON-CANCER; COLORECTAL-CANCER; FOOD MUTAGENS; PAN RESIDUES; DIETARY-FAT; FRIED MEAT; RISK; PRODUCTS; CARCINOGEN; 2-AMINO-1-METHYL-6-PHENYLIMIDAZO<4,5-B>PYRIDINE AB Meats cooked at high temperatures sometimes contain heterocyclic amines (HCAs) that are known mutagens and animal carcinogens, but their carcinogenic potential in humans has not been established. To investigate the association between HCAs and cancer, sources of exposure to these compounds need to be determined. Beef is the most frequently consumed meat in the United States and for this study we determined HCA values in beef samples cooked in ways to represent US cooking practices, the results of which can be used in epidemiological studies to estimate HCA exposure from dietary questionnaires. We measured five HCAs [2-amino-3-methylimidazo[4,5-f]quinoline (IQ), 2-amino-3,4-dimethylimidazo[4,5f]quinoline (MeIQ), 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx), 2-amino-3,4,8-trimethylimidazo[4,5f]quinoxaline (DiMeIQx) and 2-amino-1-methyl-6-phenylimidazo-[4,5-b]pyridine (Ph1P)] in different types of cooked beef using solid-phase extraction and HPLC. Steak and hamburger patties were pan-fried, oven-broiled, and grilled/barbecued to four levels of doneness (rare, medium, well done or very well done), while beef roasts were oven cooked to three levels of doneness (rare, medium or well done). The measured values of the specific HCAs varied with the cut of beef, cooking method, and doneness level. In general, MeIQx content increased with doneness under each cooking condition for steak and hamburger patties, up to 8.2 ng/g. PhIP was the predominant HCA produced in steak (1.9 to 30 ng/g), but was formed only in very well done fried or grilled hamburger. DiMeIQx was found in trace levels in pan-fried steaks only, while IQ and MeIQ were not detectable in any of the samples. Roast beef did not contain any of the HCAs, but the gravy made from the drippings from well done roasts had 2 ng/g of PhIP and 7 ng/g of MeIQx. Epidemiological studies need to consider the type of meat, cooking method and degree of doneness/surface browning in survey questions to adequately assess an individual's exposure to HCAs. (C) 1998 Elsevier Science Ltd. All rights reserved. C1 NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA. Univ Calif Lawrence Livermore Natl Lab, Biol & Biotechnol Res Program, Livermore, CA 94550 USA. USDA ARS, Beltsville Agr Res Ctr, Nutrient Requirements & Funct Lab, Beltsville, MD 20705 USA. NCI, Early Detect Branch, DCPC, NIH, Rockville, MD 20892 USA. RP Sinha, R (reprint author), NCI, Div Canc Epidemiol & Genet, NIH, Execut Plaza N,Rm 430,6130 Execut Blvd, Bethesda, MD 20892 USA. RI Sinha, Rashmi/G-7446-2015 OI Sinha, Rashmi/0000-0002-2466-7462 FU NCI NIH HHS [CA55861, YO1CP2-0523-01] NR 29 TC 199 Z9 202 U1 0 U2 20 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0278-6915 J9 FOOD CHEM TOXICOL JI Food Chem. Toxicol. PD APR PY 1998 VL 36 IS 4 BP 279 EP 287 DI 10.1016/S0278-6915(97)00162-2 PG 9 WC Food Science & Technology; Toxicology SC Food Science & Technology; Toxicology GA ZT097 UT WOS:000074048100002 PM 9651044 ER PT J AU Sinha, R Knize, MG Salmon, CP Brown, ED Rhodes, D Felton, JS Levander, OA Rothman, N AF Sinha, R Knize, MG Salmon, CP Brown, ED Rhodes, D Felton, JS Levander, OA Rothman, N TI Heterocyclic amine content of pork products cooked by different methods and to varying degrees of doneness SO FOOD AND CHEMICAL TOXICOLOGY LA English DT Article DE heterocyclic amines; pork; pan-fry; oven-broil; grill; barbecue; microwave; MeIQx; DiMeIQx; PhIP; IQ; MeIQ; meat; hot dog; sausage; pork chop; ham steak ID FRIED MEAT; URINARY-EXCRETION; AROMATIC-AMINES; FOOD MUTAGENS; PAN RESIDUES; CANCER; CARCINOGEN; RISK; FAT; 2-AMINO-1-METHYL-6-PHENYLIMIDAZO<4,5-B>PYRIDINE AB Heterocyclic amines (HCAs) are known mutagens and animal carcinogens produced in meats cooked at high temperature. As pork is the second most frequently consumed meat in the United States, five predominant HCAs [2-amino-3-methylimidazo[4,5-f]quinoline (IQ), 2-amino-3,4-dimethylimidazo[4,5-f]quinoline (MeIQ), 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx), 2-amino-3,4,8-trimethylimidazo[4,5-f]quinoxaline (DiMeIQx) and 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP)] were measured in various pork products, cooked by different techniques and to varying doneness levels. Pork chops and ham slices were pan-fried and oven-broiled; bacon was pan-fried, oven-broiled or microwaved: hot dogs were pan-fried, oven-broiled, grilled/barbecued or boiled; sausage links and patties were pan-fried. All the products were cooked to three levels of doneness: just until done, well done or very well done. HCA type and level varied substantially by pork product, cooking method and doneness level. The highest PhIP levels were found in well done and very well done oven-broiled bacon; for very well done 30.3 and 4.0 ng per gram of meat of PhIP and MeIQx, respectively. Pan-fried very well done sausage patties contained 5.4 ng of MeIQx per gram of meat, while sausage links contained 1.3 ng per gram of meat. MeIQx was formed in well done and very well done pan-fried but not broiled pork chops. Hot dogs or ham slices had low or undetectable levers of HCAs. These results demonstrate that epidemiological studies investigating the relationship between HCA intake and cancer risk need to incorporate type of meat, cooking method and degree of doneness/surface browning into questions to assess adequately an individual's HCA exposure. (C) 1998 Elsevier Science Ltd. All rights reserved. C1 NCI, Div Canc Epidemiol & Genet, NIH, Rockville, MD 20892 USA. Univ Calif Lawrence Livermore Natl Lab, Biol & Biotechnol Res Program, Livermore, CA 94550 USA. USDA ARS, Nutrients Requirements & Funct Lab, BHNRC, Beltsville, MD 20705 USA. RP Sinha, R (reprint author), NCI, Div Canc Epidemiol & Genet, NIH, Execut Plaza N,Rm 430,6130 Execut Blvd, Rockville, MD 20892 USA. RI Sinha, Rashmi/G-7446-2015 OI Sinha, Rashmi/0000-0002-2466-7462 FU NCI NIH HHS [CA55861, YO1CP2-0523-01] NR 30 TC 149 Z9 149 U1 0 U2 12 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0278-6915 J9 FOOD CHEM TOXICOL JI Food Chem. Toxicol. PD APR PY 1998 VL 36 IS 4 BP 289 EP 297 DI 10.1016/S0278-6915(97)00159-2 PG 9 WC Food Science & Technology; Toxicology SC Food Science & Technology; Toxicology GA ZT097 UT WOS:000074048100003 PM 9651045 ER PT J AU He, X Goldsmith, CM Marmary, Y Wellner, RB Parlow, AF Nieman, LK Baum, BJ AF He, X Goldsmith, CM Marmary, Y Wellner, RB Parlow, AF Nieman, LK Baum, BJ TI Systemic action of human growth hormone following adenovirus-mediated gene transfer to rat submandibular glands SO GENE THERAPY LA English DT Article DE gene therapeutics; systemic protein delivery; growth hormone; salivary glands ID IN-VIVO; EPITHELIAL-CELLS; THERAPY; EXPRESSION; DELIVERY; INJECTION AB We have previously suggested that although salivary glands function in an exocrine manner they might none the less offer a useful way to deliver therapeutic proteins systemically. As a direct functional test of this hypothesis, we constructed a recombinant adenovirus (AdCMVhGH) encoding human growth hormone (hGH) and then studied the biological action of hGH produced following transfer of the hGH gene to rat submandibular glands. At 48 h following infusion of AdCMVhGH into these glands via cannulation of the main excretory duct, serum levels of hGH were approximately 16 ng/ml and rat insulin-like growth factor-1 was elevated approximately 25%. Moreover, serum chemistry profiles of rats subjected to in vivo gene transfer displayed alterations in the BUN:creatinine ratio and triglyceride levels presumably reflecting the anabolic actions of the hGH. These results provide the first demonstration of systemic biological action from a transgene product secreted in an endocrine fashion from the salivary glands. C1 NIDR, GTTB, NIH, Bethesda, MD 20892 USA. NICHD, Dev Endocrinol Branch, Bethesda, MD USA. Univ Calif Los Angeles, Harbor Gen Hosp, Pituitary Hormones & Antisera Ctr, Torrance, CA USA. RP Baum, BJ (reprint author), NIDR, GTTB, NIH, 10 Ctr Dr,MSC 1190,Bldg 10,Room 1N113, Bethesda, MD 20892 USA. NR 27 TC 76 Z9 77 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0969-7128 J9 GENE THER JI Gene Ther. PD APR PY 1998 VL 5 IS 4 BP 537 EP 541 DI 10.1038/sj.gt.3300622 PG 5 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA ZH127 UT WOS:000073075500015 PM 9614579 ER PT J AU Cook, RM Franklin, WA Moore, MD Johnson, BE Miller, YE AF Cook, RM Franklin, WA Moore, MD Johnson, BE Miller, YE TI Mutational inactivation of aminoacylase-1 in a small cell hung cancer cell line SO GENES CHROMOSOMES & CANCER LA English DT Article ID HUMAN LUNG-CANCER; CHROMOSOMAL REGION 3P21; SHORT ARM; ACYLPEPTIDE HYDROLASE; HOMOZYGOUS DELETION; TUMOR-SUPPRESSOR; FHIT GENE; MOLECULAR ANALYSIS; CARCINOMA; EXPRESSION AB Small cell lung cancer (SCLC) cell lines and tumors invariably exhibit loss of heterozygosity (LOH) or, in rare cases, homozygous deletions involving part or all of chromosome arm 3p, suggesting the presence of I or more tumor-suppressor genes in this region, The gene encoding aminoacylase-l (ACY1) is Localized on chromosome segment 3p21.1. ACY1 enzymatic activity, protein, and mRNA have been demonstrated to be expressed at either undetectable or very low levels in a group of SCLC cell lines and tumors, The demonstration of mutational inactivation of ACY1 would support the hypothesis that ACY1 inactivation in SCLC confers a selective growth advantage, One of four SCLC cell lines with undetectable Acy1 enzymatic activity and protein exhibited a compound mutation: nonconservative missense point mutations at codons 195 and 254. No wildtype sequence transcripts were identified in the tell line, Although nonmutational mechanisms for low or undetectable ACY1 enzymatic activity, protein, and mRNA expression are most frequently operant in SCLC, the demonstration of a mutation supports selection for AC:YI inactivation. Analysis of normal liver and a liver metastasis from the same patient from whom the NCI-HT I I cell line was derived demonstrated that the mutation was neither germline nor an early event in the development of SCLC. It is of interest that several genes involved in the regulation of intracellular protein degradation are encoded by chromosome band 3p21 and display unusual expression in SCLC, The presence of other loci involved in protein degradation on chromosome band 3p21 and their aberrant expression in SCLC suggest that a variety of mechanisms involved in the normal degradation of intracellular proteins may be perturbed in this neoplasm. (C) 1998 Wiley Liss, Inc.dagger C1 Univ Colorado, Ctr Hlth Sci, Vet Affairs Med Ctr, Dept Med,Div Pulm Sci & Crit Care Med, Denver, CO 80220 USA. Univ Colorado, Ctr Hlth Sci, Dept Pathol, Denver, CO 80220 USA. NCI, Med Branch, Bethesda, MD 20892 USA. Univ Colorado, Ctr Hlth Sci, Vet Affairs Med Ctr, Dept Med,Div Med Oncol, Denver, CO 80220 USA. RP Miller, YE (reprint author), Univ Colorado, Ctr Hlth Sci, Vet Affairs Med Ctr, Dept Med,Div Pulm Sci & Crit Care Med, 1055 Clermont St, Denver, CO 80220 USA. FU NCI NIH HHS [CA46934, CA58187] NR 43 TC 10 Z9 12 U1 1 U2 2 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 1045-2257 J9 GENE CHROMOSOME CANC JI Gene Chromosomes Cancer PD APR PY 1998 VL 21 IS 4 BP 320 EP 325 DI 10.1002/(SICI)1098-2264(199804)21:4<320::AID-GCC5>3.0.CO;2-0 PG 6 WC Oncology; Genetics & Heredity SC Oncology; Genetics & Heredity GA ZF861 UT WOS:000072940600005 PM 9559343 ER PT J AU Drake, J AF Drake, J TI The Mom and Pop Editorial Shop SO GENETICS LA English DT Editorial Material C1 NIEHS, Mol Genet Lab E301, Res Triangle Pk, NC 27709 USA. RP Drake, J (reprint author), NIEHS, Mol Genet Lab E301, Res Triangle Pk, NC 27709 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU GENETICS PI BALTIMORE PA 428 EAST PRESTON ST, BALTIMORE, MD 21202 USA SN 0016-6731 J9 GENETICS JI Genetics PD APR PY 1998 VL 148 IS 4 BP 1409 EP 1411 PG 3 WC Genetics & Heredity SC Genetics & Heredity GA ZJ175 UT WOS:000073187000003 PM 9560360 ER PT J AU Lobachev, KS Shor, BM Tran, HT Taylor, W Keen, JD Resnick, MA Gordenin, DA AF Lobachev, KS Shor, BM Tran, HT Taylor, W Keen, JD Resnick, MA Gordenin, DA TI Factors affecting inverted repeat stimulation of recombination and deletion in Saccharomyces cerevisiae SO GENETICS LA English DT Article ID DENSITY LIPOPROTEIN RECEPTOR; BACTERIAL TRANSPOSON TN5; REPEATED DNA-SEQUENCES; ESCHERICHIA-COLI; SECONDARY STRUCTURE; PRECISE EXCISION; FAMILIAL HYPERCHOLESTEROLEMIA; GENETIC INSTABILITY; REPLICATION FORKS; BACILLUS-SUBTILIS AB Inverted DNA repeats are an at-risk motif for genetic instability that can induce both deletions and recombination in yeast. We investigated the role of the length of inverted repeats and size of the DNA separating the repeats for deletion and recombination. Stimulation of both deletion and recombination was directly related to the size of inverted repeats and inversely related to the size of intervening spacers. A perfect palindrome, formed by two 1.0-kb URA3-inverted repeats, increased intra-and interchromosomal recombination in the adjacent region 2,400-fold and 17,000-fold, respectively. The presence of a strong origin of replication in the spacer reduced both rates of deletion and recombination. These results support a model in which the stimulation of deletion and recombination by inverted repeats is initiated by a secondary structure formed between single-stranded DNA of inverted repeats during replication. C1 NIEHS, Mol Genet Lab, Res Triangle Pk, NC 27709 USA. St Petersburg State Univ, Dept Genet, St Petersburg 199034, Russia. RP Gordenin, DA (reprint author), NIEHS, Mol Genet Lab, Mail Drop D3-01,111 TW Alexander Dr,POB 12233, Res Triangle Pk, NC 27709 USA. OI Gordenin, Dmitry/0000-0002-8399-1836 NR 100 TC 94 Z9 96 U1 0 U2 3 PU GENETICS PI BALTIMORE PA 428 EAST PRESTON ST, BALTIMORE, MD 21202 USA SN 0016-6731 J9 GENETICS JI Genetics PD APR PY 1998 VL 148 IS 4 BP 1507 EP 1524 PG 18 WC Genetics & Heredity SC Genetics & Heredity GA ZJ175 UT WOS:000073187000014 PM 9560370 ER PT J AU McGill, CB Holbeck, SL Strathern, JN AF McGill, CB Holbeck, SL Strathern, JN TI The chromosome bias of misincorporations during double-strand break repair is not altered in mismatch repair-defective strains of Saccharomyces cerevisiae SO GENETICS LA English DT Article ID DNA-BASE PAIRS; GENETIC-RECOMBINATION; MEIOTIC RECOMBINATION; DUPLEX OLIGONUCLEOTIDES; SPECIFICALLY BINDS; ESCHERICHIA-COLI; YEAST; MODEL; MSH2; PMS1 AB Recombinational repair of a site-specific, double-strand DNA break (DSB) results in increased reversion frequency for nearby mutations. Although some models for DSB repair predict that newly synthesized DNA will be inherited equally by both the originally broken chromosome and the chromosome that served as a template, the DNA synthesis errors are almost exclusively found on the chromosome that had the original DSB (introduced by the HO endonuclease). To determine whether mismatch repair acts on the template chromosome in a directed fashion to restore mismatches to the initial sequence, these experiments were repeated in mismatch repair-defective (pms1, mlh1, and msh2) backgrounds. The results suggest that mismatch repair is not responsible for the observed bias. C1 NCI, Frederick Canc Res & Dev Ctr, ABL Basic Res Program, Gene Regulat & Chromosome Biol Lab, Frederick, MD 21702 USA. RP Strathern, JN (reprint author), NCI, Frederick Canc Res & Dev Ctr, ABL Basic Res Program, Gene Regulat & Chromosome Biol Lab, Box B,Bldg 539, Frederick, MD 21702 USA. EM strather@ncifcrf.gov NR 51 TC 18 Z9 19 U1 0 U2 0 PU GENETICS PI BALTIMORE PA 428 EAST PRESTON ST, BALTIMORE, MD 21202 USA SN 0016-6731 J9 GENETICS JI Genetics PD APR PY 1998 VL 148 IS 4 BP 1525 EP 1533 PG 9 WC Genetics & Heredity SC Genetics & Heredity GA ZJ175 UT WOS:000073187000015 PM 9560371 ER PT J AU Nossal, NG AF Nossal, NG TI A new look at old mutants of T4 DNA polymerase SO GENETICS LA English DT Article ID DEOXYRIBONUCLEIC ACID POLYMERASE; MUTATION FREQUENCY; CB120 ANTIMUTATOR; BIOCHEMICAL BASIS; BACTERIOPHAGE-T4; FRAGMENT AB The DNA polymerase and nuclease activities of bacteriophage T4 DNA polymerase mutants are discussed in the context of the crystal structure of the closely related bacteriophage RB69 DNA polymerase. C1 NIDDKD, Mol & Cellular Biol Lab, NIH, Bethesda, MD 20892 USA. RP Nossal, NG (reprint author), NIDDKD, Mol & Cellular Biol Lab, NIH, Bldg 8,Rm 2A-19, Bethesda, MD 20892 USA. EM ngn@helix.nih.gov NR 25 TC 15 Z9 16 U1 0 U2 0 PU GENETICS PI BALTIMORE PA 428 EAST PRESTON ST, BALTIMORE, MD 21202 USA SN 0016-6731 J9 GENETICS JI Genetics PD APR PY 1998 VL 148 IS 4 BP 1535 EP 1538 PG 4 WC Genetics & Heredity SC Genetics & Heredity GA ZJ175 UT WOS:000073187000016 PM 9560372 ER PT J AU Paddison, P Abedon, ST Dressman, HK Gailbreath, K Tracy, J Mosser, E Neitzel, J Guttman, B Kutter, E AF Paddison, P Abedon, ST Dressman, HK Gailbreath, K Tracy, J Mosser, E Neitzel, J Guttman, B Kutter, E TI The roles of the bacteriophage T4 r genes in lysis inhibition and fine-structure genetics: A new perspective SO GENETICS LA English DT Article ID EVEN BACTERIOPHAGES; SELECTION; MECHANISM; LAMBDA AB Seldom has the study of a set of genes contributed more to our understanding of molecular genetics than has the characterization of the rapid-lysis genes of bacteriophage T4. For example, T4 rII mutants were used to define gene structure and mutagen effects at the molecular level and to help unravel the genetic code. The large-plaque morphology of these mutants reflects a block in expressing lysis inhibition (LIN), the ability to delay lysis for several hours in response to sensing external related phages attacking the cell, which is a unique and highly adaptive attribute of the T-l family of phages. However, surprisingly little is known about the mechanism of LIN, or how the various r genes affect its expression. Here, we review the extensive old literature about the r genes and the lysis process and try to sort out the major players affecting lysis inhibition. We confirm that superinfection can induce lysis inhibition even while infected cells are lysing, suggesting that the signal response is virtually instantaneous and thus probably the result of post-translational regulation. We identify the rI gene as ORF tk.-2, based on sequence analysis of canonical rI mutants. The rI gene encodes a peptide of 97 amino acids (M-r = 11.1 KD; pI = 4.8) that probably is secreted into the periplasmic space. This gene is widely conserved among T-even phage. We then present a model for LIN, postulating that rI is largely responsible for regulating the gpt holin protein in response to superinfection. The evidence suggests that the rIIA and B genes are not directly involved in lysis inhibition; rather, when they are absent, an alternate pathway for lysis develops which depends on the presence of genes from any of several possible prophages and is not sensitive to lysis inhibition. C1 Evergreen State Coll, Olympia, WA 98505 USA. Ohio State Univ, Dept Microbiol, Columbus, OH 43210 USA. NIEHS, Res Triangle Pk, NC 27709 USA. RP Kutter, E (reprint author), Evergreen State Coll, Olympia, WA 98505 USA. EM kutterb@elwha.evergreen.edu RI Abedon, Stephen/C-7712-2012 NR 62 TC 39 Z9 45 U1 0 U2 2 PU GENETICS PI BALTIMORE PA 428 EAST PRESTON ST, BALTIMORE, MD 21202 USA SN 0016-6731 J9 GENETICS JI Genetics PD APR PY 1998 VL 148 IS 4 BP 1539 EP 1550 PG 12 WC Genetics & Heredity SC Genetics & Heredity GA ZJ175 UT WOS:000073187000017 PM 9560373 ER PT J AU Schaaper, RM AF Schaaper, RM TI Antimutator mutants in bacteriophage T4 and Escherichia coli SO GENETICS LA English DT Article ID DNA-POLYMERASE FUNCTION; SPONTANEOUS MUTATION; REPLICATION; FIDELITY; MUTAGENESIS; IDENTIFICATION; EXONUCLEASE; SPECIFICITY; MECHANISMS; INCREASES AB Antimutators are mutant strains that have reduced mutation rates compared to the corresponding wild-type strain. Their existence, along with mutator mutants that have higher mutation rates compared to the wild-type strain, are powerful evidence that mutation rates are genetically controlled. Compared to mutator mutants, antimutators have a very distinguishing property. Because they prevent normally occurring mutations, they, uniquely, are capable of providing insight into the mechanisms of spontaneous mutations. In this review, antimutator mutants are discussed in bacteriophage T4 and the bacterium Escherichia coli, with regard to their properties, possible mechanisms, and implications for the sources of spontaneous mutations in these two organisms. C1 NIEHS, Mol Genet Lab, Res Triangle Pk, NC 27709 USA. RP Schaaper, RM (reprint author), NIEHS, Mol Genet Lab, 111 TW Alexander Dr,Box 12233, Res Triangle Pk, NC 27709 USA. NR 36 TC 33 Z9 34 U1 1 U2 3 PU GENETICS PI BALTIMORE PA 428 EAST PRESTON ST, BALTIMORE, MD 21202 USA SN 0016-6731 J9 GENETICS JI Genetics PD APR PY 1998 VL 148 IS 4 BP 1579 EP 1585 PG 7 WC Genetics & Heredity SC Genetics & Heredity GA ZJ175 UT WOS:000073187000021 PM 9560377 ER PT J AU Smith, LA Drake, JW AF Smith, LA Drake, JW TI Aspects of the ultraviolet photobiology of some T-even bacteriophages SO GENETICS LA English DT Article ID SPONTANEOUS MUTATION; ESCHERICHIA-COLI; UV-RESISTANCE; DNA; MUTAGENESIS; CYTOSINE; DEAMINATION; DEFICIENT; MECHANISM; REPAIR AB Bacteriophage T4 DNA metabolism is largely insulated from that of its host, although some host functions assist in the repair of T4 DNA damage. Environmental factors sometimes affect survival and mutagenesis after ultraviolet (UV) irradiation of T4, and can affect mutagenesis in many organisms. We therefore tested the effect of certain environmental factors and host genetic defects upon spontaneous and UV- induced mutagenesis and survival in T4 and some related T-even phages. Plating at pH 9 enhances UV resistance in T4 by about 14% compared to pH 7. The host cAMP regulatory system affects host survival after UV irradiation but does not affect T4 survival. Thermal rescue, the increasing survival of irradiated T4 with increasing plating temperature, occurs also in phage T6, but only weakly in phages T2 and RB69; this temperature effect is not altered by supplementing infected cells with additional Holliday resolvase (gp49) early in infection. Phage RB69 turns out to have almost 50% greater UV resistance than T4, but has a genome of about the same size; RB69 is UV-mutable but does not produce r mutants, which are easily seen in T2, T4, and T6. Spontaneous mutagenesis in T4 shows no dependence on medium and little dependence on temperature overall, but mutation rates can increase and probably decrease with temperature at specific sites. UV mutagenesis is not affected by incubating irradiated particles under various conditions before plating, in contrast to phage S13. C1 NIEHS, Mol Genet Lab E301, Res Triangle Pk, NC 27709 USA. RP Drake, JW (reprint author), NIEHS, Mol Genet Lab E301, Res Triangle Pk, NC 27709 USA. EM drake@niehs.nih.gov NR 32 TC 8 Z9 8 U1 0 U2 3 PU GENETICS PI BALTIMORE PA 428 EAST PRESTON ST, BALTIMORE, MD 21202 USA SN 0016-6731 J9 GENETICS JI Genetics PD APR PY 1998 VL 148 IS 4 BP 1611 EP 1618 PG 8 WC Genetics & Heredity SC Genetics & Heredity GA ZJ175 UT WOS:000073187000024 PM 9560380 ER PT J AU Umar, A Risinger, JI Glaab, WE Tindall, KR Barrett, JC Kunkel, TA AF Umar, A Risinger, JI Glaab, WE Tindall, KR Barrett, JC Kunkel, TA TI Functional overlap in mismatch repair by human MSH3 and MSH6 SO GENETICS LA English DT Article ID CARCINOMA CELL-LINES; DNA-BASE PAIRS; SACCHAROMYCES-CEREVISIAE MSH2; SIMPLE REPETITIVE DNA; MICROSATELLITE INSTABILITY; SPECIFICALLY BINDS; DUPLEX OLIGONUCLEOTIDES; HETERODUPLEX REPAIR; MUTATOR PHENOTYPES; ENDOMETRIAL CANCER AB Three human genes, hMSH2, hMSH3, and hMSH6, are homologues of the bacterial MutS gene whose products bind DNA mismatches to initiate strand-specific repair of DNA replication errors. Several studies suggest that a complex of hMSH2.hMSH6 (hMutS alpha) functions primarily in repair of base base mismatches or single extra bases, whereas a hMSH2.hMSH3 comples (hMutS beta) functions chiefly in repair of heteroduplexes containing two to four extra bases. In the present study, we compare results with a tumor cell line (HHUA) that is mutant in both hMSH3 and hMSH6 to results with derivative clones containing either wild-type hMSH3 or wild-type hMSH6, introduced by microcell-mediated transfer of chromosome 5 or 2, respectively. HHUA cells exhibit marked instability at 12 different microsatellite loci composed of repeat units of 1 to 4 base pairs. Compared to normal cells, HHUA cells have mutation rates at the HPRT locus that are elevated 500-fold for base substitutions and 2400-fold for single-base frameshifts. Extracts of HHUA cells are defective in strand-specific repair of substrates containing base-base mismatches or 1-4 extra bases. Transfer of either chromosome 5 (hMSH3) or 2 (hMSH6) into HHUA cells partially corrects instatility at the microsatellite loci and also the substitution and frameshift mutator phenotypes at the HPRT locus. Extracts of these lines can repair some, but not all, heteroduplexes. The combined mutation rate and mismatch repair specificity data suggest that both hMSH3 and hMSH6 can independently participate in repair of replication errors containing base.base mismatches or 1-4 extra bases. Thus, these two gene products share redundant roles in controlling mutation rates in human cells. C1 NIEHS, Mol Genet Lab, Res Triangle Pk, NC 27709 USA. NIEHS, Mol Carcinogenesis Lab, Res Triangle Pk, NC 27709 USA. NIEHS, Lab Environm Carcinogenesis & Mutagenesis, Res Triangle Pk, NC 27709 USA. Univ N Carolina, Curriculum Genet & Mol Biol, Chapel Hill, NC 27599 USA. Univ N Carolina, Curriculum Toxicol, Chapel Hill, NC 27599 USA. RP Kunkel, TA (reprint author), NIEHS, Mol Genet Lab, E3-01,POB 12233, Res Triangle Pk, NC 27709 USA. EM kunkel@niehs.nih.gov NR 58 TC 111 Z9 112 U1 0 U2 5 PU GENETICS PI BALTIMORE PA 428 EAST PRESTON ST, BALTIMORE, MD 21202 USA SN 0016-6731 J9 GENETICS JI Genetics PD APR PY 1998 VL 148 IS 4 BP 1637 EP 1646 PG 10 WC Genetics & Heredity SC Genetics & Heredity GA ZJ175 UT WOS:000073187000027 PM 9560383 ER PT J AU Drake, JW Charlesworth, B Charlesworth, D Crow, JF AF Drake, JW Charlesworth, B Charlesworth, D Crow, JF TI Rates of spontaneous mutation SO GENETICS LA English DT Review ID HERPES-SIMPLEX VIRUS; COMPLETE NUCLEOTIDE-SEQUENCE; MISMATCH REPAIR DEFICIENCY; VESICULAR STOMATITIS-VIRUS; BOVINE LEUKEMIA-VIRUS; HEAVY-CHAIN GENE; DROSOPHILA-MELANOGASTER; ESCHERICHIA-COLI; CAENORHABDITIS-ELEGANS; INBREEDING DEPRESSION AB Rates of spontaneous mutation per genome as measured in the laboratory are remarkably similar within broad groups of organisms but differ strikingly among groups, Mutation rates in RNA viruses, whose genomes contain ca. 10(4) bases, are roughly 1 per genome per replication for lytic viruses and roughly 0.1 per genome per replication for retroviruses and a retrotransposon. Mutation rates in microbes with DNA-based chromosomes are close to 1/300 per genome per replication; in this group, therefore, rates per base pair vary inversely and hugely as genome sizes vary from 6 x 10(3) to 4 x 10(7) bases or base pairs. Mutation rates in higher eukaryotes are roughly 0.1-100 per genome per sexual generation but are currently indistinguishable from 1/300 per cell division per effective genome (which excludes the fraction of the genome in which most mutations are neutral). It is now possible to specify some of the evolutionary forces that shape these diverse mutation rates. C1 NIEHS, Mol Genet Lab E301, Res Triangle Pk, NC 27709 USA. Univ Edinburgh, Inst Cell Anim & Populat Biol, Edinburgh EH9 3JT, Midlothian, Scotland. Univ Wisconsin, Dept Genet, Madison, WI 53706 USA. RP Drake, JW (reprint author), NIEHS, Mol Genet Lab E301, Res Triangle Pk, NC 27709 USA. EM drake@niehs.nih.gov RI Charlesworth, Deborah/F-3071-2011 NR 160 TC 1102 Z9 1125 U1 17 U2 173 PU GENETICS PI BALTIMORE PA 428 EAST PRESTON ST, BALTIMORE, MD 21202 USA SN 0016-6731 J9 GENETICS JI Genetics PD APR PY 1998 VL 148 IS 4 BP 1667 EP 1686 PG 20 WC Genetics & Heredity SC Genetics & Heredity GA ZJ175 UT WOS:000073187000030 PM 9560386 ER PT J AU Lee, BS Lichtenstein, CP Faiola, B Rinckel, LA Wysock, W Curcio, MJ Garfinkel, DJ AF Lee, BS Lichtenstein, CP Faiola, B Rinckel, LA Wysock, W Curcio, MJ Garfinkel, DJ TI Posttranslational inhibition of Ty1 retrotransposition by nucleotide excision repair transcription factor TFIIH subunits Ss12p and Rad3p SO GENETICS LA English DT Article ID RNA-POLYMERASE-II; SACCHAROMYCES-CEREVISIAE GENOME; SHORT-SEQUENCE RECOMBINATION; VIRUS-LIKE PARTICLES; DNA-REPAIR; MITOTIC RECOMBINATION; XERODERMA-PIGMENTOSUM; INTEGRATION SPECIFICITY; ELEMENT TRANSPOSITION; REVERSE-TRANSCRIPTASE AB rtt4-1 (regulator of Ty transposition) is a cellular mutation that permits a high level of spontaneous Ty1 retrotransposition in Saccharomyces cerevisiae. The RTT4 gene is allelic with SSL2 (RAD25), which encodes a DNA helicase present in basal transcription (TFIIH) and nucleotide excision repair (NER) complexes. The ssl2-rtt (rtt4-1) mutation stimulates Ty1 retrotransposition, but does not alter Ty1 target site preferences, or increase cDNA or mitotic recombination. In addition to ssl2-rtt, the ssl2-dead and SSL2-1 mutations stimulate Ty1 transposition without altering the level of Ty1 RNA or proteins. However, the level of Ty1 cDNA markedly increases in the ssl2 mutants, like SSL2, certain mutations in another NER/TFIIH DNA helicase encoded by RAD3 stimulate Ty1 transposition. Although Ssl2p and Rad3p are required for NER, inhibition of Ty1 transposition is independent of Ssl2p and Rad3p NER functions. Our work suggests that NER/TFIIH subunits antagonize Ty1 transposition posttranslationally by inhibiting reverse transcription or destabilizing Ty1 cDNA. C1 NCI, Frederick Canc Res & Dev Ctr, ABL Basic Res Program, Gene Regulat & Chromosome Biol Lab, Frederick, MD 21702 USA. SUNY Albany, Wadsworth Ctr, Mol Genet Program, Albany, NY 12201 USA. SUNY Albany, Sch Publ Hlth, Albany, NY 12201 USA. RP Garfinkel, DJ (reprint author), NCI, Frederick Canc Res & Dev Ctr, ABL Basic Res Program, Gene Regulat & Chromosome Biol Lab, POB B, Frederick, MD 21702 USA. FU NIGMS NIH HHS [GM52072, R01 GM052072] NR 90 TC 50 Z9 50 U1 0 U2 0 PU GENETICS PI BALTIMORE PA 428 EAST PRESTON ST, BALTIMORE, MD 21202 USA SN 0016-6731 J9 GENETICS JI Genetics PD APR PY 1998 VL 148 IS 4 BP 1743 EP 1761 PG 19 WC Genetics & Heredity SC Genetics & Heredity GA ZJ175 UT WOS:000073187000035 PM 9560391 ER PT J AU Huang, JD Cope, MJTV Mermall, V Strobel, MC Kendrick-Jones, J Russell, LB Mooseker, MS Copeland, NG Jenkins, NA AF Huang, JD Cope, MJTV Mermall, V Strobel, MC Kendrick-Jones, J Russell, LB Mooseker, MS Copeland, NG Jenkins, NA TI Molecular genetic dissection of mouse unconventional myosin-VA: Head region mutations SO GENETICS LA English DT Article ID DICTYOSTELIUM-DISCOIDEUM MYOSIN; X-RAY STRUCTURE; HYPERTROPHIC CARDIOMYOPATHY; ANGSTROM RESOLUTION; PURKINJE-CELLS; MOTOR DOMAIN; CHAIN GENE; COMPLEX; EXPRESSION; PROTEINS AB The mouse dilute (d) locus encodes unconventional myosin-VA (MyoVA). Mice carrying null alleles of dilute have a lightened coat color and die from a neurological disorder resembling ataxia and opisthotonus within three weeks of birth. Immunological and ultrastructural studies suggest that MyoVA is involved in the transport of melanosomes in melanocytes and smooth endoplasmic reticulum in cerebellar Purkinje cells. In studies described here, we have used an RT-PCR-based sequencing approach to identify the mutations responsible for 17 viable dilute alleles that vary in their effects on coat color and the nervous system. Seven of these mutations mapped to the MyoVA motor domain and are reported here. Crystallographic modeling and mutant expression studies were used to predict how these mutations might affect motor domain function and to attempt to correlate these effects with the mutant phenotype. C1 NCI, Frederick Canc Res & Dev Ctr, ABL Basic Res Program, Frederick, MD 21702 USA. MRC, Mol Biol Lab, Cambridge CB2 2QH, England. Yale Univ, Dept Biol, New Haven, CT 06520 USA. Yale Univ, Dept Pathol, New Haven, CT 06520 USA. Yale Univ, Dept Cell Biol, New Haven, CT 06520 USA. Oak Ridge Natl Lab, Div Biol, Oak Ridge, TN 37831 USA. RP Jenkins, NA (reprint author), NCI, Frederick Canc Res & Dev Ctr, ABL Basic Res Program, POB B,Bldg 539, Frederick, MD 21702 USA. FU NIDDK NIH HHS [DK-25387]; NIEHS NIH HHS [1-Y01-ES-50318-00] NR 41 TC 48 Z9 48 U1 0 U2 0 PU GENETICS PI BALTIMORE PA 428 EAST PRESTON ST, BALTIMORE, MD 21202 USA SN 0016-6731 J9 GENETICS JI Genetics PD APR PY 1998 VL 148 IS 4 BP 1951 EP 1961 PG 11 WC Genetics & Heredity SC Genetics & Heredity GA ZJ175 UT WOS:000073187000053 PM 9560408 ER PT J AU Huang, JD Mermall, V Strobel, MC Russell, LB Mooseker, MS Copeland, NG Jenkins, NA AF Huang, JD Mermall, V Strobel, MC Russell, LB Mooseker, MS Copeland, NG Jenkins, NA TI Molecular genetic dissection of mouse unconventional myosin-VA: Tail region mutations SO GENETICS LA English DT Article ID MESSENGER-RNA; EXON SEQUENCES; DILUTE GENE; SACCHAROMYCES-CEREVISIAE; GRISCELLI DISEASE; PURKINJE-CELLS; LOCALIZATION; CLONING; IDENTIFICATION; SUBSTITUTIONS AB We used an RT-PCR-based sequencing approach to identify the mutations responsible for 17 viable dilute alleles, a mouse-coat-color locus encoding unconventional myosin-VA. Ten of the mutations mapped to the MyoVA tail and are reported here. These mutations represent the first extensive collection of tail mutations reported for any unconventional mammalian myosin. They identify sequences important for tail function and identify domains potentially involved in cargo binding and/or proper folding of the MyoVA tail. Our results also provide support for the notion that different myosin tail isoforms produced by alternative splicing encode important cell-ripe-specific functions. C1 NCI, Frederick Canc Res & Dev Ctr, ABL Basic Res Program, Frederick, MD 21702 USA. Yale Univ, Dept Biol, New Haven, CT 06520 USA. Yale Univ, Dept Pathol, New Haven, CT 06520 USA. Yale Univ, Dept Cell Biol, New Haven, CT 06520 USA. Oak Ridge Natl Lab, Oak Ridge, TN 37831 USA. RP Jenkins, NA (reprint author), NCI, Frederick Canc Res & Dev Ctr, ABL Basic Res Program, POB B,Bldg 539, Frederick, MD 21702 USA. EM jenkins@ncifcrf.gov FU NIDDK NIH HHS [DK-25387]; NIEHS NIH HHS [1-Y01-ES-50318-00] NR 50 TC 83 Z9 83 U1 0 U2 2 PU GENETICS PI BALTIMORE PA 428 EAST PRESTON ST, BALTIMORE, MD 21202 USA SN 0016-6731 J9 GENETICS JI Genetics PD APR PY 1998 VL 148 IS 4 BP 1963 EP 1972 PG 10 WC Genetics & Heredity SC Genetics & Heredity GA ZJ175 UT WOS:000073187000054 PM 9560409 ER PT J AU Pruitt, KD AF Pruitt, KD TI WebWise: Guide to the Institute of Molecular Biology Genome Sequencing Center - Jena Web site SO GENOME RESEARCH LA English DT Editorial Material C1 NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20894 USA. RP Pruitt, KD (reprint author), NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20894 USA. EM pruitt@ncbi.nlm.nih.gov NR 4 TC 1 Z9 1 U1 0 U2 0 PU COLD SPRING HARBOR LAB PRESS PI PLAINVIEW PA 1 BUNGTOWN RD, PLAINVIEW, NY 11724 USA SN 1054-9803 J9 GENOME RES JI Genome Res. PD APR PY 1998 VL 8 IS 4 BP 334 EP 338 PG 5 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity GA ZJ425 UT WOS:000073214400002 PM 9548968 ER PT J AU Torigoe, K Harada, T Kusaba, H Uchiumi, T Kohno, K Green, ED Scherer, SW Tsui, LC Schlessinger, D Kuwano, M Wada, M AF Torigoe, K Harada, T Kusaba, H Uchiumi, T Kohno, K Green, ED Scherer, SW Tsui, LC Schlessinger, D Kuwano, M Wada, M TI Localization of 67 exons on a YAC contig spanning 1.5 Mb around the multidrug resistance gene region of human chromosome 7q21.1 SO GENOMICS LA English DT Article ID YEAST ARTIFICIAL CHROMOSOMES; P-GLYCOPROTEIN GENE; DNA-SEQUENCES; CELL-LINES; COMPLEMENTARY-DNA; DRUG RESISTANCE; HAMSTER-CELLS; HUMAN CANCER; MOUSE CELLS; AMPLIFICATION AB A contig of 21 nonchimeric yeast artificial chromosomes (YACs) was previously assembled across 1.5 Mb of the multidrug resistance (MDR) gene (PGY1 and PGY3) region of human chromosome 7q21.1. This region of the human genome has now been subjected to exon amplification to detect the presence of additional genes. Exon tapping was performed directly on the YACs. Sixty-seven gene fragments were isolated and characterized by sequence analysis and comparison with public databases. The localization of these exons in the 1.5-Mb region was determined by hybridization to YAC clones, and they were localized in 11 subregions of YAC contigs. The exon collection includes 21 exons that were identical to known cDNA sequences of PGY1, PGY3, sorcin (SRI), the cDNA similar to the delta subunit of the human amiloride-sensitive Na(-) channel (SCNED), and 4 cDNAs with unknown function; 43 exons that showed homology/similarity to known cDNA sequences of mouse DMP1, rat COT, mouse and human NADHD, human MDC, 3 cDNAs encoding possible membrane proteins, and 21 other cDNAs; and 3 exons that shared no homology/similarity with any sequence in public databases. The nucleotide sequences of all the PGY1 and PGY3 exons were identical to the corresponding cDNA sequences previously determined, and these exons were localized to the expected positions on the appropriate YAC clones. No other member of the MDR gene family thus appeared to be present in the 1.5-Mb region. The integrated physical and exon maps should prove valuable for both fine mapping and determination of a complete gene map of this segment of the genome. (C) 1998 Academic Press. C1 Kyushu Univ, Dept Biochem, Sch Med, Higashi Ku, Fukuoka 81282, Japan. Natl Human Genome Res Inst, NIH, Bethesda, MD 20892 USA. Hosp Sick Children, Res Inst, Dept Genet, Toronto, ON M5G 1X8, Canada. Washington Univ, Sch Med, Dept Mol Microbiol, St Louis, MO USA. RP Wada, M (reprint author), Kyushu Univ, Dept Biochem, Sch Med, Higashi Ku, Fukuoka 81282, Japan. EM wada@biochem1.med.kyusyu-u.ac.jp RI Tsui, Lap-chee/A-1081-2010; Howe, Jennifer/I-9013-2012; Scherer, Stephen /B-3785-2013 OI Scherer, Stephen /0000-0002-8326-1999 NR 52 TC 6 Z9 6 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0888-7543 J9 GENOMICS JI Genomics PD APR 1 PY 1998 VL 49 IS 1 BP 14 EP 22 DI 10.1006/geno.1997.5200 PG 9 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA ZH973 UT WOS:000073166900002 PM 9570944 ER PT J AU Kalyanaraman, S Copeland, NG Gilbert, DG Jenkins, NA Gautam, N AF Kalyanaraman, S Copeland, NG Gilbert, DG Jenkins, NA Gautam, N TI Structure and chromosomal localization of mouse G protein subunit gamma 4 gene SO GENOMICS LA English DT Article ID SIGNAL TRANSDUCTION; BETA; EVOLUTION; SEQUENCES; COMPLEX; CDNA AB The G protein gamma subunits are members of a multigene family and are implicated in determining the specificity of receptor-G: protein interaction. The gene structures for many of the gamma subunits remain to be determined. Here, we report the gene structure for the brain-specific gamma 4 subunit and its map position on a mouse chromosome. The gene (Gng4) comprises at least three exons spanning over 20 kb. The 225-bp coding region, which spans two exons, is interrupted by a large 18.2-kb intron whose position is conserved in other gamma subunit genes. There is a putative additional intron in the 5' untranslated region just upstream of the translation initiation codon. Introns are present in most of the other gamma subunits at this position. The mouse Gng4 gene is mapped to chromosome 13. (C) 1998 Academic Press. C1 Washington Univ, Sch Med, Dept Anesthesiol, St Louis, MO 63110 USA. Washington Univ, Sch Med, Dept Genet, St Louis, MO 63110 USA. NCI, Frederick Canc Res & Dev Ctr, Mammalian Genet Lab, ABL Basic Res Program, Frederick, MD 21702 USA. RP Gautam, N (reprint author), Washington Univ, Sch Med, Dept Anesthesiol, Box 8054, St Louis, MO 63110 USA. EM gautam@morpheus.wustl.edu NR 25 TC 12 Z9 13 U1 0 U2 0 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0888-7543 J9 GENOMICS JI Genomics PD APR 1 PY 1998 VL 49 IS 1 BP 147 EP 151 DI 10.1006/geno.1998.5223 PG 5 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA ZH973 UT WOS:000073166900019 PM 9570961 ER PT J AU Ma, JX Ramachandran, S Fiedorek, FT Zeldin, DC AF Ma, JX Ramachandran, S Fiedorek, FT Zeldin, DC TI Mapping of the CYP2J cytochrome P450 genes to human chromosome 1 and mouse chromosome 4 SO GENOMICS LA English DT Article ID INSITU HYBRIDIZATION; ACID; EXPRESSION; CLONING AB CYP26 subfamily cytochromes P450 catalyze the NADPH-dependent oxidation of arachidonic acid to several unique eicosanoids that possess numerous biological activities including modulation of ion transport, control of bronchial and vascular smooth muscle tone, and stimulation of peptide hormone secretion. We have identified sequence variants in the 3' untranslated regions of two mouse Cyp2j genes (Cyp2j5 and Cyp2j6) and used a PCR-based oligonucleotide hybridization assay to mag both genes to the central region of chromosome 4 distal to the Jun oncogene. The corresponding human CYP2J gene (CYP2J2) has been assigned to human chromosome 1 on as panel of somatic hybrid cell lines and to 1p31.2-p31.2 by fluorescence in situ hybridization analysis. The proximity of the Cyp2j cluster to the Cyp4a cluster suggests that these genes may be part of a cassette of P450 genes involved in the oxidation of fatty acids. (C) 1998 Academic Press. C1 NIEHS, Pulm Pathobiol Lab, NIH, Res Triangle Pk, NC 27709 USA. Univ N Carolina, Dept Med, Chapel Hill, NC 27599 USA. RP Zeldin, DC (reprint author), NIEHS, Pulm Pathobiol Lab, NIH, 111 TW Alexander Dr, Res Triangle Pk, NC 27709 USA. FU NIDDK NIH HHS [DK-44074] NR 21 TC 18 Z9 24 U1 0 U2 0 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0888-7543 J9 GENOMICS JI Genomics PD APR 1 PY 1998 VL 49 IS 1 BP 152 EP 155 DI 10.1006/geno.1998.5235 PG 4 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA ZH973 UT WOS:000073166900020 PM 9570962 ER PT J AU Gao, X Copeland, NG Gilbert, DJ Jenkins, NA Gridley, T AF Gao, X Copeland, NG Gilbert, DJ Jenkins, NA Gridley, T TI Assignment of the murine Notch2 and Notch3 genes to chromosomes 3 and 17 SO GENOMICS LA English DT Article ID MOUSE GENOME; INTEGRATION; EXPRESSION; LOCATION; LINKAGE; HOMOLOG C1 Jackson Lab, Bar Harbor, ME 04609 USA. NCI, Frederick Canc Res & Dev Ctr, Mammalian Genet Lab, ABL Basic Res Program, Frederick, MD 21702 USA. RP Gridley, T (reprint author), Jackson Lab, 600 Main St, Bar Harbor, ME 04609 USA. FU NINDS NIH HHS [NS36437] NR 13 TC 3 Z9 3 U1 0 U2 0 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0888-7543 J9 GENOMICS JI Genomics PD APR 1 PY 1998 VL 49 IS 1 BP 160 EP 161 DI 10.1006/geno.1997.5211 PG 2 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA ZH973 UT WOS:000073166900023 PM 9570965 ER PT J AU Riley, MW AF Riley, MW TI Successful aging SO GERONTOLOGIST LA English DT Letter C1 NIA, NIH, Bethesda, MD 20892 USA. RP Riley, MW (reprint author), NIA, NIH, Bethesda, MD 20892 USA. NR 4 TC 21 Z9 22 U1 0 U2 3 PU GERONTOLOGICAL SOCIETY AMER PI WASHINGTON PA 1275 K STREET NW SUITE 350, WASHINGTON, DC 20005-4006 USA SN 0016-9013 J9 GERONTOLOGIST JI Gerontologist PD APR PY 1998 VL 38 IS 2 BP 151 EP 151 PG 1 WC Gerontology SC Geriatrics & Gerontology GA ZG587 UT WOS:000073018600001 PM 9573658 ER PT J AU Schmitz, L Favara, BE AF Schmitz, L Favara, BE TI Nosology and pathology of Langerhans cell histiocytosis SO HEMATOLOGY-ONCOLOGY CLINICS OF NORTH AMERICA LA English DT Review ID SOLITARY EOSINOPHILIC GRANULOMA; SELF-HEALING RETICULOHISTIOCYTOSIS; BRONCHOALVEOLAR LAVAGE FLUID; NEEDLE ASPIRATION CYTOLOGY; CYTOMETRIC DNA-CONTENT; FRONTAL-LOBE; ELECTRON-MICROSCOPY; BIRBECK GRANULES; TEMPORAL-LOBE; FACTOR-XIIIA AB In this article, Langerhans cell histiocytosis (LCH) is described with a nosological perspective. The epidermal Langerhans cell, which most closely resembles the key lesional cell, is characterized. The basic lesion of LCH, its patterns in different sites, diagnostic methods, and results of special studies are detailed. Current concepts of pathogenesis also are discussed. C1 N Pathol Associates, N Mem Med Ctr, Robbinsdale, MN 55422 USA. Univ Utah, Dept Pathol, Salt Lake City, UT USA. Univ Minnesota, Dept Pathol, Minneapolis, MN 55455 USA. NIH, Rocky Mt Labs, Hamilton, MT USA. RP Schmitz, L (reprint author), N Pathol Associates, N Mem Med Ctr, 3300 Oakdale N, Robbinsdale, MN 55422 USA. NR 116 TC 90 Z9 98 U1 0 U2 2 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0889-8588 J9 HEMATOL ONCOL CLIN N JI Hematol. Oncol. Clin. North Am. PD APR PY 1998 VL 12 IS 2 BP 221 EP + DI 10.1016/S0889-8588(05)70507-4 PG 27 WC Oncology; Hematology SC Oncology; Hematology GA ZG236 UT WOS:000072980800003 PM 9561897 ER PT J AU Grois, NG Favara, BE Mostbeck, GH Prayer, D AF Grois, NG Favara, BE Mostbeck, GH Prayer, D TI Central nervous system disease in Langerhans cell histiocytosis SO HEMATOLOGY-ONCOLOGY CLINICS OF NORTH AMERICA LA English DT Article ID MULTIFOCAL EOSINOPHILIC GRANULOMA; CENTRAL DIABETES-INSIPIDUS; PITUITARY-STALK; CEREBELLAR DEGENERATION; POSTERIOR PITUITARY; HORMONE DEFICIENCY; PURKINJE-CELLS; FRONTAL-LOBE; MR FINDINGS; CHILDREN AB Central nervous system (CNS) disease in Langerhans cell histiocytosis (LCH) is a poorly understood complication of yet unknown frequency. By far the most common manifestation is in the hypothalamic-pituitary system with diabetes insipidus as the leading sign, followed by other endocrinopathies and hypothalamic dysfunction. However, essentially all other parts of the CNS may be involved. On the one hand, space-occupying histiocytic infiltrates may lead to size-and site-depending symptoms, extending from adjacent bone lesions or arising from the meninges or choroid plexus. On the other hand, a progressive neurological deterioration can occur with mainly cerebellar-pontine symptoms. Ln this article, these clinical patterns are described in correlation with the morphology on MR imaging and histopathology. Further, the therapeutic strategies are reviewed critically, and guidelines for the management of patients with LCH-related CNS disease are presented. C1 St Anna Childrens Hosp, A-1090 Vienna, Austria. Univ Utah, Dept Pathol, Salt Lake City, UT USA. NIH, Rocky Mt Labs, Hamilton, MT USA. Univ Hosp Vienna, Dept Radiol, Vienna, Austria. RP Grois, NG (reprint author), St Anna Childrens Hosp, Kinderspitalgasse 6, A-1090 Vienna, Austria. NR 86 TC 122 Z9 123 U1 1 U2 4 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0889-8588 J9 HEMATOL ONCOL CLIN N JI Hematol. Oncol. Clin. North Am. PD APR PY 1998 VL 12 IS 2 BP 287 EP + DI 10.1016/S0889-8588(05)70511-6 PG 20 WC Oncology; Hematology SC Oncology; Hematology GA ZG236 UT WOS:000072980800007 PM 9561901 ER PT J AU Egeler, RM Neglia, JP Arico, M Favara, BE Heitger, A Nesbit, ME Nicholson, HS AF Egeler, RM Neglia, JP Arico, M Favara, BE Heitger, A Nesbit, ME Nicholson, HS TI The relation of Langerhans cell histiocytosis to acute leukemia, lymphomas, and other solid tumors - The LCH-Malignancy Study Group of the Histiocyte Society SO HEMATOLOGY-ONCOLOGY CLINICS OF NORTH AMERICA LA English DT Article ID ACUTE MYELOID-LEUKEMIA; ACUTE PROMYELOCYTIC LEUKEMIA; ASSOCIATION; ETOPOSIDE; EPIPODOPHYLLOTOXINS; NEOPLASMS; CHILDREN; THERAPY; BONE AB The frequency of Langerhans cell histiocytosis (LCH) and a malignant neoplasm occurring in the same individual appears to be greater than previously recognized. To define the occurrence and the pattern of these events, a Study Group of the Histiocyte Society initiated a registry of patients in whom this association occurred synchronously or asynchronously. Evaluation of 54 patients detected two patterns of associations between LCH and other disorders. First, it is possible that therapy of LCH promotes a secondary malignancy. Second, it is possible that a genetic predisposition, with or without the immunosuppression associated therapy for the malignancy, plays a role in the development and expression of disseminated LCH. Data collected by the LCH Malignancy Study Group may provide insights into the etiology and pathophysiology of LCH. C1 Univ Alberta, Alberta Childrens Hosp, So Alberta Childrens Canc Program, Tom Baker Canc Ctr, Calgary, AB T2T 5C7, Canada. Erasmus Univ, Sophia Childrens Hosp, Div Pediat Oncol, Rotterdam, Netherlands. Univ Minnesota, Sch Med, Minneapolis, MN 55455 USA. Univ Pavia, Policlin San Matteo, IRCCS, Dept Pediat, I-27100 Pavia, Italy. Univ Utah, Dept Pathol, Salt Lake City, UT USA. NIH, Rocky Mt Labs, Hamilton, MT USA. Univ Innsbruck, Childrens Hosp, Dept Pediat, A-6020 Innsbruck, Austria. Oregon Hlth & Sci Univ, Dept Pediat, NRC5, Portland, OR 97201 USA. RP Egeler, RM (reprint author), Univ Alberta, Alberta Childrens Hosp, So Alberta Childrens Canc Program, Tom Baker Canc Ctr, Calgary, AB T2T 5C7, Canada. NR 22 TC 112 Z9 117 U1 0 U2 0 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0889-8588 J9 HEMATOL ONCOL CLIN N JI Hematol. Oncol. Clin. North Am. PD APR PY 1998 VL 12 IS 2 BP 369 EP + DI 10.1016/S0889-8588(05)70516-5 PG 11 WC Oncology; Hematology SC Oncology; Hematology GA ZG236 UT WOS:000072980800012 PM 9561906 ER PT J AU Deng, DX Chakrabarti, S Waalkes, MP Cherian, MG AF Deng, DX Chakrabarti, S Waalkes, MP Cherian, MG TI Metallothionein and apoptosis in primary human hepatocellular carcinoma and metastatic adenocarcinoma SO HISTOPATHOLOGY LA English DT Article DE adenocarcinoma; apoptosis; metallothionein; metastasis; primary hepatocellular carcinoma ID PRIMARY BREAST CARCINOMAS; IMMUNOHISTOCHEMICAL LOCALIZATION; HUMAN-LIVER; COLORECTAL ADENOCARCINOMA; PROTECTS DNA; EXPRESSION; TUMORS; CELLS; CADMIUM; MOUSE AB Aims: Differences in expression of metallothionein (MT) have been reported in various human tumours. MT is mainly expressed in proliferating epithelial tumour cells but in human hepatocellular carcinoma (HCC) there is only a minimal expression of MT, Since MT is a zinc binding protein and certain inducers of MT including zinc play a role in apoptosis, studies were undertaken to compare the expression of MT and the presence of apoptotic cells (APPC) in both primary HCC and metastatic adenocarcinoma. Methods and results: Histological sections of 13 cases of primary HCC and eight cases of metastatic adenocarcinoma were obtained from archival samples. They were stained for MT using a polyclonal antibody which crossreacts readily with human MT and for APPC by the TUNEL technique. Normal human liver had consistent MT staining with no detectable APPC, The primary HCC showed moderate MT staining with a small number of APPC while metastatic adenocarcinoma showed no MT staining with a large number of APPC. Conclusions: These results suggest a relationship between absence of MT and appearance of APPC in human liver tumours, especially in metastatic adenocarcinomas. C1 Univ Western Ontario, Dept Pathol, London, ON N6A 5C1, Canada. NCI, Frederick Canc Res & Dev Ctr, Biol Carcinogenesis & Dev Program, Frederick, MD USA. RP Cherian, MG (reprint author), Univ Western Ontario, Dept Pathol, London, ON N6A 5C1, Canada. NR 43 TC 45 Z9 53 U1 0 U2 1 PU BLACKWELL SCIENCE LTD PI OXFORD PA P O BOX 88, OSNEY MEAD, OXFORD OX2 0NE, OXON, ENGLAND SN 0309-0167 J9 HISTOPATHOLOGY JI Histopathology PD APR PY 1998 VL 32 IS 4 BP 340 EP 347 PG 8 WC Cell Biology; Pathology SC Cell Biology; Pathology GA ZH462 UT WOS:000073112700007 PM 9602331 ER PT J AU Vargas, FR Roessler, E Gaudenz, K Belloni, E Whitehead, AS Kirke, PN Mills, JL Hooper, G Stevenson, RE Cordeiro, I Correia, P Felix, T Gereige, R Cunningham, ML Canun, S Antonarakis, SE Strachan, T Tsui, LC Scherer, SW Muenke, M AF Vargas, FR Roessler, E Gaudenz, K Belloni, E Whitehead, AS Kirke, PN Mills, JL Hooper, G Stevenson, RE Cordeiro, I Correia, P Felix, T Gereige, R Cunningham, ML Canun, S Antonarakis, SE Strachan, T Tsui, LC Scherer, SW Muenke, M TI Analysis of the human Sonic Hedgehog coding and promoter regions in sacral agenesis, triphalangeal thumb, and mirror polydactyly SO HUMAN GENETICS LA English DT Article ID VARIABLE EXPRESSION; GENE; MAPS; 7Q36; DROSOPHILA; PROTEINS; FAMILY; MUTATIONS; CYCLOPIA; POLARITY AB The human Sonic Hedgehog gene (SHH) is one of the vertebrate homologs related to the Drosophila segment polarity gene hedgehog. The entire coding and promoter region of the SHH gene, including 2 kb 5' of the transcriptional start site has been screened for mutations in families with autosomal dominant sacral agenesis and autosomal dominant triphalangeal thumb, two conditions previously known to be Linked to 7q36. We have also studied the SHH gene in five families with minor polydactyly associated with tibial hemimelia and in 51 unrelated patients with neural tube defects. Except for two sequence variants in exon 3, no mutations were found in these disease categories. C1 Univ Penn, Childrens Hosp Philadelphia, Sch Med, Div Human Genet & Mol Biol,Dept Pediat, Philadelphia, PA 19104 USA. Univ Penn, Childrens Hosp Philadelphia, Sch Med, Div Human Genet & Mol Biol,Dept Genet, Philadelphia, PA 19104 USA. Hosp Sick Children, Dept Genet, Toronto, ON M5G 1X8, Canada. Trinity Coll, Dublin, Ireland. FIOCRUZ, IFF, BR-21045900 Rio De Janeiro, Brazil. Hosp Clin Porto Alegre, Porto Alegre, RS, Brazil. Univ S Florida, All Childrens Hosp, St Petersburg, FL 33701 USA. Univ Washington, Seattle, WA 98195 USA. Dr Manuel Gea Gonzalez Gen Hosp, Mexico City, DF, Mexico. Hlth Res Board, Dublin, Ireland. Geneva Med Sch, Geneva, Switzerland. NICHHD, NIH, Bethesda, MD 20892 USA. Univ Newcastle Upon Tyne, Newcastle Upon Tyne NE1 7RU, Tyne & Wear, England. Princess Margaret Rose Orthopaed Hosp, Edinburgh EH10 7ED, Midlothian, Scotland. Greenwood Genet Ctr, Greenwood, SC 29646 USA. Hosp Santa Maria, Lisbon, Portugal. RP Muenke, M (reprint author), Natl Human Genome Res Inst, Med Genet Branch, NIH, 10 Ctr Dr,MSC 1852,Bldg 10,Room 10-C-101C, Bethesda, MD 20892 USA. RI Felix, Temis/B-8073-2010; Tsui, Lap-chee/A-1081-2010; Howe, Jennifer/I-9013-2012; Scherer, Stephen /B-3785-2013; Antonarakis, Stylianos/N-8866-2014; belloni, elena/H-9909-2013; OI Felix, Temis/0000-0002-8401-6821; Scherer, Stephen /0000-0002-8326-1999; Antonarakis, Stylianos/0000-0001-8907-5823; Belloni, Elena/0000-0003-3214-0780 FU NICHD NIH HHS [5T32HD07107, HD01054, HD28732] NR 35 TC 35 Z9 35 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0340-6717 J9 HUM GENET JI Hum. Genet. PD APR PY 1998 VL 102 IS 4 BP 387 EP 392 DI 10.1007/s004390050709 PG 6 WC Genetics & Heredity SC Genetics & Heredity GA ZM546 UT WOS:000073551000002 PM 9600232 ER PT J AU Hodgkinson, CA Nakayama, A Li, H Swenson, LB Opdecamp, K Asher, JH Arnheiter, H Glaser, T AF Hodgkinson, CA Nakayama, A Li, H Swenson, LB Opdecamp, K Asher, JH Arnheiter, H Glaser, T TI Mutation at the anophthalmic white locus in Syrian hamsters: haploinsufficiency in the Mitf gene mimics human Waardenburg syndrome type 2 SO HUMAN MOLECULAR GENETICS LA English DT Article ID HELIX-LOOP-HELIX; MICROPHTHALMIA GENE; MODIFIER GENES; HUMAN HOMOLOG; MOUSE; DEFECTS; DISEASE; MUTANTS; ZIPPER; MODELS AB Mutations in MITF (microphthalmia transcription factor) cause Waardenburg syndrome type 2 (WS2A) in humans, an autosomal dominant disorder consisting of deafness and hypopigmentation. Phenotypes vary significantly within WS2 pedigrees, and there is generally no correlation between the predicted biochemical properties of mutant MITF proteins and disease severity, We have identified a nonsense mutation in the Mitf gene of the anophthalmic white (Wh) Syrian hamster that destabilizes its mRNA and prevents the encoded basic helix-loop-helix leucine zipper (bHLHzip) protein from dimerizing or binding DNA target sites, Although the resulting polypeptide does not act as a dominant-negative species in vitro, the Wh mutation is inherited as a semi-dominant trait, It thus more closely resembles WS2 than comparable Mitf alleles in laboratory mice and rats, which are expressed as purely recessive traits. C1 Univ Michigan, Howard Hughes Med Inst, Dept Internal Med, Ann Arbor, MI 48109 USA. Univ Michigan, Howard Hughes Med Inst, Dept Human Genet, Ann Arbor, MI 48109 USA. Michigan State Univ, Dept Zool, E Lansing, MI 48824 USA. Michigan State Univ, Grad Program Genet, E Lansing, MI 48824 USA. NINDS, Lab Dev Neurogenet, NIH, Bethesda, MD 20892 USA. RP Hodgkinson, CA (reprint author), Univ Michigan, Howard Hughes Med Inst, Dept Internal Med, Ann Arbor, MI 48109 USA. NR 33 TC 28 Z9 32 U1 1 U2 3 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0964-6906 J9 HUM MOL GENET JI Hum. Mol. Genet. PD APR PY 1998 VL 7 IS 4 BP 703 EP 708 DI 10.1093/hmg/7.4.703 PG 6 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA ZF320 UT WOS:000072885700015 PM 9499424 ER PT J AU Bertheau, P Steinberg, SM Merino, MJ AF Bertheau, P Steinberg, SM Merino, MJ TI C-erbB-2, p53, and nm23 gene product expression in breast cancer in young women: Immunohistochemical analysis and clinicopathologic correlation SO HUMAN PATHOLOGY LA English DT Article DE breast cancer; young woman; immunohistochemistry; nm23; c-erbB2; p53 ID PROTEIN EXPRESSION; PROGNOSTIC FACTOR; CARCINOMA; INDICATOR; FEATURES; TABLES; STAGE; AGE AB We studied c-erbB-2, p53, and nm23 gene products in 112 primary breast carcinomas. Fifty patients were aged 35 years or younger, and 62 were aged 36 to 50. Clinicopathological criteria including clinical stage, hormone receptor status, histological types, histological grades, and lymph node status, were reviewed. Disease-free survival (DFS) and overall survival (OS) were analyzed. Immunohistochemical findings were assessed semiquantitatively. Correlation between clinicopathological criteria, survival data, and immunohistochemical findings have been made. Patients aged younger than 35 years with stage I to II disease had a shorter DFS (P=.03) than older patients. However, no other clinicopathological finding was associated with age. Neither was there association between age and c-erbB-2, p53, or nm23 patterns of expression. p53 positivity was associated with high histological grade (P =.003) and with progesterone receptor negativity (P=.045). Nm23 nuclear positivity was associated with early clinical stages (P =.011) and with absence of axillary lymph node metastasis (P=.007). p53 and c-erbB-2 overexpression were associated with shorter OS while nm23 nuclear positivity was associated with longer OS in univariate and multivariate analyses. Univariate analyses showed that c-erbB-2 or nm23 were potentially important prognostic factors in women aged 35 years or younger while p53 was associated with prognosis in women aged 36 to 50. Cox model analysis indicated that c-erbB-2 alone was associated with prognosis in women 35 years and younger, whereas p53 alone was associated with prognosis in 36- to 50-year-old women. These results suggest that breast cancer in the youngest women has some biological specificity. Copyright (C) 1998 by W.B. Saunders Company. C1 Hop St Louis, Lab Surg Pathol, F-75010 Paris, France. NCI, Biostat & Data Management Sect, Div Clin Sci, NIH, Bethesda, MD 20892 USA. NCI, Pathol Lab, NIH, Bethesda, MD 20892 USA. RP Bertheau, P (reprint author), Hop St Louis, Serv Anat Pathol, 1 Ave Claude Vellefaux, F-75010 Paris, France. NR 36 TC 55 Z9 61 U1 0 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0046-8177 J9 HUM PATHOL JI Hum. Pathol. PD APR PY 1998 VL 29 IS 4 BP 323 EP 329 DI 10.1016/S0046-8177(98)90111-3 PG 7 WC Pathology SC Pathology GA ZG990 UT WOS:000073060800004 PM 9563780 ER PT J AU Kumar, S Krenacs, L Medeiros, J Elenitoba-Johnson, KSJ Greiner, TC Sorbara, L Kingma, DW Raffeld, M Jaffe, ES AF Kumar, S Krenacs, L Medeiros, J Elenitoba-Johnson, KSJ Greiner, TC Sorbara, L Kingma, DW Raffeld, M Jaffe, ES TI Subcutaneous panniculitic T-cell lymphoma is a tumor of cytotoxic T lymphocytes SO HUMAN PATHOLOGY LA English DT Article DE T-cell; cytotoxic; subcutaneous; lymphoma; Epstein-Barr virus; polymerase chain reaction; apoptosis ID POLYMERASE CHAIN-REACTION; NON-HODGKINS-LYMPHOMAS; CLINICOPATHOLOGICAL ENTITY; HEMOPHAGOCYTIC SYNDROME; RESISTANCE; APOPTOSIS; PERFORIN; GAMMA; LYSIS; CLASSIFICATION AB Subcutaneous panniculitic T cell lymphoma (SCPTCL) is characterized by primary involvement of the subcutaneous fat in a manner mimicking panniculitis. We studied 16 cases of this lymphoma to define its immunophenotypical profile as well as cellular origin. Involvement of the subcutaneous fat in a lacelike pattern with neoplastic cells rimming individual fat spaces was present in all cases. All 16 cases were of T cell phenotype. Thirteen of the 16 cases were CD8+, whereas three were negative for both CD4 and CD8. Twelve cases were stained for beta F1; of these, eight were beta F1+ and four were beta F1-. Focal staining for CD56 and CD30 was seen in 2 of 13 and two of eight cases, respectively. Intense diffuse positivity for the cytotoxic granular proteins T cell intracellular antigen-1 (TIA-1) and perforin was present in all cases, indicating an origin from cytotoxic T lymphocytes. Ten cases studied for Epstein-Barr viral sequences were negative. Eight of 9 cases with amplifiable DNA showed a clonal TCR gamma gene rearrangement by polymerase chain reaction. Controls included seven cases of benign panniculitis and seven other peripheral T cell lymphomas involving the skin and subcutaneous tissues: two peripheral T cell lymphomas, not otherwise specified (PTL,NOS), four anaplastic large cell. lymphomas (ALCL), one T/NK cell, lymphoma. The seven cases of panniculitis lacked cytological atypia and were characterized by an admixture of CD4+ and CD8+ cells with interspersed aggregates of L26+ B cells. Only infrequent cells showed staining for TIA-1 and perforin. In the control cases of T cell lymphoma, the infiltrate had a tendency for dermal and sometimes even epidermal involvement, with sheeting out of malignant cells, in contrast to the characteristic subcutaneous localization and rimming of fat spaces noted in SCPTCL. The two PTL, NOS were CD4+ and negative for both TLA-I and perforin. Although the remaining controls expressed TIA-1 and perforin, in keeping with their cytotoxic T or natural killer (NK) cell origin, histological and other immunophenotypical features allowed distinction from SCPTCL. Five cases of SCPTCL were also stained for apoptosis using a tdt-mediated end labeling kit. All cases showed numerous positive apoptotic bodies, suggesting apoptosis as the mechanism of cell death in these tumors. Our study indicates that SCPTCL constitutes a distinctive clinicopathological entity derived from cytotoxic T lymphocytes and should be differentiated from other benign and malignant lymphoid infiltrates involving the subcutis. The apoptosis seen in these tumors may be mediated by release of cytotoxic granular proteins. Copyright (C) 1998 by W.B. Saunders Company. C1 NCI, Hematopathol Sect, NIH, Bethesda, MD 20892 USA. RP Jaffe, ES (reprint author), NCI, Hematopathol Sect, NIH, Bldg 10,Room 2N 202,10 Ctr Dr,MSC 1500, Bethesda, MD 20892 USA. RI Krenacs, Laszlo/L-8063-2014 OI Krenacs, Laszlo/0000-0001-6541-3031 NR 33 TC 132 Z9 146 U1 0 U2 2 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0046-8177 J9 HUM PATHOL JI Hum. Pathol. PD APR PY 1998 VL 29 IS 4 BP 397 EP 403 DI 10.1016/S0046-8177(98)90122-8 PG 7 WC Pathology SC Pathology GA ZG990 UT WOS:000073060800015 PM 9563791 ER PT J AU Lanczycki, CJ Johnson, CA Trus, BL Conway, JF Steven, AC Martino, RL AF Lanczycki, CJ Johnson, CA Trus, BL Conway, JF Steven, AC Martino, RL TI Parallel computing strategies for determining viral capsid structure by cryoelectron microscopy SO IEEE COMPUTATIONAL SCIENCE & ENGINEERING LA English DT Article ID HERPES-SIMPLEX VIRUS; X-RAY CRYSTALLOGRAPHY; 3-DIMENSIONAL RECONSTRUCTION; VISUALIZATION; MICROGRAPHS; PENTONS AB To calculate a full 3D structural model of a virus capsid, researchers analyze cryo-electron micrographs that contain many, randomly oriented images of the virus. The authors use parallel computing techniques to improve the performance of the computational algorithms that determine each particle's orientation and generate the 3D model. This enhanced computational performance allows analysis of many more particles and a more precise determination of their orientations, letting researchers study important details of virus capsids at higher resolutions. C1 NIH, Computat Biosci & Engn Lab, Bethesda, MD 20892 USA. NIH, Struct Biol Res Lab, Bethesda, MD 20892 USA. RP Lanczycki, CJ (reprint author), NIH, Computat Biosci & Engn Lab, Bldg 12A,Rm 2033, Bethesda, MD 20892 USA. RI Conway, James/A-2296-2010 OI Conway, James/0000-0002-6581-4748 NR 20 TC 4 Z9 4 U1 0 U2 2 PU IEEE COMPUTER SOC PI LOS ALAMITOS PA 10662 LOS VAQUEROS CIRCLE, PO BOX 3014, LOS ALAMITOS, CA 90720-1314 USA SN 1070-9924 J9 IEEE COMPUT SCI ENG JI IEEE Comput. Sci. Eng. PD APR-JUN PY 1998 VL 5 IS 2 BP 76 EP 91 DI 10.1109/99.683745 PG 16 WC Computer Science, Theory & Methods; Engineering, Electrical & Electronic; Mathematics, Applied SC Computer Science; Engineering; Mathematics GA ZV451 UT WOS:000074305900010 ER PT J AU Ruttimann, UE Unser, M Rawlings, RR Rio, D Ramsey, NF Mattay, VS Hommer, DW Frank, JA Weinberger, DR AF Ruttimann, UE Unser, M Rawlings, RR Rio, D Ramsey, NF Mattay, VS Hommer, DW Frank, JA Weinberger, DR TI Statistical analysis of functional MRI data in the wavelet domain SO IEEE TRANSACTIONS ON MEDICAL IMAGING LA English DT Article DE functional magnetic resonance imaging; multiresolution analysis; statistical models; wavelet transform ID HUMAN BRAIN; SENSORY STIMULATION; IMAGE COMPRESSION; ACTIVATION; TRANSFORMS; MICROCALCIFICATIONS; MULTIRESOLUTION; LOCALIZATION; ONDELETTES; MAMMOGRAMS AB The use of the wavelet transform is explored for the detection of differences between brain functional magnetic resonance images (fMRT's) acquired under two different experimental conditions. The method benefits from the fact that a smooth and spatially localized signal can be represented by a small set of localized wavelet coefficients, while the power of white noise is uniformly spread throughout the wavelet space. Hence, a statistical procedure is developed that uses the imposed decomposition orthogonality to locate wavelet-space partitions with large signal-to-noise ratio (SNR), and subsequently restricts the testing for significant wavelet coefficients to these partitions. This results in a higher SNR and a smaller number of statistical tests, yielding a lower detection threshold compared to spatial-domain testing and, thus, a higher detection sensitivity without increasing type I errors, The multiresolution approach of the wavelet method is particularly suited to applications where the signal bandwidth and/or the characteristics of an imaging modality cannot be well specified. The proposed method was applied to compare two different fMRI acquisition modalities, Differences of the respective useful signal bandwidths could be clearly demonstrated; the estimated signal, due to the smoothness of the wavelet representation, yielded more compact regions of neuroactivity than standard spatial-domain testing. C1 NIAAA, Clin Studies Lab, NIH, Bethesda, MD 20892 USA. NIMH, Clin Brain Disorders Branch, NIH, Washington, DC 20032 USA. NIH, Lab Diagnost Radiol Res, Off Intramural Res, Bethesda, MD 20892 USA. Ecole Polytech Fed Lausanne, Swiss Fed Inst Technol, Biomed Imaging Grp, DMT IOA, CH-1015 Lausanne, Switzerland. RP Unser, M (reprint author), Ecole Polytech Fed Lausanne, Swiss Fed Inst Technol, Biomed Imaging Grp, DMT IOA, CH-1015 Lausanne, Switzerland. RI Unser, Michael/A-1550-2008 NR 56 TC 101 Z9 105 U1 1 U2 4 PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017-2394 USA SN 0278-0062 J9 IEEE T MED IMAGING JI IEEE Trans. Med. Imaging PD APR PY 1998 VL 17 IS 2 BP 142 EP 154 DI 10.1109/42.700727 PG 13 WC Computer Science, Interdisciplinary Applications; Engineering, Biomedical; Engineering, Electrical & Electronic; Imaging Science & Photographic Technology; Radiology, Nuclear Medicine & Medical Imaging SC Computer Science; Engineering; Imaging Science & Photographic Technology; Radiology, Nuclear Medicine & Medical Imaging GA 100XE UT WOS:000074840000002 PM 9688147 ER PT J AU Ding, YH Smith, KJ Garboczi, DN Utz, U Biddison, WE Wiley, DC AF Ding, YH Smith, KJ Garboczi, DN Utz, U Biddison, WE Wiley, DC TI Two human T cell receptors bind in a similar diagonal mode to the HLA-A2/Tax peptide complex using different TCR amino acids SO IMMUNITY LA English DT Article ID MHC CLASS-I; LYMPHOTROPIC VIRUS TYPE-1; 3-DIMENSIONAL STRUCTURE; CRYSTAL-STRUCTURE; H-2K(B) MOLECULE; VIRAL PEPTIDES; ALPHA-BETA; RECOGNITION; ORIENTATION; LYMPHOCYTES AB The three-dimensional structure of a human alpha beta T cell receptor (TCR), B7, bound to the HLA-A2 molecule/HTLV-1 Tax peptide complex was determined by x-ray crystallography. Although different from the A6 TCR, previously studied, in 16 of the 17 residues that contact HLA-A2/Tax, the B7 TCR binds in a similar diagonal manner, only slightly tipped and rotated, relative to the A6 TCR. The structure explains data from functional assays on the specificity differences between the B7 and A6 TCRs for agonist, partial agonist, and null peptides. The existence of a structurally similar diagonal binding mode for TCRs favors mechanisms based on the formation of geometrically defined supramolecular assemblies for initiating signaling. C1 Harvard Univ, Howard Hughes Med Inst, Dept Cellular & Mol Biol, Cambridge, MA 02138 USA. Childrens Hosp, Howard Hughes Med Inst, Dept Med, Mol Med Lab, Boston, MA 02115 USA. Inst Rech Clin Montreal, Immunol Lab, Montreal, PQ H2W 1R7, Canada. NINDS, Mol Immunol Sect, Neuroimmunol Branch, NIH, Bethesda, MD 20892 USA. RP Wiley, DC (reprint author), Harvard Univ, Howard Hughes Med Inst, Dept Cellular & Mol Biol, Cambridge, MA 02138 USA. EM wiley@xtal0.harvard.edu NR 44 TC 365 Z9 368 U1 0 U2 7 PU CELL PRESS PI CAMBRIDGE PA 1050 MASSACHUSETTES AVE, CIRCULATION DEPT, CAMBRIDGE, MA 02138 USA SN 1074-7613 J9 IMMUNITY JI Immunity PD APR PY 1998 VL 8 IS 4 BP 403 EP 411 DI 10.1016/S1074-7613(00)80546-4 PG 9 WC Immunology SC Immunology GA ZK664 UT WOS:000073348000003 PM 9586631 ER PT J AU Comeau, MR Johnson, R DuBose, RF Petersen, M Gearing, P VandenBos, T Park, L Farrah, T Buller, RM Cohen, JI Strockbine, LD Rauch, C Spriggs, MK AF Comeau, MR Johnson, R DuBose, RF Petersen, M Gearing, P VandenBos, T Park, L Farrah, T Buller, RM Cohen, JI Strockbine, LD Rauch, C Spriggs, MK TI A poxvirus-encoded semaphorin induces cytokine production from monocytes and binds to a novel cellular semaphorin receptor, VESPR SO IMMUNITY LA English DT Article ID GROWTH CONE GUIDANCE; MONOCLONAL-ANTIBODIES; SURFACE MOLECULE; AXON GUIDANCE; B-CELLS; EXPRESSION; IDENTIFICATION; PLEXIN; SEQUENCE; PROTEINS AB The vaccinia virus A39R protein is a member of the semaphorin family. A39R.Fc protein was used to affinity purify an A39R receptor from a human B cell line. Tandem mass spectrometry of receptor peptides yielded partial amino acid sequences that allowed the identification of corresponding cDNA clones. Sequence analysis of this receptor indicated that it is a novel member of the plexin family and identified a semaphorin-like domain within this family, thus suggesting an evolutionary relationship between receptor and ligand. A39R up-regulated ICAM-1 on, and induced cytokine production from, human monocytes. These data, then, describe a receptor for an immunologically active semaphorin and suggest that it may serve as a prototype for other plexin-semaphorin binding pairs. C1 Immunex Res & Dev Corp, Dept Mol Biol, Seattle, WA 98101 USA. Immunex Res & Dev Corp, Dept Prot Chem, Seattle, WA 98101 USA. Immunex Res & Dev Corp, Dept Bioinformat, Seattle, WA 98101 USA. Immunex Res & Dev Corp, Dept Biochem, Seattle, WA 98101 USA. St Louis Univ, Dept Mol Biol & Immunol, St Louis, MO 63104 USA. NIAID, Viral Dis Lab, NIH, Bethesda, MD 20892 USA. RP Spriggs, MK (reprint author), Immunex Res & Dev Corp, Dept Mol Biol, 51 Univ St, Seattle, WA 98101 USA. EM spriggs@immunex.com NR 47 TC 190 Z9 195 U1 0 U2 6 PU CELL PRESS PI CAMBRIDGE PA 1050 MASSACHUSETTES AVE, CIRCULATION DEPT, CAMBRIDGE, MA 02138 USA SN 1074-7613 J9 IMMUNITY JI Immunity PD APR PY 1998 VL 8 IS 4 BP 473 EP 482 DI 10.1016/S1074-7613(00)80552-X PG 10 WC Immunology SC Immunology GA ZK664 UT WOS:000073348000009 PM 9586637 ER PT J AU Mage, RG AF Mage, RG TI Diversification of rabbit V-H genes by gene-conversion-like and hypermutation mechanisms SO IMMUNOLOGICAL REVIEWS LA English DT Review ID SOMATIC HYPERMUTATION; IMMUNOGLOBULIN GENES; GERMINAL-CENTERS; REGION SEQUENCES; ALICIA RABBITS; B-CELLS; EXPRESSION; RAG-2; REARRANGEMENT; MUTAGENESIS AB Where, when and how does V-H diversification occur in the rabbit? Early diversification by gene-conversion and somatic hypermutation in rabbit appendix and chicken bursa of Fabricius are similar processes; the chicken bursa and the rabbit appendix have homologous functions. However, diversification in bursa starts during embryonic development whereas it starts in rabbit appendix about 2 weeks after birth in the presence of antigens and superantigens that may contribute to positive and negative selection, affect B-cell expansion and mold the repertoire. The biochemical steps leading to diversification by gene conversion are unknown. However elevated levels of RAD51 mRNA in both chicken bursa and young rabbit appendix suggest that repair of double strand breaks may be involved. The base changes found in expressed rabbit V-H sequences derived from rearrangement of known germline V-H genes followed by one or more gene conversions occur with frequencies similar to those found in analyses of somatic hypermutation. The Ser codons in CDR1 and CDR2 of rabbit V(H)1 genes are all AGY rather than TCN, suggesting that they may represent intrinsic hotspots for hypermutation comparable to those described in human and mouse V-H. Somatic hypermutation may further refine antibody affinities in rabbit germinal centers. C1 NIAID, Mol Immunogenet Sect, Immunol Lab, Bethesda, MD 20892 USA. RP Mage, RG (reprint author), NIAID, Mol Immunogenet Sect, Immunol Lab, Bldg 10,Rm 11N311,10 Ctr Dr MSC 1892, Bethesda, MD 20892 USA. NR 45 TC 19 Z9 19 U1 0 U2 2 PU MUNKSGAARD INT PUBL LTD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0105-2896 J9 IMMUNOL REV JI Immunol. Rev. PD APR PY 1998 VL 162 BP 49 EP 54 DI 10.1111/j.1600-065X.1998.tb01428.x PG 6 WC Immunology SC Immunology GA ZK393 UT WOS:000073316200005 PM 9602351 ER PT J AU Winter, DB Gearhart, PJ AF Winter, DB Gearhart, PJ TI Dual enigma of somatic hypermutation of immunoglobulin variable genes: targeting and mechanism SO IMMUNOLOGICAL REVIEWS LA English DT Review ID POINT MUTATIONS; VDJ GENES; VH GENES; DIVERSIFICATION; SEQUENCES; RECOMBINATION; DIVERSITY; KAPPA; ANTIBODIES; TRANSGENES AB The immunoglobulin loci are uniquely unstable regions of the genome which undergo as much mutation and selection in a matter of days as a species can undergo in generations of evolution. We have studied the mutational pattern and targeting of this unusual hypermutation process over the past 16 years. The pattern of somatic mutations in rearranged variable (V) genes differs from the pattern of meiotic mutations, indicating that a different mechanism generates hypermutation than generates spontaneous mutation. Hypermutations begin on the 5' end of rearranged V genes downstream of the transcription initiation site and continue through the V exon and into the 3'-flanking region before tapering off. Mutations are located randomly throughout the DNA sequence and exhibit strand bias. The targeting of mutations to the region in and around the rearranged V gene appears to require interactions between the promoter and downstream intronic DNA sequences. The same mechanism that initiates hypermutation around V genes may also produce double-strand breaks that catalyze homologous recombination between rearranged V genes on two chromosomal alleles. With this data we have built a model of hypermutation which predicts that V-region DNA is destabilized at the nuclear matrix during transcription and undergoes strand breaks. C1 NIA, Gerontol Res Ctr, Mol Genet Lab, NIH, Baltimore, MD 21224 USA. RP Gearhart, PJ (reprint author), NIA, Gerontol Res Ctr, Mol Genet Lab, NIH, Box 1,5600 Nathan Shock Dr, Baltimore, MD 21224 USA. NR 33 TC 25 Z9 25 U1 0 U2 0 PU MUNKSGAARD INT PUBL LTD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0105-2896 J9 IMMUNOL REV JI Immunol. Rev. PD APR PY 1998 VL 162 BP 89 EP 96 DI 10.1111/j.1600-065X.1998.tb01432.x PG 8 WC Immunology SC Immunology GA ZK393 UT WOS:000073316200009 PM 9602355 ER PT J AU Hemmer, B Vergelli, M Pinilla, C Houghten, R Martin, R AF Hemmer, B Vergelli, M Pinilla, C Houghten, R Martin, R TI Probing degeneracy in T-cell recognition using peptide combinatorial libraries SO IMMUNOLOGY TODAY LA English DT Article ID CYTOTOXIC LYMPHOCYTES-T; POSITIVE SELECTION; RECEPTOR LIGANDS; ALPHA-BETA; COMPLEX; MOLECULE; PROTEIN; ALLOREACTIVITY; SPECIFICITY; BINDING AB Recent studies have demonstrated flexibility of the T-cell receptor (TCX) with respect to recognition of peptide bound to self major histocompatibility complex (MHC). With the introduction of peptide combinatorial libraries, it has become possible to dissect the extent of degeneracy in T-cell recognition. On the basis of these novel findings, Bernhard Hemmer and colleagues propose a conceptual framework for lymphocyte selection and survival and the occurrence of autoimmunity. C1 NINDS, Cellular Immunol Sect, Neuroimmunol Branch, NIH, Bethesda, MD 20892 USA. Univ Maryland, Dept Neurol, Baltimore, MD 21201 USA. Torrey Pines Inst Mol Studies, San Diego, CA 92121 USA. Multiple Peptide Syst, San Diego, CA 92121 USA. RP Hemmer, B (reprint author), NINDS, Cellular Immunol Sect, Neuroimmunol Branch, NIH, Bethesda, MD 20892 USA. EM rmartnib@box-h.nih.gov NR 44 TC 108 Z9 108 U1 0 U2 0 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0167-5699 J9 IMMUNOL TODAY JI Immunol. Today PD APR PY 1998 VL 19 IS 4 BP 163 EP 168 DI 10.1016/S0167-5699(97)01217-6 PG 6 WC Immunology SC Immunology GA ZG548 UT WOS:000073014700005 PM 9577092 ER PT J AU Igietseme, JU Perry, LL Ananaba, GA Uriri, IM Ojior, OO Kumar, SN Caldwell, HD AF Igietseme, JU Perry, LL Ananaba, GA Uriri, IM Ojior, OO Kumar, SN Caldwell, HD TI Chlamydial infection in inducible nitric oxide synthase knockout mice SO INFECTION AND IMMUNITY LA English DT Article ID PELVIC INFLAMMATORY DISEASE; T-CELL CONTROL; GAMMA-INTERFERON; GENITAL-INFECTION; TRACHOMATIS INFECTION; MEDIATED INHIBITION; MOLECULAR MECHANISM; IMMUNE-RESPONSE; IN-VIVO; MACROPHAGES AB Type 1 CD4(+)-T-cell-mediated immunity is crucial for the resolution of chlamydial infection of the murine female genital tract. Previous studies demonstrating a correlation between CD4(+)-T-cell-mediated inhibition of chlamydial growth and gamma interferon (IFN-gamma)-mediated induction of nitric oxide synthase suggested a potential role for the nitric oxide (NO) effector pathway in the clearance of Chlamydia from genital epithelial cells by the immune system. To clarify the role of this pathway, the growth levels of Chlamydia trachomatis organisms in normal (iNOS(+/+)) mice and in genetically engineered mice lacking the inducible nitric oxide synthase (iNOS) gene (iNOS(-/-)mice) were compared. There was no significant difference in the course of genital chlamydial infections in iNOS(+/+) and iNOS(-/-)mice as determined by recovery of Chlamydia organisms shed from genital epithelial cells. Dissemination of Chlamydia to the spleen and lungs occurred to a greater extent in iNOS(-/-)than in iNOS(+/+) mice, which correlated with a marginal increase in the susceptibility of macrophages from iNOS(-/-)mice to chlamydial infection in vitro. However, infections were rapidly cleared from all affected tissues, with no clinical signs of disease. The finding of minimal dissemination in iNOS(-/-)mice suggested that activation of the iNOS effector pathway was not the primary target of IFN-gamma during CD4(+)-T-cell-mediated control of chlamydial growth in macrophages because previous reports demonstrated extensive and often fatal dissemination of Chlamydia in mice lacking IFN-gamma. In summary, these results indicate that the iNOS effector pathway is not required for elimination of Chlamydia from epithelial cells lining the female genital tract of mice although it may contribute to the control of dissemination of C. trachomatis by infected macrophages. C1 Morehouse Sch Med, Dept Microbiol & Immunol, Atlanta, GA 30310 USA. Spelman Coll, Dept Biol, Atlanta, GA 30314 USA. NIAID, Rocky Mt Labs, Intracellular Parasites Lab, NIH, Hamilton, MT 59840 USA. RP Igietseme, JU (reprint author), Morehouse Sch Med, Dept Microbiol & Immunol, 720 Westview Dr SW, Atlanta, GA 30310 USA. FU NCRR NIH HHS [G12 RR003034, RR03034, RR115598]; NIAID NIH HHS [AI41231, R01 AI041231] NR 45 TC 68 Z9 69 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 USA SN 0019-9567 J9 INFECT IMMUN JI Infect. Immun. PD APR PY 1998 VL 66 IS 4 BP 1282 EP 1286 PG 5 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA ZD630 UT WOS:000072706100002 PM 9529043 ER PT J AU Yeung, MK Donkersloot, JA Cisar, JO Ragsdale, PA AF Yeung, MK Donkersloot, JA Cisar, JO Ragsdale, PA TI Identification of a gene involved in assembly of Actinomyces naeslundii T14V type 2 fimbriae SO INFECTION AND IMMUNITY LA English DT Article ID GRAM-POSITIVE BACTERIA; VISCOSUS T14V; ESCHERICHIA-COLI; CELL-WALL; SURFACE-PROTEINS; POLYMORPHONUCLEAR LEUKOCYTES; SEQUENCE; COAGGREGATION; EXPRESSION; CLEAVAGE AB The nucleotide sequence of the Actinomyces naeslundii T14V type 2 fimbrial structural subunit gene, fimA, and the 3' flanking DNA region was determined. The fimA gene encoded a 535-amino-acid precursor subunit protein (FimA) which included both N-terminal leader and C-terminal cell wall sorting sequences. A second gene, designated orf365, that encoded a 365-amino-acid protein which contained a putative transmembrane segment was identified immediately 3' to fimA. Mutants in which either fimA or orf365 was replaced with a kanamycin resistance gene did not participate in type 2 fimbriae-mediated coaggregation with Streptococcus oralis 34. Type 2 fimbrial antigen was not detected in cell extracts of the fimA mutant by Western blotting with anti-A. naeslundii type 2 fimbrial antibody, but the subunit protein was detected in extracts of the orf365 mutant. The subunit protein detected in this mutant also was immunostained by an antibody raised against a synthetic peptide representing the C-terminal 20 amino acid residues of the predicted FimA. The antipeptide antibody reacted with FimA isolated from the recombinant Escherichia coli clone containing fimA but did not react with purified type 2 fimbriae in extracts of the wild-type strain, These results indicate that synthesis of type 2 fimbriae in A. naeslundii T14V may involve posttranslational cleavage of both the N-terminal and C-terminal peptides of the precursor subunit and also the expression of orf365. C1 Univ Texas, Hlth Sci Ctr, Dept Pediat Dent, San Antonio, TX 78284 USA. NIDR, Oral Infect & Immun Branch, NIH, Bethesda, MD 20892 USA. RP Yeung, MK (reprint author), Univ Texas, Hlth Sci Ctr, Dept Pediat Dent, 7703 Floyd Curl Dr, San Antonio, TX 78284 USA. FU NIDCR NIH HHS [DE11102] NR 50 TC 52 Z9 53 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 USA SN 0019-9567 J9 INFECT IMMUN JI Infect. Immun. PD APR PY 1998 VL 66 IS 4 BP 1482 EP 1491 PG 10 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA ZD630 UT WOS:000072706100030 PM 9529071 ER PT J AU Wortham, C Grinberg, L Kaslow, DC Briles, DE McDaniel, LS Lees, A Flora, M Snapper, CM Mond, JJ AF Wortham, C Grinberg, L Kaslow, DC Briles, DE McDaniel, LS Lees, A Flora, M Snapper, CM Mond, JJ TI Enhanced protective antibody responses to PspA after intranasal or subcutaneous injections of PspA genetically fused to granulocyte-macrophage colony-stimulating factor or interleukin-2 SO INFECTION AND IMMUNITY LA English DT Article ID STREPTOCOCCUS-PNEUMONIAE; SURFACE PROTEIN; IMMUNE-RESPONSE; FUSION PROTEIN; B-SUBUNIT; ANTIGEN; VACCINES; ADJUVANT; PEPTIDE; MICE AB Antibody to pneumococcal surface protein A (PspA) has been shown to be protective for Streptococcus pneumoniae infections in mice. In an attempt to define a model for inducing protective antibody to PspA in the absence of adjuvant, we designed two genetic fusions, PspA-interleukin-2 [IL-2]) and PspA-granulocyte-macrophage colony-stimulating factor (GM-CSF). These constructs maintained high cytokine function in vitro, as tested by their activity on IL-2 or GM-CSP-dependent cell lines. While intranasal immunization with PspA induced no detectable anti-PspA response, both PspA-IL-2 and PspA-GM-CSF stimulated high immunoglobulin G1 (IgG1) antibody responses, Interestingly, only the PspA-IL-2, not the PspA-GM-CSF, construct stimulated IgG2a antibody responses, suggesting that this construct directed the response along a TH1-dependent pathway. Comparable enhancement of the anti-PspA response with similar isotype profiles was observed after subcutaneous immunization as well. The enhancement observed with PspA-IL-2 was dependent on IL-2 activity in that it was not seen in IL-2 receptor knockout mice, while PspA in alum induced high-titer antibody in these mice, The antibody was tested for its protective activity in a mouse lethality model using S. pneumoniae WU-R2. Passive transfer of 1:90 dilutions of sera from mice immunized with PspA-IL-2 and PspA-GM-CSF elicited protection of CBA/N mice against intravenous challenge with over 170 50% lethal doses of capsular type 3 strain WU2, Only 0.17 mu g or less of IgG antibody to PspA was able to provide passive protection against otherwise fatal challenge with S. pneumoniae. The data demonstrate that designing protein-cytokine fusions may be a useful approach for mucosal immunization and can induce high-titer systemic protective antibody responses. C1 Uniformed Serv Univ Hlth Sci, Dept Med, Bethesda, MD 20814 USA. Uniformed Serv Univ Hlth Sci, Dept Pathol, Bethesda, MD 20814 USA. Uniformed Serv Univ Hlth Sci, Biomed Instrumentat Ctr, Bethesda, MD 20814 USA. NIAID, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA. Univ Alabama, Dept Microbiol, Birmingham, AL 35294 USA. Univ Mississippi, Med Ctr, Dept Surg, Jackson, MS 39216 USA. Univ Mississippi, Med Ctr, Dept Microbiol, Jackson, MS 39216 USA. RP Mond, JJ (reprint author), Uniformed Serv Univ Hlth Sci, Dept Med, 4301 Jones Bridge Rd, Bethesda, MD 20814 USA. FU NIAID NIH HHS [1RO1-AI36588] NR 34 TC 45 Z9 46 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 USA SN 0019-9567 J9 INFECT IMMUN JI Infect. Immun. PD APR PY 1998 VL 66 IS 4 BP 1513 EP 1520 PG 8 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA ZD630 UT WOS:000072706100034 PM 9529075 ER PT J AU Lange, RW Hayden, PJ Chignell, CF Luster, MI AF Lange, RW Hayden, PJ Chignell, CF Luster, MI TI Anthralin stimulates keratinocyte-derived proinflammatory cytokines via generation of reactive oxygen species SO INFLAMMATION RESEARCH LA English DT Article DE anthralin; inflammation; chemokines; keratinocyte ID TUMOR-NECROSIS-FACTOR; FACTOR-ALPHA; KAPPA-B; INTERLEUKIN-8 GENE; FREE-RADICALS; INFLAMMATION; EXPRESSION; CELLS; BLOOD; LIPOPOLYSACCHARIDE AB Objective and Design: Topical application of anthralin, used in the treatment of psoriasis, is often accompanied by severe skin inflammation, presumably due to free radical products of the drug. The role of inflammatory cytokines and their induction by anthralin-derived reactive oxygen species were studied in cultures of normal human keratinocytes (NHKs). Materials and Methods: Anthralin was added to cultures of NHKs in the presence or absence of various antioxidants, including superoxide dismutase, tetramethylthiourea, N-acetylcysteine and vitamin E and relative changes in cytokine secretion and in the number of mRNA transcripts were examined. In addition, NHKs were either treated with neutralizing antibodies to tumor necrosis factor (TNF)-alpha or transfected with a CAT-linked IL-8 promoter to establish the direct effects of anthralin on chemokine synthesis. Results: Anthralin, at concentrations between 5 mu M and 25 mu M, caused a marked increase in granulocyte macrophage-colony stimulating factor (GM-CSF), interleukin (IL)-6, IL-8 and TNF alpha synthesis that was selectively inhibited by specific antioxidants. Furthermore, anthralin induced chemokine secretion without the need of primary cytokines. Conclusions: Taken together, these studies suggest that oxygen radicals generated from anthralin are responsible for the induction of inflammatory cytokines which, in turn contributes to their dermal toxicity. C1 NIEHS, Environm Immunol Sect, NIH, Res Triangle Pk, NC 27709 USA. N Carolina State Univ, Dept Toxicol, Raleigh, NC 27695 USA. NIEHS, Mol Biophys Lab, NIH, Res Triangle Pk, NC 27709 USA. NIOSH, Hlth Effects Lab Div, Toxicol & Mol Biol Res Branch, Morgantown, WV 26505 USA. RP Lange, RW (reprint author), Univ Pittsburgh, Dept Environm & Occupat Hlth, RIDC Pk,260 Kappa Dr, Pittsburgh, PA 15238 USA. EM lange+@pitt.edu NR 35 TC 21 Z9 22 U1 0 U2 1 PU BIRKHAUSER VERLAG AG PI BASEL PA VIADUKSTRASSE 40-44, PO BOX 133, CH-4010 BASEL, SWITZERLAND SN 1023-3830 J9 INFLAMM RES JI Inflamm. Res. PD APR PY 1998 VL 47 IS 4 BP 174 EP 181 DI 10.1007/s000110050313 PG 8 WC Cell Biology; Immunology SC Cell Biology; Immunology GA ZL646 UT WOS:000073456000005 PM 9628260 ER PT J AU Oshima, H Nakano, H Nohara, C Kobata, T Nakajima, A Jenkins, NA Gilbert, DJ Copeland, NG Muto, T Yagita, H Okumura, K AF Oshima, H Nakano, H Nohara, C Kobata, T Nakajima, A Jenkins, NA Gilbert, DJ Copeland, NG Muto, T Yagita, H Okumura, K TI Characterization of murine CD70 by molecular cloning and mAb SO INTERNATIONAL IMMUNOLOGY LA English DT Article DE CD27; CD70; T cell co-stimulation ID TUMOR-NECROSIS-FACTOR; T-CELL ACTIVATION; FACTOR RECEPTOR FAMILY; AUTOANTIBODY PRODUCTION; COSTIMULATORY ACTIVITY; GENE FAMILY; CD27; LIGAND; MEMBER; EXPRESSION AB CD27, a member of the tumor necrosis factor (TNF) receptor family, has been implicated in T cell activation, T cell development and T-dependent antibody production by B cells. Its ligand CD70 has been identified only in humans, and, thus, physiological and pathological roles of the CD70-CD27 interaction remain to be determined in an experimental animal system, In the present study, we identified murine (m) CD70 by molecular cloning, and characterized its expression and function by generating an anti-mCD70 mAb, The mCD70 cDNA encoded a type II transmembrane glycoprotein of the TNF family, having 56.5% identity to the human CD70 amino acid sequence, The mCd70 gene was assigned in the central region of chromosome 17, To explore the expression and function of mCD70, we generated cDNA transfectants and anti-mCD70 mAb (FR70), which inhibited binding of a murine CD27-Fc fusion protein (mCD27-lg) to mCD70 transfectants. FR70, as well as mCD27-lg, immunoprecipitated a 30-33 kDa surface protein from A20 and mCD70-P815 cells but not from P815 cells. The mCD70 transfectants exhibited a potent co-stimulatory activity for anti-CD3-stimulated T cell proliferation, which was blocked by FR70 far more efficiently than mCD27-lg, FR70 also abrogated the CD28-independent co-stimulatory activity of A20 cells, The expression of mCD70 was detected on splenic T cells after stimulation with anti-CD3 and anti-CD28 mAb, and on splenic B cells after stimulation with anti-CD40 mAb. Cross-linking of surface Ig by anti-IgM mAb did not induce the mCD70 expression but enhanced the anti-CD40-induced mCD70 expression on splenic B cells. These results suggest a contribution of CD70 to murine T-B cognate interaction as proposed in the human system, FR70 will be useful for further investigating the physiological and pathological roles of the CD70-CD27 interaction in T cell development, T-dependent antibody production and various disease models in the murine system. C1 Juntendo Univ, Sch Med, Dept Immunol, Bunkyo Ku, Tokyo 113, Japan. Univ Tokyo, Fac Med, Dept Surg 1, Tokyo 113, Japan. Japan Sci & Technol Corp, CREST, Kawaguchi 332, Japan. Nippon Med Sch, Dept Joint Dis & Rheumatism, Tokyo 113, Japan. NCI, Frederick Canc Res & Dev Ctr, ABL Basic Res Program, Mammalian Genet Lab, Frederick, MD 21702 USA. RP Yagita, H (reprint author), Juntendo Univ, Sch Med, Dept Immunol, Bunkyo Ku, 2-1-1 Hongo, Tokyo 113, Japan. OI Nakano, Hiroyasu/0000-0003-4843-1427 NR 46 TC 83 Z9 85 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0953-8178 J9 INT IMMUNOL JI Int. Immunol. PD APR PY 1998 VL 10 IS 4 BP 517 EP 526 DI 10.1093/intimm/10.4.517 PG 10 WC Immunology SC Immunology GA ZL129 UT WOS:000073401700017 PM 9620608 ER PT J AU Lisignoli, G Pozzi, C Toneguzzi, S Tomassetti, M Monaco, MCG Facchini, A AF Lisignoli, G Pozzi, C Toneguzzi, S Tomassetti, M Monaco, MCG Facchini, A TI Different pattern of cytokine production and mRNA expression by lymphoid and non-lymphoid cells isolated from human palatine tonsil SO INTERNATIONAL JOURNAL OF CLINICAL & LABORATORY RESEARCH LA English DT Article DE cytokine; lymphocyte; reverse transcriptase polymerase chain reaction; stromal cells ID FOLLICULAR DENDRITIC CELLS; NASOPHARYNGEAL; PROLIFERATION; PHENOTYPE; CHILDREN; DISPLAY; NODES; GAMMA AB To investigate the cytokines involved in the interaction between circulating (B and T lymphocytes) and non-circulating (stromal cells) elements present in lymphoid tissue, highly purified populations were isolated from human tonsils and the cytokine production and mRNA expression (interleukin-1 alpha, -2, -4, -5, -6, -8, -10, leukocyte inhibitory factor, granulocyte-macrophage colony-stimulating factor, and interferon-gamma) were assessed both by immunoassay and reverse transcriptase polymerase chain reaction under resting conditions and after activation with tumor necrosis factor-alpha. Under basal conditions most cytokines were not detected, except for interleukin-8 which was produced by T lymphocytes and lymphoid cells. Activation by tumor necrosis factor-alpha-induced interleukin-8 production by B lymphocytes. Tonsillar T lymphocytes expressed mRNA for interleukin-1 alpha, -8, -10, -4, leukocyte inhibitory factor, and interferon-gamma, only interleukin-4 was expressed by resting peripheral blood T lymphocytes. Tonsillar B lymphocytes were mRNA positive for interleukin-1 alpha, -8, -10, leukocyte inhibitory factor, and interferon-gamma; these were not expressed by peripheral blood B lymphocytes. Stromal cells constitutively produce interleukin-6 whose levels increased 5 times upon tumor necrosis factor-alpha activation Granulocyte-macrophage colony-stimulating factor and interleukin-8 were detected only after tumor necrosis factor-alpha activation. Only stromal cells constitutively express interleukin-6 and granulocyte-macrophage colony-stimulating factor and show a cytokine pattern different from that described for other non-lymphoid cells, such as follicular dendritic cells. These data indicate that in the human tonsil population, lymphoid and non-lymphoid cells can be distinguished by different patterns of cytokine expression. C1 Ist Ric Codivilla Putti IOR, Lab Immunol & Genet, I-40136 Bologna, Italy. NINDS, Lab Mol Med & Neurosci, NIH, Bethesda, MD 20892 USA. Univ Bologna, Dipartimento Med Interna & Gastroenterol, I-40138 Bologna, Italy. RP Facchini, A (reprint author), Ist Ric Codivilla Putti IOR, Lab Immunol & Genet, Via Barbiano 1-10, I-40136 Bologna, Italy. NR 22 TC 3 Z9 3 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0940-5437 J9 INT J CLIN LAB RES JI Int. J. Clin. Lab. Res. PD APR PY 1998 VL 28 IS 1 BP 23 EP 28 DI 10.1007/s005990050013 PG 6 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA ZG970 UT WOS:000073058300003 PM 9594359 ER PT J AU Iwasaki, K Isaacs, KR Jacobowitz, DM AF Iwasaki, K Isaacs, KR Jacobowitz, DM TI Brain-derived neurotrophic factor stimulates neurite outgrowth in a calretinin-enriched neuronal culture system SO INTERNATIONAL JOURNAL OF DEVELOPMENTAL NEUROSCIENCE LA English DT Article DE calcium-binding protein; Sholl analysis; growth factors; tissue culture; thalamic eminence ID CALCIUM-BINDING PROTEIN; RAT HIPPOCAMPAL-NEURONS; GROWTH-FACTOR; IMMUNOHISTOCHEMICAL LOCALIZATION; DOPAMINERGIC-NEURONS; CHOLINERGIC NEURONS; CALBINDIN D-28K; FACTOR PROMOTES; NERVOUS-SYSTEM; SLICE CULTURES AB A calretinin enriched cell culture system which comprised approximately 40% of the total neuronal population of the E14 rat embryo was established from the region of the thalamic eminence (TE), and the effects of several neurotrophins on the neurite growth of calretinin-immunoreactive (CR-IR) neurons was investigated. A 4-day treatment of BDNF significantly increased the ratio of CR-IR to microtubule-associated protein 2-immunoreactive neurons at concentrations between 50 and 250 ng/ml. IGF-I at 100 ng/ml and TGF-alpha at 250 ng/ml also increased this ratio. None of the neurotrophins examined increased the number of primary neurites. BDNF did, however, increase the number of secondary neurites. BDNF-treated primary and secondary neurites were also significantly longer than neurites from neurons in control cultures. IGF-I elicited an increase in primary neurite length, but did not affect either number or length of secondary neurites. TGF-alpha had no effect on either number or length of the primary and secondary neurites. These results indicate that the maturation and development of CR-IR neurites is specifically affected by BDNF. It is suggested that BDNF increases the CR concentration above the threshold of detection by immunohistochemistry in cells and stimulates the sprouting of secondary CR-IR neurites. Published by Elsevier Science Ltd. C1 NIMH, Clin Sci Lab, Bethesda, MD 20892 USA. RP Isaacs, KR (reprint author), Howard Hughes Med Inst, 4000 Jones Bridge Rd, Chevy Chase, MD 20815 USA. EM isaacsk@hhmi.org NR 50 TC 13 Z9 13 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0736-5748 J9 INT J DEV NEUROSCI JI Int. J. Dev. Neurosci. PD APR PY 1998 VL 16 IS 2 BP 135 EP 145 DI 10.1016/S0736-5748(98)00011-2 PG 11 WC Developmental Biology; Neurosciences SC Developmental Biology; Neurosciences & Neurology GA 112PM UT WOS:000075503100007 PM 9762586 ER PT J AU Otsuki, T Wang, JX Demuth, I Digweed, M Liu, JM AF Otsuki, T Wang, JX Demuth, I Digweed, M Liu, JM TI Assessment of mitomycin C sensitivity in Fanconi anemia complementation group C gene (Fac) knock-out mouse cells SO INTERNATIONAL JOURNAL OF HEMATOLOGY LA English DT Article DE Fanconi anemia; mitomycin C; cell cycle; hematopoiesis; cytogenetics ID CLONING AB Fanconi anemia (FA) is a genetic disorder defined by cellular hypersensitivity to DNA cross-linking agents, such as mitomycin C (MMC). MMC causes increased FA cell death, chromosome breakage, and accumulation in the G2 phase of the cell cycle. Recently, Fanconi anemia complementation group C (fac) gene knock-out mice have been developed, and SV40-transformed fibroblasts were established from fac homozygous knock-out (-/-), heterozygous (+/-), and wild-type mice (+/+). MMC sensitivity of these cell lines was assessed by three methods: colony-formation assay in the presence of MMC, chromosome breakage, and cell cycle analysis to detect G2 phase arrest. The fac knock-out fibroblasts (-/-) showed a significantly higher sensitivity to MMC than did fibroblasts from wild-type (+/+) or heterozygous (+/-)mice (three experiments). In addition, we analyzed hematopoietic progenitor colony assays of bone marrow cells from fac knock-out (-/-) and heterozygous (+/-) mice. CFU-E, BFU-E, and CFU-GM colony formation from fac nullizygous mouse progenitors was markedly diminished by MMC when compared to growth of progenitors from heterozygous mice. These results show that fac knock-out mouse cells mimic the behavior of human FA-C patient cells in terms of MMC hypersensitivity. The fac knock-out mouse may be used to model some aspects of human FA and should be useful for understanding the function of the FAC protein. (C) 1998 Elsevier Science Ireland Ltd. All rights reserved. C1 NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA. RP Liu, JM (reprint author), NHLBI, Hematol Branch, NIH, Bldg 10,Room 7C213, Bethesda, MD 20892 USA. NR 13 TC 8 Z9 8 U1 1 U2 1 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0925-5710 J9 INT J HEMATOL JI Int. J. Hematol. PD APR PY 1998 VL 67 IS 3 BP 243 EP 248 PG 6 WC Hematology SC Hematology GA ZR101 UT WOS:000073936400004 PM 9650445 ER PT J AU Rivadeneira, ED Popescu, NC Zimonjic, DB Cheng, GS Nelson, PJ Ross, MD Dipaolo, JA Klotman, ME AF Rivadeneira, ED Popescu, NC Zimonjic, DB Cheng, GS Nelson, PJ Ross, MD Dipaolo, JA Klotman, ME TI Sites of recombinant adeno-associated virus integration SO INTERNATIONAL JOURNAL OF ONCOLOGY LA English DT Article DE gene therapy; AAVS1; fluorescent chromosome in situ; hybridization; parvovirus; insertional mutagenesis ID ADENOASSOCIATED VIRUS; TARGETED INTEGRATION; DIRECT VISUALIZATION; NEOMYCIN RESISTANCE; VIRAL INTEGRATION; MAMMALIAN-CELLS; DETROIT-6 CELLS; FRAGILE SITES; CELLULAR DNA; VECTOR AB Adeno-associated virus (AAV), a defective parvovirus, is considered a promising vector for the delivery of therapeutic genes to cells. Both wild-type and recombinant AAV display a wide tropism and integrate into the host genome, in the absence of helper virus, establishing a latent infection. A unique characteristic of wild-type AAV and a potential advantage for use as a delivery system for gene therapy is the site-specific integration of wild-type virus within a small region of chromosome 19, 19q13.3-qter (AAVS1), in up to 85% of cell lines infected with the virus. Although recombinant AAVs, containing only the inverted terminal repeats of wild-type virus, can integrate efficiently into the host genome, specificity for the AAVS1 site appears to be lost. To address this question, the integration characteristics of two recombinant AAVs lacking the rep and cap genes in HeLa cells were examined. Analysis of Southern blots indicated that none of twenty-six cell clones generated after infection with either one of the recombinant AAVs demonstrated integration within the AAVS1 locus on chromosome 19. Analysis of five of the cell lines by fluorescent chromosome in situ hybridization confirmed the loss of chromosome 19 specificity. Each integration site mapped near a known fragile site and/or location of a proto-oncogene or growth regulatory gene. Retention of site-specific integration of wild-type AAV will require the inclusion of additional AAV-specific sequences within the recombinant vectors. C1 NIH, Tumor Cell Biol Lab, Bethesda, MD 20892 USA. NIH, Biol Lab, Bethesda, MD 20892 USA. RP Klotman, ME (reprint author), Mt Sinai Sch Med, 1 Gustave L Levy Pl, New York, NY 10029 USA. RI klotman, mary/A-1921-2016 NR 33 TC 14 Z9 15 U1 0 U2 0 PU PROFESSOR D A SPANDIDOS PI ATHENS PA 1, S MERKOURI ST, EDITORIAL OFFICE,, ATHENS 116 35, GREECE SN 1019-6439 J9 INT J ONCOL JI Int. J. Oncol. PD APR PY 1998 VL 12 IS 4 BP 805 EP 810 PG 6 WC Oncology SC Oncology GA ZC379 UT WOS:000072572000008 PM 9499439 ER PT J AU Theodossiou, C Cook, JA Fisher, J Teague, D Liebmann, JE Russo, A Mitchell, JB AF Theodossiou, C Cook, JA Fisher, J Teague, D Liebmann, JE Russo, A Mitchell, JB TI Interaction of gemcitabine with paclitaxel and cisplatin in human tumor cell lines SO INTERNATIONAL JOURNAL OF ONCOLOGY LA English DT Article DE combination therapy; gemcitabine; cisplatin; paclitaxel; radiation; antagonism ID CANCER-CELLS; PHASE-II; 2',2'-DIFLUORODEOXYCYTIDINE; 2',2'-DIFLUORO-2'-DEOXYCYTIDINE; TAXOL; RADIOSENSITIZATION; NUCLEOSIDES; METABOLISM; TOXICITY AB We have used clonogenic survival assays and flow cytometry of human lung A549, breast MCF7 and pancreas adenocarcinoma P-SW cell lines to examine the effects of gemcitabine (2'-deoxy-2',2'-difluorocytidine) in combination with cisplatin, paclitaxel or radiation. Additive cell killing was observed for all cell lines when they were treated with cisplatin for 1 h followed by varying concentrations of gemcitabine for 24 h. Likewise, additive cell killing was noted in all cell lines when treated with gemcitabine for 24 h followed by varying doses of radiation. When A549 cells were exposed to gemcitabine for 24 h followed by a 1 h exposure to cisplatin, synergistic effects were noted. Using the latter regimen, MCF7 cells demonstrated additive cell kill, while the P-SW cells showed a more complex relationship with additive killing below 50 nM gemcitabine and less than additive effect above 50 nM gemcitabine. All three cell lines were also tested with various gemcitabine/paclitaxel combinations. When gemcitabine and paclitaxel were incubated concurrently, gemcitabine antagonized the cell kill produced by paclitaxel. All cell lines showed less than additive killing when either gemcitabine incubation preceded the paclitaxel incubation or the paclitaxel incubation preceded the gemcitabine incubation. Our results show that gemcitabine acts as a radiation sensitizer to increase the effects of radiation. Likewise, we demonstrate that the only uniformly beneficial drug combination schedule in all three cell lines was when cisplatin incubation preceded gemcitabine incubation. The gemcitabine/paclitaxel combinations were much more disturbing with respect to potential clinical trials. Our results would caution any planned clinical trials combining paclitaxel with gemcitabine to be reconsidered because of the potential for less than additive and even antagonistic effects of the combination. C1 NCI, Radiat Biol Branch, NIH, Bethesda, MD 20892 USA. RP Mitchell, JB (reprint author), NCI, Radiat Biol Branch, NIH, Bldg 10,Room B3-B69, Bethesda, MD 20892 USA. NR 37 TC 51 Z9 54 U1 0 U2 2 PU PROFESSOR D A SPANDIDOS PI ATHENS PA 1, S MERKOURI ST, EDITORIAL OFFICE,, ATHENS 116 35, GREECE SN 1019-6439 J9 INT J ONCOL JI Int. J. Oncol. PD APR PY 1998 VL 12 IS 4 BP 825 EP 832 PG 8 WC Oncology SC Oncology GA ZC379 UT WOS:000072572000011 PM 9499442 ER PT J AU Munck-Wikland, E Heselmeyer, K Lindholm, J Kuylenstierna, R Auer, G Engel, G AF Munck-Wikland, E Heselmeyer, K Lindholm, J Kuylenstierna, R Auer, G Engel, G TI Stromelysin-3 mRNA expression in dysplasias and invasive epithelial cancer of the larynx SO INTERNATIONAL JOURNAL OF ONCOLOGY LA English DT Article DE stromelysin-3 mRNA; metalloproteinase; laryngeal cancer; dysplasia ID CELL CARCINOMA; BREAST-CANCER; GENE; P53; HEAD; PROGRESSION AB Matrix metalloproteinases are believed to play an important role in tumor progression, invasion and metastasis. In order to investigate if the expression of stromelysin-3 (ST3) mRNA could add prognostic information concerning invasive laryngeal cancer and/or be indicative of a high risk for tumor progression in laryngeal dysplasias ST3 expression was analyzed by in situ hybridisation of formalin fixed paraffin embedded laryngeal specimens. Furthermore, all specimens underwent image cytometry (ICM) DNA analysis, and, p53 immunostaining. Invasive epithelial cancer, both localized (T1, T2) cancers, cured, as well as not cured, by radiotherapy, and cases with regional lymph node metastases were studied. Furthermore, high grade and low grade dysplasias, selected for rapid, slow and non-progression, as well as non-neoplastic inflammatory lesions were investigated. Expression of the ST3 gene was found in 9 out of 14 (64%) invasive cancer lesions, and in 3 out of 10 (30%) dysplasias, thus indicating that ST3 expression correlates to tumor progression. The ST3 positive laryngeal cancer lesions displayed a higher degree of DNA aberration than the ST3 negative lesions thus suggesting that ST3 positivity could indicate highly malignant tumors. Of the three ST3 positive dysplasias, the first progressed rapidly to cancer in situ with suspected microinvasion. The second ST3 positive dysplasia progressed to invasive cancer within five months. The third ST3 positive dysplasia had been radically excised and hereby cured. All but one of the dysplastic lesions showed p53 immunoreactivity, and all dysplasias exhibited aneuploid cells. ST3 expression appears to be a late event in the multistage process of carcinogenesis and could prove useful as an indicator of dysplasias with imminent risk for progression to invasive cancer. C1 Karolinska Inst & Hosp, Dept Otorhinolaryngol, Radiumhemmet, S-17177 Stockholm, Sweden. Karolinska Inst & Hosp, Dept Tumor Pathol, Radiumhemmet, S-17177 Stockholm, Sweden. Karolinska Inst & Hosp, Dept Oncol, Radiumhemmet, S-17177 Stockholm, Sweden. NIH, Natl Ctr Human Genome Res, Diagnost Dev Branch, Bethesda, MD 20892 USA. Danderyd Hosp, Dept Pathol, S-18288 Danderyd, Sweden. RP Munck-Wikland, E (reprint author), Karolinska Inst & Hosp, Dept Otorhinolaryngol, Radiumhemmet, S-17177 Stockholm, Sweden. NR 29 TC 14 Z9 16 U1 0 U2 0 PU PROFESSOR D A SPANDIDOS PI ATHENS PA 1, S MERKOURI ST, EDITORIAL OFFICE,, ATHENS 116 35, GREECE SN 1019-6439 J9 INT J ONCOL JI Int. J. Oncol. PD APR PY 1998 VL 12 IS 4 BP 859 EP 864 PG 6 WC Oncology SC Oncology GA ZC379 UT WOS:000072572000016 PM 9499447 ER PT J AU Helias, C Vazeille-Falcoz, M Le Goff, F Abalain-Colloc, ML Rodhain, F Carle, P Whitcomb, RF Williamson, DL Tully, JG Bove, JM Chastel, C AF Helias, C Vazeille-Falcoz, M Le Goff, F Abalain-Colloc, ML Rodhain, F Carle, P Whitcomb, RF Williamson, DL Tully, JG Bove, JM Chastel, C TI Spiroplasma turonicum sp. nov. from Haematopota horse flies (Diptera : Tabanidae) in France SO INTERNATIONAL JOURNAL OF SYSTEMATIC BACTERIOLOGY LA English DT Article DE Spiroplasma turonicum sp. nov.; Mollicutes; Diptera ID MOLLICUTES; ECOLOGY AB Strain Tab4c(T), a helical prokaryote that was isolated from the body of a Haematopota sp. fly collected in Champchevrier, Indre-et-Loire, Touraine, France, was found to be a member of the class Mollicutes, The cells of strain Tab4c(T) were small, motile helices that were devoid of a cell wall. The organism passed through filters with mean pore diameters as small as 0.20 mm, Strain Tab4c(T) grew rapidly in liquid SP-4 medium at both 30 and 37 degrees C, The organism fermented glucose but did not hydrolyse arginine or urea, and did not require serum for growth. In preliminary electrophoretic analyses, the cell protein patterns of strain Tab4c(T) were distinct from those of 14 other spiroplasmas found in mosquitoes, deer flies and horse flies from Europe and the Far-East. In reciprocal metabolism inhibition and deformation serological tests, employing antigens and antisera representative of spiroplasma groups I-XXXIII (including all sub-groups), plus ungrouped strains BARC 1901 and BARC 2649, no serological relationship with Tab4c(T) was found. The G+C content of the DNA of strain Tab4c(T) was about 25+/-1 mol% and its genome size was 1.305 kbp. It is proposed that spiroplasma strain Tab4c(T) be assigned to group XVII (presently vacant) and that strain (ATCC 700271(T)) is the type strain of a new species, Spiroplasma turonicum. C1 Fac Med, Dept Microbiol & Sante Publ, F-29285 Brest, France. Inst Pasteur, Unite Syst Vectoriels, F-75724 Paris, France. INRA, Biol Cellulaire & Mol Lab, F-33883 Villenave Dornon, France. USDA, Vegetable Lab, Beltsville, MD 20705 USA. SUNY Stony Brook, Dept Anat Sci, Stony Brook, NY 11794 USA. NIAID, Frederick Canc Res Facil, Mycoplasma Sect, Mol Microbiol Lab, Frederick, MD 21702 USA. RP Chastel, C (reprint author), Fac Med, Dept Microbiol & Sante Publ, F-29285 Brest, France. NR 28 TC 2 Z9 3 U1 0 U2 1 PU SOC GENERAL MICROBIOLOGY PI READING PA MARLBOROUGH HOUSE, BASINGSTOKE RD, SPENCERS WOODS, READING, BERKS, ENGLAND RG7 1AE SN 0020-7713 J9 INT J SYST BACTERIOL JI Int. J. Syst. Bacteriol. PD APR PY 1998 VL 48 BP 457 EP 461 PN 2 PG 5 WC Microbiology SC Microbiology GA ZT073 UT WOS:000074045700015 PM 9731284 ER PT J AU Prendergast, RA Iliff, CE Coskuncan, NM Caspi, RR Sartani, G Tarrant, TK Lutty, GA McLeod, DS AF Prendergast, RA Iliff, CE Coskuncan, NM Caspi, RR Sartani, G Tarrant, TK Lutty, GA McLeod, DS TI T cell traffic and the inflammatory response in experimental autoimmune uveoretinitis SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Article ID POSITIVE DENDRITIC CELLS; BLOOD-RETINAL BARRIER; MICROGLIAL CELLS; S-ANTIGEN; RAT; MACROPHAGES; ADHESION; IRIS; EYE; EXPRESSION AB PURPOSE. TO quantify S-antigen-specific (S-Ag) T cells in the retina after adoptive transfer, and to evaluate their role in the initiation and progress of destructive ocular inflammation in experimental autoimmune uveoretinitis (EAU). METHODS. Lewis rats were administered 10 X 10(6) S-Ag-specific T cells from the SP35 cell line or 10 X 10(6) concanavalin A-stimulated syngeneic spleen cell lymphoblasts labeled with lipophilic PKH26 fluorescent dye immediately before intravenous inoculation. Labeled cells in each retina mere counted at various times from 4 to 120 hours after cell transfer by fluorescence microscopic analysis of each dissociated retina. Recipient eyes were examined within the same period by light and confocal microscope. RESULTS. SP35 T cells showed a biphasic distribution in the retina. The first peak of 160 cells/retina was noted at 24 hours. A steady decline of labeled cells at 48 and 72 hours mas followed by a rapid increase at 96 and 120 hours, Concanavalin A-stimulated, control-labeled cell populations showed an identical peak at 21 hours but a persistent decline thereafter; only two or three T cells were present in each retina at 120 hours. Concurrent inoculation of SP35 cells and nonspecific T cell blasts did not produce more SP35 cells than control cells in the retina at an) time. Microscopic analysis showed mononuclear cell infiltration of the iris, ciliary body, and aqueous humor at 48 hours, which intensified rapidly and persisted through 120 hours. Retinal inflammation did not begin until 80 hours. Mononuclear cell adherence to vascular endothelium and perivascular macrophage infiltration of the innermost layers progressed to edema, and profound destructive inflammation and loss of retinal stratification were observed at 120 hours. CONCLUSIONS. There is no evidence of a blood-ocular or blood-retinal barrier to activated T cell blasts. Autologous S-Ag does not provoke a more rapid entry of specific T cells at that site. The data confirm that anterior segment inflammation precedes retinal inflammation, even though S-Ag-specific T cells were present in the retina within a few hours after cell transfer. Because S-Ag is clearly present in the retina, delay in antigen presentation at that site may account for the temporal difference between retinal and anterior segment inflammation. C1 Johns Hopkins Univ, Sch Med, Wilmer Eye Inst, Baltimore, MD 21287 USA. NEI, NIH, Bethesda, MD 20892 USA. RP Prendergast, RA (reprint author), Johns Hopkins Univ, Sch Med, Wilmer Eye Inst, 600 N Wolfe St, Baltimore, MD 21287 USA. FU NEI NIH HHS [EY07047, EY01765] NR 35 TC 91 Z9 94 U1 0 U2 1 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD APR PY 1998 VL 39 IS 5 BP 754 EP 762 PG 9 WC Ophthalmology SC Ophthalmology GA ZE198 UT WOS:000072767900013 PM 9538882 ER PT J AU Kobayashi, H Sun, BF Han, ES Kim, MK Le, N Wang, QC Nelson, DL Pastan, I Waldmann, TA Paik, CH Carrasquillo, JA AF Kobayashi, H Sun, BF Han, ES Kim, MK Le, N Wang, QC Nelson, DL Pastan, I Waldmann, TA Paik, CH Carrasquillo, JA TI Epitope blocking: Positive and negative effects on the biodistribution of I-125-labeled anti-Tac disulfide-stabilized Fv fragment of two antibodies against different epitopes of the circulating antigen SO JAPANESE JOURNAL OF CANCER RESEARCH LA English DT Article DE Fv fragment; iodine-125; epitope; radioimmunodetection; monoclonal antibody ID SOLUBLE INTERLEUKIN-2 RECEPTOR; RADIOLABELED MONOCLONAL-ANTIBODY; HAIRY-CELL LEUKEMIA; SINGLE-CHAIN FV; HUMAN T-CELLS; NUDE-MICE; IMMUNOGLOBULIN FORMS; TUMOR XENOGRAFTS; CEA ANTIBODIES; COLON CANCER AB Prior in vivo studies using the I-125-labeled anti-Tac disulfide-stabilized variable region fragment (I-125-anti-Tac dsFv) of monoclonal antibody in the presence of the circulating soluble alpha subunit of the interleukin-2. receptor (sIL-2R alpha) have shown formation of complexes which interfere with biodistribution. In this study we evaluated the effects of preinjecting HuTac and 7G7/B6, two immunoglobulin Gs (IgGs) that recognize different epitopes of sIL-2R alpha, on the biodistribution of I-125-anti-Tac dsFv in mice bearing SP2/Tac tumor xenografts, which produce sIL-2R alpha, or on nude mice injected with 500 ng of sIL-2R alpha. We also evaluated the biodistribution in mice of I-125-labeled sIL-2R alpha injected alone or with HuTac and 7G7/B6, Injection of either HuTac or 7G7/B6 resulted in complexes with the sIL-2R alpha in serum. Injection of HuTac before I-125-anti-Tac dsFv, in SP2/Tac tumor-bearing mice, resulted in faster clearance of the dsFv from the blood (7.6% ID/g at 30 min), compared to 23.2% ID/g for the no-antibody control; preinjection of 7G7/B6 prolonged the retention of I-125-anti-Tac dsFv to 35.3% ID/g, with more complexes in serum. In mice pre-injected with 7G7/B6 the concentration of I-125-anti-Tac dsFv in tumor was lower (5.2+/-0.3% ID/g) than in mice preinjected with HuTac (7.9+/-1.2% ID/g) or in the control group (5.6+/-0.7% ID/g). In conclusion, while both IgGs formed complexes with sIL-2R alpha and prolonged its retention, preinjection of 7G7/B6 was detrimental, because the increased circulating sIL-2R alpha still had the epitope recognized by the dsFv available for binding and neutralized the anti-Tac dsFv upon injection, whereas preinjection of HuTac blocked the epitope. C1 NCI, Dept Nucl Med, Warren G Magnuson Clin Ctr, NIH, Bethesda, MD 20892 USA. NCI, Mol Biol Lab, Div Basic Sci, NIH, Bethesda, MD 20892 USA. NCI, Metab Branch, Div Clin Sci, NIH, Bethesda, MD 20892 USA. RP Carrasquillo, JA (reprint author), NCI, Dept Nucl Med, Warren G Magnuson Clin Ctr, NIH, 10 Ctr Dr,MSC 1180, Bethesda, MD 20892 USA. RI Carrasquillo, Jorge/E-7120-2010; OI Carrasquillo, Jorge/0000-0002-8513-5734 NR 51 TC 3 Z9 3 U1 0 U2 1 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0910-5050 J9 JPN J CANCER RES JI Jpn. J. Cancer Res. PD APR PY 1998 VL 89 IS 4 BP 436 EP 444 PG 9 WC Oncology SC Oncology GA ZM458 UT WOS:000073542200014 PM 9617350 ER PT J AU Rogers, AS Futterman, DK Moscicki, AB Wilson, CM Ellenberg, J Vermund, SH AF Rogers, AS Futterman, DK Moscicki, AB Wilson, CM Ellenberg, J Vermund, SH TI The REACH project of the adolescent medicine HIV/AIDS research network: Design, methods, and selected characteristics of participants SO JOURNAL OF ADOLESCENT HEALTH LA English DT Article DE adolescents; multicenter research; AIDS; HIV infection ID HUMAN-IMMUNODEFICIENCY-VIRUS; NEW-YORK-CITY; UNITED-STATES; TYPE-1 SEROCONVERSION; HIV-INFECTION; AIDS; SEROPREVALENCE; HEALTH; RISK; PREVALENCE AB Purpose: To describe the Reaching for Excellence in Adolescent Care and Health (REACH) Project of the Adolescent Medicine Human Immunodeficiency Virus/ Acquired Immunodeficiency Syndrome (HIV/AIDS) Research Network, a unique collaborative effort to conceive and implement a research design intended to examine HIV pathogenesis, pubertal hormonal variation, and the effects of sexually transmitted disease comorbidity in HIV-infected youth to improve their health care. Methods: This multidisciplinary team has drawn on basic science and clinical experience to produce a study design with relevant and feasible study aims and testable hypotheses. Particular attention has been paid to centralized training and quality control practices. Standardized measurements include direct and computer interviews, physical examination, laboratory analysis, and medical chart abstraction. The protocol has been approved by local institutional review boards. Results: A highly standardized and quality control monitored protocol has been implemented at 16 sites throughout the United States collecting historical, observational, and laboratory data in a group of HIV-infected adolescents and HIV-negative controls. Preliminary data collected on subjects are consistent with published reports of the sociodemographic and clinical characteristics of the HIV epidemic in sexually active youth, thus supporting the integrity of the protocol development process. The study population is, for the most part, in older adolescence, predominantly minority and female, and with publicly financed or no health insurance. Conclusions: The REACH Project is positioned to address questions about the clinical course, immunologic profile, and viral dynamics in HIV-positive youth, and thus is able to inform drug development and management strategies for this understudied population. (C) Society for Adolescent Medicine, 1998. C1 NICHD, Pediat Adolescent & Maternal AIDS Branch, CRMC, Bethesda, MD 20892 USA. Albert Einstein Coll Med, Dept Pediat, New York, NY USA. Univ Calif San Francisco, Dept Pediat, San Francisco, CA 94143 USA. Univ Alabama, Dept Med, Birmingham, AL 35294 USA. Westat Inc, Rockville, MD USA. Univ Birmingham, Dept Epidemiol, Birmingham, AL USA. RP Rogers, AS (reprint author), NICHD, Pediat Adolescent & Maternal AIDS Branch, CRMC, Execut Bldg Room 4B11,6100 Execut Blvd,MSC 7510, Bethesda, MD 20892 USA. OI Vermund, Sten/0000-0001-7289-8698 NR 43 TC 94 Z9 94 U1 3 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 1054-139X J9 J ADOLESCENT HEALTH JI J. Adolesc. Health PD APR PY 1998 VL 22 IS 4 BP 300 EP 311 DI 10.1016/S1054-139X(97)00279-6 PG 12 WC Psychology, Developmental; Public, Environmental & Occupational Health; Pediatrics SC Psychology; Public, Environmental & Occupational Health; Pediatrics GA ZF377 UT WOS:000072891400004 PM 9561462 ER PT J AU Rantanen, T Heikkinen, E AF Rantanen, T Heikkinen, E TI The role of habitual physical activity in preserving muscle strength from age 80 to 85 years SO JOURNAL OF AGING AND PHYSICAL ACTIVITY LA English DT Article DE aging; prospective study; body composition; maximal voluntary strength ID WOMEN; ABILITY; MEN; 75-YEAR-OLD AB The aim of this study was to examine alterations in maximal isometric strength of multiple muscle groups over 5 years and to compare strength changes between individuals who maintained a high level of physical activity and others who did not. As a part of the Evergreen Project, 20 men and 59 women participated in at least one strength test at the age of 80 and again 5 years later. Men displayed no decrease in lean body mass over the follow-up, and the only significant strength decrease was in elbow flexion strength. In women, both lean body mass and muscle strength decreased significantly (except trunk extension strength). Overall, those men and women who were considered to have maintained a high level of activity retained their strength at a higher level than the more sedentary participants. Older people should be encouraged to continue physically demanding activities to maintain muscle strength at an adequate level for independent living. C1 NIA, Epidemiol Demog & Biometry Program, NIH, Bethesda, MD 20892 USA. Univ Jyvaskyla, Finnish Ctr Interdisciplinary Gerontol, SF-40351 Jyvaskyla, Finland. RP Rantanen, T (reprint author), NIA, Epidemiol Demog & Biometry Program, NIH, Gateway Bldg,room 3C309,7201 Wisconsin Ave,MSC 95, Bethesda, MD 20892 USA. RI Rantanen, Taina/O-6579-2016 OI Rantanen, Taina/0000-0002-1604-1945 NR 27 TC 12 Z9 14 U1 1 U2 1 PU HUMAN KINETICS PUBL INC PI CHAMPAIGN PA 1607 N MARKET ST, CHAMPAIGN, IL 61820-2200 USA SN 1063-8652 J9 J AGING PHYS ACTIV JI J. Aging Phys. Act. PD APR PY 1998 VL 6 IS 2 BP 121 EP 132 PG 12 WC Geriatrics & Gerontology; Gerontology; Sport Sciences SC Geriatrics & Gerontology; Sport Sciences GA ZH274 UT WOS:000073090700003 ER PT J AU Hirvensalo, M Lampinen, P Rantanen, T AF Hirvensalo, M Lampinen, P Rantanen, T TI Physical exercise in old age: An eight-year follow-up study on involvement, motives, and obstacles among persons age 65-84 SO JOURNAL OF AGING AND PHYSICAL ACTIVITY LA English DT Article DE aging; longitudinal study; sport activities; participation ID TRENDS; FINLAND AB This study examined changes in involvement in physical exercise and the motives for and obstacles to participation over an 8-year period in a representative sample of senior residents of Jyvaskyla, Finland. The participants were noninstitutionalized seniors age 65-84 years at baseline in 1988. The most common form of physical exercise was walking for fitness. In men, participation in supervised exercise classes and performing calisthenic exercises at home increased over the follow-up. In women, physical exercise generally declined. The most important reason quoted for nonparticipation at both baseline and follow-up was poor health (65-88%). Among those who reported participation in supervised physical exercise, the most important motives were health promotion (80%) and social reasons (40-50%). The main obstacles were poor health (19-38%) and lack of interest (28-26%). It is an important challenge to remove obstacles to participation in physical activity in old age and to give older people every opportunity to get involved. C1 Univ Jyvaskyla, Dept Educ Phys, FIN-40351 Jyvaskyla, Finland. Univ Jyvaskyla, Finnish Ctr Interdisciplinary Gerontol, Jyvaskyla, Finland. NIA, Epidemiol Demog & Biometry Program, NIH, Bethesda, MD 20892 USA. RP Hirvensalo, M (reprint author), Univ Jyvaskyla, Dept Educ Phys, POB 35, FIN-40351 Jyvaskyla, Finland. RI Rantanen, Taina/O-6579-2016 OI Rantanen, Taina/0000-0002-1604-1945 NR 28 TC 42 Z9 42 U1 0 U2 7 PU HUMAN KINETICS PUBL INC PI CHAMPAIGN PA 1607 N MARKET ST, CHAMPAIGN, IL 61820-2200 USA SN 1063-8652 J9 J AGING PHYS ACTIV JI J. Aging Phys. Act. PD APR PY 1998 VL 6 IS 2 BP 157 EP 168 PG 12 WC Geriatrics & Gerontology; Gerontology; Sport Sciences SC Geriatrics & Gerontology; Sport Sciences GA ZH274 UT WOS:000073090700006 ER PT J AU Chan, CC Li, Y Sun, B Li, Q Matteson, DM Shen, DB Nussenblatt, RB Zhai, YF AF Chan, CC Li, Y Sun, B Li, Q Matteson, DM Shen, DB Nussenblatt, RB Zhai, YF TI Recombinant adenovirus encoding gp100 modulates experimental melanin-protein induced uveitis (EMIU) SO JOURNAL OF AUTOIMMUNITY LA English DT Article DE experimental melanin-protein induced uveitis (EMIU); bovine melanin protein (BMP); antigen-specific melanoma vaccine; recombinant adenovirus encoding gp100; interleukin-l2p40 ID EXPERIMENTAL AUTOIMMUNE UVEORETINITIS; NONOBESE DIABETIC MICE; TUMOR-INFILTRATING LYMPHOCYTES; ANTIGEN GP100; MELANOCYTE LINEAGE; ANTERIOR UVEITIS; ORAL TOLERANCE; MULTIPLE EPITOPES; CYSTIC-FIBROSIS; GENE-THERAPY AB Experimental melanin-protein induced uveitis (EMIU) is a T-cell mediated autoimmune uveitis induced by immunization with bovine uveal melanin protein. Gp100, a melanocyte lineage-specific protein, is identified as a human melanoma antigen. A recombinant adenovirus construct encoding gp100 (Ad2CMV-gp100) has been used as a vaccine for cancer therapy. This study examines the effect of Ad2CMV-gp100 on EMIU. To induce EMIU, rats were injected intraperitoneally on day 7 before immunization with ad2CMV-gp100, control adenovirus encoding LacZ (Ad2CMV-LacZ), or no virus. On day 21 after immunization, the right eye was processed for histology and the left eye was analysed for cytokines by quantitative reverse transcriptase-polymerase chain reaction. Western blot analysis showed that uveal melanin-protein contains gp100. In three independent experiments, ocular inflammation was significantly suppressed, and expression of ocular IL-12p40 mRNA was much lower in the rats which received Ad2CMV-gp100 before immunization than in those that received Ad2CMV-LacZ or no virus. No abnormalities developed in rats which received Ad2CMV-gp100 or Ad2CMV-LacZ alone. Therefore, Ad2CMV-gp100 injection prevents the development of EMIU, at least in part, through cytokine regulation. (C) 1998 Academic Press Limited. C1 NEI, Immunol Lab, NIH, Bethesda, MD 20892 USA. Human Genome Sci Inc, Rockville, MD USA. RP Chan, CC (reprint author), NEI, Immunol Lab, NIH, Bldg 10,Rm 10N103,10 Ctr Dr MSC 1858, Bethesda, MD 20892 USA. EM ccc@helix.nih.gov NR 52 TC 7 Z9 7 U1 0 U2 1 PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0896-8411 J9 J AUTOIMMUN JI J. Autoimmun. PD APR PY 1998 VL 11 IS 2 BP 111 EP 118 DI 10.1006/jaut.1997.0187 PG 8 WC Immunology SC Immunology GA ZR290 UT WOS:000073959300001 PM 9650089 ER PT J AU Merkel, TJ Barros, C Stibitz, S AF Merkel, TJ Barros, C Stibitz, S TI Characterization of the bvgR locus of Bordetella pertussis SO JOURNAL OF BACTERIOLOGY LA English DT Article ID ESCHERICHIA-COLI GENOME; VIR-REPRESSED GENES; NUCLEOTIDE-SEQUENCE; DNA-SEQUENCE; VIRULENCE FACTORS; TRANSPOSON TN501; MERCURIC-RESISTANCE; PLASMID R100; REGION; SYSTEM AB Bordetella pertussis, the causative agent of whooping cough, produces a wide array of factors that are associated with its ability to cause disease. The expression and regulation of these virulence factors is dependent upon the bvg locus (originally designated the vir locus), which encodes two proteins: BvgA, a 23-kDa cytoplasmic protein, and BvgS, a 135-kDa transmembrane protein. It is proposed that BvgS responds to environmental signals and interacts with BvgA, a transcriptional regulator which upon modification by BvgS binds to specific promoters and activates transcription. An additional class of genes is repressed by the bvg locus. Expression of this class, the bvg-repressed genes (vrgs [for vir-repressed genes]), is reduced under conditions in which expression of the aforementioned bvg-activated virulence factors is maximal; this repression is dependent upon the presence of an intact bvgAS locus. We have previously identified a locus required for regulation of all of the known bvg-repressed genes in B. pertussis. This locus, designated bvgR, maps to a location immediately downstream of bvgAS. We have undertaken deletion and complementation studies, as well as sequence analysis, in order to identify the bvgR open reading frame and identify the cis-acting sequences required for regulated expression of bvgR. Studies utilizing transcriptional fusions of bvgR to the gene encoding alkaline phosphatase have demonstrated that bvgR is activated at the level of transcription and that this activation is dependent upon an intact bvgAS locus. C1 NIDR, OIIB, NIH, Bethesda, MD 20892 USA. US FDA, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. RP Merkel, TJ (reprint author), NIDR, OIIB, NIH, Bldg 30,Rm 303,30 Convent Dr,MSC 4350, Bethesda, MD 20892 USA. NR 46 TC 59 Z9 63 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 USA SN 0021-9193 J9 J BACTERIOL JI J. Bacteriol. PD APR PY 1998 VL 180 IS 7 BP 1682 EP 1690 PG 9 WC Microbiology SC Microbiology GA ZE273 UT WOS:000072775500010 PM 9537363 ER PT J AU Winterling, KW Chafin, D Hayes, JJ Sun, J Levine, AS Yasbin, RE Woodgate, R AF Winterling, KW Chafin, D Hayes, JJ Sun, J Levine, AS Yasbin, RE Woodgate, R TI The Bacillus subtilis DinR binding site: Redefinition of the consensus sequence SO JOURNAL OF BACTERIOLOGY LA English DT Article ID ESCHERICHIA-COLI; DNA DAMAGE; LEXA REPRESSOR; RECA GENES; PROTEIN; EXPRESSION; AFFINITY; IDENTIFICATION; COMPETENCE; OPERATOR AB Recently, the DinR protein was established as the cellular repressor of the SOS response in the bacterium Bacillus subtilis. It is believed that DinR functions as the repressor by binding to a consensus sequence located in the promoter region of each SOS gene. The binding site for DinR is believed to be synonymous with the formerly identified Cheo box, a region of 12 bp displaying dyad symmetry (GAAC-N-4-GTTC). Electrophoretic mobility shift assays revealed that highly purified DinR does bind to such sites located upstream of the dinA, dins, dinC, and dins genes. Furthermore, detailed mutational analysis of the B. subtilis recA operator indicates that some nucleotides are more important than others for maintaining efficient DinR binding. For example, nucleotide substitutions immediately 5' and 3' of the Cheo box as well as those in the N-4, region appear to affect DinR binding. This data, combined with computational analyses of potential binding sites in other grampositive organisms, yields a new consensus (DinR box) of 5'-CGAACRNRYGTTYC-3'. DNA footprint analysis of the B. subtilis dins and recA DinR boxes revealed that the DinR box is centrally located within a DNA region of 31 bp that is protected from hydroxyl radical cleavage in the presence of DinR. Furthermore, while DinR is predominantly monomeric in solution, it apparently binds to the DinR box in a dimeric state. C1 NICHHD, Sect DNA Replicat Repair & Mutagenesis, Bethesda, MD 20892 USA. Univ Maryland, Dept Sci Biol, Baltimore, MD 21228 USA. Univ Maryland, Mol & Cellular Biol Program, Baltimore, MD 21228 USA. Univ Rochester, Sch Med & Dent, Dept Biochem & Biophys, Rochester, NY 14642 USA. Univ Texas, Dept Cell & Mol Biol, Richardson, TX 75083 USA. RP Woodgate, R (reprint author), NICHD, NIH, Bldg 6,Room 1A13,9000 Rockville Pike, Bethesda, MD 20892 USA. EM woodgate@helix.nih.gov FU NCI NIH HHS [T32 CA009363, CA09363D-16A1]; NIGMS NIH HHS [R01 GM052426, R01GM52426] NR 28 TC 77 Z9 78 U1 1 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 USA SN 0021-9193 J9 J BACTERIOL JI J. Bacteriol. PD APR PY 1998 VL 180 IS 8 BP 2201 EP 2211 PG 11 WC Microbiology SC Microbiology GA ZG800 UT WOS:000073041000030 PM 9555905 ER PT J AU Rao, VSR Lam, K Qasba, PK AF Rao, VSR Lam, K Qasba, PK TI Three dimensional structure of the soybean agglutinin-Gal/GalNac complexes by homology modeling SO JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS LA English DT Article ID PROTEIN CARBOHYDRATE COMPLEXES; ARABINOSE-BINDING PROTEIN; RAY CRYSTAL-STRUCTURE; CONCANAVALIN-A; COMPUTER-SIMULATION; PEA LECTIN; SPECIFICITY; LACTOSE; SITE AB Complexes of soybean agglutinin (SBA) with galactose (Gal) and N-acetyl galactosamine (GalNAc) have been modeled based on its homology to erythrina corallodendron (EcorL) lectin. The three dimensional structure of SEA-Gal modeled with homology techniques agrees well with SBA-(beta-LacNAc)(2)Gal-R complex determined by X-ray crystallographic techniques at the beta-sheet regions and the regions where Ca2+ and Mn2+ ions bind. However, significant deviations have been observed between the modeled and the X-ray structures, particularly at the loop regions where the polypeptide chain could not be unequivocally traced in the X-ray structure. The hydrogen bonding scheme, predicted from the homology model, shows that the invariant residues i.e. Asp, Gly, Asn, and aromatic residues (Phe) found in all other legume lectins, bind Gal, slightly in a different way than reported in X-ray structure of SBA-pentasaccharide complex. The higher binding affinity of GalNAc over Gal to SBA is due to additional hydrophobic interactions with Tyr107 rather than a hydrogen bond between N-acetamide group of the sugar and the side chain of Asp88 as suggested from X-ray crystal structure studies. Our modeling also suggest that the variation in the length of the loop D observed among galactose binding legume lectins may not have any effect on the binding of sugar at the monosaccharide specific site of the lectins. C1 NCI, Frederick Canc Res & Dev Ctr, Struct Glycobiol Sect, Lab Expt & Computat Biol, Frederick, MD 21702 USA. RP Qasba, PK (reprint author), NCI, Frederick Canc Res & Dev Ctr, Struct Glycobiol Sect, Lab Expt & Computat Biol, Frederick, MD 21702 USA. EM qasba@helix.nih.gov NR 18 TC 7 Z9 8 U1 2 U2 7 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 530 WALNUT STREET, STE 850, PHILADELPHIA, PA 19106 USA SN 0739-1102 EI 1538-0254 J9 J BIOMOL STRUCT DYN JI J. Biomol. Struct. Dyn. PD APR PY 1998 VL 15 IS 5 BP 853 EP 860 PG 8 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA ZN401 UT WOS:000073642200003 PM 9619508 ER PT J AU Sharrock, WJ AF Sharrock, WJ TI Bone and the hematopoietic and immune systems: A report of the proceedings of a scientific workshop SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Article ID A-INDUCED OSTEOPENIA; INTERFERON-GAMMA; MARROW CULTURES; STROMAL CELLS; IN-VIVO; MICE; OSTEOPOROSIS; OSTEOCLASTS; RESORPTION; PRECURSORS AB Recent observations underscore the linkage between endochondral bone formation and the establishment of hematopoietic marrow and suggest that interactions among bone, marrow, and the immune system persist in the mature skeleton. A workshop was held at the National Institutes of Health, Bethesda, Maryland, to discuss recent work on these interactions and to identify new areas of research. Marrow stromal cells include the precursors of the osteochondrogenic lineage, exert important influences on osteoclastogenesis and lymphopoiesis, and mediate the effects of some systemic factors on bone turnover. Recent evidence indicates that hematopoietic cells can influence the differentiation of osteogenic cells and suggests that mature lymphocytes can influence osteoclastic and osteoblastic functions. However, interpretation of experiments may be confounded by the potential for stage-specific responses within a cell lineage, the likelihood that divergent pathways compete for limited pools of precursor cells, and the possibility that important cells or factors are still unidentified. Further, in vitro models may be limited by species and anatomical site specificities, the absence of intermediary or accessory cells, and the absence of normal marrow spatial organization and cellular interactions with the extracellular matrix. Nevertheless, current approaches hold the potential for significant advances in our understanding of the relationships between bone and the hematopoietic and immune systems. Refinements of in vitro systems, the use of genetically manipulated mice, and the examination of clinical syndromes promise important insights. Collaborations among bone biologists, hematologists, and immunologists, and between basic scientists and clinical investigators, will be crucial for continued progress. C1 NIAMSD, Musculoskeletal Dis Branch, Extramural Program, NIH, Bethesda, MD 20892 USA. Albert Einstein Med Ctr, Philadelphia, PA 19141 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Yale Univ, New Haven, CT USA. Univ Texas, Hlth Sci Ctr, San Antonio, TX 78285 USA. Univ Toronto, Toronto, ON, Canada. Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. Helen Hayes Hosp, W Haverstraw, NY USA. Rutgers State Univ, New Brunswick, NJ 08903 USA. Univ Penn, Sch Med, Philadelphia, PA 19104 USA. Albert Einstein Med Ctr, Philadelphia, PA 19141 USA. St Vincents Inst Med Res, Fitzroy, Vic 3065, Australia. Univ Penn, Sch Vet Med, Philadelphia, PA 19104 USA. Oklahoma Med Res Fdn, Oklahoma City, OK 73104 USA. Univ Washington, Sch Med, Seattle, WA 98195 USA. Univ Michigan, Sch Med, Ann Arbor, MI 48109 USA. Stanford Univ, Sch Med, Stanford, CA 94305 USA. Washington Univ, St Louis, MO USA. Temple Univ, Sch Med, Philadelphia, PA 19122 USA. Merck Sharp & Dohme Res Labs, W Point, PA USA. Hanson Ctr Canc Res, Adelaide, SA, Australia. Univ Minnesota, Sch Med, Minneapolis, MN 55455 USA. NCI, Frederick, MD 21701 USA. RP Sharrock, WJ (reprint author), NIAMSD, Musculoskeletal Dis Branch, Extramural Program, NIH, Natcher Bldg,Room 5A2-37A,45 Ctr Dr, Bethesda, MD 20892 USA. NR 28 TC 30 Z9 32 U1 0 U2 1 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD APR PY 1998 VL 13 IS 4 BP 537 EP 543 DI 10.1359/jbmr.1998.13.4.537 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA ZE554 UT WOS:000072805200001 PM 9556053 ER PT J AU Dieudonne, S Xu, T Chou, JY Kuznetsov, SA Satomura, K Mankani, M Fedarko, NS Smith, EP Robey, PG Young, MF AF Dieudonne, S Xu, T Chou, JY Kuznetsov, SA Satomura, K Mankani, M Fedarko, NS Smith, EP Robey, PG Young, MF TI Immortalization and characterization of bone marrow stromal fibroblasts from a patient with a loss of function mutation in the estrogen receptor-alpha gene SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Article ID GROWTH-FACTOR-BETA; INSITU HYBRIDIZATION; PROTEIN-KINASE; MESSENGER-RNA; FACTOR-I; CELLS; EXPRESSION; DIFFERENTIATION; OSTEOPOROSIS; OSTEOBLASTS AB A male patient with abnormal postpubertal bone elongation was shown earlier to have a mutation in both alleles of the estrogen receptor, resulting in a nonfunctional gene. Marrow stromal fibroblasts (MSFs) derived from this patient were called HERKOs (human estrogen receptor knock outs), and in order to obtain continuous HERKO cell lines, they were immortalized using a recombinant adenovirus-origin-minus SV40 virus. MSFs are unique cells because they support hematopoesis and contain a mixed population of precursor cells for bane, cartilage, and fat. Three established cell lines (HERKO2, HERKO4, and HERKO7) were characterized and compared with the heterogeneous population of nonimmortalized HERKOs for their osteogenic potential. We performed Northern analysis of matrix genes implicated in bone development and metabolism and an in vivo bone formation assay by transplanting the cells subcutaneously into immunodeficient mite. All three HERKO lines expressed high amounts of collagen 1A1, osteopontin, osteonectin, fibronectin, decorin, biglycan, and alkaline phosphatase. Except for osteopontin, expression of these genes was slightly lower compared with nonimmortalized HERKOs. In the in vivo bone formation assay, the heterogeneous population of nonimmortalized HERKOs formed bone with high efficiency, while the HERKO lines induced a high-density, bone-like matrix. Finally, all HERKO cell types secreted high levels of insulin-like growth factor I and interleukin-6 into the culture medium relative to tells of normal human subjects. In summary, these lines of HERKO cells retain several of the phenotypic traits of MSFs after immortalization, including matrix and cytokine production, and provide a valuable source of a unique human material for future studies involving estrogen action in bone and bone marrow metabolism. C1 NIDR, Craniofacial & Skeletal Dis Branch, NIH, Bethesda, MD 20892 USA. NICHHD, Heritable Disorders Branch, NIH, Bethesda, MD 20892 USA. Johns Hopkins Univ, Sch Med, Dept Med, Baltimore, MD 21205 USA. Univ Cincinnati, Childrens Hosp, Med Ctr, Coll Med,Dept Pediat,Div Endocrinol, Cincinnati, OH USA. RP Dieudonne, S (reprint author), NIDR, Craniofacial & Skeletal Dis Branch, NIH, Bldg 30,Room 222,9000 Rockville Pike, Bethesda, MD 20892 USA. RI Robey, Pamela/H-1429-2011 OI Robey, Pamela/0000-0002-5316-5576 FU NIAMS NIH HHS [R01 AR42358] NR 43 TC 12 Z9 13 U1 0 U2 1 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD APR PY 1998 VL 13 IS 4 BP 598 EP 608 DI 10.1359/jbmr.1998.13.4.598 PG 11 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA ZE554 UT WOS:000072805200008 PM 9556060 ER PT J AU Jarnik, M Simon, MN Steven, AC AF Jarnik, M Simon, MN Steven, AC TI Cornified cell envelope assembly: a model based on electron microscopic determinations of thickness and projected density SO JOURNAL OF CELL SCIENCE LA English DT Article DE terminal differentiation; cornified cell envelope; keratinocyte; covalent cross-linking; transglutaminase; loricrin; electron microscopy ID HUMAN EPIDERMAL-KERATINOCYTES; PROLINE-RICH PROTEIN-1; CROSS-LINKED ENVELOPE; EXPRESSION PATTERNS; PSORIATIC EPIDERMIS; LORICRIN; TRANSGLUTAMINASE; INVOLUCRIN; DIFFERENTIATION; IDENTIFICATION AB In stratifying squamous epithelia, the cornified cell envelope (CE), a peripheral layer of crosslinked protein, is assembled sequentially from precursor proteins initially dispersed in the cytoplasm. Its major component is loricrin (37 kDa in mouse), which contributes from approx. 60% to >80% of the protein mass in different tissues. Despite its importance to the mechanical resilience and impenetrability of these tissues, detailed information has not been obtained on CE structure, even on such basic properties as its thickness or uniformity across a given CE or from tissue to tissue. To address this issue, we have studied CEs isolated from three murine epithelia, namely epidermis, forestomach and footpad, by electron microscopy of metal-shadowed specimens and scanning transmission electron microscopy (STEM) of unstained specimens. The former data reveal that the cytoplasmic surface is smoothly textured whereas the extracellular surface is corrugated, and that the average thickness is 15.3+/-1.2 nm, and strikingly uniform. Measurements of mass-per-unit-area from the STEM images yielded values of approx, 7.0+/-0.8 kDa/nm(2), which were remarkably consistent over all three tissues. These data imply that the mature CE has a uniquely defined thickness. To explain its uniformity, we postulate that loricrin forms a molecular monolayer, not a variable number of multiple layers. In this scenario, the packing density is one loricrin monomer per 7 nm(2), and loricrin should have an elongated shape, 2.5-3.0 nm wide by approx. 11 nm long. Moreover, we anticipate that any inter-tissue variations in the mechanical properties of CEs should depend more on protein composition and cross-linking pattern than on the thickness of the protein layer deposited. C1 NIAMSD, Struct Biol Lab, NIH, Bethesda, MD 20892 USA. Brookhaven Natl Lab, Dept Biol, Upton, NY 11973 USA. RP Steven, AC (reprint author), NIAMSD, Struct Biol Lab, NIH, Bldg 6,Room B2-34,MSC 2717, Bethesda, MD 20892 USA. EM Alasdair_Steven@nih.gov FU NCRR NIH HHS [P41-RR01777] NR 54 TC 43 Z9 43 U1 0 U2 1 PU COMPANY OF BIOLOGISTS LTD PI CAMBRIDGE PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE, CAMBS, ENGLAND CB4 4DL SN 0021-9533 J9 J CELL SCI JI J. Cell Sci. PD APR PY 1998 VL 111 BP 1051 EP 1060 PN 8 PG 10 WC Cell Biology SC Cell Biology GA ZN660 UT WOS:000073668900003 PM 9512501 ER PT J AU Chmielowska, J Coghill, RC Maisog, JM Carson, RE Herscovitch, P Honda, M Chen, R Hallett, M AF Chmielowska, J Coghill, RC Maisog, JM Carson, RE Herscovitch, P Honda, M Chen, R Hallett, M TI Positron emission tomography [O-15]water studies with short interscan interval for single-subject and group analysis: Influence of background subtraction SO JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM LA English DT Article DE positron emission tomography; single subject; short interscan interval; [O-15]water ID CEREBRAL BLOOD-FLOW; PRIMARY MOTOR CORTEX; PET ACTIVATION; MOVEMENT; OPINION; IMAGES AB Use of short interscan interval [O-15]water positron emission tomography (PET) studies reduces the overall study duration and may allow an increased number of scans for single-subject analysis of unique cases (e.g., stroke). The pur pose of this study was to examine how subtraction of residual radioactivity from the previous injection (corrected scan) compared to nonsubtraction (uncorrected scan) in a PET short interscan interval (6 minutes) study affects single-subject and group data analysis using a motor activation task. Two currently widely used analytic strategies, Worsley's method and the SPM technique, were applied. Excellent agreement between activation maps obtained from corrected and uncorrected data sets was obtained both in single-subject analyses performed on data sets from the six normal subjects and three stroke (subcortical infarct) patients, and in group analysis (six normal subjects) within a particular statistical method. The corrected and uncorrected data were very similar in the (1) number of activated brain regions; (2) size of clusters of activated brain voxels; (3) Talairach coordinates of the activated region; and (4) t or Z value of the peak intensity for every significantly activated motor brain structure (both for large activations such as in motor cortex and small activations such as in putamen and thalamus). [O-15]Water PET data obtained with a short interscan interval (6 minutes) produce similar results whether or not the background is subtracted. Thus, if injection dose and timing are constant, one can achieve the advantage of a short interscan interval without the added complexity of correcting for background radioactivity. C1 NINDS, NIH, Human Motor Control Sect, Med Neurol Branch, Bethesda, MD 20892 USA. NIDR, Pain Neurosensory Mechanisms Branch, Bethesda, MD 20892 USA. NIH, Sect Funct Brain Imaging, Psychol & Psychopathol Lab, Bethesda, MD 20892 USA. NIH, Positron Emiss Tomog Dept, Ctr Clin, Bethesda, MD 20892 USA. RP Hallett, M (reprint author), NINDS, NIH, Human Motor Control Sect, Med Neurol Branch, Bldg 10,Room 5N226,10 Ctr Dr,MSC 1428, Bethesda, MD 20892 USA. RI Chen, Robert/B-3899-2009; Carson, Richard/H-3250-2011 OI Chen, Robert/0000-0002-8371-8629; Carson, Richard/0000-0002-9338-7966 NR 29 TC 17 Z9 17 U1 1 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0271-678X J9 J CEREBR BLOOD F MET JI J. Cereb. Blood Flow Metab. PD APR PY 1998 VL 18 IS 4 BP 433 EP 444 PG 12 WC Endocrinology & Metabolism; Hematology; Neurosciences SC Endocrinology & Metabolism; Hematology; Neurosciences & Neurology GA ZE999 UT WOS:000072852700012 PM 9538909 ER PT J AU Bicout, DJ Szabo, A AF Bicout, DJ Szabo, A TI Escape through a bottleneck undergoing non-Markovian fluctuations SO JOURNAL OF CHEMICAL PHYSICS LA English DT Article ID PASSAGE AB The Zwanzig model for the kinetics of escape through a fluctuating bottleneck is generalized to handle fluctuations that can be described by a non-Markovian Gaussian process. Our formulation is based on a multidimensional Fokker-Planck equation with a quadratic sink term. It is shown that the calculation of the time dependence of the survival probability can be reduced to a matrix eigenvalue problem. The elegant Wang-Wolynes expression, first derived using path integral techniques, for the effective rate constant that determines the asymptotic behavior of the survival probability, is recovered. When the fluctuations are described by Langevin dynamics (i.e., diffusion in position and velocity space) on a harmonic potential, analytical expressions for the survival probability and effective rate constant for all values of the friction, are derived. As a function of the friction constant, these exhibit "Kramers turnover" behavior. (C) 1998 American Institute of Physics. [S0021-9606(98)50613-7]. C1 NIDDK, Chem Phys Lab, NIH, Bethesda, MD 20892 USA. RP Bicout, DJ (reprint author), NIDDK, Chem Phys Lab, NIH, Bldg 5,Rm 136, Bethesda, MD 20892 USA. RI Szabo, Attila/H-3867-2012 NR 5 TC 22 Z9 22 U1 0 U2 6 PU AMER INST PHYSICS PI WOODBURY PA CIRCULATION FULFILLMENT DIV, 500 SUNNYSIDE BLVD, WOODBURY, NY 11797-2999 USA SN 0021-9606 J9 J CHEM PHYS JI J. Chem. Phys. PD APR 1 PY 1998 VL 108 IS 13 BP 5491 EP 5497 DI 10.1063/1.475937 PG 7 WC Chemistry, Physical; Physics, Atomic, Molecular & Chemical SC Chemistry; Physics GA ZD913 UT WOS:000072738000038 ER PT J AU McLachlan, JA Newbold, RR Teng, CT Korach, KS AF McLachlan, JA Newbold, RR Teng, CT Korach, KS TI Environmental estrogens: Orphan receptors and genetic imprinting SO JOURNAL OF CLEAN TECHNOLOGY ENVIRONMENTAL TOXICOLOGY AND OCCUPATIONAL MEDICINE LA English DT Article DE environmental estrogens; genetic imprinting; orphan receptors ID MALE-MICE; LACTOTRANSFERRIN GENE; PRENATAL EXPOSURE; DIETHYLSTILBESTROL; EXPRESSION; SUPERFAMILY AB Many chemicals in the environment function like female sex hormones-estrogens. This functional signal apparently is mediated by a member of the nuclear hormone receptor gene family. This gene family and the chemicals it recognizes seem to be growing;family members for which no known ligand exists are called orphan receptors. One consequence of exposure to estrogens early in development is the feminization of the male reproductive system which occurs at both the gross structural and genetic levels. This imprinting of genes has implications for reproductive health which are only now being considered. C1 NIEHS, Reprod & Dev Toxicol Lab, Res Triangle Pk, NC 27709 USA. RP McLachlan, JA (reprint author), Tulane Univ, Xavier Ctr Bioenvironm Reesearch, 1430 Tulane Ave, New Orleans, LA 70112 USA. OI Korach, Kenneth/0000-0002-7765-418X NR 19 TC 0 Z9 0 U1 0 U2 0 PU PRINCETON SCIENTIFIC PUBL INC PI PRINCETON PA PO BOX 2155, PRINCETON, NJ 08543 USA SN 1052-1062 J9 J CLEAN TECHNOL E T JI J. Clean Technol. Environ. Toxicol. Occup. Med. PD APR-JUN PY 1998 VL 7 IS 2 BP 221 EP 226 PG 6 WC Environmental Sciences; Toxicology SC Environmental Sciences & Ecology; Toxicology GA ZX731 UT WOS:000074549000007 ER PT J AU Collins, MT Skarulis, MC Bilezikian, JP Silverberg, SJ Spiegel, AM Marx, SJ AF Collins, MT Skarulis, MC Bilezikian, JP Silverberg, SJ Spiegel, AM Marx, SJ TI Treatment of hypercalcemia secondary to parathyroid carcinoma with a novel calcimimetic agent SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID CALCIUM-SENSING RECEPTOR; CA2+-SENSING RECEPTOR; HYPERPARATHYROIDISM; EXPRESSION; MUTATIONS; CLONING; CELLS; GENE AB Parathyroid carcinoma is one cause of primary hyperparathyroidism, a condition in which there is hypercalcemia and dysregulated hypersecretion of PTH. In normal, and in some neoplastic parathyroid cells, PTH secretion is mediated by the cell surface calcium-sensing receptor. We describe the first therapeutic use of a novel molecule, a calcimimetic, that has agonist action at the calcium-sensing receptor. A 78-yr-old man with parathyroid carcinoma was admitted with hypercalcemia, markedly elevated PTH, and a change in mental status. He was treated for 17 days with conventional therapy, which included saline hydration, furosemide, pamidronate, and calcitonin. This was ineffective, and on hospital day 18, calcimimetic at a dose of 50 mg, orally, every 6 h was added. On hospital day 25, the dose was increased to 100 mg, orally, every 6 h, and on hospital day 30, saline and furosemide were discontinued. He was discharged on hospital day 40. With several dose adjustments, he has been treated with monotherapy calcimimetic for over 600 days and has not required any other interventions for his parathyroid carcinoma. Mean daily precalcimimetic treatment values of serum ionized calcium and PTH were 1.83 mmol/L and 872 pg/mL, respectively. During hospitalization, at the lower dose of calcimimetic, calcium and PTH decreased to 1.67 mmol/L and 538 pg/mL; with the higher dose they further decreased to 1.51 mmol/L and 444 pg/mL. Since discharge, and despite increasing levels of PTH, serum calcium has remained high, but lower than the admission level and acutely responsive to changes in calcimimetic doses. This compound, a calcimimetic, the first of a new class of compounds with activity at the calcium-sensing receptor, has been used to treat a patient with parathyroid carcinoma. During 2 yr of treatment, no adverse clinical effects have been observed, and it appears to have been effective at controlling hypercalcemia. C1 NICHHD, Dev Endocrinol Branch, NIH, Bethesda, MD 20892 USA. NIDDKD, Metab Dis Branch, NIH, Bethesda, MD 20892 USA. Columbia Univ Coll Phys & Surg, Dept Med, New York, NY 10032 USA. Columbia Univ Coll Phys & Surg, Dept Pharmacol, New York, NY 10032 USA. RP Collins, MT (reprint author), NICHHD, Dev Endocrinol Branch, NIH, 10 Ctr Dr,MSC1862,Bldg 10,Room 10N262, Bethesda, MD 20892 USA. EM collinsm@cc1.nichd.nih.gov FU NIDDK NIH HHS [R01 DK032333] NR 18 TC 106 Z9 109 U1 0 U2 1 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X EI 1945-7197 J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD APR PY 1998 VL 83 IS 4 BP 1083 EP 1088 DI 10.1210/jc.83.4.1083 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA ZG029 UT WOS:000072957800008 PM 9543122 ER PT J AU Papanicolaou, DA Yanovski, JA Cutler, GB Chrousos, GP Nieman, LK AF Papanicolaou, DA Yanovski, JA Cutler, GB Chrousos, GP Nieman, LK TI A single midnight serum cortisol measurement distinguishes Cushing's syndrome from pseudo-Cushing states SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article; Proceedings Paper CT 76th Annual Meeting of the Endocrine-Society CY JUN 15-18, 1994 CL ANAHEIM, CA SP Endocrine Soc ID CORTICOTROPIN-RELEASING HORMONE; PITUITARY-ADRENAL AXIS; DISEASE; DIAGNOSIS; HYPERCORTISOLISM; DEPRESSION; SECRETION; PATIENT; PATTERN; RHYTHM AB Cushing's syndrome (CS) may be difficult to distinguish from pseudo-Cushing states (PCS) based on physical findings or urinary glucocorticoid excretion. As the lack of diurnal variation in serum cortisol is characteristic of CS, we studied whether diurnal cortisol determinations could discriminate CS from PCS. Two hundred and sixty-three patients were evaluated: 240 had CS, and 23 had PCS. Urine was collected for 24 h for measurement of cortisol and 17-hydroxy-corticosteroids (17OHCS). Blood was drawn at 2300, 2330, 0000, 0030, and 0100 h and at 0600, 0630, 0700, 0730, and 0800 h the next morning for serum cortisol determination. The main outcome measure was the sensitivity of these parameters for the diagnosis of CS at 100% specificity. A midnight cortisol value greater than 7.5 mu g/dL correctly identified 225 of 234 patients with CS and all PCS patients. This sensitivity (96%) was superior to that obtained for any other measure, including urinary cortisol (45%), 17OHCS (22%), any other individual cortisol time point (10-92%), the morning (23%) or the evening (93%) cortisol mean, and the ratio (11%) of morning to evening values. We conclude that at 100% Specificity, a Single serum cortisol value above 7.5 mu g/dL at midnight discriminates CS from PCS with higher sensitivity than 24-h urinary cortisol or 17OHCS, or other individual or combined measures of serum cortisol. C1 NICHHD, Dev Endocrinol Branch, NIH, Bethesda, MD 20892 USA. RP Papanicolaou, DA (reprint author), NICHHD, Dev Endocrinol Branch, NIH, Bldg 10,Room 10N262,10 Ctr Dr,MSC 1862, Bethesda, MD 20892 USA. EM papanicd@cc1nichd.nih.gov NR 31 TC 140 Z9 145 U1 0 U2 0 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X EI 1945-7197 J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD APR PY 1998 VL 83 IS 4 BP 1163 EP 1167 DI 10.1210/jc.83.4.1163 PG 5 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA ZG029 UT WOS:000072957800023 PM 9543134 ER PT J AU Tataranni, PA Christin, L Snitker, S Paolisso, G Ravussin, E AF Tataranni, PA Christin, L Snitker, S Paolisso, G Ravussin, E TI Pima Indian males have lower beta-adrenergic sensitivity than Caucasian males SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID BODY-WEIGHT GAIN; ENERGY-EXPENDITURE; CARDIOVASCULAR REACTIVITY; INSULIN; DETERMINANTS; METABOLISM; OBESITY; SYSTEM; FAT; MEN AB The sympathetic nervous system controls cardiovascular homeostasis and regulates energy metabolism. Pima Indians, a population with a low prevalence of hypertension and a high prevalence of obesity, have low sympathetic nervous activity, compared with Caucasians. Preliminary findings suggest that they may also have a low beta-adrenergic sensitivity. We studied beta-adrenergic sensitivity in 87 nondiabetic normotensive individuals [52 Pina Indians (35 males/17 females) and 35 Caucasians (24 males/11 females)], matched for age and body weight. Chronotropic sensitivity to beta-adrenergic stimulation was assessed by the dose of isoproterenol necessary to increase heart rate by 25 beats per minute [chronotropic dose-25 (CD25)]. Despite a similar basal heart rate and arterial blood pressure, Pimas tended to have lower beta-adrenergic sensitivity than Caucasians (CD25 = 2.37 +/- significant in males (CD25 = 3.03 +/- 2.99 vs. 1.85 +/- 1.56 mu g, P = 0.02) but not in females (CD25 = 1.01 +/- 1.17 vs. 0.96 +/- 0.61 mu g, P = 0.99). In males only, CD25 was positively correlated to percent body fat (r = 0.36, P < 0.01). After adjustment far percent body fat, beta-adrenergic sensitivity was still significantly lower in Pima than in Caucasian males (CD25 = 3.44 +/- 2.24 vs. 2.57 +/- 1.60 mu g, P = 0.05). In conclusion, our data suggest that increased adiposity is accompanied by decreased beta-adrenergic sensitivity in males only. However, at each level of adiposity, Pima Indian males have lower beta-adrenergic sensitivity than Caucasian males. In combination with a low sympathetic nervous system activity, a reduced beta-adrenergic sensitivity may contribute to the low prevalence of hypertension and the high prevalence of obesity observed in Pima Indians. C1 NIDDKD, Clin Diabet & Nutr Sect, NIH, Phoenix, AZ 85016 USA. RP Ravussin, E (reprint author), NIDDKD, Clin Diabet & Nutr Sect, NIH, 4212 N 16Th St, Phoenix, AZ 85016 USA. EM Eric_Ravussin@nih.gov OI Paolisso, Giuseppe/0000-0002-2137-455X NR 36 TC 15 Z9 16 U1 0 U2 0 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X EI 1945-7197 J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD APR PY 1998 VL 83 IS 4 BP 1260 EP 1263 DI 10.1210/jc.83.4.1260 PG 4 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA ZG029 UT WOS:000072957800042 PM 9543153 ER PT J AU Gautier, JF Mourier, A de Kerviler, E Tarentola, A Bigard, AX Villette, JM Guezennec, CY Cathelineau, G AF Gautier, JF Mourier, A de Kerviler, E Tarentola, A Bigard, AX Villette, JM Guezennec, CY Cathelineau, G TI Evaluation of abdominal fat distribution in noninsulin-dependent diabetes mellitus: Relationship to insulin resistance SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID ADIPOSE-TISSUE DISTRIBUTION; BODY-FAT; TOLERANCE-TEST; OBESE WOMEN; COMPUTED-TOMOGRAPHY; WAIST CIRCUMFERENCE; CARDIOVASCULAR RISK; GLUCOSE-TOLERANCE; VISCERAL FAT; IN-VIVO AB Accumulation of visceral adipose tissue is associated with metabolic complications such as noninsulin-dependent diabetes mellitus. The aim of this study was to evaluate the effect of abdominal adipose tissue on insulin sensitivity in subjects with noninsulin-dependent diabetes mellitus (NIDDM). Areas of abdominal fat were calculated from axial magnetic resonance images obtained at the level of the umbilicus in 21 men with NIDDM [age, 45.6+/-8.3 (+/-SD) yr; body mass index, 29.3+/-4.5 kg/m(-2); total body fat (skinfold thickness), 26.8+/-5.4%; waist to hip ratio, 0.97+/-0.07; duration of diabetes, 59+/-47 months; hemoglobin A(1c), 8.1+/-1.5%]. Insulin sensitivity was evaluated by an insulin tolerance test. The areas of deep abdominal fat and sc abdominal fat were, respectively, 135.3+/-55.1 and 211.8+/-99.1 cm(2). The blood glucose disappearance rate was 2.11+/-0.87%/min and was negatively related to deep abdominal fat (r = 0.72; P = 0.0025). In contrast, areas of sc abdominal fat, total body fat, body mass index, and waist to hip ratio were not related to the blood glucose disappearance rate. Plasma triglyceride concentrations averaged 1.8+/-0.8 mmol/L and were positively related to deep abdominal fat (r = 0.69; P = 0.0018). We conclude that insulin sensitivity is strongly related to visceral adipose tissue accumulation NIDDM. C1 Hop St Louis, Serv Diabetol & Hormonol, F-75475 Paris 10, France. Hop St Louis, Serv Radiol, F-75475 Paris 10, France. IMASSA, Ctr Essais Vol, Dept Physiol Syst, F-91223 Bretigny Sur Orge, France. RP Gautier, JF (reprint author), NIDDKD, NIH, 4212 N 16Th St, Phoenix, AZ 85016 USA. OI Tarantola, Arnaud/0000-0002-6946-7958 NR 43 TC 65 Z9 66 U1 0 U2 0 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X EI 1945-7197 J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD APR PY 1998 VL 83 IS 4 BP 1306 EP 1311 DI 10.1210/jc.83.4.1306 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA ZG029 UT WOS:000072957800049 PM 9543160 ER PT J AU Stratakis, CA Vottero, A Brodie, A Kirschner, LS DeAtkine, D Lu, Q Yue, W Mitsiades, CS Flor, AW Chrousos, GP AF Stratakis, CA Vottero, A Brodie, A Kirschner, LS DeAtkine, D Lu, Q Yue, W Mitsiades, CS Flor, AW Chrousos, GP TI The aromatase excess syndrome is associated with feminization of both sexes and autosomal dominant transmission of aberrant P450 aromatase gene transcription SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID HUMAN CHORIONIC-GONADOTROPIN; INDUCED STEROIDOGENIC RESPONSE; HENNY FEATHERING TRAIT; HUMAN BREAST CANCERS; CYTOCHROME-P450 GENE; HUMAN TESTIS; FAMILIAL GYNECOMASTIA; PRECOCIOUS PUBERTY; EXPRESSION; ESTROGEN AB Increased extraglandular aromatization has been reported as the cause of familial gynecomastia. We studied a kindred with aromatase excess inherited in an autosomal dominant manner, in which affected males had heterosexual precocity and/or gynecomastia, and affected females had isosexual precocity and/or macromastia. The propositus was a 9-yr-old boy with gynecomastia. His 7.5-yr-old sister had precocious puberty, and their father and paternal grandmother had peripubertal gynecomastia and macromastia, respectively. Serum concentrations of gonadal and adrenal steroid hormones were determined before and after the administration of corticotropin and/or hCG. Aromatase activity was determined by [H-3]Delta(4)-androstenedione to [H-3]estrone conversion by cultured, skin fibroblasts and/or Epstein-Barr virus-transformed lymphocytes and was detected by immunohistochemistry and/or Western analysis. Linkage was examined with a polymorphism of the aromatase (P450arom) gene. The P450arom messenger ribonucleic acid was analyzed by rapid amplification of complementary DNA (cDNA) ends, ribonuclease protection assay, and RT-PCR. hCG testing demonstrated a high rate of conversion of Delta(4)-androstenedione to estrone and of testosterone to estradiol in the propositus and his father. Treatment of the propositus and his sister was initiated with an aromatase inhibitor (testolactone) and a GnRH analog, which successfully delayed skeletal and pubertal development In both children. Markedly increased aromatase activity was found in the patients' fibroblasts and Epstein-Barr virus-transformed lymphocytes. The P450arom polymorphism segregated with the disease in the family. A new 5'-splice variant was present in the patients' P450arom messenger ribonucleic acid, thus identifying yet another first exon of this gene, which appears to be aberrantly expressed in this family. In conclusion, a family with the aromatase excess syndrome is described, in which the condition was inherited in an autosomal dominant manner, led to feminizing manifestations in both sexes, and was associated with the aberrant utilization of a novel transcript of the P450arom gene. C1 NICHHD, Unit Genet & Endocrinol, Sect Pediat Endocrinol, Dev Endocrinol Branch,NIH, Bethesda, MD 20892 USA. Univ Maryland, Dept Pharmacol, Baltimore, MD 21201 USA. St Vincents Hosp, Southview Med Grp, Birmingham, AL 35205 USA. Georgetown Univ, Dept Pediat, Washington, DC 20007 USA. RP Stratakis, CA (reprint author), NICHHD, Unit Genet & Endocrinol, Sect Pediat Endocrinol, Dev Endocrinol Branch,NIH, Bldg 10,Room 10N 262,10 Ctr Dr,MSC 1862, Bethesda, MD 20892 USA. EM stratakc@cc1.nichd.nih.gov FU NCI NIH HHS [CA-62483] NR 65 TC 90 Z9 91 U1 2 U2 8 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X EI 1945-7197 J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD APR PY 1998 VL 83 IS 4 BP 1348 EP 1357 DI 10.1210/jc.83.4.1348 PG 10 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA ZG029 UT WOS:000072957800056 PM 9543166 ER PT J AU Diehr, P Patrick, DL Bild, DE Burke, GL Williamson, JD AF Diehr, P Patrick, DL Bild, DE Burke, GL Williamson, JD TI Predicting future years of healthy life for older adults SO JOURNAL OF CLINICAL EPIDEMIOLOGY LA English DT Article DE aged; healthy life expectancy; QALY; clinical trials; survival; cost-benefit; health status; discounting ID SELF-RATED HEALTH; SUSPECTED MYOCARDIAL-INFARCTION; COST-EFFECTIVENESS; TRIAL; MORTALITY AB Cost-effectiveness studies often need to compare the cost of a program to the lifetime benefits of the program, but estimates of lifetime benefits are not routinely available, especially for older adults. We used data from two large longitudinal studies of older adults (ages 65-100) to estimate transition probabilities from one health state to another, and used those probabilities to estimate the mean additional years of healthy life that an older adult of specified age, sex, and health status would experience. We found, for example, that 65-year-old women in excellent health can expect 16.8 years of healthy life in the future, compared to only 8.5 years for women in poor health. We also provide estimates of discounted years of healthy life and future life expectancy. These estimates may be used to extend the effective length of the study period in cost-effectiveness studies, to examine the impact of chronic diseases or risk factors on year of healthy life, or to investigate the relationship of years of life to years of healthy life. Several applications are described. (C) 1998 Elsevier Science Inc. C1 Univ Washington, Dept Biostat, Seattle, WA 98195 USA. Univ Washington, Dept Hlth Serv, Seattle, WA 98195 USA. NHLBI, Div Epidemiol & Clin Applicat, Bethesda, MD 20892 USA. Wake Forest Univ, Bowman Gray Sch Med, Dept Publ Hlth Sci, Winston Salem, NC 27103 USA. Johns Hopkins Univ, Sch Med, Welch Ctr Prevent Epidemiol & Clin Res, Ctr Aging & Hlth, Baltimore, MD 21218 USA. RP Diehr, P (reprint author), Univ Washington, Dept Biostat, Box 357232, Seattle, WA 98195 USA. FU NHLBI NIH HHS [N01-HC-85079, N01-HC-85086] NR 27 TC 28 Z9 28 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0895-4356 J9 J CLIN EPIDEMIOL JI J. Clin. Epidemiol. PD APR PY 1998 VL 51 IS 4 BP 343 EP 353 DI 10.1016/S0895-4356(97)00298-9 PG 11 WC Health Care Sciences & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA ZD317 UT WOS:000072673100010 PM 9539891 ER PT J AU Tonjum, T Welty, DB Jantzen, E Small, PL AF Tonjum, T Welty, DB Jantzen, E Small, PL TI Differentiation of Mycobacterium ulcerans, M-marinum, and M-haemophilum: Mapping of their relationships to M-tuberculosis by fatty acid profile analysis, DNA-DNA hybridization, and 16S rRNA gene sequence analysis SO JOURNAL OF CLINICAL MICROBIOLOGY LA English DT Article ID RIBOSOMAL-RNA SEQUENCE; BURULI ULCER; INFECTION; IDENTIFICATION; RELATEDNESS; LEPRAE; HUMANS; TOXIN; BLOT AB Although Mycobacterium ulcerans, M. marinum, and M. haemophilum are closely related, their exact taxonomic placements have not been determined. We performed gas chromatography of fatty acids and alcohols, as well as DNA-DNA hybridization and 16S rRNA gene sequence analysis, to clarify their relationships to each other and to M. tuberculosis. M. ulcerans and M. marinum were most closely related to one another, and each displayed very strong genetic affinities to M. tuberculosis; they are actually the two mycobacterial species outside the M. tuberculosis complex most closely related to M. tuberculosis. M. haemophilum was more distinct from M. ulcerans and M. marinum, and it appeared to be as related to these two species as to RI tuberculosis. These results are important with regard to the development of diagnostic and epidemiological tools such as species specific DNA probes and PCR assays for M. ulcerans, M. marinum, and M. haemophilum. In addition, the finding that M. ulcerans and M. marinum are more closely related to M. tuberculosis than are other pathogenic mycobacterial species suggests that they may be evaluated as useful models for studying the pathogenesis of M. tuberculosis. M. marinum may be particularly useful in this regard since strains of this species grow much more rapidly than M. tuberculosis and yet can cause systemic disease in immunocompromised hosts. C1 Univ Oslo, Natl Hosp, Inst Microbiol, Sect Mol Microbiol, N-0027 Oslo, Norway. Natl Inst Publ Hlth, Dept Vaccinol, N-0403 Oslo, Norway. NIH, Rocky Mt Lab, Microscopy Sect, Hamilton, MT USA. RP Tonjum, T (reprint author), Univ Michigan, Sch Med, Dept Immunol & Microbiol, 5641 Med Sci Bldg 2, Ann Arbor, MI 48109 USA. NR 58 TC 121 Z9 122 U1 0 U2 3 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 USA SN 0095-1137 J9 J CLIN MICROBIOL JI J. Clin. Microbiol. PD APR PY 1998 VL 36 IS 4 BP 918 EP 925 PG 8 WC Microbiology SC Microbiology GA ZC324 UT WOS:000072565800012 PM 9542909 ER PT J AU McSharry, JM Lurain, NS Drusano, GL Landay, A Manischewitz, J Nokta, M O'Gorman, M Shapiro, HM Weinberg, A Reichelderfer, P Crumpacker, C AF McSharry, JM Lurain, NS Drusano, GL Landay, A Manischewitz, J Nokta, M O'Gorman, M Shapiro, HM Weinberg, A Reichelderfer, P Crumpacker, C TI Flow cytometric determination of ganciclovir susceptibilities of human cytomegalovirus clinical isolates SO JOURNAL OF CLINICAL MICROBIOLOGY LA English DT Article ID INFECTION; RESISTANCE; FOSCARNET AB A flow cytometric assay has been developed for the measurement of susceptibilities to ganciclovir of laboratory strains and clinical isolates of human cytomegalovirus (HCMV). The assay uses fluorochrome-labeled monoclonal antibodies to HCMV immediate-early and late antigens to identify HCMV-infected cells and flow cytometry to detect and quantitate the number of antigen-positive cells. By this assay, the 50 and 90% inhibitory concentrations (IC50 and IC90, respectively) of ganciclovir for the AD169 strain of HCMV were 1.7 and 9.2 mu M, respectively, and the IC50 for the ganciclovir-resistant D6/3/1 derivative of the AD169 strain was greater than 12 mu M. The ganciclovir susceptibilities of 17 HCMV clinical isolates were also dctermined by flow cytometric analysis of the effect of ganciclovir on late-antigen synthesis in HCMV-infected cells. The average IC50 of ganciclovir for drug-sensitive HCMV clinical isolates was 3.79 mu M (+/-2.60). The plaque-reduction assay for these clinical isolates yielded an average IC50 of 2.80 mu M (+/-1.46). Comparison of the results of the flow cytometry assays with those obtained from the plaque-reduction assays demonstrated acceptable bias and precision. Flow cytometric and plaque-reduction analysis of cells infected with ganciclovir-resistant clinical isolates failed to show a reduction in the percentage of late-antigen-positive cells or PFU, even at 96 mu M ganciclovir. The flow cytometric assay for determining ganciclovir susceptibility of HCMV is quantitative, and objective, and potentially automatable, and its results are reproducible among laboratories. C1 Albany Med Coll, Dept Microbiol Mol Genet & Immunol, Albany, NY 12208 USA. Rush Presbyterian St Lukes Med Ctr, Chicago, IL 60153 USA. US FDA, Bethesda, MD 20892 USA. Univ Texas, Med Branch, Galveston, TX 77555 USA. Northwestern Univ, Childrens Mem Hosp, Chicago, IL 60614 USA. Univ Colorado, Med Ctr, Denver, CO 80262 USA. NIH, Bethesda, MD 20892 USA. Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. RP McSharry, JM (reprint author), Albany Med Coll, Dept Microbiol Mol Genet & Immunol, A-68,47 New Scotland Ave, Albany, NY 12208 USA. EM jim_mcsharry@ccgateway.amc.edu FU NIAID NIH HHS [N01-AI35172, AI30883, AI32367] NR 22 TC 21 Z9 23 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 USA SN 0095-1137 J9 J CLIN MICROBIOL JI J. Clin. Microbiol. PD APR PY 1998 VL 36 IS 4 BP 958 EP 964 PG 7 WC Microbiology SC Microbiology GA ZC324 UT WOS:000072565800019 PM 9542916 ER PT J AU Heerema, NA Sather, HN Sensel, MG Kraft, P Nachman, JB Steinherz, PG Lange, BJ Hutchinson, RS Reaman, GH Trigg, ME Arthur, DC Gaynon, PS Uckun, FM AF Heerema, NA Sather, HN Sensel, MG Kraft, P Nachman, JB Steinherz, PG Lange, BJ Hutchinson, RS Reaman, GH Trigg, ME Arthur, DC Gaynon, PS Uckun, FM TI Frequency and clinical significance of cytogenetic abnormalities in pediatric T-lineage acute lymphoblastic leukemia: A report from the children's cancer group SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID ACUTE LYMPHOCYTIC-LEUKEMIA; CELL LEUKEMIA; CHROMOSOMAL TRANSLOCATIONS; PRESENTING FEATURES; INTENSIVE THERAPY; BIOLOGIC FEATURES; CHILDHOOD; GENE; RECEPTOR; PROGNOSIS AB Purpose: Nonrandom chromosomal translocations are frequently observed in pediatric patients with acute lymphoblastic leukemia (ALL). Specific translocations, such as t(4;11) and t(9;22), identify subgroups of B-lineage ALL patients who have an increased risk of treatment failure, The current study wets conducted to determine the prognostic significance of chromosomal translocations in T-lineage ALL patients, Materials and Methods: The study included 169 children with newly diagnosed T-lineage ALL enrolled between 1988 and 1995 on risk-adjusted protocols of the Children's Cancer Group (CCG) who had centrally reviewed cytogenetics data, Outcome analyses used standard life-table methods. Results: Presenting features for the current cohort were similar to those of concurrently enrolled patients for whom cytogenetic data were not accepted on central review, The majority of patients (80.5%) were assigned to CCG protocols for high-risk ALL and 86.4% had pseudodiploid (9 = 80) or normal diploid (9 = 66) karyotypes; modal chromosome number was not a significant prognostic factor, Overall, 103 of 169 (61%) patients had an abnormal karyotype, including 31 with del(6q), 29 with 14q11 breakpoints, 15 with del(9p), 11 with trisomy 8, nine with 11q23 breakpoints, nine with 14q32 translocations, and eight with 7q32-q36 breakpoints. Thirteen patients had the specific 14q11 translocation t(11;14)(p13;q11) and all were classified as poor risk, Patients with any of these translocations had outcomes similar to those with normal diploid karyotypes, Conclusion: Chromosomal abnormalities, including specific nonrandom translocations, were frequently observed in a large group of children with T-lineage ALL, but were not significant prognostic factors for this cohort. Thus, contemporary intensive treatment programs result in favorable outcomes for the majority of T-lineage ALL patients, regardless of karyotypic abnormalities, and such features do not identify patients at higher risk for relapse. (C) 1998 by American Society of Clinical Oncology. C1 Indiana Univ, Sch Med, Dept Med & Mol Genet, Indianapolis, IN 46202 USA. Univ So Calif, Dept Prevent Med, Los Angeles, CA 90089 USA. Childrens Canc Grp, Grp Operat Ctr, Arcadia, CA USA. Univ Chicago, Dept Pediat Hematol Oncol, Chicago, IL 60637 USA. Mem Sloan Kettering Canc Ctr, Dept Pediat, New York, NY 10021 USA. Childrens Hosp Philadelphia, Div Oncol, Philadelphia, PA 19104 USA. Univ Michigan, Dept Pediat Hematol Oncol, Ann Arbor, MI 48109 USA. George Washington Univ, Washington, DC USA. Childrens Natl Med Ctr, Dept Hematol Oncol, Washington, DC 20010 USA. Univ Iowa Hosp & Clin, Div Bone Marrow Transplantat, Iowa City, IA 52242 USA. NCI, Pathol Lab, Dept Clin Cytogenet, Bethesda, MD 20892 USA. Univ Wisconsin, Dept Pediat Hematol Oncol, Madison, WI USA. Wayne Hughes Inst, St Paul, MN USA. Childrens Canc Grp, Acute Lymphoblast Leukemia Biol Reference Lab, St Paul, MN USA. RP Heerema, NA (reprint author), Indiana Univ, Sch Med, Dept Med & Mol Genet, 975 W Walnut St, Indianapolis, IN 46202 USA. FU NCI NIH HHS [CA-13539, CA-60437] NR 53 TC 74 Z9 75 U1 0 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD APR PY 1998 VL 16 IS 4 BP 1270 EP 1278 PG 9 WC Oncology SC Oncology GA ZF220 UT WOS:000072875700006 PM 9552025 ER PT J AU Alexander, HR Bartlett, DL Libutti, SK Fraker, DL Moser, T Rosenberg, SA AF Alexander, HR Bartlett, DL Libutti, SK Fraker, DL Moser, T Rosenberg, SA TI Isolated hepatic perfusion with tumor necrosis factor and melphalan for unresectable cancers confined to the liver SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article; Proceedings Paper CT 50th Annual Cancer Symposium of the Society-of-Surgical-Oncology CY MAR 17-23, 1997 CL CHICAGO, ILLINOIS SP Soc Surg Oncol ID ISOLATED LIMB PERFUSION; PROSPECTIVE RANDOMIZED TRIAL; HEPATOCELLULAR-CARCINOMA; COLORECTAL-CARCINOMA; ARTERIAL INFUSION; INTERFERON-GAMMA; UVEAL MELANOMA; PLASMA-LEVELS; FACTOR-ALPHA; MITOMYCIN-C AB Purpose: To evaluate the efficacy and systemic and regional toxicities of hyperthermic isolated hepatic perfusion (IHP) using tumor necrosis factor (TNF) and melphalan for the treatment of unresectable primary or metastatic cancers confined to the liver. Patients and Methods: Thirty-four patients (18 men and 16 women; mean age, 49 years) underwent a 60-minute hyperthermic (39.5 degrees to 40.0 degrees C) IHP performed by laparotomy that used TNF 1.0 mg and melphalan 1.5 mg/kg. Perfusion inflow was through the gastroduodenal artery and outflow was from a cannula positioned in an isolated segment of retrohepatic inferior vena cava (IVC). Infrahepatic IVC and portal venous blood flow were shunted to the axillary vein using an external venoveno bypass circuit. Complete vascular isolation of the liver was confirmed by an I-131-labelled human serum albumin monitoring technique. Results: There was no operative mortality. Seventy-five percent of patients had reversible grade III or IV (National Cancer Institute Common Toxicity Criteria) hepatic toxicity with one treatment-related mortality (3%) because of hepatic venoocclusive disease. In 33 assessable patients, the overall response rate was 75% (complete response, one patient [3%]; partial response, 26 patients [72%]). With ct median potential follow-up of 15 months, the mean duration of response was 9 months (range, 2 to 30 months). Conclusion: IHP with TNF and melphalan results in significant regression of bulky hepatic cancers confined to the liver in the majority of patients. Based on these initial results, further refinement of this treatment technique is warranted; perhaps by the combination of IHP with other regional treatment strategies to provide long-term control of unresectable cancers confined to liver. (C) 1998 by American Society of Clinical Oncology. C1 NCI, Surg Branch, Surg Metab Sect, NIH, Bethesda, MD 20892 USA. RP Alexander, HR (reprint author), NCI, Surg Branch, Surg Metab Sect, NIH, Bldg 10,Room 2B17, Bethesda, MD 20892 USA. EM hra@pop.nci.nih.gov NR 65 TC 153 Z9 157 U1 0 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD APR PY 1998 VL 16 IS 4 BP 1479 EP 1489 PG 11 WC Oncology SC Oncology GA ZF220 UT WOS:000072875700036 PM 9552055 ER PT J AU Busatto, G Shiao, YH Parenti, AR Baffa, R Ruol, A Plebani, M Rugge, M AF Busatto, G Shiao, YH Parenti, AR Baffa, R Ruol, A Plebani, M Rugge, M TI p16/CDKN2 alterations and pRb expression in oesophageal squamous carcinoma SO JOURNAL OF CLINICAL PATHOLOGY-MOLECULAR PATHOLOGY LA English DT Article DE pRb; pl6/CDKN2; oesophageal cancer; oesophageal tumorigenesis ID TUMOR-SUPPRESSOR GENE; RETINOBLASTOMA-PROTEIN; ESOPHAGEAL CARCINOMAS; ALTERED EXPRESSION; CELL CARCINOMA; HUMAN CANCERS; CDKN2 GENE; RB PROTEIN; MUTATIONS; P16 AB Background-Upregulation of the cell cycle associated genes, p16/CDKN2 and the retinoblastoma susceptibility gene (Rb), is commonly seen during the proliferation of normal cells. An inverse relation between the expression of p16/CDKN2 and Rb has been noted in many tumours, but has not yet been determined in oesophageal squamous carcinoma. Aims-To investigate p16/CDKN2 genetic alterations and both the p16/CDKN2 and the Rb protein (pRb) immunophenotypes in oesophageal squamous carcinoma. Methods-Twenty primary oesophageal squamous carcinomas were examined for mutations in p16/CDKN2 by the polymerase chain reaction, single stranded conformational polymorphism, and DNA sequencing. Synthesis of p16/CDKN2 and pRb proteins was determined by immunohistochemistry in 19 specimens of formalin fixed, paraffin wax embedded tissues. Results-Mutations of p16/CDKN2 were not detected in exons 1 and 2. In only one case, G to C and C to T base changes were detected in a non-coding region of exon 3. Expression of p16/CDKN2 and Rb was observed in both normal and neoplastic areas of tissue sections, indicating neither consistent homozygous deletion nor consistent hypermethylation of the genes in tumours. Fourteen tumours showed an inverse expression of p16/CDKN2 and Rb. An increased percentage of cells that immunostained positively for p16/CDKN2 but not for pRb was observed in eight tumours, five of which had no detectable pRb, suggesting defective Rb expression in these oesophageal squamous carcinomas. Conclusions-These results indicate that p16/CDKN2 mutations occur infrequently in oesophageal squamous carcinoma. The alteration of the Rb gene is suggested as an important step in the development of these tumours. C1 Univ Padua, Ist Anat Patol, I-35100 Padua, Italy. ULSS, I-35100 Padua, Italy. NCI, Comparat Carcinogenesis Lab, Frederick Canc Res & Dev Ctr, NIH, Frederick, MD 21702 USA. Thomas Jefferson Univ, Jefferson Med Coll, Dept Urol, Philadelphia, PA 19107 USA. Univ Padua, Ist Patol Chirurg, I-35100 Padua, Italy. Azienda Osped Padova, Serv Med Lab, I-35100 Padua, Italy. RP Rugge, M (reprint author), Univ Padua, Dept Pathol, Via Aristide Gabelli 61, I-35121 Padua, Italy. RI Rugge, Massimo/K-7525-2016 NR 34 TC 15 Z9 16 U1 0 U2 0 PU BRITISH MED JOURNAL PUBL GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 1366-8714 J9 J CLIN PATHOL-MOL PA JI J. Clin. Pathol.-Mol. Pathol. PD APR PY 1998 VL 51 IS 2 BP 80 EP 84 PG 5 WC Pathology SC Pathology GA ZP892 UT WOS:000073799100004 ER PT J AU Hoffman-Goetz, L Dwiggins, S AF Hoffman-Goetz, L Dwiggins, S TI Teaching public health practitioners about health communication: The MPH curriculum experience SO JOURNAL OF COMMUNITY HEALTH LA English DT Article ID MEDIA CAMPAIGN; PROMOTION AB The dissemination of health information to the public often occurs through the mass media. Media strategies as a component of behavior change assume knowledge of communication theories and methods by public health practitioners. We surveyed the curricula of 52 accredited graduate programs leading to the Master's in Public Health (MPH) degree to assess their communication component. Graduate bulletins for admission year 1996 were examined for public health mission statement, goals and objectives of the MPH training program, and for course titles. Courses were identified as having a communication focus if the terms communication, information, marketing or media were used in the title. There were a total of 82 communication courses offered, with 65 courses in 26 Schools of Public Health (SPH), 13 courses in 18 Community Health and Preventive Medicine departments (CHPM), and 4 courses in 8 Community Health Education departments (CHE). The difference in mean number of health communication courses was significant by type of MPH program (p < 0.003) with SPH offering an average of 3 courses, CHPM departments offering an average pf 1 course, and CHE offering an average of 0.5 course. The distribution of communication courses ranged from 10 courses to 0 courses per program. Seven SPH offered 3 or more communication courses, whereas 5 SPH offered no health communication courses in the MPH curriculum. These data point to a shortcoming in the training of MPH students in health communication theory and skills as ascertained by course titles in graduate bulletins. C1 NCI, Int Canc Informat Ctr, Bethesda, MD 20892 USA. RP Hoffman-Goetz, L (reprint author), Univ Waterloo, Fac Appl Hlth Sci, Dept Hlth Studies & Gerontol, Waterloo, ON N2L 3G1, Canada. NR 14 TC 3 Z9 3 U1 0 U2 2 PU HUMAN SCI PRESS INC PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013-1578 USA SN 0094-5145 J9 J COMMUN HEALTH JI J. Community Health PD APR PY 1998 VL 23 IS 2 BP 127 EP 135 DI 10.1023/A:1018761407950 PG 9 WC Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA ZL528 UT WOS:000073442700004 PM 9591204 ER PT J AU Duman, JG Li, N Verleye, D Goetz, FW Wu, DW Andorfer, CA Benjamin, T Parmelee, DC AF Duman, JG Li, N Verleye, D Goetz, FW Wu, DW Andorfer, CA Benjamin, T Parmelee, DC TI Molecular characterization and sequencing of antifreeze proteins from larvae of the beetle Dendroides canadensis SO JOURNAL OF COMPARATIVE PHYSIOLOGY B-BIOCHEMICAL SYSTEMIC AND ENVIRONMENTAL PHYSIOLOGY LA English DT Article DE antifreeze proteins; thermal hysteresis proteins; Dendroides canadensis; insect cold tolerance; freeze avoidance ID THERMAL HYSTERESIS PROTEIN; TENEBRIO-MOLITOR; LITHOBIUS-FORFICATUS; FISH ANTIFREEZES; JUVENILE-HORMONE; ANTARCTIC FISH; FAT-BODY; ICE; PURIFICATION; GLYCOPROTEINS AB The deduced amino acid sequences of antifreeze proteins (AFPs) from larvae of the beetle Dendroides canadensis were determined from both complementary DNAs (cDNAs) and from peptide sequencing. These consisted of proteins with a 25-residue signal peptide and mature proteins 83 (Dendroides antifreeze protein; DAFP-1) or 84 (DAFP-2) amino acids in length which differed at only two positions. Peptide sequencing yielded sequences which overlapped exactly with those of the deduced cDNA sequences of DAFF-1 and DAFP-2, while the partial sequence of another AFP (DAFP-3) matched 21 of 28 residues. Seven 12- or 13-mer repeating units are present in these antifreeze proteins with a consensus sequence consisting of: Cys-Thr-X-3-Ser-X-5-X-6-Cys-X-8-X-9-Ala-X-11-Thr-X-13, where X-3 and X-11 tend toward charged residues, X-5 tends toward threonine or serine, X-6 toward asparagine or aspartate, X-9 toward asparagine or lysine, and X-13 toward alanine in the 13-mers. The most interesting feature of these proteins is that throughout the length of the mature antifreeze proteins every sixth residue is a cysteine. These sequences are not similar to any of the known fish AFPs, but they are similar to AFPs from the beetle Tenebrio molitor. C1 Univ Notre Dame, Dept Biol Sci, Notre Dame, IN 46556 USA. NCI, Div Basic Sci, Expt Carcinogenesis Lab, Bethesda, MD 20892 USA. RP Duman, JG (reprint author), Univ Notre Dame, Dept Biol Sci, Notre Dame, IN 46556 USA. EM john.g.duman.@nd.edu NR 49 TC 63 Z9 79 U1 2 U2 11 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0174-1578 J9 J COMP PHYSIOL B JI J. Comp. Physiol. B-Biochem. Syst. Environ. Physiol. PD APR PY 1998 VL 168 IS 3 BP 225 EP 232 DI 10.1007/s003600050140 PG 8 WC Physiology; Zoology SC Physiology; Zoology GA ZJ893 UT WOS:000073264300010 PM 9591363 ER PT J AU Helder, MN Karg, H Bervoets, TJM Vukicevic, S Burger, EH D'Souza, RN Woltgens, JHM Karsenty, G Bronckers, ALJJ AF Helder, MN Karg, H Bervoets, TJM Vukicevic, S Burger, EH D'Souza, RN Woltgens, JHM Karsenty, G Bronckers, ALJJ TI Bone morphogenetic protein-7 (osteogenic protein-1, OP-1) and tooth development SO JOURNAL OF DENTAL RESEARCH LA English DT Article DE bone morphogenetic protein-7; tooth formation; in situ hybridization; immunolocalization; gene knockout ID GROWTH-FACTOR-BETA; BABOON PAPIO-URSINUS; ODONTOBLAST DIFFERENTIATION; DENTIN FORMATION; GENE-EXPRESSION; I RECEPTORS; INDUCTION; CELLS; EMBRYOGENESIS; LOCALIZATION AB Bone morphogenetic proteins (BMPs) form a family of growth factors originally isolated from extracellular bone matrix that are capable of inducing bone formation ectopically. We studied the expression, tissue localization, and function of BMP-7 (OP-1) during tooth development in rodents. Patterns of BMP-7 gene expression and peptide distribution indicated that BMP-7 was present in dental epithelium during the dental lamina, bud, and cap stages. During the bell stage, BMP-7 mRNA expression and protein distribution shifted from dental epithelium toward the dental mesenchyme. With advancing differentiation of odontoblasts, BMP-7 protein staining in the dental papilla became restricted to the layer of fully functional odontoblasts in the process of depositing (pre)dentin. Secretory stage ameloblasts exhibited weak immunostaining for BMP-7. A restricted pattern of staining in ameloblasts became apparent in post-secretory stages of amelogenesis. Also, cells of the forming periodontal ligament were immunopositive. Histological analysis of tooth development in neonatal BMP-7-deficient mice did not reveal obvious changes compared with wild-type mice. We conclude that, in developing dental tissues, BMP-7 has distribution and expression patterns similar to those of other BMP members but is not an essential growth factor for tooth development, possibly because of functional redundancy with other BMP members or related growth factors. C1 Free Univ Amsterdam, ACTA, Dept Oral Cell Biol, NL-1081 BT Amsterdam, Netherlands. Md Anderson Canc Ctr, Dept Mol Genet, Houston, TX USA. NIH, Bone Res Branch, Bethesda, MD 20892 USA. Univ Texas, Dent Branch, Dept Anat Sci, Houston, TX USA. RP Bronckers, ALJJ (reprint author), Free Univ Amsterdam, ACTA, Dept Oral Cell Biol, NL-1081 BT Amsterdam, Netherlands. OI D'Souza, Rena/0000-0002-1505-5173 FU NIAMS NIH HHS [AR-41059]; NIDCR NIH HHS [DE-10617] NR 45 TC 61 Z9 69 U1 0 U2 2 PU AMER ASSOC DENTAL RESEARCH PI ALEXANDRIA PA 1619 DUKE ST, ALEXANDRIA, VA 22314 USA SN 0022-0345 J9 J DENT RES JI J. Dent. Res. PD APR PY 1998 VL 77 IS 4 BP 545 EP 554 PG 10 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA ZE543 UT WOS:000072803900007 PM 9539457 ER PT J AU Norman, JE Bailey, JJ Berson, AS Haisty, WK Levy, D Macfarlane, PM Rautaharju, PM AF Norman, JE Bailey, JJ Berson, AS Haisty, WK Levy, D Macfarlane, PM Rautaharju, PM TI NHLBI workshop on the utilization of ECG databases - Preservation and use of existing ECG databases and development of future resources SO JOURNAL OF ELECTROCARDIOLOGY LA English DT Article DE ECG databases; digital ECGs; longitudinal studies ID LEFT-VENTRICULAR HYPERTROPHY; HEART-RATE-VARIABILITY; POPULATION; RISK AB Baseline examinations and periodic reexaminations in longitudinal population studies, together with ongoing surveillance for morbidity and mortality, provide unique opportunities for seeking ways to enhance the value of the electrocardiogram (ECG) recorded with digital technology as an inexpensive and noninvasive tool for prognosis and diagnosis. Clinicians, epidemiologists, and engineers from industry, government, and academic medical centers gathered at a workshop sponsored by the National Heart, Lung, and Blood Institute (NHLBI) on June 11-12, 1997, to discuss the research potential of ECG databases, their preservation and accession, and standards for recording and storage. Databases considered were those acquired in ongoing and future NHLBI-funded studies and in clinical settings in which the ECG continues to provide valuable information for evaluation and treatment. The accessibility of existing databases, the quality of their data, and the availability of ancillary demo,oraphic and clinical information were major themes. Also discussed were appropriate statistical methodologies to be used with these data for developing and testing ECG algorithms. The workshop participants affirmed the value of these databases and urged the establishment of an ECG advisory and review group to (1) resolve technical and proprietary issues for the utilization of currently existing databases; (2) develop standards for recording, storage, and utilization of ECGs in future NHLBI-supported studies; (3) oversee the creation of a national ECG database resource, consisting of an archive of ECG databases from past and ongoing NHLBI-supported studies, and a registry of ECG databases that would eventually include digital ECGs from populations currently underrepresented in the demographic spectrum of the NHLBI databases. C1 NIH, Bethesda, MD 20892 USA. Wake Forest Univ, Bowman Gray Sch Med, Winston Salem, NC USA. Framingham Heart Dis Epidemiol Study, Framingham, MA USA. Royal Infirm, Glasgow G31 2ER, Lanark, Scotland. RP Norman, JE (reprint author), NHLBI, 2 Rockledge Ctr,Room 8148,6701 Rockledge Dr,MSC 7, Bethesda, MD 20892 USA. NR 10 TC 12 Z9 14 U1 0 U2 1 PU CHURCHILL LIVINGSTONE INC MEDICAL PUBLISHERS PI PHILADELPHIA PA CURTIS CENTER, INDEPENDENCE SQUARE WEST, PHILADELPHIA, PA 19106-3399 USA SN 0022-0736 J9 J ELECTROCARDIOL JI J. Electrocardiol. PD APR PY 1998 VL 31 IS 2 BP 83 EP 89 DI 10.1016/S0022-0736(98)90038-3 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA ZK151 UT WOS:000073290500002 PM 9588653 ER PT J AU Territo, PR Smits, AW AF Territo, PR Smits, AW TI Whole-body composition of Xenopus laevis larvae: Implications for lean body mass during development SO JOURNAL OF EXPERIMENTAL BIOLOGY LA English DT Article DE Xenopus laevis; development; growth; body composition; protein content; lipid content; nucleic acid content; lean body mass; energy balance ID SALMO-GAIRDNERI; PROTEIN; TEMPERATURE; METABOLISM; EMBRYOS; GROWTH; DNA AB Body composition in developing animals has been extensively investigated in fish larvae and bird embryos. However, no studies to date have attempted to determine whole-animal body composition or lean body mass (MLB) in developing amphibians. The present study investigates how body composition changes during development in Xenopus laevis and the potential implications of MLB for substrate turnover, energy stores, oxygen consumption and other physiological measures, Whole-animal composition was determined during development from eggs (NF stage 1) to 2 weeks post-feeding (NF 50-51), which represents two-thirds of the developmental period. Wet and dry masses were found to be highly correlated, with water content remaining constant at 93 % of wet mass. Whole-animal nucleic acid content was linearly correlated with both wet and dry masses, and declined relative to mass as development progressed. Similarly, total protein content was linearly correlated with wet and dry masses; however, total protein content increased with developmental stage. Amounts of individual neutral lipids were variable although, overall, total neutral lipid content declined progressively with development, The stoichiometric energy balance paralleled the changes seen in mass-specific Mo,, with the energy primarily from lipids fueling respiration up to NF 44-45. Quantification of total body composition revealed that lipid stores greatly influenced the calculations of M-LB and therefore had profound underestimating effects on the mass-specific expression of numerous physiological measures through development. C1 Univ Nevada, Dept Biol Sci, Las Vegas, NV 89154 USA. Quinnipiac Coll, Dept Biol Sci, Hamden, CT 06518 USA. RP Territo, PR (reprint author), NHLBI, Cardiac Energet Lab, NIH, Bldg 1,Room B3-07,9000 Rockville Pike, Bethesda, MD 20892 USA. NR 49 TC 4 Z9 4 U1 0 U2 6 PU COMPANY OF BIOLOGISTS LTD PI CAMBRIDGE PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE, CAMBS, ENGLAND CB4 4DL SN 0022-0949 J9 J EXP BIOL JI J. Exp. Biol. PD APR PY 1998 VL 201 IS 7 BP 1013 EP 1022 PG 10 WC Biology SC Life Sciences & Biomedicine - Other Topics GA ZL570 UT WOS:000073447600011 PM 9487105 ER PT J AU Ludert, JE Mason, BB Angel, J Tang, BZ Hoshino, Y Feng, NG Vo, PT Mackow, EM Ruggeri, FM Greenberg, HB AF Ludert, JE Mason, BB Angel, J Tang, BZ Hoshino, Y Feng, NG Vo, PT Mackow, EM Ruggeri, FM Greenberg, HB TI Identification of mutations in the rotavirus protein VP4 that alter sialic-acid-dependent infection SO JOURNAL OF GENERAL VIROLOGY LA English DT Article ID RHESUS ROTAVIRUS; BINDING; HEMAGGLUTININ; CELLS; NEUTRALIZATION; ENHANCEMENT; CULTURE; TRYPSIN; VIRUS AB To explore further the role of VP4 as the rotavirus cell attachment protein, VP7 monoreassortants derived from the sialic-acid-dependent simian strain RRV and from the sialic-acid-independent human strains D, DS-1 and ST-3 were tested for susceptibility of infectivity of neuraminidase-treated MA-104 cells, Infectivity of RRV x D VP7 and RRV x ST-3 VP7 monoreassortants decreased when sialic acid was removed from the cell surface, However, of three separate RRV x DS-1 VP7 monoreassortants tested, only one was sialic-acid-dependent, Sequence analysis showed that both sialic-acid-independent strains contained a single amino acid change, Lys to Arg, at position 187, In addition, sialic-acid-independent infectivity was seen in one of 14 RRV VP4 neutralization escape mutants tested, and this strain was found to have a Gly to Glu change at amino acid position 150. These results indicate that positions 150 and 187 of VP4 play an important role in early rotavirus-cell interactions. C1 Stanford Univ, Sch Med, Dept Med, Stanford, CA 94305 USA. Wyeth Lederle Vaccines & Pediat, Marietta, PA 17547 USA. NIAID, Bethesda, MD 20892 USA. Ist Super Sanita, Ultrastrutture Lab, Rome, Italy. Vet Affairs Med Ctr, Palo Alto, CA 94304 USA. RP Ludert, JE (reprint author), Inst Venezolano Invest Cient, Ctr Microbiol & Biol Celular, Apartado 21827, Caracas 1020A, Venezuela. RI Ruggeri, Franco/B-5707-2013 FU NIAID NIH HHS [R01 AI044917, R01AI21632]; NIDDK NIH HHS [DK38707] NR 27 TC 23 Z9 26 U1 0 U2 0 PU SOC GENERAL MICROBIOLOGY PI READING PA MARLBOROUGH HOUSE, BASINGSTOKE RD, SPENCERS WOODS, READING, BERKS, ENGLAND RG7 1AE SN 0022-1317 J9 J GEN VIROL JI J. Gen. Virol. PD APR PY 1998 VL 79 BP 725 EP 729 PN 4 PG 5 WC Biotechnology & Applied Microbiology; Virology SC Biotechnology & Applied Microbiology; Virology GA ZF357 UT WOS:000072889400011 PM 9568967 ER PT J AU Agostini, HT Ryschkewitsch, CF Stoner, GL AF Agostini, HT Ryschkewitsch, CF Stoner, GL TI JC virus Type 1 has multiple subtypes: three new complete genomes SO JOURNAL OF GENERAL VIROLOGY LA English DT Article ID PROGRESSIVE MULTIFOCAL LEUKOENCEPHALOPATHY; CEREBROSPINAL-FLUID; HUMAN BRAIN; TRANSMISSION; INDIVIDUALS; DISEASE; URINE AB The complete genomes of three new Type 1 strains of JC virus (JCV) from urine have been analysed. These were subtype 1A, subtype 1B and Type 4 as assigned from a short typing fragment in the VP1 gene. They differ from Mad1 (subtype 1A) by less than 1.0% of the DNA sequence. Based on its complete genome, the JCV Type 4 strain falls into a Type 1 subgroup. Type 4, with several Type 3-like sites in the short typing fragment, is a possible recombinant strain. The consensus of Type 1 DNA sequences is distinguished within the coding region from both Type 2 (strain GS/B) and five Type 3 (African and African American) strains at 64 sites. Most mutations are silent, but at 21 positions amino acid changes occur. Our findings define the subtypes of JCV Type 1 and support the validity of genotyping within the short VP1 fragment. C1 NINDS, Neurotoxicol Sect, NIH, Bethesda, MD 20892 USA. RP Stoner, GL (reprint author), NINDS, Neurotoxicol Sect, NIH, Bldg 36,Room 4A-29, Bethesda, MD 20892 USA. NR 18 TC 36 Z9 36 U1 0 U2 0 PU SOC GENERAL MICROBIOLOGY PI READING PA MARLBOROUGH HOUSE, BASINGSTOKE RD, SPENCERS WOODS, READING, BERKS, ENGLAND RG7 1AE SN 0022-1317 J9 J GEN VIROL JI J. Gen. Virol. PD APR PY 1998 VL 79 BP 801 EP 805 PN 4 PG 5 WC Biotechnology & Applied Microbiology; Virology SC Biotechnology & Applied Microbiology; Virology GA ZF357 UT WOS:000072889400019 PM 9568975 ER PT J AU Lietard, J Loreal, O Theret, N Campion, JP L'Helgoualc'h, A Turlin, B Ramee, MP Yamada, Y Clement, B AF Lietard, J Loreal, O Theret, N Campion, JP L'Helgoualc'h, A Turlin, B Ramee, MP Yamada, Y Clement, B TI Laminin isoforms in non-tumoral and tumoral human livers - Expression of alpha 1, alpha 2, beta 1, beta 2 and gamma 1 chain mRNA and an alpha chain homologous to the alpha 2 chain SO JOURNAL OF HEPATOLOGY LA English DT Article DE basement membrane; hepatic stellate cells; hepatocellular carcinoma; hepatoma cells; human liver; laminins; metastasis ID RAT-LIVER; DIFFERENTIAL EXPRESSION; MULTIDOMAIN PROTEIN; RECEPTOR LBP-32; A-CHAIN; CELLS; CLONING; HEPATOCYTES; LIPOCYTES; CULTURE AB Background/Aims: Laminins, the major non-collagenous basement membrane components, are involved in various biological processes. Laminin isoforms have never been characterized in human livers. The expression of five laminin mRNA was investigated in livers with or without cancer and in hepatoma cells and, by comparison, in both rat hepatoma and hepatic stellate cells. Methods: Laminin alpha 1, alpha 2, beta 1, beta 2 and gamma 1 mRNA was detected by northern blot and/or RT-PCR in livers without chronic disease (n=5), in both tumoral and non-tumoral areas of livers with hepatocellular carcinomas (n=13) or metastases (n=18), in human HBGC2 and rat Faza-567 hepatoma cell lines, and in 6-day-old rat hepatic stellate cell cultures. Results: Laminin alpha 1, alpha 2 and beta 1 mRNA were found in 25-33% and gamma 1 mRNA in 58% of the livers, the signal for laminin beta 2 mRNA being faint in all the samples. Laminin alpha 2, beta 1, beta 2 and gamma 1 mRNA were expressed in hepatoma and stellate cells. The laminin alpha 2 cDNA probe recognized a 3.5 kb mRNA different from the expected 9 kb mRNA. Using degenerated oligonucleotides, RT-PCR products from both rat hepatoma and stellate cells revealed 90% identity with the alpha 2 chain sequence. Antibodies against peptide deduced from the conserved C-terminal domain of both al and alpha 2 chains recognized polypeptides corresponding to the degradation products of alpha 2 chain in liver extracts and both media and cell layers from hepatoma and stellate cells. In addition, a Mr=130000 polypeptide was revealed by these antibodies in liver extracts and cell layers, which was consistent with the expected size deduced from the 3.5 kb mRNA. Conclusions: This first report on laminin isoforms in human livers indicates that laminin 1 (alpha 1-beta 1-gamma 1), 2 (alpha 2-beta 1-gamma 1), 3 (alpha 1-beta 2-gamma 1) and 4 (alpha 2-beta 2-gamma 1) mRNA and a polypeptide homologous to the alpha 2 isoform, which could correspond to a truncated form of this chain, are usually expressed in non-tumoral and/or tumoral livers. C1 Hop Pontchaillou, INSERM U456, Unite Detoxicat & Reparat Tissulaire, Rennes, France. Hop Pontchaillou, INSERM U49, Unite Rech Hepatol, Rennes, France. Hop Pontchaillou, Lab Anat Pathol B, Rennes, France. NIDR, Craniofacial Dev Biol & Regenerat Branch, Bethesda, MD 20892 USA. RP Clement, B (reprint author), Fac Med & Pharm, INSERM U456, 2 Ave Professeur Leon Bernard, F-35043 Rennes, France. EM bruno.clement@univ-rennes1.fr RI Loreal, Olivier/G-3366-2013; Theret, Nathalie/I-2871-2015; Clement, Bruno/E-5546-2016 NR 35 TC 6 Z9 7 U1 0 U2 2 PU MUNKSGAARD INT PUBL LTD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0168-8278 J9 J HEPATOL JI J. Hepatol. PD APR PY 1998 VL 28 IS 4 BP 691 EP 699 DI 10.1016/S0168-8278(98)80294-8 PG 9 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA ZE005 UT WOS:000072747400021 PM 9566839 ER PT J AU Henderson, CE Ownby, D Klebanoff, M Levine, RJ AF Henderson, CE Ownby, D Klebanoff, M Levine, RJ TI Stability of immunoglobulin E (IgE) in stored obstetric sera SO JOURNAL OF IMMUNOLOGICAL METHODS LA English DT Article DE allergen; immunoglobulin; pregnancy ID CHILDREN AB Objective: To determine the stability of immunoglobulin E levels in obstetric sera. Methods: AlaSTAT(R) and AlaTOP(R) (Diagnostic Products) were used to assay total and specific IgE levels in obstetric sera collected in Memphis, TN and Portland, OR. The samples were collected from the Collaborative Perinatal Project (CPP) between 1959 and 1965 and stored at -20 degrees C. The assay results were compared with IgE levels found in sera collected at the same locations for the Calcium for Pre-eclampsia Prevention Study (CPEP) and stored since 1992 at -70 degrees C, The samples were also assayed for cockroach (CR) and mouse urine specific IgE using the AlaSTAT(R) assay (Diagnostic Products:). Results: Total IgE and specific IgE to CR and mouse urine were detectable in older and recent samples. The median total IgE for the recent and older Portland samples was 26 IU/ml and 65 IU/ml, respectively. The median total IgE was identical (40 IU/ml) in the recent and older Memphis samples. Conclusion: Long-term storage does not diminish the ability to measure serum IgE, Levels of IEE in sera stored 32-37 years were equal to or greater than levels in sera stored for 5 years. (C) 1998 Elsevier Science B.V. All rights reserved. C1 NICHD, Div Epidemiol Stat & Prevent Res, NIH, Bethesda, MD USA. NIH, Off Res Womens Hlth, Bethesda, MD 20892 USA. Henry Ford Hosp, Div Allergy, Detroit, MI 48202 USA. Montefiore Med Ctr, Dept Obstet & Gynecol, Bronx, NY 10467 USA. RP Henderson, CE (reprint author), Bldg 6100,Room 7B,9000 Rockville Pike MSC 7510, Bethesda, MD 20892 USA. NR 10 TC 18 Z9 18 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0022-1759 J9 J IMMUNOL METHODS JI J. Immunol. Methods PD APR 1 PY 1998 VL 213 IS 1 BP 99 EP 101 DI 10.1016/S0022-1759(98)00014-3 PG 3 WC Biochemical Research Methods; Immunology SC Biochemistry & Molecular Biology; Immunology GA ZW373 UT WOS:000074404500008 PM 9671128 ER PT J AU Muller, JR Marcu, KB AF Muller, JR Marcu, KB TI Stimulation of murine B lymphocytes induces a DNA exonuclease whose activity on switch-mu DNA is specifically inhibited by other germ-line switch region RNAs SO JOURNAL OF IMMUNOLOGY LA English DT Article ID IMMUNOGLOBULIN HEAVY-CHAIN; EPSILON-TRANSCRIPTS; MESSENGER-RNA; CELLS; INDUCTION; INTERLEUKIN-4; EXPRESSION; GENES; LYMPHOMA; IGA AB The Ig heavy chain class switch in B lymphocytes involves a unique genetic recombination that fuses specific regions within the Ig locus and deletes intervening sequences, Here we describe a novel exonuclease activity in nuclear lysates of B cells in an in vitro assay, This activity was induced in B lymphocytes after treatment with either LPSs or CD40 ligand/anti-delta-dextran, both of which induce switch recombination, and considerably less activity was detected in untreated or anti-S-dextran-treated B cells, Con A-stimulated spleen cells, liver cells, or a number of cell lines, The exonuclease activity was dependent on divalent cations, and both 3' and 5' labels were efficiently removed from DNA substrates, The presence of RNase A, but not RNase H, inhibited exonucleolytic digestion, suggesting that a ribonucleoprotein is responsible for the exonucleolysis, The DNA digestion appears to be nonspecific, since DNA substrates with either switch-mu or unrelated sequence were hydrolyzed with comparable efficiency. Germ-line switch region transcripts (Ig gamma 1, Ig gamma 3, and Ig alpha) strongly inhibited the exonucleolysis of switch-mu DNA but not that of unrelated control DNA, while switch antisense RNA or tRNA were much less effective inhibitors. C1 SUNY Stony Brook, Dept Biochem & Cell Biol, Stony Brook, NY 11794 USA. NCI, Genet Lab, NIH, Bethesda, MD 20892 USA. RP Marcu, KB (reprint author), SUNY Stony Brook, Dept Biochem & Cell Biol, Life Sci Bldg,Room 324, Stony Brook, NY 11794 USA. FU NIGMS NIH HHS [GM26939] NR 29 TC 3 Z9 3 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD APR 1 PY 1998 VL 160 IS 7 BP 3337 EP 3341 PG 5 WC Immunology SC Immunology GA ZD573 UT WOS:000072700100033 PM 9531292 ER PT J AU Southwood, S Sidney, J Kondo, A del Guercio, MF Appella, E Hoffman, S Kubo, RT Chesnut, RW Grey, HM Sette, A AF Southwood, S Sidney, J Kondo, A del Guercio, MF Appella, E Hoffman, S Kubo, RT Chesnut, RW Grey, HM Sette, A TI Several common HLA-DR types share largely overlapping peptide binding repertoires SO JOURNAL OF IMMUNOLOGY LA English DT Article ID CLASS-II MOLECULES; COMPLEX-CLASS-II; MELANOMA ANTIGEN GP100; T-LYMPHOCYTE RESPONSE; BASIC-PROTEIN PEPTIDE; HEPATITIS-C VIRUS; IMMUNOGENIC PEPTIDES; VACCINE DEVELOPMENT; MULTIPLE-SCLEROSIS; CELL RESPONSES AB The peptide binding specificities of HLA-DRB1*0401, DRB1*0101, and DRB1*0701 have been analyzed by the use of large collections of synthetic peptides corresponding to naturally occurring sequences. The results demonstrated that nearly all peptides binding to these DR molecules bear a motif characterized by a large aromatic or hydrophobic residue in position 1 (Y, F, W, L, I, V, M) and a small, noncharged residue in position 6 (S, T, C, A, P, V, I, L, M). In addition, allele-specific secondary effects and secondary anchors were defined, and these parameters were utilized to derive allele-specific motifs and algorithms. By the combined use of such algorithms, peptides capable of degenerate DRB1*0101, DRB1*0401, and DRB1*0701 binding were identified. Additional experiments utilizing a panel of quantitative assays specific for nine additional common DR molecules identified a large set of DR molecules, which includes at least the DRB1*0101, DRB1*0401, DRB1*0701, DRB5*0101, DRB1*1501, DRB1*0901, and DRB1*1302 allelic products, characterized by overlapping peptide-binding repertoires. These results have implications for understanding the molecular interactions involved in peptide-DR binding, as well as the genetic and structural basis of MHC polymorphism. These results also have potential practical implications for the development of epitope-based prophylactic and therapeutic vaccines. C1 Epimmune Inc, San Diego, CA 92121 USA. Takara, Otsu, Shiga, Japan. NCI, NIH, Bethesda, MD 20892 USA. USN, Med Res Inst, Malaria Program, Bethesda, MD 20889 USA. Cytel Corp, San Diego, CA 92121 USA. La Jolla Inst Allergy & Immunol, San Diego, CA 92121 USA. RP Sette, A (reprint author), Epimmune Inc, 6555 Nancy Ridge Rd,Suite 200, San Diego, CA 92121 USA. EM asette@epimmune.com FU NIAID NIH HHS [N01-AI-45241] NR 94 TC 402 Z9 414 U1 0 U2 6 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD APR 1 PY 1998 VL 160 IS 7 BP 3363 EP 3373 PG 11 WC Immunology SC Immunology GA ZD573 UT WOS:000072700100037 PM 9531296 ER PT J AU Ludviksson, BR Sneller, MC Chua, KS Talar-Williams, C Langford, CA Ehrhardt, RO Fauci, AS Strober, W AF Ludviksson, BR Sneller, MC Chua, KS Talar-Williams, C Langford, CA Ehrhardt, RO Fauci, AS Strober, W TI Active wegener's granulomatosis is associated with HLA-DR+ CD4(+) T cells exhibiting an unbalanced Th1-type T cell cytokine pattern: Reversal with IL-10 SO JOURNAL OF IMMUNOLOGY LA English DT Article ID INTERCELLULAR-ADHESION MOLECULE-1; SYSTEMIC LUPUS-ERYTHEMATOSUS; E-SELECTIN; LEISHMANIA-MAJOR; FOLLOW-UP; ANTICYTOPLASMIC AUTOANTIBODIES; EXPRESS PROTEINASE-3; DISEASE-ACTIVITY; BINDING-PROTEIN; IFN-GAMMA AB Wegener's granulomatosis (WG) is a granulomatous vasculitis that affects the upper respiratory tract, lung, and kidney, Since T cells make up a significant proportion of cells infiltrating granulomatous lesions in WG, we investigated the proliferative response and cytokine profile of T cells from these patients, PBMCs were isolated from 12 patients with active WG, 7 patients with inactive disease, and 12 healthy normal donors, PBMCs from clinically active WG patients exhibited increased proliferation following stimulation with either PMA/ionomycin or anti-CD2 and anti-CD28, when compared with normal donors, In addition, these PBMCs exhibited increased secretion of IFN-gamma, but not of IL-4, IL-5, or IL-10, Furthermore, TNF-alpha production from PBMCs and CD4(+) T cells isolated from patients with WG was elevated, when compared with healthy donors, In further studies, we investigated the ability of WG patients' monocytes to produce IL-12 and showed that both inactive and active patients produced increased amounts of IL-12, Finally, the in vitro IFN-gamma production by WG PBMC is inhibited in a dose-dependent manner by exogenous IL-10, These data suggest that T cells from WG patients overproduce IFN-gamma and TNF-alpha, probably due to dysregulated IL-12 secretion, and that IL-10 may therefore have therapeutic implications for this disease. C1 NIAID, Mucosal Immun Sect, Clin Invest Lab, NIH, Bethesda, MD 20892 USA. NIAID, Immunoregulat Lab, NIH, Bethesda, MD 20892 USA. RP Ludviksson, BR (reprint author), NIAID, Mucosal Immun Sect, Clin Invest Lab, NIH, Bldg 10,Room 11N-238,10 Ctr Dr, Bethesda, MD 20892 USA. OI Ludviksson, Bjorn/0000-0002-6445-148X NR 56 TC 156 Z9 162 U1 1 U2 3 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD APR 1 PY 1998 VL 160 IS 7 BP 3602 EP 3609 PG 8 WC Immunology SC Immunology GA ZD573 UT WOS:000072700100065 PM 9531324 ER PT J AU Bukh, J Kim, JP Govindarajan, S Apgar, CL Foung, SKH Wages, J Yun, AJ Shapiro, M Emerson, SU Purcell, RH AF Bukh, J Kim, JP Govindarajan, S Apgar, CL Foung, SKH Wages, J Yun, AJ Shapiro, M Emerson, SU Purcell, RH TI Experimental infection of chimpanzees with hepatitis G virus and genetic analysis of the virus SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article; Proceedings Paper CT 16th Annual Meeting of the American-Society-for-Virology CY JUL, 1997 CL BOZEMAN, MONTANA SP Amer Soc Virol ID A-E-HEPATITIS; C VIRUS; MOLECULAR-CLONING; AMPLIFICATION; SEQUENCE; GENOMES; PATIENT; AGENT; PCR AB Hepatitis G virus (HGV) was transmitted to 2 chimpanzees by inoculation with human plasma containing similar to 10(8) genome equivalents (GE) of HGV, The infection was characterized by the late appearance (weeks 10 and 11 after inoculation [pi]) of viremia that persisted throughout the 120-week fellow-up, Serum HGV titer increased steadily until it plateaued at 10(6)-10(7) GE/mL, However, despite this relatively high titer, neither of the chimpanzees developed hepatitis, The sequence of the viral genome, recovered from each chimpanzee at week 77 pi, differed from that of the inoculum by 5 nt (2 aa) and 27 nt (2 aa). Two more chimpanzees were inoculated with a first-passage plasma pool. The chimpanzee inoculated with similar to 10(6.7) GE of HGV had viremia at week 1 pi. However, the viral titer increased with the same kinetics as observed in the first passage, The second chimpanzee inoculated with similar to 10(4.7) GE Of HGV had late appearance (week 7 pi) of viremia. C1 NIAID, Infect Dis Lab, Hepatitis Viruses Sect, NIH, Bethesda, MD 20892 USA. Bioqual Inc, Rockville, MD USA. Genelabs Technol Inc, Redwood City, CA USA. Univ So Calif, Rancho Los Amigos Hosp, Downey, CA 90242 USA. RP Bukh, J (reprint author), NIAID, Infect Dis Lab, Hepatitis Viruses Sect, NIH, Bldg 7,Room 201,7 Ctr Dr,MSC 0740, Bethesda, MD 20892 USA. FU NCI NIH HHS [CO-56000]; NIAID NIH HHS [AI-52705] NR 25 TC 44 Z9 46 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5801 S ELLIS AVENUE, CHICAGO, IL 60637 USA SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD APR PY 1998 VL 177 IS 4 BP 855 EP 862 PG 8 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA ZD747 UT WOS:000072719400004 PM 9534956 ER PT J AU Woody, MA Krakauer, T Ulrich, RG Stiles, BG AF Woody, MA Krakauer, T Ulrich, RG Stiles, BG TI Differential immune responses to staphylococcal Enterotoxin B mutations in a hydrophobic loop dominating the interface with major histocompatibility complex class II receptors SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article ID TOXIC-SHOCK-SYNDROME; T-CELLS; SELECTIVE EXPANSION; CYTOKINE RELEASE; HUMAN-DISEASE; SYNDROME TSS; SUPERANTIGEN; MICE; INTERFERON; ANTIBODIES AB Bacterial superantigens, such as staphylococcal enterotoxin B (SEB), can trigger acute pathologic effects in humans. A hydrophobic loop on the surface of SEB and other bacterial superantigens, centered around a conserved leucine (L45) residue, is essential for binding to class II major histocompatibility complex molecules. Single residue changes of wild type SEB, designated Q43P, F44P, or L45R, resulted in nonlethal proteins at a dose equivalent to 30 murine LD50 of SEB. Relative to SEB, the mutant proteins did not elevate serum concentrations of proinflammatory cytokines in mice and caused minimal proliferation of human lymphocytes. Anti-SEB titers of mice immunized with Q43P, F44P, L45R, or SEB were similar and protected 77%-100% of animals against a lethal SEB challenge. Levels of toxin-specific IgG1, IgG2a, IgG2b, and IgG3 in mice immunized with SEB, Q43P, or F44P were equivalent, but animals immunized with L45R had significantly elevated levels of IgG2a and IgG2b. Vaccines against staphylococcal superantigens should focus on this critical leucine residue. C1 USA, Med Res Inst Infect Dis, Dept Immunol & Mol Biol, Frederick, MD USA. RP Woody, MA (reprint author), NCI, Frederick Canc Res & Dev Ctr, Lab Leukocyte Biol, Bldg 567,Rm 210, Frederick, MD 21702 USA. NR 49 TC 20 Z9 21 U1 0 U2 1 PU UNIV CHICAGO PRESS PI CHICAGO PA 5801 S ELLIS AVENUE, CHICAGO, IL 60637 USA SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD APR PY 1998 VL 177 IS 4 BP 1013 EP 1022 PG 10 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA ZD747 UT WOS:000072719400024 PM 9534976 ER PT J AU Crowe, JE Gilmour, PS Murphy, BR Chanock, RM Duan, LX Pomerantz, RJ Pilkington, GR AF Crowe, JE Gilmour, PS Murphy, BR Chanock, RM Duan, LX Pomerantz, RJ Pilkington, GR TI Isolation of a second recombinant human respiratory syncytial virus monoclonal antibody fragment (Fab RSVF2-5) that exhibits therapeutic efficacy in vivo SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article ID F-GLYCOPROTEIN; COTTON RATS; RSV; PURIFICATION; LIBRARY AB A second human respiratory syncytial virus (RSV)-neutralizing monoclonal antibody was isolated and its binding site was identified. Fab F2-5 is a broadly reactive fusion (F) protein-specific recombinant Fab generated by antigen selection from a random combinatorial library displayed on the surface of filamentous phage. In an in vitro plaque-reduction test, the Fab RSVF2-5 neutralized the infectivity of a variety of field isolates representing viruses of both RSV subgroups A and B. The Fab recognized an antigenic determinant that differed from the only other human anti-F monoclonal antibody (RSV Fab 19) described thus far. A single dose of 4.0 mg of Fab RSVF2-5/kg of body weight administered by inhalation was sufficient to achieve a 2000-fold reduction in pulmonary virus titer in RSV-infected mice. The antigen-binding domain of Fab RSVF2-5 offers promise as part of a prophylactic regimen for RSV infection in humans. C1 NIAID, Infect Dis Lab, NIH, Bethesda, MD 20892 USA. Thomas Jefferson Univ, Jefferson Med Coll, Dept Med,Div Infect Dis, Ctr Human Virol,Dorrance Hamilton Labs, Philadelphia, PA 19107 USA. Intracel Corp, Issaquah, WA USA. RP Crowe, JE (reprint author), Vanderbilt Univ, Med Ctr, D-7235 MCN,1161 21st Ave S, Nashville, TN 37232 USA. RI Crowe, James/B-5549-2009 OI Crowe, James/0000-0002-0049-1079 NR 12 TC 20 Z9 21 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5801 S ELLIS AVENUE, CHICAGO, IL 60637 USA SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD APR PY 1998 VL 177 IS 4 BP 1073 EP 1076 PG 4 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA ZD747 UT WOS:000072719400033 PM 9534985 ER PT J AU Liapi, C Takahashi, N Raynaud, F Evain-Brion, D Anderson, WB AF Liapi, C Takahashi, N Raynaud, F Evain-Brion, D Anderson, WB TI Effects of [D-Ala(1)] peptide T-NH2 and HIV envelope glycoprotein gp120 on cyclic AMP dependent protein kinases in normal and psoriatic human fibroblasts SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Article DE cAMP dependent protein kinases; gp120 protein; peptide T; psoriasis ID HUMAN-IMMUNODEFICIENCY-VIRUS; IMPROVES PSORIASIS; RECEPTOR-BINDING; RETINOIC ACID; CELLS; ZIDOVUDINE; INFECTION; AIDS; MODULATION; LESIONS AB In addition to acquired immunodeficiency syndrome (AIDS), persons infected with human immunodeficiency virus often develop cutaneous manifestations, including severe psoriasis, In previous studies, we have established that psoriatic fibroblasts and erythrocytes obtained from psoriatic patients exhibit: decreased levels of cyclic adenosine monophosphate (cAMP) dependent protein kinase (PKA) activity and of 8-azido-[P-32]cAMP binding to the RI and Rn regulatory subunits of PKA, Because treatment of patients with peptide T (an octapeptide sequence found in the human immunodeficiency virus envelope glycoprotein gp120) has been observed to result in an improvement in the psoriatic condition, studies were initiated to determine if peptide T and gp120 protein treatment of normal and psoriatic human fibroblasts resulted in any changes in PKA. Exposure of psoriatic fibroblasts to peptide T resulted in a time (4 h to 6 d) and dose (10(-14)-10(-8) M) dependent increase in the levels of 8-azido-[P-32]cAMP binding to the RI and RII regulatory subunits of PKA, along with a corresponding increase in PKA activity. Peptide T exhibited a biphasic dose dependent response, with maximal effects on PKA noted at 10(-12) M peptide T. Treatment of normal human fibroblasts with peptide T did not result in any change in PKA levels, Conversely, treatment of normal human fibroblasts for 18 h with gp120 protein (10(-13) M) resulted in a significant decrease in the levels of 8-azido-[P-32]cAMP binding to RI and RII and in PKA activity. The presence of peptide T blocked this effect of the gp120 protein. These results indicate that peptide T and gp120 protein may inversely alter the intracellular levels of 8-azido-[P-32]cAMP binding to RI and RII, and of PKA activity in susceptible cells, These observed changes in the cyclic AMP-PKA signaling pathway, a biochemical marker for psoriasis, may offer some mechanistic insight into the noted beneficial effects of peptide T treatment, including an improvement in psoriatic lesions. C1 NCI, Cellular Oncol Lab, NIH, Bethesda, MD 20892 USA. NCI, Biol Chem Lab, NIH, Bethesda, MD 20892 USA. Univ Paris 05, Fac Sci Pharmaceut & Biol Paris, INSERM, Paris, France. RP Anderson, WB (reprint author), NCI, Cellular Oncol Lab, NIH, Bldg 37,Room 1E14, Bethesda, MD 20892 USA. NR 54 TC 8 Z9 11 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD APR PY 1998 VL 110 IS 4 BP 332 EP 337 DI 10.1046/j.1523-1747.1998.00149.x PG 6 WC Dermatology SC Dermatology GA ZD914 UT WOS:000072738200005 PM 9540970 ER PT J AU Hertl, M Karr, RW Amagai, M Katz, SI AF Hertl, M Karr, RW Amagai, M Katz, SI TI Heterogeneous MHC II restriction pattern of autoreactive desmoglein 3 specific T cell responses in pemphigus vulgaris patients and normals SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Article DE autoreactivity; desmosome; MHC II; T lymphocytes ID MAJOR HISTOCOMPATIBILITY COMPLEX; HLA-DR; JEWISH PATIENTS; SELF-PEPTIDES; BINDING; AUTOANTIBODIES; SUSCEPTIBILITY; MOLECULES; RESIDUES; DISEASE AB Pemphigus vulgaris is a life threatening bullous autoimmune disease of the skin mediated by autoantibodies against desmoglein 3 (Dsg3) on epidermal keratinocytes. Pemphigus vulgaris patients exhibit T cell responses against Dsg3 that may serve as a target to modulate the production of pathogenic autoantibodies. Healthy carriers of major histocompatibility complex class II alleles identical or similar to those that are highly prevalent in pemphigus vulgaris, namely DR beta 1*0402 and DR beta 1*1401, also mount T cell responses against Dsg3. We thus wanted to determine whether these prevalent major histocompatibility complex class II alleles restricted Dsg3 specific T cell responses. A CD4(+) T cell line ti om the DR beta 1*0402(+) patient PV9 was stimulated by Dsg3 with DR beta 1*0402(+) L cells as antigen-presenting cells, A CD4(+) T cell line and six CD4(+) T cell clones from the DR11/14(+) patient PV8, and six CD4(+) T cell clones from the DR11(+) healthy donor C6, required DR11/DQ beta 1*0301(+) peripheral blood mononuclear cells but not DR11(+) L cells as antigen-presenting cells and were strongly inhibited by anti-Dq antibodies, indicating that they were restricted by HLA-DQ beta 1*0301. A CD4(+) T cell line and three T cell clones from the DR11(+) healthy donor C11 were differentially stimulated by Dsg3 with L cells expressing one of several DR11 alleles, T cell recognition of Dsg3 was thus not only restricted by the pemphigus vulgaris associated DR beta 1*0402 allele, but also by several DR11 alleles, some of which are highly homologous to DR beta 1*-0402, and by HLA-DQ beta 1*0301. C1 NCI, Dermatol Branch, Bethesda, MD 20892 USA. GD Searle & Co, Dept Immunol, St Louis, MO USA. Keio Univ, Tokyo, Japan. RP Hertl, M (reprint author), RWTH Aachen, Univ Klinikum, Hautklin, Pauwelsstr 30, D-52072 Aachen, Germany. RI Amagai, Masayuki/K-5325-2013 OI Amagai, Masayuki/0000-0003-3314-7052 NR 23 TC 40 Z9 40 U1 0 U2 2 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD APR PY 1998 VL 110 IS 4 BP 388 EP 392 DI 10.1046/j.1523-1747.1998.00156.x PG 5 WC Dermatology SC Dermatology GA ZD914 UT WOS:000072738200015 PM 9540980 ER PT J AU Pack, S Turner, ML Zhuang, ZP Vortmeyer, AO Boni, R Skarulis, M Marx, SJ Darling, TN AF Pack, S Turner, ML Zhuang, ZP Vortmeyer, AO Boni, R Skarulis, M Marx, SJ Darling, TN TI Cutaneous tumors in patients with multiple endocrine neoplasia type 1 show allelic deletion of the MEN1 gene SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Article DE angiofibroma; collagenoma; FISH; lipoma; tumor suppressor gene ID TUBEROUS SCLEROSIS; HYBRIDIZATION; CELLS AB Multiple endocrine neoplasia type 1 (MEN1), the heritable tendency to develop tumors of the parathyroid, pituitary, and entero-pancreatic endocrine tissues, is the consequence of a germline mutation in the MEN1 gene, Endocrine tumors in these patients result when the mutant MEN1 allele is accompanied by loss of the normal MEN1 allele, Recently it was reported that MEN1 patients also exhibit several cutaneous tumors, including multiple angiofibromas, collagenomas, and lipomas. The purpose of this study was to examine skin lesions from patients with MEN1 for allelic loss of the MEN1 gene. Skin lesions from five patients with MEN1 were examined using fluorescence in situ hybridization, Six angiofibromas, three collagenomas, and one lipoma showed allelic deletion of the MEN1 gene, Allelic deletion was not observed in a melanocytic nevus or acrochordon from patients with MEN1. It was also not observed in an angiofibroma from a patient with tuberous sclerosis, These results suggest that loss of function of the wild-type MEN1 gene product plays a role in the development of angiofibromas, collagenomas, and lipomas in patients with MEN1. C1 NCI, Dermatol Branch, Bethesda, MD 20892 USA. NCI, Pathol Lab, Bethesda, MD 20892 USA. NIDDKD, Metab Dis Branch, NIH, Bethesda, MD 20892 USA. RP Darling, TN (reprint author), NCI, Dermatol Branch, Bldg 10,Room 12N238,10 Ctr Dr MSC 1908, Bethesda, MD 20892 USA. RI Pack, Svetlana/C-2020-2014; OI Darling, Thomas/0000-0002-5161-1974 NR 17 TC 56 Z9 56 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD APR PY 1998 VL 110 IS 4 BP 438 EP 440 DI 10.1046/j.1523-1747.1998.00140.x PG 3 WC Dermatology SC Dermatology GA ZD914 UT WOS:000072738200023 PM 9540988 ER PT J AU Chiang, C Litingtung, Y Bolinger, M Beachy, P Westphal, H Dlugosz, A AF Chiang, C Litingtung, Y Bolinger, M Beachy, P Westphal, H Dlugosz, A TI Targeted disruption of Sonic hedgehog reveals an essential role in hair follicle morphogenesis. SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract C1 Univ Michigan, Ann Arbor, MI 48109 USA. Johns Hopkins Univ, Baltimore, MD USA. NCI, Bethesda, MD 20892 USA. NICHD, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD APR PY 1998 VL 110 IS 4 BP 474 EP 474 PG 1 WC Dermatology SC Dermatology GA ZD914 UT WOS:000072738200038 ER PT J AU Darling, T Yee, C Bauer, JW Hintner, H Yancey, K AF Darling, T Yee, C Bauer, JW Hintner, H Yancey, K TI Genetic mosaicism demonstrated using laser capture microdissection: Partial correction of a germline mutation by a second mutation in COL17A1. SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract C1 Dept Dermatol, Salzburg, Austria. NIH, Bethesda, MD 20892 USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD APR PY 1998 VL 110 IS 4 BP 474 EP 474 PG 1 WC Dermatology SC Dermatology GA ZD914 UT WOS:000072738200043 ER PT J AU Day, P Lowy, D Schiller, J Roden, R AF Day, P Lowy, D Schiller, J Roden, R TI Papillomavirus assembly occurs at distinct nuclear structures, with viral DNA encapsidation being dependent upon a non-structural viral protein. SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract C1 NCI, Cellular Oncol Lab, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD APR PY 1998 VL 110 IS 4 BP 484 EP 484 PG 1 WC Dermatology SC Dermatology GA ZD914 UT WOS:000072738200103 ER PT J AU Asada, H Klaus-Kovtun, V Golding, H Katz, SI Blauvelt, A AF Asada, H Klaus-Kovtun, V Golding, H Katz, SI Blauvelt, A TI Human herpesvirus 6 (HHV6) infects dendritic cells (DC) and suppresses HIV replication in co-infected cultures. SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract C1 US FDA, Div Viral Prod, Bethesda, MD 20014 USA. NCI, Dermatol Branch, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD APR PY 1998 VL 110 IS 4 BP 485 EP 485 PG 1 WC Dermatology SC Dermatology GA ZD914 UT WOS:000072738200108 ER PT J AU Jakob, T Brown, MJ Udey, MC AF Jakob, T Brown, MJ Udey, MC TI Adherens junction-like contacts of skin-derived dendritic cells and keratinocytes in vitro. SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract C1 NCI, Dermatol Branch, Bethesda, MD 20892 USA. NCI, Expt Immunol Branch, Bethesda, MD 20892 USA. RI Jakob, Thilo/J-1621-2012 NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD APR PY 1998 VL 110 IS 4 BP 487 EP 487 PG 1 WC Dermatology SC Dermatology GA ZD914 UT WOS:000072738200116 ER PT J AU Kikuchi, A Franzoso, G Siebenlist, U Udey, MC AF Kikuchi, A Franzoso, G Siebenlist, U Udey, MC TI NF kappa B/REL protein expression and activity in a model of dendritic cell (DC) activation and maturation. SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract C1 NIAID, Immunoregulat Lab, Bethesda, MD 20892 USA. NCI, Dermatol Branch, Bethesda, MD 20892 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD APR PY 1998 VL 110 IS 4 BP 487 EP 487 PG 1 WC Dermatology SC Dermatology GA ZD914 UT WOS:000072738200120 ER PT J AU Yamada, N Katz, S AF Yamada, N Katz, S TI Induction of mature dendritic cells from a murine epidermal dendritic cell line (XS52) using interleukin-4. SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract C1 NCI, Dermatol Branch, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD APR PY 1998 VL 110 IS 4 BP 488 EP 488 PG 1 WC Dermatology SC Dermatology GA ZD914 UT WOS:000072738200123 ER PT J AU Steinert, PM Candi, E Tarcsa, E Kartasova, T Marekov, LN AF Steinert, PM Candi, E Tarcsa, E Kartasova, T Marekov, LN TI Small proline rich proteins serve to modulate the biomechanical properties of epithelial cornified cell envelopes. SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract C1 NIAMSD, Skin Biol Lab, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD APR PY 1998 VL 110 IS 4 BP 491 EP 491 PG 1 WC Dermatology SC Dermatology GA ZD914 UT WOS:000072738200144 ER PT J AU Hildesheim, J Foster, RA Chamberlin, M Vogel, JC AF Hildesheim, J Foster, RA Chamberlin, M Vogel, JC TI Characterization of the functional domains of the human POU transcription factor Skn-1a. SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract C1 NICHD, Heritable Disorders Branch, NIH, Bethesda, MD USA. NCI, Dermatol Branch, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD APR PY 1998 VL 110 IS 4 BP 493 EP 493 PG 1 WC Dermatology SC Dermatology GA ZD914 UT WOS:000072738200154 ER PT J AU Jang, SI Rossi, A Ceci, R Markova, NG Steinert, PM AF Jang, SI Rossi, A Ceci, R Markova, NG Steinert, PM TI Positive and negative elements control the expression of the human loricrin gene promoter. SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract C1 NIAMS, Skin Biol Lab, NIH, Bethesda, MD USA. Univ Roma Tor Vergata, Dept Expt Med, Rome, Italy. SUNY Stony Brook, Dept Oral Biol, Stony Brook, NY 11794 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD APR PY 1998 VL 110 IS 4 BP 493 EP 493 PG 1 WC Dermatology SC Dermatology GA ZD914 UT WOS:000072738200156 ER PT J AU Zoeteweij, JP Zaitseva, M Klaus-Koytun, V Golding, H Blauvelt, A AF Zoeteweij, JP Zaitseva, M Klaus-Koytun, V Golding, H Blauvelt, A TI Cytokines regulate the HIV co-receptor CXCR4 on cultured human Langerhans cells (cLC). SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract C1 US FDA, Div Viral Prod, Bethesda, MD 20014 USA. NCI, Dermatol Branch, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD APR PY 1998 VL 110 IS 4 BP 498 EP 498 PG 1 WC Dermatology SC Dermatology GA ZD914 UT WOS:000072738200187 ER PT J AU Budinger, L Borradori, L Yee, C Merk, HF Yancey, KB Hertl, M AF Budinger, L Borradori, L Yee, C Merk, HF Yancey, KB Hertl, M TI Autoreactive CD4+ T-cell responses to the extracellular domain (ECD) of bullous pemphigoid antigen 2 (BPAG2) in BP patients. SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract C1 Thomas Jefferson Univ, Jefferson Med Coll, Dept Dermatol & Cutaneous Biol, Philadelphia, PA 19107 USA. NCI, Chemoprevent Lab, Bethesda, MD 20892 USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD APR PY 1998 VL 110 IS 4 BP 499 EP 499 PG 1 WC Dermatology SC Dermatology GA ZD914 UT WOS:000072738200190 ER PT J AU Vindevoghel, L Kon, A Lechleider, RJ Roberts, AB Kouba, DJ Mauviel, A AF Vindevoghel, L Kon, A Lechleider, RJ Roberts, AB Kouba, DJ Mauviel, A TI Identification of the first human gene target for the TGF-beta/SMAD signaling pathway: COL7A1. SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract C1 Thomas Jefferson Univ, Jefferson Med Coll, Dept Dermatol & Cutaneous Biol, Philadelphia, PA 19107 USA. NCI, Chemoprevent Lab, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD APR PY 1998 VL 110 IS 4 BP 499 EP 499 PG 1 WC Dermatology SC Dermatology GA ZD914 UT WOS:000072738200188 ER PT J AU Walker, PS Jakob, T Krieg, AM Udey, MC Vogel, J AF Walker, PS Jakob, T Krieg, AM Udey, MC Vogel, J TI Activation of skin-derived dendritic cells by CpG-containing oligodeoxynucleotides (ODN) with immunostimulatory activity. SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract C1 NCI, Dermatol Branch, Bethesda, MD 20892 USA. Univ Iowa, Dept Med, Iowa City, IA 52242 USA. RI Jakob, Thilo/J-1621-2012 NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD APR PY 1998 VL 110 IS 4 BP 500 EP 500 PG 1 WC Dermatology SC Dermatology GA ZD914 UT WOS:000072738200195 ER PT J AU Bale, SJ Falk, RT Rogers, GR AF Bale, SJ Falk, RT Rogers, GR TI The basal cell nevus syndrome (Gorlin Syndrome): Genotype-phenotype correlation. SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract C1 NIAMS, Genet Studies Sect, Skin Biol Lab, NIH, Bethesda, MD USA. NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD APR PY 1998 VL 110 IS 4 BP 502 EP 502 PG 1 WC Dermatology SC Dermatology GA ZD914 UT WOS:000072738200211 ER PT J AU Schiffer, D Podsakoff, G Kurzmann, G Vogel, JC Hengge, UR AF Schiffer, D Podsakoff, G Kurzmann, G Vogel, JC Hengge, UR TI Adeno-associated virus (AAV) efficiently expresses transgenes in epidermis and hair follicles in vivo: Comparison with naked plasmid DNA. SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract C1 Univ Essen Gesamthsch, Dept Dermatol, Essen, Germany. Avigen, Alameda, CA USA. NCI, Dermatol Branch, NIH, Bethesda, MD 20892 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD APR PY 1998 VL 110 IS 4 BP 503 EP 503 PG 1 WC Dermatology SC Dermatology GA ZD914 UT WOS:000072738200212 ER PT J AU Marekov, LN Steinert, PM AF Marekov, LN Steinert, PM TI Complex ceramides are bound to involucrin, envoplakin, desmoplakin, periplakin and perhaps other proteins of human foreskin epidermal cornified cell envelopes. SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract C1 NIAMS, Skin Biol Lab, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD APR PY 1998 VL 110 IS 4 BP 505 EP 505 PG 1 WC Dermatology SC Dermatology GA ZD914 UT WOS:000072738200229 ER PT J AU Lazarova, Z Hsu, R Darling, TN Luke, MC Yee, C Yancey, KB AF Lazarova, Z Hsu, R Darling, TN Luke, MC Yee, C Yancey, KB TI Anti-epiligrin cicatricial pemphigoid (CP): Clinical and immunopathologic features of 21 patients. SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract C1 NCI, Dermatol Branch, DCS, NIH, Bethesda, MD 20892 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD APR PY 1998 VL 110 IS 4 BP 507 EP 507 PG 1 WC Dermatology SC Dermatology GA ZD914 UT WOS:000072738200236 ER PT J AU Masunaga, T Shimizu, H Yancey, KB Nishikawa, T AF Masunaga, T Shimizu, H Yancey, KB Nishikawa, T TI Altered ultrastructural localization of the C-terminus of bullous pemphigoid antigen 2 (BPAG2) in human skin lacking laminin 5. SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract C1 Keio Univ, Sch Med, Dept Dermatol, Tokyo, Japan. KOSE Corp, Basic Res Lab, Tokyo, Japan. NIH, Dermatol Branch, Bethesda, MD 20892 USA. NR 0 TC 5 Z9 5 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD APR PY 1998 VL 110 IS 4 BP 508 EP 508 PG 1 WC Dermatology SC Dermatology GA ZD914 UT WOS:000072738200244 ER PT J AU Vodegel, RM Kiss, M de Jong, MCJM Pas, HH Altmayer, A Molnar, K Husz, S van der Meer, JB Yancey, KB Jonkman, MF AF Vodegel, RM Kiss, M de Jong, MCJM Pas, HH Altmayer, A Molnar, K Husz, S van der Meer, JB Yancey, KB Jonkman, MF TI The use of skin substrates deficient in basement membrane (BM) molecules for the diagnosis of subepidermal autoimmune bullous diseases. SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract C1 Univ Groningen Hosp, Dept Dermatol, Groningen, Netherlands. Albert Szent Gyorgyi Med Univ, Dept Dermatol, H-6701 Szeged, Hungary. NIH, Dermatol Branch, Bethesda, MD 20892 USA. RI Jonkman, Marcel/H-4647-2011 NR 0 TC 0 Z9 0 U1 0 U2 1 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD APR PY 1998 VL 110 IS 4 BP 514 EP 514 PG 1 WC Dermatology SC Dermatology GA ZD914 UT WOS:000072738200281 ER PT J AU Yang, JM Steinert, PM Kim, SY AF Yang, JM Steinert, PM Kim, SY TI Transglutaminase 1 is induced by irritant treatment in normal human dermal fibroblasts. SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract C1 NIAMS, Skin Biol Lab, NIH, Bethesda, MD USA. Sungkyunkwan Univ, Dept Dermatol, Seoul, South Korea. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD APR PY 1998 VL 110 IS 4 BP 532 EP 532 PG 1 WC Dermatology SC Dermatology GA ZD914 UT WOS:000072738200391 ER PT J AU Kim, SY Lee, JH Steinert, PM AF Kim, SY Lee, JH Steinert, PM TI The differential expression of transglutaminases 1, 2, and 3 in normal human brain. SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract C1 NIAMS, Skin Biol Lab, NIH, Bethesda, MD USA. Chungnam Natl Univ, Dept Dermatol, Taejon, South Korea. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD APR PY 1998 VL 110 IS 4 BP 535 EP 535 PG 1 WC Dermatology SC Dermatology GA ZD914 UT WOS:000072738200408 ER PT J AU Morasso, MI Jang, SI Dlugosz, AA AF Morasso, MI Jang, SI Dlugosz, AA TI Control of terminal epidermal differentiation by D1x3. SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract C1 NIAMS, Skin Biol Lab, NIH, Bethesda, MD USA. Univ Michigan, Tumor Virus Biol Lab, Ann Arbor, MI 48109 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD APR PY 1998 VL 110 IS 4 BP 544 EP 544 PG 1 WC Dermatology SC Dermatology GA ZD914 UT WOS:000072738200463 ER PT J AU Traupe, H Vogel, M Hennies, HC Reis, A Steinert, P Raghunath, M AF Traupe, H Vogel, M Hennies, HC Reis, A Steinert, P Raghunath, M TI New approaches in the diagnosis of lamellar ichthyosis allowing selection of patients for gene analysis and future gene therapy. SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract C1 Univ Munster, Dept Dermatol, D-4400 Munster, Germany. Univ Hosp Rudolf Virchow, Inst Human Genet, Berlin, Germany. NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD APR PY 1998 VL 110 IS 4 BP 546 EP 546 PG 1 WC Dermatology SC Dermatology GA ZD914 UT WOS:000072738200473 ER PT J AU Matsunaga, N Sakai, C Hearing, VJ AF Matsunaga, N Sakai, C Hearing, VJ TI Expression of agouti signal protein in murine skin characterized by immunostaining with an agouti antibody (alpha PEP16). SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract C1 NIH, Cell Biol Lab, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD APR PY 1998 VL 110 IS 4 BP 569 EP 569 PG 1 WC Dermatology SC Dermatology GA ZD914 UT WOS:000072738200610 ER EF