FN Thomson Reuters Web of Science™ VR 1.0 PT J AU Jeong, JS Roualt, T Levine, R AF Jeong, JS Roualt, T Levine, R TI Identification of a heme sensing domain in iron-regulatory protein 2(IRP2) SO FREE RADICAL BIOLOGY AND MEDICINE LA English DT Meeting Abstract CT 11th Annual Meeting of the Society-for-Free-Radical-Biology-and-Medicine CY NOV 17-21, 2004 CL St Thomas, VI SP Soc Free Rad Biol & Med C1 NHLBI, Biochem Lab, NIH, Bethesda, MD 20892 USA. NICHD, Cell Biol & Metab Branch, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0891-5849 J9 FREE RADICAL BIO MED JI Free Radic. Biol. Med. PY 2004 VL 37 SU 1 BP S109 EP S109 PG 1 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 875YK UT WOS:000225458900334 ER PT J AU Kadiiska, M AF Kadiiska, M TI Biomarkers of oxidative stress. Are plasma antioxidants markers of ozone exposure? SO FREE RADICAL BIOLOGY AND MEDICINE LA English DT Meeting Abstract CT 11th Annual Meeting of the Society-for-Free-Radical-Biology-and-Medicine CY NOV 17-21, 2004 CL St Thomas, VI SP Soc Free Rad Biol & Med C1 NIEHS, NIH, Res Triangle Pk, NC 27709 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0891-5849 J9 FREE RADICAL BIO MED JI Free Radic. Biol. Med. PY 2004 VL 37 SU 1 BP S36 EP S36 PG 1 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 875YK UT WOS:000225458900089 ER PT J AU Kadiiska, M Nesnow, S Liu, J Waalkes, M Mason, R AF Kadiiska, M Nesnow, S Liu, J Waalkes, M Mason, R TI Arsenic methylation and oxidant injury by ESR in vivo and in vitro. SO FREE RADICAL BIOLOGY AND MEDICINE LA English DT Meeting Abstract CT 11th Annual Meeting of the Society-for-Free-Radical-Biology-and-Medicine CY NOV 17-21, 2004 CL St Thomas, VI SP Soc Free Rad Biol & Med C1 NIEHS, NIH, Res Triangle Pk, NC USA. NCI, Res Triangle Pk, NC USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0891-5849 J9 FREE RADICAL BIO MED JI Free Radic. Biol. Med. PY 2004 VL 37 SU 1 BP S21 EP S21 PG 1 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 875YK UT WOS:000225458900044 ER PT J AU Katori, T Thomas, DT Miranda, KM Lee, MJ Tocchetti, CG Mancardi, D Wink, DA Kass, DA Paolocci, N AF Katori, T Thomas, DT Miranda, KM Lee, MJ Tocchetti, CG Mancardi, D Wink, DA Kass, DA Paolocci, N TI Peroxynitrite vs. nitroxyl: Divergent effects on in vivo basal and beta-stimulated cardiac contractility SO FREE RADICAL BIOLOGY AND MEDICINE LA English DT Meeting Abstract CT 11th Annual Meeting of the Society-for-Free-Radical-Biology-and-Medicine CY NOV 17-21, 2004 CL St Thomas, VI SP Soc Free Rad Biol & Med C1 Johns Hopkins Univ, Baltimore, MD USA. NCI, Bethesda, MD 20892 USA. Univ Arizona, Tucson, AZ USA. RI Miranda, Katrina/B-7823-2009 NR 0 TC 0 Z9 0 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0891-5849 J9 FREE RADICAL BIO MED JI Free Radic. Biol. Med. PY 2004 VL 37 SU 1 BP S85 EP S85 PG 1 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 875YK UT WOS:000225458900254 ER PT J AU Mancardi, D Ridnour, L Donzelli, S Miranda, KM Thomas, D Katori, T Espey, M Paolocci, N Wink, D AF Mancardi, D Ridnour, L Donzelli, S Miranda, KM Thomas, D Katori, T Espey, M Paolocci, N Wink, D TI The nitroxyl donors Angeli's salt and IPA/NO afford equal cardiac early preconditioning-like effect that is independent of mitochondrial katp channel activation. SO FREE RADICAL BIOLOGY AND MEDICINE LA English DT Meeting Abstract CT 11th Annual Meeting of the Society-for-Free-Radical-Biology-and-Medicine CY NOV 17-21, 2004 CL St Thomas, VI SP Soc Free Rad Biol & Med C1 NCI, NIH, RBB, Bethesda, MD 20892 USA. Univ Arizona, Tucson, AZ USA. Johns Hopkins Med Inst, Baltimore, MD 21205 USA. RI Miranda, Katrina/B-7823-2009 NR 0 TC 2 Z9 2 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0891-5849 J9 FREE RADICAL BIO MED JI Free Radic. Biol. Med. PY 2004 VL 37 SU 1 BP S86 EP S87 PG 2 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 875YK UT WOS:000225458900260 ER PT J AU Mason, R Detweiler, C Lardinois, O Deterding, L de Montellano, PO Tomer, K AF Mason, R Detweiler, C Lardinois, O Deterding, L de Montellano, PO Tomer, K TI Identification of the myoglobin tyrosyl radical by immuno-spin trapping and its dimerization SO FREE RADICAL BIOLOGY AND MEDICINE LA English DT Meeting Abstract CT 11th Annual Meeting of the Society-for-Free-Radical-Biology-and-Medicine CY NOV 17-21, 2004 CL St Thomas, VI SP Soc Free Rad Biol & Med C1 NIEHS, NIH, Res Triangle Pk, NC 27709 USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0891-5849 J9 FREE RADICAL BIO MED JI Free Radic. Biol. Med. PY 2004 VL 37 SU 1 BP S21 EP S21 PG 1 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 875YK UT WOS:000225458900046 ER PT J AU Matsumoto, A Matsumoto, S Sowers, A Kuppusomy, P Mitchell, J Subramanian, S Krishna, M Matsumoto, KI AF Matsumoto, A Matsumoto, S Sowers, A Kuppusomy, P Mitchell, J Subramanian, S Krishna, M Matsumoto, KI TI Assessment of absolute oxygen concentration in normal mouse tissues using low field magnetic resonance spectroscopy SO FREE RADICAL BIOLOGY AND MEDICINE LA English DT Meeting Abstract CT 11th Annual Meeting of the Society-for-Free-Radical-Biology-and-Medicine CY NOV 17-21, 2004 CL St Thomas, VI SP Soc Free Rad Biol & Med C1 NCI, NIH, Bethesda, MD 20892 USA. Ohio State Univ, Daviv Heart & Lund Res Inst Med, Columbus, OH 43210 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0891-5849 J9 FREE RADICAL BIO MED JI Free Radic. Biol. Med. PY 2004 VL 37 SU 1 BP S184 EP S184 PG 1 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 875YK UT WOS:000225458900559 ER PT J AU Matsumoto, KI Bernardo, M Subramanian, S Choyke, P Mitchell, J Krishna, M Lizak, M AF Matsumoto, KI Bernardo, M Subramanian, S Choyke, P Mitchell, J Krishna, M Lizak, M TI Tissue oxygen level dependent magnetic resonance imaging (TOLD-MRI) SO FREE RADICAL BIOLOGY AND MEDICINE LA English DT Meeting Abstract CT 11th Annual Meeting of the Society-for-Free-Radical-Biology-and-Medicine CY NOV 17-21, 2004 CL St Thomas, VI SP Soc Free Rad Biol & Med C1 NCI, NIH, Bethesda, MD 20892 USA. NINDS, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 2 U2 8 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0891-5849 J9 FREE RADICAL BIO MED JI Free Radic. Biol. Med. PY 2004 VL 37 SU 1 BP S184 EP S185 PG 2 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 875YK UT WOS:000225458900560 ER PT J AU Nagababu, E Efrat, M Ramasamy, S Mayevsky, A Rifkind, J AF Nagababu, E Efrat, M Ramasamy, S Mayevsky, A Rifkind, J TI The vasoactivie nitric oxide species formed in the red cell during nitrite reduction in vivo SO FREE RADICAL BIOLOGY AND MEDICINE LA English DT Meeting Abstract CT 11th Annual Meeting of the Society-for-Free-Radical-Biology-and-Medicine CY NOV 17-21, 2004 CL St Thomas, VI SP Soc Free Rad Biol & Med C1 NIA, NIH, Baltimore, MD 21224 USA. Bar Ilan Univ, Ramat Gan, Israel. NR 0 TC 0 Z9 0 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0891-5849 J9 FREE RADICAL BIO MED JI Free Radic. Biol. Med. PY 2004 VL 37 SU 1 BP S87 EP S88 PG 2 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 875YK UT WOS:000225458900264 ER PT J AU Pluta, R Dejam, AA Gladwin, M Oldfiled, E AF Pluta, R Dejam, AA Gladwin, M Oldfiled, E TI Nitrite infusions prevent delayed cerebral vasospasm in a primate model of subarachnoid hemorrhage SO FREE RADICAL BIOLOGY AND MEDICINE LA English DT Meeting Abstract CT 11th Annual Meeting of the Society-for-Free-Radical-Biology-and-Medicine CY NOV 17-21, 2004 CL St Thomas, VI SP Soc Free Rad Biol & Med C1 NINDS, NIH, Bethesda, MD 20892 USA. NIDDK, NIH, Bethesda, MD 20892 USA. NHLBI, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0891-5849 J9 FREE RADICAL BIO MED JI Free Radic. Biol. Med. PY 2004 VL 37 SU 1 BP S81 EP S81 PG 1 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 875YK UT WOS:000225458900240 ER PT J AU Ramirez, DC Gomez-Mejiba, SE Mason, RP AF Ramirez, DC Gomez-Mejiba, SE Mason, RP TI Immuno-spin trapping detection of DNA-centered radicals: Development, validation and in vitro, ex vivo and in vivo applications SO FREE RADICAL BIOLOGY AND MEDICINE LA English DT Meeting Abstract CT 11th Annual Meeting of the Society-for-Free-Radical-Biology-and-Medicine CY NOV 17-21, 2004 CL St Thomas, VI SP Soc Free Rad Biol & Med C1 NIEHS, Lab Pharmacol & Chem, NIH, Res Triangle Pk, NC USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0891-5849 J9 FREE RADICAL BIO MED JI Free Radic. Biol. Med. PY 2004 VL 37 SU 1 BP S111 EP S111 PG 1 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 875YK UT WOS:000225458900342 ER PT J AU Ridnour, LA Isenberg, JS Espey, MG Thomas, DD Roberts, DD Wink, DA AF Ridnour, LA Isenberg, JS Espey, MG Thomas, DD Roberts, DD Wink, DA TI Nitric oxide modulation of molecular target proteins in human vascular endothelial cells SO FREE RADICAL BIOLOGY AND MEDICINE LA English DT Meeting Abstract CT 11th Annual Meeting of the Society-for-Free-Radical-Biology-and-Medicine CY NOV 17-21, 2004 CL St Thomas, VI SP Soc Free Rad Biol & Med C1 NCI, 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 PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0891-5849 J9 FREE RADICAL BIO MED JI Free Radic. Biol. Med. PY 2004 VL 37 SU 1 BP S70 EP S70 PG 1 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 875YK UT WOS:000225458900206 ER PT J AU Shiva, S Wang, XD Dejam, A Huang, Z Schechter, A Gladwin, M AF Shiva, S Wang, XD Dejam, A Huang, Z Schechter, A Gladwin, M TI Regulation of nitrite production from no in blood by plasma proteins SO FREE RADICAL BIOLOGY AND MEDICINE LA English DT Meeting Abstract CT 11th Annual Meeting of the Society-for-Free-Radical-Biology-and-Medicine CY NOV 17-21, 2004 CL St Thomas, VI SP Soc Free Rad Biol & Med C1 NHLBI, CV Branch, Vasc Therapeut Sect, CCMD, Bethesda, MD 20892 USA. NHLBI, Vasc Therapeut Sect, Biol Chem Lab, NIDDK, Bethesda, MD 20892 USA. NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0891-5849 J9 FREE RADICAL BIO MED JI Free Radic. Biol. Med. PY 2004 VL 37 SU 1 BP S100 EP S101 PG 2 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 875YK UT WOS:000225458900309 ER PT J AU Staib, F Robles, AL Varticovski, L Wang, XW Hussain, P Harris, CC AF Staib, F Robles, AL Varticovski, L Wang, XW Hussain, P Harris, CC TI P53-dependent gene expression profiles in response to different types of cellular stress SO FREE RADICAL BIOLOGY AND MEDICINE LA English DT Meeting Abstract CT 11th Annual Meeting of the Society-for-Free-Radical-Biology-and-Medicine CY NOV 17-21, 2004 CL St Thomas, VI SP Soc Free Rad Biol & Med C1 NCI, Human Carcinogenesis Lab, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0891-5849 J9 FREE RADICAL BIO MED JI Free Radic. Biol. Med. PY 2004 VL 37 SU 1 BP S72 EP S73 PG 2 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 875YK UT WOS:000225458900215 ER PT J AU Wang, XD Harris, A Huang, Z Dejam, A Shiva, S Gladwin, M AF Wang, XD Harris, A Huang, Z Dejam, A Shiva, S Gladwin, M TI Detection of S-nitrosated proteins in human red cells and plasma by biotinylation SO FREE RADICAL BIOLOGY AND MEDICINE LA English DT Meeting Abstract CT 11th Annual Meeting of the Society-for-Free-Radical-Biology-and-Medicine CY NOV 17-21, 2004 CL St Thomas, VI SP Soc Free Rad Biol & Med C1 NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0891-5849 J9 FREE RADICAL BIO MED JI Free Radic. Biol. Med. PY 2004 VL 37 SU 1 BP S97 EP S97 PG 1 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 875YK UT WOS:000225458900293 ER PT J AU Woods, C Tak, W Maki, A Kadiiska, M Connor, H Mason, R Cunningham, M Rusyn, I AF Woods, C Tak, W Maki, A Kadiiska, M Connor, H Mason, R Cunningham, M Rusyn, I TI The role of hepatocyte and Kupffer cell derived free radicals in peroxisome proliferator induced carcinogenesis SO FREE RADICAL BIOLOGY AND MEDICINE LA English DT Meeting Abstract CT 11th Annual Meeting of the Society-for-Free-Radical-Biology-and-Medicine CY NOV 17-21, 2004 CL St Thomas, VI SP Soc Free Rad Biol & Med C1 Univ N Carolina, Chapel Hill, NC USA. NIEHS, Res Triangle Pk, NC 27709 USA. RI Rusyn, Ivan/S-2426-2016 NR 0 TC 0 Z9 0 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0891-5849 J9 FREE RADICAL BIO MED JI Free Radic. Biol. Med. PY 2004 VL 37 SU 1 BP S29 EP S30 PG 2 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 875YK UT WOS:000225458900072 ER PT J AU Zhao, YF Chaiswing, L Velez, J Batinic-Haberle, I Colburn, N Oberley, T Clair, DS AF Zhao, YF Chaiswing, L Velez, J Batinic-Haberle, I Colburn, N Oberley, T Clair, DS TI P53 translocation to mitochondria precedes its nuclear translocation and targets mitochondrial oxidative defense protein - Manganese superoxide dismutase SO FREE RADICAL BIOLOGY AND MEDICINE LA English DT Meeting Abstract CT 11th Annual Meeting of the Society-for-Free-Radical-Biology-and-Medicine CY NOV 17-21, 2004 CL St Thomas, VI SP Soc Free Rad Biol & Med C1 Univ Kentucky, Lexington, KY 40506 USA. Univ Wisconsin, Madison, WI 53706 USA. Duke Univ, Durham, NC 27706 USA. NCI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 1 U2 2 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0891-5849 J9 FREE RADICAL BIO MED JI Free Radic. Biol. Med. PY 2004 VL 37 SU 1 BP S170 EP S170 PG 1 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 875YK UT WOS:000225458900518 ER PT J AU Zhong, Z Kai, Y Connor, HD Sun, JJ Mason, RP Lemasters, JJ AF Zhong, Z Kai, Y Connor, HD Sun, JJ Mason, RP Lemasters, JJ TI C-sinenesis polyphenols prevent decreased mitochondrial DNA in small-for-size liver grafts SO FREE RADICAL BIOLOGY AND MEDICINE LA English DT Meeting Abstract CT 11th Annual Meeting of the Society-for-Free-Radical-Biology-and-Medicine CY NOV 17-21, 2004 CL St Thomas, VI SP Soc Free Rad Biol & Med C1 Univ N Carolina, Chapel Hill, NC 27515 USA. NIEHS, NIH, Res Triangle Pk, NC USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0891-5849 J9 FREE RADICAL BIO MED JI Free Radic. Biol. Med. PY 2004 VL 37 SU 1 BP S45 EP S45 PG 1 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 875YK UT WOS:000225458900124 ER PT J AU Cassina, P Cassina, A Castellanos, R Pehar, M Mason, RP Barbeito, L Radi, R AF Cassina, P Cassina, A Castellanos, R Pehar, M Mason, RP Barbeito, L Radi, R TI Protein tyrosyl radical detection in ALS transgenic animal models by DMPO nitrone adduct immuno-spin trapping SO FREE RADICAL BIOLOGY AND MEDICINE LA English DT Meeting Abstract CT 12th Biennial Meeting of the Society-for-Free-Radical-Research-International CY MAY 05-09, 2004 CL Buenos Aires, ARGENTINA SP Soc Free Radical Res Int C1 Univ Republica, Dept Histol, Montevideo, Uruguay. Univ Republica, Dept Bioquim, Montevideo, Uruguay. Inst Clemente Estable, Dept Neurobiol Celular & Mol, Montevideo, Uruguay. NIEHS, Lab Pharmacol & Chem, Res Triangle Pk, NC USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0891-5849 J9 FREE RADICAL BIO MED JI Free Radic. Biol. Med. PY 2004 VL 36 SU 1 BP S153 EP S153 PG 1 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 819MY UT WOS:000221320200407 ER PT J AU Pessach, I Leto, T Shmelzer, Z Dinauer, M Levy, R AF Pessach, I Leto, T Shmelzer, Z Dinauer, M Levy, R TI NADPH oxidase-associated diaphorase activity supported by the C-terminal of gp91phox is independent of cytosolic phospholipase A2 SO FREE RADICAL BIOLOGY AND MEDICINE LA English DT Meeting Abstract CT 12th Biennial Meeting of the Society-for-Free-Radical-Research-International CY MAY 05-09, 2004 CL Buenos Aires, ARGENTINA SP Soc Free Radical Res Int C1 Ben Gurion Univ Negev, IL-84105 Beer Sheva, Israel. Soroka Med Ctr, IL-84101 Beer Sheva, Israel. NIH, Bethesda, MD 20892 USA. Indiana Univ, Indianapolis, IN 46204 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0891-5849 J9 FREE RADICAL BIO MED JI Free Radic. Biol. Med. PY 2004 VL 36 SU 1 BP S60 EP S60 PG 1 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 819MY UT WOS:000221320200150 ER PT J AU Rhee, SG AF Rhee, SG TI Regulation of intracellular level of hydrogen peroxide via peroxiredoxins (PRXS) SO FREE RADICAL BIOLOGY AND MEDICINE LA English DT Meeting Abstract CT 12th Biennial Meeting of the Society-for-Free-Radical-Research-International CY MAY 05-09, 2004 CL Buenos Aires, ARGENTINA SP Soc Free Radical Res Int C1 NHLBI, Lab Cell Signaling, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0891-5849 J9 FREE RADICAL BIO MED JI Free Radic. Biol. Med. PY 2004 VL 36 SU 1 BP S46 EP S46 PG 1 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 819MY UT WOS:000221320200112 ER PT J AU Vaz, S Detweiler, CD Mason, RP Augusto, O AF Vaz, S Detweiler, CD Mason, RP Augusto, O TI Immuno- and MS-detection of ribonuclease radicals produced from peroxynitrite and myeloperoxidase/H2O2/NO2-center dot SO FREE RADICAL BIOLOGY AND MEDICINE LA English DT Meeting Abstract CT 12th Biennial Meeting of the Society-for-Free-Radical-Research-International CY MAY 05-09, 2004 CL Buenos Aires, ARGENTINA SP Soc Free Radical Res Int C1 Univ Sao Paulo, Inst Quim, Dept Bioquim, BR-01498 Sao Paulo, Brazil. NIEHS, Lab Pharmacol & Chem, NIH, Res Triangle Pk, NC 27709 USA. RI Augusto, Ohara/D-3839-2012 OI Augusto, Ohara/0000-0002-7220-4286 NR 0 TC 0 Z9 0 U1 1 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0891-5849 J9 FREE RADICAL BIO MED JI Free Radic. Biol. Med. PY 2004 VL 36 SU 1 BP S72 EP S72 PG 1 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 819MY UT WOS:000221320200180 ER PT J AU Otto, M AF Otto, M TI Virulence factors of the coagulase-negative staphylococci SO FRONTIERS IN BIOSCIENCE LA English DT Review DE microbiology; bacteria; virulence; Staphylococcus; Staphylococcus epidermidis; coagulase-negative; biofilm; attachment; autolysin; exopolysaccharide; modulin; MSCRAMM; quorum sensing; agr; global regulation; resistance; Review ID POLYSACCHARIDE INTERCELLULAR ADHESIN; ACCESSORY GENE REGULATOR; FIBRONECTIN-BINDING PROTEIN; CATHETER-ASSOCIATED INFECTION; HUMAN-IMMUNODEFICIENCY-VIRUS; GONOCOCCAL GROWTH INHIBITOR; URINARY-TRACT INFECTION; GRAM-POSITIVE BACTERIA; SMALL-COLONY VARIANTS; AMINO-ACID-SEQUENCE AB Coagulase-negative staphylococci (CNS) have gained substantial interest as pathogens involved in nosocomial, particularly catheter-related infections. The pathogenic potential of CNS is mainly due to their capacity to form biofilms on indwelling medical devices. In a biofilm, the bacteria are protected against antibiotics and from attacks by the immune system. The factors contributing to biofilm formation are among the best-studied virulence factors of CNS and comprise factors involved in the adhesion to a catheter surface and in cell accumulation. CNS usually persist in the host in relative silence, but may cause sepsis, for which the recently found inflammatory peptides called phenol-soluble modulins are prime candidates. Many CNS also produce several lipases, proteases, and other exoenzymes, which possibly contribute to the persistence of CNS in the host and may degrade host tissue. We are also beginning to understand how regulators of virulence trigger the expression of virulence factors in CNS. A better conception of the mechanisms underlying the pathogenicity and the frequently encountered antibiotic resistance of CNS may help to develop novel, efficient antistaphylococcal therapeutics. C1 NIAID, Lab Human Bacterial Pathogenesis, Rocky Mt Labs, NIH, Hamilton, MT 59840 USA. RP Otto, M (reprint author), NIAID, Lab Human Bacterial Pathogenesis, Rocky Mt Labs, NIH, 903 S 4th St, Hamilton, MT 59840 USA. OI Otto, Michael/0000-0002-2222-4115 NR 200 TC 73 Z9 78 U1 1 U2 18 PU FRONTIERS IN BIOSCIENCE INC PI MANHASSET PA C/O NORTH SHORE UNIV HOSPITAL, BIOMEDICAL RESEARCH CENTER, 350 COMMUNITY DR, MANHASSET, NY 11030 USA SN 1093-9946 J9 FRONT BIOSCI JI Front. Biosci. PD JAN PY 2004 VL 9 BP 841 EP 863 DI 10.2741/1295 PG 23 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 746XW UT WOS:000186773800077 PM 14766414 ER PT J AU Qiang, YW Rudikoff, S AF Qiang, YW Rudikoff, S TI Wnt signaling in B and T lymphocytes SO FRONTIERS IN BIOSCIENCE LA English DT Article DE signal transduction; Wnt; beta catenin; B cell; T cell; review ID RHO-ASSOCIATED KINASE; BETA-CATENIN; GENE-EXPRESSION; TRANSCRIPTION FACTOR; CELL DEVELOPMENT; MULTIPLE-MYELOMA; HMG-BOX; ACTIN CYTOSKELETON; SECRETED PROTEINS; ALPHA-ENHANCER AB Wnt signaling has been shown to be critical for proper embryonic development as well as growth regulation of certain adult tissues. Defects in Wnt pathways have additionally been associated with a number of human cancers. However, it is only recently that a role for Wnts in the immune system has come to be appreciated. Wnts have now been shown to play significant roles in early stage development of both B and T lineage cells. Current studies suggest that proliferation and/or survival of these cells is associated with activation of the 'canonical' Wnt/beta-catenin pathway. Functional Wnt signaling appears to also occur in end stage B (plasma) cells where both the 'canonical' and the Wnt/RhoA pathways are activated. Herein, we review the current understanding of Wnt signaling in B and T cell development and the potential involvement of Wnt cascades in lymphoid neoplasia. C1 NCI, Mol & Cellular Biol Lab, NIH, Bethesda, MD 20892 USA. RP Rudikoff, S (reprint author), NCI, Mol & Cellular Biol Lab, NIH, Bldg 37,Rm 1D-18, Bethesda, MD 20892 USA. NR 80 TC 15 Z9 15 U1 0 U2 0 PU FRONTIERS IN BIOSCIENCE INC PI MANHASSET PA C/O NORTH SHORE UNIV HOSPITAL, BIOMEDICAL RESEARCH CENTER, 350 COMMUNITY DR, MANHASSET, NY 11030 USA SN 1093-9946 J9 FRONT BIOSCI JI Front. Biosci. PD JAN PY 2004 VL 9 BP 1000 EP 1010 DI 10.2741/1309 PG 11 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 746XW UT WOS:000186773800089 PM 14766426 ER PT J AU El-Omar, EM Rabkin, CS Chow, WH AF El-Omar, EM Rabkin, CS Chow, WH TI Increased risk of noncardia gastric cancer associated with proinflammatory cytokine gene polymorphisms - Reply SO GASTROENTEROLOGY LA English DT Letter ID INTERLEUKIN-1 POLYMORPHISMS; HELICOBACTER-PYLORI; ATROPHIC GASTRITIS; CARCINOMA C1 Univ Aberdeen, Dept Med & Therapeut, Aberdeen, Scotland. NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. RP El-Omar, EM (reprint author), Univ Aberdeen, Dept Med & Therapeut, Polwarth Bldg, Aberdeen, Scotland. NR 7 TC 0 Z9 0 U1 1 U2 6 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 JAN PY 2004 VL 126 IS 1 BP 383 EP 384 DI 10.1053/j.gastro.2003.11.033 PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 760GM UT WOS:000187803300058 ER PT S AU Agarwal, SK Burns, L Sukhodolets, KE Kennedy, PA Obungu, VH Hickman, AB Mullendore, ME Whitten, I Skarulis, MC Simonds, WF Mateo, C Crabtree, JS Scacheri, PC Ji, YM Novotny, EA Garrett-Beal, L Ward, JM Libutti, SK Alexander, HR Cerrato, A Parisi, MJ Santa Anna-A, S Oliver, B Chandrasekharappa, SC Collins, FS Spiegel, AM Marx, SJ AF Agarwal, SK Burns, L Sukhodolets, KE Kennedy, PA Obungu, VH Hickman, AB Mullendore, ME Whitten, I Skarulis, MC Simonds, WF Mateo, C Crabtree, JS Scacheri, PC Ji, YM Novotny, EA Garrett-Beal, L Ward, JM Libutti, SK Alexander, HR Cerrato, A Parisi, MJ Santa Anna-A, S Oliver, B Chandrasekharappa, SC Collins, FS Spiegel, AM Marx, SJ BE Wiedenmann, B Christofori, GM Hocker, M Reubi, JC TI Molecular pathology of the MEN1 gene SO GASTROENTEROPANCREATIC NEUROENDOCRINE TUMOR DISEASE: MOLECULAR AND CELL BIOLOGICAL ASPECTS SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article; Proceedings Paper CT 2nd International Conference on Molecular and Cell Biological Aspects of Gastroenteropancreatic Neuroendocrine Tumor Disease CY JUN 19-21, 2003 CL Berlin, GERMANY SP Novartis DE MEN1; menin; oncogene; tumor suppressor; AP1; insulinoma; gastrinoma; carcinoid; hyperparathyroidism ID MULTIPLE ENDOCRINE NEOPLASIA; FACTOR JUND; TYPE-1; TUMORS; SUPPRESSOR; MUTATIONS; TRANSCRIPTION; LOCALIZES; DELETION; PRODUCT AB Multiple endocrine neoplasia type 1 (MEND, among all syndromes, causes tumors in the highest number of tissue types. Most of the tumors are hormone producing (e.g., parathyroid, enteropancreatic endocrine, anterior pituitary) but some are not (e.g., angiofibroma). MEN1 tumors are multiple for organ type, for regions of a discontinuous organ, and for subregions of a continuous organ. Cancer contributes to late mortality; there is no effective prevention or cure for MEN1 cancers. Morbidities are more frequent from benign than malignant tumor, and both are indicators for screening. Onset age is usually earlier in a tumor type of MEN1 than of nonhereditary cases. Broad trends contrast with those in nonneoplastic excess of hormones (e.g., persistent hyperinsulinemic hypoglycemia of infancy). Most germline or somatic mutations in the MEN] gene predict truncation or absence of encoded menin. Similarly, 11q13 loss of heterozygosity in tumors predicts inactivation of the other MEN] copy. MEN] somatic mutation is prevalent in nonhereditary, MEN1-like tumor types. Compiled germline and somatic mutations show almost no genotype/phenotype relation. Normal menin is 67 kDa, widespread, and mainly nuclear. It may partner with junD, NF-kB, PEM, SMAD3, RPA2, FANCD2, NM23beta, nonmuscle myosin heavy chain II-A, GFAP, and/or vimentin. These partners have not clarified menin's pathways in normal or tumor tissues. Animal models have opened approaches to menin pathways. Local overexpression of menin in Drosophila reveals its interaction with the junkinase pathway. The Men1+/- mouse has robust MEN1; its most important difference from human MEN1 is marked hyperplasia of pancreatic islets, a tumor precursor stage. C1 NIDDK, NIH, Bethesda, MD 20892 USA. Natl Human Genome Res Inst, Natl Inst Hlth, Bethesda, MD 20892 USA. NCI, NIH, Bethesda, MD 20892 USA. Natl Inst Deafness & Commun Disorders, Natl Inst Hlth, Bethesda, MD 20892 USA. RP Marx, SJ (reprint author), NIDDK, NIH, Bldg 10,Room 9C-101, Bethesda, MD 20892 USA. EM stephenm@intra.niddk.nih.gov RI Agarwal, Sunita/D-1428-2016 OI Agarwal, Sunita/0000-0002-7557-3191 NR 38 TC 91 Z9 94 U1 0 U2 7 PU NEW YORK ACAD SCIENCES PI NEW YORK PA 2 EAST 63RD ST, NEW YORK, NY 10021 USA SN 0077-8923 BN 1-57331-492-7 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2004 VL 1014 BP 189 EP 198 DI 10.1196/annals.1294.020 PG 10 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Endocrinology & Metabolism; Gastroenterology & Hepatology; Multidisciplinary Sciences SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Endocrinology & Metabolism; Gastroenterology & Hepatology; Science & Technology - Other Topics GA BAE71 UT WOS:000221898100020 PM 15153434 ER PT J AU De Silanes, IL Fan, JS Galban, CJ Spencer, RG Becker, KG Gorospe, M AF De Silanes, IL Fan, JS Galban, CJ Spencer, RG Becker, KG Gorospe, M TI Global analysis of HuR-Regulated gene expression in colon cancer systems of reducing complexity SO GENE EXPRESSION LA English DT Article DE cDNA arrays; RNA-protein complexes; posttranscriptional regulation; mRNA turnover; cancer model ID RNA-BINDING-PROTEIN; FACTOR MESSENGER-RNA; RICH ELEMENT; CELL-LINES; CYCLOOXYGENASE-2 EXPRESSION; ELAV PROTEIN; STABILIZATION; MICROARRAY; STABILITY; GROWTH AB HuR, a protein that binds to target mRNAs and can enhance their stability and translation, is increasingly recognized as a pivotal regulator of gene expression during cell division and tumorigenesis. We sought to identify collections of HuR-regulated mRNAs in colon cancer cells by systematic, cDNA array-based assessment of gene expression in three systems of varying complexity. First, comparison of gene expression profiles among tumors with different HuR abundance revealed highly divergent gene expression patterns, and virtually no changes in previously reported HuR target mRNAs. Assessment of gene expression patterns in a second system of reduced complexity, cultured colon cancer cells expressing different HuR levels, rendered more conserved sets of HuR-regulated mRNAs. However, the definitive identification of direct HuR target mRNAs required a third system of still lower complexity, wherein HuR-RNA complexes immunoprecipitated from colon cancer cells were subject to cDNA array hybridization to elucidate the endogenous HuR-bound mRNAs. Comparison of the transcript sets identified in each system revealed a strikingly limited overlap in HuR-regulated mRNAs. The data derived from this systematic analysis of HuR-regulated genes highlight the value of low-complexity, biochemical characterization of protein-RNA interactions. More importantly, however, the data underscore the broad usefulness of integrated approaches comprising systems of low complexity (protein-nucleic acid) and high complexity (cells, tumors) to comprehensively elucidate the gene regulatory events that underlie biological processes. C1 NIA, LCMB, NIH, Intramural Res Program,Res Resources Branch, Baltimore, MD 21224 USA. NIA, Intramural Res Program, NIH, Cellular & Mol Biol Lab, Baltimore, MD 21224 USA. NIA, Intramural Res Program, NIH, Clin Invest Lab, Baltimore, MD 21224 USA. RP De Silanes, IL (reprint author), NIA, LCMB, NIH, Intramural Res Program,Res Resources Branch, Box 12,5600 Nathan Shock Dr, Baltimore, MD 21224 USA. EM myriam-gorospe@nih.gov OI Becker, Kevin/0000-0002-6794-6656 NR 44 TC 32 Z9 32 U1 0 U2 1 PU COGNIZANT COMMUNICATION CORP PI ELMSFORD PA 3 HARTSDALE ROAD, ELMSFORD, NY 10523-3701 USA SN 1052-2166 J9 GENE EXPRESSION JI Gene Expr. PY 2004 VL 12 IS 1 BP 49 EP 59 PG 11 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA 858MC UT WOS:000224194900005 ER PT J AU Stockton, P Gonzales, JJ Stem, NP Epstein, SA AF Stockton, P Gonzales, JJ Stem, NP Epstein, SA TI Treatment patterns and outcomes of depressed medically ill and non-medically ill patients in community psychiatric practice SO GENERAL HOSPITAL PSYCHIATRY LA English DT Article DE depression; physical comorbidity; community; psychiatry ID PRIMARY-CARE PATIENTS; RANDOMIZED CONTROLLED-TRIAL; MENTAL-DISORDERS; MAJOR DEPRESSION; MINOR DEPRESSION; ILLNESS; COMORBIDITY; INTERVENTION; DISABILITY; PREVALENCE AB The prevalence of depression among the medically ill, the recognition of depression in general medical practice, and the association between depression and medical illness have all been a focus for research in recent years. Less is known about the process and outcomes of depression care in the medically ill compared with the non-medically ill, but some studies suggest that those with concomitant physical illness have poorer outcomes. In a study of community psychiatric practice, a sample of 53 patients with no medical comorbidity (NMI) was compared with 50 patients, categorized by higher (HMI) or lower (LMI) levels of physical comorbidity, approximately 5 months after beginning treatment for a current episode of major depression. No differences were found in treatments received or in mental health outcomes between the three groups. The HMI group showed greater impairment in social and occupational functioning at baseline and significantly greater improvement in these variables at follow-up. Since medical comorbidity does not appear to adversely affect treatment decisions or outcomes in community psychiatric practice, depressed, physically ill patients should be encouraged to seek treatment, regardless of their medical condition or level of disability. (C) 2004 Elsevier Inc. All rights reserved. C1 Georgetown Univ, Med Ctr, Dept Psychiat, Washington, DC 20007 USA. NIMH, Div Serv & Intervent Res, Washington, DC USA. RP Stockton, P (reprint author), Georgetown Univ, Med Ctr, Dept Psychiat, Washington, DC 20007 USA. EM pstock01@georgetown.edu FU NIMH NIH HHS [MH55572] NR 34 TC 9 Z9 9 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0163-8343 J9 GEN HOSP PSYCHIAT JI Gen. Hosp. Psych. PD JAN-FEB PY 2004 VL 26 IS 1 BP 2 EP 8 DI 10.1016/S0163-8343(03)00094-X PG 7 WC Psychiatry SC Psychiatry GA 772AW UT WOS:000188819000002 PM 14757295 ER PT J AU Kasai, K Takahashi, M Osumi, N Sinnarajah, S Takeo, T Ikeda, H Kehrl, JH Itoh, G Arnheiter, H AF Kasai, K Takahashi, M Osumi, N Sinnarajah, S Takeo, T Ikeda, H Kehrl, JH Itoh, G Arnheiter, H TI The G12 family of heterotrimeric G proteins and Rho GTPase mediate Sonic hedgehog signalling SO GENES TO CELLS LA English DT Article ID CELL-SHAPE CHANGES; CUBITUS INTERRUPTUS; KINASE; PHOSPHORYLATION; PROLIFERATION; DROSOPHILA; ACTIVATION; PATHWAY; BINDING; GROWTH AB Sonic hedgehog (Shh) is a secreted morphogen crucial for cell fate decision, cellular proliferation, and patterning during vertebrate development. The intracellular Shh signalling is transduced by Smoothened (Smo), a seven-transmembrane spanning protein that belongs to the G-protein coupled receptor family. Among four families of Galpha subunits, Galphai has been thought to be responsible for transducing Shh signalling, while several lines of evidence indicated that other signalling pathways may be involved. We found that the G12 family of heterotrimeric G proteins and the small GTPase RhoA are involved in Shh/Smo-mediated cellular responses, including stimulation of target gene promoter and inhibition of neurite outgrowth of neuroblastoma cells. We also found that the G12/RhoA pathway is responsible for Smo-induced nuclear import of GLI3 which is thought to transduce Shh signals to nucleus. Furthermore, misexpression of a G12-specific GTPase-activating protein in rat neural tubes leads to pertubation of motor neurone and interneurone development, mimicking the effects of decreased Shh signalling. These results show that Shh signalling is mediated in part by activating G12 family coupled signalling pathways. The participation of RhoA, a pivotal molecular switch in many signal transduction pathways, may help explain how Shh can trigger a variety of cellular responses. C1 Aichi Med Univ, Sch Med, Dept Pathol, Aichi 4801195, Japan. NINDS, Mammalian Dev Sect, Lab Dev Neurogenet, NIH, Bethesda, MD 20892 USA. Tohoku Univ, Grad Sch Med, Dept Dev Neurobiol, Sendai, Miyagi 9808575, Japan. NIAID, B Cell Mol Biol Sect, Immunoregulat Lab, NIH, Bethesda, MD 20892 USA. RP Kasai, K (reprint author), Aichi Med Univ, Sch Med, Dept Pathol, Aichi 4801195, Japan. EM kkasai@amugw.aichi-med-u.ac.jp OI Kehrl, John/0000-0002-6526-159X NR 53 TC 48 Z9 48 U1 0 U2 1 PU BLACKWELL PUBLISHING LTD PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 1356-9597 J9 GENES CELLS JI Genes Cells PD JAN PY 2004 VL 9 IS 1 BP 49 EP 58 DI 10.1111/j.1365-2443.2004.00701.x PG 10 WC Cell Biology; Genetics & Heredity SC Cell Biology; Genetics & Heredity GA 764UL UT WOS:000188224400005 PM 14723707 ER PT S AU Patterson, GH Lippincott-Schwartz, J AF Patterson, GH Lippincott-Schwartz, J BE Brovko, AP Bornhop, DJ Raghavachari, R Achilefu, SI TI Development of a photoactivatable fluorescent protein from Aequorea victoria GFP SO GENETICALLY ENGINEERED AND OPTICAL PROBES FOR BIOMEDICAL APPLICATIONS II SE PROCEEDINGS OF THE SOCIETY OF PHOTO-OPTICAL INSTRUMENTATION ENGINEERS (SPIE) LA English DT Proceedings Paper CT Conference on Genetically Engineered and Optical Probes for Biomedical Applications II CY JAN 24-27, 2004 CL San Jose, CA SP SPIE DE photoactivation; fluorescence imaging; T203; green fluorescent protein ID EXCITED-STATE DYNAMICS; LIVING CELLS; STRUCTURAL BASIS; GENE-EXPRESSION; EXCITATION; MUTANTS; MARKER; RED; UV AB Photoactivation, the rapid conversion of photoactivatable molecules to a fluorescent state by intense irradiation, can be used to mark and monitor selected molecules within cells(1). We report a photoactivatable variant of the Aequorea victoria green fluorescent protein (GFP) based on a mutation at position 203 that upon intense irradiation with 413 nm light exhibits a stable 60-100 fluorescence increase under 488 nm excitation. The photoactivated form of this mutant named photoactivatable GFP (PA-GFP), is stable under a number of conditions. PA-GFP can be used to analyze protein dynamics in living cells, offering enormous potential for addressing outstanding questions in protein trafficking and turnover, organelle dynamics, and cell lineage patterns. C1 NICHHD, Cell Biol & Metab Branch, NIH, Bethesda, MD 20892 USA. RP Patterson, GH (reprint author), NICHHD, Cell Biol & Metab Branch, NIH, Bethesda, MD 20892 USA. NR 35 TC 1 Z9 1 U1 4 U2 12 PU SPIE-INT SOC OPTICAL ENGINEERING PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98227-0010 USA SN 0277-786X BN 0-8194-5237-8 J9 P SOC PHOTO-OPT INS PY 2004 VL 5329 BP 13 EP 22 DI 10.1117/12.532886 PG 10 WC Biochemical Research Methods; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA BAL96 UT WOS:000222771800002 ER PT J AU Marth, GT Czabarka, E Murvai, J Sherry, ST AF Marth, GT Czabarka, E Murvai, J Sherry, ST TI The allele frequency spectrum in genome-wide human variation data reveals signals of differential demographic history in three large world populations SO GENETICS LA English DT Article ID SINGLE-NUCLEOTIDE POLYMORPHISMS; DNA-SEQUENCE VARIATION; HUMAN-CHROMOSOME 22; LINKAGE DISEQUILIBRIUM; HAPLOTYPE BLOCKS; SNP MAP; MICROSATELLITE MUTATIONS; POSITIVE SELECTION; NATURAL-SELECTION; GENETIC-EVIDENCE AB We have studied a genome-wide set of single-nucleotide polymorphism (SNP) allele frequency measures for African-American, East Asian, and European-American samples. For this analysis we derived a simple, closed mathematical formulation for the spectrum of expected allele frequencies when the sampled populations have experienced nonstationary demographic histories. The direct calculation generates the spectrum orders of magnitude faster than coalescent simulations do and allows us to generate spectra for a large number of alternative histories on a multidimensional parameter grid. Model-fitting experiments rising this grid reveal significant population-specific differences among the demographic histories that best describe the observed allele frequency spectra. European and Asian spectra show a bottleneck-shaped history: a reduction of effective population size in the past followed by a recent phase of size recovery. In contrast, the African-American spectrum shows a history of moderate but interrupted population expansion. These differences are expected to have profound consequences for the design of medical association studies. The analytical methods developed for this study, i.e., a closed mathematical formulation for the allele frequency spectrum, correcting the ascertainment bias introduced by shallow SNP sampling, and dealing with variable sample sizes provide a general framework for the analysis of public variation data. C1 Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20894 USA. RP Marth, GT (reprint author), Boston Coll, Dept Biol, 140 Commonwelth Ave, Chestnut Hill, MA 02467 USA. EM marth@bc.edu NR 65 TC 186 Z9 188 U1 0 U2 11 PU GENETICS SOC AM PI BETHESDA PA 9650 ROCKVILLE AVE, BETHESDA, MD 20814 USA SN 0016-6731 J9 GENETICS JI Genetics PD JAN PY 2004 VL 166 IS 1 BP 351 EP 372 DI 10.1534/genetics.166.1.351 PG 22 WC Genetics & Heredity SC Genetics & Heredity GA 800IK UT WOS:000220021800031 PM 15020430 ER PT J AU McCutchan, TF Rathore, D Li, J AF McCutchan, TF Rathore, D Li, J TI Compensatory evolution in the human malaria parasite Plasmodium ovale SO GENETICS LA English DT Article ID RNA SECONDARY STRUCTURE; RIBOSOMAL-RNAS; SELECTION AB The fixation of neutral mutations in a population depends on the effective population size of the species, which can fluctuate dramatically within a few generations, the mutation rate, and the selection intensity associated with the individual mutations. We observe compensatory mutations and intermediate states in populations of the malaria parasite Plasmodium ovale. The appearance of compensatory mutations and intermediate states in P. ovale raises interesting questions about population structure that could have considerable impact on the control of the associated disease. C1 NIAID, Growth & Dev Sect, LMVR, NIH, Bethesda, MD 20892 USA. Virginia Polytech Inst & State Univ, Virginia Bioinformat Inst, Blacksburg, VA 24061 USA. RP McCutchan, TF (reprint author), NIAID, Growth & Dev Sect, LMVR, NIH, 4 Ctr Dr,Room 126, Bethesda, MD 20892 USA. EM tmccutchan@niaid.nih.gov NR 13 TC 5 Z9 5 U1 0 U2 1 PU GENETICS PI BALTIMORE PA 428 EAST PRESTON ST, BALTIMORE, MD 21202 USA SN 0016-6731 J9 GENETICS JI Genetics PD JAN PY 2004 VL 166 IS 1 BP 637 EP 640 DI 10.1534/genetics.166.1.637 PG 4 WC Genetics & Heredity SC Genetics & Heredity GA 800IK UT WOS:000220021800052 PM 15020451 ER PT J AU Acosta, MT Arcos-Burgos, M Muenke, M AF Acosta, MT Arcos-Burgos, M Muenke, M TI Attention deficit/hyperactivity disorder (ADHD): Complex phenotype, simple genotype? SO GENETICS IN MEDICINE LA English DT Review DE attention-deficit/hyperactivity disorder; autism; schizophrenia; epistasis; pleiotropy ID DEFICIT-HYPERACTIVITY DISORDER; DOPAMINE-D4 RECEPTOR GENE; CATECHOL-O-METHYLTRANSFERASE; SMITH-MAGENIS-SYNDROME; SUBSTANCE USE DISORDERS; DUPLICATION POLYMORPHISM UPSTREAM; HAPLOTYPE RELATIVE RISK; III REPEAT POLYMORPHISM; 22Q11 DELETION SYNDROME; TRAUMATIC BRAIN INJURY AB Complex genetic traits refer to those phenotypes not fitting patterns of Mendelian segregation and/or assortment but exhibiting a preferential familial clustering that cannot be explained by cultural or environmental causes. Attention-deficit/hyperactivity disorder (ADHD) is the most common neurodevelopmental disorder of childhood and probably the most controversial. ADHD has been considered a complex genetic trait based upon the absence of a clear-cut boundary between affected and unaffected status. Furthermore, its high comorbidity with other disorders strongly suggests complex epistatic or pleiotropic effects acting in common with the environmental influences. This implies that the same gene or genes is or are associated with different and concurrently occurring phenotypes. In this study, we will review clinical and epidemiological aspects related to the ADHD phenotype, which are considered either as categorical or continuous traits. We also will discuss genetic models underlying the complexity of this behavioral phenotype and the probable role of epistatic interactions between major genes contributing to the ADHD phenotype. C1 Childrens Natl Med Ctr, Dept Neurol, Washington, DC 20010 USA. NHGRI, Med Genet Branch, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. RP Acosta, MT (reprint author), Childrens Natl Med Ctr, Dept Neurol, 111 Michigan Ave NW, Washington, DC 20010 USA. NR 195 TC 34 Z9 36 U1 12 U2 20 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1098-3600 J9 GENET MED JI Genet. Med. PD JAN-FEB PY 2004 VL 6 IS 1 BP 1 EP 15 DI 10.1097/01.GIM.0000110413.07490.OB PG 15 WC Genetics & Heredity SC Genetics & Heredity GA 764PU UT WOS:000188215900001 PM 14726804 ER PT J AU Aravind, L Iyer, LM Leipe, DD Koonin, EV AF Aravind, L Iyer, LM Leipe, DD Koonin, EV TI A novel family of P-loop NTPases with an unusual phyletic distribution and transmembrane segments inserted within the NTPase domain SO GENOME BIOLOGY LA English DT Article ID MULTIPLE SEQUENCE ALIGNMENT; BINDING PROTEINS; MAXIMUM-LIKELIHOOD; ESCHERICHIA-COLI; GENOMIC CONTEXT; PSI-BLAST; EVOLUTION; ATPASES; MOTIF; CLASSIFICATION AB Background: Recent sequence-structure studies on P-loop-fold NTPases have substantially advanced the existing understanding of their evolution and functional diversity. These studies provide a framework for characterization of novel lineages within this fold and prediction of their functional properties. Results: Using sequence profile searches and homology-based structure prediction, we have identified a previously uncharacterized family of P-loop NTPases, which includes the neuronal membrane protein and receptor tyrosine kinase substrate Kidins220/ARMS, which is conserved in animals, the F-plasmid PifA protein involved in phage T7 exclusion, and several uncharacterized bacterial proteins. We refer to these ( predicted) NTPases as the KAP family, after Kidins220/ARMS and PifA. The KAP family NTPases are sporadically distributed across a wide phylogenetic range in bacteria but among the eukaryotes are represented only in animals. Many of the prokaryotic KAP NTPases are encoded in plasmids and tend to undergo disruption to form pseudogenes. A unique feature of all eukaryotic and certain bacterial KAP NTPases is the presence of two or four transmembrane helices inserted into the P-loop NTPase domain. These transmembrane helices anchor KAP NTPases in the membrane such that the P-loop domain is located on the intracellular side. We show that the KAP family belongs to the same major division of the P-loop NTPase fold with the AAA+, ABC, RecA-like, VirD4-like, PilT-like, and AP/NACHT-like NTPase classes. In addition to the KAP family, we identified another small family of predicted bacterial NTPases, with two transmembrane helices inserted into the P-loop domain. This family is not specifically related to the KAP NTPases, suggesting independent acquisition of the transmembrane helices. Conclusions: We predict that KAP family NTPases function principally in the NTP-dependent dynamics of protein complexes, especially those associated with the intracellular surface of cell membranes. Animal KAP NTPases, including Kidins220/ARMS, are likely to function as NTP-dependent regulators of the assembly of membrane-associated signaling complexes involved in neurite growth and development. One possible function of the prokaryotic KAP NTPases might be in the exclusion of selfish replicons, such as viruses, from the host cells. Phylogenetic analysis and phyletic patterns suggest that the common ancestor of the animals acquired a KAP NTPase via lateral transfer from bacteria. However, an earlier transfer into eukaryotes followed by multiple losses in several eukaryotic lineages cannot be ruled out. C1 NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20894 USA. RP Aravind, L (reprint author), NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20894 USA. EM aravind@ncbi.nlm.nih.gov NR 53 TC 22 Z9 22 U1 0 U2 2 PU BIOMED CENTRAL LTD PI LONDON PA MIDDLESEX HOUSE, 34-42 CLEVELAND ST, LONDON W1T 4LB, ENGLAND SN 1465-6914 J9 GENOME BIOL JI Genome Biol. PY 2004 VL 5 IS 5 AR R30 DI 10.1186/gb-2004-5-5-r30 PG 10 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA 821ZP UT WOS:000221502400007 PM 15128444 ER PT J AU Haugen, AC Kelley, R Collins, JB Tucker, CJ Deng, CC Afshari, CA Brown, JM Ideker, T Van Houten, B AF Haugen, AC Kelley, R Collins, JB Tucker, CJ Deng, CC Afshari, CA Brown, JM Ideker, T Van Houten, B TI Integrating phenotypic and expression profiles to map arsenic-response networks SO GENOME BIOLOGY LA English DT Article ID ACUTE PROMYELOCYTIC LEUKEMIA; SACCHAROMYCES-CEREVISIAE REQUIRES; OXIDATIVE DNA-DAMAGE; TRANSCRIPTION FACTORS; REGULATORY NETWORKS; SHIKIMATE PATHWAY; CONFERRING RESISTANCE; ENVIRONMENTAL-CHANGES; MULTIDRUG-RESISTANCE; TRIOXIDE AS2O3 AB Background: Arsenic is a nonmutagenic carcinogen affecting millions of people. The cellular impact of this metalloid in Saccharomyces cerevisiae was determined by profiling global gene expression and sensitivity phenotypes. These data were then mapped to a metabolic network composed of all known biochemical reactions in yeast, as well as the yeast network of 20,985 protein-protein/protein-DNA interactions. Results: While the expression data unveiled no significant nodes in the metabolic network, the regulatory network revealed several important nodes as centers of arsenic-induced activity. The highest-scoring proteins included Fhl1, Msn2, Msn4, Yap1, Cad1 ( Yap2), Pre1, Hsf1 and Met31. Contrary to the gene-expression analyses, the phenotypic-profiling data mapped to the metabolic network. The two significant metabolic networks unveiled were shikimate, and serine, threonine and glutamate biosynthesis. We also carried out transcriptional profiling of specific deletion strains, confirming that the transcription factors Yap1, Arr1 (Yap8), and Rpn4 strongly mediate the cell's adaptation to arsenic-induced stress but that Cad1 has negligible impact. Conclusions: By integrating phenotypic and transcriptional profiling and mapping the data onto the metabolic and regulatory networks, we have shown that arsenic is likely to channel sulfur into glutathione for detoxification, leads to indirect oxidative stress by depleting glutathione pools, and alters protein turnover via arsenation of sulfhydryl groups on proteins. Furthermore, we show that phenotypically sensitive pathways are upstream of differentially expressed ones, indicating that transcriptional and phenotypic profiling implicate distinct, but related, pathways. C1 Univ Calif San Diego, Dept Bioengn, La Jolla, CA 92093 USA. NIEHS, Mol Genet Lab, NIH, Res Triangle Pk, NC 27709 USA. NIEHS, Natl Ctr Toxicogenom, Microarray Ctr, NIH, Res Triangle Pk, NC 27709 USA. Stanford Univ, Sch Med, Dept Radiat Oncol, Stanford, CA 94305 USA. RP Ideker, T (reprint author), Univ Calif San Diego, Dept Bioengn, 9500 Gilman Dr, La Jolla, CA 92093 USA. EM Trey@bioeng.ucsd.edu; Vanhout1@niehs.nih.gov FU NCI NIH HHS [CA 67166, P01 CA067166] NR 78 TC 116 Z9 120 U1 1 U2 4 PU BIOMED CENTRAL LTD PI LONDON PA MIDDLESEX HOUSE, 34-42 CLEVELAND ST, LONDON W1T 4LB, ENGLAND SN 1465-6914 J9 GENOME BIOL JI Genome Biol. PY 2004 VL 5 IS 12 AR R95 DI 10.1186/gb-2004-5-12-r95 PG 18 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA 875YY UT WOS:000225460600007 PM 15575969 ER PT J AU Johnston, R Wang, B Nuttall, R Doctolero, M Edwards, P Lu, JN Vainer, M Yue, HB Wang, XH Minor, J Chan, C Lash, A Goralski, T Parisi, M Oliver, B Eastman, S AF Johnston, R Wang, B Nuttall, R Doctolero, M Edwards, P Lu, JN Vainer, M Yue, HB Wang, XH Minor, J Chan, C Lash, A Goralski, T Parisi, M Oliver, B Eastman, S TI FlyGEM, a full transcriptome array platform for the Drosophila community SO GENOME BIOLOGY LA English DT Article ID GENE-EXPRESSION; MELANOGASTER; MICROARRAYS; SEQUENCE; DESIGN; SEX AB We have constructed a DNA microarray to monitor expression of predicted genes in Drosophila. By using homotypic hybridizations, we show that the array performs reproducibly, that dye effects are minimal, and that array results agree with systematic northern blotting. The array gene list has been extensively annotated and linked-out to other databases. Incyte and the NIH have made the platform available to the community via academic microarray facilities selected by an NIH committee. C1 NIDDKD, Cellular & Dev Biol Lab, NIH, Bethesda, MD 20892 USA. Incyte Genom, Palo Alto, CA 94304 USA. Natl Lib Med, Natl Ctr Biotechnol Informat, Gene Express Omnibus, Bethesda, MD 20892 USA. RP Oliver, B (reprint author), NIDDKD, Cellular & Dev Biol Lab, NIH, 50 South Dr,Room 3339, Bethesda, MD 20892 USA. EM oliver@helix.nih.gov FU NIDDK NIH HHS [Z01 DK015600-10] NR 24 TC 7 Z9 7 U1 0 U2 0 PU BIOMED CENTRAL LTD PI LONDON PA MIDDLESEX HOUSE, 34-42 CLEVELAND ST, LONDON W1T 4LB, ENGLAND SN 1465-6914 J9 GENOME BIOL JI Genome Biol. PY 2004 VL 5 IS 3 AR R19 DI 10.1186/gb-2004-5-3-r19 PG 11 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA 780AC UT WOS:000189345300013 PM 15003122 ER PT J AU Koonin, EV Fedorova, ND Jackson, JD Jacobs, AR Krylov, DM Makarova, KS Mazumder, R Mekhedov, SL Nikolskaya, AN Rao, BS Rogozin, IB Smirnov, S Sorokin, AV Sverdlov, AV Vasudevan, S Wolf, YI Yin, JJ Natale, DA AF Koonin, EV Fedorova, ND Jackson, JD Jacobs, AR Krylov, DM Makarova, KS Mazumder, R Mekhedov, SL Nikolskaya, AN Rao, BS Rogozin, IB Smirnov, S Sorokin, AV Sverdlov, AV Vasudevan, S Wolf, YI Yin, JJ Natale, DA TI A comprehensive evolutionary classification of proteins encoded in complete eukaryotic genomes SO GENOME BIOLOGY LA English DT Review ID HORIZONTAL GENE-TRANSFER; 18S RIBOSOMAL-RNA; SACCHAROMYCES-CEREVISIAE; STRUCTURAL GENOMICS; COG DATABASE; PHYLOGENETIC CLASSIFICATION; ARABIDOPSIS-THALIANA; MICROBIAL GENOMES; ANIMAL PHYLOGENY; TARGET SELECTION AB Background: Sequencing the genomes of multiple, taxonomically diverse eukaryotes enables in-depth comparative-genomic analysis which is expected to help in reconstructing ancestral eukaryotic genomes and major events in eukaryotic evolution and in making functional predictions for currently uncharacterized conserved genes. Results: We examined functional and evolutionary patterns in the recently constructed set of 5,873 clusters of predicted orthologs (eukaryotic orthologous groups or KOGs) from seven eukaryotic genomes: Caenorhabditis elegans, Drosophila melanogaster, Homo sapiens, Arabidopsis thaliana, Saccharomyces cerevisiae, Schizosaccharomyces pombe and Encephalitozoon cuniculi. Conservation of KOGs through the phyletic range of eukaryotes strongly correlates with their functions and with the effect of gene knockout on the organism's viability. The approximately 40% of KOGs that are represented in six or seven species are enriched in proteins responsible for housekeeping functions, particularly translation and RNA processing. These conserved KOGs are often essential for survival and might approximate the minimal set of essential eukaryotic genes. The 131 single-member, pan-eukaryotic KOGs we identified were examined in detail. For around 20 that remained uncharacterized, functions were predicted by in-depth sequence analysis and examination of genomic context. Nearly all these proteins are subunits of known or predicted multiprotein complexes, in agreement with the balance hypothesis of evolution of gene copy number. Other KOGs show a variety of phyletic patterns, which points to major contributions of lineage-specific gene loss and the 'invention' of genes new to eukaryotic evolution. Examination of the sets of KOGs lost in individual lineages reveals co-elimination of functionally connected genes. Parsimonious scenarios of eukaryotic genome evolution and gene sets for ancestral eukaryotic forms were reconstructed. The gene set of the last common ancestor of the crown group consists of 3,413 KOGs and largely includes proteins involved in genome replication and expression, and central metabolism. Only 44% of the KOGs, mostly from the reconstructed gene set of the last common ancestor of the crown group, have detectable homologs in prokaryotes; the remainder apparently evolved via duplication with divergence and invention of new genes. Conclusions: The KOG analysis reveals a conserved core of largely essential eukaryotic genes as well as major diversification and innovation associated with evolution of eukaryotic genomes. The results provide quantitative support for major trends of eukaryotic evolution noticed previously at the qualitative level and a basis for detailed reconstruction of evolution of eukaryotic genomes and biology of ancestral forms. C1 NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20894 USA. RP NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20894 USA. EM koonin@ncbi.nlm.nih.gov RI Abrams, Natalie/F-4845-2011 OI Abrams, Natalie/0000-0001-9698-2819 NR 133 TC 252 Z9 261 U1 3 U2 24 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1465-6906 EI 1474-760X J9 GENOME BIOL JI Genome Biol. PY 2004 VL 5 IS 2 AR R7 DI 10.1186/gb-2004-5-2-r7 PG 28 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA 769UQ UT WOS:000188668500006 PM 14759257 ER PT J AU Miller, LD McPhie, P Suzuki, H Kato, Y Liu, ET Cheng, SY AF Miller, LD McPhie, P Suzuki, H Kato, Y Liu, ET Cheng, SY TI Multi-tissue gene-expression analysis in a mouse model of thyroid hormone resistance SO GENOME BIOLOGY LA English DT Article ID STEROID-RECEPTOR COACTIVATOR-1; FATTY-ACID SYNTHASE; C-ERBA-BETA; GLYCEROL-3-PHOSPHATE DEHYDROGENASE; TRANSCRIPTIONAL REGULATION; THYROTROPE TUMOR; MESSENGER-RNA; BREAST-CANCER; CYCLIN D1; MICE AB Background: Resistance to thyroid hormone (RTH) is caused by mutations of the thyroid hormone receptor beta (TRbeta) gene. To understand the transcriptional program underlying TRbeta mutant-induced phenotypic expression of RTH, cDNA microarrays were used to profile the expression of 11,500 genes in a mouse model of human RTH. Results: We analyzed transcript levels in cerebellum, heart and white adipose tissue from a knock-in mouse (TRbeta(PV/PV) mouse) that harbors a human mutation (referred to as PV) and faithfully reproduces human RTH. Because TRbeta(PV/PV) mice have elevated thyroid hormone (T3), to define T3-responsive genes in the context of normal TRbeta, we also analyzed T3 effects in hyperthyroid wildtype gender-matched littermates. Microarray analysis revealed 163 genes responsive to T3 treatment and 187 genes differentially expressed between TRbeta(PV/PV) mice and wild-type littermates. Both the magnitude and gene make-up of the transcriptional response varied widely across tissues and conditions. We identified genes modulated in T3-dependent PV-independent, T3- and PV-dependent, and T3- independent PV-dependent pathways that illuminated the biological consequences of PV action in vivo. Most T3- responsive genes that were dysregulated in the heart and white adipose tissue of TRbeta(PV/PV) mice were repressed in T3- treated wild-type mice and upregulated in TRbeta(PV/PV) mice, suggesting the inappropriate activation of T3-suppressed genes in RTH. Conclusions: Comprehensive multi-tissue gene-expression analysis uncovered complex multiple signaling pathways that mediate the molecular actions of TRbeta mutants in vivo. In particular, the T3-independent mutant-dependent genomic response unveiled the contribution of a novel 'change-of-function' of TRbeta mutants to the pathogenesis of RTH. Thus, the molecular actions of TRbeta mutants are more complex than previously envisioned. C1 NCI, Mol Biol Lab, Bethesda, MD 20892 USA. Agcy Sci Technol & Res, Genome Inst Singapore, Singapore 138672, Singapore. NIDDKD, NIH, Bethesda, MD 20892 USA. RP Cheng, SY (reprint author), NCI, Mol Biol Lab, Bldg 37, Bethesda, MD 20892 USA. EM sycheng@helix.nih.gov RI Liu, Edison/C-4141-2008; Miller, Lance/A-5633-2009 NR 64 TC 27 Z9 29 U1 0 U2 0 PU BIOMED CENTRAL LTD PI LONDON PA MIDDLESEX HOUSE, 34-42 CLEVELAND ST, LONDON W1T 4LB, ENGLAND SN 1465-6914 J9 GENOME BIOL JI Genome Biol. PY 2004 VL 5 IS 5 AR R31 DI 10.1186/gb-2004-5-5-r31 PG 17 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA 821ZP UT WOS:000221502400008 PM 15128445 ER PT J AU Oliver, B Leblanc, B AF Oliver, B Leblanc, B TI How many genes in a genome? SO GENOME BIOLOGY LA English DT Review AB Despite the current good level of annotation, the Drosophila genome still holds surprises. A recent study has added perhaps 2,000 genes to the predicted total, and raises a number of questions about how genome annotation data should be stored and presented. C1 NIDDKD, Cellular & Dev Biol Lab, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. Univ Sherbrooke, Fac Sci, Dept Biol, Sherbrooke, PQ J1K 2R1, Canada. RP Oliver, B (reprint author), NIDDKD, Cellular & Dev Biol Lab, NIH, Dept Hlth & Human Serv, 50 South Dr, Bethesda, MD 20892 USA. NR 8 TC 1 Z9 1 U1 0 U2 1 PU BIOMED CENTRAL LTD PI LONDON PA MIDDLESEX HOUSE, 34-42 CLEVELAND ST, LONDON W1T 4LB, ENGLAND SN 1465-6914 J9 GENOME BIOL JI Genome Biol. PY 2004 VL 5 IS 1 AR 204 PG 3 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA 759PX UT WOS:000187747000005 ER PT J AU Parada, LA McQueen, PG Misteli, T AF Parada, LA McQueen, PG Misteli, T TI Tissue-specific spatial organization of genomes SO GENOME BIOLOGY LA English DT Article ID ORDER CHROMATIN ARRANGEMENTS; NUCLEAR ARCHITECTURE; CELL-NUCLEI; INTERPHASE NUCLEI; MAMMALIAN-CELLS; GENE ACTIVITY; EARLY G1; CHROMOSOMES; MITOSIS; COMPARTMENTALIZATION AB Background: Genomes are organized in vivo in the form of chromosomes. Each chromosome occupies a distinct nuclear subvolume in the form of a chromosome territory. The spatial positioning of chromosomes within the interphase nucleus is often nonrandom. It is unclear whether the nonrandom spatial arrangement of chromosomes is conserved among tissues or whether spatial genome organization is tissue-specific. Results: Using two-dimensional and three-dimensional fluorescence in situ hybridization we have carried out a systematic analysis of the spatial positioning of a subset of mouse chromosomes in several tissues. We show that chromosomes exhibit tissue-specific organization. Chromosomes are distributed tissue-specifically with respect to their position relative to the center of the nucleus and also relative to each other. Subsets of chromosomes form distinct types of spatial clusters in different tissues and the relative distance between chromosome pairs varies among tissues. Consistent with the notion that nonrandom spatial proximity is functionally relevant in determining the outcome of chromosome translocation events, we find a correlation between tissue-specific spatial proximity and tissue-specific translocation prevalence. Conclusions: Our results demonstrate that the spatial organization of genomes is tissue-specific and point to a role for tissue-specific spatial genome organization in the formation of recurrent chromosome arrangements among tissues. C1 NCI, NIH, Bethesda, MD 20892 USA. NIH, Math & Stat Lab, Div Computat Biol, Ctr Informat Technol, Bethesda, MD 20892 USA. RP Misteli, T (reprint author), NCI, NIH, Bethesda, MD 20892 USA. EM mistelit@mail.nih.gov NR 36 TC 196 Z9 201 U1 0 U2 11 PU BIOMED CENTRAL LTD PI LONDON PA MIDDLESEX HOUSE, 34-42 CLEVELAND ST, LONDON W1T 4LB, ENGLAND SN 1465-6914 J9 GENOME BIOL JI Genome Biol. PY 2004 VL 5 IS 7 AR R44 DI 10.1186/gb-2004-5-7-r44 PG 9 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA 834RX UT WOS:000222429500009 PM 15239829 ER PT J AU Parisi, M Nuttall, R Edwards, P Minor, J Naiman, D Lu, JN Doctolero, M Vainer, M Chan, C Malley, J Eastman, S Oliver, B AF Parisi, M Nuttall, R Edwards, P Minor, J Naiman, D Lu, JN Doctolero, M Vainer, M Chan, C Malley, J Eastman, S Oliver, B TI A survey of ovary-, testis-, and soma-biased gene expression in Drosophila melanogaster adults SO GENOME BIOLOGY LA English DT Article ID LINE SEX DETERMINATION; GERM-LINE; TRANSLATIONAL REPRESSION; CAENORHABDITIS-ELEGANS; BINDING-PROTEIN; DIFFERENTIATION; MUTATIONS; GENOME; CHROMOSOME; SEQUENCE AB Background: Sexual dimorphism results in the formation of two types of individuals with specialized reproductive roles and is most evident in the germ cells and gonads. Results: We have undertaken a global analysis of transcription between the sexes using a 31,464 element FlyGEM microarray to determine what fraction of the genome shows sex-biased expression, what tissues express these genes, the predicted functions of these genes, and where these genes map onto the genome. Females and males (both with and without gonads), dissected testis and ovary, females and males with genetically ablated germlines, and sex-transformed flies were sampled. Conclusions: Using any of a number of criteria, we find extensive sex-biased expression in adults. The majority of cases of sex differential gene expression are attributable to the germ cells. There is also a large class of genes with soma-biased expression. There is little germline-biased expression indicating that nearly all genes with germline expression also show sex-bias. Monte Carlo simulations show that some genes with sex-biased expression are non-randomly distributed in the genome. C1 NIDDKD, Cellular & Dev Biol Lab, NIH, US Dept HHS, Bethesda, MD 20892 USA. Incyte Genom, Palo Alto, CA 94304 USA. Johns Hopkins Univ, Dept Math Sci, Baltimore, MD 21218 USA. NIH, Ctr Informat Technol, US Dept HHS, Bethesda, MD 20892 USA. RP Parisi, M (reprint author), NIDDKD, Cellular & Dev Biol Lab, NIH, US Dept HHS, Bethesda, MD 20892 USA. EM michaelpa@intra.niddk.nih.gov RI Naiman, Daniel/A-3304-2010 OI Naiman, Daniel/0000-0001-6504-9081 FU NIDDK NIH HHS [Z01 DK015600-10] NR 72 TC 170 Z9 172 U1 0 U2 23 PU BIOMED CENTRAL LTD PI LONDON PA MIDDLESEX HOUSE, 34-42 CLEVELAND ST, LONDON W1T 4LB, ENGLAND SN 1465-6914 J9 GENOME BIOL JI Genome Biol. PY 2004 VL 5 IS 6 AR R40 DI 10.1186/gb-2004-5-6-r40 PG 18 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA 825YH UT WOS:000221794300009 PM 15186491 ER PT J AU Shabalina, SA Spiridonov, NA AF Shabalina, SA Spiridonov, NA TI The mammalian transcriptome and the function of non-coding DNA sequences SO GENOME BIOLOGY LA English DT Editorial Material ID MATRIX-ATTACHMENT REGIONS; RNA UNTRANSLATED REGIONS; PRE-MESSENGER-RNA; INTERGENIC REGIONS; HUMAN GENOME; TRANSLATION INITIATION; SELECTIVE CONSTRAINT; CONSERVED SEQUENCES; POLYADENYLATED RNA; EXPRESSED GENES AB For decades, researchers have focused most of their attention on protein-coding genes and proteins. With the completion of the human and mouse genomes and the accumulation of data on the mammalian transcriptome, the focus now shifts to non-coding DNA sequences, RNA-coding genes and their transcripts. Many non-coding transcribed sequences are proving to have important regulatory roles, but the functions of the majority remain mysterious. C1 NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20894 USA. US FDA, Div Therapeut Prot, Ctr Drug Evaluat & Res, Bethesda, MD 20892 USA. RP Shabalina, SA (reprint author), NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20894 USA. EM shabalin@ncbi.nlm.nih.gov RI Shabalina, Svetlana/N-8939-2013; Spiridonov, Nikolay/B-6287-2014 OI Shabalina, Svetlana/0000-0003-2272-7473; NR 73 TC 76 Z9 86 U1 0 U2 5 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1474-760X J9 GENOME BIOL JI Genome Biol. PY 2004 VL 5 IS 4 AR 105 DI 10.1186/gb-2004-5-4-105 PG 8 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA 808QX UT WOS:000220584700002 PM 15059247 ER PT J AU Yamaoka, K Saharinen, P Pesu, M Holt, VET Silvennoinen, O O'Shea, JJ AF Yamaoka, K Saharinen, P Pesu, M Holt, VET Silvennoinen, O O'Shea, JJ TI The Janus kinases (Jaks) SO GENOME BIOLOGY LA English DT Review ID PROTEIN-TYROSINE KINASES; CELL-SURFACE EXPRESSION; MICE LACKING JAK3; PSEUDOKINASE DOMAIN; SIGNAL-TRANSDUCTION; DEVELOPMENTAL DEFECTS; INTERFERON-ALPHA/BETA; LYMPHOID DEVELOPMENT; DROSOPHILA; JAK/STAT AB The Janus kinase (Jak) family is one of ten recognized families of non-receptor tyrosine kinases. Mammals have four members of this family, Jak1, Jak2, Jak3 and Tyrosine kinase 2 (Tyk2). Birds, fish and insects also have Jaks. Each protein has a kinase domain and a catalytically inactive pseudo-kinase domain, and they each bind cytokine receptors through amino-terminal FERM (Band-4.1, ezrin, radixin, moesin) domains. Upon binding of cytokines to their receptors, Jaks are activated and phosphorylate the receptors, creating docking sites for signaling molecules, especially members of the signal transducer and activator of transcription (Stat) family. Mutations of the Drosophila Jak ( Hopscotch) have revealed developmental defects, and constitutive activation of Jaks in flies and humans is associated with leukemia-like syndromes. Through the generation of Jak-deficient cell lines and gene-targeted mice, the essential, nonredundant functions of Jaks in cytokine signaling have been established. Importantly, deficiency of Jak3 is the basis of human autosomal recessive severe combined immunodeficiency ( SCID); accordingly, a selective Jak3 inhibitor has been developed, forming a new class of immunosuppressive drugs. C1 NIAMSD, Mol Immunol & Inflammat Branch, NIH, Bethesda, MD 20892 USA. Univ Helsinki, Biomedicum Helsinki, Mol & Canc Biol Lab, FIN-00014 Helsinki, Finland. Univ Tampere, Inst Med Technol, FIN-33014 Tampere, Finland. Tampere Univ Hosp, Dept Clin Microbiol, FIN-33014 Tampere, Finland. RP NIAMSD, Mol Immunol & Inflammat Branch, NIH, Bethesda, MD 20892 USA. EM osheajo@mail.nih.gov RI Pesu, marko/L-6344-2013; Saharinen, Pipsa/C-9601-2016 OI Saharinen, Pipsa/0000-0003-2652-0584 NR 56 TC 226 Z9 237 U1 1 U2 25 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1465-6906 EI 1474-760X J9 GENOME BIOL JI Genome Biol. PY 2004 VL 5 IS 12 AR 253 DI 10.1186/gb-2004-5-12-253 PG 6 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA 875YY UT WOS:000225460600006 PM 15575979 ER PT J AU Wolf, YI Rogozin, IB Koonin, EV AF Wolf, YI Rogozin, IB Koonin, EV TI Coelomata and not ecdysozoa: Evidence from genome-wide phylogenetic analysis SO GENOME RESEARCH LA English DT Article ID MAXIMUM-LIKELIHOOD; ANIMAL PHYLOGENY; MODEL ORGANISMS; GENE-SEQUENCES; EVOLUTION; TREES; INFERENCE; DATABASE; CONFIDENCE; MORPHOLOGY AB Relative positions of nematodes, arthropods, and chordates in animal phylogeny remain uncertain. The traditional tree topology joins arthropods with chordates in a coelomate clade, whereas nematodes, which lack a coelome, Occupy a basal position. However, the Current leading hypothesis, based on phylogenetic trees for 18S ribosomal RNA and several proteins, joins nematodes with arthropods in a clade of molting animals, Ecdysozoa. We performed a phylogenetic analysis of over 500 sets of orthologous proteins, which are represented in plants, animals, and fungi, using maximum likelihood, maximum parsimony, and distance methods. Additionally, to increase the statistical power of topology tests, the same methods were applied to concatenated alignments of subunits of eight conserved macromolecular complexes. The majority of the methods, when applied to most of the orthologous clusters, both concatenated and individual, grouped the fly with humans to the exclusion of the nematode, in support of the coelomate phylogeny. Trees were also constructed using information on insertions and deletions in orthologous proteins, combinations of domains in multidomain proteins, and presence-absence of species in clusters of orthologs. All of these approaches supported the coelomate clade and showed concordance between evolution of protein sequences and higher-level evolutionary events, such as domain fusion or gene loss. C1 Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20894 USA. RP Koonin, EV (reprint author), Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20894 USA. EM koonin@ncbi.nim.nih.gov NR 44 TC 156 Z9 162 U1 1 U2 5 PU COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT PI COLD SPRING HARBOR PA 1 BUNGTOWN RD, COLD SPRING HARBOR, NY 11724 USA SN 1088-9051 J9 GENOME RES JI Genome Res. PD JAN PY 2004 VL 14 IS 1 BP 29 EP 36 DI 10.1101/gr.1347404 PG 8 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity GA 761FD UT WOS:000187889600004 PM 14707168 ER PT J AU Rahman, L Bliskovski, V Kaye, FJ Zajac-Kaye, M AF Rahman, L Bliskovski, V Kaye, FJ Zajac-Kaye, M TI Evolutionary conservation of a 2-kb intronic sequence flanking a tissue-specific alternative exon in the PTBP2 gene SO GENOMICS LA English DT Article DE intron conservation; alternative pre-mRNA processing; polypyrimidine tract-binding protein family; nPTB ID TRACT-BINDING-PROTEIN; RNA-BINDING; MESSENGER-RNA; 3'-SPLICE-SITE SELECTION; MOUSE; SEX; ORGANIZATION; COUNTERPART; ANTAGONIZES; REPRESSION AB nPTB is a member of the polypyrimidine tract-binding (PTB) protein family, which participates in alternative pre-mRNA processing. Tissue-specific splicing of exon 10 in nPTB (HGMW-approved symbol PTBP2) may play an important role in regulating the functional activity of nPTB in neuronal versus nonneuronal cells. In this study, we found that 297 consecutive intronic nucleotides flanking this alternatively spliced exon 10 were identical between human, green monkey, mouse, rat, and pig, while 207 consecutive intronic nucleotides were identical between human and bird DNA. In addition, a 2-kb sequence spanning this intron region showed 85 and 70% conservation in mammal and bird DNA, respectively. Unexpected intergenic sequence conservation between human and mouse genomes has recently been identified. We have now identified intragenic (intronic) sequence conservation from mammals to birds. The striking conservation of this large segment of flanking intronic sequence suggests an important role in tissue-specific splice site selection and may function in regulating the production of functional nPTB. Published by Elsevier Inc. C1 NCI, Basic Res Lab, Canc Res Ctr, NIH, Bethesda, MD 20892 USA. NCI, Dept Genet, Canc Res Ctr, NIH, Bethesda, MD 20892 USA. RP Zajac-Kaye, M (reprint author), NCI, Basic Res Lab, Canc Res Ctr, NIH, Bldg 37,Room 6040,37 Convent Dr MSC 4255, Bethesda, MD 20892 USA. RI kaye, frederic/E-2437-2011 NR 45 TC 18 Z9 21 U1 0 U2 1 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0888-7543 J9 GENOMICS JI Genomics PD JAN PY 2004 VL 83 IS 1 BP 76 EP 84 DI 10.1016/S0888-7543(03)00207-6 PG 9 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA 759WZ UT WOS:000187775700009 PM 14667811 ER PT J AU Kryger, M Monjan, A Bliwise, D Ancoli-Israel, S AF Kryger, M Monjan, A Bliwise, D Ancoli-Israel, S TI Sleep, health, and aging - Bridging the gap between science and clinical practice SO GERIATRICS LA English DT Article DE sleep; insomnia; apnea; cancer; nocturia incontinence ID NURSING-HOME RESIDENTS; DAYTIME SLEEPINESS; CIRCADIAN-RHYTHMS; ELDERLY PERSONS; OLDER-ADULTS; RISK-FACTORS; COMMUNITY; MORTALITY; DISEASE; FALLS AB Problems with sleep are common with advancing years and occur in over half of adults age 65 and older. It has been estimated that insomnia affects about a third of the older population in this country. This inability to have restful sleep at night results in excessive daytime sleepiness, attention and memory problems, depressed mood, falls, and lowered quality of life. Other factors associated with aging, such as disease, changes in environment, or concurrent age-related,processes also may contribute to problems of sleep. Data indicate that age by itself does not predict incident complaints of insomnia, even in the presence of lowered sleep efficiency and decreased proportion of slow-wave sleep. Rather, the prevalence of insomnia and other sleep disorders is high in the geriatric population due to the associated comorbidities common in late life. It is now evident that disturbance in sleep can also lead to adverse changes in functioning of a number of body systems. C1 Univ Manitoba, Winnipeg, MB, Canada. St Boniface Gen Hosp, Sleep Disorders Ctr, Winnipeg, MB R2H 2A6, Canada. NIA, Neurobiol Aging Branch, Neurosci & Neurophysiol Aging Program, NIH, Bethesda, MD 20892 USA. Emory Univ, Sch Med, Program Sleep Aging & Chronobiol, Atlanta, GA 30322 USA. Univ Calif San Diego, La Jolla, CA 92093 USA. RP Kryger, M (reprint author), Univ Manitoba, Winnipeg, MB, Canada. NR 36 TC 51 Z9 57 U1 0 U2 2 PU ADVANSTAR COMMUNICATIONS PI DULUTH PA 131 W FIRST ST, DULUTH, MN 55802 USA SN 0016-867X J9 GERIATRICS JI Geriatrics PD JAN PY 2004 VL 59 IS 1 BP 24 EP + PG 5 WC Geriatrics & Gerontology SC Geriatrics & Gerontology GA 766RK UT WOS:000188389200007 PM 14755865 ER PT J AU Han, SSW Liu, Y Tyler-Polsz, C Rao, MS Fischer, I AF Han, SSW Liu, Y Tyler-Polsz, C Rao, MS Fischer, I TI Transplantation of glial-restricted precursor cells into the adult spinal cord: Survival, glial-specific differentiation, and preferential migration in white matter SO GLIA LA English DT Article DE gliogenesis; spinal cord injury; transplantation; cell therapy ID CENTRAL-NERVOUS-SYSTEM; NEURAL STEM-CELL; TRANSCRIPTION FACTOR; OLIGODENDROCYTE DIFFERENTIATION; PROGENITOR CELLS; RAT; CNS; PROLIFERATION; LINEAGE; EXPRESSION AB Glial-restricted precursor (GRP) cells are among a number of candidate cells for transplantation repair of CNS injury. The isolation and characterization of these cells in vitro have been described previously, but their in vivo properties are not well understood. We examined the fate and migration of grafted fetal GRP cells harvested from alkaline phosphatase-expressing transgenic rats into intact and injured spinal cord. Transplanted GRP cells survived for at least 6 weeks and differentiated along astrocytic and oligodendrocytic but not neuronal lineages. Cells grafted into the intact spinal cord exhibited robust migration along longitudinal white matter tracts and by 6 weeks migrated more than 15 mm. In contrast, migration of GRP cells in the gray matter was very limited. We then examined the phenotypic properties of proliferating endogenous precursors in response to injury by BrdU labeling. The predominant proliferating population seen after injury consisted of GRP-like cells with Nkx2.2/olig2 phenotype. Incorporation of BrdU by endogenous cells suggests that the environment provides proliferation signals and is permissive to glial precursor survival. To test if exogenous GRP cells would respond similarly, we transplanted GRP cells into a lateral funiculus injury. GRP cells survived and differentiated along glial lineages and migrated along white matter tracts in the injured spinal cord. Directed homing toward the lesion was not seen and there was no significant bias in differentiation between cells transplanted into injured and uninjured spinal cord. GRP cell transplants may therefore provide a cellular transplant that can respond to appropriate endogenous cues to produce therapeutic molecules and new glial cells after injury. (C) 2003 Wiley-Liss, Inc. C1 Drexel Univ, Coll Med, Dept Neurobiol & Anat, Philadelphia, PA 19129 USA. NIA, Neurosci Lab, Gerontol Res Ctr, Baltimore, MD 21224 USA. RP Fischer, I (reprint author), Drexel Univ, Coll Med, Dept Neurobiol & Anat, 2900 Queen Lane, Philadelphia, PA 19129 USA. RI Fischer, Itzhak/D-1080-2012 OI Fischer, Itzhak/0000-0003-3187-8740 NR 49 TC 89 Z9 93 U1 0 U2 1 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0894-1491 J9 GLIA JI Glia PD JAN 1 PY 2004 VL 45 IS 1 BP 1 EP 16 DI 10.1002/glia.10282 PG 16 WC Neurosciences SC Neurosciences & Neurology GA 754CJ UT WOS:000187284900001 PM 14648541 ER PT J AU Liu, Y Rao, MS AF Liu, Y Rao, MS TI Olig genes are expressed in a heterogeneous population of precursor cells in the developing spinal cord SO GLIA LA English DT Article DE Olig; Nkx2.2; oligodendrocyte; astrocyte; differentiation ID NEUROEPITHELIAL STEM-CELLS; CENTRAL-NERVOUS-SYSTEM; OLIGODENDROCYTE DIFFERENTIATION; TRANSCRIPTION FACTOR; RESTRICTED PRECURSORS; SUBVENTRICULAR ZONE; PROGENITOR CELLS; LINEAGE; NKX2.2; ORIGIN AB Recent results from multiple laboratories have identified Olig genes as important in regulating glial differentiation. Here we show that Olig2 expression at early stages of development (prior to E16.5) identifies a domain in the developing spinal cord, which contains a heterogeneous population of progenitors that includes stem cells and glial progenitors. We show that Nkx2.2 and Olig2, which are present initially in nonoverlapping domains, are coexpressed at later stages, likely due to a second wave of Olig expression. We find that Olig1, like Olig2, is present in cells that coexpress astrocytic and radial glial markers and that Olig1/2 double knockouts lead to a loss of oligodendrocytes with preservation of NG2 expression. These results coupled with previously published data indicate that Olig1/2 and Nkx2.2, while clearly important in regulating early progenitor cell differentiation, do not unambiguously demonstrate the existence of an oligodendrocyte-neuron precursor or negate the existing retroviral lineage and clonal analysis data that suggest the existence of other types of precursors such as oligodendrocyte-astrocyte precursors or neuronal precursors. Published 2003 Wiley-Liss, Inc.dagger C1 NIA, Neurosci Lab, Baltimore, MD 21224 USA. Univ Utah, Sch Med, Dept Neurobiol & Anat, Salt Lake City, UT USA. RP Rao, MS (reprint author), NIA, Neurosci Lab, 5600 Nathan Shock Dr, Baltimore, MD 21224 USA. NR 33 TC 45 Z9 46 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0894-1491 J9 GLIA JI Glia PD JAN 1 PY 2004 VL 45 IS 1 BP 67 EP 74 DI 10.1002/glia.10303 PG 8 WC Neurosciences SC Neurosciences & Neurology GA 754CJ UT WOS:000187284900007 PM 14648547 ER PT S AU Charmandari, E Kino, T Chrousos, GP AF Charmandari, E Kino, T Chrousos, GP BE Kino, T Charmandari, E Chrousos, GP TI Glucocorticoids and their actions - An introduction SO GLUCOCORTICOID ACTION: BASIC AND CLINICAL IMPLICATIONS SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article; Proceedings Paper CT Conference on Basic and Clinical Implications of Glucocorticoid Action CY JUN 17-18, 2003 CL Bethesda, MD SP NIH, NICHHD, NIH, Off Rare Dis, Takeda Pharmaceut N Amer DE glucocorticoid receptor (GR); immune response; HPA axis ID RECEPTOR BETA ISOFORM; RESISTANCE/HYPERSENSITIVITY SYNDROMES; CLINICAL IMPLICATIONS; STRESS SYSTEM; RESISTANCE; MECHANISMS; NEUROENDOCRINE; EXPRESSION; MEDIATORS; MULTIPLE C1 NICHHD, Pediat & Reprod Endocrinol Branch, NIH, Bethesda, MD 20892 USA. RP Charmandari, E (reprint author), NICHHD, Pediat & Reprod Endocrinol Branch, NIH, Bldg 10,Room 9D42,10 Ctr Dr MSC 1583, Bethesda, MD 20892 USA. EM charmane@mail.nih.gov; charmane@mail.nih.gov RI Charmandari, Evangelia/B-6701-2011 NR 32 TC 38 Z9 41 U1 0 U2 3 PU NEW YORK ACAD SCIENCES PI NEW YORK PA 2 EAST 63RD ST, NEW YORK, NY 10021 USA SN 0077-8923 BN 1-57331-557-5 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2004 VL 1024 BP 1 EP 8 DI 10.1196/annals.1321.001 PG 8 WC Cell Biology; Endocrinology & Metabolism; Multidisciplinary Sciences SC Cell Biology; Endocrinology & Metabolism; Science & Technology - Other Topics GA BAN61 UT WOS:000222981400001 PM 15265770 ER PT S AU Webster, JI Moayeri, M Sternberg, EM AF Webster, JI Moayeri, M Sternberg, EM BE Kino, T Charmandari, E Chrousos, GP TI Novel repression of the glucocorticoid receptor by anthrax lethal toxin SO GLUCOCORTICOID ACTION: BASIC AND CLINICAL IMPLICATIONS SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article; Proceedings Paper CT Conference on Basic and Clinical Implications of Glucocorticoid Action CY JUN 17-18, 2003 CL Bethesda, MD SP NIH, NICHHD, NIH, Off Rare Dis, Takeda Pharmaceut N Amer DE GR; anthrax lethal toxin; HPA axis ID PITUITARY-ADRENAL AXIS; CHRONIC-FATIGUE-SYNDROME; CORTICOTROPIN-RELEASING HORMONE; RHEUMATIC AUTOIMMUNE DISORDERS; INFLAMMATORY-BOWEL-DISEASE; BLOOD MONONUCLEAR-CELLS; P-GLYCOPROTEIN ACTIVITY; I MDR-I; BACILLUS-ANTHRACIS; PROTECTIVE ANTIGEN AB Death from anthrax has been reported to occur from systemic shock. The lethal toxin (LeTx) is the major effector of anthrax mortality. Although the mechanism of entry of this toxin into cells is well understood, its actions once inside the cell are not as well understood. LeTx is known to cleave and inactivate MAPKKs. We have recently shown that LeTx represses the glucocorticoid receptor (GR) both in vitro and in vivo. This repression is partial and specific, repressing the glucocorticoid, progesterone, and estrogen receptor alpha, but not the mineralocorticoid or estrogen receptor P. This toxin does not affect GR ligand or DNA binding, and we have suggested that it may function by removing/inactivating one or more of the many cofactors involved in nuclear hormone receptor signaling. Although the precise involvement of this nuclear hormone receptor repression in LeTx toxicity is unknown, examples of blunted HPA axis and glucocorticoid signaling in numerous autoimmune/inflammatory diseases suggest that such repression of critically important receptors could have deleterious effects on health. C1 NIMH, Sect Neuroendocrine Immunol & Behav, NIH, Bethesda, MD 20892 USA. NIAID, Dept Hlth & Human Serv, NIH, Bethesda, MD 20892 USA. RP Sternberg, EM (reprint author), NIMH, Sect Neuroendocrine Immunol & Behav, NIH, Bldg 36,Rm 1A23,36 Convent Dr,MSC 4020, Bethesda, MD 20892 USA. EM sternbee@mail.nih.gov RI Webster Marketon, Jeanette/H-5613-2011 OI Webster Marketon, Jeanette/0000-0002-3627-1094 NR 147 TC 5 Z9 6 U1 0 U2 1 PU NEW YORK ACAD SCIENCES PI NEW YORK PA 2 EAST 63RD ST, NEW YORK, NY 10021 USA SN 0077-8923 BN 1-57331-557-5 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2004 VL 1024 BP 9 EP 23 DI 10.1196/annals.1321.003 PG 15 WC Cell Biology; Endocrinology & Metabolism; Multidisciplinary Sciences SC Cell Biology; Endocrinology & Metabolism; Science & Technology - Other Topics GA BAN61 UT WOS:000222981400002 PM 15265771 ER PT S AU Sengupta, S Wasylyk, B AF Sengupta, S Wasylyk, B BE Kino, T Charmandari, E Chrousos, GP TI Physiological and pathological consequences of the interactions of the p53 tumor suppressor with the glucocorticoid, androgen, and estrogen receptors SO GLUCOCORTICOID ACTION: BASIC AND CLINICAL IMPLICATIONS SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article; Proceedings Paper CT Conference on Basic and Clinical Implications of Glucocorticoid Action CY JUN 17-18, 2003 CL Bethesda, MD SP NIH, NICHHD, NIH, Off Rare Dis, Takeda Pharmaceut N Amer DE hematological malignancies; stress erythropoiesis; Addison's disease; Cushing's syndrome; anemia; skin carcinogenesis; cancer progression ID WILD-TYPE P53; RAT HEPATOMA-CELLS; RADIATION-INDUCED APOPTOSIS; REFRACTORY PROSTATE-CANCER; MOUSE SKIN CARCINOGENESIS; DIAMOND-BLACKFAN ANEMIA; HUMAN BREAST-CANCER; BCL-XL INDUCTION; NITRIC-OXIDE; ERYTHROID PROGENITORS AB The p53 tumor suppressor plays a key role in protection from the effects of different physiological stresses (DNA damage, hypoxia, transcriptional defects, etc.), and loss of its activity has dire consequences, such as cancer. Its activity is finely tuned through interactions with other important regulatory circuits in the cell. Recently, striking evidence has emerged for crosstalk with another class of important regulators, the steroid hormone receptors, and in particular the glucocorticoid (GR), androgen (AR), and estrogen (ER) receptors. These receptors are important in maintaining homeostasis in response to internal and external stresses (GR) and in the development, growth, and maintenance of the male and female reproductive systems (AR and ER, respectively). We review how p53 interacts closely with these receptors, to the extent that they share the same E3 ubiquitin ligase, the MDM2 oncoprotein. We discuss the different physiological contexts in which such interactions occur, and also how these interactions have been undermined in various pathological situations. We will describe future areas for research, with special emphasis on GR, and how certain common features, such as cytoplasmic anchoring of p53 by the receptors, may become targets for the development of therapeutic interventions. Given the importance of GR in inflammation, erythropoiesis, and autoimmune diseases, and the importance of AR and ER in prostate and breast cancer (respectively), the studies on p53 interactions with the steroid receptors will be an important domain in the near future. C1 ULP, INSERM, CNRS, Inst Genet & Biol Mol & Cellulaire, F-67401 Illkirch Graffenstaden, France. NCI, Lab Human Carcinogenesis, NIH, Bethesda, MD 20892 USA. RP Wasylyk, B (reprint author), ULP, INSERM, CNRS, Inst Genet & Biol Mol & Cellulaire, 1 Rue Laurent Fries,BP 10142, F-67401 Illkirch Graffenstaden, France. EM boh@igbmc.u-strasbg.fr OI Sengupta, Sagar/0000-0002-6365-1770; WASYLYK, Bohdan/0000-0002-1718-1237 NR 136 TC 49 Z9 51 U1 1 U2 6 PU NEW YORK ACAD SCIENCES PI NEW YORK PA 2 EAST 63RD ST, NEW YORK, NY 10021 USA SN 0077-8923 BN 1-57331-557-5 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2004 VL 1024 BP 54 EP 71 DI 10.1196/annals.1321.005 PG 18 WC Cell Biology; Endocrinology & Metabolism; Multidisciplinary Sciences SC Cell Biology; Endocrinology & Metabolism; Science & Technology - Other Topics GA BAN61 UT WOS:000222981400004 PM 15265773 ER PT S AU De Martino, MU Alesci, S Chrousos, GP Kino, T AF De Martino, MU Alesci, S Chrousos, GP Kino, T BE Kino, T Charmandari, E Chrousos, GP TI Interaction of the glucocorticoid receptor and the chicken ovalbumin upstream promoter-transcription factor II (COUP-TFII) - Implications for the actions of glucocorticoids on glucose, lipoprotein, and xenobiotic metabolism SO GLUCOCORTICOID ACTION: BASIC AND CLINICAL IMPLICATIONS SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article; Proceedings Paper CT Conference on Basic and Clinical Implications of Glucocorticoid Action CY JUN 17-18, 2003 CL Bethesda, MD SP NIH, NICHHD, NIH, Off Rare Dis, Takeda Pharmaceut N Amer DE protein-protein interaction; gluconeogenesis; phosphoenol-pyruvate carboxykinase (PEPCK); cholesterol; apolipoproteins; P450CYP7A; xenobiotic metabolism; P450CYP3A ID PHOSPHOENOLPYRUVATE CARBOXYKINASE GENE; APOLIPOPROTEIN-A-I; INDUCED INSULIN-RESISTANCE; NEGATIVE CROSS-TALK; BILE-ACID SYNTHESIS; NF-KAPPA-B; ACCESSORY FACTORS; DNA-BINDING; CHOLESTEROL 7-ALPHA-HYDROXYLASE; POSSIBLE MECHANISM AB Glucocorticoids; exert their extremely diverse effects on numerous biologic activities of humans via only one protein module, the glucocorticoid receptor (GR). The GR binds to the glucocorticoid response elements located in the promoter region of target genes and regulates their transcriptional activity. In addition, GR associates with other transcription factors through direct protein-protein interactions and mutually represses or stimulates each other's transcriptional activities. The latter activity of GR may be more important than the former one, granted that mice harboring a mutant GR, which is active in terms of protein-protein interactions but inactive in terms of transactivation via DNA, survive and procreate, in contrast to mice with a deletion of the entire GR gene that die immediately after birth. We recently found that GR physically interacts with the chicken ovalbumin upstream promoter-transcription factor II (COUP-TFII), which plays a critical role in the metabolism of glucose, cholesterol, and xenobiotics, as well as in the development of the central nervous system in fetus. GR stimulates COUP-TFII-induced transactivation by attracting cofactors via its activation function-1, while COUP-TFII represses the GR-governed transcriptional activity by tethering corepressors, such as the silencing mediator for retinoid and thyroid hormone receptors (SMRT) and the nuclear receptor corepressors (NCoRs) via its C-terminal domain. Their mutual interaction may play an important role in gluconeogenesis, lipoprotein metabolism, and enzymatic clearance of clinically important compounds and bioactive chemicals, by regulating their rate-limiting enzymes and molecules, including the phosphoenolpyruvate carboxykinase (PEPCK), the cytochrome P450 CYP3A and CYP7A, and several apolipoproteins. It appears that glucocorticoids exert their intermediary effects partly via physical interaction with COUP-TFII. C1 NICHHD, Pediat & Reprod Endocrinol Branch, NIH, Bethesda, MD 20892 USA. RP Kino, T (reprint author), NICHHD, Pediat & Reprod Endocrinol Branch, NIH, Bldg 10,Rm 9D42,10 Ctr Dr MSC 1583, Bethesda, MD 20892 USA. EM kinot@mail.nih.gov; kinot@mail.nih.gov NR 82 TC 26 Z9 26 U1 0 U2 2 PU NEW YORK ACAD SCIENCES PI NEW YORK PA 2 EAST 63RD ST, NEW YORK, NY 10021 USA SN 0077-8923 BN 1-57331-557-5 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2004 VL 1024 BP 72 EP 85 DI 10.1196/annals.1321.006 PG 14 WC Cell Biology; Endocrinology & Metabolism; Multidisciplinary Sciences SC Cell Biology; Endocrinology & Metabolism; Science & Technology - Other Topics GA BAN61 UT WOS:000222981400005 PM 15265774 ER PT S AU Lu, NZ Cidlowski, JA AF Lu, NZ Cidlowski, JA BE Kino, T Charmandari, E Chrousos, GP TI The origin and functions of multiple human glucocorticoid receptor isoforms SO GLUCOCORTICOID ACTION: BASIC AND CLINICAL IMPLICATIONS SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article; Proceedings Paper CT Conference on Basic and Clinical Implications of Glucocorticoid Action CY JUN 17-18, 2003 CL Bethesda, MD SP NIH, NICHHD, NIH, Off Rare Dis, Takeda Pharmaceut N Amer DE glucocorticoid receptor isoforms; alternative splicing; phosphorylation; ubiquitination; receptor mobility ID HORMONE-BINDING DOMAIN; KAPPA-B-ALPHA; HELA S3 CELLS; UBIQUITIN-PROTEASOME PATHWAY; HUMAN PROGESTERONE-RECEPTOR; HUMAN ESTROGEN-RECEPTOR; MOUSE LYMPHOMA-CELLS; BETA-ISOFORM; DNA-BINDING; LIVING CELLS AB Glucocorticoid hormones are necessary for life and are essential in all aspects of human health and disease. The actions of glucocorticoids are mediated by the glucocorticoid receptor (GR), which binds glucocorticoid hormones and regulates gene expression, cell signaling, and homeostasis. Decades of research have focused on the mechanisms of action of one isoform of GR, GRalpha. However, in recent years, increasing numbers of human GR (hGR) isoforms have been reported. Evidence obtained from this and other laboratories indicates that multiple hGR isoforms are generated from one single hGR gene via mutations and/or polymorphisms, transcript alternative splicing, and alternative translation initiation. Each hGR protein, in turn, is subject to a variety of posttranslational modifications, and the nature and degree of posttranslational modification affect receptor function. We summarize here the processes that generate and modify various hGR isoforms with a focus on those that impact the ability of hGR to regulate target genes. We speculate that unique receptor compositions and relative receptor proportions within a cell determine the specific response to glucocorticoids. Unchecked expression of some isoforms, for example hGRbeta, has been implicated in various diseases. C1 Natl Inst Environm Hlth Sci, Lab Signal Transduct Mol Endocrinol Grp, Dept Hlth & Human, NIH, Res Triangle Pk, NC 27709 USA. RP Cidlowski, JA (reprint author), Natl Inst Environm Hlth Sci, Lab Signal Transduct Mol Endocrinol Grp, Dept Hlth & Human, NIH, 111 Alexander Dr, Res Triangle Pk, NC 27709 USA. EM cidlowski@niehs.nih.gov NR 166 TC 113 Z9 124 U1 0 U2 8 PU NEW YORK ACAD SCIENCES PI NEW YORK PA 2 EAST 63RD ST, NEW YORK, NY 10021 USA SN 0077-8923 BN 1-57331-557-5 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2004 VL 1024 BP 102 EP 123 DI 10.1196/annals.1321.008 PG 22 WC Cell Biology; Endocrinology & Metabolism; Multidisciplinary Sciences SC Cell Biology; Endocrinology & Metabolism; Science & Technology - Other Topics GA BAN61 UT WOS:000222981400007 PM 15265776 ER PT S AU Elenkov, IJ AF Elenkov, IJ BE Kino, T Charmandari, E Chrousos, GP TI Glucocorticoids and the Th1/Th2 balance SO GLUCOCORTICOID ACTION: BASIC AND CLINICAL IMPLICATIONS SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article; Proceedings Paper CT Conference on Basic and Clinical Implications of Glucocorticoid Action CY JUN 17-18, 2003 CL Bethesda, MD SP NIH, NICHHD, NIH, Off Rare Dis, Takeda Pharmaceut N Amer DE glucocorticoids; stress; interleukin-12; interleukin-10; Th1 cells; Th2 cells; autoinummity; allergy; inflammation; rheumatoid arthritis; multiple sclerosis ID CORTICOTROPIN-RELEASING HORMONE; PITUITARY-ADRENAL AXIS; IL-12 PRODUCTION; IMMUNE-SYSTEM; MAST-CELLS; T-CELLS; INTERLEUKIN-10 PRODUCTION; RHEUMATOID-ARTHRITIS; CD4(+) LYMPHOCYTES; AUTOIMMUNE-DISEASE AB Evidence accumulated over the last 5-10 years indicates that glucocorticoids (GCs) inhibit the production of interleukin (IL)-12, interferon (IFN)-gamma, IFN-alpha, and tumor necrosis factor (TNF)-alpha by antigen-presenting cells (APCs) and T helper (Th)1 cells, but upregulate the production of IL-4, EL-10, and IL-13 by Th2 cells. Through this mechanism increased levels of GCs may systemically cause a selective suppression of the Th1-cellular immunity axis, and a shift toward Th2-mediated Immoral immunity, rather than generalized immunosuppression. During an immune response and inflammation, the activation of the stress system, and thus increased levels of systemic GCs through induction of a Th2 shift, may actually protect the organism from systemic "overshooting" with Th1/pro-inflammatory cytokines and other products of activated macrophages with tissue-damaging potential. However, conditions associated with significant changes of GCs levels, such as acute or chronic stress or cessation of chronic stress, severe exercise, and pregnancy and postpartum, through modulation of the Th1/Th2 balance may affect the susceptibility to or the course of infections as well as autoimmune and atopic/allergic diseases. C1 Natl Inst Mental Hlth, Clin Neuroendocrinol Branch, NIH, Bethesda, MD 20892 USA. RP Elenkov, IJ (reprint author), Natl Inst Mental Hlth, Clin Neuroendocrinol Branch, NIH, Bldg 10,Room 2D46,10 Ctr Dr, Bethesda, MD 20892 USA. EM Elenkovi@mail.nih.gov NR 59 TC 267 Z9 294 U1 1 U2 19 PU NEW YORK ACAD SCIENCES PI NEW YORK PA 2 EAST 63RD ST, NEW YORK, NY 10021 USA SN 0077-8923 BN 1-57331-557-5 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2004 VL 1024 BP 138 EP 146 DI 10.1196/annals.1321.010 PG 9 WC Cell Biology; Endocrinology & Metabolism; Multidisciplinary Sciences SC Cell Biology; Endocrinology & Metabolism; Science & Technology - Other Topics GA BAN61 UT WOS:000222981400009 PM 15265778 ER PT S AU Alesci, S De Martino, MU Kino, T Ilias, I AF Alesci, S De Martino, MU Kino, T Ilias, I BE Kino, T Charmandari, E Chrousos, GP TI L-carnitine is a modulator of the glucocorticoid receptor alpha SO GLUCOCORTICOID ACTION: BASIC AND CLINICAL IMPLICATIONS SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article; Proceedings Paper CT Conference on Basic and Clinical Implications of Glucocorticoid Action CY JUN 17-18, 2003 CL Bethesda, MD SP NIH, NICHHD, NIH, Off Rare Dis, Takeda Pharmaceut N Amer DE glucocorticoid receptor alpha; immunity; cytokines ID PHOSPHATIDYLCHOLINE SPECIES COMPOSITION; FETAL-RAT LUNGS; PROPIONIC ACIDEMIA; BETAMETHASONE; SHOCK; INTERLEUKIN-12; COMBINATIONS; EXCRETION; TRANSPORT; CYTOKINE AB L-Carnitine (LC) is a nutrient with an essential role in cellular energy production. At high doses, LC can mimic some of the biological activities of glucocorticoids, particularly immunomodulation. To explore the molecular bases of this property, we tested the influence of LC on glucocorticoid receptor-alpha (GRalpha) functions. LC reduced the binding capacity of GRalpha, induced its nuclear translocation, and stimulated its transcriptional activity. Moreover, LC suppressed TNFalpha and IL-12 release from human monocytes; in glucocorticoid-like fashion. We conclude that pharmacologic doses of LC can activate GRalpha and, via this mechanism, regulate glucocorticoid-responsive genes, potentially sharing some of the biological and therapeutic properties of glucocorticoids. C1 NIMH, CNR, NIH, Bethesda, MD 20892 USA. Natl Inst Child Hlth & Human Dev, Pediat & Reprod Endocrinol Branch, NIH, Bethesda, MD USA. Univ Patras, Fac Med, Dept Pharmacol, Rion Patras, Greece. RP Alesci, S (reprint author), NIMH, CNR, NIH, 10 Ctr Dr,Bldg 10,Rm 2D46,MSC 1284, Bethesda, MD 20892 USA. EM alescisa@mail.nih.gov NR 34 TC 12 Z9 16 U1 0 U2 1 PU NEW YORK ACAD SCIENCES PI NEW YORK PA 2 EAST 63RD ST, NEW YORK, NY 10021 USA SN 0077-8923 BN 1-57331-557-5 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2004 VL 1024 BP 147 EP 152 DI 10.1196/annals.1321.012 PG 6 WC Cell Biology; Endocrinology & Metabolism; Multidisciplinary Sciences SC Cell Biology; Endocrinology & Metabolism; Science & Technology - Other Topics GA BAN61 UT WOS:000222981400010 PM 15265779 ER PT S AU Kino, T Chrousos, GP AF Kino, T Chrousos, GP BE Kino, T Charmandari, E Chrousos, GP TI Human immunodeficiency virus type-1 accessory protein Vpr - A causative agent of the AIDS-related insulin resistance/lipodystrophy syndrome? SO GLUCOCORTICOID ACTION: BASIC AND CLINICAL IMPLICATIONS SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article; Proceedings Paper CT Conference on Basic and Clinical Implications of Glucocorticoid Action CY JUN 17-18, 2003 CL Bethesda, MD SP NIH, NICHHD, NIH, Off Rare Dis, Takeda Pharmaceut N Amer DE Vpr; HIV-1 accessory protein; insulin resistance; lipodystrophy syndrome ID FORKHEAD TRANSCRIPTION FACTOR; YEAST SCHIZOSACCHAROMYCES-POMBE; CELL-CYCLE ARREST; LONG TERMINAL REPEAT; ANTIRETROVIRAL-THERAPY; HIV-1 VPR; DNA-DAMAGE; NUCLEAR RECEPTOR; GLUCOCORTICOID-RECEPTOR; INFECTED PATIENTS AB Recent advances in the development of three different types of antiviral drugs, the nucleotide and non-nucleotide analogues acting as reverse transcriptase inhibitors (NRTIs) and the nonpeptidic viral protease inhibitors (PI), and their introduction in the management of patients with AIDS, either alone or in combination, have dramatically improved the clinical course of the disease and prolonged life expectancy in patients with AIDS. The increase in life expectancy in association with the long-term use of the above antiviral agents, however, have generated novel morbidities and complications. Central among them is the quite common AIDS-related insulin resistance and lipodystrophy syndrome, which is characterized by a striking phenotype and marked metabolic disturbances. To look for the pathologic causes of this particular syndrome, we focused on one of the HIV-1 accessory proteins, Vpr, which has multiple functions, such as virion incorporation, nuclear translocation of the HIV-1 preintegration complex, nucleo-cytoplasmic shuttling, transcriptional activation, and induction of apoptosis. Vpr may also act like a hormone, which is secreted into the extracellular space and affects the function of distant organs. Vpr functions as a coactivator of the glucocorticoid receptor and potentiates the action of glucocorticoid hormones, thereby inducing tissue glucocorticoid hypersensitivity. Vpr also arrests host cells at the G2/M phase of the cell cycle by interacting with novel 14-3-3 proteins. Vpr facilitates the interaction of 14-3-3 and its partner protein Cdc25C, which is critical for the transition of G2/M checkpoint in the cell cycle, and suppresses its activity by segregating it into the cytoplasm. The same Vpr protein also suppresses the association of 14-3-3 with other partner molecules, the Foxo transcription factors. Since the Foxo proteins function as negative transcription factors for insulin, Vpr may cause resistance of tissues to insulin. Through these two newly identified functions of Vpr, namely, coactivation of glucocorticoid receptor activity and inhibition of insulin effects on Foxo proteins, Vpr may participate in the development of AIDS-related insulin resistance/lipodystrophy syndrome. C1 NICHHD, Pediat & Reprod Endocrinol Branch, NIH, Bethesda, MD 20892 USA. RP Kino, T (reprint author), NICHHD, Pediat & Reprod Endocrinol Branch, NIH, Bldg 10,Rm 9D42,10 Ctr Dr MSC 1583, Bethesda, MD 20892 USA. EM kinot@mail.nih.gov; kinot@mail.nih.gov NR 98 TC 20 Z9 21 U1 0 U2 1 PU NEW YORK ACAD SCIENCES PI NEW YORK PA 2 EAST 63RD ST, NEW YORK, NY 10021 USA SN 0077-8923 BN 1-57331-557-5 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2004 VL 1024 BP 153 EP 167 DI 10.1196/annals.1321.013 PG 15 WC Cell Biology; Endocrinology & Metabolism; Multidisciplinary Sciences SC Cell Biology; Endocrinology & Metabolism; Science & Technology - Other Topics GA BAN61 UT WOS:000222981400011 PM 15265780 ER PT S AU Charmandari, E Kino, T Chrousos, GP AF Charmandari, E Kino, T Chrousos, GP BE Kino, T Charmandari, E Chrousos, GP TI Familial/sporadic glucocorticoid resistance - Clinical phenotype and molecular mechanisms SO GLUCOCORTICOID ACTION: BASIC AND CLINICAL IMPLICATIONS SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article; Proceedings Paper CT Conference on Basic and Clinical Implications of Glucocorticoid Action CY JUN 17-18, 2003 CL Bethesda, MD SP NIH, NICHHD, NIH, Off Rare Dis, Takeda Pharmaceut N Amer DE glucocorticoid receptor; glucocorticoid resistance; tissue sensitivity to glucocorticoids; mutations in the GR gene ID PRIMARY CORTISOL RESISTANCE; HORMONE-BINDING DOMAIN; RECEPTOR BETA ISOFORM; NUCLEAR-RECEPTOR; TRANSCRIPTIONAL COACTIVATOR; RESISTANCE/HYPERSENSITIVITY SYNDROMES; GR GENE; EXPRESSION; MULTIPLE; MUTATION AB Glucocorticoids regulate a variety of biologic processes and exert profound influences on many physiologic functions. Their actions are mediated by the glucocorticoid receptor (GR), which belongs to the nuclear receptor family of ligand-dependent transcription factors. Alterations in tissue sensitivity to glucocorticoids may manifest as states of resistance or hypersensitivity. Glucocorticoid resistance is a rare, familial or sporadic, condition characterized by generalized, partial target-tissue resistance to glucocorticoids. Compensatory elevations in circulating adrenocorticotropic hormone (ACTH) concentrations lead to increased production of adrenal steroids with mineralocorticoid and/or androgenic activity and their corresponding clinical manifestations, as well as increased urinary free-cortisol excretion in the absence of symptomatology suggestive of hypercortisolism. The molecular basis of the condition has been ascribed to mutations in the GR gene, which impair normal glucocorticoid signal transduction, altering tissue sensitivity to glucocorticoids. The present review focuses on the mechanisms of GR action and the clinical manifestations and molecular mechanisms of familial/sporadic glucocorticoid resistance. C1 NICHHD, Pediat & Reprod Endocrinol Branch, NIH, Bethesda, MD 20892 USA. RP Charmandari, E (reprint author), NICHHD, Pediat & Reprod Endocrinol Branch, NIH, Bldg 10,Room 9D42,10 Ctr Dr MSC 1583, Bethesda, MD 20892 USA. EM charmane@mail.nih.gov; charmane@mail.nih.gov RI Charmandari, Evangelia/B-6701-2011 NR 57 TC 38 Z9 46 U1 0 U2 1 PU NEW YORK ACAD SCIENCES PI NEW YORK PA 2 EAST 63RD ST, NEW YORK, NY 10021 USA SN 0077-8923 BN 1-57331-557-5 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2004 VL 1024 BP 168 EP 181 DI 10.1196/annals.1321.014 PG 14 WC Cell Biology; Endocrinology & Metabolism; Multidisciplinary Sciences SC Cell Biology; Endocrinology & Metabolism; Science & Technology - Other Topics GA BAN61 UT WOS:000222981400012 PM 15265781 ER PT S AU Nagaich, AK Rayasam, GV Martinez, ED Becker, M Qiu, Y Johnson, TA Elbi, C Fletcher, TM John, S Hager, GL AF Nagaich, AK Rayasam, GV Martinez, ED Becker, M Qiu, Y Johnson, TA Elbi, C Fletcher, TM John, S Hager, GL BE Kino, T Charmandari, E Chrousos, GP TI Subnuclear trafficking and gene targeting by steroid receptors SO GLUCOCORTICOID ACTION: BASIC AND CLINICAL IMPLICATIONS SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article; Proceedings Paper CT Conference on Basic and Clinical Implications of Glucocorticoid Action CY JUN 17-18, 2003 CL Bethesda, MD SP NIH, NICHHD, NIH, Off Rare Dis, Takeda Pharmaceut N Amer DE glucocorticoid receptor; nuclear receptor; chromatin; progesterone receptor; laser crosslinking; chaperone; FRAP; protein dynamics ID LASER CROSS-LINKING; GLUCOCORTICOID-RECEPTOR; IN-VIVO; LIVING CELLS; CHROMATIN; DNA; TRANSCRIPTION; FRAMES; PROMOTER; PROTEINS AB Through the use of novel imaging techniques, we have observed direct steroid receptor binding to a tandem array of a hormone-responsive promoter in living cells. We found that the glucocorticoid receptor (GR) exchanges rapidly with regulatory elements in the continued presence of ligand. We have also reconstituted a GR-dependent nucleoprotein transition with chromatin assembled on promoter DNA, and we discovered that GR is actively displaced from the chromatin template during the chromatin remodeling process. Using high-intensity UV laser crosslinking, we have observed highly periodic interactions of GR with promoter chromatin. These periodic binding events are dependent on GR-directed hSWI/SNF remodeling of the template and require the presence of ATP. Both the in vitro and in vivo results are consistent with a dynamic model ("hit-and-run") in which GR first binds to chromatin after ligand activation, recruits a remodeling activity, and is simultaneously lost from the template. We also find that receptor mobility in the nucleoplasm is strongly enhanced by molecular chaperones. These observations indicate that multiple mechanisms are involved in transient receptor interactions with nucleoplasmic targets. C1 NCI, Lab Receptor Biol & Gene Express, NIH, Bethesda, MD 20892 USA. RP Hager, GL (reprint author), NCI, Lab Receptor Biol & Gene Express, NIH, Bldg 41,B602,41 Lib Dr, Bethesda, MD 20892 USA. EM hagerg@exchange.nih.gov NR 27 TC 35 Z9 36 U1 0 U2 3 PU NEW YORK ACAD SCIENCES PI NEW YORK PA 2 EAST 63RD ST, NEW YORK, NY 10021 USA SN 0077-8923 BN 1-57331-557-5 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2004 VL 1024 BP 213 EP 220 DI 10.1196/annals.1321.02 PG 8 WC Cell Biology; Endocrinology & Metabolism; Multidisciplinary Sciences SC Cell Biology; Endocrinology & Metabolism; Science & Technology - Other Topics GA BAN61 UT WOS:000222981400014 PM 15265783 ER PT J AU Eyster, ME Sanders, J Goedert, JJ AF Eyster, ME Sanders, J Goedert, JJ TI Viral clearance occurs very early during the natural resolution of hepatitis C virus infection in persons with haemophilia SO HAEMOPHILIA LA English DT Article; Proceedings Paper CT Digestive Disease Week Meeting/104th Annual Meeting of the American-Gastroenterological-Association CY MAY 17-22, 2003 CL ORLANDO, FLORIDA SP Amer Gastroenterol Assoc DE haemophilia; hepatitis C; spontaneous hepatitis C virus RNA clearance ID NON-B HEPATITIS; NON-A; FACTOR-VIII; HCV RNA; PERSISTENCE; TRANSFUSION; INTERFERON; PREVALENCE; OUTBREAK; GLOBULIN AB We studied spontaneous hepatitis C virus (HCV) RNA clearance in 12 haemophilic patients. In their earliest anti-HCV positive samples, HCV RNA was undetectable in eight patients (66%), positive by polymerase chain reaction (PCR) but negative by branched-DNA (bDNA) in three others, and quantifiable by bDNA (4839 IU/mL) in only one patient. In contrast, in earliest anti-HCV positive samples from eight matched controls who had persistent viremia, HCV RNA was quantifiable by bDNA in seven (P = 0.0008) and at higher levels (range 4644-678 515 IU/mL; median 43 532 IU/mL). From initial HCV infection, HCV RNA cleared in 7 months or less in four patients and in 1-2 years in six others. HCV persisted for 5 years before clearance in the absence of repeated exposure in one patient. We conclude that HCV clearance usually but not always occurs within 1-2 years after infection and is more likely in those with lower than in those with higher early viral loads. C1 Penn State Univ, Milton S Hershey Med Ctr, Coll Med, Dept Med,Div Hematol Oncol, Hershey, PA 17033 USA. NCI, Viral Epidemiol Branch, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. RP Eyster, ME (reprint author), Penn State Univ, Milton S Hershey Med Ctr, Coll Med, Dept Med,Div Hematol Oncol, POB 850,MC 46, Hershey, PA 17033 USA. NR 23 TC 15 Z9 15 U1 0 U2 0 PU BLACKWELL PUBLISHING LTD PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 1351-8216 J9 HAEMOPHILIA JI Haemophilia PD JAN PY 2004 VL 10 IS 1 BP 75 EP 80 DI 10.1046/j.1351-8216.2003.00836.x PG 6 WC Hematology SC Hematology GA 761FZ UT WOS:000187892000011 PM 14962224 ER PT J AU Arena, P Levin, B Fleming, LE Friedman, MA Blythe, D AF Arena, P Levin, B Fleming, LE Friedman, MA Blythe, D TI A pilot study of the cognitive and psychological correlates of chronic ciguatera poisoning SO HARMFUL ALGAE LA English DT Article DE neuropsychologic effects; ciguatera fish poisoning; mannitol; harmful algal blooms; marine toxins; ciguatoxin ID COMMON-SOURCE OUTBREAK; MYELINATED AXONS; CHRONIC FATIGUE; MANNITOL; IDENTIFICATION; EPIDEMIOLOGY; ISLAND AB Ciguatera fish poisoning is the most frequently reported seafood-toxin illness in the world, caused by the consumption of coral reef fishes contaminated with a group of natural toxins produced by minute phytoplankton (dinoflagellates). These toxins are potent and cause both acute and chronic neurologic disease in humans. Although ciguatera fish poisoning is associated with established neurotoxins in animal models, and with known peripheral nervous system effects in humans, this pilot study was the first to explore possible central nervous system effects associated with chronic ciguatera poisoning in humans. In a matched cohort design, 12 cases and 12 their age and gender matched friend controls underwent a battery of neuropsychological tests. The results indicated that although their scores on objective neuropsychological tests did not differ significantly from matched controls, persons with ciguatera reported a higher degree of toxicity-related symptomatology and endorsed significantly more depressive symptomatology than controls. Future research should explore larger numbers of persons with both acute and chronic ciguatera, with and without mannitol treatment. (C) 2004 Elsevier B.V All rights reserved. C1 Univ Miami, Rosenstiel Sch Marine & Atmospher Sci, NIEHS Marine & Freshwater Biomed Sci, Miami, FL 33149 USA. Univ Miami, Sch Med, Dept Neurol Epidemiol & Publ Hlth, Miami, FL 33136 USA. RP Fleming, LE (reprint author), Univ Miami, Rosenstiel Sch Marine & Atmospher Sci, NIEHS Marine & Freshwater Biomed Sci, Miami, FL 33149 USA. EM lfleming@med.miami.edu NR 54 TC 13 Z9 17 U1 0 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1568-9883 J9 HARMFUL ALGAE JI Harmful Algae PD JAN PY 2004 VL 3 IS 1 BP 51 EP 60 DI 10.1016/j.hal.2003.08.006 PG 10 WC Marine & Freshwater Biology SC Marine & Freshwater Biology GA 812US UT WOS:000220865000006 ER PT J AU Chen, GB Kook, H Zeng, WH Young, NS Maciejewski, JP AF Chen, GB Kook, H Zeng, WH Young, NS Maciejewski, JP TI Is there a direct effect of antithymocyte globulin on hematopoiesis? SO HEMATOLOGY JOURNAL LA English DT Article DE ATG; aplastic anemia; CD34+cells; immunosuppression ID SEVERE APLASTIC-ANEMIA; COLONY-STIMULATING FACTOR; SAA-WORKING-PARTY; ANTILYMPHOCYTE GLOBULIN; HORSE ANTILYMPHOCYTE; PROGENITOR CELLS; NORMAL MARROW; IMMUNOSUPPRESSION; CYCLOSPORINE; LYMPHOCYTES AB The efficacy of immunosuppressive therapy in aplastic anemia (AA) provides the strongest argument to support its immune-mediated pathophysiology. While several immunosuppressive effects of antithymocyte globulin (ATG) can be demonstrated in vitro, some reports have implied that the activity of ATG in AA may be rather due to a variety of positive hematopoietic effects. We studied the effects of horse (h) and rabbit (r) ATG on marrow progenitors in vitro. Both types of ATG bound to CD34 cells and, in colony assays performed with total marrow cells, hATG had a dose-dependent, triphasic effect, with maximal increase in colony formation between 1 and 10 mug/ml and inhibition between 100 and 1000 mug/ml. As determined using CD34 cells, these effects did not require accessory cells. rATG showed similar activity, but was about 10-fold more potent than hATG. In the presence of complement, no increased cytotoxicity was observed. At concentrations equivalent to those measured in patients immediately after infusion, ATG showed moderate suppression of colony formation, while the stimulatory concentrations in vitro correspond to those seen in vivo within the first weeks after ATG administration. In control experiments, the patterns of the biologic effects of preimmune rIgG or hIgG preparations were similar to those of rATG and hATG, indicating a nonspecific nature of the effects of ATG on progenitor cells. Biological activity in methylcellulose cultures was observed with the F(ab)(2) fragments but was not found in purified Fc IgG. In summary, the spectrum of effects of ATG on hematopoietic progenitors is dependent upon the concentrations of ATG and may not be related to its antigenic specificity. C1 NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA. RP Maciejewski, JP (reprint author), NHLBI, Hematol Branch, NIH, Bldg 10,Room 7C108, Bethesda, MD 20892 USA. EM maciejj@cc.ccf.org NR 33 TC 4 Z9 5 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1466-4860 J9 HEMATOL J JI Hematol. J. PY 2004 VL 5 IS 3 BP 255 EP 261 DI 10.1038/sj.thj.6200398 PG 7 WC Hematology SC Hematology GA 902TI UT WOS:000227379000010 PM 15167913 ER PT J AU Andreola, F Calvisi, DF Elizondo, G Jakowlew, SB Mariano, J Gonzalez, FJ De Luca, LM AF Andreola, F Calvisi, DF Elizondo, G Jakowlew, SB Mariano, J Gonzalez, FJ De Luca, LM TI Reversal of liver fibrosis in aryl hydrocarbon receptor null mice by dietary vitamin A depletion SO HEPATOLOGY LA English DT Article ID GROWTH-FACTOR-BETA; PROLIFERATOR-ACTIVATED RECEPTORS; STELLATE CELL ACTIVATION; HEPATIC-FIBROSIS; TGF-BETA; RETINOIDS; DISEASE AB Aryl hydrocarbon receptor (AHR)-null mice display a liver fibrosis phenotype that is associated with a concomitant increase in liver retinoid concentration, tissue transglutaminase type II (TGaseII) activity, transforming growth factorbeta (TGFbeta) overexpression, and accumulation of collagen. To test the hypothesis that this phenotype might be triggered by the observed increase in liver retinoid content, we induced the condition of retinoid depletion by feeding AHR-null mice a vitamin A- deficient diet with the purpose to reverse the phenotype. Liver retinoid content decreased sharply within the first few weeks on the retinoid-deficient diet. Analysis of TGFbeta1, TGFbeta2, and TGFbeta3 expression revealed a reduction to control levels in the AHR -/- mice accompanied by parallel changes in TGaseII protein levels. In addition, we observed an increase in the TGFbeta receptors, TGFbeta RI and TGFbeta RII, as well as in Smad4, and their reduction to wild-type mouse liver levels in AHR -/- mice fed the retinoid-deficient diet. Reduction of peroxisomal proliferator-activated receptor gamma (PPARgamma) messenger RNA (mRNA) and protein levels in AHR -/- mice was consistent with the presence of hepatic stellate cell (HSC) activation and liver fibrosis. Vitamin A deficiency normalized PPARgamma expression in AHR -/- mice. In conclusion, livers from AHR -/- mice fed the vitamin A-deficient diet showed a decrease in collagen deposition, consistent with the absence of liver fibrosis. C1 NCI, Cellular Carcinogenesis & Tumor Promot Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. NCI, Expt Carcinogenesis Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. IPN, CINVESTAV, Secc Externa Toxicol, Mexico City 07738, DF, Mexico. NCI, Lab Cell & Canc Biol Branch, Ctr Canc Res, NIH, Rockville, MD USA. NCI, Lab Metab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP De Luca, LM (reprint author), NCI, Cellular Carcinogenesis & Tumor Promot Lab, Ctr Canc Res, NIH, Bldg 37,Room 4054C,37 Convent Dr, Bethesda, MD 20892 USA. EM luigi_de_luca@nih.gov NR 21 TC 19 Z9 21 U1 1 U2 2 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD JAN PY 2004 VL 39 IS 1 BP 157 EP 166 DI 10.1002/hep.20004 PG 10 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 805OK UT WOS:000220375400020 PM 14752834 ER PT J AU Promrat, K Lutchman, G Uwaifo, GI Freedman, RJ Soza, A Heller, T Doo, E Ghany, M Premkumar, A Park, Y Liang, TJ Yanovski, JA Kleiner, DE Hoofnagle, JH AF Promrat, K Lutchman, G Uwaifo, GI Freedman, RJ Soza, A Heller, T Doo, E Ghany, M Premkumar, A Park, Y Liang, TJ Yanovski, JA Kleiner, DE Hoofnagle, JH TI A pilot study of ploglitazone treatment for nonalcoholic steatohepatitis SO HEPATOLOGY LA English DT Article ID FATTY LIVER-DISEASE; NATURAL-HISTORY; CRYPTOGENIC CIRRHOSIS; INSULIN SENSITIVITY; RISK-FACTORS; METFORMIN; TROGLITAZONE; ROSIGLITAZONE; ASSOCIATION; RESISTANCE AB Nonalcoholic steatohepatitis (NASH) is a common chronic liver disease for which there is no known effective therapy. A proportion of patients with NASH progress to advanced fibrosis and cirrhosis. NASH is considered one of the clinical features of the metabolic syndrome in which insulin resistance plays a central role. This prospective study evaluates the role of insulin-sensitizing agent in treatment of NASH. Eighteen nondiabetic patients with biopsy-proven NASH were treated with pioglitazone (30 mg daily) for 48 weeks. Tests of insulin sensitivity and body composition as well as liver biopsies were performed before and at the end of treatment. By 48 weeks, serum alanine aminotransferase values fell to normal in 72% of patients. Hepatic fat content and size as determined by magnetic resonance imaging decreased, and glucose and free fatty acid sensitivity to insulin were uniformly improved. Histological features of steatosis, cellular injury, parenchymal inflammation, Mallory bodies, and fibrosis were significantly improved from baseline (all P < 0.05). Using strict criteria, histological improvement occurred in two-thirds of patients. Pioglitazone was well tolerated; the main side effects were weight gain (averaging 4%) and an increase in total body adiposity. In conclusion, these results indicate that treatment with an insulin-sensitizing agent can lead to improvement in biochemical and histological features of NASH and support the role of insulin resistance in the pathogenesis of this disease. The long-term safety and benefits of pioglitazone require further study. C1 NIDDK, Liver Dis Sect, Digest Dis Branch, NIH,DHHS, Bethesda, MD USA. Natl Inst Child Hlth & Dev, Unit Growth & Obes, Sect Womens Hlth, Dev Endocrinol Branch,NIH,DHHS, Bethesda, MD USA. NCI, Pathol Lab, NIH, DHHS, Bethesda, MD 20892 USA. NIH, Dept Diagnost Radiol, Warren G Magnuson Clin Ctr, DHHS, Bethesda, MD 20892 USA. RP Hoofnagle, JH (reprint author), Bldg 31,Room 9A27,31 Ctr Dr, Bethesda, MD 20892 USA. EM HoofnagleJ@extra.niddk.nih.gov RI Soza, Alejandro/C-2907-2009; Uwaifo, Gabriel/M-2361-2016; OI Uwaifo, Gabriel/0000-0002-6962-9304; Kleiner, David/0000-0003-3442-4453 FU NICHD NIH HHS [ZO1-HD-00641] NR 35 TC 439 Z9 460 U1 0 U2 11 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD JAN PY 2004 VL 39 IS 1 BP 188 EP 196 DI 10.1002/hep.20012 PG 9 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 805OK UT WOS:000220375400023 PM 14752837 ER PT J AU Kirk, GD Lesi, OA Mendy, M Akano, AO Sam, O Goedert, JJ Hainaut, P Hall, AJ Whittle, H Montesano, R AF Kirk, GD Lesi, OA Mendy, M Akano, AO Sam, O Goedert, JJ Hainaut, P Hall, AJ Whittle, H Montesano, R TI The Gambia Liver Cancer Study: Infection with hepatitis B and C and the risk of hepatocellular carcinoma in West Africa SO HEPATOLOGY LA English DT Article ID VIRUS-INFECTION; CIRRHOTIC-PATIENTS; DUAL INFECTION; UNITED-STATES; E-ANTIGEN; ETIOLOGY; GENDER; PREVALENCE; AGE; TRANSMISSION AB Hepatocellular carcinoma (HCC) is the most common cancer in The Gambia. Hepatitis B virus (HBV) infection is endemic, with 15% to 20% of the population being chronic carriers, whereas hepatitis C virus (HCV) prevalence is low. We recruited 216 incident cases of HCC and 408 controls from three sites. HBV carriage was present in 61% (129/211) of HCC patients and 16% (64/402) of controls, whereas 19% (36/191) of HCC patients were HCV seropositive compared with 3% (11/382) of controls. HCC patients with HCV were notably older and were more likely to be female than those with HBV. Increased HCC risk was strongly associated with chronic HBV (odds ratio, 16.7; 95% Cl, 9.7-28.7), HCV (16.7; 6.9-40.1), and dual infection (35.3; 3.9-323). We interpret the additive nature of risk with coinfection as representative of HBV and HCV acting primarily through shared steps in the multistage process of hepatocarcinogenesis. HCV infection was not observed among younger participants, suggesting a possible cohort effect. Reasons for the striking age and gender differences in HCC associated with HBV compared with HCV are unclear, but transmission patterns and age at exposure may be factors. In conclusion, in a standardized evaluation of well-characterized study participants from The Gambia, most cases of HCC are attributable to HBV (57%), but HCV adds a significant fraction (20%), especially among older patients and females. If HCV transmission is not perpetuated in future cohorts, focusing available resources on HB vaccination efforts could greatly ameliorate a major cause of cancer death in sub-Saharan Africa. C1 NCI, Viral Epidemiol Branch, DCEG, NIH,DHHS, Bethesda, MD 20892 USA. Int Agcy Res Canc, Gambia Hepatitis Intervent Study, Banjul, Gambia. Int Agcy Res Canc, Gambia Hepatitis Intervent Study, F-69372 Lyon, France. MRC Labs, Banjul, Gambia. Govt Gambia, Royal Victoria Hosp, Dept Med Serv, Banjul, Gambia. London Sch Hyg & Trop Med, London WC1, England. RP Kirk, GD (reprint author), NCI, Viral Epidemiol Branch, DCEG, NIH,DHHS, 6120 Execut Blvd,EPS-8003,MSC-7248, Bethesda, MD 20892 USA. EM kirkg@mail.nih.gov RI Kirk, Gregory/A-8484-2009; Hainaut, Pierre /B-6018-2012 OI Hainaut, Pierre /0000-0002-1303-1610 FU NCI NIH HHS [N01CP40521] NR 50 TC 94 Z9 96 U1 1 U2 3 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD JAN PY 2004 VL 39 IS 1 BP 211 EP 219 DI 10.1002/hep.20027 PG 9 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 805OK UT WOS:000220375400026 PM 14752840 ER PT J AU Grove, WS Harrison, EA AF Grove, WS Harrison, EA TI Benzodioxole chemistry. 5. Dramatic substituent effect in the reaction of carbonyl-bridged cyclic carbonates with methoxide ion SO HETEROCYCLES LA English DT Article DE benzodioxoledione; 2-cyclopenten-1-one; cyclohexadienecarboxylate ID CYCLOPENTENONES; AROMATIZATION AB Benzodioxolediones (2c-e) undergo high-yield conversion to cyclopentenones (3c-e) in K2CO3/MeOH at room temperature, while analogs (2a) and (2b) yield exclusively cyclohexadiene carboxylates (1a and 1b) under these conditions. Isolation of intermediate 6(R,R'=Me R"=Ph) from the reaction of 2c with K2CO3/MeOH at 5-10degreesC suggests that 3 is formed in a process triggered by attack of OMe(-) at the ester carbonyl of 2. C1 Penn State Univ, Dept Chem, York, PA 17403 USA. NIDDKD, Med Chem Sect, Chem Lab, NIH, Bethesda, MD 20892 USA. RP Harrison, EA (reprint author), Penn State Univ, Dept Chem, York Campus,1031 Edgecomb Ave, York, PA 17403 USA. EM eah1@psu.edu NR 10 TC 1 Z9 1 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0385-5414 J9 HETEROCYCLES JI Heterocycles PD JAN 1 PY 2004 VL 63 IS 1 BP 1 EP + PG 5 WC Chemistry, Organic SC Chemistry GA 763UK UT WOS:000188118700001 ER PT J AU Hampton, RR Buckmaster, CA Anuszkiewicz-Lundgren, D Murray, EA AF Hampton, RR Buckmaster, CA Anuszkiewicz-Lundgren, D Murray, EA TI Method for making selective lesions of the hippocampus in macaque monkeys using NMDA and a longitudinal surgical approach SO HIPPOCAMPUS LA English DT Article DE MRI; longitudinal; ibotenic acid; excitotoxin; medial temporal lobe ID RHESUS-MONKEY; EXCITOTOXIC LESIONS; NEUROTOXIC LESIONS; MEMORY IMPAIRMENT; AMYGDALA; PERFORMANCE; BRAIN; RECOGNITION; RETENTION; CORTEX AB We describe a method for making selective lesions of the hippocampus in macaque monkeys, using a magnetic resonance imaging (MRI)-guided stereotaxic approach in which the excitotoxin N-methyl-D-aspartic acid (NMDA) is injected at intervals along a single needle track that extends longitudinally through the rostrocaudal extent of the hippocampus. Procedures were conducted on six rhesus monkeys (Macaca mulatta) and were assessed with either in vivo MRI (n = 3) or postmortem microscopic examination of the tissue after standard histological processing of the brains (n = 3). Based on our extensive experience with the standard stereotaxic procedure in which ibotenic acid (IBO) is injected via the dorsal approach, we report that the new method provides a viable and potentially advantageous alternative to the standard procedure. First, the longitudinal approach combined with N-methyl-D-aspartic acid (NMDA) injections increases the reliability and efficacy of hippocampal excitotoxic lesions, probably by limiting the leakage of injectant into the ventricles. Second, the present procedure led to more rapid postoperative recovery compared with that after the standard procedure. Third, because the new method requires fewer needle penetrations than the standard method, it most likely reduces the chances of infarction in extrahippocampal tissue. Finally, the new surgical approach may provide a mechanism for infusing agents into the hippocampus from a single cannula. Published (C) 2003 Wiley-Liss, Inc.dagger C1 NIMH, Neuropsychol Lab, Sect Neurobiol Learning & Memory, NIH, Bethesda, MD 20892 USA. RP Hampton, RR (reprint author), NIMH, Neuropsychol Lab, Sect Neurobiol Learning & Memory, NIH, Bldg 49,Room 1B-80, Bethesda, MD 20892 USA. EM robert@ln.nimh.nih.gov OI Murray, Elisabeth/0000-0003-1450-1642 NR 27 TC 11 Z9 12 U1 0 U2 1 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 1050-9631 J9 HIPPOCAMPUS JI Hippocampus PY 2004 VL 14 IS 1 BP 9 EP 18 DI 10.1002/hipo.10150 PG 10 WC Neurosciences SC Neurosciences & Neurology GA 780EZ UT WOS:000189360500004 PM 15058478 ER PT J AU Nelson, TJ Backlund, PS Alkon, DL AF Nelson, TJ Backlund, PS Alkon, DL TI Hippocampal protein-protein interactions in spatial memory SO HIPPOCAMPUS LA English DT Article DE learning; memory; protein-protein interactions; mass spectrometry; calcium-binding proteins; calmodulin; complexin; stathmin ID LONG-TERM POTENTIATION; CALCIUM-BINDING PROTEINS; KINASE-C; SYNAPTIC PLASTICITY; MASS-SPECTROMETRY; GENE-EXPRESSION; MESSENGER-RNA; WATER-MAZE; DROSOPHILA; ACTIVATION AB Memory consolidation in mammalian brain is accompanied by widespread reorganization of synaptic contacts and dendritic structure. Understanding of the protein-protein interactions that underlie these structural changes has been hampered by the difficulty of studying protein-protein interactions produced in vivo by signaling, learning, and other physiological responses using current methodologies. Using a novel technique that separates interacting proteins from noninteracting proteins on the basis of their protein-target affinity, we identified 16 proteins for which protein-target binding is altered in vivo by spatial learning, including stathmin, complexin 1, 14-3-3, and several structural proteins including F-actin capping protein, tubulin, GFAP, and actin. Interactions between complexin and its targets (p25alpha and Drac1-like protein) and the interaction between CapZ and tubulin were calcium-dependent. The preponderance of structural proteins and proteins involved in synapse formation and reorganization of growth cones among proteins undergoing memory-specific changes in protein-protein interactions suggests that synaptic structural reorganization is a predominant feature of the consolidation phase of memory. (C) 2004 Wiley-Liss, Inc. C1 Blanchette Rockefeller Neurosci Inst, Rockville, MD 20850 USA. NIHCD, Sect Metab Anal & Mass Spect, LCMB, NIH, Bethesda, MD USA. RP Nelson, TJ (reprint author), Blanchette Rockefeller Neurosci Inst, 9601 Med Ctr Dr, Rockville, MD 20850 USA. EM tjnelson@brni-jhu.org NR 66 TC 40 Z9 42 U1 0 U2 1 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 1050-9631 J9 HIPPOCAMPUS JI Hippocampus PY 2004 VL 14 IS 1 BP 46 EP 57 DI 10.1002/hipo.10152 PG 12 WC Neurosciences SC Neurosciences & Neurology GA 780EZ UT WOS:000189360500008 PM 15058482 ER PT J AU Hampton, RR Hampstead, BM Murray, EA AF Hampton, RR Hampstead, BM Murray, EA TI Selective hippocampal damage in rhesus monkeys impairs spatial memory in an open-field test SO HIPPOCAMPUS LA English DT Article DE navigation; macaque; primate; temporal lobe; retention ID PRIMATE HIPPOCAMPUS; NEUROTOXIC LESIONS; FORNIX TRANSECTION; HUMAN NAVIGATION; EPISODIC MEMORY; PLACE; LOCATION; CORTEX; REPRESENTATION; ASSOCIATIONS AB The hippocampus is critical for remembering locations in a wide variety of species, including humans. However, recent findings from monkeys following selective hippocampal lesions have been equivocal. To approximate more closely the situations in which rodents and birds are tested, we used a spatial memory task in which rhesus monkeys (Macaca mulatta) moved about freely in a large room, on a tether. We used MRI-guided stereotaxic surgery to produce selective hippocampal lesions in five monkeys, and retained five unoperated control monkeys. In the study phase of each trial of the matching-to-location task, monkeys found food in one site in an array of identical foraging sites. During the test, which occurred after a delay, monkeys could return to the site where the food had been found during study to obtain more food. In Experiment 1, normal monkeys showed a small significant tendency to return directly to a site where they had previously found food that day. Operated monkeys showed no such matching tendency. In Experiment 2, further training produced reliable matching-to-location performance in both groups at short delays, but monkeys with selective hippocampal lesions rapidly forgot the location of the food. In Experiment 3, we tested whether monkeys used a "cognitive map" to encode the location of the hidden food, by requiring them to relocate the food from a starting location different from that used during study. As a group, monkeys were more accurate than expected by chance, indicating that they did encode the rewarded location with respect to allocentric landmarks; however, both groups of monkeys were significantly worse at relocating the food when required to approach from a different location. In Experiment 4, probe trials using symmetrical test arrays found no evidence for egocentric coding of the rewarded location. (C) 2004 Wiley-Liss, Inc. C1 NIMH, Neuropsychol Lab, Sect Neurobiol Learning & Memory, NIH, Bethesda, MD 20892 USA. RP Hampton, RR (reprint author), NIMH, Neuropsychol Lab, Sect Neurobiol Learning & Memory, NIH, Bldg 49,Room 1B80,49 Convent Dr, Bethesda, MD 20892 USA. EM robert@in.nimh.nih.gov OI Murray, Elisabeth/0000-0003-1450-1642 NR 51 TC 51 Z9 52 U1 0 U2 3 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1050-9631 J9 HIPPOCAMPUS JI Hippocampus PY 2004 VL 14 IS 7 BP 808 EP 818 DI 10.1002/hipo.10217 PG 11 WC Neurosciences SC Neurosciences & Neurology GA 862SI UT WOS:000224510800003 PM 15382251 ER PT J AU Kottilil, S Jagannatha, S Lu, A Liu, SY McLaughlin, M Metcalf, JA Dewar, R Campbell, C Koratich, C Maldarelli, F Masur, H Polis, MA AF Kottilil, S Jagannatha, S Lu, A Liu, SY McLaughlin, M Metcalf, JA Dewar, R Campbell, C Koratich, C Maldarelli, F Masur, H Polis, MA TI Changes in hepatitis C viral response after initiation of highly active antiretroviral therapy and control of HIV viremia in chronically co-infected individuals SO HIV CLINICAL TRIALS LA English DT Article DE HAART; HCV; HIV ID HUMAN-IMMUNODEFICIENCY-VIRUS; PROTEASE INHIBITORS; COINFECTED PATIENTS; IMMUNE RECOVERY; PLUS RIBAVIRIN; HCV RNA; PROGRESSION AB Background: HIV seropositive individuals co-infected with hepatitis C virus (HCV) have an increased risk for liver cirrhosis. We examined the long-term effect of controlling HIV infection with highly active antiretroviral therapy (HAART) on HCV viremia among co-infected patients. Method: HIV/HCV co-infected patients who initiated HAART and were able to control HIV viremia to <500 copies/mL were evaluated. HIV and HCV viremia were measured at each time point from frozen plasma samples by using bDNA methodology. Liver function tests and CD4+ and CD8+ T cell counts of all patients were obtained at each time point. Results: Seventeen co-infected patients met criteria for study from a cohort of 156 patients. Median time to achieve an HIV viral load (VL) <500 copies/mL after initiation of HAART was 28 weeks (range, 5-225 weeks). Thirteen of 17 patients had increases in HCV VL. Slope analysis of HCV VL vs. HIV VL was -0.14 (p =.0496), demonstrating a 0.14 log increase in HCV VL concomitant with control of HIV viremia. HCV viremia returned toward baseline levels in the 16 patients who maintained HIV suppression for 6 months. None cleared HCV after initiation of HAART during this time. Alkaline phosphatase, ALT, and AST levels were not significantly changed from baseline nor correlated with change in HCV VL (p >.05). Conclusion: Control of HIV viremia may result in an early increase in HCV viremia. In this study, for every 1 log decrease of HIV VL there was a 0.14 log increase of HCV VL. The exact mechanism of this flare seen with control of HIV viremia is unknown. However, HAART alone was not able to eliminate or significantly reduce the HCV viremia in this cohort of co-infected patients. C1 NIAID, Immunoregulat Lab, NIH, Bethesda, MD 20892 USA. NCI, SAIC, Bethesda, MD 20892 USA. NCI, HIV Drug Resistance Program, Bethesda, MD 20892 USA. NIH, Dept Crit Care Med, Bethesda, MD 20892 USA. RP Kottilil, S (reprint author), NIAID, Immunoregulat Lab, NIH, Bldg 10,room 6A11,9000 Wisconsin Ave, Bethesda, MD 20892 USA. EM Skottilil@niaid.nih.gov OI Polis, Michael/0000-0002-9151-2268 NR 21 TC 8 Z9 10 U1 0 U2 0 PU THOMAS LAND PUBLISHERS, INC PI ST LOUIS PA 255 JEFFERSON RD, ST LOUIS, MO 63119 USA SN 1528-4336 J9 HIV CLIN TRIALS JI HIV Clin. Trials PD JAN-FEB PY 2004 VL 5 IS 1 BP 25 EP 32 DI 10.1310/CVEU-980Q-MPRA-XRG8 PG 8 WC Infectious Diseases; Pharmacology & Pharmacy SC Infectious Diseases; Pharmacology & Pharmacy GA 803DF UT WOS:000220211100006 PM 15002084 ER PT J AU Krupitsky, E Zvartau, E Karandashova, G Horton, NJ Schoolwerth, KR Bryant, K Samet, JH AF Krupitsky, E Zvartau, E Karandashova, G Horton, NJ Schoolwerth, KR Bryant, K Samet, JH TI The onset of HIV infection in the Leningrad region of Russia: a focus on drug and alcohol dependence SO HIV MEDICINE LA English DT Article DE AIDS; alcohol and drug dependence; HIV; HIV prevalence; Russia ID RISK BEHAVIORS; CONSUMPTION; USERS AB Objectives Within 5 years, 5 million Russians may be infected with HIV. Currently, injection drug use is the major risk factor for HIV. As Russia's alcohol consumption per capita is among the highest in the world, alcohol-associated behaviours may be an important contributor to the HIV epidemic. Our objective was to examine the prevalence of HIV infection among drug- and alcohol-dependent patients in a regional narcology hospital and in the general population in Leningrad. Methods All patients in the Narcology Hospital, Leningrad Regional Center of Addictions (LRCA), were tested for HIV antibody between 1997 and 2001. We reviewed these clinical records (i.e. serostatus, gender, age, and addiction) and data from the HIV/AIDS Center in the Leningrad Region (1997-2001). Results From 1997 to 2001, HIV prevalence at the LRCA increased from 0 to 12.7% overall, 33.4% among drug-dependent patients and 1.2% among alcohol-dependent patients. During the same 5-year period (1997-2001), 2826 persons were registered at the HIV/AIDS Center: 6, 6, 519 780, and 1983 persons in 1997, 1998, 1999, 2000 and 2001, respectively. Conclusions HIV infection is exploding in the Leningrad Region, currently in injection drug users (IDUs) but potentially more broadly. The known high per capita alcohol intake in Russia heightens concern regarding the sexual transmission of HIV. Interventions to prevent such a development should include use, and assessment of the effectiveness, of known HIV prevention measures for at-risk and infected individuals. C1 St Petersburg State Univ, St Petersburg Sci Res Ctr Addict & Psychopharmaco, St Petersburg, Russia. Smith Coll, Dept Math, Northampton, MA 01063 USA. Boston Univ, Sch Med, Gen Internal Med Sect, CARE Unit,Dept Med, Boston, MA 02215 USA. Boston Univ, Sch Med, Gen Internal Med Sect, CARE Unit,Dept Social & Behav Sci, Boston, MA 02215 USA. Boston Univ, Sch Publ Hlth, Gen Internal Med Sect, CARE Unit,Dept Social & Behav Sci, Boston, MA 02215 USA. Boston Univ, Sch Publ Hlth, Gen Internal Med Sect, CARE Unit,Dept Med, Boston, MA 02215 USA. NIAAA, NIH, Bethesda, MD USA. RP Samet, JH (reprint author), Boston Med Ctr, CARE Unit, Gen Internal Med Sect, 91 E Concord St,Suite 200, Boston, MA 02118 USA. EM jsamet@bu.edu RI Horton, Nicholas/A-2493-2008; OI Horton, Nicholas/0000-0003-3332-4311 FU NIAAA NIH HHS [R01-AA11785] NR 18 TC 31 Z9 32 U1 0 U2 1 PU BLACKWELL PUBLISHING LTD PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 1464-2662 J9 HIV MED JI HIV Med. PD JAN PY 2004 VL 5 IS 1 BP 30 EP 33 DI 10.1111/j.1468-1293.2004.00182.x PG 4 WC Infectious Diseases SC Infectious Diseases GA 812UF UT WOS:000220863700006 PM 14731167 ER PT J AU Nwosu, BU Coco, M Jones, J Barnes, KM Yanovski, JA Baron, J AF Nwosu, BU Coco, M Jones, J Barnes, KM Yanovski, JA Baron, J TI Short stature with normal growth hormone stimulation testing: Lack of evidence for partial growth hormone deficiency or insensitivity SO HORMONE RESEARCH LA English DT Article DE growth hormone deficiency; short stature ID IDIOPATHIC SHORT STATURE; GH PROVOCATIVE TEST; CHILDREN; CHILDHOOD; DIAGNOSIS; ADULTS; RECEPTOR; THERAPY; INSULIN; HYPOGLYCEMIA AB Objectives: To test the hypothesis that children with short stature and peak stimulated GH (pGH) of 7 - 10 mug/l have partial GH deficiency and to test the hypothesis that short children with normal pGH but low IGF-I levels have partial GH deficiency or partial GH insensitivity. Design and Patients: Retrospective analysis of the clinical and biochemical profiles of 76 children who underwent an evaluation for short stature ( height <5th percentile) that included two, sex steroid-primed GH stimulation tests. Results: Patients with pGH <7 mug/l ( n = 14) differed significantly from those with pGH <7 μg/l ( n = 62), having greater midparental height (MPH) SDS, a greater disparity between height SDS and MPH SDS, and lower IGF-I SDS. Patients with pGH of 7 - 10 μg/l ( n = 12) did not have characteristics intermediate between those with pGH <7 mug/l and those with pGH greater than or equal to10 mug/l, but instead resembled those with pGH greater than or equal to10 mug/l. Patients with pGH greater than or equal to7 mug/l, but low IGF-I (< - 2 SDS) ( n = 5), did not show characteristics intermediate between those with pGH <7 mug/l and those with pGH greater than or equal to7 mug/l and normal IGF-I. Conclusions: These data do not support either the hypothesis that children with pGH of 7 - 10 mug/l have partial GH deficiency or the hypothesis that children with normal pGH but subnormal IGF-I levels have partial GH deficiency or insensitivity. Copyright (C) 2004 S. Karger AG, Basel. C1 NICHHD, Dev Endocrinol Branch, NIH, Bethesda, MD 20892 USA. RP Baron, J (reprint author), NICHHD, Dev Endocrinol Branch, NIH, Bldg 10 RM 10N262,10 Ctr Dr MSC 1862, Bethesda, MD 20892 USA. EM jeffrey_baron@nih.gov OI Nwosu, Benjamin/0000-0003-2212-0276; Yanovski, Jack/0000-0001-8542-1637 NR 30 TC 7 Z9 7 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0301-0163 J9 HORM RES JI Horm. Res. PY 2004 VL 62 IS 2 BP 97 EP 102 DI 10.1159/000079711 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 852LR UT WOS:000223757300009 PM 15256821 ER PT J AU Conroy, S Jenkins, D Stratakis, C Wassif, WS Cooper, J AF Conroy, S Jenkins, D Stratakis, C Wassif, WS Cooper, J TI Atrial myxoma: a cardiocutaneous syndrome SO HOSPITAL MEDICINE LA English DT Article ID RECURRENT CARDIAC MYXOMA; CARNEY COMPLEX; FEATURES C1 Bedford Hosp, Dept Med, Bedford MK42 9DJ, England. Bedford Hosp, Dept Chem Pathol, Bedford MK42 9DJ, England. Bedford Hosp, Dept Cardiol, Bedford MK42 9DJ, England. Papworth Hosp, Cambridge CB3 8RE, England. NICHD, Unit Genet & Endocrinol, Dev Endocrinol Branch, NIH, Bethesda, MD USA. RP Conroy, S (reprint author), Bedford Hosp, Dept Med, Bedford MK42 9DJ, England. RI Conroy, Simon/B-8832-2009 NR 10 TC 1 Z9 1 U1 0 U2 0 PU MARK ALLEN PUBLISHING LTD PI LONDON PA CROXTED MEWS, 286A-288 CROXTED ROAD, LONDON SE24 9BY, ENGLAND SN 1462-3935 J9 HOSP MED JI Hosp. Med PD JAN PY 2004 VL 65 IS 1 BP 56 EP 57 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 763ZK UT WOS:000188163400018 PM 14964803 ER PT J AU Soares, HD Williams, SA Snyder, PJ Gao, F Stiger, T Rohlff, C Herath, A Sunderland, T Putnam, K White, WF AF Soares, HD Williams, SA Snyder, PJ Gao, F Stiger, T Rohlff, C Herath, A Sunderland, T Putnam, K White, WF TI Proteomic approaches in drug discovery and development SO HUMAN BRAIN PROTEOME SE INTERNATIONAL REVIEW OF NEUROBIOLOGY LA English DT Review ID PROTEIN-PROTEIN INTERACTIONS; IMAGING MASS-SPECTROMETRY; ALZHEIMERS-DISEASE; CEREBROSPINAL-FLUID; FUNCTIONAL PROTEOMICS; PHAGE DISPLAY; 2-DIMENSIONAL ELECTROPHORESIS; HUMAN HIPPOCAMPUS; INTERACTION MAP; PDZ DOMAIN C1 Pfizer Global Res & Dev, Groton, CT 06340 USA. Oxford Glycosci, Abingdon OX1 3QX, Oxon, England. NIMH, Bethesda, MD 20892 USA. RP Soares, HD (reprint author), Pfizer Global Res & Dev, Groton, CT 06340 USA. OI Snyder, Peter/0000-0003-0555-4654 NR 104 TC 9 Z9 9 U1 0 U2 0 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA SN 0074-7742 J9 INT REV NEUROBIOL PY 2004 VL 61 BP 97 EP + PG 33 WC Neurosciences SC Neurosciences & Neurology GA BBD73 UT WOS:000225040300005 PM 15482813 ER PT J AU Chen, JB Peters, U Foster, C Chatterjee, N AF Chen, JB Peters, U Foster, C Chatterjee, N TI A haplotype-based test of association using data from cohort and nested case-control epidemiologic studies SO HUMAN HEREDITY LA English DT Article DE nested case-control studies; haplotype; genotype; Cox proportional hazards model ID LARGE CANCER PREVENTION; UNRELATED INDIVIDUALS; GENOTYPE DATA; REGRESSION-MODEL; DISEASE; RISK; POLYMORPHISMS; LOCUS; CASE/CONTROL; FREQUENCIES AB Haplotype-based risk models can lead to powerful methods for detecting the association of a disease with a genomic region of interest. In population-based studies of unrelated individuals, however, the haplotype status of some subjects may not be discernible without ambiguity from available locus-specific genotype data. A score test for detecting haplotype-based association using genotype data has been developed in the context of generalized linear models for analysis of data from cross-sectional and retrospective studies [ 1]. In this article, we develop a test for association using genotype data from cohort and nested case-control studies where subjects are prospectively followed until disease incidence or censoring (end of follow-up) occurs. Assuming a proportional hazard model for the haplotype effects, we derive an induced hazard function of the disease given the genotype data, and hence propose a test statistic based on the associated partial likelihood. The proposed test procedure can account for differential follow-up of subjects, can adjust for possibly time-dependent environmental co-factors and can make efficient use of valuable age-at-onset information that is available on cases. We provide an algorithm for computing the test statistic using readily available statistical software. Utilizing simulated data in the context of two genomic regions GPX1 and GPX3, we evaluate the validity of the proposed test for small sample sizes and study its power in the presence and absence of missing genotype data. Copyright (C) 2004 S. Karger AG, Basel. C1 NCI, Biostat Branch, Div Canc Epidemiol & Genet, Rockville, MD 20852 USA. NCI, Nutr Epidemiol Branch, Div Canc Epidemiol & Genet, Rockville, MD 20852 USA. Johns Hopkins Univ, Sch Med, Dept Pediat, Baltimore, MD 21205 USA. RP Chen, JB (reprint author), NCI, Biostat Branch, Div Canc Epidemiol & Genet, 6120 Execut Blvd EPS 8089, Rockville, MD 20852 USA. EM chenjin@mail.nih.gov NR 33 TC 11 Z9 11 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0001-5652 J9 HUM HERED JI Hum. Hered. PY 2004 VL 58 IS 1 BP 18 EP 29 DI 10.1159/000081453 PG 12 WC Genetics & Heredity SC Genetics & Heredity GA 883LK UT WOS:000226013100003 PM 15604561 ER PT J AU Schulze, TG McMahon, FJ AF Schulze, TG McMahon, FJ TI Defining the phenotype in human genetic studies: Forward genetics and reverse phenotyping SO HUMAN HEREDITY LA English DT Article DE phenotypes; assessment; reliability; validity; covariate ID COMPLEX HUMAN-DISEASES; SIB-PAIR ANALYSIS; LINKAGE ANALYSIS; DIAGNOSTIC-CRITERIA; BIPOLAR DISORDER; MENTAL-DISORDERS; FAMILY-HISTORY; SCHIZOPHRENIA; ASSOCIATION; VALIDITY AB The definition of phenotypes for genetic study is a challenging endeavor. Just as we apply strict quality standards to genotype data, we should expect that phenotypes meet consistently high standards of reproducibility and validity. The methods for achieving accurate phenotype assignment in the research setting - the 'research diagnosis' - are different from the methods used in clinical diagnosis in the patient care setting. We evaluate some of the main challenges of phenotype definition in human genetics, and begin to outline a set of standards to which phenotypes used in genetics studies may aspire with the goal of increasing the quality and reproducibility of linkage and association studies. Revisiting the traditional phenotype definitions through a focus on familial components and heritable endophenotypes is a time-honored approach. Reverse phenotyping, where phenotypes are refined based on genetic marker data, may be a promising new approach. The stakes are high, since the success of gene mapping in genetically complex disorders hinges on the ability to delineate the target phenotype with accuracy and precision. Copyright (C) 2004S. Karger AG, Basel. C1 Univ Heidelberg, Cent Inst Mental Hlth, Div Genet Epidemiol Pscyhiat, D-68159 Mannheim, Germany. NIMH, Genet Basis Mood & Anxiety Disorders Mood & Anxie, NIH, US Dept HHS, Bethesda, MD 20892 USA. RP Schulze, TG (reprint author), Univ Heidelberg, Cent Inst Mental Hlth, Div Genet Epidemiol Pscyhiat, J5, D-68159 Mannheim, Germany. EM schulze@zi-mannheim.de RI McMahon, Francis/A-7290-2009; Schulze, Thomas/H-2157-2013; OI McMahon, Francis/0000-0002-9469-305X NR 57 TC 74 Z9 75 U1 0 U2 1 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0001-5652 J9 HUM HERED JI Hum. Hered. PY 2004 VL 58 IS 3-4 BP 131 EP 138 DI 10.1159/000083539 PG 8 WC Genetics & Heredity SC Genetics & Heredity GA 911FU UT WOS:000227988800003 PM 15812169 ER PT J AU Pankow, JS Heiss, G Evans, GW Sholinsky, P Province, MA Coon, H Ellison, RC Miller, MB AF Pankow, JS Heiss, G Evans, GW Sholinsky, P Province, MA Coon, H Ellison, RC Miller, MB TI Familial aggregation and genome-wide linkage analysis of carotid artery plaque: The NHLBI Family Heart Study SO HUMAN HEREDITY LA English DT Article DE carotid artery plaque; genome-wide scan; heritability; atherosclerosis; linkage analysis ID INTIMA-MEDIA THICKNESS; B-MODE ULTRASOUND; ATHEROSCLEROSIS RISK; PARENTAL HISTORY; WALL THICKNESS; GENETIC-BASIS; CORONARY; DISEASE; STROKE; HERITABILITY AB Objective: To evaluate familial and genetic influences on carotid artery plaque, a qualitative marker of the systemic burden of atherosclerosis. Methods: The design was a cross-sectional study of 2,223 members of 525 randomly-ascertained families and 2,514 members of 589 high coronary heart disease (CHD) risk families from 4 U. S. communities. Results: The prevalence of plaque was 33, 36, and 47%, respectively, among probands with 0, 1, and 2 or more first-degree relatives with a history of CHD. There was evidence of sibling aggregation of plaque in random families (OR = 1.89; 95% CI: 1.44, 2.48), but associations were substantially attenuated when adjusted for major cardiovascular disease risk factors. A genome scan with 420 microsatellite markers revealed no regions of significant or suggestive linkage for plaque in 342 affected sibling pairs, although suggestive linkage (LOD score: 2.43) was found on chromosome 2p11.2 (D2S1790) in pairs aged 55 years or younger. Other markers with nominal evidence for linkage (p < 0.05) were found on chromosomes 2p25, 2q24-q32, 6q21-q23, 7p12-p21, 7q11-q21, 8q24, 12q12-q13, 18p11, 21q21 and Xp11, Xq12, and Xq24. Conclusions: There was modest familial aggregation of carotid artery plaque, but a genome-wide scan indicated no regions of significant or suggestive linkage. Copyright (C) 2004 S. Karger AG, Basel. C1 Univ Minnesota, Div Epidemiol, Minneapolis, MN 55454 USA. Univ N Carolina, Dept Epidemiol, Chapel Hill, NC USA. Univ N Carolina, Dept Biostat, Chapel Hill, NC USA. Wake Forest Sch Med, Dept Publ Hlth Sci, Winston Salem, NC USA. NHLBI, Epidemiol & Biometry Program, Bethesda, MD 20892 USA. Washington Univ, Div Biostat, St Louis, MO USA. Univ Utah, Dept Psychiat, Salt Lake City, UT USA. Boston Univ, Sch Med, Prevent Med & Epidemiol Sect, Boston, MA 02118 USA. RP Pankow, JS (reprint author), Univ Minnesota, Div Epidemiol, 1300 S 2nd St,Suite 300, Minneapolis, MN 55454 USA. EM pankow@epi.umn.edu OI Ellison, Robert Curtis/0000-0002-0582-7467; Coon, Hilary/0000-0002-8877-5446; Pankow, James/0000-0001-7076-483X FU NHLBI NIH HHS [N01 HC 25104, N01 HC 25105, N01 HC 25106, N01 HC 25107, N01 HC 25108, N01 HC 25109] NR 57 TC 17 Z9 17 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0001-5652 J9 HUM HERED JI Hum. Hered. PY 2004 VL 57 IS 2 BP 80 EP 89 DI 10.1159/000077545 PG 10 WC Genetics & Heredity SC Genetics & Heredity GA 827ZA UT WOS:000221941000003 PM 15192280 ER PT J AU Adams, S Chun, H Uribe, M Mitchell, S Marincola, F Stroncek, D AF Adams, S Chun, H Uribe, M Mitchell, S Marincola, F Stroncek, D TI Use of a multi channel dynamic temperature measurment system (MTAS) to determine the efficiency of GeneAmp PCR System 9700 SO HUMAN IMMUNOLOGY LA English DT Meeting Abstract CT 30th Annual Meeting of the American-Society-for-Histocompatibility-and-Immunogenetics CY OCT 02-06, 2004 CL San Antonio, TX SP Amer Soc Histocompatibil & Immunogenet C1 NIH, HLA Lab, Dept Transfus Med, Bethesda, MD USA. Appropriate Tech Resources, Laurel, MD USA. NR 0 TC 0 Z9 0 U1 1 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0198-8859 J9 HUM IMMUNOL JI Hum. Immunol. PY 2004 VL 65 SU 1 BP S113 EP S113 DI 10.1016/j.humimm.2004.07.215 PG 1 WC Immunology SC Immunology GA 861OC UT WOS:000224425300218 ER PT J AU Bettinotti, MP Slezak, S Caruccio, L Stroncek, D AF Bettinotti, MP Slezak, S Caruccio, L Stroncek, D TI Comprehensive analysis of human CMV T cell response reveals epitopes common to both HLA class I and class II restriction SO HUMAN IMMUNOLOGY LA English DT Meeting Abstract CT 30th Annual Meeting of the American-Society-for-Histocompatibility-and-Immunogenetics CY OCT 02-06, 2004 CL San Antonio, TX SP Amer Soc Histocompatibil & Immunogenet C1 NIH, DTM, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0198-8859 J9 HUM IMMUNOL JI Hum. Immunol. PY 2004 VL 65 SU 1 BP S72 EP S72 DI 10.1016/j.humimm.2004.07.136 PG 1 WC Immunology SC Immunology GA 861OC UT WOS:000224425300139 ER PT J AU Frahm, N Yusim, K Hraber, P Adams, S Marincola, F Korber, B Brander, C AF Frahm, N Yusim, K Hraber, P Adams, S Marincola, F Korber, B Brander, C TI Extensive HLA class I binding promiscuity among EBV- and HIV-derived cytotoxic T lymphocyte epitopes SO HUMAN IMMUNOLOGY LA English DT Meeting Abstract CT 30th Annual Meeting of the American-Society-for-Histocompatibility-and-Immunogenetics CY OCT 02-06, 2004 CL San Antonio, TX SP Amer Soc Histocompatibil & Immunogenet C1 Massachusetts Gen Hosp, Partners AIDS Res Ctr, Charlestown, MA USA. Los Alamos Natl Lab, Los Alamos, NM USA. Santa Fe Inst, Santa Fe, NM 87501 USA. NIH, Ctr Clin, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0198-8859 J9 HUM IMMUNOL JI Hum. Immunol. PY 2004 VL 65 SU 1 BP S2 EP S2 PG 1 WC Immunology SC Immunology GA 861OC UT WOS:000224425300004 ER PT J AU Kowalski, RJ Post, DR Britz, JA Mannon, RB Daller, JA Reed, EF Burdick, JF AF Kowalski, RJ Post, DR Britz, JA Mannon, RB Daller, JA Reed, EF Burdick, JF TI Predictive value of the Cylex (R) Immuknow (TM) assay in kidney recipients SO HUMAN IMMUNOLOGY LA English DT Meeting Abstract CT 30th Annual Meeting of the American-Society-for-Histocompatibility-and-Immunogenetics CY OCT 02-06, 2004 CL San Antonio, TX SP Amer Soc Histocompatibil & Immunogenet C1 Cylex Inc, Prod Dev, Columbia, MD USA. NIDDK, Transplantat Branch, NIH, DHHS, Bethesda, MD USA. Univ Texas, Med Branch, Galveston, TX 77550 USA. Univ Calif Los Angeles, Immunogenet Ctr, Los Angeles, CA USA. Div Transplantat Hlth Resources & Serv Adm, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0198-8859 J9 HUM IMMUNOL JI Hum. Immunol. PY 2004 VL 65 SU 1 BP S65 EP S65 DI 10.1016/j.humimm.2004.07.122 PG 1 WC Immunology SC Immunology GA 861OC UT WOS:000224425300125 ER PT J AU Nambiar, A Adams, S Oblitas, J Leitman, S Duquesnoy, R Stroncek, D Marincola, F AF Nambiar, A Adams, S Oblitas, J Leitman, S Duquesnoy, R Stroncek, D Marincola, F TI Analysis of platelet increments in HLA alloimmunized patients verifies the HLA matchmaker algorithm SO HUMAN IMMUNOLOGY LA English DT Meeting Abstract CT 30th Annual Meeting of the American-Society-for-Histocompatibility-and-Immunogenetics CY OCT 02-06, 2004 CL San Antonio, TX SP Amer Soc Histocompatibil & Immunogenet C1 NIH, Bethesda, MD 20892 USA. Univ Pittsburgh, Med Ctr, Pittsburgh, PA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0198-8859 J9 HUM IMMUNOL JI Hum. Immunol. PY 2004 VL 65 SU 1 BP S68 EP S68 DI 10.1016/j.humimm.2004.07.127 PG 1 WC Immunology SC Immunology GA 861OC UT WOS:000224425300130 ER PT J AU Uribe, MR Adams, S Marincola, F Stronceck, D AF Uribe, MR Adams, S Marincola, F Stronceck, D TI Correlation of data obtained utilizing MTAS thermal cycler validation systems and unexpected primer annealing SO HUMAN IMMUNOLOGY LA English DT Meeting Abstract CT 30th Annual Meeting of the American-Society-for-Histocompatibility-and-Immunogenetics CY OCT 02-06, 2004 CL San Antonio, TX SP Amer Soc Histocompatibil & Immunogenet C1 NIH, HLA Lab, DTM, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0198-8859 J9 HUM IMMUNOL JI Hum. Immunol. PY 2004 VL 65 SU 1 BP S77 EP S77 DI 10.1016/j.humimm.2004.07.145 PG 1 WC Immunology SC Immunology GA 861OC UT WOS:000224425300148 ER PT J AU Uribe, MR Adams, S Shupert, WL Stroncek, D Connors, M Marincola, F AF Uribe, MR Adams, S Shupert, WL Stroncek, D Connors, M Marincola, F TI Association between HLA-1357, KIR genes and HIV progression SO HUMAN IMMUNOLOGY LA English DT Meeting Abstract CT 30th Annual Meeting of the American-Society-for-Histocompatibility-and-Immunogenetics CY OCT 02-06, 2004 CL San Antonio, TX SP Amer Soc Histocompatibil & Immunogenet C1 Natl Inst Hlth, HLA Lab, DTM, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0198-8859 J9 HUM IMMUNOL JI Hum. Immunol. PY 2004 VL 65 SU 1 BP S68 EP S68 DI 10.1016/j.humimm.2004.07.128 PG 1 WC Immunology SC Immunology GA 861OC UT WOS:000224425300131 ER PT J AU Zhang, H Di, WY Zhang, J Xu, HX Fang, ZY Zhao, TM AF Zhang, H Di, WY Zhang, J Xu, HX Fang, ZY Zhao, TM TI An unusuall HLA haplotype carrying two expressional HLA-A allels: A24020101 and A1102 SO HUMAN IMMUNOLOGY LA English DT Meeting Abstract CT 30th Annual Meeting of the American-Society-for-Histocompatibility-and-Immunogenetics CY OCT 02-06, 2004 CL San Antonio, TX SP Amer Soc Histocompatibil & Immunogenet C1 Suzhou Red Cross Blood Ctr, HLA Lab, Suzhou, Jiangsu, Peoples R China. NIAID, Natl Inst Hlth, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0198-8859 J9 HUM IMMUNOL JI Hum. Immunol. PY 2004 VL 65 SU 1 BP S93 EP S93 DI 10.1016/j.humimm.2004.07.175 PG 1 WC Immunology SC Immunology GA 861OC UT WOS:000224425300178 ER PT J AU Karban, AS Okazaki, T Panhuysen, CIM Gallegos, T Potter, JJ Bailey-Wilson, JE Silverberg, MS Duerr, RH Cho, JH Gregersen, PK Wu, YQ Achkar, JP Dassopoulos, T Mezey, E Bayless, TM Nouvet, FJ Brant, SR AF Karban, AS Okazaki, T Panhuysen, CIM Gallegos, T Potter, JJ Bailey-Wilson, JE Silverberg, MS Duerr, RH Cho, JH Gregersen, PK Wu, YQ Achkar, JP Dassopoulos, T Mezey, E Bayless, TM Nouvet, FJ Brant, SR TI Functional annotation of a novel NFKB1 promoter polymorphism that increases risk for ulcerative colitis SO HUMAN MOLECULAR GENETICS LA English DT Article ID NF-KAPPA-B; INFLAMMATORY-BOWEL-DISEASE; TRANSCRIPTION FACTOR; CROHNS-DISEASE; C-REL; CHROMOSOMAL LOCALIZATION; IL-10-DEFICIENT MICE; SUSCEPTIBILITY LOCI; DISEQUILIBRIUM TEST; GENE POLYMORPHISMS AB Nuclear Factor-kappaB (NF-kappaB) is a major transcription regulator of immune response, apoptosis and cell-growth control genes, and is upregulated in inflammatory bowel disease (IBD), both ulcerative colitis (UC) and Crohn's disease. The NFKB1 gene encodes the NF-kappaB p105/p50 isoforms. Genome-wide screens in IBD families show evidence for linkage on chromosome 4q where NFKB1 maps. We sequenced the NFKB1 promoter, exon 1 and all coding exons in 10 IBD probands and two controls, and identified six nucleotide variants, including a common insertion/deletion promoter polymorphism (-94ins/delATTG). Using pedigree-based transmission disequilibrium tests, we observed modest evidence for linkage disequilibrium (LD), independent of linkage, between the -94delATTG allele and UC in 131 out of 235 IBD pedigrees with UC offspring (P=0.047-0.052). This allele was also more frequent in the 156 non-Jewish UC probands from the 235 IBD pedigrees than in 149 non-Jewish controls (P=0.015). The -94delATTG association with UC was replicated in a second set of 258 unrelated, non-Jewish UC cases and 653 new, non-Jewish controls (P=0.021). Nuclear proteins from normal human colon tissue and colonic cell lines, but not ileal tissue, showed significant binding to -94insATTG but not to -94delATTG containing oligonucleotides. NFKB1 promoter/exon 1 luciferase reporter plasmid constructs containing the -94delATTG allele and transfected into either HeLa or HT-29 cell lines showed less promoter activity than comparable constructs containing the -94insATTG allele. Therefore, we have identified the first potentially functional polymorphism of NFKB1 and demonstrated its genetic association with a common human disease, ulcerative colitis. C1 Johns Hopkins Univ, Sch Med, Dept Med,Gastroenterol Div, Harvey M & Lyn P Meyerhoff Inflammatory Bowel Dis, Baltimore, MD 21231 USA. Boston Univ, Sch Med, Boston, MA 02118 USA. NHGRI, NIH, Baltimore, MD USA. Univ Toronto, Dept Med, Toronto, ON, Canada. Univ Toronto, Dept Surg, Toronto, ON, Canada. Mt Sinai Hosp, Toronto, ON M5G 1X5, Canada. Univ Pittsburgh, Sch Med, Dept Med, Div Gastroenterol Hepatol & Nutr, Pittsburgh, PA USA. Univ Chicago Hosp, Dept Med, Gastroenterol Sect, Martin Boyer Labs, Chicago, IL 60637 USA. N Shore Long Isl Jewish Res Inst, Ctr Genom & Human Genet, Manhasset, NY USA. Cleveland Clin Fdn, Dept Gastroenterol, Cleveland, OH 44195 USA. Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA. RP Brant, SR (reprint author), Johns Hopkins Univ, Sch Med, Dept Med,Gastroenterol Div, Harvey M & Lyn P Meyerhoff Inflammatory Bowel Dis, 1503 E Jefferson St,Room B136, Baltimore, MD 21231 USA. RI Silverberg, Mark/B-4183-2008; OI Bailey-Wilson, Joan/0000-0002-9153-2920; Duerr, Richard/0000-0001-6586-3905 FU NCRR NIH HHS [RR00052, RR00055]; NIDDK NIH HHS [R01DK58189] NR 65 TC 217 Z9 225 U1 0 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 JAN 1 PY 2004 VL 13 IS 1 BP 35 EP 45 DI 10.1093/hmg/ddh008 PG 11 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA 756KF UT WOS:000187463700005 PM 14613970 ER PT J AU Touitou, I Lesage, S McDermott, M Cuisset, L Hoffman, H Dode, C Shoham, N Aganna, E Hugot, JP Wise, C Waterham, H Pugnere, D Demaille, J de Menthiere, CS AF Touitou, I Lesage, S McDermott, M Cuisset, L Hoffman, H Dode, C Shoham, N Aganna, E Hugot, JP Wise, C Waterham, H Pugnere, D Demaille, J de Menthiere, CS TI Infevers: An evolving mutation database for auto-inflammatory syndromes SO HUMAN MUTATION LA English DT Article DE database; MEFV; TNFRSF1A; MVK; CARD 15; PSTPIP1; CIAS1; autoinflammatory disease ID ENCODING MEVALONATE KINASE; PERIODIC FEVER SYNDROME; DISORDERS; DISEASE; FAMILY AB The Infevers database (http://fmf.igh.cnrs-fr/infevers/) was established in 2002 to provide investigators with access to a central source of information about all sequence variants associated with periodic fevers: Familial Mediterranean fever (IMF), TNF Receptor Associated Periodic Syndrome (TRAPS), Hyper IgD Syndrome (HIDS), Familial Cold Autoinflammatory Syndrome/Muckle-Wells Syndrome/Chronic Infantile Neurological Cutaneous and Articular Syndrome (FCAS/MWS/CINCA). The prototype of this group of disorders is IMF, a recessive disease characterized by recurrent bouts of unexplained inflammation. FMF is the pivotal member of an expanding family of autoinflammatory disorders, a new term coined to describe illnesses resulting from a defect of the innate immune response. Therefore, we decided to extend the Infevers database to genes connected with autoinflammatory diseases. We present here the biological content of the Infevers database, including the introduction of two new entries: Crohn/Blau and Pyogenic sterile arthritis, pyoderma gangrenosum and acne (PAPA syndrome). Infevers has a range of query capabilities, allowing for simple or complex interrogation of the database. Currently, the database contains 291 sequence variants in related genes (MEFV, TNFRSF1A, MVK, CARD15, PSTPIP1, and CIAS1), consisting of published data and personal communications, which has revealed or refined the preferential mutational sites for each gene. This database will continue to evolve in its content and to improve in its presentation. (C) 2004 Wiley-Liss, Inc. C1 Hosp Ade Villeneuve, Genet Lab, Montpellier, France. CEPH, Fdn Jean Dausset, Paris, France. Barts & London Queen Mary Sch Med & Dent, London, England. Hop Cochin, Lab Biochim Genet, F-75674 Paris, France. Med Coll Georgia, Dept Pediat, Allergy Immunol Sect, Augusta, GA 30912 USA. NIAMSD, NIH, Bethesda, MD 20892 USA. Texas Scottish Rite Hosp Children, Sarah M & Charles E Seay Ctr Musculoskeletal Res, Dallas, TX USA. Emma Childrens Hosp, Amsterdam, Netherlands. Acad Med Ctr, Lab Genet Metab Dis, Dept Pediat, Amsterdam, Netherlands. Inst Genet Humaine, Montpellier, France. RP Touitou, I (reprint author), Hosp Ade Villeneuve, Genet Lab, Montpellier, France. EM Isabelle.touitou@igh.cnrs.fr RI Hugot, Jean-Pierre/F-6594-2012; OI Wise, Carol/0000-0002-6790-2194 NR 13 TC 149 Z9 154 U1 0 U2 5 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1059-7794 J9 HUM MUTAT JI Hum. Mutat. PY 2004 VL 24 IS 3 BP 194 EP 198 DI 10.1002/humu.20080 PG 5 WC Genetics & Heredity SC Genetics & Heredity GA 846GW UT WOS:000223304800002 PM 15300846 ER PT J AU Consolandi, C Frosini, A Pera, C Ferrara, GB Bordoni, R Castiglioni, B Rizzi, E Mezzelani, A Bernardi, LR De Bellis, G Battaglia, C AF Consolandi, C Frosini, A Pera, C Ferrara, GB Bordoni, R Castiglioni, B Rizzi, E Mezzelani, A Bernardi, LR De Bellis, G Battaglia, C TI Polymorphism analysis within the HLA-A locus by universal oligonucleotide array SO HUMAN MUTATION LA English DT Article DE HLA-A; SNP; genotyping; mutation detection; universal array; PCR-LDR ID POLYMERASE-CHAIN-REACTION; EXPRESSION; SYSTEM AB Human leukocyte antigen (HLA) class I genes present some of the most complex single nucleotide polymorphism (SNP) patterns in the human genome. HLA typing is therefore extremely challenging. In this article, we use the ligation detection reaction (LDR) combined with a universal array (UA) as a robust and efficient method to analyze SNPs within the HLA-A region that includes HLA-A alleles of interest for immunotherapy in tumor diseases. The LDR, combined with a UA platform, has been optimized for the detection of 27 alleles distributed within exons 2 and 3 of HLA-A. The assay involves the amplification by PCR of the HLA-A genomic region (1,900 bp), the cycled ligation reaction, followed by the capture of ligated products through hybridization onto a UA. Each slide was designed to allow the detection of up to eight samples in parallel. The PCR/LDR/UA HLA-A assay was evaluated by analyzing 62 individuals (31 homozygous and 31 heterozygous) previously typed by direct sequencing. We demonstrate that the microarray genotyping procedure described here is a robust and efficient method for unambiguous detection of HLA alleles. HLA genotyping by PCR/LDR/UA is in perfect agreement with typing obtained by direct sequencing. Our results clearly demonstrate that the combination of enzymatic processing (LDR) and a demultiplexing hybridization onto a UA is a robust tool for SNP discrimination within the highly polymorphic HLA region. We demonstrate the specificity and efficiency of such an approach, suggesting the feasibility of a PCR/LDR/UA low resolution HLA typing procedure. (C) 2004 Wiley-Liss, Inc. C1 ITB, CNR, I-20090 Segrate, MI, Italy. IBBA, Segrate, Italy. Univ Genoa, Dept Oncol Biol & Genet, Genoa, Italy. Natl Canc Inst, IST, Genoa, Italy. Univ Milan, Dipartimento Sci Tecnol Biomed, Segrate, Italy. Univ Milan, CISI, Segrate, Italy. RP De Bellis, G (reprint author), ITB, CNR, Via F Ili Cervi 93, I-20090 Segrate, MI, Italy. EM gianluca.debellis@itb.cnr.it RI Rizzi, Ermanno/J-7448-2012; Castiglioni, Bianca/G-9856-2013; De Bellis, Gianluca/H-9725-2013; Mezzelani, Alessandra/B-3355-2014; Battaglia, Cristina /E-5166-2017; OI De Bellis, Gianluca/0000-0002-1622-4477; Battaglia, Cristina /0000-0003-3025-9657; Castiglioni, Bianca/0000-0003-2326-6701; rizzi, ermanno/0000-0002-9898-2326; MEZZELANI, ALESSANDRA/0000-0001-7563-5869 NR 11 TC 21 Z9 24 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1059-7794 J9 HUM MUTAT JI Hum. Mutat. PY 2004 VL 24 IS 5 BP 428 EP 434 DI 10.1002/humu.20098 PG 7 WC Genetics & Heredity SC Genetics & Heredity GA 866HQ UT WOS:000224765000008 PM 15459953 ER PT J AU Goldin, E Stahl, S Cooney, AM Kaneski, CR Gupta, S Brady, RO Ellis, JR Schiffmann, R AF Goldin, E Stahl, S Cooney, AM Kaneski, CR Gupta, S Brady, RO Ellis, JR Schiffmann, R TI Transfer of a mitochondrial DNA fragment to MCOLN1 causes an inherited case of mucoliplidosis IV SO HUMAN MUTATION LA English DT Article DE mucolipidosis IV; MCOLN1; mtDNA; MTND5; insertion ID MUCOLIPIDOSIS TYPE-IV; HUMAN-GENOME; NUCLEUS; GENE; INFORMATION; SEQUENCES; EVOLUTION AB A patient with mucolipidosis-IV heterozygous for two mutations in MCOLN1 expressed only her father's cDNA mutation c.1207C>T predicting an R403C change in mucolipin. She inherited a 93bp segment from mitochondrial NADH dehydrogenase 5 (MTND5) from her mother that was inserted in,frame prior to the last nucleotide of exon 2 of MCOLN1 (c.236(-)237ins93). This alteration abolished proper splicing of MCOLN1. The splice site at the end of the exon was not used due to an inhibitory effect of the inserted segment, resulting in two aberrant splice products containing stop codons in the downstream intron. These products were eliminated via nonsense-mediated decay. This is the first report of an inherited transfer of mitochondrial nuclear DNA causing a genetic disease. The elimination of the splice site by the mitochondrial DNA requires a change in splicing prediction models. (C) 2004 Wiley-Liss, Inc. C1 NINDS, Dev & Metabol Neurol Branch, NIH, Bethesda, MD 20892 USA. NIH, Mol Interact Resource, Div Bioeng & Phys Sci, Off Res Serv, Bethesda, MD 20892 USA. RP Goldin, E (reprint author), NINDS, Dev & Metabol Neurol Branch, NIH, Bldg 10,Rm 3D04,9000 Rockville Pike, Bethesda, MD 20892 USA. EM goldine@ninds.nih.gov OI Kaneski, Christine/0000-0003-1453-2502 NR 18 TC 37 Z9 40 U1 1 U2 1 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1059-7794 J9 HUM MUTAT JI Hum. Mutat. PY 2004 VL 24 IS 6 BP 460 EP 465 DI 10.1002/humu.20094 PG 6 WC Genetics & Heredity SC Genetics & Heredity GA 874RW UT WOS:000225368500002 PM 15523648 ER PT J AU Maranchie, JK Afonso, A Albert, PS Kalyandrug, S Phillips, JL Zhou, S Peterson, J Ghadimi, BM Hurley, K Riss, J Vasselli, JR Ried, T Zbar, B Choyke, P Walther, MM Klausner, RD Linehan, WM AF Maranchie, JK Afonso, A Albert, PS Kalyandrug, S Phillips, JL Zhou, S Peterson, J Ghadimi, BM Hurley, K Riss, J Vasselli, JR Ried, T Zbar, B Choyke, P Walther, MM Klausner, RD Linehan, WM TI Solid renal tumor severity in von Hippel Lindau disease is related to germline deletion length and location SO HUMAN MUTATION LA English DT Article DE VHL; germline deletion; phenotype; genotype; renal neoplasms; HSPC300; C3orf10 ID SUPPRESSOR GENE; CELL CARCINOMA; PHENOTYPE; MUTATIONS; FAMILIES AB von Hippel Lindau disease (VHL) is an autosomal dominant familial cancer syndrome linked to alteration of the VHL tumor suppressor gene. Affected patients are predisposed to develop pheochromocytomas and cystic and solid tumors of the kidney, CNS, pancreas, retina, and epididymis. However, organ involvement varies considerably among families and has been shown to correlate with the underlying germline alteration. Clinically, we observed a paradoxically lower prevalence of renal cell carcinoma (RCC) in patients with complete germline deletion of VHL. To determine if a relationship existed between the type of VHL deletion and disease, we retrospectively evaluated 123 patients from 55 families with large germline VHL deletions, including 42 intragenic partial deletions and 13 complete VHL deletions, by history and radiographic imaging. Each individual and family was scored for cystic or solid involvement of CNS, pancreas, and kidney, and for pheochromocytoma. Germline deletions were mapped using a combination of fluorescent in situ hybridization (FISH) and quantitative Southern and Southern blot analysis. An age-adjusted comparison demonstrated a higher prevalence of RCC in patients with partial germline VHL deletions relative to complete deletions (48.9 vs. 22.6%, p=0.007). This striking phenotypic dichotomy was not seen for cystic renal lesions or for CNS (p=0.22), pancreas (p=0.72), or pheochromocytoma (p=0.34). Deletion mapping revealed that development of RCC had an even greater correlation with retention of HSPC300 (C3orf10), located within the 30-kb region of chromosome 3p, immediately telomeric to VHL (52.3 vs. 18.9%, p <0.001), suggesting the presence of a neighboring gene or genes critical to the development and maintenance of RCC. Careful correlation of genotypic data with objective phenotypic measures will provide further insight into the mechanisms of tumor formation. (C) 2003 Wiley-Liss, Inc. C1 NCI, Urol Oncol Branch, Bethesda, MD 20892 USA. NCI, Genet Branch, Bethesda, MD USA. NIH, Dept Radiol, Bethesda, MD USA. NCI, Biometr Res Branch, Bethesda, MD USA. Capital Technol Informat Serv CTIS Inc, Bethesda, MD USA. NCI, Immunobiol Lab, Frederick, MD USA. RP Linehan, WM (reprint author), NCI, Urol Oncol Branch, CCR,Bldg 10 Rm 2B47, Bethesda, MD 20892 USA. OI Maranchie, Jodi/0000-0002-8534-9468 NR 19 TC 47 Z9 52 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 1059-7794 J9 HUM MUTAT JI Hum. Mutat. PY 2004 VL 23 IS 1 BP 40 EP 46 DI 10.1002/humu.10302 PG 7 WC Genetics & Heredity SC Genetics & Heredity GA 759QQ UT WOS:000187748700006 PM 14695531 ER PT J AU Kondrashov, AS Rogozin, IB AF Kondrashov, AS Rogozin, IB TI Context of deletions and insertions in human coding sequences SO HUMAN MUTATION LA English DT Article DE mutation; hot spot; deletion; insertion; mutable motif; nucleotide context; repeat; microsatellite ID HUMAN INHERITED DISEASE; BASE-PAIR SUBSTITUTION; HUMAN GENETIC-DISEASE; DNA-POLYMERASE-ETA; ESCHERICHIA-COLI; MUTATIONAL SPECIFICITY; ADENOMATOUS-POLYPOSIS; FRAMESHIFT MUTATION; GENOME INSTABILITY; SYNTHESIS ERRORS AB We studied the dependence of the rate of short deletions and insertions on their contexts using the data on mutations within coding exons at 19 human loci that cause mendelian diseases. We confirm that periodic sequences consisting of three to five or more nucleotides are mutagenic. Mutability of sequences with strongly biased nucleotide composition is also elevated, even when mutations within homonucleotide runs longer than three nucleotides are ignored. In contrast, no elevated mutation rates have been detected for imperfect direct or inverted repeats. Among known candidate contexts, the indel context GTAAGT and regions with purine-pyrimidine imbalance between the two DNA strands are mutagenic in our sample, and many others are not mutagenic. Data on mutation hot spots suggest two novel contexts that increase the deletion rate. Comprehensive analysis of mutability of all possible contexts of lengths four, six, and eight indicates a substantially elevated deletion rate within YYYTG and similar sequences, which is one of the two contexts revealed by the hot spots. Possible contexts that increase the insertion rate (AT(A/C)(A/C)GCC and TACCRC) and decrease deletion (TATCGC) or insertion (GCGG) rates have also been identified. Two-thirds of deletions remove a repeat, and over 80% of insertions create a repeat, i.e., they are duplications. Published 2003 Wiley-Liss, Inc.(dagger) C1 NIH, Natl Ctr Biotechnol Informat, Bethesda, MD 20894 USA. RP Kondrashov, AS (reprint author), NIH, Natl Ctr Biotechnol Informat, Bldg 38A, Bethesda, MD 20894 USA. EM kondrashov@ncbi.nlm.nih.gov NR 61 TC 48 Z9 49 U1 1 U2 3 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 1059-7794 J9 HUM MUTAT JI Hum. Mutat. PY 2004 VL 23 IS 2 BP 177 EP 185 DI 10.1002/humu.10312 PG 9 WC Genetics & Heredity SC Genetics & Heredity GA 770GX UT WOS:000188715800010 PM 14722921 ER PT J AU Berman, JJ Henson, DE AF Berman, JJ Henson, DE TI Request, respectfully, return to rudiments - Reply SO HUMAN PATHOLOGY LA English DT Letter C1 NCI, Canc Diag Program, DCTD, NIH, Rockville, MD USA. George Washington Univ, Med Ctr, Washington, DC 20052 USA. RP Berman, JJ (reprint author), NCI, Canc Diag Program, DCTD, NIH, Rockville, MD USA. NR 4 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 0046-8177 J9 HUM PATHOL JI Hum. Pathol. PD JAN PY 2004 VL 35 IS 1 BP 137 EP 138 DI 10.1016/j.humpath.2003.10.005 PG 2 WC Pathology SC Pathology GA 770HD UT WOS:000188716400021 ER PT J AU Cardillo, C Campia, U Iantorno, M Panza, JA AF Cardillo, C Campia, U Iantorno, M Panza, JA TI Enhanced vascular activity of endogenous endothelin-1 in obese hypertensive patients SO HYPERTENSION LA English DT Article DE endothelin; hypertension, obesity; vasculature; atherosclerosis ID BLOOD-PRESSURE; DEFICIENT RATS; GENE VARIANT; INSULIN; RECEPTOR; CELLS; TONE; ANTAGONISTS; EXPRESSION; ARTERIES AB Hypertensive patients have increased endothelin-1-dependent vasoconstrictor tone. This abnormality, however, might not be uniformly present in all forms of hypertension, as suggested by experimental studies showing that endothelin-1 activity is enhanced predominantly in low-renin, high-volume models and in insulin-resistant states. Because hypertension in obesity is commonly associated with both expanded plasma volume and insulin resistance, this study sought to determine whether increased body mass index (BMI) in hypertensive patients relates to activation of the endothelin-1 system. Forearm blood flow (FBF) responses ( plethysmography) to intra-arterial infusion of an ETA receptor blocker (BQ-123) were analyzed in hypertensive patients and normotensive control subjects according to BMI. The vasodilator response to BQ-123 was significantly higher in hypertensive patients than in control subjects (P<0.001). During BQ-123, a significant increase in FBF from baseline was observed in obese (BMI&GE;30 kg/m(2); P<0.001) and overweight (BMI, 27 to 29.9 kg/m(2); P=0.04) but not in lean (BMI<27 kg/m(2); P=0.83) hypertensive patients. In contrast, no significant change in FBF was observed during BQ-123 either in obese (P=0.53), overweight (P=0.76), or lean (P=0.93) normotensive subjects. Moreover, a significant correlation between BMI and the vasodilator response to ETA blockade was observed in hypertensive subjects (R=0.53; P=0.005) but not in control subjects (R=0.11; P=0.58). In human hypertension, increased BMI is associated with enhanced ETA-dependent vasoconstrictor activity, suggesting that this abnormality may play a role in the pathophysiology of obesity-related hypertension and that targeting the endothelin-1 system may be useful in the treatment of these patients. C1 Washington Hosp Ctr, Washington, DC 20010 USA. NHLBI, Bethesda, MD 20892 USA. Univ Cattolica Sacro Cuore, Rome, Italy. RP Panza, JA (reprint author), Washington Hosp Ctr, 110 Irving St NW,Suite 2A 74, Washington, DC 20010 USA. NR 26 TC 87 Z9 91 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0194-911X J9 HYPERTENSION JI Hypertension PD JAN PY 2004 VL 43 IS 1 BP 36 EP 40 DI 10.1161/01.HYP.0000103868.45064.81 PG 5 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 757NA UT WOS:000187567300007 PM 14656951 ER PT J AU Stamm, BH Tuma, F Norris, FH Piland, NF Van der Hart, O Fairbank, JA Stamm, HE Higson-Smith, C Barbanel, L Levant, RF AF Stamm, BH Tuma, F Norris, FH Piland, NF Van der Hart, O Fairbank, JA Stamm, HE Higson-Smith, C Barbanel, L Levant, RF TI The terror part of terrorism SO IEEE ENGINEERING IN MEDICINE AND BIOLOGY MAGAZINE LA English DT Article ID POSTTRAUMATIC-STRESS-DISORDER; ANXIETY DISORDERS; HEALTH; TRAUMA; METAANALYSIS; DISASTER; ABUSE; WOMEN; RISK C1 Idaho State Univ, Inst Rural Hlth, Pocatello, ID 83209 USA. NIMH, Bethesda, MD 20892 USA. Natl Ctr PTSD, Execut Div, White River Jct, VT USA. Dartmouth Coll Sch Med, Hanover, NH USA. Univ Utrecht, Dept Clin Psychol, Utrecht, Netherlands. Duke Univ, Med Ctr, Dept Psychiat & Behav Sci, Durham, NC USA. Wind River Hist Ctr, Dubois, WY USA. CUNY Brooklyn Coll, Sch Psychol, Grad Program, New York, NY USA. Nova SE Univ, Ctr Psychosocial Studies, Ft Lauderdale, FL 33314 USA. RP Stamm, BH (reprint author), Idaho State Univ, Inst Rural Hlth, Campus Box 8174, Pocatello, ID 83209 USA. EM bhstamm@isu.edu RI Fairbank, John/F-8972-2013 OI Fairbank, John/0000-0003-2604-7256 NR 79 TC 1 Z9 1 U1 2 U2 4 PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC PI PISCATAWAY PA 445 HOES LANE, PISCATAWAY, NJ 08855-4141 USA SN 0739-5175 J9 IEEE ENG MED BIOL JI IEEE Eng. Med. Biol. Mag. PD JAN-FEB PY 2004 VL 23 IS 1 BP 149 EP 161 PG 13 WC Engineering, Biomedical; Medical Informatics SC Engineering; Medical Informatics GA 818AH UT WOS:000221217500021 PM 15154272 ER PT J AU Stokes, WS AF Stokes, WS TI Selecting appropriate animal models and experimental designs for endocrine disruptor research and testing studies SO ILAR JOURNAL LA English DT Editorial Material DE alternatives; animal models; endocrine disruptors; experimental variables; in vitro systems; toxicology; validation ID MICE AB Evidence that chemicals in the environment may cause developmental and reproductive abnormalities in fish and wildlife by disrupting normal endocrine functions has increased concern about potential adverse human health effects from such chemicals. US laws have now been enacted that require the US Environmental Protection Agency (EPA) to develop and validate a screening program to identify chemicals in food and water with potential endocrine-disrupting activity. EPA subsequently proposed an Endocrine Disruptor Screening Program that uses in vitro and in vivo test systems to identify chemicals that may adversely affect humans and ecologically important animal species. However. the endocrine system can be readily modulated by many experimental factors, including diet and the genetic background of the selected animal strain or stock. It is therefore desirable to minimize or avoid factors that cause or contribute to experimental variation in endocrine disruptor research and testing studies. Standard laboratory animal diets contain high and variable levels of phytoestrogens. which can modulate physiologic and behavioral responses similar to both endogenous estrogen as well as exogenous estrogenic chemicals. Other studies have determined that some commonly used outbred mice and rats are less responsive to estrogenic substances than certain inbred mouse and rat strains for various estrogen-sensitive endpoints. It is therefore critical to select appropriate biological models and diets for endocrine disruptor studies that provide optimal sensitivity and specificity to accomplish the research or testing objectives. An introduction is provided to 11 other papers in this issue that review these and other important laboratory animal experimental design considerations in greater detail. and that review laboratory animal and in vitro models currently being used or evaluated for endocrine disruptor research and testing. Selection of appropriate animal models and experimental design parameters for endocrine disruptor research and testing will minimize confounding experimental variables, increase the likelihood of replicable experimental results, and contribute to more reliable and relevant test systems. C1 US PHS, Res Triangle Pk, NC USA. NIEHS, Natl Toxicol Program, Interagcy Ctr Evaluat Alternat Toxicol Methods, NIH, Res Triangle Pk, NC 27709 USA. RP Stokes, WS (reprint author), US PHS, Res Triangle Pk, NC USA. NR 27 TC 25 Z9 26 U1 0 U2 9 PU INST LABORATORY ANIMAL RESEARCH, NATL RES COUNCIL PI WASHINGTON PA 500 FIFTH ST, N W, WASHINGTON, DC 20001 USA SN 1084-2020 J9 ILAR J JI ILAR J. PY 2004 VL 45 IS 4 BP 387 EP 393 PG 7 WC Veterinary Sciences SC Veterinary Sciences GA 862GZ UT WOS:000224480300001 PM 15454677 ER PT J AU Thigpen, JE Setchell, KDR Saunders, HE Haseman, JK Grant, MG Forsythe, DB AF Thigpen, JE Setchell, KDR Saunders, HE Haseman, JK Grant, MG Forsythe, DB TI Selecting the appropriate rodent diet for endocrine disruptor research and testing studies SO ILAR JOURNAL LA English DT Article DE daidzein; endocrine disruptors; genistein; phytoestrogen; rodent diets; uterotrophic assay ID RAT UTEROTROPHIC BIOASSAY; ESTROGEN-RECEPTOR-BETA; SPRAGUE-DAWLEY RATS; IMMATURE CD-1 MICE; OECD PROGRAM; MOUSE BIOASSAY; SEXUAL DEVELOPMENT; BISPHENOL-A; IN-VITRO; PHYTOESTROGENS AB Selecting the optimum diet for endocrine disruptor (ED) research and testing studies in rodents is critical because the diet may determine the sensitivity to detect or properly evaluate an ED compound. Dietary estrogens can profoundly influence many molecular and cellular event actions on estrogen receptors and estrogen-sensitive genes. The source, concentration, relative potency, and significance of dietary estrogens in rodent diets are reviewed, including dietary factors that focus specifically on total metabolizable energy and phytoestrogen content, which potentially affect ED studies in rodents. Research efforts to determine dietary factors in commercially available rodent diets that affect uterotrophic assays and the time of vaginal opening in immature CD-I mice are summarized. A checklist is provided of important factors to consider when selecting diets for ED research and testing studies in rodents. Specific metabolizable energy levels are recommended for particular bioassays. Discussions include the between-batch variation in content of the phytoestrogens daidzein and genistein. the effects of total metabolizable energy and phytoestrogens on the timing (i.e., acceleration) of vaginal opening, and increased uterine weight in immature CD-I mice. It is concluded that rodent diets differ significantly in estrogenic activity primarily due to the large variations in phytoestrogen content. therefore animal diets used in all ED studies should ideally be free of endocrine-rnodulating compounds. C1 NIEHS, Qual Assurance Lab, Comparat Med Branch, NIH, Res Triangle Pk, NC 27709 USA. Cincinnati Childrens Hosp, Med Ctr, Dept Pediat, Clin Mass Spectrometry, Cincinnati, OH USA. RP Thigpen, JE (reprint author), NIEHS, Qual Assurance Lab, Comparat Med Branch, NIH, POB 12233, Res Triangle Pk, NC 27709 USA. NR 63 TC 56 Z9 57 U1 0 U2 6 PU INST LABORATORY ANIMAL RESEARCH, NATL RES COUNCIL PI WASHINGTON PA 500 FIFTH ST, N W, WASHINGTON, DC 20001 USA SN 1084-2020 J9 ILAR J JI ILAR J. PY 2004 VL 45 IS 4 BP 401 EP 416 PG 16 WC Veterinary Sciences SC Veterinary Sciences GA 862GZ UT WOS:000224480300003 PM 15454679 ER PT J AU Walker, VR Korach, KS AF Walker, VR Korach, KS TI Estrogen receptor knockout mice as a model for endocrine research SO ILAR JOURNAL LA English DT Article DE estrogen receptor; knock-out mice; reproductive phenotypes; transgenic mice ID MAMMARY-GLAND DEVELOPMENT; ALPHA ER-ALPHA; FEMALE MICE; REPRODUCTIVE PHENOTYPES; NULL MICE; TARGETED DISRUPTION; SEX REVERSAL; BETA; GENE; MOUSE AB The biological effects of estrogen in mammalian target tissues are important for multiple organ systems including the male and female reproductive tract and the neuroendocrine, skeletal, and cardiovascular systems. Numerous physiological effects of estradiol are modulated by the estrogen receptor (ER), a Class I member of the nuclear receptor superfamily. However, more recent studies have also implicated nongenomic effects of estrogen, which may involve a membrane-binding site. The two forms of the ER are the classical estrogen receptor-alpha (ERalpha) and the more recently discovered estrogen receptor-beta (ERbeta). Gene-targeting techniques were used to generate mice lacking either functional ERalpha (alphaERKO), ERbeta (betaERKO), or both ERs (alphabetaERKO) to provide a model for evaluating estrogen receptor action. These knockout models provide a unique too] to stud), the effects of estrogen in the context of the whole animal and to discern the role of each ER in various tissues. The reproductive phenotypes as well as some of the nonreproductive phenotypes of the different ERKO models are summarized. C1 NIEHS, Lab Reprod & Dev Toxicol, Receptor Biol Sect, NIH, Res Triangle Pk, NC 27709 USA. NIEHS, Lab Reprod & Dev Toxicol, Receptor Biol Sect, NIH, Res Triangle Pk, NC 27709 USA. RP Walker, VR (reprint author), NIEHS, Lab Reprod & Dev Toxicol, Receptor Biol Sect, NIH, POB 12233, Res Triangle Pk, NC 27709 USA. OI Korach, Kenneth/0000-0002-7765-418X NR 41 TC 46 Z9 51 U1 2 U2 5 PU INST LABORATORY ANIMAL RESEARCH, NATL RES COUNCIL PI WASHINGTON PA 500 FIFTH ST, N W, WASHINGTON, DC 20001 USA SN 1084-2020 J9 ILAR J JI ILAR J. PY 2004 VL 45 IS 4 BP 455 EP 461 PG 7 WC Veterinary Sciences SC Veterinary Sciences GA 862GZ UT WOS:000224480300008 PM 15454684 ER PT J AU Combs, CA Balaban, R AF Combs, CA Balaban, R TI Enzyme-dependent fluorescence recovery after photobleaching of NADH: In vivo and in vitro applications to the study of enzyme kinetics SO IMAGING IN BIOLOGICAL RESEARCH, PT A SE METHODS IN ENZYMOLOGY LA English DT Review ID REDUCED PYRIDINE NUCLEOTIDE; INFRARED LASER-PULSES; PERFUSED RAT HEARTS; OXIDATIVE-PHOSPHORYLATION; HYPOXIC STATE; LIVING CELLS; REDOX STATE; ED-FRAP; MICROSCOPY; HETEROGENEITY C1 NHLBI, Light Microscopy Facil, NIH, Bethesda, MD 20892 USA. NHLBI, Cardiac Energet Lab, NIH, Bethesda, MD 20892 USA. RP Combs, CA (reprint author), NHLBI, Light Microscopy Facil, NIH, Bldg 10, Bethesda, MD 20892 USA. NR 40 TC 7 Z9 7 U1 1 U2 5 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA SN 0076-6879 J9 METHOD ENZYMOL JI Methods Enzymol. PY 2004 VL 385 BP 257 EP + PG 34 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BAG85 UT WOS:000222143000015 PM 15130744 ER PT J AU Bulte, JWM Arbab, AS Douglas, T Frank, JA AF Bulte, JWM Arbab, AS Douglas, T Frank, JA TI Preparation of magnetically labeled cells for cell tracking by magnetic resonance imaging SO IMAGING IN BIOLOGICAL RESEARCH, PT B SE METHODS IN ENZYMOLOGY LA English DT Review ID SUPERPARAMAGNETIC IRON-OXIDE; RAT SPINAL-CORD; IN-VIVO TRACKING; STEM-CELLS; CONTRAST AGENTS; TRANSFECTION AGENTS; MAMMALIAN-CELLS; TAT PEPTIDE; POLYAMIDOAMINE DENDRIMERS; FUNCTIONAL RECOVERY C1 Johns Hopkins Univ, Sch Med, Dept Radiol, Baltimore, MD 21205 USA. Johns Hopkins Univ, Sch Med, Inst Cell Engn, Baltimore, MD 21205 USA. NIH, Lab Diagnost Radiol Res, Expt Neuroimaging Sect, Bethesda, MD 20892 USA. Montana State Univ, Dept Chem & Biochem, Bozeman, MT 59717 USA. RP Bulte, JWM (reprint author), Johns Hopkins Univ, Sch Med, Dept Radiol, Baltimore, MD 21205 USA. RI Bulte, Jeff/A-3240-2008; Douglas, Trevor/F-2748-2011 OI Bulte, Jeff/0000-0003-1202-1610; FU NINDS NIH HHS [R01 NS045062] NR 88 TC 137 Z9 154 U1 1 U2 9 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA SN 0076-6879 J9 METHOD ENZYMOL JI Methods Enzymol. PY 2004 VL 386 BP 275 EP 299 PG 25 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BAG86 UT WOS:000222143800013 PM 15120257 ER PT J AU Racanelli, V Behrens, SE Aliberti, J Rehermann, B AF Racanelli, V Behrens, SE Aliberti, J Rehermann, B TI Dendritic cells transfected with cytopathic self-replicating RNA induce crosspriming of CD8(+) T cells and antiviral immunity SO IMMUNITY LA English DT Article ID MHC CLASS-I; CHRONIC HEPATITIS-C; EXOGENOUS ANTIGEN; VIRUS-INFECTION; CROSS-PRESENTATION; VIRAL CLEARANCE; RESPONSES; VACCINE; TOLERANCE; MOLECULES AB A potential shortcoming of nonlive vaccines is their relative inefficiency in generating T cell responses, thus limiting their application in infections requiring cellular immunity. Here, we present a system to induce cellular immunity and to study the immunological implications of time-delayed dendritic cell (DC) apoptosis and antigen reprocessing in vivo. We generated a self-replicating cytopathic pestivirus RNA to enhance production and presentation of hepatitis C virus (HCV) antigens and to induce apoptosis in DC 24-48 hr after transfection. Replicon-transfected H-2(b) DCs used to immunize HLA-A2 transgenic mice induced protection upon challenge with a vaccinia virus expressing HCV antigens. Induction of cell death enhanced the immunogenicity of DC-associated antigen. Transfer of cellular material from vaccine DCs to endogenous antigen presenting cells was visualized in lymph nodes and spleen, and crossprimed CD8+ T cells were characterized. The findings are relevant for the rational design of vaccines against noncytopathic pathogens like HCV. C1 NIDDK, Liver Dis Sect, Digest Dis Branch, DHHS,NIH, Bethesda, MD 20892 USA. Univ Giessen, Inst Virol, D-35392 Giessen, Germany. NIAID, Immunobiol Sect, Parasit Dis Lab, DHHS,NIH, Bethesda, MD 20892 USA. RP Rehermann, B (reprint author), NIDDK, Liver Dis Sect, Digest Dis Branch, DHHS,NIH, Bethesda, MD 20892 USA. EM rehermann@nih.gov RI Aliberti, Julio/G-4565-2012; Aliberti, Julio/I-7354-2013; OI Aliberti, Julio/0000-0003-3420-8478; RACANELLI, Vito/0000-0002-8639-1940 NR 53 TC 45 Z9 51 U1 0 U2 0 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 1074-7613 J9 IMMUNITY JI Immunity PD JAN PY 2004 VL 20 IS 1 BP 47 EP 58 DI 10.1016/S1074-7613(03)00353-4 PG 12 WC Immunology SC Immunology GA 821EG UT WOS:000221442200006 PM 14738764 ER PT J AU Wang, HY Lee, DA Peng, GY Guo, Z Li, YC Kiniwa, Y Shevach, EM Wang, RF AF Wang, HY Lee, DA Peng, GY Guo, Z Li, YC Kiniwa, Y Shevach, EM Wang, RF TI Tumor-specific human CD4(+) regulatory T cells and their ligands: Implications for immunotherapy SO IMMUNITY LA English DT Article ID IMMUNOLOGICAL SELF-TOLERANCE; CONTROLLING AUTOIMMUNITY; CD8-T-CELL MEMORY; CD4-T-CELL HELP; LUNG-CANCER; ANTIGEN; IMMUNITY; IDENTIFICATION; RESPONSES; INDUCTION AB Regulatory T cells play an important role in the maintenance of immunological self-tolerance by suppressing immune responses against autoimmune diseases and cancer. Little is known, however, about the nature of the physiological target antigens for CD4(+) regulatory T (Treg) cells. Here we report the identification of the LAGE1 protein as a ligand for tumor-specific CD4(+) Treg cell clones generated from the tumor-infiltrating lymphocytes (TILs) of cancer patients. Phenotypic and functional analyses demonstrated that they were antigen-specific CD4(+) Treg cells expressing CD25 and GITR molecules and possessing suppressive activity on the proliferative response of naive CD4+ T cells to anti-CD3 antibody stimulation. Ligand-specific activation and cell-cell contact were required for TIL102 Treg cells to exert suppressive activity on CD4+ effector cells. These findings suggest that the presence of tumor-specific CD4(+) Treg cells at tumor sites may have a profound effect on the inhibition of T cell responses against cancer. C1 Baylor Coll Med, Ctr Cell & Gene Therapy, Houston, TX 77030 USA. Baylor Coll Med, Dept Immunol, Houston, TX 77030 USA. NIAID, Immunol Lab, NIH, Bethesda, MD 20892 USA. RP Wang, RF (reprint author), Baylor Coll Med, Ctr Cell & Gene Therapy, Houston, TX 77030 USA. EM rongfuw@bcm.tmc.edu NR 42 TC 312 Z9 336 U1 2 U2 15 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 1074-7613 J9 IMMUNITY JI Immunity PD JAN PY 2004 VL 20 IS 1 BP 107 EP 118 DI 10.1016/S1074-7613(03)00359-5 PG 12 WC Immunology SC Immunology GA 821EG UT WOS:000221442200011 PM 14738769 ER PT J AU Jin, P Panelli, MC Marincola, FM Wang, E AF Jin, P Panelli, MC Marincola, FM Wang, E TI Cytokine polymorphism and its possible impact on cancer SO IMMUNOLOGIC RESEARCH LA English DT Article DE cytokine; cytokine polymorphism; immune responses ID SINGLE-NUCLEOTIDE POLYMORPHISMS; DENSITY OLIGONUCLEOTIDE ARRAYS; SEVERE COMBINED IMMUNODEFICIENCY; DOSE RECOMBINANT INTERLEUKIN-2; CUTANEOUS MALIGNANT-MELANOMA; INNATE IMMUNE-RESPONSE; RENAL-CELL CARCINOMA; TNF PROMOTER REGION; TOLL-LIKE RECEPTORS; FACTOR-KAPPA-B AB Human cancer is an unpredictable disease as is its response to therapy. The intrinsic genetic heterogeneity and instability of cancer cells could in part explain such behavior. However, it is possible that, individual variation in the genetic make-up of humans may affect the relationship between host and cancer cells and, therefore, be, at least in part responsible for this extraordinary variation. Human gene polymorphism has been shown indeed to play a role in immune responses; among the immune-related genes, cytokines are often polymorphic. Some polymorphisms of cytokine and cytokine receptor may have direct functional significance by altering directly and indirectly the level of gene expression and/or its function; other may only demarcate a genetic linkage to a particular haplotype associated with a given clinical condition. The majority of polymorphisms found in cytokines or their receptors are located in the promoter, intronic and 3' untranslated regions. These sequence variations can still affect gene expression and function. In this review will we summarize the current knowledge about the role of cytokine polymorphism in disease and more specifically in cancer. C1 NIH, Ctr Clin, Dept Transfus Med, Immunogenet Sect, Bethesda, MD 20892 USA. RP Wang, E (reprint author), NIH, Ctr Clin, Dept Transfus Med, Immunogenet Sect, Bethesda, MD 20892 USA. EM EWang@mail.cc.nih.gov NR 89 TC 15 Z9 16 U1 0 U2 2 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 USA SN 0257-277X J9 IMMUNOL RES JI Immunol. Res. PY 2004 VL 30 IS 2 BP 181 EP 190 DI 10.1385/IR:30:2:181 PG 10 WC Immunology SC Immunology GA 861WY UT WOS:000224450500005 PM 15477659 ER PT J AU Furumoto, Y Gonzalez-Espinosa, C Gomez, G Kovarova, M Odom, S Parravicini, V Ryan, JJ Rivera, J AF Furumoto, Y Gonzalez-Espinosa, C Gomez, G Kovarova, M Odom, S Parravicini, V Ryan, JJ Rivera, J TI Rethinking the role of Src family protein tyrosine kinases in the allergic response - New insights on the functional coupling of the high affinity IgE receptor SO IMMUNOLOGIC RESEARCH LA English DT Article DE allergy; cytokines degranulation; Fc epsilon RI; Fyn; IgE; Lyn; mast cells ID FC-EPSILON-RI; MAST-CELL ACTIVATION; LYN-DEFICIENT MICE; IMMUNOGLOBULIN-E RECEPTOR; AUTOIMMUNE-DISEASE; MEMBRANE DOMAINS; RBL-2H3 CELLS; MUTANT MICE; B-CELLS; FYN AB Antigen-induced cross-linking of immunoglobulin E (IgE) antibodies bound to the high-affinity IgE receptor (FcepsilonRI), on mast cells results in the release of mediators that initiate an inflammatory response. This normal immune response has been abducted by immunological adaptation, through the production of IgE antibodies to normally innocuous substances, to cause allergic disease. Therefore, understanding the molecular requirements in IgE-dependent mast-cell activation holds promise for therapeutic intervention in disease. Recent investigation on the functional coupling of FcepsilonRI to the intracellular signaling apparatus has provided paradigm-altering insights on the importance and function of Src family protein tyrosine kinases (Src PTK) in mast-cell activation. In this synopsis, we review the current knowledge on the role of the Src PTKs, Fyn and Lyn, in mast-cell activation and discuss the implications of our findings on allergic disease. C1 NIAMSD, Mol Immunol & Inflammat Branch, Mol Inflammat Sect, NIH, Bethesda, MD 20892 USA. RP Rivera, J (reprint author), NIAMS, NIH, Bldg 10,Room 9N228,10 Ctr Dr,MSC 1820, Bethesda, MD 20892 USA. EM juan_rivera@nih.gov NR 67 TC 14 Z9 15 U1 0 U2 1 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 USA SN 0257-277X J9 IMMUNOL RES JI Immunol. Res. PY 2004 VL 30 IS 2 BP 241 EP 253 DI 10.1385/IR:30:2:241 PG 13 WC Immunology SC Immunology GA 861WY UT WOS:000224450500010 PM 15477664 ER PT B AU de Mello-Coelho, V Rangel, LBA Morin, PJ Taub, DD AF de Mello-Coelho, V Rangel, LBA Morin, PJ Taub, DD GP MEDIMOND TI Preadipocyte-like cells in the aging thymus SO IMMUNOLOGY 2004: AUTOIMMUNITY, GENETIC AND DEGENERATIVE DISORDERS, MALIGNANCIES, AND TRANSPLANTATION LA English DT Proceedings Paper CT 12th Annual International Congress of Immunology/4th Annual Conference of the Federation-of-Clinical-Immunology-Societies (FOCIS) CY JUL 18-23, 2004 CL Montreal, CANADA SP Federat Clin Immunol Soc ID NEUROTROPHIN RECEPTOR; EXPRESSION; THYMOCYTE AB Gene expression changes in the thymi with progressive aging were analyzed by cDNA microarray. The increased expression of BDNF and NGF-R p75 were initially noted in the microarray analyses of aging thymi and were further substantiated using real time RT-PCR and immunohistology. Hyperexpression of BDNF and NGF-R p75 was detected in a unique multivacuolated cell population in the septa and within the thymic parenchyma of aged mice. These cells exhibited a phenotype similar to adipocytes undergoing differentiation based on their morphology and specific staining with Oil-Red-O and adipocyte differentiation markers. The inverse correlation between the loss of thymocytes and increased presence of preadipocyte-like cells with advancing age suggest that adipogenic cells may play a part in the thymic involution process. C1 NIA, Immunol Lab, NIH, Baltimore, MD 21224 USA. RP de Mello-Coelho, V (reprint author), NIA, Immunol Lab, NIH, Baltimore, MD 21224 USA. NR 11 TC 2 Z9 2 U1 0 U2 0 PU MEDIMOND PUBLISHING CO PI BOLOGNA PA VIA RUBBIANI 6/2, 40124 BOLOGNA, ITALY BN 88-7587-074-8 PY 2004 BP 279 EP 284 PG 6 WC Genetics & Heredity; Immunology; Transplantation SC Genetics & Heredity; Immunology; Transplantation GA BBQ57 UT WOS:000227161200053 ER PT B AU Winders, BR Schwartz, RH Bruniquel, D AF Winders, BR Schwartz, RH Bruniquel, D GP MEDIMOND TI Methylation of Cytokine genes in murine naive T cells SO IMMUNOLOGY 2004: CYTOKINE NETWORK, REGULATORY CELLS, SIGNALING, AND APOPTOSIS LA English DT Proceedings Paper CT 12th Annual International Congress of Immunology/4th Annual Conference of the Federation-of-Clinical-Immunology-Societies (FOCIS) CY JUL 18-23, 2004 CL Montreal, CANADA SP Federat Clin Immunol Soc ID GAMMA PROMOTER DEMETHYLATION; IFN-GAMMA; INTERFERON-GAMMA; DNA METHYLATION; IMMUNE-SYSTEM; EXPRESSION; DIFFERENTIATION; LYMPHOCYTES; ANERGY AB We have shown that DNA methylation of the Interleukin-2 (IL-2) and Interferon-gamma (IFN-gamma) promoters inhibits their transcriptional activity, and we defined a small region in each promoter that when hypomethylated in T cells correlates with the gene's transcriptional activity. Surprisingly, in naive T cells, the IL-2 promoter is hypermethylated while the IFN-gamma promoter is hypomethylated. To be certain that these observations were not due to differences in the techniques used to measure CpG methylation, we examined both bisulfite sequencing and methylation sensitive restriction enzyme approaches to assess the methylation status of both genes in naive T cells. Our results confirm that the IL-2 promoter is largely methylated in naive CD4(+) T cells, while the IFN-gamma promoter is not. The possible reasons for this biological situation are discussed. C1 NIAID, NIH, Lab Cellular & Mol Immunol, Bethesda, MD 20892 USA. RP Winders, BR (reprint author), NIAID, NIH, Lab Cellular & Mol Immunol, 9000 Rockville Pike, Bethesda, MD 20892 USA. NR 13 TC 0 Z9 0 U1 0 U2 0 PU MEDIMOND PUBLISHING CO PI BOLOGNA PA VIA RUBBIANI 6/2, 40124 BOLOGNA, ITALY BN 88-7587-069-1 PY 2004 BP 47 EP 51 PG 5 WC Cell Biology; Immunology SC Cell Biology; Immunology GA BBQ61 UT WOS:000227166900010 ER PT B AU Borrego, F Masilamani, M Sanni, TB Kabat, J Coligan, JE AF Borrego, F Masilamani, M Sanni, TB Kabat, J Coligan, JE GP MEDIMOND TI CD94/NKG2A inhibitory receptor trafficking and membrane dynamics SO IMMUNOLOGY 2004: CYTOKINE NETWORK, REGULATORY CELLS, SIGNALING, AND APOPTOSIS LA English DT Proceedings Paper CT 12th Annual International Congress of Immunology/4th Annual Conference of the Federation-of-Clinical-Immunology-Societies (FOCIS) CY JUL 18-23, 2004 CL Montreal, CANADA SP Federat Clin Immunol Soc ID CELL IMMUNE SYNAPSE; NATURAL-KILLER; ACTIVATING RECEPTORS; LIPID RAFTS; NK CELLS; POLARIZATION; CYTOSKELETON; RECOGNITION; TARGETS; SIGNAL AB CD94/NKG2A is an inhibitory receptor expressed by most human natural killer (NK) cells and a subset of T cells that recognizes human leukocyte antigen E (HLA-E) on potential target cells. CD94/NKG2A continuously recycles to and from the cell surface in a process requiring energy and the cytoskeleton that is independent of the inhibitory signaling. CD94/NKG2A receptors are endocytosed into EEA1(+) early endosomes. The endocytosed CD94/NKG2A fails to co-localize with transferrin receptor or Rab-4, suggesting that it traffics through specialized intracellular compartments after exiting the EEA1(+) early endosomes. Photobleaching experiments revealed that CD94/NKG2A receptors move freely within the plasma membrane and accumulate at the site of contact with the ligand. The ligated CD94/NKG2A at the site of contact with target is markedly less mobile than the non-ligated receptor. We observed that not only are GM1 ganglioside(+), cholesterol(+) lipid rafts not required for receptor polarization, they are excluded from the site of receptor contact with the ligand. Furthermore, co-ligation of CD94/NKG2A with FcepsilonFR1 activation receptors prevents the formation of lipid raft patches characteristic of activation receptor ligation. These results suggest that immobilization of the CD94/NKG2A receptors at ligation sites likely promotes sustenance of the inhibitory signal and lipid raft exclusion might aid in preventing formation of the activation signaling complexes. C1 NIAID, Receptor Cell Biol Sect, Lab Allerg Dis, NIH, Rockville, MD USA. RP Borrego, F (reprint author), NIAID, Receptor Cell Biol Sect, Lab Allerg Dis, NIH, Rockville, MD USA. NR 19 TC 0 Z9 0 U1 0 U2 0 PU MEDIMOND PUBLISHING CO PI BOLOGNA PA VIA RUBBIANI 6/2, 40124 BOLOGNA, ITALY BN 88-7587-069-1 PY 2004 BP 93 EP 97 PG 5 WC Cell Biology; Immunology SC Cell Biology; Immunology GA BBQ61 UT WOS:000227166900018 ER PT B AU Pritz, CJ Joshi, S Lai, PK AF Pritz, CJ Joshi, S Lai, PK GP MEDIMOND TI Effect of carrier protein on CTL-epitope presentation SO IMMUNOLOGY 2004: CYTOKINE NETWORK, REGULATORY CELLS, SIGNALING, AND APOPTOSIS LA English DT Proceedings Paper CT 12th Annual International Congress of Immunology/4th Annual Conference of the Federation-of-Clinical-Immunology-Societies (FOCIS) CY JUL 18-23, 2004 CL Montreal, CANADA SP Federat Clin Immunol Soc ID CYTOTOXIC T-LYMPHOCYTES; IMMUNIZATION C1 CSR, Div Biol Basis Dis, NIH, Bethesda, MD 20892 USA. RP Lai, PK (reprint author), CSR, Div Biol Basis Dis, NIH, Bethesda, MD 20892 USA. NR 4 TC 0 Z9 0 U1 0 U2 0 PU MEDIMOND PUBLISHING CO PI BOLOGNA PA VIA RUBBIANI 6/2, 40124 BOLOGNA, ITALY BN 88-7587-069-1 PY 2004 BP 217 EP 221 PG 5 WC Cell Biology; Immunology SC Cell Biology; Immunology GA BBQ61 UT WOS:000227166900040 ER PT B AU Giri, B Collins, GD Madara, K Weeraratna, AT Taub, DD AF Giri, B Collins, GD Madara, K Weeraratna, AT Taub, DD GP MEDIMOND TI Flotillin-1 plays a novel role in T cell adhesion and migration after post exposure to the chemokine, CXCL12 SO IMMUNOLOGY 2004: CYTOKINE NETWORK, REGULATORY CELLS, SIGNALING, AND APOPTOSIS LA English DT Proceedings Paper CT 12th Annual International Congress of Immunology/4th Annual Conference of the Federation-of-Clinical-Immunology-Societies (FOCIS) CY JUL 18-23, 2004 CL Montreal, CANADA SP Federat Clin Immunol Soc ID LIPID RAFTS; ACTIVATION; PROTEINS; DOMAINS; PATHWAY AB Lipid rafts play an important role in signal integration and cellular activation by the T-cell antigen receptor (TCR). Flotillins are lipid raft-associated proteins, which have been recently implicated in neuronal regeneration, insulin signaling and T-cell receptor signaling. However, a precise functional role for flotillins in chemokine signaling and function remain to be defined. To this end, we have isolated lipid rafts derived from human T-cells and T cell lines pre- and post activation and analyzed both cytoplasm and raft preparations for flotillin expression. Here, we present evidence that flotillin-1, redistributes to lipid rafts in primary human T cells and Jurkat T cells post CXCL12 treatment and associates with several other lipid raft proteins including LAT, LCK, cb1, CD48, LFA1a and CXCR4. Using RNAi technology, we found that the loss of flotillin-1 expression results in an inhibition of CXCL12-mediated calcium mobilization, chemotaxis and adhesion. Together, these results suggest that flotillin-1 plays a critical role in chemokine receptor function in human T cells. C1 NIA, Intramural Res Program, Immunol Lab, NIH, Baltimore, MD USA. RP Giri, B (reprint author), NIA, Intramural Res Program, Immunol Lab, NIH, 5600 Nathan Shock Dr, Baltimore, MD USA. NR 14 TC 0 Z9 0 U1 0 U2 0 PU MEDIMOND PUBLISHING CO PI BOLOGNA PA VIA RUBBIANI 6/2, 40124 BOLOGNA, ITALY BN 88-7587-069-1 PY 2004 BP 391 EP 395 PG 5 WC Cell Biology; Immunology SC Cell Biology; Immunology GA BBQ61 UT WOS:000227166900072 ER PT B AU Borrego, F Maasho, K Masilamani, M Basu, S Valas, R Coligan, JE AF Borrego, F Maasho, K Masilamani, M Basu, S Valas, R Coligan, JE GP MEDIMOND TI TCR signals control the cell surface expression of leukocyte-associated immunoglobulin-like receptor 1 (LAIR-1) in activated T cells SO IMMUNOLOGY 2004: CYTOKINE NETWORK, REGULATORY CELLS, SIGNALING, AND APOPTOSIS LA English DT Proceedings Paper CT 12th Annual International Congress of Immunology/4th Annual Conference of the Federation-of-Clinical-Immunology-Societies (FOCIS) CY JUL 18-23, 2004 CL Montreal, CANADA SP Federat Clin Immunol Soc ID IG-LIKE RECEPTOR-1; COLONY-STIMULATING FACTOR; INHIBITORY RECEPTOR; DIFFERENTIATION; RESPONSES; SHP-1 AB In order to prevent hyperreactivity by the immune system, tight regulation of effector function is necessary. One way of achieving this regulation is through down-regulation of cell-mediated immune response by inhibitory receptors. One of these, LAIR-1 is a transmembrane glycoprotein with a single extracellular Ig-like domain and a cytoplasmic tail containing two immunoreceptor tyrosine-based inhibition motifs (ITIM). LAIR-1 is constitutively expressed on the majority of human mononuclear leukocytes and functions as an inhibitory receptor on human NK cells, T cells, B cells, macrophages, and dendritic cells. The role of LAIR-1 has been extensively studied in NK cells, but its expression by T cells and the role that it plays in these cells has not been well characterized. In this study, we show that in freshly isolated peripheral blood T cells, LAIR-1 is differentially expressed in T cell subsets. CD8(+) T cells express higher levels of LAIR-1 than CD4(+) T cells, and naive CD4(+) and CD8(+) T cells express higher levels of LAIR-1 than memory cells. Activation of peripheral blood T cells by cross-linking with anti-CD3 mAb increases the cell surface expression of LAIR-1 in proliferating cells. This increase in LAIR-1 expression is the result of new synthesis and not the translocation of an intracellular pool. TCR induced expression of LAIR-1 requires p38 and Erk signaling. We also show that cross-linking of LAIR-1 inhibits TCR mediated activation both in cultured and freshly isolated CD4(+) and CD8(+) T cells. C1 NIAID, Receptor Cell Biol Sect, Lab Allerg Dis, NIH, Rockville, MD 20852 USA. RP Borrego, F (reprint author), NIAID, Receptor Cell Biol Sect, Lab Allerg Dis, NIH, Rockville, MD 20852 USA. NR 21 TC 0 Z9 0 U1 0 U2 0 PU MEDIMOND PUBLISHING CO PI BOLOGNA PA VIA RUBBIANI 6/2, 40124 BOLOGNA, ITALY BN 88-7587-069-1 PY 2004 BP 441 EP 446 PG 6 WC Cell Biology; Immunology SC Cell Biology; Immunology GA BBQ61 UT WOS:000227166900080 ER PT B AU Bystrom, J Swartz, JM Wynn, TA Domachowske, JB Rosenberg, HF AF Bystrom, J Swartz, JM Wynn, TA Domachowske, JB Rosenberg, HF GP MEDIMOND TI Interleukin-5 and gene transcription in mouse bone marrow in vivo SO IMMUNOLOGY 2004: GENOMIC ISSUES, IMMUNE SYSTEM ACTIVATION AND ALLERGY LA English DT Proceedings Paper CT 12th Annual International Congress of Immunology/4th Annual Conference of the Federation-of-Clinical-Immunology-Societies (FOCIS) CY JUL 18-23, 2004 CL Montreal, CANADA SP Federat Clin Immunol Soc AB The Th2 cytokine interleukin 5 (IL-5) promotes the expansion and maturation of eosinophil progenitors in bone marrow. In a gene array study published earlier this year [Bystrom, et al. Blood 2004; 103: 868877], we utilized a four-way subtractive approach to identify IL-5 responsive transcripts in mouse bone marrow in vivo. Among the results, our gene array findings suggested that the protease inhibitor, plasminogen activator inhibitor-2 (PAI-2), might be a heretofore unrecognized component of eosinophilic leukocytes. We have since identified biologically active PAI- 2 at high concentrations in human eosinophils (182 +/- 44 ng/ 10(6) cells), localized to the specific granules. Similarly, together with subsequent characterization of the expanding IL-5 receptor-a positive subpopulations of cells in mouse bone marrow, our array findings suggest a potentially intriguing discordance between transcript and receptor protein expression that remains to be fully elucidated. C1 NIAID, Lab Allerg Dis, NIH, Bethesda, MD 20892 USA. RP Bystrom, J (reprint author), NIAID, Lab Allerg Dis, NIH, Bethesda, MD 20892 USA. NR 5 TC 0 Z9 0 U1 0 U2 0 PU MEDIMOND PUBLISHING CO PI BOLOGNA PA VIA RUBBIANI 6/2, 40124 BOLOGNA, ITALY BN 88-7587-073-X PY 2004 BP 9 EP 14 PG 6 WC Genetics & Heredity; Immunology SC Genetics & Heredity; Immunology GA BBQ62 UT WOS:000227168200003 ER PT J AU Chase, HP Hayward, AP Eisenbarth, GS AF Chase, HP Hayward, AP Eisenbarth, GS TI Clinical trials for the prevention of type I diabetes SO IMMUNOLOGY OF TYPE 1 DIABETES, SECOND EDITION SE ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY LA English DT Article ID ISLET-CELL ANTIBODIES; REGULATORY T-CELLS; GLUTAMIC-ACID DECARBOXYLASE; NEWLY-DIAGNOSED PATIENTS; LIFE-TABLE ANALYSIS; NOD MICE; INSULIN-TREATMENT; RANDOMIZED-TRIAL; ORAL INSULIN; RECENT-ONSET C1 Univ Colorado, Hlth Sci Ctr, Barbara Davis Ctr Childhood Diabet, Denver, CO USA. NIH, Bethesda, MD USA. RP Chase, HP (reprint author), Univ Colorado, Hlth Sci Ctr, Barbara Davis Ctr Childhood Diabet, Denver, CO USA. NR 92 TC 0 Z9 0 U1 0 U2 2 PU KLUWER ACADEMIC/PLENUM PUBL PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0065-2598 J9 ADV EXP MED BIOL JI Adv.Exp.Med.Biol. PY 2004 VL 552 BP 291 EP 305 PG 15 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA BBR83 UT WOS:000227491100014 PM 15622969 ER PT S AU Santos, IKFD Valenzuela, JG Ribeiro, JMC De Castro, M Costa, JN Costa, AM Da Silva, ER Neto, OBR Rocha, C Daffre, S Ferreira, BR Da Silva, JS Szabo, MP Bechara, GH AF Santos, IKFD Valenzuela, JG Ribeiro, JMC De Castro, M Costa, JN Costa, AM Da Silva, ER Neto, OBR Rocha, C Daffre, S Ferreira, BR Da Silva, JS Szabo, MP Bechara, GH BE Bokma, BH Blouin, EF Bechara, GH TI Gene discovery in Boophilus microplus, the cattle tick - The transcriptomes of ovaries, salivary glands, and hemocytes SO IMPACT OF ECOLOGICAL CHANGES ON TROPICAL ANIMAL HEALTH AND DISEASE CONTROL SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article; Proceedings Paper CT 7th Biennial Conference of the Society-for-Tropical-Veterinary-Medicine CY JUN 22-27, 2003 CL Iguacu Falls, BRAZIL SP USDA, Agr Res Serv, Anim & Plant Hlth Inspect Serv, Cooperat State Res, Educ & Extens Serv, CNPq, CAPES, Fda Amparo & Pesquisa Estado Sao Paulo, Valee Sa, Merial DE Boophilus microplus; transcriptomes; salivary glands; ovary; hemocytes AB The quest for new control strategies for ticks can profit from high throughput genomics. In order to identify genes that are involved in oogenesis and development, in defense, and in hematophagy, the transcriptomes of ovaries, hemocytes, and salivary glands from rapidly ingurgitating females, and of salivary glands from males of Boophilus microplus were PCR amplified, and the expressed sequence tags (EST) of random clones were mass sequenced. So far, more than 1,344 EST have been generated for these tissues, with approximately 30% novelty, depending on the the tissue studied. To date approximately 760 nucleotide sequences from B. microplus are deposited in the NCBI database. Mass sequencing of partial cDNAs of parasite genes can build up this scant database and rapidly generate a large quantity of useful information about potential targets for immunobiological or chemical control. C1 Empresa Brasileira Pesquisa Agropecuaria, Ctr Genet Resources & Biotechnol, Brasilia, DF, Brazil. Univ Sao Paulo, Ribeirao Preto Sch Med, BR-14049 Ribeirao Preto, SP, Brazil. Univ Estadual Paulista, Sch Agron & Vet Sci, Jaboticabal, SP, Brazil. NIAID, Sect Vector Biol, NIH, Bethesda, MD 20892 USA. Univ Sao Paulo, Inst Biol, Sao Paulo, SP, Brazil. RP Santos, IKFD (reprint author), Univ Sao Paulo, Fac Med Ribeirao Preto, Dept Bioquim & Imunol, Avenida Bandeirantes 3900, BR-14049900 Ribeirao Preto, SP, Brazil. EM imsantos@rpm.fmrp.usp.br RI Silva, Joao/A-4484-2008; Ferreira, Beatriz/C-2003-2012; Daffre, Sirlei/M-4233-2013; Bechara, Gervasio/E-5023-2015; de Miranda Santos, Isabel/D-5261-2016; OI Ferreira, Beatriz/0000-0002-6781-2236; Bechara, Gervasio/0000-0003-4619-3744; Ribeiro, Jose/0000-0002-9107-0818 NR 3 TC 34 Z9 36 U1 2 U2 4 PU NEW YORK ACAD SCIENCES PI NEW YORK PA 2 EAST 63RD ST, NEW YORK, NY 10021 USA SN 0077-8923 BN 1-57331-504-4 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2004 VL 1026 BP 242 EP 246 DI 10.1196/annals.1307.037 PG 5 WC Public, Environmental & Occupational Health; Infectious Diseases; Multidisciplinary Sciences; Tropical Medicine; Veterinary Sciences SC Public, Environmental & Occupational Health; Infectious Diseases; Science & Technology - Other Topics; Tropical Medicine; Veterinary Sciences GA BBO56 UT WOS:000226725500037 PM 15604500 ER PT J AU Bornstein, MH Arterberry, ME Mash, C AF Bornstein, MH Arterberry, ME Mash, C TI Long-term memory for an emotional interpersonal interaction occurring at 5 months of age SO INFANCY LA English DT Article ID STILL-FACE; REGULATORY BEHAVIORS; RECOGNITION MEMORY; INFANTS; 3-MONTH-OLD; ATTENTION; YOUNG AB We examined infants' long-term retention of a single unique emotional experience into early childhood. Twenty-month-olds who had participated in a still-face procedure at 5 months (experience group) fixated the face of the person who had instigated the still face significantly less than the faces of 2 other novel persons. Control 20-month-olds (no-experience group) looked longer overall and fixated the target person equally or more than the 2 novel persons. In short, children who interacted with a stranger in the laboratory under both natural and anomalous social conditions just once when they were infants apparently retained a specific memory of that person and the experience into toddlerhood. C1 NICHHD, Bethesda, MD 20892 USA. RP Bornstein, MH (reprint author), NICHHD, Suite 8030,6705 Rockledge Dr, Bethesda, MD 20892 USA. EM Marc_H_Bornstein@nih.gov NR 56 TC 11 Z9 11 U1 0 U2 1 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1525-0008 J9 INFANCY JI Infancy PY 2004 VL 6 IS 3 BP 407 EP 416 DI 10.1207/s15327078in0603_6 PG 10 WC Psychology, Developmental SC Psychology GA 884BU UT WOS:000226060400006 ER PT J AU Coban, C Philipp, MT Purcell, JE Keister, DB Okulate, M Martin, DS Kumar, N AF Coban, C Philipp, MT Purcell, JE Keister, DB Okulate, M Martin, DS Kumar, N TI Induction of Plasmodium falciparum transmission-blocking antibodies in nonhuman primates by a combination of DNA and protein immunizations SO INFECTION AND IMMUNITY LA English DT Article ID CYTOTOXIC T-LYMPHOCYTES; VACCINE CANDIDATE; ANTIGEN PFS25; MALARIA; IMMUNOGENICITY; IMMUNITY AB Malaria transmission-blocking vaccination can effectively reduce and/or eliminate transmission of parasites from the human host to the mosquito vector. The immunity achieved by inducing an antibody response to surface antigens of male and female gametes and parasite stages in the mosquito. Our laboratory has developed DNA vaccine constructs, based on Pfs25 (a Plasmodium falciparum surface protein of 25 kDa), that induce a transmission-blocking immune response in mice (C. A. Lobo, R. Dhar, and N. Kumar, Infect. Immun. 67:1688-1693, 1999). To evaluate the safety, immunogenicity, and efficacy of the Pfs25 DNA vaccine in non-human primates, we immunized rhesus macaques (Macaca mulatta) with a DNA vaccine plasmid encoding Pfs25 or a Pfg27-Pfs25 hybrid or with the plasmid (empty plasmid) alone. Immunization with four doses of these DNA vaccine constructs elicited antibody titers that were high but nonetheless unable to reduce the parasite's infectivity in membrane feeding assays. Further boosting of the antibody response with recombinant Pfs25 formulated in Montanide ISA-720 increased antibody titers (30-fold) and significantly blocked transmission of P. falciparum gametocytes to Anopheles mosquitoes (similar to90% reduction in oocyst numbers in the midgut). Our data show that a DNA prime-protein boost regimen holds promise for achieving transmission-blocking immunity in areas where malaria is endemic and could be effective in eradicating malaria in isolated areas where the level of malaria endemicity is low. C1 Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Johns Hopkins Malaria Res Inst, Dept Mol Microbiol & Immunol, Baltimore, MD 21205 USA. NIH, Malaria Vaccines Dev Unit, Bethesda, MD 20892 USA. Tulane Univ, Ctr Hlth Sci, Tulane Natl Primate Res Ctr, Div Bacteriol & Parasitol, Covington, LA 70433 USA. Tulane Univ, Ctr Hlth Sci, Tulane Natl Primate Res Ctr, Div Vet Med, Covington, LA 70433 USA. RP Kumar, N (reprint author), Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Johns Hopkins Malaria Res Inst, Dept Mol Microbiol & Immunol, 615 N Wolfe St, Baltimore, MD 21205 USA. RI Coban, Cevayir/B-2129-2012 FU NCRR NIH HHS [M01 RR000722, P51 RR000164, RR00164]; NIAID NIH HHS [AI47089, R01 AI047089] NR 28 TC 43 Z9 45 U1 2 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0019-9567 J9 INFECT IMMUN JI Infect. Immun. PD JAN PY 2004 VL 72 IS 1 BP 253 EP 259 DI 10.1128/IAI.72.1.253-259.2004 PG 7 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 758JR UT WOS:000187631600030 PM 14688103 ER PT J AU Coban, C Ishii, KJ Stowers, AW Keister, DB Klinman, DM Kumar, N AF Coban, C Ishii, KJ Stowers, AW Keister, DB Klinman, DM Kumar, N TI Effect of CpG oligodeoxynucleotides on the immunogenicity of Pfs25, a Plasmodium falciparum transmission-blocking vaccine antigen SO INFECTION AND IMMUNITY LA English DT Article ID MEROZOITE SURFACE PROTEIN-1; IMMUNE-RESPONSES; SYNTHETIC OLIGODEOXYNUCLEOTIDES; MALARIA VACCINE; BACTERIAL-DNA; CUTTING EDGE; ANTIBODIES; ADJUVANTS; MOTIFS; MICE AB Antibodies directed against Pfs25, a protein present on the surface of zygotes and ookinetes of Plasmodium falciparum, completely block pathogen transmission. We evaluated the immunomodulatory effect of CpG oligodeoxynucleotides (ODN) on the immunogenicity of recombinant Pfs25 (rPfs25) formulated in alum (A1). Immunization of mice with rPfs25 plus CpG ODN improved both the antibody titer (a 30-fold-higher antibody response than that with rPfs25-A1 alone) and avidity. Coadministration of CpG ODN dramatically enhanced the titer of immunoglobulin G2A (IgG2a) compared to the titer of the IgG1-dominant response caused by rPfs25-A1 alone, and the sera from the CpG ODN-coadministered group completely blocked the transmission of P. falciparum parasites to mosquitoes, as determined by membrane feeding assays. However, transmission-blocking experiments revealed that blocking efficacy was dependent on high-titer antibody levels, independent of isotypes. These results suggest that CpG ODN can be used as an adjuvant to enhance the immunogenicity of rPfs25 as a malaria transmission-blocking vaccine. C1 Johns Hopkins Univ, Dept Mol Microbiol & Immunol, Bloomberg Sch Publ Hlth, Malaria Res Inst, Baltimore, MD 21205 USA. US FDA, Div Viral Prod, Ctr Biol Evaluat & Res, Bethesda, MD 20014 USA. NIAID, Malaria Vaccine Dev Unit, Parasit Dis Lab, NIH, Rockville, MD USA. RP Kumar, N (reprint author), Johns Hopkins Univ, Dept Mol Microbiol & Immunol, Bloomberg Sch Publ Hlth, Malaria Res Inst, 615 N Wolfe St, Baltimore, MD 21205 USA. RI Coban, Cevayir/B-2129-2012; Ishii, Ken/B-1685-2012 OI Ishii, Ken/0000-0002-6728-3872 FU NCRR NIH HHS [M01 RR000722]; NIAID NIH HHS [AI47089, R01 AI047089] NR 37 TC 21 Z9 24 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0019-9567 J9 INFECT IMMUN JI Infect. Immun. PD JAN PY 2004 VL 72 IS 1 BP 584 EP 588 DI 10.1128/IAI.72.1.584-588.2004 PG 5 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 758JR UT WOS:000187631600067 PM 14688140 ER PT J AU Sarac, MS Peinado, JR Leppla, SH Lindberg, I AF Sarac, MS Peinado, JR Leppla, SH Lindberg, I TI Protection against anthrax toxemia by hexa-D-arginine in vitro and in vivo SO INFECTION AND IMMUNITY LA English DT Article ID BACILLUS-ANTHRACIS; LETHAL FACTOR; CRYSTAL-STRUCTURE; TOXIN; ANTIGEN; FURIN; INHIBITOR; SPECIFICITY; ACTIVATION; DELIVERY AB The anthrax toxin protective antigen precursor is activated by proteolytic cleavage by furin or a furin-like protease. We present here data demonstrating that the small stable furin inhibitor hexa-D-arginine amide delays anthrax toxin-induced toxemia both in cells and in live animals, suggesting that furin inhibition may represent a reasonable avenue for therapeutic intervention in anthrax. C1 Louisiana State Univ, Hlth Sci Ctr, Dept Biochem & Mol Biol, New Orleans, LA 70112 USA. NIAID, Microbial Pathogenesis Sect, Div Intramural Res, NIH, Bethesda, MD 20892 USA. RP Lindberg, I (reprint author), Louisiana State Univ, Hlth Sci Ctr, Dept Biochem & Mol Biol, 1901 Perdido St, New Orleans, LA 70112 USA. RI Peinado, Juan/A-3450-2011 OI Peinado, Juan/0000-0002-0004-7963 FU NIAID NIH HHS [R21 AI053517, R21 AI53517]; NIDA NIH HHS [R01 DA005084] NR 26 TC 52 Z9 57 U1 0 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0019-9567 J9 INFECT IMMUN JI Infect. Immun. PD JAN PY 2004 VL 72 IS 1 BP 602 EP 605 DI 10.1128/IAI.721.602-605.2004 PG 4 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 758JR UT WOS:000187631600071 PM 14688144 ER PT J AU Pietropaoli, AP Frampton, MW Hyde, RW Morrow, PE Oberdorster, G Cox, C Speers, DM Frasier, LM Chalupa, DC Huang, LS Utell, MJ AF Pietropaoli, AP Frampton, MW Hyde, RW Morrow, PE Oberdorster, G Cox, C Speers, DM Frasier, LM Chalupa, DC Huang, LS Utell, MJ TI Pulmonary function, diffusing capacity, and inflammation in healthy and asthmatic subjects exposed to ultrafine particles SO INHALATION TOXICOLOGY LA English DT Article ID PARTICULATE AIR-POLLUTION; AMBIENT FINE PARTICLES; EMERGENCY-ROOM VISITS; NASAL NITRIC-OXIDE; OXIDATIVE STRESS; ENVIRONMENTAL AEROSOLS; ADHESION MOLECULES; HUMAN VOLUNTEERS; DIESEL EXHAUST; TERM EXPOSURE AB Particulate air pollution is associated with asthma exacerbations and increased morbidity and mortality from respiratory causes. Ultrafine particles (particles less than 0.1 mum in diameter) may contribute to these adverse effects because they have a higher predicted pulmonary deposition, greater potential to induce pulmonary inflammation, larger surface area, and enhanced oxidant capacity when compared with larger particles on a mass basis. We hypothesized that ultrafine particle exposure Would induce airway inflammation in susceptible humans. This hypothesis was tested in a series of randomized, double-blind studies by exposing healthy subjects and mild asthmatic subjects to carbon ultrafine particles versus filtered air. Both exposures were delivered via a mouthpiece system during rest and moderate exercise. Healthy subjects were exposed to particle concentrations of 10, 25, and 50 mug/m(3), while asthmatics were exposed to 10 mug/m(3). Lung function and airway inflammation were assessed by symptom scores, pulmonary function tests, and airway nitric oxide parameters. Airway inflammatory cells were measured via induced sputum analysis in several of the protocols. There were no differences in any of these measurements in normal or asthmatic subjects when exposed to ultrafine particles at concentrations of 10 or 25 mug/m(3). However, exposing 16 normal subjects to the higher concentration of 50 mug/m(3) caused a reduction in maximal midexpiratory flow rate (-4.34 +/- 1.78% [ultrafine particles] vs. +1.08 +/- 1.86% [air], p =.042) and carbon monoxide diffusing capacity (-1.76 +/- 0.66 ml/min/mm Hg [ultrafine particles] vs. -0.18 +/- 0.41 ml/min/mm Hg [air], p =.040) at 21 h after exposure. There were no consistent differences in symptoms, induced sputum, or exhaled nitric oxide parameters in any of these studies. These results suggest that exposure to carbon ultrafine particles results in mild small-airways dysfunction together with impaired alveolar gas exchange in normal subjects. These effects do not appear related to airway inflammation. Additional studies are required to confirm these findings in normal subjects, compare them with additional susceptible patient populations, and determine their pathophysiologic mechanisms. C1 Univ Rochester, Med Ctr, Sch Med & Dent, Dept Med,Pulm & Crit Care Med Unit, Rochester, NY 14642 USA. Univ Rochester, Sch Med & Dent, Dept Environm Med, Rochester, NY USA. NIH, Dept Biostat, Bethesda, MD 20892 USA. Univ Rochester, Sch Med & Dent, Dept Biostat, Rochester, NY USA. RP Pietropaoli, AP (reprint author), Univ Rochester, Med Ctr, Sch Med & Dent, Dept Med,Pulm & Crit Care Med Unit, 601 Elmwood Ave,Box 692, Rochester, NY 14642 USA. EM Anthony_Pietropaoli@urmc.rochester.edu FU NCRR NIH HHS [RR0044]; NIEHS NIH HHS [P30 ES01247, R01 ES11853] NR 57 TC 77 Z9 82 U1 3 U2 12 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 0895-8378 J9 INHAL TOXICOL JI Inhal. Toxicol. PY 2004 VL 16 SU 1 BP 59 EP 72 DI 10.1080/08958370490443079 PG 14 WC Toxicology SC Toxicology GA 837CQ UT WOS:000222605700007 PM 15204794 ER PT J AU Ribeiro, JMC Andersen, J Silva-Neto, MAC Pham, VM Garfield, MK Valenzuela, JG AF Ribeiro, JMC Andersen, J Silva-Neto, MAC Pham, VM Garfield, MK Valenzuela, JG TI Exploring the sialome of the blood-sucking bug Rhodnius prolixus SO INSECT BIOCHEMISTRY AND MOLECULAR BIOLOGY LA English DT Article DE nitrophorin; triabin; hemostasis; pallidipin; lipocalin; proteome; transcriptome ID PLATELET-AGGREGATION INHIBITOR; OXIDE TRANSPORT PROTEIN; NITRIC-OXIDE; SALIVARY-GLAND; HIGH-AFFINITY; HISTAMINE-BINDING; TRIATOMA-PALLIDIPENNIS; BLOOD-COAGULATION; ACIDIC LIPIDS; HEME PROTEIN AB Rhodnius prolixus is a Hemiptera that feeds exclusively on vertebrate blood in all life stages. Its salivary glands produce potent pharmacological substances that counteract host hemostasis, including anti-clotting, anti-platelet, and vasodilatory substances. To obtain a further insight into the salivary biochemical and pharmacological complexity of this insect, a cDNA library was randomly sequenced, and salivary gland homogenates were fractionated by HPLC to obtain aminoterminal sequences of abundantly expressed proteins. Results indicate a remarkable expansion of the lipocalin family in Rhodnius salivary glands, among other protein sequences described. A summary of 31 new full length proteins deducted from their mRNA sequence is described, including several new members of the nitrophorin, triabin, and pallidipin families. The electronic version of the complete tables is available at http://www.ncbi.nlm.nih.gov/projects/vectors/rhodnius_prolixus. Published by Elsevier Ltd. C1 NIAID, Parasit Dis Lab, Med Entomol Sect, NIH, Bethesda, MD 20892 USA. Univ Fed Rio de Janeiro, Ctr iencias Saude, Inst Ciencias Biomed, Dept Bioquim Med, BR-21941590 Rio De Janeiro, Brazil. NIAID, Biol Resources Branch, NIH, Bethesda, MD 20892 USA. RP Ribeiro, JMC (reprint author), NIAID, Parasit Dis Lab, Med Entomol Sect, NIH, 4 Ctr Dr,Room 4-126,MSC 0425, Bethesda, MD 20892 USA. EM jribeiro@nih.gov RI Silva-Neto , Mario /C-1211-2013; Marion-Poll, Frederic/D-8882-2011; OI Silva-Neto , Mario /0000-0003-2273-194X; Marion-Poll, Frederic/0000-0001-6824-0180; Ribeiro, Jose/0000-0002-9107-0818 NR 74 TC 93 Z9 95 U1 0 U2 9 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0965-1748 J9 INSECT BIOCHEM MOLEC JI Insect Biochem. Mol. Biol. PD JAN PY 2004 VL 34 IS 1 BP 61 EP 79 DI 10.1016/j.ibmb.2003.09.004 PG 19 WC Biochemistry & Molecular Biology; Entomology SC Biochemistry & Molecular Biology; Entomology GA 772UT UT WOS:000188860500006 PM 14976983 ER PT J AU Kochin, V Pallari, HM Pant, H Eriksson, JE AF Kochin, V Pallari, HM Pant, H Eriksson, JE TI Approaches to study posttranslational regulation of intermediate filament proteins SO INTERMEDIATE FILAMENT CYTOSKELETON SE METHODS IN CELL BIOLOGY LA English DT Review ID DESORPTION/IONIZATION MASS-SPECTROMETRY; KINASE-C; PHOSPHORYLATION SITES; OKADAIC ACID; TYROSINE PHOSPHORYLATION; PHOSPHOPEPTIDE ANALYSIS; NEUROFILAMENT PROTEINS; DISTINCT MECHANISMS; SELECTIVE INHIBITOR; CDC2 KINASE C1 Univ Turku, Turku Ctr Biotechnol, FIN-20521 Turku, Finland. Abo Akad Univ, FIN-20521 Turku, Finland. Univ Turku, Dept Biol, FIN-20521 Turku, Finland. NINDS, NIH, Neurochem Lab, Bethesda, MD 20892 USA. RP Kochin, V (reprint author), Univ Turku, Turku Ctr Biotechnol, FIN-20521 Turku, Finland. NR 105 TC 5 Z9 5 U1 0 U2 4 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA SN 0091-679X J9 METHOD CELL BIOL PY 2004 VL 78 BP 373 EP 409 PG 37 WC Cell Biology SC Cell Biology GA BBU63 UT WOS:000227909200014 PM 15646626 ER PT J AU Tkaczyk, C Okayama, Y Metcalfe, DD Gilfillan, AM AF Tkaczyk, C Okayama, Y Metcalfe, DD Gilfillan, AM TI Fc gamma receptors on mast cells: Activatory and inhibitory regulation of mediator release SO INTERNATIONAL ARCHIVES OF ALLERGY AND IMMUNOLOGY LA English DT Review DE mast cells; IgG; IgE; Fc gamma RI; Fc gamma RII; Fc gamma RIII; Fc epsilon RI ID AFFINITY IGE RECEPTOR; IMMUNOGLOBULIN-E RECEPTOR; BLOOD MONONUCLEAR-CELLS; EPSILON-RI; NEGATIVE REGULATION; RECOMBINANT HUMAN; TYROSINE KINASES; IFN-GAMMA; ARACHIDONIC-ACID; GROWTH-FACTOR AB Mast cell activation and subsequent release of proinflammatory mediators are primarily a consequence of aggregation of the high affinity receptors for IgE (FcepsilonRI) on the mast cell surface following antigen-dependent ligation of FcepsilonRI-bound IgE. However, data obtained from rodent and human mast cells have revealed that IgG receptors (FcgammaR) can both promote and inhibit mast cell activation. These responses appear to be species and/or mast cell phenotype dependent. In CD34+- derived human mast cells exposed to interferon-gamma, FcgammaRI is upregulated, FcgammaRII is expressed but not upregulated, and FcgammaRIII is not expressed. In contrast, in mouse mast cells, FcgammaRII and FcgammaRIII receptors are expressed, whereas FcgammaRI is not. Aggregation of FcgammaRI on human mast cells promotes mediator release in a manner generally similar to that observed following FcepsilonRI aggregation. Aggregation of FcgammaRIIb in mouse mast cells fails to influence cellular processes; however, when coligated with FcepsilonRI, signaling events thus activated downregulate antigen-dependent mediator release. These divergent responses are a consequence of different motifs contained within the cytosolic tails of the signaling subunits of these receptors and the specific signaling molecules recruited by these receptors following ligation. The studies described imply that data obtained in rodent models regarding the influence of FcgammaRs on mast cells may not be directly translatable to the human. The exploitation of FcgammaRs for a potential therapy for the treatment of allergic disorders is discussed in this context. Copyright (C)04 S. Karger AG, Basel. C1 NIAID, Lab Allerg Dis, NIH, Bethesda, MD 20892 USA. RIKEN Yokohama Inst, Res Ctr Allergy & Immunol, Lab Allergy Transcriptome, Yokohama, Kanagawa, Japan. RP Gilfillan, AM (reprint author), NIAID, Lab Allerg Dis, NIH, Bldg 10,Room 11C206,10 Ctr Dr MSC 1881, Bethesda, MD 20892 USA. EM agilfillan@niaid.nih.gov NR 79 TC 46 Z9 47 U1 0 U2 6 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1018-2438 J9 INT ARCH ALLERGY IMM JI Int. Arch. Allergy Immunol. PY 2004 VL 133 IS 3 BP 305 EP 315 DI 10.1159/000077213 PG 11 WC Allergy; Immunology SC Allergy; Immunology GA 807KX UT WOS:000220501500013 PM 15017113 ER PT J AU Bellizzi, KM AF Bellizzi, KM TI Expressions of generativity and posttraumatic growth in adult cancer survivors SO INTERNATIONAL JOURNAL OF AGING & HUMAN DEVELOPMENT LA English DT Article ID ADJUSTMENT; MASTECTOMY; LEGACY; TRAUMA; WORLD AB Much of the psycho-oncology research that has been conducted to date has focused on understanding the negative psychological and psychosocial sequelae of cancer. However, a growing body of evidence suggests that many cancer survivors report psychological growth following a diagnosis of cancer. Further, there are few studies that examine the relationship among age, cancer, and posttraumatic growth. This study examines relationships among posttraumatic growth, generativity, age, and gender. Questionnaires were mailed to 400 randomly-selected cancer survivors from a metropolitan hospital tumor registry, with a yield of 21%. Three age cohorts were examined (26-41 years, 42-54 years, and 55-plus years). As anticipated, MANOVA showed no significant age differences in expression of generative concern among the three cohorts, but there was evidence that younger adults engage in a greater number of generative behaviors than older adults. Further, females reported more positive growth on four out of the five domains of the measure of posttraumatic growth compared to males, and the oldest cohort experienced lower levels of positive growth compared with the other two groups. Generative concern was positively correlated with the total posttraumatic growth score. Implications for theoretical and applied research on generativity and posttraumatic growth in adult cancer survivors are discussed. C1 Univ Connecticut, Storrs, CT 06269 USA. RP Bellizzi, KM (reprint author), NCI, Canc Prevent Fellowship Program, 6130 Execut Blvd,Suite 3109, Bethesda, MD 20892 USA. EM kbellizzi@comcast.net NR 33 TC 54 Z9 55 U1 1 U2 6 PU BAYWOOD PUBL CO INC PI AMITYVILLE PA 26 AUSTIN AVE, AMITYVILLE, NY 11701 USA SN 0091-4150 J9 INT J AGING HUM DEV JI Int. J. Aging Human Dev. PY 2004 VL 58 IS 4 BP 267 EP 287 DI 10.2190/DC07-CPVW-4UVE-5GK0 PG 21 WC Gerontology; Psychology, Developmental SC Geriatrics & Gerontology; Psychology GA 847XS UT WOS:000223432000002 PM 15357329 ER PT J AU Vineis, P Alavanja, M Garte, S AF Vineis, P Alavanja, M Garte, S TI Dose-response relationship in tobacco-related cancers of bladder and lung: A biochemical interpretation SO INTERNATIONAL JOURNAL OF CANCER LA English DT Review ID 26,000 NORWEGIAN MEN; CIGARETTE TAR YIELD; FOLLOW-UP; ENVIRONMENTAL EXPOSURE; SMOKING-HABITS; BLACK TOBACCO; RISK-FACTORS; WOMEN; MORTALITY; SMOKERS AB The purpose of our study is to address the challenge of evaluating carcinogenic effects at low levels of exposure to carcinogens. We examine the shape of the dose-response relationship between tobacco smoking and cancers of the bladder and lung, and the implications for the evaluation of the effects of exposure at lower levels, for example, environmental tobacco smoke (ETS). C1 Univ Turin, Dept Biomed Sci & Human Oncol, I-10126 Turin, Italy. ISI Fdn, I-10126 Turin, Italy. NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. Genet Res Inst, Milan, Italy. Sch Publ Hlth, Brunswick, NJ USA. RP Vineis, P (reprint author), Univ Turin, Dept Biomed Sci & Human Oncol, Via Santena 7, I-10126 Turin, Italy. OI Garte, Seymour/0000-0003-3284-5975 NR 36 TC 38 Z9 38 U1 0 U2 4 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 JAN 1 PY 2004 VL 108 IS 1 BP 2 EP 7 DI 10.1002/ijc.11467 PG 6 WC Oncology SC Oncology GA 745YE UT WOS:000186718300001 PM 14618608 ER PT J AU Piatigorsky, J Kozmik, Z AF Piatigorsky, J Kozmik, Z TI Cubozoan jellyfish: an Evo/Devo model for eyes and other sensory systems SO INTERNATIONAL JOURNAL OF DEVELOPMENTAL BIOLOGY LA English DT Review DE cnidaria; rhopalia; eyes/ocelli; mechanoreceptors/ears; PaxB; evolution ID HEAT-SHOCK PROTEIN; GASTROPOD HALIOTIS-ASININA; HOMEOBOX-CONTAINING GENE; SQUID LOLIGO-OPALESCENS; DOMAIN-DNA COMPLEX; HUMAN PAX6 GENE; LENS CRYSTALLINS; PAIRED DOMAIN; DEVELOPMENTAL EXPRESSION; TRANSCRIPTION FACTORS AB Cnidaria are the most basal phylum containing a well-developed visual system located on specialized sensory structures (rhopalia) with eyes and statocyts. We have been exploring the cubozoan jellyfish, Tripedalia cystophora. In addition to containing simple photoreceptive ocelli, each rhopalium in Tridedalia has a large and small complex, camera-type eye with a cellular lens containing three distinct families of crystallins which apparently serve non-lenticular functions. Thus, Tridpedalia recruited crystallins by a gene sharing strategy as have mollusks and vertebrates. Tripedalia has a single Pax gene, PaxB, which encodes a structural and functional Pax 2/5/8-like paired domain as well as an octapeptide and Pax6-like homeodomain. PaxB binds to and activates Tripedalia crystallin promoters (especially J3-crystallin) and the Drosophila rhodopsin rh6 gene in transfection tests and induces ectopic eyes in Drosophila. In situ hybridization showed that PaxB and crystallin genes are expressed in the lens, retina and statocysts. We suggest from these results that an ancestral PaxB gene was a primordial gene in eye evolution and that eyes and ears (mechanoreceptors) may have had a common evolutionary origin. Thus, the numerous structural and molecular features of Tridpalia rhopalia indicate that ancient cubozoan jellyfish are fascinating models for evo/devo insights into eyes and other sensory systems. C1 NEI, NIH, Mol & Dev Biol Lab, Bethesda, MD 20892 USA. Inst Mol Genet, Prague, Czech Republic. RP Piatigorsky, J (reprint author), NEI, NIH, Mol & Dev Biol Lab, 7 Mem Dr Bldg 7,Room 100A, Bethesda, MD 20892 USA. EM joramp@nei.nih.gov RI Kozmik, Zbynek/G-3581-2014; Kozmik, Zbynek/I-8807-2014 NR 139 TC 40 Z9 42 U1 1 U2 9 PU U B C PRESS PI BILBAO PA UNIV BASQUE COUNTRY, EDITORIAL SERVICES, PO BOX 1397, E-48080 BILBAO, SPAIN SN 0214-6282 J9 INT J DEV BIOL JI Int. J. Dev. Biol. PY 2004 VL 48 IS 8-9 SI SI BP 719 EP 729 DI 10.1387/ijdb.041851jp PG 11 WC Developmental Biology SC Developmental Biology GA 882SH UT WOS:000225958100006 PM 15558464 ER PT J AU Zelenka, PS AF Zelenka, PS TI Regulation of cell adhesion and migration in lens development SO INTERNATIONAL JOURNAL OF DEVELOPMENTAL BIOLOGY LA English DT Article DE extracellular matrix; integrin; Rho GTPase; actin cytoskeleton; Cdk5 ID CYCLIC ADP-RIBOSE; EPITHELIAL-CELLS; ALPHA-6 INTEGRIN; INTRACELLULAR CALCIUM; SIGNAL-TRANSDUCTION; BASEMENT-MEMBRANES; CATARACT FORMATION; FIBER CELLS; CYTOSKELETAL REORGANIZATION; ENDOPLASMIC-RETICULUM AB Cell movements during lens development and differentiation involve dynamic regulation of cell-matrix and cell-cell adhesion. How these processes are regulated depends on the particular array of matrix components and adhesion proteins that are expressed, as well as the signaling pathways that affect them. This review examines what is known about adhesion proteins and their regulation in the lens in light of recent findings about the mechanism of cell migration. The characteristic shape and organization of the lens depends on highly regulated cell movements during development and differentiation. Epithelial cells at the equator migrate posteriorly, bringing them into contact with factors in the vitreous humor and initiating differentiation. Elongation of the differentiating fiber cells is coupled with directed migration, posteriorly along the capsule and anteriorly along the fiber cell-epithelial interface, to generate a symmetrically organized fiber cell mass with aligned suture planes. To make these movements, cells systematically create and dissolve cell-cell and cell-matrix adhesions, form connections between these adhesions and the cytoskeleton, and generate contractile force. Since errors in cell migration may lead to aberrant lens shape or misplacement of the lens sutures, precise regulation of each step is essential for the optical quality of the lens. Recent advances in cellular developmental biology have begun to shed light on the molecular mechanisms underlying cell movements and the changes in adhesion that make them possible. This review will summarize those findings and relate them to relevant studies of the lens to provide an outline of the cellular events that lead to lens morphogenesis. C1 NEI, Mol & Dev Biol Lab, NIH, Bethesda, MD 20892 USA. RP Zelenka, PS (reprint author), NEI, Mol & Dev Biol Lab, NIH, Bethesda, MD 20892 USA. EM zelenkap@nei.nih.gov NR 91 TC 41 Z9 41 U1 0 U2 4 PU U B C PRESS PI BILBAO PA UNIV BASQUE COUNTRY, EDITORIAL SERVICES, PO BOX 1397, E-48080 BILBAO, SPAIN SN 0214-6282 J9 INT J DEV BIOL JI Int. J. Dev. Biol. PY 2004 VL 48 IS 8-9 SI SI BP 857 EP 865 DI 10.1387/ijdb.041871pz PG 9 WC Developmental Biology SC Developmental Biology GA 882SH UT WOS:000225958100019 PM 15558477 ER PT J AU Musgrove, P AF Musgrove, P TI The perils of adding up: A cautionary tale about modeling and regression analysis SO INTERNATIONAL JOURNAL OF HEALTH SERVICES LA English DT Article AB To turn incomplete or imperfectly reliable information into estimates useful for policy, some modeling is often necessary or helpful. It does not follow that every statistical relation constitutes a model. There has to be an underlying theory, and the numerical estimates must respect any definitional or accounting identities that constrain the results. Ad hoc relations that do not meet these criteria can lead to uninterpretable or meaningless values, especially when different partial values, separately estimated, are added together. The imputed values of "responsiveness" in the WHO World Health Report 2000 illustrate this danger. C1 NIH, Fogarty Int Ctr, Dis Control Prior Project, Bethesda, MD 20892 USA. RP Musgrove, P (reprint author), NIH, Fogarty Int Ctr, Dis Control Prior Project, 16 Ctr Dr,MSC 6705, Bethesda, MD 20892 USA. EM musgrovp@mail.nih.gov NR 4 TC 0 Z9 0 U1 0 U2 0 PU BAYWOOD PUBL CO INC PI AMITYVILLE PA 26 AUSTIN AVE, AMITYVILLE, NY 11701 USA SN 0020-7314 J9 INT J HEALTH SERV JI Int. J. Health Serv. PY 2004 VL 34 IS 1 BP 11 EP 14 DI 10.2190/782P-QHKT-CJNE-7D3B PG 4 WC Health Care Sciences & Services; Health Policy & Services SC Health Care Sciences & Services GA 806UB UT WOS:000220457700002 PM 15088669 ER PT J AU Kessler, RC Merikangas, KR AF Kessler, RC Merikangas, KR TI The National Comorbidity Survey Replication (NCS-R): background and aims SO INTERNATIONAL JOURNAL OF METHODS IN PSYCHIATRIC RESEARCH LA English DT Article DE community survey; epidemiologic research design; National Comorbidity Survey Replication; psychiatric epidemiology ID DISORDER SEVERITY SCALE; UNITED-STATES; MENTAL-DISORDERS; PANIC DISORDER; PSYCHIATRIC EPIDEMIOLOGY; DIAGNOSTIC INTERVIEW; TREATMENT CONTACT; MAJOR DEPRESSION; PRIMARY-CARE; DSM-III AB The National Comorbidity Survey Replication (NCS-R) is a new nationally representative community household survey of the prevalence and correlates of mental disorders in the US. The NCS-R was carried out a decade after the original NCS. The NCS-R repeats many of the questions from the NCS and also expands the NCS questioning to include assessments based on the more recent Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-TV) diagnostics system (American Psychiatric Association, 1994). The NCS-R was designed to (1) investigate time trends and their correlates over the decade of the 1990s and (2) expand the assessment of the prevalence and correlates of mental disorders beyond the assessment in the baseline NCS in order to address a number of important substantive and methodological issues that were raised by the NCS. This paper presents a brief review of these aims. C1 Harvard Univ, Sch Med, Dept Hlth Care Policy, Boston, MA 02115 USA. NIMH, Intramural Res Program, Bethesda, MD 20892 USA. RP Kessler, RC (reprint author), Harvard Univ, Sch Med, Dept Hlth Care Policy, 180 Longwood Ave, Boston, MA 02115 USA. FU NIMH NIH HHS [U01-MH60220] NR 49 TC 373 Z9 376 U1 3 U2 9 PU WHURR PUBLISHERS LTD PI LONDON PA 19B COMPTON TERRACE, LONDON N1 2UN, ENGLAND SN 1049-8931 J9 INT J METH PSYCH RES JI Int. J. Methods Psychiatr. Res. PY 2004 VL 13 IS 2 BP 60 EP 68 DI 10.1002/mpr.166 PG 9 WC Psychiatry SC Psychiatry GA 848AP UT WOS:000223439600002 PM 15297904 ER PT J AU Colpe, L Merikangas, K Cuthbert, B Bourdon, K AF Colpe, L Merikangas, K Cuthbert, B Bourdon, K TI Guest editorial SO INTERNATIONAL JOURNAL OF METHODS IN PSYCHIATRIC RESEARCH LA English DT Editorial Material ID NATIONAL-COMORBIDITY-SURVEY; REPLICATION NCS-R; EPIDEMIOLOGY C1 NIMH, Bethesda, MD 20892 USA. RP Colpe, L (reprint author), NIMH, Bethesda, MD 20892 USA. NR 12 TC 20 Z9 20 U1 5 U2 5 PU WHURR PUBLISHERS LTD PI LONDON PA 19B COMPTON TERRACE, LONDON N1 2UN, ENGLAND SN 1049-8931 J9 INT J METH PSYCH RES JI Int. J. Methods Psychiatr. Res. PY 2004 VL 13 IS 4 BP 193 EP 195 DI 10.1002/mpr.176 PG 3 WC Psychiatry SC Psychiatry GA 877PN UT WOS:000225582600001 ER PT J AU Monge, P Wesseling, C Engel, LS Keifer, M Zuurbier, M Rojas, M Partanen, T AF Monge, P Wesseling, C Engel, LS Keifer, M Zuurbier, M Rojas, M Partanen, T TI An icon-based interview for the assessment of occupational pesticide exposure in a case-control study of childhood leukemia SO INTERNATIONAL JOURNAL OF OCCUPATIONAL AND ENVIRONMENTAL HEALTH LA English DT Article DE agricultural workers; questionnaire; exposure assessment; childhood cancer; Costa Rica ID ICON/CALENDAR-BASED QUESTIONNAIRE; AGRICULTURAL HEALTH; RELIABILITY; HISTORY/; FARMERS; MIGRANT; CANCER; STYLE AB An icon-calendar interview form (ICF) for a case-control study of childhood leukemias and parental exposures to pesticides is described. It includes calendar sheets, icons for life events, crops, jobs, regions, non-agricultural jobs, application techniques and personal protection, markers for durations of exposure patterns, and checklists of pesticides. The ICF collects monthly data from two years before birth until diagnosis of cancer (index children) or until either the interview date or age 15 (controls). Data ascertainment was easy in 62% of interviews, moderately easy in 32%, and difficult in 6%. Seventy-eight subjects delivered data on specific pesticides with pesticide checklists, which improved identification of pesticides. ICF performs satisfactorily for crops, tasks, and other determinants of exposure. Data on pesticides will be further improved by introducing external data use on different crops, time periods, and regions, and by exposure modeling for 27 pesticides. C1 Univ Nacl, Cent Amer Inst Studies Tox Substances, Heredia, Costa Rica. NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. Univ Washington, Seattle, WA 98195 USA. Univ Utrecht, Inst Risk Assessment Sci, Utrecht, Netherlands. RP Monge, P (reprint author), Univ Nacl, Cent Amer Inst Studies Tox Substances, POB 86-3000, Heredia, Costa Rica. EM pmonge@una.ac.cr FU FIC NIH HHS [5 D43 TW00642-07] NR 19 TC 7 Z9 7 U1 2 U2 8 PU ABEL PUBLICATION SERVICES PI BURLINGTON PA 1611 AQUINAS COURT, BURLINGTON, NC 27215 USA SN 1077-3525 J9 INT J OCCUP ENV HEAL JI Int. J. Occup. Environ. Health PD JAN-MAR PY 2004 VL 10 IS 1 BP 72 EP 78 PG 7 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 811XJ UT WOS:000220804300009 PM 15070028 ER PT J AU Brooks, JP Smith, SL Albert, PS Camphausen, K Poggi, MM AF Brooks, JP Smith, SL Albert, PS Camphausen, K Poggi, MM TI Isolated ipsilateral in-breast event after breast conservation therapy does not affect survival: An analysis of the NCI Randomized trial SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Meeting Abstract CT 46th Annual Meeting of the American-Society-for-Therapeutic-Radiology-and-Oncology CY OCT 03-07, 2004 CL Atlanta, GA SP Amer Soc Therapeut Radiol & Oncol C1 Natl Naval Med Res Inst, Div Radiat Oncol, Bethesda, MD 20892 USA. NCI, Radiat Oncol Branch, Bethesda, MD 20892 USA. NCI, Biometr Res Branch, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0360-3016 J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PY 2004 VL 60 IS 1 SU S MA 2114 BP S403 EP S403 PG 1 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 853UP UT WOS:000223854700457 ER PT J AU Citrin, D Beecken, W Scott, T Goley, E Sproull, M Tofilon, P Camphausen, K AF Citrin, D Beecken, W Scott, T Goley, E Sproull, M Tofilon, P Camphausen, K TI Use of microarray for screening radiation induced molecular targets SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Meeting Abstract CT 46th Annual Meeting of the American-Society-for-Therapeutic-Radiology-and-Oncology CY OCT 03-07, 2004 CL Atlanta, GA SP Amer Soc Therapeut Radiol & Oncol C1 NCI, Radiat Oncol Branch, Bethesda, MD 20892 USA. Harvard Univ, Sch Med, Surg Res Labs, Childrens Hosp, Boston, MA 02115 USA. NR 0 TC 0 Z9 1 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0360-3016 J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PY 2004 VL 60 IS 1 SU S MA 2037 BP S360 EP S360 PG 1 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 853UP UT WOS:000223854700380 ER PT J AU Faraci, M Barra, S Lanino, E Dallorso, S Foppiano, F Dini, G Haupt, R Vitale, V AF Faraci, M Barra, S Lanino, E Dallorso, S Foppiano, F Dini, G Haupt, R Vitale, V TI Late effects after two different TBI regimens: Analysis of 42 transplanted children SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Meeting Abstract CT 46th Annual Meeting of the American-Society-for-Therapeutic-Radiology-and-Oncology CY OCT 03-07, 2004 CL Atlanta, GA SP Amer Soc Therapeut Radiol & Oncol C1 Natl Canc Inst, Genoa, Italy. Gaslini Childrens Res Inst, Genoa, Italy. RI Haupt, Riccardo/C-2237-2012 NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0360-3016 J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PY 2004 VL 60 IS 1 SU S MA 195 BP S249 EP S250 PG 2 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 853UP UT WOS:000223854700195 ER PT J AU Li, G Xie, H Ning, H Menard, C Coleman, CN Miller, RW AF Li, G Xie, H Ning, H Menard, C Coleman, CN Miller, RW TI Application of three-dimensional voxel fusion technique to multi-modality fusion of anatomical and functional images SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Meeting Abstract CT 46th Annual Meeting of the American-Society-for-Therapeutic-Radiology-and-Oncology CY OCT 03-07, 2004 CL Atlanta, GA SP Amer Soc Therapeut Radiol & Oncol C1 NCI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0360-3016 J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PY 2004 VL 60 IS 1 SU S MA 2410 BP S582 EP S582 PG 1 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 853UP UT WOS:000223854700753 ER PT J AU Menard, C Citrin, D Susil, RC Gharib, PA Gustafson, G Ning, H Miller, RW Ullman, KL Guion, P Pouliot, J Coleman, C Camphausen, K AF Menard, C Citrin, D Susil, RC Gharib, PA Gustafson, G Ning, H Miller, RW Ullman, KL Guion, P Pouliot, J Coleman, C Camphausen, K TI 1.5T MRI for cathether placement and treatment planning in high dose rate brachytherapy for prostate cancer SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Meeting Abstract CT 46th Annual Meeting of the American-Society-for-Therapeutic-Radiology-and-Oncology CY OCT 03-07, 2004 CL Atlanta, GA SP Amer Soc Therapeut Radiol & Oncol C1 NCI, Radiat Oncol Branch, NIH, DHHS, Bethesda, MD 20892 USA. Johns Hopkins Univ, Dept Biomed Engn, Baltimore, MD 21218 USA. NIH, Dept Diagnost Radiol, Ctr Clin, DHHS, Bethesda, MD 20892 USA. William Beaumont Hosp, Dept Radiat Oncol, Royal Oak, MI 48072 USA. Univ Calif San Francisco, Dept Radiat Oncol, San Francisco, CA 94143 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0360-3016 J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PY 2004 VL 60 IS 1 SU S MA 2209 BP S461 EP S462 PG 2 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 853UP UT WOS:000223854700552 ER PT J AU Muanza, TM Basu, S Coleman, CN Tofilon, P Camphausen, K AF Muanza, TM Basu, S Coleman, CN Tofilon, P Camphausen, K TI Urinary isoprostanes as markers of radiation-induced normal brain injury SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Meeting Abstract CT 46th Annual Meeting of the American-Society-for-Therapeutic-Radiology-and-Oncology CY OCT 03-07, 2004 CL Atlanta, GA SP Amer Soc Therapeut Radiol & Oncol C1 NCI, Radiat Oncol Branch, Bethesda, MD 20892 USA. McGill Univ, Ctr Hlth, Montreal, PQ, Canada. Uppsala Univ, Uppsala, Sweden. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0360-3016 J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PY 2004 VL 60 IS 1 SU S MA 2043 BP S363 EP S364 PG 2 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 853UP UT WOS:000223854700386 ER PT J AU Ning, H Ullman, KL Miller, RW Ayele, A Jocelyn, L Havelos, J Guion, P Xie, H Li, G Arora, B Coleman, C Menard, C AF Ning, H Ullman, KL Miller, RW Ayele, A Jocelyn, L Havelos, J Guion, P Xie, H Li, G Arora, B Coleman, C Menard, C TI A simple and reproducible method for daily verification and correction of isocenter position relative to prostatic fiducial markers using electronic portal imaging SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Meeting Abstract CT 46th Annual Meeting of the American-Society-for-Therapeutic-Radiology-and-Oncology CY OCT 03-07, 2004 CL Atlanta, GA SP Amer Soc Therapeut Radiol & Oncol C1 NCI, Radiat Oncol Branch, DHHS, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0360-3016 J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PY 2004 VL 60 IS 1 SU S MA 2458 BP S614 EP S614 PG 1 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 853UP UT WOS:000223854700801 ER PT J AU Woodard, GE AF Woodard, GE TI Chemosensory G-protein-coupled receptor signaling in the brain SO INTERNATIONAL REVIEW OF NEUROBIOLOGY, VOL 62 SE INTERNATIONAL REVIEW OF NEUROBIOLOGY LA English DT Review ID PUTATIVE PHEROMONE RECEPTORS; MAMMALIAN TASTE RECEPTORS; RAT OLFACTORY RECEPTOR; GATED CATION CHANNEL; SWEET TASTE; VOMERONASAL ORGAN; MULTIGENE FAMILY; UMAMI TASTE; SACCHARIN PREFERENCE; INFORMATION-SYSTEM C1 NIDDKD, Genet & Endocrinol Sect, Metab Dis Branch, NIH, Bethesda, MD 20892 USA. RP Woodard, GE (reprint author), NIDDKD, Genet & Endocrinol Sect, Metab Dis Branch, NIH, Bethesda, MD 20892 USA. RI Woodard, Geoffrey/A-8608-2009 NR 73 TC 0 Z9 0 U1 0 U2 3 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA SN 0074-7742 J9 INT REV NEUROBIOL PY 2004 VL 62 BP 147 EP 157 DI 10.1016/S0074-7742(04)62005-8 PG 11 WC Neurosciences SC Neurosciences & Neurology GA BBI36 UT WOS:000225608200005 PM 15530571 ER PT B AU Dalakas, MC AF Dalakas, MC BE Dalakas, MC Spath, PJ TI Witnessing the introduction use of intravenous immunoglobulin in neurology SO INTRAVENOUS IMMUNOGLOBULINS IN THE THIRD MILLENNIUM LA English DT Proceedings Paper CT 5th International Symposium on the Use of Intravenous Immunoglobulin CY SEP 25-27, 2003 CL Interlaken, SWITZERLAND SP ZLB Bioplasma AG ID GAMMA-GLOBULIN; MYASTHENIA-GRAVIS C1 NINDS, Neuromuscular Dis Sect, NIH, Bethesda, MD 20892 USA. RP Dalakas, MC (reprint author), NINDS, Neuromuscular Dis Sect, NIH, Bldg 10,Room 4N248,10 Ctr Dr MSC,1382, Bethesda, MD 20892 USA. NR 6 TC 1 Z9 1 U1 0 U2 0 PU PARTHENON PUBLISHING GROUP LTD PI LANCASTER PA CASTERTON HALL, CARNFORTH, LANCASTER LA6 2LA, ENGLAND BN 1-84214-258-5 PY 2004 BP 37 EP 39 PG 3 WC Immunology SC Immunology GA BY58U UT WOS:000189415100005 ER PT B AU Dalakas, MC AF Dalakas, MC BE Dalakas, MC Spath, PJ TI Controlled studies with high-dose intravenous immunoglobulin in the treatment of inclusion body myositis SO INTRAVENOUS IMMUNOGLOBULINS IN THE THIRD MILLENNIUM LA English DT Proceedings Paper CT 5th International Symposium on the Use of Intravenous Immunoglobulin CY SEP 25-27, 2003 CL Interlaken, SWITZERLAND SP ZLB Bioplasma AG ID INFLAMMATORY MYOPATHIES; MESSENGER-RNA; DOUBLE-BLIND; EXPRESSION; DERMATOMYOSITIS C1 NINDS, Neuromusc Dis Sect, NIH, Bethesda, MD 20892 USA. RP Dalakas, MC (reprint author), NINDS, Neuromusc Dis Sect, NIH, Bldg 10,Room 4N248,10 Ctr Dr MSC,1382, Bethesda, MD 20892 USA. NR 22 TC 0 Z9 0 U1 0 U2 0 PU PARTHENON PUBLISHING GROUP LTD PI LANCASTER PA CASTERTON HALL, CARNFORTH, LANCASTER LA6 2LA, ENGLAND BN 1-84214-258-5 PY 2004 BP 213 EP 218 PG 6 WC Immunology SC Immunology GA BY58U UT WOS:000189415100033 ER PT B AU Dalakas, MC AF Dalakas, MC BE Dalakas, MC Spath, PJ TI High-dose intravenous immunoglobulin in the treatment elf patients with stiff person syndrome: a controlled study SO INTRAVENOUS IMMUNOGLOBULINS IN THE THIRD MILLENNIUM LA English DT Proceedings Paper CT 5th International Symposium on the Use of Intravenous Immunoglobulin CY SEP 25-27, 2003 CL Interlaken, SWITZERLAND SP ZLB Bioplasma AG ID GLUTAMIC-ACID DECARBOXYLASE; IMMUNE GLOBULIN; AUTOANTIBODIES C1 NINDS, Neuromusc Dis Sect, NIH, Bethesda, MD 20892 USA. RP Dalakas, MC (reprint author), NINDS, Neuromusc Dis Sect, NIH, Bldg 10,Room 4N248,10 Ctr Dr MSC,1382, Bethesda, MD 20892 USA. NR 17 TC 0 Z9 0 U1 0 U2 0 PU PARTHENON PUBLISHING GROUP LTD PI LANCASTER PA CASTERTON HALL, CARNFORTH, LANCASTER LA6 2LA, ENGLAND BN 1-84214-258-5 PY 2004 BP 257 EP 266 PG 10 WC Immunology SC Immunology GA BY58U UT WOS:000189415100038 ER PT B AU Walker, FL Thoma, GR AF Walker, FL Thoma, GR BE Frey, F Buckley, R TI A Web-based paradigm for file migration SO IS&T'S 2004 ARCHIVING CONFERENCE, PROCEEDINGS LA English DT Proceedings Paper CT 1st IS&T Archiving Conference CY APR 20-23, 2004 CL San Antonio, TX SP Soc Imaging Sci & Technol, Tech Assoc Graph Arts, Online Comp Lib Ctr, Coalit Network Informat, Digital Lib Federat, Res Lib Grp, Museum Comp Network, Amer Inst Conservat, European Commiss Preservat & Access, SPIE, ALCTS AB The migration of files in obsolete formats to those expected to survive into the future is a key task in proposed techniques for the preservation of electronic documents. To this end, MyMorph has been developed as a web-based file migration service that allows the bulk conversion of electronic documents to PDF in a manner that minimizes certain aspects of the migration cost. It uses client software running on the user's computer to send files via SOAP to a computer system at the National Library of Medicine called DocMorph, which converts more than fifty different file formats to PDF and returns the results to the user. The MyMorph software has been beta tested since June 2002 by more than 2,000 users who have used it to convert thousands of files to PDF. Nearly all users found the software easy to learn to use, and most report that the conversion is fast. From the user's viewpoint the software minimizes the cost of migration in two ways. First, since MyMorph is freely available, anybody with a Windows-based computer and access to the Internet can use it. Second, the interface permits file migration to proceed in batch mode, requiring minimal user interaction regardless of the number of files converted. This paper describes the architecture of this web-based paradigm for file migration, and summarizes the results of the beta test. C1 Natl Lib Med, Lister Hill Natl Ctr Biomed Commun, Bethesda, MD USA. NR 7 TC 0 Z9 0 U1 0 U2 0 PU SOC IMAGING SCIENCE & TECHNOLOGY PI SPRINGFIELD PA 7003 KILWORTH LANE, SPRINGFIELD, VA 22151 USA BN 0-89208-251-8 PY 2004 BP 93 EP 97 PG 5 WC Computer Science, Information Systems; Information Science & Library Science SC Computer Science; Information Science & Library Science GA BBO37 UT WOS:000226641700021 ER PT J AU Dudko, OK Filippov, AE Klafter, J Urbakh, M AF Dudko, OK Filippov, AE Klafter, J Urbakh, M TI Following single molecules by force spectroscopy SO ISRAEL JOURNAL OF CHEMISTRY LA English DT Article ID SCANNING TUNNELING MICROSCOPE; INDIVIDUAL MOLECULES; ADHESION; ATOMS; MANIPULATION; PROBES; BONDS; CHEMISTRY; PROTEIN; MOTION AB Dynamic force spectroscopy of single molecules, in which an adhesion bond is driven away from equilibrium by a spring pulled with velocity V, is described by a model that predicts the distribution of rupture forces (mean and variance), all amenable to experimental tests. The distribution has a pronounced asymmetry, which has recently been observed experimentally. The mean rupture force follows a (ln V)(2/3) dependence on the pulling velocity and differs from earlier predictions. Interestingly, at low pulling velocities a rebinding process is observed whose signature is an intermittent behavior of the spring force that delays the rupture. Based on the rupture mechanism, we propose a new "pick-up-and-putdown" method to manipulate individual molecules with scanning probes. We demonstrate that the number of molecules picked up by the tip and deposited at a different location can be controlled by adjusting the pulling velocity of the tip and the distance of closest approach of the tip to the surface. C1 Tel Aviv Univ, Sch Chem, IL-69978 Tel Aviv, Israel. NIH, Math & Stat Comp Lab, Bethesda, MD 20892 USA. NASU, Donetsk Inst Phys & Engn, UA-83144 Donetsk, Ukraine. RP Urbakh, M (reprint author), Tel Aviv Univ, Sch Chem, IL-69978 Tel Aviv, Israel. EM urbakh@post.tau.ac.il NR 44 TC 2 Z9 2 U1 0 U2 1 PU LASER PAGES PUBL LTD PI JERUSALEM PA MERKAZ SAPIR 6/36, GIVAT SHAUL, PO BOX 35409, JERUSALEM 91352, ISRAEL SN 0021-2148 J9 ISRAEL J CHEM JI Isr. J. Chem. PY 2004 VL 44 IS 4 BP 363 EP 372 DI 10.1560/TBV9-439H-6U1D-1BDX PG 10 WC Chemistry, Multidisciplinary SC Chemistry GA 890DB UT WOS:000226490800004 ER PT B AU Lynch, P Luan, XC Prettyman, M Mericle, L Borkmann, E Schlaifer, J AF Lynch, P Luan, XC Prettyman, M Mericle, L Borkmann, E Schlaifer, J BE Srimani, PK TI An evaluation of new and old similarity ranking algorithms SO ITCC 2004: INTERNATIONAL CONFERENCE ON INFORMATION TECHNOLOGY: CODING AND COMPUTING, VOL 2, PROCEEDINGS LA English DT Proceedings Paper CT International Conference on Information Technology - Coding and Computing CY APR 05-07, 2004 CL Las Vegas, NV SP IEEE Comp Soc AB The National Library of Medicine's (NLM) IRVIS project has been evaluating "similarity ranking" algorithms that re-order search results according to their similarity to a target result. Several variations of known ranking algorithms were tested, as well as one (we believe) new one which weights terms based on word length. When the algorithms were evaluated using the OHSUMED test collection, the new word length based algorithm was found to outperform the others. C1 US Natl Lib Med, Lister Hill Natl Ctr Biomed Commun, Comp Sci Branch, Bethesda, MD USA. RP Lynch, P (reprint author), US Natl Lib Med, Lister Hill Natl Ctr Biomed Commun, Comp Sci Branch, Bethesda, MD USA. NR 5 TC 1 Z9 1 U1 0 U2 0 PU IEEE COMPUTER SOC PI LOS ALAMITOS PA 10662 LOS VAQUEROS CIRCLE, PO BOX 3014, LOS ALAMITOS, CA 90720-1264 USA BN 0-7695-2108-8 PY 2004 BP 148 EP 149 DI 10.1109/ITCC.2004.1286615 PG 2 WC Computer Science, Artificial Intelligence; Computer Science, Hardware & Architecture; Computer Science, Information Systems; Computer Science, Theory & Methods SC Computer Science GA BAA56 UT WOS:000221353100032 ER PT J AU Costin, GE AF Costin, GE TI What is the advantage of having melanin in parts of the central nervous system (e.g. substantia nigra)? SO IUBMB LIFE LA English DT Letter ID PARKINSONS-DISEASE; HUMAN BRAIN; NEUROMELANIN; IRON; NEURONS; METALS C1 NCI, Pigment Cell Biol Sect, Cell Biol Lab, NIH, Bethesda, MD 20892 USA. RP Costin, GE (reprint author), NCI, Pigment Cell Biol Sect, Cell Biol Lab, NIH, Bethesda, MD 20892 USA. EM costing@mail.nih.gov NR 21 TC 0 Z9 0 U1 0 U2 0 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1521-6543 J9 IUBMB LIFE JI IUBMB Life PD JAN PY 2004 VL 56 IS 1 BP 47 EP 49 DI 10.1080/15216540310001659029 PG 3 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 767RV UT WOS:000188467200008 PM 14992380 ER PT J AU Markowitz, JA Tinkle, MB Fischbeck, KH AF Markowitz, JA Tinkle, MB Fischbeck, KH TI Spinal muscular atrophy in the neonate SO JOGNN-JOURNAL OF OBSTETRIC GYNECOLOGIC AND NEONATAL NURSING LA English DT Article DE end of life care; genetic disorders in the neonate; spinal muscular atrophy ID MOTOR-NEURON GENE; SMN GENE; PRENATAL-DIAGNOSIS; MOLECULAR ANALYSIS; SURVIVAL; ARTHROGRYPOSIS; PROTEIN; COPIES; MOUSE; RISK AB Spinal muscular atrophy (SMA) type I is an autosomal recessive disorder characterized by loss of lower motor neurons in the spinal cord. This severe hereditary neurodegenerative disorder is an important cause of morbidity in the neonate and the leading hereditary cause of infant mortality. The characteristic degeneration of anterior horn cells in the spinal cord leads to progressive muscular weakness and atrophy of the skeletal muscles. In SMA type 1, the most severe form of SMA, death usually ensues by 2 years of age from respiratory failure or infection. Accurate diagnosis is now available through genetic testing, and progress is being made toward the development of therapy based on understanding of the disease mechanism. The neonatal nurse plays a pivotal role in identifying and caring for these medically fragile infants and in providing support and education for parents and families. C1 NINR, NIH, Bethesda, MD 20892 USA. NINDS, Neurogenet Branch, NIH, Bethesda, MD 20892 USA. RP Tinkle, MB (reprint author), NINR, NIH, 31 Ctr Dr,Rm 5B-13, Bethesda, MD 20892 USA. EM tinklem@mail.nih.gov NR 42 TC 13 Z9 14 U1 1 U2 4 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0884-2175 J9 JOGNN JI JOGNN PD JAN-FEB PY 2004 VL 33 IS 1 BP 12 EP 20 DI 10.1177/0884217503261125 PG 9 WC Nursing; Obstetrics & Gynecology SC Nursing; Obstetrics & Gynecology GA 767EZ UT WOS:000188428400005 PM 14971549 ER PT J AU Somoza, EC Winhusen, TM Bridge, TP Rotrosen, JP Vanderburg, DG Harrer, JM Mezinskis, JP Montgomery, MA Ciraulo, DA Wulsin, LR Barrett, JA AF Somoza, EC Winhusen, TM Bridge, TP Rotrosen, JP Vanderburg, DG Harrer, JM Mezinskis, JP Montgomery, MA Ciraulo, DA Wulsin, LR Barrett, JA TI An open-label pilot study of methylphenidate in the treatment of cocaine dependent patients with adult attention deficit/hyperactivity disorder SO JOURNAL OF ADDICTIVE DISEASES LA English DT Article DE cocaine dependence; attention deficit disorder; ADHD; methylphenidate ID DEFICIT HYPERACTIVITY DISORDER; DOUBLE-BLIND; ABUSERS; SYMPTOMS; PLACEBO AB A multi-site, open-label study of methylphenidate for treating patients with comorbid diagnoses of attention deficit/hyperactivity disorder and cocaine dependence was performed. Forty-one participants, who met DSM-IV criteria for adult attention deficit/hyperactivity disorder and cocaine dependence, were enrolled into this ten week outpatient study. The targeted total daily dose of methylphenidate was 60 mg (20 mg TID). Participants received individual substance abuse therapy throughout the trial. Safety measures included adverse events, vital signs, and electrocardiograms. Methylphenidate's efficacy was assessed by both objective and subjective measures. Seventy percent of the participants completed final study measures. Safety measures indicated that methylphenidate was well tolerated by the participants. Subjective efficacy measures suggested that participants evidenced improvement in both cocaine dependence and adult attention deficit/hyperactivity disorder symptoms. Quantitative benzoylecgonine indicated that only those participants categorized as being compliant showed improvement. A double-blind, placebo-controlled study of methylphenidate for this population may be warranted. C1 CinARC, Cincinnati, OH 45220 USA. Cincinnati VA UC NIDA MDRU, Cincinnati, OH 45220 USA. Univ Cincinnati, Coll Med, Dept Psychiat, Cincinnati, OH 45267 USA. Natl Inst Drug Abuse, Div Treatment Res & Dev, Bethesda, MD 20892 USA. NYU, Sch Med, New York, NY 10010 USA. VHA New York Harbor Healthcare Syst, New York, NY 10010 USA. Boston Univ, Sch Med, Dept Psychiat, MDRU,VA Boston Healthcare Syst, Boston, MA 02118 USA. RP Somoza, EC (reprint author), CinARC, 3210 Jefferson Ave, Cincinnati, OH 45220 USA. EM somoza@uc.edu OI Ciraulo, Domenic/0000-0001-7706-8765; Winhusen, Theresa/0000-0002-3364-0739 FU NIDA NIH HHS [Y01 DA 50038-00] NR 28 TC 39 Z9 39 U1 0 U2 0 PU HAWORTH PRESS INC PI BINGHAMTON PA 10 ALICE ST, BINGHAMTON, NY 13904-1580 USA SN 1055-0887 J9 J ADDICT DIS JI J. Addict. Dis. PY 2004 VL 23 IS 1 BP 77 EP 92 DI 10.1300/J069v23n01_07 PG 16 WC Substance Abuse SC Substance Abuse GA 808BX UT WOS:000220545700007 PM 15077842 ER PT J AU Cadet, JL Better, WE Tate, K Herning, RI AF Cadet, JL Better, WE Tate, K Herning, RI TI Cerebrovascular deficits in MDMA (ecstacy) abusers SO JOURNAL OF ADDICTIVE DISEASES LA English DT Meeting Abstract C1 NIDA, Mol Neuropsychiat Branch, NIH, Baltimore, MD 21224 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU HAWORTH PRESS INC PI BINGHAMTON PA 10 ALICE ST, BINGHAMTON, NY 13904-1580 USA SN 1055-0887 J9 J ADDICT DIS JI J. Addict. Dis. PY 2004 VL 23 IS 2 MA 5A BP 129 EP 129 PG 1 WC Substance Abuse SC Substance Abuse GA 820NL UT WOS:000221396400014 ER PT J AU Cadet, JL Tate, K Herning, RI Better, WE AF Cadet, JL Tate, K Herning, RI Better, WE TI Cardiovascular changes in young marijuana abusers SO JOURNAL OF ADDICTIVE DISEASES LA English DT Meeting Abstract C1 NIDA, Mol Neuropsychiat Branch, NIH, Baltimore, MD 21224 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU HAWORTH PRESS INC PI BINGHAMTON PA 10 ALICE ST, BINGHAMTON, NY 13904-1580 USA SN 1055-0887 J9 J ADDICT DIS JI J. Addict. Dis. PY 2004 VL 23 IS 2 MA 6A BP 130 EP 130 PG 1 WC Substance Abuse SC Substance Abuse GA 820NL UT WOS:000221396400015 ER PT J AU Cadet, JL Better, W Tate, K Herning, RI AF Cadet, JL Better, W Tate, K Herning, RI TI EEG deficits in MDMA (ecstasy) abusers SO JOURNAL OF ADDICTIVE DISEASES LA English DT Meeting Abstract C1 NIDA, Mol Neuropsychiat Branch, NIH, Baltimore, MD 21224 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU HAWORTH PRESS INC PI BINGHAMTON PA 10 ALICE ST, BINGHAMTON, NY 13904-1580 USA SN 1055-0887 J9 J ADDICT DIS JI J. Addict. Dis. PY 2004 VL 23 IS 2 MA 7A BP 131 EP 131 PG 1 WC Substance Abuse SC Substance Abuse GA 820NL UT WOS:000221396400016 ER PT J AU Klion, AD Nutman, TB AF Klion, AD Nutman, TB TI The role of eosinophils in host defense against helminth parasites SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Review DE immunity; resistance; cytotoxicity; nematodes ID INTERLEUKIN-5 TRANSGENIC MICE; MAJOR BASIC-PROTEIN; INFLAMMATORY CELL RECRUITMENT; SCHISTOSOMA-MANSONI; ANGIOSTRONGYLUS-CANTONENSIS; PROTECTIVE IMMUNITY; TRICHINELLA-SPIRALIS; ONCHOCERCA-VOLVULUS; TOXOCARA-CANIS; BRUGIA-MALAYI AB The precise function of eosinophils in parasitic infection in vivo remains poorly understood despite eosinophils having been shown to be potent effectors in killing parasites in vitro. Although it has long been held that the primary function of the eosinophil is protection against helminth parasites, there are little data to prove this unequivocally. Moreover, eosinophils are responsible for a considerable amount of inflammatory pathology accompanying helminth infections. This article will provide an overview of our current knowledge about eosinophils and their role, both protective and pathogenetic, in parasitic helminth infections. C1 NIAID, Helminth Immunol Sect, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA. RP Nutman, TB (reprint author), NIAID, Helminth Immunol Sect, Parasit Dis Lab, NIH, Bldg 4,Room B1-03,4 Ctr Dr, Bethesda, MD 20892 USA. OI Klion, Amy/0000-0002-4986-5326 NR 116 TC 191 Z9 200 U1 1 U2 21 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0091-6749 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD JAN PY 2004 VL 113 IS 1 BP 30 EP 37 DI 10.1016/j.jaci.2003.10.050 PG 8 WC Allergy; Immunology SC Allergy; Immunology GA 760MP UT WOS:000187837900003 PM 14713904 ER PT J AU Arbes, SJ Sever, M Mehta, J Gore, JC Schal, C Vaughn, B Mitchell, H Zeldin, DC AF Arbes, SJ Sever, M Mehta, J Gore, JC Schal, C Vaughn, B Mitchell, H Zeldin, DC TI Abatement of cockroach allergens (Bla g 1 and Bla g 2) in low-income, urban housing: Month 12 continuation results SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Article DE cockroaches; cockroach allergen; Bla g 1; Bla g 2; indoor allergens; intervention trial ID INNER-CITY CHILDREN; ASTHMA; EXPOSURE AB Background: In the first 6 months of this previously published, randomized trial, the combined intervention of occupant education, insecticide bait application, and professional cleaning significantly reduced cockroach numbers and Bla g 1 allergen levels in inner-city homes. Objective: This continuation study investigated whether the cockroach allergen reductions achieved by month 6 could be maintained through month 12 with insecticide application alone. Methods: Because we had agreed to place insecticide bait in control homes at the conclusion of the first study, intervention and control homes were treated with insecticide bait at months 6 and 9. No other intervention was conducted in either arm. Vacuumed dust and swab samples were collected at month 12. Twenty-one of the 31 original homes completed the 12-month study. Results: Among the original intervention homes, Bla g I concentrations remained essentially unchanged from months 6 to 12. However, among the crossed-over control homes, the geometric mean Bla g I concentrations (Units per gram of dust) decreased from 287 to 14.4 for kitchen floors (95% reduction), from 28.8 to 5.6 for living room floors/sofas (81% reduction), from 26.7 to 4.7 for bedroom floors (82% reduction), and from 7.2 to 2.4 for beds (67% reduction). At month 12, Bla g I concentrations did not significantly differ between intervention and crossed-over control homes (P >.64 at each location). Similar results were seen for the allergen Bla g 2. Conclusions: Reductions in cockroach allergen concentrations achieved through the combined intervention of occupant education, insecticide application, and professional cleaning can be maintained with continued cockroach control. Surprisingly, and in contrast to other studies, insecticide application alone significantly lowered allergen concentrations in the crossed-over control homes. This unexpected result is being tested further in another randomized trial. C1 NIEHS, Div Intramural Res, NIH, Res Triangle Pk, NC 27709 USA. N Carolina State Univ, Dept Entomol, Raleigh, NC 27695 USA. Rho Inc, Chapel Hill, NC USA. RP Zeldin, DC (reprint author), NIEHS, Div Intramural Res, NIH, POB 12233,MD D2-01, Res Triangle Pk, NC 27709 USA. RI Schal, Coby/A-8717-2010; OI Schal, Coby/0000-0001-7195-6358; Sever, Michelle/0000-0002-2435-1214 NR 8 TC 52 Z9 54 U1 0 U2 2 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0091-6749 EI 1097-6825 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD JAN PY 2004 VL 113 IS 1 BP 109 EP 114 DI 10.1016/j.jaci.2003.10.042 PG 6 WC Allergy; Immunology SC Allergy; Immunology GA 760MP UT WOS:000187837900014 PM 14713915 ER PT J AU Wegienka, G London, SJ Johnson, CC Ownby, DR AF Wegienka, G London, SJ Johnson, CC Ownby, DR TI Interpregnancy interval might affect the risk of childhood atopy SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Letter ID ALLERGIC SENSITIZATION; HAY-FEVER; PREECLAMPSIA; AGE C1 Henry Ford Hlth Syst, Dept Biostat & Res Epidemiol, Detroit, MI 48202 USA. NIEHS, NIH, US Dept HHS, Bethesda, MD USA. Med Coll Georgia, Augusta, GA 30912 USA. RP Wegienka, G (reprint author), Henry Ford Hlth Syst, Dept Biostat & Res Epidemiol, 1 Ford Pl, Detroit, MI 48202 USA. OI London, Stephanie/0000-0003-4911-5290 FU NIAID NIH HHS [R01 AI024156-10] NR 10 TC 6 Z9 6 U1 0 U2 0 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0091-6749 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD JAN PY 2004 VL 113 IS 1 BP 169 EP 171 DI 10.1016/j.jaci.2003.10.012 PG 3 WC Allergy; Immunology SC Allergy; Immunology GA 760MP UT WOS:000187837900023 PM 14713924 ER PT J AU Nay, WT Thorpe, GL Roberson-Nay, R Hecker, JE Sigmon, ST AF Nay, WT Thorpe, GL Roberson-Nay, R Hecker, JE Sigmon, ST TI Attentional bias to threat and emotional response to biological challenge SO JOURNAL OF ANXIETY DISORDERS LA English DT Article; Proceedings Paper CT 35th Annual Convention of the Association-for-Advancement-of-Behavior-Therapy CY NOV, 2001 CL PHILADELPHIA, PA SP Assoc Advancement Behav Therapy DE selective attention; cognitive bias; anxiety; fear; gender differences; biological challenge ID DIOXIDE-ENRICHED AIR; ANXIETY SENSITIVITY; PANIC ATTACKS; FACIAL EXPRESSIONS; INFORMATION; DISORDER; HYPERVENTILATION; PATHOGENESIS; WORDS; PREDICTORS AB Attentional bias towards threat reliably correlates with clinical anxiety status as well as elevated trait anxiety. Although such findings have led many to posit a potential causative or predictive role of threat-biased attentional processes on anxiety problems, little informative research exists. The present investigation was designed to address the role of threat-biased attentional processes on emotional/fearful responding. Eighty-seven participants provided baseline measures of anxiety vulnerability (i.e., anxiety sensitivity; unmasked/masked emotional Stroop task indices) and then underwent biological challenge procedures (inhalations of 20% carbon dioxide (CO2)-enriched air). Following challenge, participants completed measures of emotional response. Regression analyses indicated that both unmasked and masked attentional bias indices significantly predicted emotional responding above and beyond anxiety sensitivity. Exploratory analyses also revealed a gender effect, with prediction of emotional response largely attributable to females. C1 Univ Maine, Orono, ME USA. Univ Maryland, College Pk, MD 20742 USA. RP Nay, WT (reprint author), NIMH, Mood & Anxiety Disorders Program, Bldg 1,Room 3B-20, Bethesda, MD 20892 USA. EM nayw@intra.nimh.nih.gov NR 44 TC 21 Z9 22 U1 3 U2 12 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0887-6185 J9 J ANXIETY DISORD JI J. Anxiety Disord. PY 2004 VL 18 IS 5 BP 609 EP 627 DI 10.1016/j.janxdits.2003.08.003 PG 19 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 847JO UT WOS:000223388700003 PM 15275942 ER PT J AU Saldanha, LG Betz, JM Coates, PM AF Saldanha, LG Betz, JM Coates, PM TI Development of the analytical methods and reference materials program for dietary supplements at the national institutes of health SO JOURNAL OF AOAC INTERNATIONAL LA English DT Article AB The need for validated analytical methods and reference materials to identify and measure constituents in dietary supplements is essential. Such methods allow for the documentation that products meet manufacturer's specifications and contain what their labels declare. In March 2003, the U.S. Food and Drug Administration issued a proposed rule that would establish specific current good manufacturing practices for dietary supplements. This proposed rule requires that companies create a quality control unit to set specifications and ensure compliance with these specifications using scientifically valid procedures. This report provides insights and lessons learned,from 3 meetings the Office of Dietary Supplements (ODS) at the National Institutes of Health helped organize. These meetings were structured to (1) educate individuals about the importance and need for validated analytical methods and reference materials to identify and quantify constituents of dietary supplements; (2) identify resources required to fulfill this need; and (3) serve as a platform to obtain input from interested parties to help frame the research agenda for the Dietary Supplements Methods and Reference Materials Program within ODS. Stakeholder's opinions and views expressed at these 3 meetings are outlined in this report. C1 NIH, Off Dietary Supplements, Bethesda, MD 20892 USA. RP Saldanha, LG (reprint author), NIH, Off Dietary Supplements, 6100 Execut Blvd,Rm 3B01,MSC 7517, Bethesda, MD 20892 USA. EM saldanhl@mail.nih.gov NR 8 TC 13 Z9 15 U1 0 U2 1 PU AOAC INTERNATIONAL PI GAITHERSBURG PA 481 NORTH FREDRICK AVE, STE 500, GAITHERSBURG, MD 20877-2504 USA SN 1060-3271 J9 J AOAC INT JI J. AOAC Int. PD JAN-FEB PY 2004 VL 87 IS 1 BP 162 EP 165 PG 4 WC Chemistry, Analytical; Food Science & Technology SC Chemistry; Food Science & Technology GA 805KA UT WOS:000220364000030 PM 15084100 ER PT J AU Liu, AY Schisterman, EF Teoh, E AF Liu, AY Schisterman, EF Teoh, E TI Sample size and power calculation in comparing diagnostic accuracy of biomarkers with pooled assessments SO JOURNAL OF APPLIED STATISTICS LA English DT Article DE area under the curve; diagnostic biomarkers; sensitivity; specificity; receiver operating characteristic curves ID CONFIDENCE-INTERVALS; ROC CURVE; MARKERS; AREA AB When testing of a biomarker is costly, pooling of samples becomes a useful and efficient alternative (Faraggi et al., 2003). In this paper, we develop procedures for sample size and power calculations for planning a study comparing the accuracy of biomarkers in diagnosis of diseases with pooled samples. Explicit formulas are derived for several important pooling strategies. The effects of pooling samples on sample size and power of the test are also discussed. C1 NICHHD, Div Epidemiol Stat & Prevent Res, Rockville, MD 20852 USA. Univ Alabama, Birmingham, AL USA. RP Schisterman, EF (reprint author), NICHHD, Div Epidemiol Stat & Prevent Res, 6100 Execut Blvd,Room 7B05, Rockville, MD 20852 USA. OI Liu, Aiyi/0000-0002-6618-5082; Schisterman, Enrique/0000-0003-3757-641X NR 13 TC 10 Z9 10 U1 0 U2 2 PU CARFAX PUBLISHING PI BASINGSTOKE PA RANKINE RD, BASINGSTOKE RG24 8PR, HANTS, ENGLAND SN 0266-4763 J9 J APPL STAT JI J. Appl. Stat. PD JAN PY 2004 VL 31 IS 1 BP 49 EP 59 DI 10.1080/0266476032000148948 PG 11 WC Statistics & Probability SC Mathematics GA 756YV UT WOS:000187514100004 ER PT J AU Butz, AM Huss, K Mudd, K Donithan, M Rand, C Bollinger, ME AF Butz, AM Huss, K Mudd, K Donithan, M Rand, C Bollinger, ME TI Asthma management practices at home in young inner-city children SO JOURNAL OF ASTHMA LA English DT Article DE pediatric asthma; nebulizer; parental asthma management practices; anti-inflammatory medication ID HEALTH-CARE UTILIZATION; SYMPTOM PERCEPTION; CHILDHOOD ASTHMA; MEDICATION-USE; PSYCHOLOGICAL-FACTORS; MORBIDITY; PARENTS; OBSTRUCTION; EDUCATION; MORTALITY AB Information on parental asthma management practices for young children is sparse. The objective of this article is to determine if specific caregiver asthma management practices for children were associated with children's asthma morbidity. Caregivers of 100 inner-city children diagnosed with persistent asthma and participating in an ongoing asthma intervention study were enrolled and interviewed to ascertain measures of asthma morbidity, medication use, health care use (acute and primary care), and asthma management practices. Overall, asthma morbidity was high with almost two thirds of caregivers. reporting their child having one or more emergency department visits within the last 6 months and 63% receiving specialty care for their asthma. Appropriate medication use was reported predominantly as albuterol and inhaled steroids (78%). However, only 42% of caregivers reported administering asthma medicines when their child starts to cough and less than half (39%) reported having an asthma action plan. There were no significant differences by asthma severity level for any asthma management practice. In conclusion, caregivers lack knowledge regarding cough as an early asthma symptom. Caregivers should be encouraged to review asthma action plans with health care providers at each medical encounter. C1 Johns Hopkins Univ, Sch Med, Dept Pediat, Baltimore, MD 21287 USA. Johns Hopkins Univ, Sch Med, Dept Pulm & Crit Care, Baltimore, MD 21287 USA. NINR, NIH, Bethesda, MD USA. Univ Maryland, Sch Med, Dept Pediat, Baltimore, MD 21201 USA. Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Baltimore, MD USA. RP Butz, AM (reprint author), Johns Hopkins Univ, Sch Med, Dept Pediat, 600 N Wolfe St Pk 386, Baltimore, MD 21287 USA. EM abutz@jhmi.edu FU NINR NIH HHS [R01NR05060] NR 33 TC 10 Z9 10 U1 0 U2 2 PU MARCEL DEKKER INC PI NEW YORK PA 270 MADISON AVE, NEW YORK, NY 10016 USA SN 0277-0903 J9 J ASTHMA JI J. Asthma PY 2004 VL 41 IS 4 BP 433 EP 444 DI 10.1081/JAS-120033985 PG 12 WC Allergy; Respiratory System SC Allergy; Respiratory System GA 839SR UT WOS:000222805700006 PM 15281329 ER PT J AU Ge, H Chuang, YYE Zhao, SP Tong, M Tsai, MH Temenak, JJ Richards, AL Ching, WM AF Ge, H Chuang, YYE Zhao, SP Tong, M Tsai, MH Temenak, JJ Richards, AL Ching, WM TI Comparative genomics of Rickettsia prowazekii Madrid E and Breinl strains SO JOURNAL OF BACTERIOLOGY LA English DT Article ID ESCHERICHIA-COLI; CELL-DIVISION; SACCHAROMYCES-CEREVISIAE; EPIDEMIC TYPHUS; CYTOCHROME-C; AGROBACTERIUM-TUMEFACIENS; TRANSCRIPTIONAL ANALYSIS; SEQUENCE-ANALYSIS; SPOTTED-FEVER; ATP SYNTHASE AB Rickeusia prowazekii, the causative agent of epidemic typhus, has been responsible for millions of human deaths. Madrid E is an attenuated strain of R. prowazekii, while Breinl is a virulent strain. The genomic DNA sequence of Madrid E has recently been published. To study the genomic variations between Madrid E (reference) and Breinl (test) DNAs, cohybridization experiments were performed on a DNA microarray containing all 834 protein-coding genes of Madrid E. Of the 834 genes assessed, 24 genes showed 1.5- to 2.0-fold increases in hybridization signals in Breinl DNA compared to Madrid E DNA, indicating the presence of genomic variations in similar to3% of the total genes. Eighteen of these 24 genes are predicted to be involved in different functions. Southern blot analysis of five genes, virB4,ftsK, rfbE, lpx,4, and rpoH, suggested the presence of an additional paralog(s) in BreinI, which might be related to the observed increase in hybridization signals. Studies by real-time reverse transcription-PCR revealed an increase in expression of the above-mentioned five genes and five other genes. In addition to the elevated hybridization signals of 24 genes observed in the Breinl strain, one gene (rp084) showed only 1/10 the hybridization signal of Madrid E. Further analysis of this gene by PCR and sequencing revealed a large deletion flanking the whole rp084 gene and part of the rp083 gene in the virulent Breinl strain. The results of this first rickettsial DNA microarray may provide some important information for the elucidation of pathogenic mechanisms of R. prowazekii. C1 USN, Med Res Ctr, Infect Dis Directorate, Rickettsial Dis Dept, Silver Spring, MD 20910 USA. Uniformed Serv Univ Hlth Sci, Dept Prevent Med & Biometr, Bethesda, MD 20814 USA. NCI, NIH, Radiat Oncol Sci Program, Microarray Lab, Gaithersburg, MD 20877 USA. Ctr Biol Evaluat & Res, Food & Drug Adm, Div Vaccines & Related Prod Applicat, Off Vaccines Res & Review, Rockville, MD 20852 USA. RP Ching, WM (reprint author), USN, Med Res Ctr, Infect Dis Directorate, Rickettsial Dis Dept, Silver Spring, MD 20910 USA. EM chingw@nmrc.navy.mil NR 52 TC 26 Z9 27 U1 0 U2 3 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0021-9193 J9 J BACTERIOL JI J. Bacteriol. PD JAN PY 2004 VL 186 IS 2 BP 556 EP 565 DI 10.1128/JB.186.2.556-565.2004 PG 10 WC Microbiology SC Microbiology GA 763GP UT WOS:000188066800032 PM 14702324 ER PT J AU Kusumegi, T Tanaka, J Kawano, M Yonemoto, J Tohyama, C Sone, H AF Kusumegi, T Tanaka, J Kawano, M Yonemoto, J Tohyama, C Sone, H TI BMP7/ActRIIB regulates estrogen-dependent apoptosis: New biomarkers for environmental estrogens SO JOURNAL OF BIOCHEMICAL AND MOLECULAR TOXICOLOGY LA English DT Article DE steroid hormone; gene regulation; estradiol; environmental estrogen ID BREAST-CANCER CELLS; RESPONSIVE GENE; RECEPTOR-ALPHA; SIGNAL-TRANSDUCTION; BISPHENOL-A; RAT UTERUS; ACTIVIN; EXPRESSION; TRANSCRIPTION; ACTIVATION AB A ligand-receptor pair, bone morphogenetic protein-7 (BMP7) and activin receptor IIB (alpha-tRIIB), was identified from a pool of DNA fragments recovered from MCF7 cells treated with 17beta-estradiol (E2) by chromatin immunoprecipitation with antiestrogen receptor-alpha antibody. The E2 responsiveness of both genes was confirmed in MCF cells and in the mouse uterus. Repeated treatment with E2 resulted in decreased expression of both actRIIB and BMP7 mRNA in the uteri of ovariectomized mice. A single oral administration of bisphenol A (BPA), an environmental estrogen, inhibited actRIIB and BMP7 expression and apoptosis in the luminal epithelium of the mouse uterus at diestrus (or early proestrus). This decrease, due to BPA administration, was restored by an estrogen receptor (ER) antagonist suggesting that it is mediated through ERs. These results suggest that E2 and BPA suppress estrogen-dependent apoptosis of epithelial cells of the endometrium through down-regulation of actRIIB and BMP7. Thus, we propose that BMP7 and actRIIB, a ligand-receptor pair, are involved in regulation of the apoptotic signaling pathway and might therefore be new biomarkers of the effects of environmental estrogens on the female reproductive tract. (C) 2004 Wiley Periodicals, Inc. C1 Natl Inst Environm Studies, Endocrine Disruptors & Dioxin Res Project, Tsukuba, Ibaraki 3058506, Japan. JST, CREST, Kawaguchi 3320012, Japan. RP Sone, H (reprint author), NIEHS, Lab Computat Biol & Risk Anal, POB 12233, Res Triangle Pk, NC 27709 USA. EM sone@niehs.nih.gov NR 34 TC 16 Z9 16 U1 0 U2 0 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1095-6670 J9 J BIOCHEM MOL TOXIC JI J. Biochem. Mol. Toxicol. PY 2004 VL 18 IS 1 BP 1 EP 11 DI 10.1002/jbt.20004 PG 11 WC Biochemistry & Molecular Biology; Toxicology SC Biochemistry & Molecular Biology; Toxicology GA 776ND UT WOS:000189121300001 PM 14994273 ER PT J AU Zheng, ZM AF Zheng, ZM TI Regulation of alternative RNA splicing by exon definition and exon sequences in viral and mammalian gene expression SO JOURNAL OF BIOMEDICAL SCIENCE LA English DT Review DE RNA; exons; introns; RNA splicing, alternative; gene expression; RNA processing; splicing enhancers; splicing suppressors ID PRE-MESSENGER-RNA; SPINAL MUSCULAR-ATROPHY; IMMUNODEFICIENCY-VIRUS TYPE-1; PURINE-RICH ENHANCERS; FIBRONECTIN EDA EXON; NONSENSE-MEDIATED DECAY; HNRNP A/B PROTEINS; C-TERMINAL DOMAIN; MOTOR-NEURON SMN; SR-PROTEINS AB Intron removal from a pre-mRNA by RNA splicing was once thought to be controlled mainly by intron splicing signals. However, viral and other eukaryotic RNA exon sequences have recently been found to regulate RNA splicing, polyadenylation, export, and nonsense-mediated RNA decay in addition to their coding function. Regulation of alternative RNA splicing by exon sequences is largely attributable to the presence of two major cis-acting elements in the regulated exons, the exonic splicing enhancer (ESE) and the suppressor or silencer (ESS). Two types of ESEs have been verified from more than 50 genes or exons: purine-rich ESEs, which are the more common, and non-purine-rich ESEs. In contrast, the sequences of ESSs identified in approximately 20 genes or exons are highly diverse and show little similarity to each other. Through interactions with cellular splicing factors, an ESE or ESS determines whether or not a regulated splice site, usually an upstream 3' splice site, will be used for RNA splicing. However, how these elements function precisely in selecting a regulated splice site is only partially understood. The balance between positive and negative regulation of splice site selection likely depends on the cis-element's identity and changes in cellular splicing factors under physiological or pathological conditions. Copyright (C) 2004 National Science Council, ROC and S. Karger AG, Basel. C1 NCI, HIV & AIDS Malignancy Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Zheng, ZM (reprint author), NCI, HIV & AIDS Malignancy Branch, Ctr Canc Res, NIH, 10 Ctr Dr,Rm 10 S255,MSC-1868, Bethesda, MD 20892 USA. EM zhengt@exchange.nih.gov FU Intramural NIH HHS [Z99 CA999999, Z01 SC010357-08] NR 184 TC 106 Z9 108 U1 0 U2 9 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1021-7770 J9 J BIOMED SCI JI J. Biomed. Sci. PY 2004 VL 11 IS 3 BP 278 EP 294 DI 10.1159/000077096 PG 17 WC Cell Biology; Medicine, Research & Experimental SC Cell Biology; Research & Experimental Medicine GA 809QC UT WOS:000220650200001 PM 15067211 ER PT J AU Chiu, LL Chou, SW Cho, YM Ho, HY Ivy, JL Hunt, D Wang, PS Kuo, CH AF Chiu, LL Chou, SW Cho, YM Ho, HY Ivy, JL Hunt, D Wang, PS Kuo, CH TI Effect of prolonged intermittent hypoxia and exercise training on glucose tolerance and muscle GLUT4 protein expression in rats SO JOURNAL OF BIOMEDICAL SCIENCE LA English DT Article DE body mass; diabetes; glycogen; insulin resistance; skeletal muscle ID SKELETAL-MUSCLE; INSULIN-RESISTANCE; CAPILLARY RECRUITMENT; ANGIOGENESIS; KINASE; ALTITUDE; RESPONSIVENESS; TRANSPORTERS; SENSITIVITY; MORTALITY AB We compared the chronic effect of intermittent hypoxia and endurance training on the glucose tolerance and GLUT4 protein expression in rat skeletal muscle. Thirty-two Sprague-Dawley rats were matched for weight and assigned to one of the following four groups: control, endurance training, hypoxia, or hypoxia followed by endurance training. Hypoxic treatment consisted of breathing 14% O-2 for 12 h/day under normobaric conditions, and the training protocol consisted of making animals swim 2 times for 3 h/day. At the end of the 3rd week, an oral glucose tolerance test (OGTT) was performed 16 h after treatments. At the end of the 4th week, GLUT4 protein, mRNA, and glycogen storage in skeletal muscle were determined. Endurance training significantly improved OGTT results. Glycogen content and GLUT4 protein expression in the plantaris and red gastrocnemius, but not in the soleus or white gastrocnemius muscles, were also elevated. Chronic intermittent hypoxia also improved OGTT results, but did not alter GLUT4 protein expression. Additionally, hypoxia followed by exercise training produced significant increases in GLUT4 protein and mRNA in a greater number of muscles compared to endurance training alone. Both exercise training and hypoxia significantly reduced body mass, and an additive effect of both treatments was found. In conclusion, chronic intermittent hypoxia improved glucose tolerance in the absence of increased GLUT4 protein expression. This treatment facilitated the exercise training effect on muscle GLUT4 expression and glycogen storage. These new findings open the possibility of utilizing intermittent hypoxia, with or without exercise training, for the prevention and clinical treatment of type 2 diabetes or insulin resistance. Copyright (C) 2004 National Science Council, ROC and S. Karger AG, Basel. C1 Taipei Phys Educ Coll, Lab Exercise Biochem, Taipei 105, Taiwan. Chang Gung Mem Hosp, Dept Phys Med & Rehabil, Taipei 10591, Taiwan. Natl Yang Ming Univ, Dept Physiol, Taipei 112, Taiwan. Univ Texas, Dept Kinesiol, Austin, TX 78712 USA. NIDDKD, NIH, Bethesda, MD 20892 USA. RP Kuo, CH (reprint author), Taipei Phys Educ Coll, Lab Exercise Biochem, No 5 Dun Hua N Rd, Taipei 105, Taiwan. EM kch@tpec.edu.tw NR 38 TC 30 Z9 35 U1 1 U2 5 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1021-7770 J9 J BIOMED SCI JI J. Biomed. Sci. PY 2004 VL 11 IS 6 BP 838 EP 846 DI 10.1159/000081831 PG 9 WC Cell Biology; Medicine, Research & Experimental SC Cell Biology; Research & Experimental Medicine GA 877DC UT WOS:000225547000016 PM 15591781 ER PT J AU King, RB AF King, RB TI Relative influences on recent changes in the first birth ratio in the United States SO JOURNAL OF BIOSOCIAL SCIENCE LA English DT Article ID BIRTH-ORDER; FERTILITY TRANSITION; ACHIEVEMENT; PRESIDENTS; IMPACT; DEBATE; TRENDS; REBEL AB Researchers in psychology have focused a great deal of attention on the potential greater predisposition to achievement among first-born children relative to their siblings. Focusing on the United States as an example, a time series of the first birth ratio is used to show how the changing prevalence of first births relative to higher order births has altered the composition of birth cohorts, and the ratio is decomposed into four factors. Results show that the ratio increased significantly in the 1960s and early 1970s, but changed only slightly in the following decades. While more recent birth cohorts are composed of larger proportions of first-born children, the majority of children are still born as siblings. Contrary to expectations, the primary source of change was the proportion childless rather than decreasing higher order birth rates. C1 US Dept HHS, NICHHD, Populat Res Ctr, Demog & Behav Sci Branch,NIH, Washington, DC 20201 USA. RP King, RB (reprint author), US Dept HHS, NICHHD, Populat Res Ctr, Demog & Behav Sci Branch,NIH, Washington, DC 20201 USA. FU NICHD NIH HHS [T32 HD07168-22] NR 68 TC 0 Z9 0 U1 0 U2 1 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 40 WEST 20TH ST, NEW YORK, NY 10011-4211 USA SN 0021-9320 J9 J BIOSOC SCI JI J. Biosoc. Sci. PD JAN PY 2004 VL 36 IS 1 BP 1 EP 17 DI 10.1017/S0021932004006029 PG 17 WC Demography; Public, Environmental & Occupational Health; Social Sciences, Biomedical SC Demography; Public, Environmental & Occupational Health; Biomedical Social Sciences GA 776ZG UT WOS:000189148800001 PM 14989528 ER PT J AU Swain, SM Vici, P AF Swain, SM Vici, P TI The current and future role of dexrazoxane as a cardioprotectant in anthracycline treatment: expert panel review SO JOURNAL OF CANCER RESEARCH AND CLINICAL ONCOLOGY LA English DT Review DE cancer; anthracycline; doxorubicin; cardiotoxicity; dexrazoxane ID ADVANCED BREAST-CANCER; DOXORUBICIN-CONTAINING THERAPY; CLINICAL-PRACTICE GUIDELINES; PHASE-I TRIAL; RADIOTHERAPY PROTECTANTS; INDUCED CARDIOTOXICITY; CARDIAC TOXICITY; AMERICAN-SOCIETY; AGENT ICRF-187; CHEMOTHERAPY AB This article summarizes the views of an expert meeting of cardiologists and oncologists on the use of dexrazoxane in anthracycline-based chemotherapy. Anthracycline-induced cardiotoxicity remains a major concern and new trends in treatment (e.g., combination of an anthracycline with other agents) will ensure that it remains a problem. Dexrazoxane reduces this cardiotoxicity in adults and children with a range of tumor types. Further research may help to identify those patients who are at particular risk of cardiotoxicity and who would benefit the most from dexrazoxane. There are also numerous possibilities for dexrazoxane in other clinical situations, which must be addressed in future trials. C1 NIH, US Dept HHS, Bethesda, MD 20889 USA. Regina Elena Inst Canc Res, Div Med Oncol 2, I-00161 Rome, Italy. RP Swain, SM (reprint author), NIH, US Dept HHS, 8901 Wisconsin Ave,Bldg 8,Room 5101, Bethesda, MD 20889 USA. OI Swain, Sandra/0000-0002-1320-3830 NR 45 TC 86 Z9 89 U1 0 U2 2 PU SPRINGER-VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0171-5216 J9 J CANCER RES CLIN JI J. Cancer Res. Clin. Oncol. PD JAN PY 2004 VL 130 IS 1 BP 1 EP 7 DI 10.1007/s00432-003-0498-7 PG 7 WC Oncology SC Oncology GA 752UT UT WOS:000187186100001 PM 14564513 ER PT J AU Carroll, S Lu, SJ Herrera, AH Horowits, R AF Carroll, S Lu, SJ Herrera, AH Horowits, R TI N-RAP scaffolds I-Z-I assembly during myofibrillogenesis in cultured chick cardiomyocytes SO JOURNAL OF CELL SCIENCE LA English DT Article DE myofibrillogenesis; cardiomyocytes; N-RAP; actin ID NEBULIN-RELATED PROTEIN; SKELETAL-MUSCLE; CARDIAC MYOFIBRILLOGENESIS; ACTIN-FILAMENTS; STRIATED-MUSCLE; ALPHA-ACTININ; INTERCALATED DISKS; CONNECTIN TITIN; LIM PROTEIN; FILAMIN AB N-RAP is a muscle-specific protein with an N-terminal LIM domain (LIM), C-terminal actin-binding super repeats homologous to nebulin (SR) and nebulin-related simple repeats (IB) in between the two. Based on biochemical data, immunofluorescence analysis of cultured embryonic chick cardiomyocytes and the targeting and phenotypic effects of these individual GFP-tagged regions of N-RAP, we proposed a novel model for the initiation of myofibril assembly in which N-RAP organizes alpha-actinin and actin into the premyofibril I-Z-I complexes. We tested the proposed model by expressing deletion mutants of N-RAP (i.e. constructs containing two of the three regions of N-RAP) in chick cardiomyocytes and observing the effects on alpha-actinin and actin organization into mature sarcomeres. Although individually expressing either the LIM, IB, or SR regions of N-RAP inhibited alpha-actinin assembly into Z-lines, expression of either the LIM-IB fusion or the IB-SR fusion permitted normal alpha-actinin organization. In contrast, the LIM-SR fusion (LIM-SR) inhibited alpha-actinin organization into Z-lines, indicating that the IB region is critical for Z-line assembly. While permitting normal Z-line assembly, LIM-IB and IB-SR decreased sarcomeric actin staining intensity; however, the effects of LIM-IB on actin assembly were significantly more severe, as estimated both by morphological assessment and by quantitative measurement of actin staining intensity. In addition, LIM-IB was consistently retained in mature Z-lines, while mature Z-lines without significant IB-SR incorporation were often observed. We conclude that the N-RAP super repeats are essential for organizing actin filaments during myofibril assembly in cultured embryonic chick cardiomyocytes, and that they also play an important role in removal of the N-RAP scaffold from the completed myofibrillar structure. This work strongly supports the N-RAP scaffolding model of premyofibril assembly. C1 NIAMSD, Muscle Biol Lab, Dept Hlth & Human Serv, NIH, Bethesda, MD 20892 USA. RP Horowits, R (reprint author), NIAMSD, Muscle Biol Lab, Dept Hlth & Human Serv, NIH, Bethesda, MD 20892 USA. EM horowits@helix.nih.gov NR 38 TC 20 Z9 20 U1 1 U2 5 PU COMPANY OF BIOLOGISTS LTD PI CAMBRIDGE PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE CB4 4DL, CAMBS, ENGLAND SN 0021-9533 J9 J CELL SCI JI J. Cell Sci. PD JAN 1 PY 2004 VL 117 IS 1 BP 105 EP 114 DI 10.1242/jcs.00847 PG 10 WC Cell Biology SC Cell Biology GA 774XC UT WOS:000189010800011 PM 14657273 ER PT J AU Normanno, N De Luca, A Bianco, C Maiello, MR Carriero, MV Rehman, A Wechselberger, C Arra, C Strizzi, L Sanicola, M Salomon, DS AF Normanno, N De Luca, A Bianco, C Maiello, MR Carriero, MV Rehman, A Wechselberger, C Arra, C Strizzi, L Sanicola, M Salomon, DS TI Cripto-1 overexpression leads to enhanced invasiveness and resistance to anoikis in human MCF-7 breast cancer cells SO JOURNAL OF CELLULAR PHYSIOLOGY LA English DT Article ID MAMMARY EPITHELIAL-CELLS; GROWTH-FACTOR-ALPHA; CERVICAL-CARCINOMA CELLS; EGF-RELATED PEPTIDES; INDUCED APOPTOSIS; TUMOR-GROWTH; EXPRESSION; AMPHIREGULIN; PROTEIN; FAMILY AB Cripto-1 (CR-1) is an epidermal growth factor (EGF)-CFC protein that has been shown to signal through nodal/Alk-4, PI3K/Akt, and/or ras/raf/MEK/MAPK pathways in mammalian cells, and that is frequently expressed in human primary breast carcinomas. In the present study, the human estrogen receptor positive, MCF-7 breast cancer cell line, that expresses low levels of endogenous CR-1, was transfected with a CR-1 expression vector. MCF-7 CR-1 cells expressed high levels of a 25 kDa recombinant CR-1 protein that was not detected in MCF-7 cells transfected with a control vector (MCF-7 neo). Overexpression of CR-1 did not induce an estrogen independent phenotype in MCF-7 cells. In fact, MCF-7 CR-1 cells showed a response to exogenous estrogens that was similar to MCF-7 neo cells, and failed to grow in immunosuppressed mice in absence of estrogen stimulation. However, MCF-7 CR-1 cells showed a rate of proliferation in serum free conditions, and an ability to form colonies in soft-agar that were higher as compared with MCF-7 neo cells. More importantly, overexpression of CR-1 enhanced the resistance to anoikis and the invasion ability of MCF-7 cells. MCF-7 CR-1 cells showed levels of activation of both Akt and Smad-2 that were significantly higher as compared with MCF-7 neo. These findings suggest that CR-1 overexpression might be associated with the progression towards a more aggressive phenotype in breast carcinoma, through the activation of both Akt and Smad-2 signalling pathways. (C) 2003 Wiley-Liss, Inc. C1 INT Fdn Pascale, Div Haematol Oncol, I-80131 Naples, Italy. INT Fdn Pascale, Dept Expt Oncol, I-80131 Naples, Italy. NCI, Mammary Biol & Tumorigenesis Lab, NIH, Bethesda, MD 20892 USA. INT Fdn Pascale, Expt Oncol, Naples, Italy. Upper Austrian Res GmbH Zentrum, Linz, Austria. INT Fdn Pascale, Anim Facil, Linz, Austria. Biogen Inc, Cambridge, MA 02142 USA. RP Normanno, N (reprint author), INT Fdn Pascale, Div Haematol Oncol, I-80131 Naples, Italy. RI De Luca, Antonella/J-8737-2016; OI De Luca, Antonella/0000-0001-5762-447X; Arra, Claudio/0000-0003-3162-2091; Normanno, Nicola/0000-0002-7158-2605 NR 40 TC 47 Z9 52 U1 0 U2 3 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0021-9541 J9 J CELL PHYSIOL JI J. Cell. Physiol. PD JAN PY 2004 VL 198 IS 1 BP 31 EP 39 DI 10.1002/jcp.10375 PG 9 WC Cell Biology; Physiology SC Cell Biology; Physiology GA 745WF UT WOS:000186713200004 PM 14584041 ER PT J AU Wang, YH Pampou, S Fujikawa, K Varticovski, L AF Wang, YH Pampou, S Fujikawa, K Varticovski, L TI Opposing effect of angiopoietin-1 on VEGF-mediated disruption of endothelial cell-cell interactions requires activation of PKC beta SO JOURNAL OF CELLULAR PHYSIOLOGY LA English DT Article ID PROTEIN-KINASE-C; GROWTH-FACTOR; VASCULAR-PERMEABILITY; IN-VITRO; MICROVASCULAR PERMEABILITY; INDUCED INCREASE; NITRIC-OXIDE; ANGIOGENESIS; CADHERIN; TIE2 AB Angiopoietin-1 (Ang1) and vascular endothelial growth factor (VEGF) cooperate in migration and survival of endothelial cells by activation of phosphatidylinositol-3 (PI-3) kinase and mitogen activating protein (MAP) kinase pathways. However, Ang1 opposes the effect of VEGF on vascular permeability. We found that Ang1 also blocks VEGF-mediated diffusion of fluoresin isothiocyanate (FITC)-labeled albumin across an endothelial cell monolayer. VEGF-mediated vascular permeability has been attributed, in part, to activation of phospholipase A(2) and subsequent formation of platelet activating factor. However, Ang1 had no effect on VEGF-induced activation of phospholipase A(2) or the release of arachidonic acid. VEGF-mediated permeability was associated with disruption of endothelial cell junctional complexes, dissociation of beta-catenin from VE-cadherin, and accumulation of beta-catenin in the cytosol. In contrast, Ang1 enhanced the interaction of beta-catenin with VE-cadherin and impaired VEGF-mediated dissociation of this complex. Ang1 also blocked VEGF-induced translocation of protein kinase C (PKC) and beta(2) to the membrane, but had no effect on activation of PKCa. In addition, staurosporine and a PKCbeta inhibitor, LY3791 96, blocked VEGF-mediated dissociation of beta-catenin from VE-cadherin, diffusion of albumin across the endothelial cell monolayer, and translocation of PKCbeta isoforms. These data indicate that VEGF-mediated disruption of endothelial cell-cell interactions requires activation of PKCbeta isoforms and that this pathway is blocked by Ang1. (C) 2003 Wiley-Liss, Inc. C1 Beth Israel Deaconess Med Ctr, BIDMC Genom Ctr, Boston, MA 02215 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Columbia Univ, Coll Phys & Surg, Dept Med, New York, NY USA. Sapporo Med Univ, Dept Sci 4, Sapporo, Hokkaido, Japan. NCI, Off Director Lab Human Cancinogenesis, Ctr Canc Res, Bethesda, MD 20892 USA. RP Wang, YH (reprint author), Harvard Univ, Inst Med, BIDMC Genom Ctr, Room 208,4 Blackfan Circle, Boston, MA 02115 USA. FU NCI NIH HHS [CA53094] NR 52 TC 35 Z9 36 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 0021-9541 J9 J CELL PHYSIOL JI J. Cell. Physiol. PD JAN PY 2004 VL 198 IS 1 BP 53 EP 61 DI 10.1002/jcp.10386 PG 9 WC Cell Biology; Physiology SC Cell Biology; Physiology GA 745WF UT WOS:000186713200007 PM 14584044 ER PT J AU Pike, BR Flint, J Dave, JR Lu, XCM Wang, KKK Tortella, FC Hayes, RL AF Pike, BR Flint, J Dave, JR Lu, XCM Wang, KKK Tortella, FC Hayes, RL TI Accumulation of calpain and caspase-3 proteolytic fragments of brain-derived alpha II-spectrin in cerebral spinal fluid after middle cerebral artery occlusion in rats SO JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM LA English DT Article DE calpain; caspase-3; ischemia; stroke; biomarker; fodrin ID NEURON-SPECIFIC ENOLASE; ACUTE ISCHEMIC-STROKE; CENTRAL-NERVOUS-SYSTEM; CURRENT TRIAL DESIGNS; MILD HEAD-INJURY; CEREBROSPINAL-FLUID; CARDIAC-ARREST; SEPTOHIPPOCAMPAL CULTURES; DNA FRAGMENTATION; PROGNOSTIC MARKER AB Preclinical studies have identified numerous neuroprotective drugs that attenuate brain damage and improve functional outcome after cerebral ischemia. Despite this success in animal models, neuroprotective therapies in the clinical setting have been unsuccessful. Identification of biochemical markers common to preclinical and clinical cerebral ischemia will provide a more sensitive and objective measure of injury severity and outcome to facilitate clinical management and treatment. However, there are currently no effective biomarkers available for assessment of stroke. Nonerythroid (AI-spectrin is a cytoskeletal protein that is cleaved by calpain and caspase-3 proteases to signature alphaII-spectrin breakdown products (alphaII-SBDPs) after cerebral ischemia in rodents. This investigation examined accumulation of calpain- and caspase-3-cleaved alphaII-SBDPs in cerebrospinal fluid (CSF) of rodents subjected to 2 hours of transient focal cerebral ischemia produced by middle cerebral artery occlusion (MCAO) followed by reperfusion. After MCAO injury, full-length all-spectrin protein was decreased in brain tissue and increased in CSF from 24 to 72 hours after injury. Whereas alphaII-SBDPs were undetectable in sham-injured control animals, calpain but not caspase-3 specific alphaII-SBDPs were significantly increased in CSF after injury. However, caspase-3 alphaII-SBDPS were observed in CSF of some injured animals. These results indicate that alphaII-SBDP's detected in CSF after injury, particularly those mediated by calpain, may be useful diagnostic indicators of cerebral infarction that can provide important information about specific neurochemical events that have occurred in the brain after acute stroke. C1 Univ Florida, Dept Neurosci, Gainesville, FL 32610 USA. Univ Florida, Dept Psychiat, Ctr Traumat Brain Injury Studies, EL & WL McKnight Brain Inst, Gainesville, FL 32610 USA. Walter Reed Army Inst Res, Dept Neuropharmacol & Mol Biol, Div Neurosci, Silver Spring, MD USA. RP Pike, BR (reprint author), Natl Inst Gen Med Sci, Off Sci Review, Bldg 45,Room 3An 18,45 Ctr Dr,MSC 6200, Bethesda, MD 20892 USA. OI Wang, Kevin/0000-0002-9343-6473 FU NINDS NIH HHS [R01 NS39091, R01 NS40182] NR 57 TC 67 Z9 72 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0271-678X J9 J CEREBR BLOOD F MET JI J. Cereb. Blood Flow Metab. PD JAN PY 2004 VL 24 IS 1 BP 98 EP 106 DI 10.1097/01.WCB.0000098520.11962.37 PG 9 WC Endocrinology & Metabolism; Hematology; Neurosciences SC Endocrinology & Metabolism; Hematology; Neurosciences & Neurology GA 757TL UT WOS:000187577500011 PM 14688621 ER PT J AU Sagui, C Pedersen, LG Darden, TA AF Sagui, C Pedersen, LG Darden, TA TI Towards an accurate representation of electrostatics in classical force fields: Efficient implementation of multipolar interactions in biomolecular simulations SO JOURNAL OF CHEMICAL PHYSICS LA English DT Article ID PARTICLE-MESH EWALD; INTERMOLECULAR INTERACTION ENERGIES; PARTITIONED ELECTRIC PROPERTIES; MOLECULAR-DYNAMICS SIMULATIONS; CHARGE-DISTRIBUTION; POTENTIALS; MECHANICS; EXPANSIONS; SYSTEMS; MODEL AB The accurate simulation of biologically active macromolecules faces serious limitations that originate in the treatment of electrostatics in the empirical force fields. The current use of "partial charges" is a significant source of errors, since these vary widely with different conformations. By contrast, the molecular electrostatic potential (MEP) obtained through the use of a distributed multipole moment description, has been shown to converge to the quantum MEP outside the van der Waals surface, when higher order multipoles are used. However, in spite of the considerable improvement to the representation of the electronic cloud, higher order multipoles are not part of current classical biomolecular force fields due to the excessive computational cost. In this paper we present an efficient formalism for the treatment of higher order multipoles in Cartesian tensor formalism. The Ewald "direct sum" is evaluated through a McMurchie-Davidson formalism [L. McMurchie and E. Davidson, J. Comput. Phys. 26, 218 (1978)]. The "reciprocal sum" has been implemented in three different ways: using an Ewald scheme, a particle mesh Ewald (PME) method, and a multigrid-based approach. We find that even though the use of the McMurchie-Davidson formalism considerably reduces the cost of the calculation with respect to the standard matrix implementation of multipole interactions, the calculation in direct space remains expensive. When most of the calculation is moved to reciprocal space via the PME method, the cost of a calculation where all multipolar interactions (up to hexadecapole-hexadecapole) are included is only about 8.5 times more expensive than a regular AMBER 7 [D. A. Pearlman , Comput. Phys. Commun. 91, 1 (1995)] implementation with only charge-charge interactions. The multigrid implementation is slower but shows very promising results for parallelization. It provides a natural way to interface with continuous, Gaussian-based electrostatics in the future. It is hoped that this new formalism will facilitate the systematic implementation of higher order multipoles in classical biomolecular force fields. (C) 2004 American Institute of Physics. C1 N Carolina State Univ, Dept Phys, Raleigh, NC 27695 USA. NIEHS, Struct Biol Lab, Res Triangle Pk, NC 27709 USA. RP Sagui, C (reprint author), N Carolina State Univ, Dept Phys, Raleigh, NC 27695 USA. RI Pedersen, Lee/E-3405-2013 OI Pedersen, Lee/0000-0003-1262-9861 NR 50 TC 129 Z9 129 U1 0 U2 16 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 JAN 1 PY 2004 VL 120 IS 1 BP 73 EP 87 DI 10.1063/1.1630791 PG 15 WC Chemistry, Physical; Physics, Atomic, Molecular & Chemical SC Chemistry; Physics GA 757TK UT WOS:000187577400012 PM 15267263 ER PT J AU Maret, A Bourdeau, I Ding, CL Kadkol, SS Westra, WH Levine, MA AF Maret, A Bourdeau, I Ding, CL Kadkol, SS Westra, WH Levine, MA TI Expression of GCMB by intrathymic parathyroid hormone-secreting adenomas indicates their parathyroid cell origin SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID ECTOPIC PRODUCTION; DIGEORGE-SYNDROME; THYMUS; GENE; HYPOPARATHYROIDISM; TRANSPLANTATION; HYPERCALCEMIA; CARCINOMA; GLANDS; MICE AB GCMA and GCMB are related transcription factors that are critically important for embryological development of the placenta and parathyroid glands, respectively. Mice in which parathyroid glands have been surgically removed or fail to develop due to genetic loss of GCMB show continued production of PTH from a subset of thymic cells that express GCMA. In this study we examined whether human thymus produces PTH and/or GCMA and whether intrathymic PTH-secreting adenomas express GCMA or GCMB to determine the embryological origin of the secretory cells. By contrast to mouse thymus, analysis of 22 samples of human thymus tissue by RT-PCR and/or immunohistochemistry failed to demonstrate the expression of either PTH or GCMA. RT-PCR analysis of 16 intrathymic adenomas from patients with surgically cured primary hyperparathyroidism showed that these tumors expressed PTH and GCMB and not GCMA. We conclude that the normal human thymus does not express GCMA or PTH, and therefore, in contrast to the mouse, the human thymus is not a source of PTH production. Finally, intrathymic PTH-secreting adenomas express the parathyroid-specific GCMB gene, which suggests that these tumors were derived from parathyroid cells that migrated errantly during embryogenesis. C1 Johns Hopkins Univ, Sch Med, Dept Pediat, Div Pediat Endocrinol, Baltimore, MD 21287 USA. Johns Hopkins Univ, Sch Med, Illysa Ctr Mol & Cellular Endocrinol, Baltimore, MD 21287 USA. Johns Hopkins Univ, Sch Med, Dept Pathol, Baltimore, MD 21287 USA. NIH, Unit Genet & Endocrinol, Dev Endocrinol Branch, Bethesda, MD 20892 USA. Cleveland Clin, Childrens Hosp, Div Pediat, Cleveland, OH 44195 USA. RP Levine, MA (reprint author), Cleveland Clin, Childrens Hosp, Div Pediat, 9500 Euclid Ave,Mailstop A120, Cleveland, OH 44195 USA. EM levinem@ccf.org RI Levesque, Isabelle/A-1899-2012; OI Levine, Michael/0000-0003-0036-7809 NR 24 TC 18 Z9 19 U1 0 U2 0 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD JAN PY 2004 VL 89 IS 1 BP 8 EP 12 DI 10.1210/jc.2003-030733 PG 5 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 761ZU UT WOS:000187946000003 PM 14715818 ER PT J AU Simonds, WF Robbins, CM Agarwal, SK Hendy, GN Carpten, JD Marx, SJ AF Simonds, WF Robbins, CM Agarwal, SK Hendy, GN Carpten, JD Marx, SJ TI Familial isolated hyperparathyroidism is rarely caused by germline mutation in HRPT2, the gene for the hyperparathyroidism-jaw tumor syndrome SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID MULTIPLE ENDOCRINE NEOPLASIA; BENIGN HYPOCALCIURIC HYPERCALCEMIA; TYPE-1 MEN1 GENE; HEREDITARY HYPERPARATHYROIDISM; PARATHYROID CARCINOMA; CALCIUM RECEPTOR; JAPANESE; KINDREDS; LOCUS; FEATURES AB Familial isolated hyperparathyroidism (FIHP) can result occasionally from the incomplete expression of a syndromic form of familial hyperparathyroidism (HPT), specifically multiple endocrine neoplasia type 1 (MEN1), familial hypocalciuric hypercalcemia, or the hyperparathyroidism-jaw tumor syndrome (HPT-JT). The cause of FIHP has not been identified in the majority of families. We investigated 32 families with FIHP to determine the frequency of occult mutation in HRPT2, the gene causing HPT-JT. All families had negative clinical testing for MEN1, hypocalciuric hypercalcemia, and HPT-JT and negative mutational screening of MEN1 and CASR, the gene for the calcium-sensing receptor. Thus, an extended effort was made to exclude each of the principal syndromic causes of FIHP. The families were characterized by young probands ( 42 +/- 3 yr) and occasionally unusual parathyroid histology, including four families with one case of parathyroid cancer. We had speculated that there was a high frequency of occult mutation in HRPT2 among such carefully screened kindreds. This hypothesis became testable with the recent identification of that gene. Among the 32 FIHP families, only a single one was found to have a mutation in HRPT2 (679 in sAG); this mutation predicts premature truncation of its gene product, parafibromin, and thus its presumed inactivation. Even accounting for families with one of the three occult syndromes and false negative biochemical or DNA testing, these results indicate that an unexpectedly large fraction of FIHP has currently unrecognized causes. C1 NIDDKD, Metab Dis Branch, NIH, Bethesda, MD 20892 USA. NHGRI, Canc Genet Branch, NIH, Bethesda, MD 20892 USA. McGill Univ, Dept Med, Montreal, PQ H3A 1A1, Canada. McGill Univ, Dept Physiol, Montreal, PQ H3A 1A1, Canada. McGill Univ, Dept Human Genet, Montreal, PQ H3A 1A1, Canada. Royal Victoria Hosp, Calcium Res Lab, Montreal, PQ H3A 1A1, Canada. RP Simonds, WF (reprint author), Bldg 10,Room 8C-101,10 Ctr Dr,MSC 1752, Bethesda, MD 20892 USA. EM wfs@helix.nih.gov RI Agarwal, Sunita/D-1428-2016 OI Agarwal, Sunita/0000-0002-7557-3191 NR 69 TC 82 Z9 82 U1 0 U2 0 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD JAN PY 2004 VL 89 IS 1 BP 96 EP 102 DI 10.1210/jc.2003-030675 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 761ZU UT WOS:000187946000019 PM 14715834 ER PT J AU Weise, M Flor, A Barnes, KM Cutler, GB Baron, J AF Weise, M Flor, A Barnes, KM Cutler, GB Baron, J TI Determinants of growth during gonadotropin-releasing hormone analog therapy for precocious puberty SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID BINDING PROTEIN-3 LEVELS; I IGF-I; SECRETORY DYNAMICS; SOMATOMEDIN-C; CYPROTERONE-ACETATE; SKELETAL MATURATION; HEIGHT VELOCITY; CHILDREN; AGONIST; GIRLS AB In children with precocious puberty (PP), treatment with GnRH analogs (GnRHa) often decreases height velocity below normal. Based on previous animal studies, we hypothesized that this impaired growth is due to excessive advancement in growth plate senescence induced by the prior estrogen exposure. This hypothesis predicts that the height velocity during treatment will be inversely related to the severity of prior estrogen exposure. We analyzed data from 100 girls (age, 5.8 +/- 2.1 yr; mean +/- SD) with central PP who were treated with GnRHa. During GnRHa therapy, height velocity was low for age (-1.6 +/- 1.7 SD score; mean +/- SD). The absolute height velocity correlated most strongly with the bone age (BA), which we used as a surrogate marker for growth plate senescence (r = -0.727, P < 0.001). The severity of the growth abnormality (height velocity SD score for age) correlated inversely with markers of the severity of prior estrogen exposure, including duration of PP (r = -0.375, P < 0.001), Tanner breast stage (r = -0.220, P < 0.05), and BA advancement (r = -0.283, P < 0.01). Stepwise regression confirmed that BA was the best independent predictor of growth during GnRHa therapy. dThe findings are consistent with our hypothesis that impaired growth during GnRHa therapy is due, at least in part, to premature growth plate senescence induced by the prior estrogen exposure. C1 NICHHD, Dev Endocrinol Branch, NIH, Bethesda, MD 20892 USA. Eli Lilly & Co, Lilly Res Labs, Indianapolis, IN 46285 USA. RP Baron, J (reprint author), NICHHD, Dev Endocrinol Branch, NIH, Bldg 10,Room 10N262,10 Ctr Dr MSC 1862, Bethesda, MD 20892 USA. EM jbaron@mail.nih.gov NR 38 TC 26 Z9 35 U1 0 U2 0 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD JAN PY 2004 VL 89 IS 1 BP 103 EP 107 DI 10.1210/jc.2002-021999 PG 5 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 761ZU UT WOS:000187946000020 PM 14715835 ER PT J AU Flor-Cisneros, A Leschek, EW Merke, DP Barnes, KM Coco, M Cutler, GB Baron, J AF Flor-Cisneros, A Leschek, EW Merke, DP Barnes, KM Coco, M Cutler, GB Baron, J TI In boys with abnormal developmental tempo, maturation of the skeleton and the hypothalamic-pituitary-gonadal axis remains synchronous SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID CONGENITAL ADRENAL-HYPERPLASIA; PRECOCIOUS PUBERTY; LONGITUDINAL ASSESSMENT; NEUROENDOCRINE CONTROL; PHYSICAL ALTERATIONS; SEXUAL DEVELOPMENT; GROWTH VELOCITY; RHESUS-MONKEY; BONE-AGE; LEPTIN AB The primary mechanism that initiates puberty is unknown. One possible clue is that pubertal maturation often parallels skeletal maturation. Conditions that delay skeletal maturation also tend to delay the onset of puberty, whereas conditions that accelerate skeletal maturation tend to hasten the onset of puberty. To examine this relationship, we studied boys with congenital adrenal hyperplasia (n = 13) and familial male-limited precocious puberty ( n = 22), two conditions that accelerate maturational tempo, and boys with idiopathic short stature ( n = 18) in which maturational tempo is sometimes delayed. In all three conditions, the onset of central puberty generally occurred at an abnormal chronological age but a normal bone age. Boys with the greatest skeletal advancement began central puberty at the earliest age, whereas boys with the greatest skeletal delay began puberty at the latest age. Furthermore, the magnitude of the skeletal advancement or delay matched the magnitude of the pubertal advancement or delay. This synchrony between skeletal maturation and hypothalamic-pituitary-gonadal axis maturation was observed among patients within each condition and also between conditions. In contrast, the maturation of the hypothalamic-pituitary-gonadal axis did not remain synchronous with other maturational processes including weight, height, or body mass index. We conclude that in boys with abnormal developmental tempo, maturation of the skeleton and the hypothalamic-pituitary-gonadal axis remains synchronous. This synchrony is consistent with the hypothesis that in boys, skeletal maturation influences hypothalamic-pituitary-gonadal axis maturation. C1 NICHHD, Dev Endocrinol Branch, NIH, Bethesda, MD 20892 USA. NICHHD, Warren Grant Magnuson Clin Ctr, NIH, Bethesda, MD 20892 USA. NICHHD, Pediat Reprod Endocrinol Branch, NIH, Bethesda, MD 20892 USA. Eli Lilly & Co, Indianapolis, IN 46285 USA. RP Flor-Cisneros, A (reprint author), Bldg 10 RM 10N262,10 Ctr Dr MSC 1862, Bethesda, MD 20892 USA. EM flora@mail.nih.gov NR 35 TC 11 Z9 12 U1 0 U2 0 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD JAN PY 2004 VL 89 IS 1 BP 236 EP 241 DI 10.1210/jc.2002-021954 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 761ZU UT WOS:000187946000041 PM 14715856 ER PT J AU Wong, ML Licinio, J Yildiz, BO Mantzoros, CS Prolo, P Kling, M Gold, PW AF Wong, ML Licinio, J Yildiz, BO Mantzoros, CS Prolo, P Kling, M Gold, PW TI Simultaneous and continuous 24-hour plasma and cerebrospinal fluid leptin measurements: Dissociation of concentrations in central and peripheral compartments SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID BLOOD-BRAIN-BARRIER; ELECTROCHEMICAL DETECTION; STATISTICAL PERSPECTIVES; PARTIAL SATURATION; DIURNAL-VARIATION; GENE-EXPRESSION; TIME-SERIES; PITUITARY; HUMANS; RESISTANCE AB The entrance of leptin into the central nervous system is of physiological relevance to the regulation of food intake, energy balance, and neuroendocrine function. To our knowledge, the relation between plasma and lumbar cerebrospinal fluid (CSF) leptin has not been examined across the 24-h period. To evaluate the relation between plasma and CSF leptin across the 24-h period, we studied simultaneous and continuous plasma and CSF leptin in nine subjects. We measured plasma and lumbar CSF leptin every 30 min for 24 h. All subjects had diurnal periodicity in 24-h plasma leptin levels, but not in CSF levels, as assessed by analysis of covariance and cosinor analysis. Plasma leptin had a significant 24-h pattern ( P = 0.001), but CSF leptin did not. A 25-fold range of plasma leptin concentrations was reflected by a less-than-2-fold range in lumbar CSF leptin concentrations. Nocturnal increases in plasma leptin concentrations were not accompanied by commensurate changes in CSF values. It appears that leptin enters the brain by a mechanism that is highly saturable at physiological leptin concentrations and that the dynamics of plasma leptin is not accompanied by similar dynamics in CSF leptin measured at the lumbar spinal level. Therefore, it is not possible to use plasma leptin levels to predict lumbar CSF leptin concentrations. Although we acknowledge that lumbar CSF concentrations do not fully reflect the dynamics of leptin in the brain, we suggest that the nocturnal saturability of leptin transport into the central nervous system might help explain the lack of responsiveness to the central physiologic effects of leptin in states of hyperleptinemia, such as obesity. C1 Univ Calif Los Angeles, David Geffen Sch Med, Ctr Pharmacogenom, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, David Geffen Sch Med, Gonda Ctr Res Genet & Neurosci 3357A, Interdepartmental Clin Pharmacol Ctr, Los Angeles, CA 90095 USA. Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Dept Med,Div Endocrinol, Boston, MA 02215 USA. NIMH, Clin Neuroendocrinol Branch, NIH, Bethesda, MD 20892 USA. Univ Maryland, Sch Med, Baltimore, MD 21201 USA. Baltimore Vet Affairs Med Ctr, Dept Psychiat, Baltimore, MD 21201 USA. RP Licinio, J (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, Ctr Pharmacogenom, 695 Charles Young Dr S, Los Angeles, CA 90095 USA. EM licinio@ucla.edu RI Wong, Ma-Li/D-7903-2011; OI Licinio, Julio/0000-0001-6905-5884 FU NCRR NIH HHS [RR000865, RR017365, RR017611, RR16996]; NHGRI NIH HHS [HG002500]; NHLBI NIH HHS [HL04526]; NIDDK NIH HHS [DK063240, DK58785, DK58851]; NIGMS NIH HHS [GM61394]; NIMH NIH HHS [MH062777] NR 26 TC 22 Z9 23 U1 0 U2 2 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD JAN PY 2004 VL 89 IS 1 BP 258 EP 265 DI 10.1210/jc.2003-031275 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 761ZU UT WOS:000187946000044 PM 14715859 ER PT J AU Gladwin, MT AF Gladwin, MT TI Haldane, hot dogs, halitosis, and hypoxic vasodilation: the emerging biology of the nitrite anion SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Editorial Material ID GASTRIC-CANCER; NITRATE REDUCTION; DIETARY NITRATE; OXIDE; STOMACH; HUMANS; DEOXYHEMOGLOBIN; CIRCULATION; MECHANISM; KINETICS AB While it has long been known that the reduction of nitrite to nitric oxide (NO) forms iron-nitrosyl-myoglobin and is the basis of meat curing, a greater biological activity of the nitrite anion has only recently been appreciated. In the stomach, NO is formed from acidic reduction of nitrite and increases mucous barrier thickness and gastric blood flow (see the related study beginning on page 106). Nitrite levels in blood reflect NO production from endothelial NO synthase enzymes, and recent data suggest that nitrite contributes to blood flow regulation by reaction with deoxygenated hemoglobin and tissue heme proteins to form NO. C1 NIDDKD, Dept Crit Care Med, Warren G Magnuson Clin Ctr, NIH, Bethesda, MD 20892 USA. NIDDKD, Biol Chem Lab, NIH, Bethesda, MD 20892 USA. RP Gladwin, MT (reprint author), NIDDKD, Dept Crit Care Med, Warren G Magnuson Clin Ctr, NIH, Bldg 10,Room 7D-43,10 Ctr Dr, Bethesda, MD 20892 USA. EM mgladwin@nih.gov NR 26 TC 46 Z9 47 U1 1 U2 3 PU AMER SOC CLINICAL INVESTIGATION INC PI ANN ARBOR PA 35 RESEARCH DR, STE 300, ANN ARBOR, MI 48103 USA SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD JAN PY 2004 VL 113 IS 1 BP 19 EP 21 DI 10.1172/JCI200420664 PG 3 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 761XA UT WOS:000187939700004 PM 14702102 ER PT J AU Yakar, S Setser, J Zhao, H Stannard, B Haluzik, M Glatt, V Bouxsein, ML Kopchick, JJ LeRoith, D AF Yakar, S Setser, J Zhao, H Stannard, B Haluzik, M Glatt, V Bouxsein, ML Kopchick, JJ LeRoith, D TI Inhibition of growth hormone action improves insulin sensitivity in liver IGF-1-deficient mice SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID PROLIFERATOR-ACTIVATED RECEPTOR; PROMOTED TYROSYL PHOSPHORYLATION; PANCREATIC BETA-CELLS; ADIPOSE-TISSUE; PEROXISOME PROLIFERATOR; PPAR-ALPHA; FACTOR-I; INDEPENDENT MECHANISMS; CARBOHYDRATE-TOLERANCE; SIGNAL-TRANSDUCTION AB Liver IGF-1-deficient (LID) mice have a 75% reduction in circulating IGF-1 levels and, as a result, a fourfold increase in growth hormone (GH) secretion. To block GH action, LID mice were crossed with GH antagonist (GHa) transgenic mice. Inactivation of GH action in the resulting LID + GHa mice led to decreased blood glucose and insulin levels and improved peripheral insulin sensitivity. Hyperinsulinemic-euglycemic clamp studies showed that LID mice exhibit severe insulin resistance. In contrast, expression of the GH antagonist transgene in LID + GHa mice led to enhanced insulin sensitivity and increased insulin-stimulated glucose uptake in muscle and white adipose tissue. Interestingly, LID + GHa mice exhibit a twofold increase in white adipose tissue mass, as well as increased levels of serum-free fatty acids and triglycerides, but no increase in the triglyceride content of liver and muscle. In conclusion, these results show that despite low levels of circulating IGF-1, insulin sensitivity in LID mice could be improved by inactivating GH action, suggesting that chronic elevation of GH levels plays a major role in insulin resistance. These results suggest that IGF-1 plays a role in maintaining a fine balance between GH and insulin to promote normal carbohydrate and lipid metabolism. C1 NIDDKD, Diabet Branch, NIH, Bethesda, MD 20892 USA. Beth Israel Deaconess Med Ctr, Dept Surg, Boston, MA 02215 USA. Harvard Univ, Sch Med, Boston, MA USA. Ohio Univ, Coll Osteopath Med, Edison Biotechnol Inst, Athens, OH 45701 USA. RP LeRoith, D (reprint author), NIDDKD, Diabet Branch, NIH, Room 8D12,Bldg 10, Bethesda, MD 20892 USA. EM derek@helix.nih.gov NR 69 TC 149 Z9 156 U1 1 U2 2 PU AMER SOC CLINICAL INVESTIGATION INC PI ANN ARBOR PA 35 RESEARCH DR, STE 300, ANN ARBOR, MI 48103 USA SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD JAN PY 2004 VL 113 IS 1 BP 96 EP 105 DI 10.1172/JCI200417763 PG 10 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 761XA UT WOS:000187939700015 PM 14702113 ER PT J AU Xu, M Chan, Y Fischer, SH Remaley, AT AF Xu, M Chan, Y Fischer, SH Remaley, AT TI Automated procedure for improving the RNA isolation step in viral load testing for human immunodeficiency virus SO JOURNAL OF CLINICAL MICROBIOLOGY LA English DT Article ID TYPE-1 AB An automated RNA isolation procedure on the Qiagen BioRobot is described for performing viral load tests for human immunodeficiency virus (HIV) with the Amplicor HIV type 1 test. The new procedure improves the precision of the assay and requires significantly less labor than the presently used manual RNA isolation procedure. C1 NIH, Dept Lab Med, Warren Grant Magnuson Clin Ctr, Bethesda, MD 20892 USA. RP Remaley, AT (reprint author), NIH, Dept Lab Med, Warren Grant Magnuson Clin Ctr, Bldg 10,Rm 2C-433,10 Ctr Dr, Bethesda, MD 20892 USA. EM aremaley@nih.gov NR 4 TC 1 Z9 1 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0095-1137 J9 J CLIN MICROBIOL JI J. Clin. Microbiol. PD JAN PY 2004 VL 42 IS 1 BP 439 EP 440 DI 10.1128/JCM.42.1.439-440.2004 PG 2 WC Microbiology SC Microbiology GA 763VU UT WOS:000188121800078 PM 14715800 ER PT J AU Hadley, DW Jenkins, JF Dimond, E de Carvalho, M Kirsch, I Palmer, CGS AF Hadley, DW Jenkins, JF Dimond, E de Carvalho, M Kirsch, I Palmer, CGS TI Colon cancer screening practices after genetic counseling and testing for hereditary nonpolyposis colorectal cancer SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID PSYCHOLOGICAL DISTRESS; MUTATION CARRIERS; BREAST-CANCER; FAMILIES; HNPCC; RISK; SURGERY; IMPACT; WOMEN AB Purpose Hereditary nonpolyposis colorectal cancer (HNPCC) is the most common hereditary form of colon cancer. Cancer screening recommendations differ between individuals identified to carry an HNPCC mutation and those who do not carry a known family mutation. We assessed the impact of genetic counseling and testing (GCT) on the use of endoscopic screening procedures and adherence to recommended endoscopic screening guidelines in 56 asymptomatic at-risk individuals from families known to carry an HNPCC mutation. Patients and Methods We analyzed data on colonoscopy and flexible sigmoidoscopy screenings collected before GCT and 6 months and 12 months post-GCT on 17 mutation-positive and 39 true mutation-negative individuals. Main outcome measures were use of endoscopic screening and adherence to recommended guidelines for the relevant mutation status. Mutation status, age, sex, employment, and income were analyzed as predictor variables. Results Among mutation-negative individuals, use of colonoscopy and flexible sigmoidoscopy decreased significantly between pre- and post-GCT (P <.00001 and P <.0003, respectively). Among mutation-positive individuals, a nonsignificant increase (P =.24) in use was noted. Age was also associated with use of endoscopic screening after GCT (P =.03). Mutation status (odds ratio [OR], 7.5; P =.02) and employment (OR, 8.6; P =.025) were associated with nonadherence to endoscopic screening guidelines. More mutation-negative individuals strictly adhered to guidelines than did mutation-positive individuals (87% v65%). Conclusion Genetic counseling and testing for HNPCC significantly influences the use of colonic endoscopy and adherence to recommendations for colon cancer screening. C1 NHGRI, CGC, GCRU, MGB,NIH, Bethesda, MD 20892 USA. NCI, Genet Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. Natl Naval Med Res Inst, Bethesda, MD USA. Calif State Univ Los Angeles, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90032 USA. RP Hadley, DW (reprint author), NHGRI, CGC, GCRU, MGB,NIH, 10 Ctr Dr,MSC 1852,Bldg 10,Room 10 C103, Bethesda, MD 20892 USA. EM dhadley@nhgri.nih.gov NR 25 TC 94 Z9 95 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 330 JOHN CARLYLE ST, STE 300, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD JAN 1 PY 2004 VL 22 IS 1 BP 39 EP 44 DI 10.1200/JCO.2004.06.128 PG 6 WC Oncology SC Oncology GA 760DL UT WOS:000187796300008 PM 14701766 ER PT J AU Hochster, H Plimack, ER Runowicz, CD Speyer, J Wallach, RC Sorich, J Mandeli, J Wadler, S Wright, J Muggia, FM AF Hochster, H Plimack, ER Runowicz, CD Speyer, J Wallach, RC Sorich, J Mandeli, J Wadler, S Wright, J Muggia, FM TI Biweekly 72-hour 9-aminocamptothecin infusion as second-line therapy for ovarian carcinoma: Phase II study of the New York Gynecologic Oncology Group and the Eastern Cooperative Oncology Group SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID ADULT CANCER-PATIENTS; COLORECTAL-CARCINOMA; RESISTANT OVARIAN; TRIAL; TOPOTECAN; PACLITAXEL; CISPLATIN; GEMCITABINE; PHARMACODYNAMICS; CYCLOPHOSPHAMIDE AB Purpose To determine the antitumor activity of the novel topoisomerase I inhibitor 9-aminocamptothecin (9-AC) given over 72 hours every 2 weeks in patients with ovarian carcinoma previously treated with one platinum-containing regimen. Patients and Methods Patients with ovarian carcinoma who received one prior platinum-containing regimen were eligible. Patients were stratified based on whether their disease was measurable, or nonmeasurable but assessable. 9-AC 35 mug/m(2)/h was administered by continuous infusion for 72 hours every 2 weeks via ambulatory pump. Results Sixty patients were entered, 32 with measurable and 28 with nonmeasurable but assessable disease. Ten (16.7%) of 60 patients responded (95% Cl, 7.2% to 26.1%), with four complete responses and six partial remissions. The response rate for patients with measurable and nonmeasurable but assessable disease was 22% (95% Cl, 7.6% to 36.2%) and 10.7% (95% Cl, 2.3% to 28.2%), respectively. None of the responders were platinum-resistant. Nineteen patients (32%) had stable disease. The major toxicities were hematologic, with 25% of patients having grade 3 and 35% having grade 4 neutropenia, including five episodes of febrile neutropenia, 17% having grade 3 to 4 thrombocytopenia, and 27% having grade 3 to 4 anemia. Nonhematologic toxicity included grade 3 to 4 nausea (27%) and grade 3 to 4 vomiting (12%). Conclusion This phase II multicenter trial of biweekly 72 hour 9-AC infusion as second-line therapy for ovarian cancer demonstrates comparable activity to standard approved agents in patients with both measurable and nonmeasurable but assessable disease. Toxicity consists mainly of moderate but controllable myelosuppression. Further studies combining 9-AC with other agents active in ovarian cancer for use as second-line therapy are warranted. C1 NYU, Sch Med, New York, NY 10016 USA. St Lukes Roosevelt Hosp, New York, NY 10025 USA. CUNY Mt Sinai Sch Med, New York, NY 10029 USA. New York Cornell Hosp Ctr, New York, NY USA. NCI, Canc Therapy Evaluat Program, Bethesda, MD 20892 USA. RP Hochster, H (reprint author), NYU, Sch Med, 160 E 32nd St, New York, NY 10016 USA. OI Muggia, Franco/0000-0003-0703-9146 FU NCI NIH HHS [CA 21115-27, N01 CM 07003-74S, CA 16087, CA 76642, CA 21115] NR 26 TC 9 Z9 10 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 330 JOHN CARLYLE ST, STE 300, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD JAN 1 PY 2004 VL 22 IS 1 BP 120 EP 126 DI 10.1200/JCO.2004.03.016 PG 7 WC Oncology SC Oncology GA 760DL UT WOS:000187796300019 PM 14701774 ER PT J AU Rich, JN Reardon, DA Peery, T Dowell, JM Quinn, JA Penne, KL Wikstrand, CJ Van Duyn, LB Dancey, JE McLendon, RE Kao, JC Stenzel, TT Rasheed, BKA Tourt-Uhlig, SE Herndon, JE Vredenburgh, JJ Sampson, JH Friedman, AH Bigner, DD Friedman, HS AF Rich, JN Reardon, DA Peery, T Dowell, JM Quinn, JA Penne, KL Wikstrand, CJ Van Duyn, LB Dancey, JE McLendon, RE Kao, JC Stenzel, TT Rasheed, BKA Tourt-Uhlig, SE Herndon, JE Vredenburgh, JJ Sampson, JH Friedman, AH Bigner, DD Friedman, HS TI Phase II trial of gefitinib in recurrent glioblastoma SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article; Proceedings Paper CT 39th Annual Meeting of the American-Society-of-Clinical-Oncology CY MAY 31-JUN 03, 2003 CL CHICAGO, ILLINOIS SP Amer Soc Clin Oncol ID GROWTH-FACTOR RECEPTOR; TYROSINE KINASE INHIBITOR; CELL LUNG-CANCER; GENE AMPLIFICATION; EGF RECEPTOR; SOLID TUMORS; ZD1839; EXPRESSION; BRAIN; MULTIFORME AB Purpose To evaluate the efficacy and tolerability of gefitinib (ZD1839, Iressa; AstraZeneca, Wilmington, DE), a novel epidermal growth factor receptor tyrosine kinase inhibitor, in patients with recurrent glioblastoma. Patients and Methods This was an open-label, single-center phase II trial. Fifty-seven patients with first recurrence of a glioblastoma who were previously treated with surgical resection, radiation, and usually chemotherapy underwent an open biopsy or resection at evaluation for confirmation of tumor recurrence. Each patient initially received 500 mg of gefitinib orally once daily; dose escalation to 750 mg then 1,000 mg, if a patient received enzyme-inducing antiepileptic drugs or dexamethasone, was allowed within each patient. Results Although no objective tumor responses were seen among the 53 assessable patients, only 21% of patients (11 of 53 patients) had measurable disease at treatment initiation. Seventeen percent of patients (nine of 53 patients) underwent at least six 4-week cycles, and the 6-month event-free survival (EFS) was 13% (seven of 53 patients). The median EFS time was 8.1 weeks, and the median overall survival (OS) time from treatment initiation was 39.4 weeks. Adverse events were generally mild (grade I or 2) and consisted mainly of skin reactions and diarrhea. Drug-related toxicities were more frequent at higher doses. Withdrawal caused by drug-related adverse events occurred in 6% of patients (three of 53 patients). Although the presence of diarrhea positively predicted favorable OS from treatment initiation, epidermal growth factor receptor expression did not correlate with either EFS or OS. Conclusion Gefitinib is well tolerated and has activity in patients with recurrent glioblastoma. Further study of this agent at higher doses is warranted. C1 Duke Univ, Med Ctr, Dept Med, Durham, NC 27710 USA. Duke Univ, Med Ctr, Dept Pathol, Durham, NC 27710 USA. Duke Univ, Med Ctr, Dept Surg, Durham, NC 27710 USA. Duke Univ, Med Ctr, Ctr Biostat, Dept Canc, Durham, NC 27710 USA. NCI, Bethesda, MD 20892 USA. RP Rich, JN (reprint author), Duke Univ, Med Ctr, Dept Med, Box 2900, Durham, NC 27710 USA. FU NCI NIH HHS [R21 CA 91548] NR 33 TC 438 Z9 451 U1 0 U2 10 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 330 JOHN CARLYLE ST, STE 300, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD JAN 1 PY 2004 VL 22 IS 1 BP 133 EP 142 DI 10.1200/JCO.2004.08.110 PG 10 WC Oncology SC Oncology GA 760DL UT WOS:000187796300021 PM 14638850 ER PT J AU Gould, TD Zarate, CA Manji, HK AF Gould, TD Zarate, CA Manji, HK TI Glycogen synthase kinase-3: A target for novel bipolar disorder treatments SO JOURNAL OF CLINICAL PSYCHIATRY LA English DT Review ID MANIC-DEPRESSIVE ILLNESS; SMALL-MOLECULE INHIBITORS; WNT-SIGNALING PATHWAY; N-ACETYL-ASPARTATE; INOSITOL MONOPHOSPHATASE; MOOD DISORDERS; ALZHEIMERS-DISEASE; BETA-CATENIN; TAU PHOSPHORYLATION; HIPPOCAMPAL NEUROGENESIS AB The enzyme glycogen synthase kinase-3 (GSK-3) is a direct target of lithium. While originally recognized as an important molecule in a limited number of cellular processes, with unclear significance for the treatment of bipolar disorder, recent evidence suggests it has critically important cellular functions in the adult brain. GSK-3 has an essential role in a number of signaling pathways and regulates the function of a diverse number of proteins, notably transcription factors and cytoskeletal elements. The most important functions of the enzyme in regard to bipolar disorder may be critical effects on cellular resilience and neuronal plasticity. There is tremendous interest in GSK-3 inhibitors as novel therapeutic agents. and selective, small-molecule compounds are rapidly being developed for a broad range of other maladies including diabetes, Alzheimer's disease, stroke, and inflammatory conditions. In this perspectives article, we provide an overview of the molecular targets of lithium, focusing on GSK-3-regulated signaling pathways and the important functions of GSK-3 that may have relevance for the treatment of bipolar disorder. We conclude with a discussion of the GSK-3 inhibitors furthest in development and the clinical trials that may emerge. C1 NIMH, Mol Pathophysiol Lab, NIH, Bethesda, MD 20892 USA. RP Gould, TD (reprint author), NIMH, Mol Pathophysiol Lab, NIH, Bldg 49,Rm B1EE16, Bethesda, MD 20892 USA. EM gouldt@intra.nimh.nih.gov NR 154 TC 92 Z9 95 U1 0 U2 5 PU PHYSICIANS POSTGRADUATE PRESS PI MEMPHIS PA P O BOX 240008, MEMPHIS, TN 38124 USA SN 0160-6689 J9 J CLIN PSYCHIAT JI J. Clin. Psychiatry PD JAN PY 2004 VL 65 IS 1 BP 10 EP 21 PG 14 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 831JE UT WOS:000222189900002 PM 14744163 ER PT J AU Gomez-Beldarrain, M Harries, C Garcia-Monco, JC Ballus, E Grafman, J AF Gomez-Beldarrain, M Harries, C Garcia-Monco, JC Ballus, E Grafman, J TI Patients with right frontal lesions are unable to assess and use advice to make predictive judgments SO JOURNAL OF COGNITIVE NEUROSCIENCE LA English DT Article ID HUMAN PREFRONTAL CORTEX; DECISION-MAKING; RESPONSE SELECTION; WORKING-MEMORY; ORBITOFRONTAL CORTEX; RISK-TAKING; PERFORMANCE; DAMAGE; LOBES; TASK AB Frontal lobe damage impairs decision-making. Most studies have employed gambling and probabilistic tasks, which have an emotional (reward-punishment) component and found that patients with ventromedial sector lesions have exceptional difficulty performing normally on these tasks. We have recently presented an economic decision-making task to patients and normal volunteers that required them to not only forecast an economic outcome but also to weigh advice from four advisors about the possible outcome across 40 trials. We studied 20 patients with right frontal lobe lesions and 9 patients with parietal lobe lesions and compared their performance to 20 matched controls. Frontal lobe lesion patients were inconsistent at using advice and their forecasts were poor. Patients with dorsolateral but not orbito-frontal lesions showed some ability to assess advice. Patients with parietal lobe lesions were good at assessing advice but were slow at doing so; they were consistent but poor at using advice and their use of advice was unrelated to their forecasting. All three patient groups were overconfident in their own performance. In contrast, controls could both use and assess advice, their ability to use advice was mediated by their ability to assess it, and they were not overconfident. Group differences on an overall measure of accuracy on this task were associated with an ability to accurately plan. Differences in ability to assess and forecast were associated with planning and working memory performance. These findings indicate that patients with both right dorsolateral and orbito-frontal lesions may be impaired when required to make complex decisions related to forecasting and judgment. Our findings enlarge the scope of decision-making deficits seen in patients with frontal lobe lesions and indicate additional circumstances in which patients with frontal lobe lesions will have difficulty in deciding. C1 Univ Leeds, Leeds LS2 9JT, W Yorkshire, England. NIH, Bethesda, MD 20892 USA. EM mgomezab@sarenet.es OI Grafman, Jordan H./0000-0001-8645-4457 NR 48 TC 25 Z9 25 U1 4 U2 5 PU M I T PRESS PI CAMBRIDGE PA FIVE CAMBRIDGE CENTER, CAMBRIDGE, MA 02142 USA SN 0898-929X J9 J COGNITIVE NEUROSCI JI J. Cogn. Neurosci. PD JAN-FEB PY 2004 VL 16 IS 1 BP 74 EP 89 DI 10.1162/089892904322755575 PG 16 WC Neurosciences; Psychology, Experimental SC Neurosciences & Neurology; Psychology GA 764YR UT WOS:000188239200009 PM 15006038 ER PT J AU Ganeshina, O Berry, RW Petralia, RS Nicholson, DA Geinisman, Y AF Ganeshina, O Berry, RW Petralia, RS Nicholson, DA Geinisman, Y TI Differences in the expression of AMPA and NMDA receptors between axospinous perforated and nonperforated synapses are related to the configuration and size of postsynaptic densities SO JOURNAL OF COMPARATIVE NEUROLOGY LA English DT Article DE postembedding immunogold electron microscopy; serial section analyses; hippocampus; CA1 stratum radiatum; rat ID LONG-TERM POTENTIATION; RAT DENTATE GYRUS; PARTITIONED TRANSMISSION ZONES; SYNAPTIC PLASTICITY; DENDRITIC SPINES; EXCITATORY SYNAPSES; GLUTAMATE RECEPTORS; MAINTENANCE PHASE; IMMUNOGOLD LOCALIZATION; SEQUENTIAL-CHANGES AB Axospinous synapses are traditionally divided according to postsynaptic density (PSD) configuration into a perforated subtype characterized by a complex-shaped PSD and nonperforated subtype exhibiting a simple-shaped, disc-like PSD. It has been hypothesized that perforated synapses are especially important for synaptic plasticity because they have a higher efficacy of impulse transmission. The aim of the present study was to test this hypothesis. The number of postsynaptic AMPA receptors (AMPARs) is widely regarded as the major determinant of synaptic efficacy. Therefore, the expression of AMPARs was evaluated in the two synaptic subtypes and compared with that of NMDA receptors (NMDARs). Postembedding immunogold electron microscopy was used to quantify the immunoreactivity following single labeling of AMPARs or NMDARs in serial sections through the CA1 stratum radiatum of adult rats. The results showed that all perforated synapses examined were immunopositive for AMPARs. In contrast, only a proportion of nonperforated synapses (64% on average) contained immunogold particles for AMPARs. The number of immunogold particles for AMPARs was markedly and significantly higher in perforated synapses than in immunopositive nonperforated synapses. Although all synapses of both subtypes were NMDAR immunopositive perforated synapses contained significantly more immunogold particles for NMDARs than nonperforated ones. Multivariate analysis of variance revealed that the mode of AMPAR and NMDAR expression is related to the complexity of PSD configuration, not only to PSD size. These findings support the notion that perforated synapses may evoke larger postsynaptic responses relative to nonperforated synapses and, hence, contribute to an enhancement of synaptic transmission associated with some forms of synaptic plasticity. Published 2003 Wiley-Liss, Inc.(dagger) C1 Northwestern Univ, Feinberg Sch Med, Dept Cell & Mol Biol, Chicago, IL 60611 USA. Natl Inst Deafness & Other Commun Dis, Neurochem Lab, NIH, Bethesda, MD 20892 USA. RP Geinisman, Y (reprint author), Northwestern Univ, Feinberg Sch Med, Dept Cell & Mol Biol, Chicago, IL 60611 USA. OI Nicholson, Dan/0000-0002-1963-0569 FU NIA NIH HHS [AG17139] NR 70 TC 85 Z9 90 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 0021-9967 J9 J COMP NEUROL JI J. Comp. Neurol. PD JAN 1 PY 2004 VL 468 IS 1 BP 86 EP 95 DI 10.1002/cne.10950 PG 10 WC Neurosciences; Zoology SC Neurosciences & Neurology; Zoology GA 750JV UT WOS:000186988300005 PM 14648692 ER PT J AU Shatsky, M Nussinov, R Wolfson, HJ AF Shatsky, M Nussinov, R Wolfson, HJ TI FlexProt: Alignment of flexible protein structures without a predefinition of hinge regions SO JOURNAL OF COMPUTATIONAL BIOLOGY LA English DT Article DE structural comparison; hinge-bending; flexible structural comparison; efficient algorithm; protein structural alignment; hinge detection ID DOMAIN MOVEMENTS; BINDING; MECHANISMS; MOTIFS AB FlexProt is a novel technique for the alignment of flexible proteins. Unlike all previous algorithms designed to solve the problem of structural comparisons allowing hinge-bending motions, FlexProt does not require an a priori knowledge of the location of the hinge(s). Flex-Prot carries out the flexible alignment, superimposing the matching rigid subpart pairs, and detects the flexible hinge regions simultaneously. A large number of methods are available to handle rigid structural alignment. However, proteins are flexible molecules, which may appear in different conformations. Hence, protein structural analysis requires algorithms that can deal with molecular flexibility. Here, we present a method addressing specifically a flexible protein alignment task. First, the method efficiently detects maximal congruent rigid fragments in both molecules. Transforming the task into a graph theoretic problem, our method proceeds to calculate the optimal arrangement of previously detected maximal congruent rigid fragments. The fragment arrangement does not violate the protein sequence order. A clustering procedure is performed on fragment-pairs which have the same 3-D rigid transformation regardless of insertions and deletions (such as loops and turns) which separate them. Although the theoretical worst case complexity of the algorithm is O(n(6)), in practice FlexProt is highly efficient. It performs a structural comparison of a pair of proteins 300 amino acids long in about seven seconds on a standard desktop PC (400 MHz Pentium II processor with 256MB internal memory). We have performed extensive experiments with the algorithm. An assortment of these results is presented here. FlexProt can be accessed via WWW at bioinfo3d.cs.tau.ac.il/FlexProt/. C1 Tel Aviv Univ, Raymond & Beverly Sackler Fac Exact Sci, Sch Comp Sci, IL-69978 Tel Aviv, Israel. NCI, Intramural Res Support Program SAIC, Lab Expt & Computat Biol, Frederick, MD 21702 USA. Tel Aviv Univ, Sackler Sch Med, Sackler Inst Mol Med, Dept Human Genet & Mol Med, IL-69978 Tel Aviv, Israel. RP Shatsky, M (reprint author), Tel Aviv Univ, Raymond & Beverly Sackler Fac Exact Sci, Sch Comp Sci, IL-69978 Tel Aviv, Israel. EM maxshats@cs.tau.ac.il RI Wolfson, Haim/A-1837-2011 FU NCI NIH HHS [N01-CO-56000] NR 40 TC 42 Z9 45 U1 0 U2 2 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA SN 1066-5277 J9 J COMPUT BIOL JI J. Comput. Biol. PY 2004 VL 11 IS 1 BP 83 EP 106 DI 10.1089/106652704773416902 PG 24 WC Biochemical Research Methods; Biotechnology & Applied Microbiology; Computer Science, Interdisciplinary Applications; Mathematical & Computational Biology; Statistics & Probability SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Computer Science; Mathematical & Computational Biology; Mathematics GA 803MD UT WOS:000220234300006 PM 15072690 ER PT J AU Sung, MH Simon, R AF Sung, MH Simon, R TI Genomewide conserved epitope profiles of HIV-1 predicted by biophysical properties of MHC binding peptides SO JOURNAL OF COMPUTATIONAL BIOLOGY LA English DT Article DE epitope prediction; peptide property model; HIV-1; MHC binding; vaccine design; bioinformatics ID T-CELL EPITOPES; IMMUNODEFICIENCY-VIRUS TYPE-1; ARTIFICIAL NEURAL-NETWORK; DELETION MUTAGENESIS; LYMPHOCYTE EPITOPES; HLA; CD4(+); IDENTIFICATION; MOLECULES; INFECTION AB We propose a new method for predicting MHC binding of peptides using biophysical parameters of the constituent amino acids. Unlike conventional matrix-based methods, our method does not assume independent binding of the individual side chains and uses a model that simultaneously represents all the residues. The model discovers the quantified 9-mer "property model" within the longer peptides that are most common among binders. Prediction for a new peptide is based on its statistical "distance" from the extracted peptide property model. MHC-specific peptide property models were constructed from compiled binder/nonbinder data using this method. We report the results of cross-validation of the prediction method and comparison with other methods. The comparison suggests that our method performs substantially better for some MHC class II molecules and equally well for other MHC types. To demonstrate large-scale utility, 30 HIV-1 reference genomes covering diverse subtypes were analyzed. Regions that are likely to bind MHC (A2, DR1, or DR4) and that are conserved across the HIV-1 subtypes were identified. These "epitope profiles" of the diverse HIV-1 strains can also be visually presented to facilitate discovery of conserved patterns naturally occurring in the viral genomes. As an essential step in designing vaccines, the revealed patterns may provide valuable information in identifying the immunologically important regions. C1 NCI, Biometr Res Branch, NIH, Bethesda, MD 20892 USA. RP Sung, MH (reprint author), NCI, Biometr Res Branch, NIH, 6130 Execut Blvd EPN 8146,MSC 7434, Bethesda, MD 20892 USA. EM sungm@mail.nih.gov NR 39 TC 5 Z9 6 U1 0 U2 0 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA SN 1066-5277 J9 J COMPUT BIOL JI J. Comput. Biol. PY 2004 VL 11 IS 1 BP 125 EP 145 DI 10.1089/106652704773416920 PG 21 WC Biochemical Research Methods; Biotechnology & Applied Microbiology; Computer Science, Interdisciplinary Applications; Mathematical & Computational Biology; Statistics & Probability SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Computer Science; Mathematical & Computational Biology; Mathematics GA 803MD UT WOS:000220234300008 PM 15072692 ER PT J AU Zhou, XB Wang, XD Dougherty, ER Russ, D Suh, E AF Zhou, XB Wang, XD Dougherty, ER Russ, D Suh, E TI Gene clustering based on clusterwide mutual information SO JOURNAL OF COMPUTATIONAL BIOLOGY LA English DT Article DE gene microarray; clustering; mutual information; simulated annealing; bootstrap technique; K-means; fuzzy C-means ID EXPRESSION DATA; DRUG DISCOVERY; PATTERNS; NETWORKS; IDENTIFICATION; BOOTSTRAP AB Cluster analysis of gene-wide expression data from DNA microarray hybridization studies has proved to be a useful tool for identifying biologically relevant groupings of genes and constructing gene regulatory networks. The motivation for considering mutual information is its capacity to measure a general dependence among gene random variables. We propose a novel clustering strategy based on minimizing mutual information among gene clusters. Simulated annealing is employed to solve the optimization problem. Bootstrap techniques are employed to get more accurate estimates of mutual information when the data sample size is small. Moreover, we propose to combine the mutual information criterion and traditional distance criteria such as the Euclidean distance and the fuzzy membership metric in designing the clustering algorithm. The performances of the new clustering methods are compared with those of some existing methods, using both synthesized data and experimental data. It is seen that the clustering algorithm based on a combined metric of mutual information and fuzzy membership achieves the best performance. The supplemental material is available at www.gspsnap.tamu.edu/gspweb/zxb/glioma_zxb. C1 Texas A&M Univ, Zachry Engn Ctr 214, Dept Elect Engn, College Stn, TX 77843 USA. Columbia Univ, Dept Elect Engn, New York, NY 10027 USA. Univ Texas, MD Anderson Canc Ctr, Dept Pathol, Houston, TX 77030 USA. NIH, High Performance Comp & Informat Off, Ctr Informat Technol, Bethesda, MD 20892 USA. RP Dougherty, ER (reprint author), Texas A&M Univ, Zachry Engn Ctr 214, Dept Elect Engn, College Stn, TX 77843 USA. EM edward@ee.tamu.edu OI Russ, Daniel/0000-0003-4040-4416 NR 39 TC 28 Z9 30 U1 0 U2 4 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA SN 1066-5277 J9 J COMPUT BIOL JI J. Comput. Biol. PY 2004 VL 11 IS 1 BP 147 EP 161 DI 10.1089/106652704773416939 PG 15 WC Biochemical Research Methods; Biotechnology & Applied Microbiology; Computer Science, Interdisciplinary Applications; Mathematical & Computational Biology; Statistics & Probability SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Computer Science; Mathematical & Computational Biology; Mathematics GA 803MD UT WOS:000220234300009 PM 15072693 ER PT J AU Allik, J McCrae, RR AF Allik, J McCrae, RR TI Toward a geography of personality traits - Patterns of profiles across 36 cultures SO JOURNAL OF CROSS-CULTURAL PSYCHOLOGY LA English DT Article DE five-factor model; cluster analysis; multidimensional scaling ID SELF; AMERICAN; EMOTION; STEREOTYPES; PSYCHOLOGY; UNIVERSAL; NATIONS; CHINESE; STATES; VALUES AB It has long been believed that personality traits vary by geographical location, but few studies have examined the worldwide distribution of personality profiles. Using the five-factor model of personality-a comprehensive and apparently universal trait structure-we conducted secondary analyses of data from 36 cultures. Distance from the equator and mean temperature were not meaningfully related to personality factors. However, cluster analysis showed that geographically proximate cultures often have similar profiles, and multidimensional scaling showed a clear contrast of European and American cultures with Asian and African cultures. The former were higher in extraversion and openness to experience and lower in agreeableness. A second dimension reflected differences in psychological adjustment. Observed differences between cultures may be the result of differences in gene pools or in features of culture; acculturation studies and the analyses of other natural experiments are needed to understand the origins of geographical differences in personality traits. C1 Univ Tartu, EE-50090 Tartu, Estonia. NIA, Lab Personal & Cognit, DHHS, NIH, Bethesda, MD 20892 USA. RP Allik, J (reprint author), Univ Tartu, EE-50090 Tartu, Estonia. RI Allik, Juri/D-5609-2009 OI Allik, Juri/0000-0002-8358-4747 NR 56 TC 194 Z9 199 U1 8 U2 89 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0022-0221 J9 J CROSS CULT PSYCHOL JI J. Cross-Cult. Psychol. PD JAN PY 2004 VL 35 IS 1 BP 13 EP 28 DI 10.1177/0022022103260382 PG 16 WC Psychology, Social SC Psychology GA 752KY UT WOS:000187160700003 ER PT J AU Kramer, PR Nares, S Kramer, SF Grogan, D Kaiser, M AF Kramer, PR Nares, S Kramer, SF Grogan, D Kaiser, M TI Mesenchymal stem cells acquire characteristics of cells in the periodontal ligament in vitro SO JOURNAL OF DENTAL RESEARCH LA English DT Article DE mesenchymal stem cell; periodontal ligament; regeneration; repair ID MARROW STROMAL CELLS; GUIDED TISSUE REGENERATION; BONE-MARROW; EXPRESSION; PROLIFERATION; POPULATIONS; BRAIN; MICE; VIVO; FIBROBLASTS AB Mesenchymal stem cells differentiate into multiple types of cells derived from mesenchyme. Periodontal ligament cells are primarily derived from mesenchyme; thus, we expected mesenchymal stem cells to differentiate into periodontal ligament. Using a combination of immunohistochemistry and in situ hybridization on co-cultures of mesenchymal stem cells and periodontal ligament, we observed a significant increase in mesenchymal stem cells' expression of osteocalcin and osteopontin and a significant decrease in expression of bone sialoprotein, characteristics of periodontal ligament in vivo. Increased osteopontin and osteocalcin and decreased bone sialoprotein expression was detected within 7 days and maintained through 21 days of co-culture. We conclude that contact or factors from periodontal ligament induced mesenchymal stem cells to obtain periodontal-ligament-like characteristics. Importantly, analysis of the data suggests the feasibility of utilizing mesenchymal stem cells in clinical applications for repairing and/or regenerating periodontal tissue. C1 Texas A&M Univ Syst Hlth Sci Ctr, Baylor Coll Dent, Dept Biomed Sci, Dallas, TX 75246 USA. Natl Inst Dent & Craniofacial Res, Oral Infect & Immun Branch, Bethesda, MD 20892 USA. RP Kramer, PR (reprint author), Texas A&M Univ Syst Hlth Sci Ctr, Baylor Coll Dent, Dept Biomed Sci, 3302 Gaston Ave, Dallas, TX 75246 USA. OI Kramer, Phillip/0000-0003-0117-542X NR 34 TC 42 Z9 66 U1 0 U2 6 PU INT AMER ASSOC DENTAL RESEARCHI A D R/A A D R PI ALEXANDRIA PA 1619 DUKE ST, ALEXANDRIA, VA 22314-3406 USA SN 0022-0345 J9 J DENT RES JI J. Dent. Res. PD JAN PY 2004 VL 83 IS 1 BP 27 EP 34 PG 8 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 760CF UT WOS:000187792700005 PM 14691109 ER PT J AU Matsushima, S Horiguchi, Y Honda, T Fujii, S Okano, T Tanabe, M Wakayama, T Hashimoto, T Yancey, KB AF Matsushima, S Horiguchi, Y Honda, T Fujii, S Okano, T Tanabe, M Wakayama, T Hashimoto, T Yancey, KB TI A case of anti-epiligrin cicatricial pemphigoid associated with lung carcinoma and severe laryngeal stenosis: Review of Japanese cases and evaluation of risk for internal malignancy SO JOURNAL OF DERMATOLOGY LA English DT Review DE anti-epiligrin cicatricial pemphigoid; internal malignancies; laryngeal stenosis ID GASTRIC-CARCINOMA; LAMININ-5 AB A 68-year-old Japanese male with a five-year-history of lung carcinoma showed recurrent blisters and erosions on the oral and genital mucosae and the skin. The patient complained of dyspnea due to severe laryngeal stenosis and underwent a tracheostomy. A skin biopsy specimen showed a subepidermal blister and linear deposits of IgG and C3 at the basement membrane zone of the epidermis. Indirect immunofluorescence examination demonstrated circulating IgG anti-basement membrane zone autoantibodies that reacted to epiligrin on immunoblotting. Based on a diagnosis of anti-epiligrin cicatricial pemphigoid, he was treated with prednisolone, minocycline hydrochloride and nicotinamide. Although no new skin lesions appeared, he died of lung carcinoma five months after the tracheostomy. A review of reported cases with anti-epiligrin cicatricial pemphigoid in Japan disclosed that 5 of 16 cases (31.2%) were complicated by internal malignancies. C1 Osaka Red Cross Hosp, Dept Dermatol, Tenoji Ku, Osaka 5438555, Japan. Osaka Red Cross Hosp, Dept Otorhinolaryngol, Osaka 5438555, Japan. Osaka Red Cross Hosp, Dept Resp Med, Osaka 5438555, Japan. NCI, Dermatol Branch, Div Clin Sci, NIH, Bethesda, MD 20892 USA. Kurume Univ, Sch Med, Dept Dermatol, Kurume, Fukuoka, Japan. RP Horiguchi, Y (reprint author), Osaka Red Cross Hosp, Dept Dermatol, Tenoji Ku, Fudegasaki Cho, Osaka 5438555, Japan. NR 24 TC 18 Z9 18 U1 0 U2 0 PU JAPANESE DERMATOLGICAL ASSOC PI TOKYO PA TAISEI-BLDG., 14-10 HONGO 3-CHOME, BUNKYO-KU, TOKYO, 113-0033, JAPAN SN 0385-2407 J9 J DERMATOL JI J. Dermatol. PD JAN PY 2004 VL 31 IS 1 BP 10 EP 15 PG 6 WC Dermatology SC Dermatology GA 769AZ UT WOS:000188605400003 PM 14739497 ER PT J AU Bailey, JJ AF Bailey, JJ TI The triangular wave test for electrocardiographic devices: A historical perspective SO JOURNAL OF ELECTROCARDIOLOGY LA English DT Article; Proceedings Paper CT 29th Annual ISCE Conference on Research and Technology Transfer in Computerized Elecrocardiology CY APR 27-MAY 02, 2004 CL Hutchinson Isl, FL SP ISCE, Datex-Ohmeda Gems-It, Draeger-Siemens Med Syst, GE Med Syst Inc, Inovise Med Inc, Medtron, Mortara Instrument Inc, NE Montoring Inc, Philips Med Syst, Quinton Instrument Inc, Rozinn Elect Inc, Shiller AG, Welch Allyn - Cardio Control NV, Welch Allyn Inc DE baseline wander; ST segment; triangular wave test ID AMERICAN-HEART-ASSOCIATION; ST SEGMENT ANALYSIS; BASE-LINE WANDER; STANDARDIZATION; RECOMMENDATIONS; SPECIFICATIONS; COMMITTEE AB Baseline wander makes interpretation ECG recordings difficult, especially the assessment of ST deviation. Eliminating baseline wander without distorting the ST segment is a problem. The traditional high pass filter with a 0.5 Hz low frequency cutoff effectively suppresses baseline but introduces considerable distortion in the level of the ST segment. This distortion results from phase nonlinearities that occur when frequency content and wave amplitude change abruptly, as occurs where the end of the QRS complex meets the ST segment. Since the 1980s nonlinear, digital filters have been designed that can increase the low frequency Cutoff without the introduction of phase distortion. The triangular wave test, first described in the 1990 AHA Recommendations, is an objective method for measuring the ability to suppress baseline wander without affecting the ST segment. This methodology was adopted in 3 American National Standards (Diagnostic ECG in1991; Ambulatory ECGs in 1998; and Cardiac Monitors in 2002). C1 NIH, Ctr Informat Technol, Bethesda, MD 20892 USA. RP Bailey, JJ (reprint author), NIH, Ctr Informat Technol, MSC 5620,Bldg 12A,Room 2007, Bethesda, MD 20892 USA. NR 15 TC 10 Z9 10 U1 0 U2 3 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. PY 2004 VL 37 SU S BP 71 EP 73 DI 10.1016/j.electrocard.2004.08.020 PG 3 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 875XR UT WOS:000225456400015 PM 15534805 ER PT J AU Ishaque, AB Tchounwou, PB Wilson, BA Washington, T AF Ishaque, AB Tchounwou, PB Wilson, BA Washington, T TI Developmental arrest in Japanese medaka (Oryzias latipes) embryos exposed to sublethal concentrations of atrazine and arsenic trioxide SO JOURNAL OF ENVIRONMENTAL BIOLOGY LA English DT Article DE atrazine; arsenic; Japanese medaka; developmental arrest; morphological abnormalities ID EXPRESSION; CANCER; GENE; DNA AB Embryos of the Japanese medaka (Oryzias latipes) were exposed to serial concentrations of atrazine (0, 25, 50, and 100ppm) and arsenic trioxide (0, 0. 025, 0.05, 0.1ppm) until hatching. Stasis of circulation, blood islands, titanic convulsions, tube heart and mortality were observed in atrazine-treated embryos. Each endpoint exhibited a concentration-response relationship. Only 4 % of the embryos hatched in the 25 ppm, and none in the 50 and 100 ppm, probably due to cell death attributed to the embryos' inability to break from the chorion. With arsenic exposure, hatching was inversely correlated to chemical concentration: 86%, 75% and 54% for 0. 025, 0.05 and 0.1 ppm, respectively. Hatching periods were also reduced from 7-13 days in controls to 7-11 days in arsenic-treated embryos. This observation was more pronounced with the 0,05 ppm concentration, showing a reduction of about 4 days. Despite this shortage in hatching time, there were no observable morphological abnormalities, as seen with atrazine. The ecological significance of these findings and implications for the development of sublethal toxicity tests using Japanese medaka embryos are important. C1 Jackson State Univ, NIH, Ctr Environm Hlth, Environm Toxicol Res Lab, Jackson, MS 39217 USA. Univ Maryland Eastern Shore, Dept Nat Sci, Princess Anne, MD 21853 USA. RP Tchounwou, PB (reprint author), Jackson State Univ, NIH, Ctr Environm Hlth, Environm Toxicol Res Lab, Jackson, MS 39217 USA. EM paul.b.tchounwou@jsums.edu FU NCRR NIH HHS [1G12RR13459] NR 32 TC 14 Z9 14 U1 0 U2 3 PU TRIVENI ENTERPRISES PI LUCKNOW PA C/O KIRAN DALELA, 1/206 VIKAS NAGAR, KURSI RD, LUCKNOW 226 022, INDIA SN 0254-8704 J9 J ENVIRON BIOL JI J.Environ.Biol. PD JAN PY 2004 VL 25 IS 1 BP 1 EP 6 PG 6 WC Environmental Sciences SC Environmental Sciences & Ecology GA 778NZ UT WOS:000189248800002 PM 15303697 ER PT J AU Simon, SL Bouville, A Beck, HL AF Simon, SL Bouville, A Beck, HL TI The geographic distribution of radionuclide deposition across the continental US from atmospheric nuclear testing SO JOURNAL OF ENVIRONMENTAL RADIOACTIVITY LA English DT Article; Proceedings Paper CT International Conference on Radioactivity in the Environment CY SEP 01-05, 2002 CL MONACO DE fallout; nuclear testing; deposition; I-131; Cs-137 ID UNITED-STATES; FALLOUT; STRONTIUM-90 AB For the first time, calculations for the more than 3000 counties, of the US have been completed that estimate the average deposition density (Bq m(-2)) of more than 40 radionuclides in fallout from atmospheric nuclear weapons tests conducted in the US (1951-1962) and 19 radionuclides from tests conducted elsewhere in the world (1952-1963). The geographic pattern of deposition across the US, as well as the amount of fallout deposited, varied significantly depending on whether the tests were conducted within or outside of the US. Fallout deposited from the Nevada Test Site (NTS) varied geographically as a result of dispersion and dilution in the atmosphere, the wind patterns following each test, and the occurrence of localized rainfall events. In general, states immediately east of the NTS received the highest deposition from tests conducted there. In contrast, the variation in deposition across the country from global fallout was less than for NTS fallout primarily reflecting variations in annual precipitation across larger regions. Hence, in the eastern and mid-western US, where rainfall is above the national average, higher levels of global fallout were deposited than in the more and southwestern states. This paper presents a summary of the methods used and findings of our studies on fallout from NTS and global fallout, with emphasis on two of the most important radionuclides, I-131 and Cs-137. Published by Elsevier Ltd. C1 NCI, Div Canc Epidemiol & Genet, Radiat Epidemiol Branch, NIH, Bethesda, MD 20892 USA. US Dept Energy Environm Measurements Lab, New York, NY USA. RP Simon, SL (reprint author), NCI, Div Canc Epidemiol & Genet, Radiat Epidemiol Branch, NIH, Execut Plaza S,6120 Execut Blvd, Bethesda, MD 20892 USA. EM ssimon@mail.nih.gov NR 32 TC 28 Z9 28 U1 1 U2 9 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0265-931X J9 J ENVIRON RADIOACTIV JI J. Environ. Radioact. PY 2004 VL 74 IS 1-3 SI SI BP 91 EP 105 DI 10.1016/j.jenvrad.2004.01.023 PG 15 WC Environmental Sciences SC Environmental Sciences & Ecology GA 826IN UT WOS:000221822900009 PM 15063539 ER PT J AU Oleksyk, TK Novak, JM Purdue, JR Gashchak, SP Smith, MH AF Oleksyk, TK Novak, JM Purdue, JR Gashchak, SP Smith, MH TI High levels of fluctuating asymmetry in populations of Apodemus flavicollis from the most contaminated areas in Chornobyl SO JOURNAL OF ENVIRONMENTAL RADIOACTIVITY LA English DT Article DE radiocesium; Cs-137; Apodemus flavicollis; Chornobyl; chernobyl; size; shape; fluctuating asymmetry; directional asymmetry; geometric morphometrics ID HYBRID HOUSE MICE; DEVELOPMENTAL STABILITY; GENETIC-ANALYSIS; SMALL MAMMALS; INSTABILITY; CHARACTERS; FITNESS; HERITABILITY; SELECTION; UKRAINE AB Random deviations from the perfect symmetry of normally bilaterally symmetrical characters for an individual with a given genotype occur during individual development due to the influence of multiple environmental factors. Fluctuating asymmetry (FA) is often used as a measure of developmental instability, and can be estimated as the variance of the distribution of differences between the left and right sides. We addressed the question of whether levels of FA were elevated in radioactively contaminated populations living around Chornobyl compared to those in reference populations of the yellow-necked mouse (Apodemus flavicollis). In addition, we studied amounts of directional asymmetry (DA) when one side is larger than the other on average. There was a significant difference among populations, including reference populations, in the amount of both FA and DA. A higher level of FA was documented for the contaminated populations in close proximity to the failed Chornobyl reactor for both the asymmetry of size and shape. The FAs of size and shape were highest in populations from the most contaminated locations in the Chornobyl exclusion zone. Although the directional asymmetry of shape was also highest in the contaminated populations, it was not significantly different from those in most of the reference populations. Populations from less contaminated areas inside the Chornobyl exclusion zone did not express FA values different from those of the reference populations outside the affected area. FA of skulls of A. flavicollis may indicate the degree to which the level of radioactive contamination affects the development of animals at Chornobyl. However, the mechanisms leading to these effects are not clear and probably vary from population to population. There were significant correlations between the overall right to left differences for the Procrustes aligned shape configurations, centroid sizes, and intramuscular Cs-137. Detectable effects of radiation on developmental stability probably start to occur between 0.132 and 0.297 muGy/h. (C) 2003 Elsevier Ltd. All rights reserved. C1 NCI, LGD, FRDC, NIH, Frederick, MD 21702 USA. Univ Georgia, Savannah River Ecol Lab, Aiken, SC 29802 USA. Univ Georgia, Inst Ecol, Athens, GA 30602 USA. Illinois State Museum, Springfield, IL 62703 USA. Int Radioecol Lab, UA-07100 Slavutych, Ukraine. RP Oleksyk, TK (reprint author), NCI, LGD, FRDC, NIH, POB B, Frederick, MD 21702 USA. EM oleksyk@ncifcrf.gov RI Taras, Oleksyk/J-8805-2013 OI Taras, Oleksyk/0000-0002-8148-3918 NR 54 TC 24 Z9 26 U1 1 U2 14 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0265-931X EI 1879-1700 J9 J ENVIRON RADIOACTIV JI J. Environ. Radioact. PY 2004 VL 73 IS 1 BP 1 EP 20 DI 10.1016/j.jenvrad.2003.07.001 PG 20 WC Environmental Sciences SC Environmental Sciences & Ecology GA 809NP UT WOS:000220643700001 PM 15001292 ER PT J AU Fujita, Y Ito, C Mabuchi, K AF Fujita, Y Ito, C Mabuchi, K TI Surveillance of mortality among atomic bomb survivors living in the United States using the National Death Index SO JOURNAL OF EPIDEMIOLOGY LA English DT Article DE atomic bomb survivors; the United States of America; National Death Index; mortality ID JAPANESE MEN; CANCER; DISEASE; HEALTH; HAWAII AB BACKGROUND: The National Death Index is a useful source to establish the death of an individual and to determine the cause of death. We identified deaths in atomic bomb survivors in the United States who were lost to follow-up through the National Death Index, and examined the completeness of mortality ascertainment in atomic bomb survivors in the US through the National Death Index. METHODS: Since 1977, biennial medical examinations of atomic bomb survivors in the US have been conducted. The 1,073 atomic bomb survivors in the US included 764 individuals who had medical examinations at least once in sixteen years from 1977 through 1993 and 309 individuals who reported atomic bomb survivorship to medical examination project themselves. Of the 1,073 survivors living in the US, 471 people who participated in the ninth health examinations of atomic bomb survivors living in the US in 1993 were removed, and two people among the remaining 602 individuals had no information about their birth dates and Social Security numbers. An investigation of those deceased between 1979 and 1993 was conducted among 600 of the atomic bomb survivors in the US. Death certificates for atomic bomb survivors in the US were requested from the National Death Index. A comparison was made between the information on the death certificates acquired through the National Death Index and the data ascertained from the medical examination project conducted from 1979 through 1993. RESULTS: Forty-nine death certificates were obtained using the National Death Index. By sex, the dominant cause of death in females was malignant neoplasm, accounting for 53%. In males, it was circulatory disease, accounting for 37%. The National Death Index and the medical examination project determined that 57 deaths had occurred between 1979 and 1993. The sensitivity and specificity of the National Death Index is 86% and 97% respectively. CONCLUSION: It is suggested that the National Death Index is useful to follow up mortality among atomic bomb survivors in the US. C1 Shimane Med Univ, Sch Med, Dept Publ Hlth, Izumo, Shimane 6938501, Japan. Hiroshima Atom Bomb Causal Council, Hlth Management Ctr, Hiroshima, Japan. NCI, Radiat Epidemiol Branch, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. RP Fujita, Y (reprint author), Shimane Med Univ, Sch Med, Dept Publ Hlth, 89-1 Enya Cho, Izumo, Shimane 6938501, Japan. NR 19 TC 0 Z9 0 U1 0 U2 1 PU JAPAN EPIDEMIOLOGICAL ASSOC PI TOCHIGI PA JICHI MEDICAL SCHOOL, DEPT PUBLIC HEALTH, 3311-1 YAKUSHIJI, MINAMIKAWACH, TOCHIGI, 329-0498, JAPAN SN 0917-5040 J9 J EPIDEMIOL JI J. Epidemiol. PD JAN PY 2004 VL 14 IS 1 BP 17 EP 22 DI 10.2188/jea.14.17 PG 6 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 803DQ UT WOS:000220212200004 PM 15065688 ER PT J AU Joshi, MB Mallinson, DJ Dwyer, DM AF Joshi, MB Mallinson, DJ Dwyer, DM TI The human pathogen Leishmania donovani secretes a histidine acid phosphatase activity that is resistant to proteolytic degradation SO JOURNAL OF EUKARYOTIC MICROBIOLOGY LA English DT Article DE glycoprotein; hemoflagellate; protease-resistance; protozoan parasite; sandfly-vector; secretory enzyme ID LUTZOMYIA-ANTHOPHORA DIPTERA; CHYMOTRYPSIN-LIKE ENZYMES; PHLEBOTOMUS-PAPATASI; PROTEASE RESISTANCE; VECTOR COMPETENCE; TRYPSIN-LIKE; PROMASTIGOTES; BIOSYNTHESIS; INFECTION; IDENTIFICATION AB Promastigotes of all pathogenic Leishmania species secrete acid phosphatase (SAcP) activity during their growth in vitro. It has been suggested that this enzyme may play a role in the survival of the parasite within its sandfly-vector host. To carry out such functions, SAcP would have to be relatively resistant to endogenous sandfly gut-proteases. Therefore, the current study was undertaken to ascertain whether L. donovani SAcP activity was affected by treatment with various proteases. Native L. donovani SAcP was treated with a variety of serine, thiol-, metallo- and mixed-proteases and subsequently assayed for enzymatic activity. Of the eleven proteases tested, only bromelain and subtilisin treatments caused a pronounced reduction in SAcP activity. Treatment of SAcP with seven out of the remaining nine proteases, resulted in an overall enhancement in SAcP enzymatic activity ranging from similar to 10% (e.g. with trypsin) to greater than or equal to 90% (e.g. with ficin). The resistance of the Leishmania SAcP to various proteases may prolong its functional life within the sandfly gut and help to facilitate parasite infection in this host. C1 NIAID, Cell Biol Sect, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA. RP Dwyer, DM (reprint author), NIAID, Cell Biol Sect, Parasit Dis Lab, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. EM Ddwyer@niaid.nih.gov NR 34 TC 8 Z9 8 U1 1 U2 2 PU SOC PROTOZOOLOGISTS PI LAWRENCE PA 810 E 10TH ST, LAWRENCE, KS 66044 USA SN 1066-5234 J9 J EUKARYOT MICROBIOL JI J. Eukaryot. Microbiol. PD JAN-FEB PY 2004 VL 51 IS 1 BP 108 EP 112 DI 10.1111/j.1550-7408.2004.tb00171.x PG 5 WC Microbiology SC Microbiology GA 775GH UT WOS:000189032000013 PM 15068272 ER PT J AU Colt, JS Lubin, J Camann, D Davis, S Cerhan, J Severson, RK Cozen, W Hartge, P AF Colt, JS Lubin, J Camann, D Davis, S Cerhan, J Severson, RK Cozen, W Hartge, P TI Comparison of pesticide levels in carpet dust and self-reported pest treatment practices in four US sites SO JOURNAL OF EXPOSURE ANALYSIS AND ENVIRONMENTAL EPIDEMIOLOGY LA English DT Article DE pesticides; carpet dust; questionnaires; exposure assessment ID HOUSEHOLD DUST; EXPOSURE; CHILDREN; CHLORPYRIFOS AB Epidemiologic studies have used both questionnaires and carpet dust sampling to assess residential exposure to pesticides. The consistency of the information provided by these two approaches has not been explored. In a population-based case-control study of non-Hodgkin's lymphoma, carpet dust samples were collected from the homes of 513 control subjects in Detroit, Iowa, Los Angeles, and Seattle. The samples were taken from used vacuum cleaner bags and analyzed for 30 pesticides. Interviewers queried subjects about the types of pests treated in their home using a detailed questionnaire accompanied by visual aids. Geographic variations in pesticide levels were generally consistent with geographic differences in pest treatment practices. Los Angeles residents reported the most treatment for crawling insects, fleas/ticks, and termites, and Los Angeles dust samples had the highest levels of propoxur, chlorpyrifos, diazinon, permethrin, and chlordane. Iowa had the most treatment for lawn/garden weeds, and also the highest levels of 2,4-dichlorophenoxyacetic acid and dicamba. Although Seattle had the highest proportion of subjects treating for lawn/garden insects, the lawn/garden insecticides were higher in other sites. Multivariate linear regression revealed several significant associations between the type of pest treated and dust levels of specific pesticides. The strongest associations were between termite treatment and chlordane, and flea/tick treatment and permethrin. Most of the significant associations were consistent with known uses of the pesticides; few expected associations were absent. The consistency between the questionnaire data and pesticide residues measured in dust lends credibility to both methods for assessing residential exposure to pesticides. The combined techniques appear promising for epidemiologic studies. Interviewing is the only way to assess pesticide exposures before current carpets were in place. Dust sampling provides an objective measure of specific compounds to which a person may have been exposed through personal use of a pesticide or by drift-in or track-in from outside, and avoids recall bias. C1 NCI, Div Canc Epidemiol & Genet, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. SW Res Inst, San Antonio, TX USA. Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. Univ Washington, Seattle, WA 98195 USA. Mayo Clin, Rochester, MN USA. Wayne State Univ, Karmanos Canc Inst, Detroit, MI USA. Wayne State Univ, Dept Family Med, Detroit, MI USA. Univ So Calif, Los Angeles, CA USA. RP Colt, JS (reprint author), NCI, Occupat Epidemiol Branch, 6120 Execut Blvd,Room 8112, Rockville, MD 20852 USA. EM coltj@mail.nih.gov OI Cerhan, James/0000-0002-7482-178X NR 24 TC 72 Z9 73 U1 3 U2 11 PU NATURE PUBLISHING GROUP PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 1053-4245 J9 J EXPO ANAL ENV EPID JI J. Expo. Anal. Environ. Epidemiol. PD JAN PY 2004 VL 14 IS 1 BP 74 EP 83 DI 10.1038/sj.jea.7500307 PG 10 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA 764UF UT WOS:000188223900005 PM 14726946 ER PT J AU Li, J Zheng, CY Zhang, X Liu, XY Zhang, CM Goldsmith, CM Baum, BJ Wang, SL AF Li, J Zheng, CY Zhang, X Liu, XY Zhang, CM Goldsmith, CM Baum, BJ Wang, SL TI Devetoping a convenient targe animal model for gene transfer to sativary gtands in vivo SO JOURNAL OF GENE MEDICINE LA English DT Article DE gene transfer; adenovirus; miniature pig; parotid gland; salivary glands ID ADENOVIRUS-MEDIATED TRANSFER; RAT SALIVARY-GLANDS; PORCINE MODEL; RECOMBINANT ADENOVIRUS; BASEMENT-MEMBRANE; AQUAPORIN-1 CDNA; PROTEIN; SAFETY; CELLS AB Background Localized gene transfer to salivary glands has great potential for the treatment of salivary gland, systemic, and oral diseases. The minipig parotid gland, given its volume and morphological similarities to the human parotid gland, may be useful as a large animal model for pre-clinical gene transfer experiments. The purpose of this study was to perform an initial assessment of the efficacy and safety of adenoviral-vector-mediated gene transfer to parotid glands of miniature pigs. Methods AdCMVluc, a recombinant type 5 adenoviral (rAd5) vector was administered to miniature pig containing a luciferase reporter gene, parotid glands by intraductal cannulation. Five regions of gland tissue were obtained to measure the distribution of luciferase activity. The effects of time, viral dose, infusate buffer volume, and gland anatomical region on transgene expression were determined. Detailed serum chemistry and hematological analyses were performed. in addition, AdCMVlacZ, a similar rAd5 vector encoding beta-galactosidase, was also delivered to determine the parotid gland cell types transduced. Results Luciferase assays indicated that gene transfer to miniature pig salivary glands could be readily accomplished using rAd5 vectors. Highest transgene expression was found in the center of glands, which was > posterior > inferior > anterior > superior tissue regions. Expression was maximal on day 2 and declined to background by day 14, and observed in both acinar and ductal cells. Several serum chemistry and hematology parameters were transiently changed following rAd5 administration. Conclusions Transgene expression by, and inflammatory response to, rAd5 vectors in minipig parotid glands are similar to results seen earlier in rodent studies. This suggests that results of salivary gland gene transfer from rodent studies can be extended to a larger animal model, and supports the value of using minipigs for pre-clinical applications of gene transfer to these tissues. Published in 2004 by John Wiley Sons, Ltd. C1 NIDCR, GTTB, NIH, DHHS, Bethesda, MD 20892 USA. Capital Univ Med Sci, Fac Stomatol, Salivary Gland Dis Ctr, Beijing, Peoples R China. Capital Univ Med Sci, Fac Stomatol, Mol Lab Gene Therapy, Beijing, Peoples R China. RP Baum, BJ (reprint author), NIDCR, GTTB, NIH, DHHS, Bldg 10,Rm 1N113, Bethesda, MD 20892 USA. EM bbaum@dir.nider.nih.gov; songlinwang@dentist.org.cn NR 23 TC 30 Z9 34 U1 1 U2 3 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 1099-498X J9 J GENE MED JI J. Gene. Med. PD JAN PY 2004 VL 6 IS 1 BP 55 EP 63 DI 10.1002/jbm.476 PG 9 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 769QU UT WOS:000188661900006 PM 14716677 ER PT J AU Whitby, D Marshall, VA Bagni, RK Wang, CD Gamache, CJ Guzman, JR Kron, M Ebbesen, P Biggar, RJ AF Whitby, D Marshall, VA Bagni, RK Wang, CD Gamache, CJ Guzman, JR Kron, M Ebbesen, P Biggar, RJ TI Genotypic characterization of Kaposi's sarcoma-associated herpesvirus in asymptomatic infected subjects from isolated populations SO JOURNAL OF GENERAL VIROLOGY LA English DT Article ID DNA-SEQUENCES; HUMAN-HERPESVIRUS-8 INFECTION; MULTIPLE LOCI; AFRICA; VARIABILITY; PREVALENCE; ANTIBODIES; STRAINS; VIRUS; AIDS AB Molecular epidemiological studies of Kaposi's sarcoma-associated herpesvirus (KSHV) have concentrated on characterization of viral strains in tumour biopsy samples from Kaposi's sarcoma (KS) patients, mostly obtained in the United States and Europe. Tumour biopsies are a convenient source of viral DNA, as they have a high viral load compared to peripheral blood. However, sequences obtained from biopsies may not be representative of viral strains in asymptomatic subjects and information on ethnicity is often not available. Here, a population-based approach has been used to study the molecular and seroepidemiology of KSHV in isolated populations in Ecuador and Botswana. Amerindians in Ecuador had a variable prevalence of KSHV and all strains characterized were of subtype E, based on K1 sequencing. All Amerindian strains had predominant (P)-type K15 alleles and had sequences in both TO.7 and ORF 75 that appeared to be characteristic of these strains. The prevalence of KSHV in two ethnic groups in Botswana was extremely high. K1 sequences from both Bantu and San subjects were mostly of subtypes B and A5, which are typical of African KSHV strains, but the sequence from one San subject did not cluster with any known subtype. Considerable heterogeneity was seen in the TO. 7 and ORF 75 genes in the San subjects and one had a minor (M)-type K1 5 allele. The heterogeneity of the KSHV strains found in these subjects from Botswana contrasts with the homogeneity of KSHV strains in Amerindians, reflecting differences in the evolutionary history of these populations. C1 NCI, AIDS Vaccine Program, Viral Epidemiol Sect, SAIC Frederick, Frederick, MD 21701 USA. Univ Guayaquil, Natl Ctr Trop Med, Guayaquil, Ecuador. Michigan State Univ, Div Infect Dis, Dept Med, E Lansing, MI 48824 USA. Univ Aalborg, Dept Hlth Sci & Technol, Lab Stem Cell Res, Aalborg, Denmark. NCI, Viral Epidemiol Branch, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. RP Whitby, D (reprint author), NCI, AIDS Vaccine Program, Viral Epidemiol Sect, SAIC Frederick, Frederick, MD 21701 USA. EM whitbyd@ncifcrf.gov FU NCI NIH HHS [N01-CO-12400] NR 33 TC 56 Z9 63 U1 0 U2 1 PU SOC GENERAL MICROBIOLOGY PI READING PA MARLBOROUGH HOUSE, BASINGSTOKE RD, SPENCERS WOODS, READING RG7 1AG, BERKS, ENGLAND SN 0022-1317 J9 J GEN VIROL JI J. Gen. Virol. PD JAN PY 2004 VL 85 BP 155 EP 163 DI 10.1099/vir.0.19465-0 PN 1 PG 9 WC Biotechnology & Applied Microbiology; Virology SC Biotechnology & Applied Microbiology; Virology GA 770BT UT WOS:000188703900018 PM 14718630 ER PT J AU Haider, M Kreps, GL AF Haider, M Kreps, GL TI Forty years of Diffusion of Innovations: Utility and value in public health SO JOURNAL OF HEALTH COMMUNICATION LA English DT Article; Proceedings Paper CT Conference on Forty Years of Diffusion of Innovations CY APR 02, 2002 CL George Washington Univ, Sch Public Hlth, WASHINGTON, DC HO George Washington Univ, Sch Public Hlth AB This special issue is created to mark the 40th anniversary of Everett Rogers' Diffusion of Innovations (DOI) model. Diffusion is the process through which an innovation, defined as an idea perceived as new, spreads via certain communication channels over time among the members of a particular social system. A great deal of research in a variety of academic disciplines (about 5000 published studies so far) has been conducted on the diffusion of innovations over the past six decades. The areas of application for these studies range from hybrid seed corn to modem math, to the snowmobile to antibiotic drugs, to HIV/AIDS prevention (Rogers, 1995). These investigations have led to a general model of the diffusion of innovations, which can be applied to the recent spread of the Internet or to any other new idea. Everett Roger's ground-breaking model has contributed to a greater understanding of behavioral change, including the variation in rates of adoption of innovations, and it has held a broad scope of practical applications in the field of public health. C1 George Washington Univ, Sch Publ Hlth & Hlth Serv, Dept Global Hlth, Washington, DC 20052 USA. NCI, Hlth Commun & Informat Res Branch, Bethesda, MD 20892 USA. RP Haider, M (reprint author), George Washington Univ, Sch Publ Hlth & Hlth Serv, Dept Global Hlth, Washington, DC 20052 USA. NR 2 TC 44 Z9 46 U1 2 U2 17 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1081-0730 J9 J HEALTH COMMUN JI J. Health Commun. PY 2004 VL 9 SU 1 BP 3 EP 11 DI 10.1080/10810730490271430 PG 9 WC Communication; Information Science & Library Science SC Communication; Information Science & Library Science GA 802EO UT WOS:000220147000002 PM 14960400 ER PT J AU Johnson, WE Godoy, JA Palomares, F Delibes, M Fernandes, M Revilla, E O'Brien, SJ AF Johnson, WE Godoy, JA Palomares, F Delibes, M Fernandes, M Revilla, E O'Brien, SJ TI Phylogenetic and phylogeographic analysis of Iberian lynx populations SO JOURNAL OF HEREDITY LA English DT Article ID FELIS-PARDINA TEMMINCK; MITOCHONDRIAL-DNA; EVOLUTION; SUBDIVISION; SPAIN; CATUS; MICROSATELLITES; METAPOPULATION; DIVERGENCE; LANDSCAPE AB The Iberian lynx (Lynx pardinus), one of the world's most endangered cat species, is vulnerable due to habitat loss, increased fragmentation of populations, and precipitous demographic reductions. An understanding of Iberian lynx evolutionary history is necessary to develop rational management plans for the species. Our objectives were to assess Iberian lynx genetic diversity at three evolutionary timescales. First we analyzed mitochondrial DNA (mtDNA) sequence variation to position the Iberian lynx relative to other species of the genus Lynx. We then assessed the pattern of mtDNA variation of isolated populations across the Iberian Peninsula. Finally we estimated levels of gene flow between two of the most important remaining lynx populations (Donana National Park and the Sierra Morena Mountains) and characterized the extent of microsatellite locus variation in these populations. Phylogenetic analyses of 1613 bp of mtDNA sequence variation supports the hypothesis that the Iberian lynx, Eurasian lynx, and Canadian lynx diverged within a short time period around 1.53-1.68 million years ago, and that the Iberian lynx and Eurasian lynx are sister taxa. Relative to most other felid species, genetic variation in mtDNA genes and nuclear microsatellites were reduced in Iberian lynx, suggesting that they experienced a fairly severe demographic bottleneck. In addition, the effects of more recent reductions in gene flow and population size are being manifested in local patterns of molecular genetic variation. These data, combined with recent studies modeling the viability of Iberian lynx populations, should provide greater urgency for the development and implementation of rational in situ and ex situ conservation plans. C1 NCI, Lab Genom Divers, FCRDC, Frederick, MD 21702 USA. CSIC, Dept Appl Biol, Estac Biol Donana, Seville 41013, Spain. Inst Conservacao Nat, P-1050114 Lisbon, Portugal. RP Johnson, WE (reprint author), NCI, Lab Genom Divers, FCRDC, Frederick, MD 21702 USA. RI Revilla, Eloy/B-5100-2008; Godoy, Jose A./B-9288-2008; Johnson, Warren/D-4149-2016; CSIC, EBD Donana/C-4157-2011; Palomares, Francisco/F-5327-2016; Delibes, Miguel/K-2744-2014; OI Revilla, Eloy/0000-0001-5534-5581; Godoy, Jose A./0000-0001-7502-9471; Johnson, Warren/0000-0002-5954-186X; CSIC, EBD Donana/0000-0003-4318-6602; Palomares, Francisco/0000-0002-4655-7205; Delibes, Miguel/0000-0002-3569-567X; Fernandes, Margarida/0000-0001-9239-1202 NR 62 TC 55 Z9 57 U1 3 U2 48 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0022-1503 EI 1465-7333 J9 J HERED JI J. Hered. PD JAN PY 2004 VL 95 IS 1 BP 19 EP 28 DI 10.1093/jhered/esh006 PG 10 WC Evolutionary Biology; Genetics & Heredity SC Evolutionary Biology; Genetics & Heredity GA 771QQ UT WOS:000188797900003 PM 14757726 ER PT J AU Maasho, K Marusina, A Reynolds, NM Coligan, JE Borrego, F AF Maasho, K Marusina, A Reynolds, NM Coligan, JE Borrego, F TI Efficient gene transfer into the human natural killer cell line, NKL, using the Amaxa nucleofection system (TM) SO JOURNAL OF IMMUNOLOGICAL METHODS LA English DT Article DE natural killer cells; NKL; nucleofection; transfection ID GREEN FLUORESCENT PROTEIN; HEMATOPOIETIC-CELLS; NONVIABLE CELLS; MAMMALIAN-CELLS; EXPRESSION; ELECTROPORATION; CYTOTOXICITY; VECTORS; DNA AB Natural killer (NK) cell lines are useful for studying facets of NK cell biology. Such cell lines are notoriously difficult to transfect by traditional methods, a fact that has hampered NK cell biology studies for a long time. To overcome this, we investigated the use of the Amaxa nucleofection system(TM) that directly transfers DNA into the nucleus of the cell. This technology has revolutionized. transfection studies with heretofore relatively transfection resistant cell types such as T cells, B cells and dendritic cells. Despite these advances, NK cells and NK cell lines have remained relatively resistant to transfection, including nucleofection. In this study we employed cDNA for SHP1 and various Rab proteins cloned in enhanced green/yellow fluorescent protein (EGFP/EYFP) expression plasmids for transient transfections into NKL cells. The expression of EGFP/EYFP fusion proteins was analyzed by flow cytometry, immunoblot and confocal microscopic analyses. We achieved 40-70% transfection efficiency with high levels of expression in this cell line with 85-90% viability. The method used in this report proves to be far superior to existing methods for delivering DNA into this well studied NK cell line and, consequently, provides new experimental opportunities. Published by Elsevier B.V. C1 NIAID, Receptor Cell Biol Sect, Lab Allerg Dis, NIH, Rockville, MD 20852 USA. RP Coligan, JE (reprint author), NIAID, Receptor Cell Biol Sect, Lab Allerg Dis, NIH, 12441 Parklawn Dr,Room 205, Rockville, MD 20852 USA. EM jcoligan@niaid.nih.gov NR 25 TC 62 Z9 67 U1 0 U2 4 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0022-1759 J9 J IMMUNOL METHODS JI J. Immunol. Methods PD JAN PY 2004 VL 284 IS 1-2 BP 133 EP 140 DI 10.1016/j.jim.2003.10.010 PG 8 WC Biochemical Research Methods; Immunology SC Biochemistry & Molecular Biology; Immunology GA 768YJ UT WOS:000188598400013 PM 14736423 ER PT J AU Wang, DH Yuan, RW Feng, Y El-Asady, R Farber, DL Gress, RE Lucas, PJ Hadley, GA AF Wang, DH Yuan, RW Feng, Y El-Asady, R Farber, DL Gress, RE Lucas, PJ Hadley, GA TI Regulation of CD103 expression by CD8(+) T cells responding to renal allografts SO JOURNAL OF IMMUNOLOGY LA English DT Article ID GROWTH-FACTOR-BETA; LYMPHOCYTES-T; TGF-BETA; HISTOCOMPATIBILITY ANTIGENS; EPITHELIAL-CELLS; E-CADHERIN; REJECTION; INTEGRIN; MICE; RECEPTOR AB CD103 is an integrin with specificity for the epithelial cell-specific ligand, E-cadherin. Recent studies indicate that CD103 expression endows peripheral CD8 cells with a unique capacity to access the epithelial compartments of organ allografts. In the present study we used a nonvascularized mouse renal allograft model to 1) define the mechanisms regulating CD103 expression by graft-infiltrating CD8 effector populations, and 2) identify the cellular compartments in which this occurs. We report that CD8 cells responding to donor alloantigens in host lymphoid compartments do not initially express CD103, but dramatically upregulate CD103 expression to high levels subsequent to migration to the graft site. CD103(+)CD8(+) cells that infiltrated renal allografts exhibited a classic effector phenotype and were selectively localized to the graft site. CD8 cells expressing low levels of CD103 were also present in lymphoid compartments, but three-color analyses revealed that these are almost exclusively of naive phenotype. Adoptive transfer studies using TCR-transgenic CD8 cells demonstrated that donor-specific CD8 cells rapidly and uniformly up-regulate CD103 expression following entry into the graft site. Donor-specific CD8 cells expressing a dominant negative TGF-beta receptor were highly deficient in CD103 expression following migration to the graft, thereby implicating TGF-beta activity as a dominant controlling factor. The relevance of these data to conventional (vascularized) renal transplantation is confirmed. These data support a model in which TGF-beta activity present locally at the graft site plays a critical role in regulating CD103 expression, and hence the epitheliotropism, of CD8 effector populations that infiltrate renal allografts. C1 Univ Maryland, Sch Med, Med Sch Teaching Facil, Dept Surg, Baltimore, MD 21201 USA. Univ Maryland, Sch Med, Dept Microbiol & Immunol, Baltimore, MD 21201 USA. NCI, Expt Immunol Branch, NIH, Bethesda, MD 20892 USA. RP Hadley, GA (reprint author), Univ Maryland, Sch Med, Med Sch Teaching Facil, Dept Surg, Room 400,10 S Pine St, Baltimore, MD 21201 USA. EM ghadley@smail.umaryland.edu FU NIAID NIH HHS [AI 36532] NR 35 TC 39 Z9 41 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 JAN 1 PY 2004 VL 172 IS 1 BP 214 EP 221 PG 8 WC Immunology SC Immunology GA 755TN UT WOS:000187427700030 PM 14688328 ER PT J AU Cherukuri, A Shoham, T Sohn, HW Levy, S Brooks, S Carter, R Pierce, SK AF Cherukuri, A Shoham, T Sohn, HW Levy, S Brooks, S Carter, R Pierce, SK TI The tetraspanin CD81 is necessary for partitioning of coligated CD19/CD21-B cell antigen receptor complexes into signaling-active lipid rafts SO JOURNAL OF IMMUNOLOGY LA English DT Article ID HUMORAL IMMUNE-RESPONSE; B-CELLS; ANTIPROLIFERATIVE ANTIBODY; EXTRACELLULAR DOMAIN; CD81-DEFICIENT MICE; ACQUIRED-IMMUNITY; CROSS-LINKING; LYMPHOCYTES; TRANSDUCTION; COMPLEMENT AB Tetraspanins have been hypothesized to facilitate the organization of functional multimolecular membrane complexes. In B cells the tetraspanin CD81 is a component of the CD19/CD21 complex. When coligated to the B cell Ag receptor (BCR), the CD19/CD21 complex significantly enhances BCR signaling in part by prolonging the association of the BCR with signaling-active lipid rafts. In this study CD81 is shown to associate with lipid rafts upon coligation of the BCR and the CD19/CD21 complex. Using B cells from CD81-deficient mice we demonstrate that in the absence of CD81, coligated BCR and CD19/CD21 complexes fail to partition into lipid rafts and enhance BCR signaling from rafts. Furthermore, a chimeric CD19 protein that associates only weakly if at all with CD81 fails to promote the association of coligated BCR with lipid rafts. The requirement for CD81 to promote lipid raft association may define a novel mechanism by which tetraspanins function as molecular facilitators of signaling receptors. C1 NIAID, Immunogenet Lab, NIH, Rockville, MD 20852 USA. Stanford Univ, Sch Med, Dept Med, Div Oncol, Stanford, CA 94305 USA. Univ Alabama, Dept Med, Birmingham, AL 35294 USA. Univ Alabama, Dept Microbiol, Birmingham, AL 35294 USA. RP Pierce, SK (reprint author), NIAID, Immunogenet Lab, NIH, Twinbrook 2,12441 Parklawn Dr,Room 200B,MSC 8180, Rockville, MD 20852 USA. EM spierce@nih.gov FU NCI NIH HHS [CA 34233]; NIAID NIH HHS [AI 07051, AI 42265, AI 45900, T32 AI007051] NR 46 TC 90 Z9 92 U1 1 U2 5 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD JAN 1 PY 2004 VL 172 IS 1 BP 370 EP 380 PG 11 WC Immunology SC Immunology GA 755TN UT WOS:000187427700047 PM 14688345 ER PT J AU Itagaki, K Kannan, KB Singh, BB Hauser, CJ AF Itagaki, K Kannan, KB Singh, BB Hauser, CJ TI Cytoskeletal reorganization internalizes multiple transient receptor potential channels and blocks calcium entry into human neutrophils SO JOURNAL OF IMMUNOLOGY LA English DT Article ID CAPACITATIVE CA2+ ENTRY; INOSITOL TRISPHOSPHATE RECEPTOR; MAMMALIAN TRP HOMOLOGS; STORE DEPLETION; CATION CHANNELS; FUNCTIONAL EXPRESSION; SIGNALING COMPLEX; DROSOPHILA TRP; INFLUX; CELLS AB DStore-operated calcium entry (SOCE) is required for polymorphonuclear neutrophil (PMN) activation in response to G protein-coupled agonists. Some immunocytes express proteins homologous to the Drosophila transient receptor potential gene (trp) calcium channel. TRP proteins assemble into heterotetrameric ion channels and are known to support SOCE in overexpression systems, but the evidence that TRP proteins support SOCE and are functionally important in wild-type cells remains indirect. We therefore studied the expression and function of TRP proteins in primary human PMN. TRPC1, TRPC3, TRPC4, and TRPC6 were all expressed as mRNA as well as membrane proteins. Immunofluorescence microscopy demonstrated localization of TRPC1, TRPC3, and TRPC4 to the PMN cell membrane and their internalization after cytoskeletal reorganization by calyculin A (CalyA). Either TRPC internalization by CalyA or treatment with the inositol triphosphate receptor inhibitor 2-aminoethoxydiphenyl borane resulted in the loss of PMN SOCE. Cytochalasin D (CytoD) disrupts actin filaments, thus preventing cytoskeletal reorganization, and pretreatment with CytoD rescued PMN SOCE from inhibition by CalyA. Comparative studies of CytoD and 2-aminoethoxydiphenyl borane inhibition of PMN cationic entry after thapsigargin or platelet-activating factor suggested that SOCE occurs through both calcium-specific and nonspecific pathways. Taken together, these studies suggest that the multiple TRPC proteins expressed by human PMN participate in the formation of at least two store-operated calcium channels that have differing ionic permeabilities and regulatory characteristics. C1 Univ Med & Dent New Jersey, Sch Med, Dept Surg, Newark, NJ 07103 USA. NIH, Physiol Sect, Bethesda, MD 20892 USA. RP Hauser, CJ (reprint author), Univ Med & Dent New Jersey, Sch Med, Dept Surg, MSB G-524,185 S Orange Ave, Newark, NJ 07103 USA. EM hausercj@umdnj.edu OI Singh, Brij/0000-0003-0535-5997 FU NIDCR NIH HHS [R01 DE017102, R01 DE017102-01A1, R01 DE017102-02, R01 DE017102-03, R01 DE017102-04, R01 DE017102-05, R01 DE017102-06A1, R01 DE017102-07]; NIGMS NIH HHS [GM 59179] NR 52 TC 49 Z9 51 U1 0 U2 1 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD JAN 1 PY 2004 VL 172 IS 1 BP 601 EP 607 PG 7 WC Immunology SC Immunology GA 755TN UT WOS:000187427700074 PM 14688372 ER PT J AU Kobayashi, SD Voyich, JM Braughton, KR Whitney, AR Nauseef, WM Malech, HL DeLeo, FR AF Kobayashi, SD Voyich, JM Braughton, KR Whitney, AR Nauseef, WM Malech, HL DeLeo, FR TI Gene expression profiling provides insight into the pathophysiology of chronic granulomatous disease SO JOURNAL OF IMMUNOLOGY LA English DT Article ID HUMAN POLYMORPHONUCLEAR LEUKOCYTES; INGESTED APOPTOTIC CELLS; NEUTROPHIL APOPTOSIS; ENHANCED APOPTOSIS; CYTOCHROME-B; METALLOTHIONEIN; INFLAMMATION; MACROPHAGES; PROTEIN; IDENTIFICATION AB Human polymorphonuclear leukocytes (PMNs or neutrophils) kill invading microorganisms with reactive oxygen species (ROS) and cytotoxic granule components. PMNs from individuals with X-linked chronic granulomatous disease (XCGD) do not produce ROS, thereby rendering these individuals more susceptible to infection. In addition, XCGD patients develop tissue granulomas that obstruct vital organs, the mechanism(s) for which are unknown. To gain insight into the molecular processes that contribute to the pathophysiology of XCGD, including formation of granulomas, we compared global gene expression in PMNs from XCGD patients and healthy control individuals. Genes encoding mediators of inflammation and host defense, including CD11c, CD14, CD54, FcgammaR1, FcalphaR, CD120b, TLR5, IL-4R, CCR1, p47(phox), p40(phox), IL-8, CXCL1, Nramp1, and calgranulins A and B; were up-regulated constitutively in unstimulated XCGD patient PMNs. By comparing transcript levels in normal and XCGD PMNs after phagocytosis, we discovered 206 genes whose expression changed in the presence and the absence of ROS, respectively. Notably, altered Bcl2-associated X protein synthesis accompanied defective neutrophil apoptosis in XCGD patients. We hypothesize that granuloma formation in XCGD patients reflects both increased proinflammatory activity and defective PMN apoptosis, and we conclude that ROS contribute directly or indirectly to the resolution of the inflammatory response by influencing PMN gene transcription. C1 NIAID, Rocky Mt Lab, Lab Human Bacterial Pathogenesis, NIH, Hamilton, MT 59840 USA. Univ Iowa, Inflammat Program, Coralville, IA 52241 USA. Iowa City Vet Adm Med Ctr, Coralville, IA 52241 USA. NIAID, Lab Host Defences, NIH, Bethesda, MD 20892 USA. RP DeLeo, FR (reprint author), NIAID, Rocky Mt Lab, Lab Human Bacterial Pathogenesis, NIH, 903 S 4th St, Hamilton, MT 59840 USA. EM fdeleo@niaid.nih.gov OI DeLeo, Frank/0000-0003-3150-2516 FU BLRD VA [I01 BX000513]; NIAID NIH HHS [AI 34879-15] NR 41 TC 97 Z9 104 U1 0 U2 1 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD JAN 1 PY 2004 VL 172 IS 1 BP 636 EP 643 PG 8 WC Immunology SC Immunology GA 755TN UT WOS:000187427700078 PM 14688376 ER PT J AU Powell, DJ Rosenberg, SA AF Powell, DJ Rosenberg, SA TI Phenotypic and functional maturation of tumor antigen-reactive CD8(+) T lymphocytes in patients undergoing multiple course peptide vaccination SO JOURNAL OF IMMUNOTHERAPY LA English DT Article DE human antigen/peptide/epitope; vaccination; tumor immunity; T lymphocytes; differentiation ID MELANOMA PATIENTS; IN-VIVO; SYNTHETIC PEPTIDES; IMMUNE-RESPONSE; CELL RESPONSES; GP100; EPITOPES; MEMORY; CTL; ACTIVATION AB Successful immunotherapy with peptide vaccines depends on the in vivo generation of sufficient numbers of anti-tumor T cells with appropriate phenotypic and functional characteristics to mediate tumor destruction. Herein, we report the induction of high frequencies of circulating CD8(+) T cells (4.8% to 38.1%) directed against the native gp100:209-217 peptide derived from the gp100 melanoma-melanocyte tumor antigen in five HLA-A*0201 patients at high risk of recurrence of melanoma after multiple courses of immunization with modified gp100:209-217(210M) peptide in IFA. Longitudinal peripheral blood mononuclear cell (PBMC) analysis revealed a phenotypic shift of native peptide-specific CD8(+) T cells from an early effector to an effector memory (CD27(-) CD28(-) CD62L(-) CD45RO(+)) phenotype with repeated immunizations and functional maturation that correlated with gp100:209-217 peptide-specific T-cell precursor frequencies. Postimmunization PBMC exhibited direct ex vivo recognition of melanoma cell lines in ELISPOT analysis, showed lytic capability against peptide-pulsed target cells, and proliferated in response to native peptide stimulation. One year after final immunization, circulating vaccine-specific CD8(+) T cells persisted in patients' PBMC with a maintained effector memory phenotype. The results herein demonstrate the efficacy of a multiple course peptide-immunization strategy for the generation of high frequencies of tumor antigen-specific T cells in vivo, and further show that continued peptide immunization results in the escalating generation of functionally mature, tumor-reactive effector memory CD8(+) T lymphocytes. C1 NCI, Surg Branch, NIH, Bethesda, MD 20892 USA. RP Rosenberg, SA (reprint author), NCI, Surg Branch, NIH, Bldg 10,Room 2B42,10 Ctr Dr,MCS 1502, Bethesda, MD 20892 USA. FU NCI NIH HHS [Z01 SC003811-31] NR 36 TC 56 Z9 60 U1 4 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1053-8550 J9 J IMMUNOTHER JI J. Immunother. PD JAN-FEB PY 2004 VL 27 IS 1 BP 36 EP 47 DI 10.1097/00002371-200401000-00004 PG 12 WC Oncology; Immunology; Medicine, Research & Experimental SC Oncology; Immunology; Research & Experimental Medicine GA 758EF UT WOS:000187619600004 PM 14676632 ER PT J AU Maloney, EM Nagai, M Hisada, M Soldan, SS Goebel, PB Carrington, M Sawada, T Brennan, MB Cranston, B Hanchard, B Jacobson, S AF Maloney, EM Nagai, M Hisada, M Soldan, SS Goebel, PB Carrington, M Sawada, T Brennan, MB Cranston, B Hanchard, B Jacobson, S TI Prediagnostic human T lymphotropic virus type I provirus loads were highest in Jamaican children who developed seborrheic dermatitis and severe anemia SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article; Proceedings Paper CT 10th International Conference on Human Retrovirology CY JUN, 2001 CL DUBLIN, IRELAND ID TROPICAL SPASTIC PARAPARESIS; HTLV-I; INFECTIVE DERMATITIS; CELL LEUKEMIA; LYMPHOCYTES; MYELOPATHY; DNA AB In a recent clinical analysis of 308 Jamaican children, human T lymphotropic virus type I (HTLV-I) infection was found to be associated with significantly higher incidence rates of seborrheic dermatitis, eczema, and persistent hyperreflexia of the lower limbs and with nonsignificantly increased rates of severe anemia and abnormal lymphocytes. Results of examination of HTLV-I viral markers in the 28 HTLV-I-infected children provided virologic support for the epidemiologic associations of HTLV-I with seborrheic dermatitis and severe anemia in childhood. C1 NCI, Viral Epidemiol Branch, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. Natl Inst Neurol Disorders & Stroke, Lab Neuroimmunol, Bethesda, MD USA. NCI, Basic Res Program, SAIC Frederick, Frederick, MD 21701 USA. Eisai & Co Ltd, Tsukuba Res Labs, Tsukuba, Ibaraki 30026, Japan. Univ W Indies, Dept Pathol, Kingston 7, Jamaica. RP Maloney, EM (reprint author), NCI, Viral Epidemiol Branch, Div Canc Epidemiol & Genet, 6120 Execut Blvd,EPS-8006,MSC 7248, Rockville, MD 20852 USA. FU NCI NIH HHS [N01-CP31006, N01-CP-33043-21, N01-CP-40548] NR 17 TC 14 Z9 16 U1 0 U2 2 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD JAN 1 PY 2004 VL 189 IS 1 BP 41 EP 45 DI 10.1086/380567 PG 5 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 759DP UT WOS:000187723300006 PM 14702151 ER PT J AU Lei, BF Liu, MY Chesney, GL Musser, JM AF Lei, BF Liu, MY Chesney, GL Musser, JM TI Identification of new candidate vaccine antigens made by Streptococcus pyogenes: Purification and characterization of 16 putative extracellular lipoproteins SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article ID GROUP-A STREPTOCOCCUS; PROTECTIVE IMMUNE-RESPONSES; TOXIC-SHOCK-SYNDROME; BINDING PROTEIN-B; SYNTHETIC PEPTIDE; GENOME SEQUENCE; INTRANASAL IMMUNIZATION; BACTERICIDAL ANTIBODIES; NEISSERIA-MENINGITIDIS; STAPHYLOCOCCUS-AUREUS AB Putative extracellular lipoproteins made by group A Streptococcus ( GAS) are the focus of this study, which was designed to identify new candidate vaccine antigens. Bioinformatic analysis of a serotype M1 GAS strain identified 30 open-reading frames encoding putative lipoproteins. The genes encoding the mature form of 29 of these proteins were cloned, and 16 recombinant proteins were overexpressed in Escherichia coli and purified to apparent homogeneity. The genes encoding these 16 proteins were highly conserved in GAS strains for which genome sequence data are available (serotypes M1, M3, M5, M12, M18, and M28). Mice inoculated subcutaneously with GAS and humans with GAS pharyngitis and invasive infections seroconverted to most of the 16 recombinant proteins, which indicates that these lipoproteins were produced during infection. The blood of mice actively immunized with 5 of the 16 recombinant proteins had significantly (P<.05) increased growth-inhibitory activity, compared with the blood of unimmunized mice, which identified these proteins as potential new vaccine candidates. C1 NIAID, Lab Human Bacterial Pathogenesis, Rocky Mt Labs, NIH, Hamilton, MT 59840 USA. RP Musser, JM (reprint author), NIAID, Lab Human Bacterial Pathogenesis, Rocky Mt Labs, NIH, 903 S 4th St, Hamilton, MT 59840 USA. NR 61 TC 56 Z9 57 U1 0 U2 3 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD JAN 1 PY 2004 VL 189 IS 1 BP 79 EP 89 DI 10.1086/380491 PG 11 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 759DP UT WOS:000187723300012 PM 14702157 ER PT J AU Johnston, JJ Lichter-Konecki, U Wilson, E Cobb, BR Evans, BM Schnur, RE Wong, LJC AF Johnston, JJ Lichter-Konecki, U Wilson, E Cobb, BR Evans, BM Schnur, RE Wong, LJC TI Discordant PKU phenotype in one family due to disparate genotypes and a novel mutation SO JOURNAL OF INHERITED METABOLIC DISEASE LA English DT Article ID PHENYLALANINE-HYDROXYLASE GENE; PRENATAL-DIAGNOSIS; PHENYLKETONURIA; HYPERPHENYLALANINEMIA; INHERITANCE; DISORDERS; SIBLINGS; RFLP; PCR AB Classical phenylketonuria (PKU) and mild hyperphenylalaninaemia (MHP) are two ends of the broad diagnostic spectrum in phenylalanine hydroxylase (PAH) deficiency. We have analysed a family in which classical PKU, MHP and a normal phenotype occurred in family members with different mutations. Sequence analysis revealed three mutations segregating in the family. The individual with classical PKU had two previously reported deleterious mutations. A third novel mutation was identified in the other two individuals. This report demonstrates that when discordant phenotypes occur in a family, without protein loading or phenylalanine tolerance test, complete analysis of the PAH gene may be performed in order to support the diagnosis and assist in accurate genetic counselling and patient management. C1 Georgetown Univ, Med Ctr, Inst Mol & Human Genet, Washington, DC 20007 USA. NHGRI, NIH, Bethesda, MD 20892 USA. Cooper Univ Hosp, Robert Wood Johnson Med Sch, Dept Pediat, Camden, NJ USA. RP Wong, LJC (reprint author), Georgetown Univ, Med Ctr, Inst Mol & Human Genet, M4000,3800 Reservoir Rd NW, Washington, DC 20007 USA. EM wonglj@georgetown.edu FU PHS HHS [273-99-P-0009] NR 15 TC 2 Z9 3 U1 1 U2 2 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0141-8955 J9 J INHERIT METAB DIS JI J. Inherit. Metab. Dis. PY 2004 VL 27 IS 2 BP 157 EP 163 DI 10.1023/B:BOLI.0000028782.39513.20 PG 7 WC Endocrinology & Metabolism; Genetics & Heredity; Medicine, Research & Experimental SC Endocrinology & Metabolism; Genetics & Heredity; Research & Experimental Medicine GA 823ED UT WOS:000221591600005 PM 15159646 ER PT J AU Schueler, UH Kolter, T Kaneski, CR Zirzow, GC Sandhoff, K Brady, RO AF Schueler, UH Kolter, T Kaneski, CR Zirzow, GC Sandhoff, K Brady, RO TI Correlation between enzyme activity and substrate storage in a cell culture model system for Gaucher disease SO JOURNAL OF INHERITED METABOLIC DISEASE LA English DT Article ID CONDURITOL-B-EPOXIDE; LYSOSOMAL STORAGE; GANGLIOSIDE BIOSYNTHESIS; BETA-GLUCOSIDASE; MOUSE; MACROPHAGES; GLUCOCEREBROSIDASE; DEGRADATION; DEFICIENCY; GLYCOSPHINGOLIPIDS AB Gaucher disease, the most common sphingolipidosis, is caused by a decreased activity of glucosylceramide beta-glucosidase, resulting in the accumulation of glucosylceramide in macrophage-derived cells known as Gaucher cells. Much of the storage material is thought to originate from the turnover of cell membranes, such as phagocytosed red and white blood cells. In this study, an in vitro model of Gaucher disease was developed by treating the murine macrophage cell line J774 with a specific inhibitor of glucosylceramide beta-glucosidase, conduritol B-epoxide, and feeding red blood cell ghosts, in order to mimic the disease state. It was found in this model system that glucosylceramide beta-glucosidase activity could be reduced to about 11-15% of the normal control level before increased storage of glucosylceramide occurred. This in vitro system allows insight into the correlation between enzyme activity and lipid storage as predicted by the theory of residual enzyme activity that was proposed by Conzelmann and Sandhoff. C1 Univ Bonn, Kekule Inst Organ Chem & Biochem, D-53121 Bonn, Germany. NINDS, Dev & Metab Neurol Branch, NIH, Bethesda, MD 20892 USA. RP Schueler, UH (reprint author), Univ Bonn, Kekule Inst Organ Chem & Biochem, Gerhard Domagk Str 1, D-53121 Bonn, Germany. OI Kaneski, Christine/0000-0003-1453-2502 NR 35 TC 65 Z9 67 U1 0 U2 1 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0141-8955 J9 J INHERIT METAB DIS JI J. Inherit. Metab. Dis. PY 2004 VL 27 IS 5 BP 649 EP 658 DI 10.1023/B:BOLI.0000042959.44318.7c PG 10 WC Endocrinology & Metabolism; Genetics & Heredity; Medicine, Research & Experimental SC Endocrinology & Metabolism; Genetics & Heredity; Research & Experimental Medicine GA 857EX UT WOS:000224100100012 PM 15669681 ER PT J AU Hanley, WB Azen, C Koch, R Michals-Matalon, K AF Hanley, WB Azen, C Koch, R Michals-Matalon, K TI Maternal phenylketonuria collaborative study (MPKUCS) - The 'outliers' SO JOURNAL OF INHERITED METABOLIC DISEASE LA English DT Article ID FETAL ALCOHOL SYNDROME; MILD HYPERPHENYLALANINEMIA; UNTREATED PREGNANCIES; INTERNATIONAL SURVEY; BIRTH-DEFECTS; PROTECTS; SISTERS; ALLELE AB Analysis of outcome data from 305 of the 414 offspring from the Maternal Phenylketonuria Collaborative Study (MPKUCS), plus 70 control offspring, revealed significant deficits in the IQ (intelligence quotient), as measured by the Wechsler Intelligence Scale for Children-Revised (WISC-R), when maternal metabolic control during pregnancy was delayed and/or inadequate. There were, however, 23 'outliers' (7.5% of the 305) in which the offspring's intellectual IQ was worse (n=10) or better (n=13) than expected. The aim of this study was to determine whether collection parameters were incomplete or whether these subjects were true biological variants influenced by other undetected factors or, perhaps, by modifier genes. Among the 10 offspring whose intellectual functioning was worse than expected, additional complications were uncovered that could explain the poor outcome. Four of the 13 offspring with higher than expected IQ had mothers with mild variants of PKU in which the insult to the fetus would not be expected to be as profound. For the other nine offspring whose intellectual performance was better than expected, there was no explanation, based on the parameters studied. We hypothesize that modifier genes will, at times, protect the fetus despite high maternal concentrations of phenylalanine. Not all offspring from the same (untreated) PKU mother may be similarly affected. Finding the source of these modifiers might effect the treatment of MPKU. C1 Hosp Sick Children, Div Clin & Metab Genet, PKU Programme, Toronto, ON M5G 1X8, Canada. Childrens Hosp Los Angeles, Div Med Genet, PKU Program, Los Angeles, CA 90027 USA. Univ Texas, Med Branch, Dept Pediat, Galveston, TX 77550 USA. Childrens Hosp Reutlingen, Reutlingen, Germany. Childrens Hosp, Boston, MA 02115 USA. NICHHD, Mental Retardat & Dev Disabil Branch, Bethesda, MD 20892 USA. RP Hanley, WB (reprint author), Hosp Sick Children, Div Clin & Metab Genet, PKU Programme, Room 11101 A,Elm Wing,555 Univ Ave, Toronto, ON M5G 1X8, Canada. EM whanley@sickkids.ca FU NICHD NIH HHS [N01-HD-2-3149, N01-HD-2-3155, N01-HD-3156, N01-HD-2-3148] NR 34 TC 4 Z9 6 U1 0 U2 1 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0141-8955 J9 J INHERIT METAB DIS JI J. Inherit. Metab. Dis. PY 2004 VL 27 IS 6 BP 711 EP 723 DI 10.1023/B:BOLI.0000045758.86492.54 PG 13 WC Endocrinology & Metabolism; Genetics & Heredity; Medicine, Research & Experimental SC Endocrinology & Metabolism; Genetics & Heredity; Research & Experimental Medicine GA 865KW UT WOS:000224702700001 PM 15505376 ER PT J AU Ortega, JD Leon, F Alonso, JM Llamazares, AA Rodan, E Robledo, T Mesa, M Bootello, A Martinez-Cocera, C AF Ortega, JD Leon, F Alonso, JM Llamazares, AA Rodan, E Robledo, T Mesa, M Bootello, A Martinez-Cocera, C TI Flurocytometric analysis of induced sputum cells in an asthmatic population SO JOURNAL OF INVESTIGATIONAL ALLERGOLOGY AND CLINICAL IMMUNOLOGY LA English DT Article DE induced sputum; asthma; ECP; adhesion molecules; CD23; CD25; lymphocytes; eosinophils ID INVESTIGATE AIRWAY INFLAMMATION; ADHESION MOLECULES; CATIONIC PROTEIN; EOSINOPHILS; EXPRESSION; INFILTRATION; ACTIVATION; SEVERITY; MARKERS; INDEXES AB Background: Bronchial mucosal inflammation is the major pathogenic process in asthma. In the latest years, induced sputum (IS) examination has become an important non-invasive method of assessing airway inflammation. Flow cytometry has been recently applied to the study of IS though it is not exempt of methodological difficulties. The aim of the present study was to further study if the fluorocytometric analysis of IS could represent a reliable tool to assess the presence of bronchial activated lymphocytes in stable mild asthmatic patients. Methods: Induced sputa from controls and asthmatic patients were processed in isotonic 3mM dithiothreitol (DTT), a mucolytic agent required for cell dispersion. The individualized cells were then stained with monoclonal antibodies for three-colour flow-cytometric analysis. Total IgE and ECP were measured in serum and in the sputum fluid phase. Results: The cellularity of asthmatic sputa is enriched in eosinophils (mean, 26.63%) with respect to controls, but not in lymphocytes. However, lymphocytes from asthmatics show increased surface expression of activation markers (CD25 in T cells, CD23 in B cells). Surprisingly, no differences were observed in the detected levels of CD54 on IS lymphocytes and eosinophils between asthmatics and non-asthmatics. Furthermore, there was a significantly higher concentration of ECP and total IgE in the sputum from the asthmatic group. Conclusion: Fluorocytometric analysis of induced sputum is a reliable non-invasive method for the study of bronchial immune cells. It could provide complementary information on activated cells in the bronchial mucosa even in non-smokers, mild and stable asthmatics and it is reasonable to speculate that it will be useful in monitoring the effect of the treatment in these patients. C1 Hosp Virgen Concha, Allergy Unit, Zamora 49022, Spain. NIAID, Clin Invest Lab, NIH, Bethesda, MD USA. H Clin San Carlos, Dept Allergy, Madrid, Spain. Hosp Ramon y Cajal, Dept Immunol, E-28034 Madrid, Spain. RP Ortega, JD (reprint author), Hosp Virgen Concha, Allergy Unit, Avenida Requejo 35, Zamora 49022, Spain. EM jdort@mixmail.com NR 30 TC 7 Z9 7 U1 0 U2 0 PU HOGREFE & HUBER PUBLISHERS PI GOTTINGEN PA ROHNSWEG 25, D-37085 GOTTINGEN, GERMANY SN 1018-9068 J9 J INVEST ALLERG CLIN JI J. Invest. Allergol. Clin. Immunol. PY 2004 VL 14 IS 2 BP 108 EP 113 PG 6 WC Allergy; Immunology SC Allergy; Immunology GA 840QV UT WOS:000222875300003 ER PT J AU Udey, MC AF Udey, MC TI Skin dendritic cells in immunity and autoimmunity SO JOURNAL OF INVESTIGATIVE DERMATOLOGY SYMPOSIUM PROCEEDINGS LA English DT Article; Proceedings Paper CT 51st Annual Montagna Symposium on the Biology of Skin CY AUG 16-20, 2002 CL SNOWMASS, COLORADO ID SYSTEMIC-LUPUS-ERYTHEMATOSUS; SUPPRESSOR T-CELLS; LANGERHANS CELLS; SUBSETS; RECOGNITION; RESPONSES; TOLERANCE; RECEPTORS; IMMATURE; LESIONS C1 NCI, Dermatol Branch, Canc Res Ctr, NIH, Bethesda, MD 20892 USA. RP Udey, MC (reprint author), NCI, Dermatol Branch, Canc Res Ctr, NIH, Bldg 10,Room 12 N238, Bethesda, MD 20892 USA. EM udey@helix.nih.gov NR 32 TC 8 Z9 9 U1 0 U2 1 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 1087-0024 J9 J INVEST DERM SYMP P JI J. Invest. Dermatol. Symp. Proc. PD JAN PY 2004 VL 9 IS 1 BP 15 EP 17 DI 10.1111/j.1087-0024.2004.00838.x PG 3 WC Dermatology SC Dermatology GA 764FB UT WOS:000188195800003 PM 14870979 ER PT J AU von Eschenbach, AC AF von Eschenbach, AC TI Andrew C. von Eschenbach, MD, director, National Cancer Institute SO JOURNAL OF INVESTIGATIVE MEDICINE LA English DT Editorial Material C1 NCI, Bethesda, MD 20892 USA. Univ Texas, MD Anderson Canc Ctr, Prostate Canc Res Program, Houston, TX 77030 USA. RP von Eschenbach, AC (reprint author), NCI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU B C DECKER INC PI HAMILTON PA 20 HUGHSON ST SOUTH, PO BOX 620, L C D 1, HAMILTON, ONTARIO L8N 3K7, CANADA SN 1081-5589 J9 J INVEST MED JI J. Invest. Med. PD JAN PY 2004 VL 52 IS 1 BP 1 EP 5 PG 5 WC Medicine, General & Internal; Medicine, Research & Experimental SC General & Internal Medicine; Research & Experimental Medicine GA 765ER UT WOS:000188254600001 PM 14989365 ER PT J AU Anderson, PD Huizing, M Gahl, WA AF Anderson, PD Huizing, M Gahl, WA TI Hermansky-Pudlak syndrome type-4 (HPS-4); Clinical and molecular characteristics SO JOURNAL OF INVESTIGATIVE MEDICINE LA English DT Meeting Abstract CT Western Regional Meeting of the American-Federation-for-Medical-Research CY JAN 28-31, 2004 CL CARMEL, CALIFORNIA SP Amer Federat Med Res C1 NHGRI, Med Genet Branch, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU B C DECKER INC PI HAMILTON PA 20 HUGHSON ST SOUTH, PO BOX 620, L C D 1, HAMILTON, ONTARIO L8N 3K7, CANADA SN 1081-5589 J9 J INVEST MED JI J. Invest. Med. PD JAN PY 2004 VL 52 IS 1 BP S100 EP S100 PG 1 WC Medicine, General & Internal; Medicine, Research & Experimental SC General & Internal Medicine; Research & Experimental Medicine GA 765ER UT WOS:000188254600142 ER PT J AU Anderson, PD Huizing, M Gahl, WA AF Anderson, PD Huizing, M Gahl, WA TI Hermansky-Pudlak syndrome type-4 (HPS-4); Clinical and molecular characteristics. SO JOURNAL OF INVESTIGATIVE MEDICINE LA English DT Meeting Abstract CT Western Regional Meeting of the American-Federation-for-Medical-Research CY JAN 28-31, 2004 CL CARMEL, CALIFORNIA SP Amer Federat Med Res C1 NHGRI, Med Genet Branch, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU B C DECKER INC PI HAMILTON PA 20 HUGHSON ST SOUTH, PO BOX 620, L C D 1, HAMILTON, ONTARIO L8N 3K7, CANADA SN 1081-5589 J9 J INVEST MED JI J. Invest. Med. PD JAN PY 2004 VL 52 IS 1 BP S91 EP S91 PG 1 WC Medicine, General & Internal; Medicine, Research & Experimental SC General & Internal Medicine; Research & Experimental Medicine GA 765ER UT WOS:000188254600092 ER PT J AU Durst, I Vu, H Ianosi-Irimie, M Pridjian, C Bagrov, A Fedorova, O Pridjian, G Puschett, JB AF Durst, I Vu, H Ianosi-Irimie, M Pridjian, C Bagrov, A Fedorova, O Pridjian, G Puschett, JB TI Antibodies to Marinobufagenin reduce blood pressure in a rat model of preeclampsia. SO JOURNAL OF INVESTIGATIVE MEDICINE LA English DT Meeting Abstract CT Southern Regional Meeting of the American-Federation-for-Medical-Research CY FEB 12-14, 2004 CL NEW ORLEANS, LOUISIANA SP Amer Federat Med Res C1 Tulane Univ, Sch Med, Dept Med, Nephrol Sect, New Orleans, LA 70112 USA. Tulane Univ, Sch Med, Dept Obstet & Gynecol, New Orleans, LA 70112 USA. NIA, Cardiovasc Sci Lab, NIH, Baltimore, MD 21224 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU B C DECKER INC PI HAMILTON PA 20 HUGHSON ST SOUTH, PO BOX 620, L C D 1, HAMILTON, ONTARIO L8N 3K7, CANADA SN 1081-5589 J9 J INVEST MED JI J. Invest. Med. PD JAN PY 2004 VL 52 IS 1 BP S318 EP S318 PG 1 WC Medicine, General & Internal; Medicine, Research & Experimental SC General & Internal Medicine; Research & Experimental Medicine GA 765ER UT WOS:000188254600915 ER PT J AU Ryder, KM Tylavsky, F Strotmeyer, E Harris, T Shorr, R AF Ryder, KM Tylavsky, F Strotmeyer, E Harris, T Shorr, R CA Hlth ABC Study TI Low initiation of fracture reducing therapy in older women with reduced bone density. SO JOURNAL OF INVESTIGATIVE MEDICINE LA English DT Meeting Abstract CT Southern Regional Meeting of the American-Federation-for-Medical-Research CY FEB 12-14, 2004 CL NEW ORLEANS, LOUISIANA SP Amer Federat Med Res C1 NIA, Bethesda, MD 20892 USA. RI Strotmeyer, Elsa/F-3015-2014 NR 0 TC 0 Z9 0 U1 0 U2 0 PU B C DECKER INC PI HAMILTON PA 20 HUGHSON ST SOUTH, PO BOX 620, L C D 1, HAMILTON, ONTARIO L8N 3K7, CANADA SN 1081-5589 J9 J INVEST MED JI J. Invest. Med. PD JAN PY 2004 VL 52 IS 1 BP S303 EP S303 PG 1 WC Medicine, General & Internal; Medicine, Research & Experimental SC General & Internal Medicine; Research & Experimental Medicine GA 765ER UT WOS:000188254600832 ER PT J AU Stevenson, JJ Beard, BC Wilson, SH Smerdon, MJ AF Stevenson, JJ Beard, BC Wilson, SH Smerdon, MJ TI Base excision repair of specifically damaged chromatin substrates using trypsin digestion of histone tails to mimic histone hyperacetylation. SO JOURNAL OF INVESTIGATIVE MEDICINE LA English DT Meeting Abstract CT Western Regional Meeting of the American-Federation-for-Medical-Research CY JAN 28-31, 2004 CL CARMEL, CALIFORNIA SP Amer Federat Med Res C1 Washington State Univ, Sch Mol Biosci, Pullman, WA 99164 USA. NIEHS, Struct Biol Lab, Res Triangle Pk, NC 27709 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU B C DECKER INC PI HAMILTON PA 20 HUGHSON ST SOUTH, PO BOX 620, L C D 1, HAMILTON, ONTARIO L8N 3K7, CANADA SN 1081-5589 J9 J INVEST MED JI J. Invest. Med. PD JAN PY 2004 VL 52 IS 1 BP S157 EP S157 PG 1 WC Medicine, General & Internal; Medicine, Research & Experimental SC General & Internal Medicine; Research & Experimental Medicine GA 765ER UT WOS:000188254600463 ER PT J AU Constantinou, M Waters, SL Steel, CJ Poole, KG Marino, PS Ind, PW Rhodes, CG Aigbirhio, FI Moore, A Pike, VW Luthra, SK AF Constantinou, M Waters, SL Steel, CJ Poole, KG Marino, PS Ind, PW Rhodes, CG Aigbirhio, FI Moore, A Pike, VW Luthra, SK TI Flixotide (TM)-pressurized metered-dose inhalers loaded with [F-18]fluticasone propionate particles for drug deposition studies in humans with PET-formulation and analysis SO JOURNAL OF LABELLED COMPOUNDS & RADIOPHARMACEUTICALS LA English DT Article DE fluticasone propionate; pressurized metered-dose inhaler; fluorine-18; [S-fluoromethyl-F-18]fluticasone propionate; particle-size analysis; PET ID SUPPORTED NUCLEOPHILIC-SUBSTITUTION; FLUTICASONE PROPIONATE; LUNG DEPOSITION; ACETONIDE; KINETICS; PHARMACOLOGY; RECEPTOR; AEROSOL AB Fluticasone propionate (FP) is a potent anti-inflammatory synthetic steroid, used for the treatment of asthma. Flixotide(TM) is a formulated pressurized metered-dose inhaler (pMDI) that contains small-micronized FP particles in a blend of CFC propellants. Our objective was to develop a radiotracer method for accurately measuring the regional deposition of FP within the human lung using positron emission tomography (PET), which would be of important clinical interest. Flixotide(TM) pMDIs were used to prepare [F-18]FP pMDIs labeled isotopically with the positron emitter, fluorine-18 (t(1/2) = 109.7 min). FP particles from Flixotide(TM) pMDIs were mixed with [F-18]FP formulated into a pMDI and sonicated at room temperature. The drug delivery of [F-18]FP pMDI (250 mug of FP per actuation dose) was assessed for particle size distribution and dose uniformity. The distributions of FP and [F-18]FP across particle size in such preparations were measured with an Andersen cascade impactor. This procedure was shown to provide an emitted dose from a [F-18]FP pMDI of 246 +/- 19 mug/per metered dose. The particle size distribution as measured by mass median aerodynamic diameter (MMAD) (The mass median aerodynamic diameter (MMAD) and the geometric standard deviation (GSD) for each distribution were calculated. MMAD is defined as the aerodynamic diameter around which the mass of particles is equally distributed and the GSD is a measure of the dispersion of these particle diameters around the MMAD) from a commercial Flixotide(TM) pMDI was 2.6 +/- 0.2 mum and agreed well with that from an [F-18]FP pMDI (2.8 +/- 0.1 mum). The MMAD and geometric standard deviation (GSD) of newly formulated [F-18]FP pMDIs were unaffected by the formulation procedure. [F-18]FP was distributed with good uniformity with respect to the mass of FP for particles greater than 0.43 mum. Hence, the radiolabeled pMDI is a suitable source of radiotracer for the regional measurement of lung deposition for inhaled FP in human subjects with PET. Copyright (C) 2003 John Wiley Sons, Ltd. C1 Hammersmith Hosp, Hammersmith Imanet Ltd, London W12 0NN, England. Hammersmith Hosp, MRC, Ctr Clin Sci, London W12 0NN, England. Univ Cambridge, Sch Clin, Addenbrookes Hosp, Wolfson Brain Imaging Ctr, Cambridge CB2 2QQ, England. GlaxoSmithKline PLC, Greenford, Middx, England. NIMH, Mol Imaging Branch, Bethesda, MD 20892 USA. RP Constantinou, M (reprint author), Hammersmith Hosp, Hammersmith Imanet Ltd, Cyclotron Bldg,Du Cane Rd, London W12 0NN, England. EM maria.constantinou@csc.mrc.ac.uk NR 33 TC 6 Z9 6 U1 0 U2 4 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 0362-4803 J9 J LABELLED COMPD RAD JI J. Label. Compd. Radiopharm. PD JAN PY 2004 VL 47 IS 1 BP 55 EP 70 DI 10.1002/jlcr.797 PG 16 WC Biochemical Research Methods; Chemistry, Medicinal; Chemistry, Analytical SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Chemistry GA 771EB UT WOS:000188771700008 ER PT J AU Howard, OMZ Dong, HF Robbins, PF Carlos, C Finn, O Oppenheim, JJ AF Howard, OMZ Dong, HF Robbins, PF Carlos, C Finn, O Oppenheim, JJ TI Some tumor antigens, like autoantigens, are chemotactic for mononuclear cells and utilize chemokine receptors SO JOURNAL OF LEUKOCYTE BIOLOGY LA English DT Meeting Abstract CT 37th Annual Meeting of the Society-for-Leukocyte-Biology CY OCT 21-23, 2004 CL Toronto, CANADA SP Soc Leukocyte Biol C1 NCI Frederick Ctr Canc Res, Mol Immunoregulat Lab, Ft Detrick, MD 21702 USA. SAIC Frederick, Ft Detrick, MD 21702 USA. NCI, Surg Branch, Bethesda, MD 20892 USA. Univ Pittsburgh, Sch Med, Dept Immunol, Pittsburgh, PA 15261 USA. Univ Pittsburgh, Inst Canc, Pittsburgh, PA 15261 USA. RI Howard, O M Zack/B-6117-2012 OI Howard, O M Zack/0000-0002-0505-7052 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 0741-5400 J9 J LEUKOCYTE BIOL JI J. Leukoc. Biol. PY 2004 SU S BP 19 EP 20 PG 2 WC Cell Biology; Hematology; Immunology SC Cell Biology; Hematology; Immunology GA 851KD UT WOS:000223683100008 ER PT J AU Barlic, J McDermott, DH Merrell, MN Gonzales, J Via, L Murphy, PM AF Barlic, J McDermott, DH Merrell, MN Gonzales, J Via, L Murphy, PM TI IL-15 and IL-2 oppositely regulate expression of the chemokine receptor CX3CR1 through selective NFAT1-and NFAT2-dependent mechanisms SO JOURNAL OF LEUKOCYTE BIOLOGY LA English DT Meeting Abstract CT 37th Annual Meeting of the Society-for-Leukocyte-Biology CY OCT 21-23, 2004 CL Toronto, CANADA SP Soc Leukocyte Biol C1 NIAID, Host Def Lab, NIH, Mol Signaling Sect, Bethesda, MD USA. NIAID, Immunogenet Lab, NIH, Tuberculosis Res Sect, Bethesda, MD 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 0741-5400 J9 J LEUKOCYTE BIOL JI J. Leukoc. Biol. PY 2004 SU S BP 22 EP 22 PG 1 WC Cell Biology; Hematology; Immunology SC Cell Biology; Hematology; Immunology GA 851KD UT WOS:000223683100015 ER PT J AU Dong, HF Yang, D Su, SB Caspi, RR Howard, OMZ Oppenheim, JJ AF Dong, HF Yang, D Su, SB Caspi, RR Howard, OMZ Oppenheim, JJ TI The retinal autoantigens, interphotoreceptor retinoid-binding protein (IRBP) and S Antigen, are chemotactic for CXCR3 and CXCR5 expressing lymphocytes and immature dendritic cells SO JOURNAL OF LEUKOCYTE BIOLOGY LA English DT Meeting Abstract CT 37th Annual Meeting of the Society-for-Leukocyte-Biology CY OCT 21-23, 2004 CL Toronto, CANADA SP Soc Leukocyte Biol C1 NCI, LMI, Bethesda, MD 20892 USA. NEI, NIH, Bethesda, MD 20892 USA. RI Howard, O M Zack/B-6117-2012 OI Howard, O M Zack/0000-0002-0505-7052 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 0741-5400 J9 J LEUKOCYTE BIOL JI J. Leukoc. Biol. PY 2004 SU S BP 22 EP 22 PG 1 WC Cell Biology; Hematology; Immunology SC Cell Biology; Hematology; Immunology GA 851KD UT WOS:000223683100017 ER PT J AU Wang, JM Sun, RH Iribarren, P Zhang, N Zhou, Y Gong, WH Cho, EH Lockett, S Chertov, O Bednar, F Rogers, TJ Oppenheim, JJ AF Wang, JM Sun, RH Iribarren, P Zhang, N Zhou, Y Gong, WH Cho, EH Lockett, S Chertov, O Bednar, F Rogers, TJ Oppenheim, JJ TI The neutrophil granule protein Cathepsin G is a chemotactic agonist for the G protein coupled formyl peptide receptor FPR SO JOURNAL OF LEUKOCYTE BIOLOGY LA English DT Meeting Abstract CT 37th Annual Meeting of the Society-for-Leukocyte-Biology CY OCT 21-23, 2004 CL Toronto, CANADA SP Soc Leukocyte Biol C1 Natl Canc Inst Frederick, Ctr Canc Res, Mol Immunoregulat Lab, Ft Detrick, MD 21702 USA. Natl Canc Inst Frederick, SAIC Frederick, Basic Res Program, Ft Detrick, MD 21702 USA. Natl Canc Inst Frederick, SAIC Frederick, Image Anal Lab, Ft Detrick, MD 21702 USA. Temple Univ, Sch Med, Philadelphia, PA 19140 USA. RI Cho, Edward/B-3727-2012 OI Cho, Edward/0000-0002-0278-334X 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 0741-5400 J9 J LEUKOCYTE BIOL JI J. Leukoc. Biol. PY 2004 SU S BP 24 EP 24 PG 1 WC Cell Biology; Hematology; Immunology SC Cell Biology; Hematology; Immunology GA 851KD UT WOS:000223683100024 ER PT J AU Iribarren, P Ying, GG Zhou, Y Gong, WH Zhang, N Yu, ZX Le, YY Cui, YH Wang, JM AF Iribarren, P Ying, GG Zhou, Y Gong, WH Zhang, N Yu, ZX Le, YY Cui, YH Wang, JM TI Humanin, a newly identified neuroprotective factor, uses the G-protein coupled receptor FPRL1 as a functional receptor SO JOURNAL OF LEUKOCYTE BIOLOGY LA English DT Meeting Abstract CT 37th Annual Meeting of the Society-for-Leukocyte-Biology CY OCT 21-23, 2004 CL Toronto, CANADA SP Soc Leukocyte Biol C1 NCI, CCR, SAIC Frederick Inc, Mol Immunoregulat Lab, Frederick, MD 21702 USA. NCI, CCR, SAIC Frederick Inc, Basic Res Program, Frederick, MD 21702 USA. NHLBI, Pathol Sect, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 1 U2 3 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0741-5400 J9 J LEUKOCYTE BIOL JI J. Leukoc. Biol. PY 2004 SU S BP 36 EP 36 PG 1 WC Cell Biology; Hematology; Immunology SC Cell Biology; Hematology; Immunology GA 851KD UT WOS:000223683100068 ER PT J AU Shannon, JG Heinzen, RA AF Shannon, JG Heinzen, RA TI Differential maturation and cytokine production by human dendritic cells following infection by virulent or avirulent Coxiella burnetii SO JOURNAL OF LEUKOCYTE BIOLOGY LA English DT Meeting Abstract CT 37th Annual Meeting of the Society-for-Leukocyte-Biology CY OCT 21-23, 2004 CL Toronto, CANADA SP Soc Leukocyte Biol C1 NIAID, Rocky Mt Labs, Intracellular Parasites Lab, NIH, Hamilton, MT 59840 USA. RI Shannon, Jeffrey/A-5735-2009 OI Shannon, Jeffrey/0000-0003-4211-4308 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 0741-5400 J9 J LEUKOCYTE BIOL JI J. Leukoc. Biol. PY 2004 SU S BP 40 EP 40 PG 1 WC Cell Biology; Hematology; Immunology SC Cell Biology; Hematology; Immunology GA 851KD UT WOS:000223683100081 ER PT J AU Rodriguez-Galan, MC Watanabe, M Young, HA AF Rodriguez-Galan, MC Watanabe, M Young, HA TI Toxicity vs. antitumor activity of IL-12 and IL-18 cDNA injections in C57BL/6 mice SO JOURNAL OF LEUKOCYTE BIOLOGY LA English DT Meeting Abstract CT 37th Annual Meeting of the Society-for-Leukocyte-Biology CY OCT 21-23, 2004 CL Toronto, CANADA SP Soc Leukocyte Biol C1 NCI, Frederick Canc Res & Dev Ctr, Expt Immunol Lab, Frederick, MD 21702 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 0741-5400 J9 J LEUKOCYTE BIOL JI J. Leukoc. Biol. PY 2004 SU S BP 56 EP 56 PG 1 WC Cell Biology; Hematology; Immunology SC Cell Biology; Hematology; Immunology GA 851KD UT WOS:000223683100139 ER PT J AU Glass, WG Subbarao, K Murphy, BM Murphy, PM AF Glass, WG Subbarao, K Murphy, BM Murphy, PM TI Mechanisms of host defense following pulmonary infection of the mouse lung SO JOURNAL OF LEUKOCYTE BIOLOGY LA English DT Meeting Abstract CT 37th Annual Meeting of the Society-for-Leukocyte-Biology CY OCT 21-23, 2004 CL Toronto, CANADA SP Soc Leukocyte Biol C1 NIAID, 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 0741-5400 J9 J LEUKOCYTE BIOL JI J. Leukoc. Biol. PY 2004 SU S BP 62 EP 62 PG 1 WC Cell Biology; Hematology; Immunology SC Cell Biology; Hematology; Immunology GA 851KD UT WOS:000223683100161 ER PT J AU Cao, XL Ito, Y AF Cao, XL Ito, Y TI Preparation and purification of epigallocatechin by high-speed countercurrent chromatography (HSCCC) SO JOURNAL OF LIQUID CHROMATOGRAPHY & RELATED TECHNOLOGIES LA English DT Article DE preparation; purification; epigallocatechin; HSCCC ID TEA; POLYPHENOLS AB Epigallocatechin (EGC) was prepared by the degallation of Epigallocatechin-O-3-gallate (EGCG). EGCG was completely converted to EGC and gallic acid by adding 4 mg tarmase/100 mg EGCG at the concentration of 2 mg/mL under pH 6.0, at 35degreesC for 30 min. EGC was then separated from the reaction mixture by HSCCC, using a two-phase solvent system composed of hexane-ethyl acetate-water (1/9/10, v/v/v). Finally, 1.3 g of EGC at 97% purity was prepared from about 2.3 g of EGCG at 85% purity, indicating that EGC was almost completely recovered by HSCCC. C1 NHLBI, Biophys Chem Lab, NIH, Bethesda, MD 20892 USA. Beijing Technol & Business Univ, Beijing Key Lab Plant Resource Res & Dev, Beijing, Peoples R China. RP Ito, Y (reprint author), NHLBI, Biophys Chem Lab, NIH, Bldg 50,Rm 3334, Bethesda, MD 20892 USA. EM itoy@nhlbi.nih.gov NR 6 TC 24 Z9 26 U1 5 U2 10 PU MARCEL DEKKER INC PI NEW YORK PA 270 MADISON AVE, NEW YORK, NY 10016 USA SN 1082-6076 J9 J LIQ CHROMATOGR R T JI J. Liq. Chromatogr. Relat. Technol. PY 2004 VL 27 IS 1 BP 145 EP 152 DI 10.1081/JLC-120027091 PG 8 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 777MP UT WOS:000189182400010 ER PT J AU Cao, XL Lewis, JR Ito, Y AF Cao, XL Lewis, JR Ito, Y TI Application of high-speed countercurrent chromatography to the separation of black tea theaflavins SO JOURNAL OF LIQUID CHROMATOGRAPHY & RELATED TECHNOLOGIES LA English DT Article DE high-speed countercurrent chromatography; theaflavins; black tea; theaflavin monogallates ID THEAFLAVIN-3,3'-DIGALLATE; PROLIFERATION; CELLS; DNA AB High-speed countercurrent chromatography (HSCCC) has been applied for the separation of four theaflavins (TFs). The results indicated that pure TF and theaflavin-3,3'- O-digallate (TFDG) can be obtained by HSCCC using a solvent system composed of hexane-ethyl acetate-methanol-water (1.25: 5: 1.25: 5, v/v/v/v). Although the separation of two TF monogallates is incomplete under all the solvent systems examined, peak cutting yielded a small amount of pure theaflavin-3-O-gallate (TF3MG) and theaflavin-3'-O-monogallate (TF3'MG). Thus, preparative HPLC has been employed as a complementary method for the separation of two TF monogallates. The HSCCC isolation of TFs from the solvent extract of black tea infusion has proved to be successful by gradient elution, based on the solvent system mentioned above. C1 Beijing Technol & Business Univ, Beijing Key Lab Plant Resource Res & Dev, Beijing, Peoples R China. Unilever Res, Bedford, England. RP Ito, Y (reprint author), NHLI, Lab Biophys Chem, NIH, Bldg 50,Rm 3334, Bethesda, MD 20892 USA. EM itoy@nhlbi.nih.gov NR 8 TC 13 Z9 16 U1 3 U2 4 PU MARCEL DEKKER INC PI NEW YORK PA 270 MADISON AVE, NEW YORK, NY 10016 USA SN 1082-6076 J9 J LIQ CHROMATOGR R T JI J. Liq. Chromatogr. Relat. Technol. PY 2004 VL 27 IS 12 BP 1893 EP 1902 DI 10.1081/JLC-120038775 PG 10 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 831RL UT WOS:000222213700006 ER PT J AU Gosse, BK Ito, Y Huang, RC AF Gosse, BK Ito, Y Huang, RC TI Optimization of active saponin, arganine C, for microbicidal external use SO JOURNAL OF LIQUID CHROMATOGRAPHY & RELATED TECHNOLOGIES LA English DT Article DE tighemelin; arganine C; countercurrent chromatography; saponin ID COUNTERCURRENT CHROMATOGRAPHY; TRITERPENOID SAPONINS AB The antiviral activities of the saponins, arganine C, and tieghemelin were described earlier [Gosse, B.K.; Gnabre, J.N.; Ito, Y.; Huang, R.C.; J. Liq. Chrom. Rel. Technol. 2002, 25 (20), 3199-3211]. In this paper, conversion of tieghemelin to arganine C, a stronger antiviral entry saponin for a new microbicide is described. The crude saponin fraction (arganine C/tieghemilin = 1 : 2) obtained by high-speed countercurrent chromatography (HSCCC) [Ito, Y.: CRC Crit. Rev. Anal. Chem. 1986, 17 (1), 65-143], was treated with 2-ethoxy-1-ethoxycarbonyl-1,2-dihydroquinoline (EEDQ) in dimethylfomiamide (DMF) and refluxed for 5 hr. The reaction mixture shows a single peak which represents arganine C by HSCCC. From 700 mg of the crude sample, 500 mg of pure arganine was obtained. C1 NHLBI, Lab Biophys Chem, NIH, Bethesda, MD 20892 USA. Johns Hopkins Univ, Dept Biol, Baltimore, MD USA. Inst Natl Polytech, Dept Chim Ind, Lab Substances Nat Bioact, Yamoussoukro, Cote Ivoire. RP Ito, Y (reprint author), NHLBI, Lab Biophys Chem, NIH, Bldg 50,Rm 3334,50 S Dr, Bethesda, MD 20892 USA. EM itoy@nhlbi.nih.gov NR 9 TC 5 Z9 5 U1 2 U2 2 PU MARCEL DEKKER INC PI NEW YORK PA 270 MADISON AVE, NEW YORK, NY 10016 USA SN 1082-6076 J9 J LIQ CHROMATOGR R T JI J. Liq. Chromatogr. Relat. Technol. PY 2004 VL 27 IS 12 BP 1947 EP 1953 DI 10.1081/JLC-120038780 PG 7 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 831RL UT WOS:000222213700011 ER PT J AU Kohler, N Chou, E Ito, Y Winterhalter, P AF Kohler, N Chou, E Ito, Y Winterhalter, P TI Development of a new preparative spiral-coil low-speed rotary countercurrent chromatographic (spiral-coil LSRCCC) method SO JOURNAL OF LIQUID CHROMATOGRAPHY & RELATED TECHNOLOGIES LA English DT Article DE low-speed rotary CCC; spiral coil assembly; CCC; caffeine; theophylline; dipeptides; scale-up AB A new prototype, large-scale countercurrent chromatograph was constructed. It was equipped, with a three-layer spiral column made from a continuous piece of convoluted Teflon tubing (8.5 mm I.D. and 9.7 m in length), which was accommodated in a spirally carved foam plastic holder. Two different types of two-phase solvent systems were used to evaluate stationary phase retention and mixing effect between stationary and mobile phases, i.e., chloroform/water (1 : 1, v/v) for separation of caffeine and theophylline; and 1-butanol/acetic acid/water (4: 1 : 5, v/v/v) for separation of dipeptides, valyl-tyrosine (val-tyr), and tryptophyl-tyrosine (trp-tyr). A set of different elution modes (inside-outside and head-tail), and rotational speed (0-400 rpm) was assessed for stationary phase retention and separation efficiency. The elution mode of inside to outside of the spiral for the lower mobile phase or the opposite direction for the upper mobile phase, is rated the best for stationary phase retention due to observed spiral effect for liquid movement. Different operational parameters, such as rpm and flow rate of the mobile phase were evaluated for separation efficiency and speed. The obtained data revealed that the spiral effect and Archimedean screw force were two important contributing factors for yielding the enhanced speed and higher partition efficiency, compared to conventional low-speed rotary countercurrent chromatography. C1 Tech Univ Carolo Wilhelmina Braunschweig, Inst Food Chem, D-38106 Braunschweig, Germany. Pharma Tech Res Corp, Baltimore, MD USA. NHLBI, Biophys Chem Lab, NIH, Bethesda, MD 20892 USA. RP Winterhalter, P (reprint author), Tech Univ Carolo Wilhelmina Braunschweig, Inst Food Chem, Schleinitzstr 20, D-38106 Braunschweig, Germany. EM p.winterhalter@tu-bs.de NR 9 TC 15 Z9 15 U1 0 U2 6 PU MARCEL DEKKER INC PI NEW YORK PA 270 MADISON AVE, NEW YORK, NY 10016 USA SN 1082-6076 J9 J LIQ CHROMATOGR R T JI J. Liq. Chromatogr. Relat. Technol. PY 2004 VL 27 IS 16 BP 2547 EP 2560 DI 10.1081/JLC-200028392 PG 14 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 858AL UT WOS:000224162400006 ER PT J AU Yang, FQ Ito, Y AF Yang, FQ Ito, Y TI On-line flow-injection detection system and its application to the measurement of ethanol transfer and osmosis rate in centrifugal precipitation chromatography SO JOURNAL OF LIQUID CHROMATOGRAPHY & RELATED TECHNOLOGIES LA English DT Article DE on-line flow-injection method; centrifugal precipitation chromatography; mass transfer; osmosis; ethanol; seal-free continuous-flow centrifuge ID AMMONIUM-SULFATE; FRACTIONATION AB An on-line flow-injection detection system is newly designed and successfully used in the basic research on determination of the mass transfer and osmosis rates of ethanol through the membrane in centrifugal precipitation chromatography. The system improves the linearity range of the calibration curve, which showed linearity coefficient of correlation of 0.998 between 10 and 80% ethanol solution. C1 NHLBI, Biophys Chem Lab, NIH, Bethesda, MD 20892 USA. RP Ito, Y (reprint author), NHLBI, Biophys Chem Lab, NIH, Bldg 50,Rm 33334,50 South Dr MSC 8014, Bethesda, MD 20892 USA. EM itoy@nhlbi.nih.gov NR 8 TC 2 Z9 2 U1 1 U2 3 PU MARCEL DEKKER INC PI NEW YORK PA 270 MADISON AVE, NEW YORK, NY 10016 USA SN 1082-6076 J9 J LIQ CHROMATOGR R T JI J. Liq. Chromatogr. Relat. Technol. PY 2004 VL 27 IS 19 BP 2979 EP 2985 DI 10.1081/JLC-200032601 PG 7 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 866DP UT WOS:000224754300001 ER PT J AU Shinomiya, K Ito, Y AF Shinomiya, K Ito, Y TI Effects of the planetary motion of a coiled column on protein separation by the nonsynchronous coil planet centrifuge SO JOURNAL OF LIQUID CHROMATOGRAPHY & RELATED TECHNOLOGIES LA English DT Article DE nonsynchronous coil planet centrifuge; planetary motion; protein separation; countercurrent chromatography; polymer phase system; retention of stationary phase; cytochrome C; myoglobin; lysozyme ID POLYMER PHASE SYSTEMS; COUNTERCURRENT CHROMATOGRAPHIC-SEPARATION; CELL-SEPARATION; ROTATING SEALS; CORIOLIS-FORCE; ASSEMBLIES AB The effects of rotational speed and direction of revolution of the coiled separation column on protein separation were examined using a rotary-seal-free nonsynchronous coil planet centrifuge (CPC) fabricated in our laboratory. This apparatus has a unique feature that allows a freely adjustable rotational speed of the coiled separation column at a given revolution speed. The separation was performed using a set of stable proteins including cytochrome C, myoglobin, and lysozyme with an aqueous-aqueous polymer phase system composed of 12.5% (w/w) polyethylene glycol (PEG) 1000 and 12.5% (w/w) dibasic potassium phosphate. A series of experiments revealed that the head to tail elution mode produced better stationary phase retention and higher peak resolution regardless of the choice of the mobile phase. The best result was obtained in the head to tail elution mode by the clockwise (CW) coil rotation for the lower mobile phase or by the counterclockwise (CCW) coil rotation for the upper mobile phase, both under CCW revolution of the rotor. C1 Nihon Univ, Coll Pharm, Funabashi, Chiba 2748555, Japan. NHLBI, Biophys Chem Lab, NIH, Bethesda, MD 20892 USA. RP Shinomiya, K (reprint author), Nihon Univ, Coll Pharm, 7-7-1 Narashinodai, Funabashi, Chiba 2748555, Japan. EM kshino@pha.nihon-u.ac.jp NR 20 TC 8 Z9 8 U1 1 U2 3 PU MARCEL DEKKER INC PI NEW YORK PA 270 MADISON AVE, NEW YORK, NY 10016 USA SN 1082-6076 J9 J LIQ CHROMATOGR R T JI J. Liq. Chromatogr. Relat. Technol. PY 2004 VL 27 IS 20 BP 3243 EP 3255 DI 10.1081/JLC-200034913 PG 13 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 871VH UT WOS:000225164200007 ER PT J AU Fera, F Yongbi, MN van Gelderen, P Frank, JA Mattay, VS Duyn, JH AF Fera, F Yongbi, MN van Gelderen, P Frank, JA Mattay, VS Duyn, JH TI EPI-BOLD fMRI of human motor cortex at 1.5 T and 3.0 T: Sensitivity dependence on echo time and acquisition bandwidth SO JOURNAL OF MAGNETIC RESONANCE IMAGING LA English DT Article DE BOLD; fMRI; brain; optimization; EPI ID PRIMARY VISUAL-CORTEX; FUNCTIONAL MRI; SPIRAL ACQUISITION; HUMAN BRAIN; TESLA; CONTRAST; ACTIVATION; INFLOW; SIGNAL AB Purpose: To investigate the sensitivity dependence of BOLD functional imaging on MRI acquisition parameters in motor stimulation experiments using a finger tapping paradigm. Materials and Methods: Gradient-echo echo-planar fMRI experiments were performed at 1.5 T and 3.0 T with varying acquisition echo time and bandwidth, and with a 4 mm isotropic voxel size. To analyze the BOLD sensitivity, the relative contributions of BOLD signal amplitude and thermal and physiologic noise sources were evaluated, and statistical t-scores were compared in the motor area. Results: At 1.5 T, the number of activated pixels and the average t-score showed a relatively broad optimum over a TE range of 60-160 msec. At 3.0 T, an optimum range was observed between TEs of 30-130 msec. Averaged over nine subjects, maxima in the number of pixels and t-score values were 59% and 18% higher at 3.0 T than at 1.5 T, respectively, an improvement that was lower than the observed 100% to 110% increase in signal-to-noise ratio at 3.0 T. Conclusion: The somewhat disappointing increase in t-scores at 3.0 T was attributed to the increased contribution of physiologic noise at the higher field strength under the given experimental conditions. At both field strengths, reducing the effective image acquisition bandwidth from 35 to 17 Hz per pixel did not affect or only marginally affect the BOLD sensitivity. C1 NINDS, Lab Funct & Mol Imaging, NIH, Bethesda, MD 20892 USA. NIMH, Clin Brain Disorder Branch, NIH, Bethesda, MD 20892 USA. CNR, Inst Expt Med & Biotechnol, Cosenza, Italy. NIH, Lab Diagnost Radiol Res, Ctr Clin, Bethesda, MD 20892 USA. RP NINDS, Lab Funct & Mol Imaging, NIH, Bldg 10,Room B1D724,9000 Rockville Pike, Bethesda, MD 20892 USA. EM jhd@helix.nih.gov RI Duyn, Jozef/F-2483-2010 NR 31 TC 47 Z9 47 U1 0 U2 3 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1053-1807 EI 1522-2586 J9 J MAGN RESON IMAGING JI J. Magn. Reson. Imaging PD JAN PY 2004 VL 19 IS 1 BP 19 EP 26 DI 10.1002/jmri.10440 PG 8 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 762VC UT WOS:000188002000004 PM 14696216 ER PT J AU Nagae-Poetscher, LM Bonekamp, D Barker, PB Brant, LJ Kaufmann, WE Horska, A AF Nagae-Poetscher, LM Bonekamp, D Barker, PB Brant, LJ Kaufmann, WE Horska, A TI Asymmetry and gender effect in functionally lateralized cortical regions: A proton MRS imaging study SO JOURNAL OF MAGNETIC RESONANCE IMAGING LA English DT Article DE magnetic resonance spectroscopy; lateralization; gender; thalamus; Wernicke's area ID MAGNETIC-RESONANCE-SPECTROSCOPY; HUMAN POSTERIOR THALAMUS; HUMAN BRAIN; METABOLITE CONCENTRATIONS; FRONTAL LOBES; VOLUME; SEX; HIPPOCAMPUS; HANDEDNESS; HETEROGENEITY AB Purpose: to compare metabolite concentrations and ratios in gray matter regions known for their anatomical/functional asymmetry and evaluate gender effect. Materials and Methods: Proton MRS imaging was performed at 1.5 T with TR/TE 2300/280 msec in 20 healthy right-handed subjects (mean age 29.6 +/- 5.3 years, 10 men). Concentrations of N-acetyl aspartate (NAA), choline (Cho), and creatine (Cr), and the peak area ratios NAA/Cho, NAA/Cr, and Cho/Cr were evaluated in hippocampal and parahippocampal gyri, thalamus, insula, Broca's and Wernicke's areas (and corresponding contralateral areas), primary and secondary visual areas, temporal, inferior parietal, cingulate, supplemental motor, dorsolateral prefrontal, and sensorimotor areas. Linear mixed-effects regression models were used for statistical analyses. Results: NAA concentration and NAA/Cho were higher in the left thalamus by 21.9% and 20%, respectively (both P < 0.001). NAA concentration was 13% higher in the region contralateral to Wernicke's area (P < 0.02). No gender differences were found. Conclusion: Metabolite concentrations and ratios were symmetric and gender independent in most brain regions, however small hemispheric side differences in the thalamus and in Wernicke's area were found. C1 Johns Hopkins Univ, Sch Med, Russell H Morgan Dept Radiol & Radiol Sci, Baltimore, MD 21205 USA. Kennedy Krieger Inst, FM Kirby Res Ctr Funct Brain Imaging, Baltimore, MD USA. Free Univ Berlin, Univ Klinikum Benjamin Franklin, D-1000 Berlin, Germany. NIA, Gerontol Res Ctr, NIH, Baltimore, MD 21224 USA. Johns Hopkins Univ, Sch Med, Dept Pathol, Baltimore, MD 21205 USA. Johns Hopkins Univ, Sch Med, Dept Neurol, Baltimore, MD 21205 USA. Johns Hopkins Univ, Sch Med, Dept Pediat, Baltimore, MD 21205 USA. Johns Hopkins Univ, Sch Med, Dept Psychiat & Behav Sci, Baltimore, MD 21205 USA. RP Horska, A (reprint author), Johns Hopkins Univ, Sch Med, Russell H Morgan Dept Radiol & Radiol Sci, 217 Traylor Bldg,720 Rutland Ave, Baltimore, MD 21205 USA. EM ahorska@mri.jhu.edu FU NCRR NIH HHS [RR15241]; NIA NIH HHS [R03AG17364] NR 40 TC 36 Z9 38 U1 1 U2 4 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1053-1807 J9 J MAGN RESON IMAGING JI J. Magn. Reson. Imaging PD JAN PY 2004 VL 19 IS 1 BP 27 EP 33 DI 10.1002/jmri.10429 PG 7 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 762VC UT WOS:000188002000005 PM 14696217 ER PT J AU Rajnarayanan, RV Wang, K AF Rajnarayanan, RV Wang, K TI Ion-pair assisted recovery of matrix-assisted laser desorption/ionization mass spectral signals from SDS-containing peptide-protein mixtures SO JOURNAL OF MASS SPECTROMETRY LA English DT Article DE matrix-assisted laser desorption/ionization; mass spectrometry; ion pair; sodium dodecyl sulfate; peptide; protein ID SODIUM DODECYL-SULFATE; POLYACRYLAMIDE-GEL-ELECTROPHORESIS; TIME-OF-FLIGHT; 2-LAYER SAMPLE PREPARATION; MALDI-MS; DESORPTION IONIZATION; SPECTROMETRY; REMOVAL; CHROMATOGRAPHY; IDENTIFICATION AB We have developed a simple and effective means of using alkylammonium ion-pairing agents, such as cetyltetramethylammonium bromide, to recover matrix assisted laser desorption/ionization mass spectrometric (MALDI-MS) signals from sodium dodecyl sulfate (SDS)-containing protein and peptide samples. A two-layer method of matrix preparation, with a bottom matrix layer of ion-pairing agents and a top matrix layer of SDS protein samples, is essential for reproducible MALDI mass spectra with good recovery. Both buffer ions and ion-pairing agents have profound effects on signal recovery and can be rapidly and systematically optimized. This practical technique, termed ion-pair assisted recovery (IPAR), is compatible with major SDS-based biotechniques and can be easily incorporated into high-throughput proteomic analysis. Copyright (C) 2004 John Wiley Sons, Ltd. C1 NIAMSD, Muscle Biol Lab, Muscle Proteom & Nanotechnol Sect, NIH, Bethesda, MD 20892 USA. RP Wang, K (reprint author), NIAMSD, Muscle Biol Lab, Muscle Proteom & Nanotechnol Sect, NIH, 50 South Dr, Bethesda, MD 20892 USA. EM wangk@exchange.nih.gov NR 34 TC 11 Z9 11 U1 1 U2 5 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 1076-5174 J9 J MASS SPECTROM JI J. Mass Spectrom. PD JAN PY 2004 VL 39 IS 1 BP 79 EP 85 DI 10.1002/jms.572 PG 7 WC Biophysics; Chemistry, Organic; Spectroscopy SC Biophysics; Chemistry; Spectroscopy GA 771EG UT WOS:000188772200009 PM 14760616 ER PT J AU O'Brien, SJ AF O'Brien, SJ TI Genetic architecture of complex diseases: Lessons from AIDS SO JOURNAL OF MEDICAL GENETICS LA English DT Meeting Abstract CT British Human Genetics Conference CY SEP 13-15, 2004 CL Univ York, York, ENGLAND HO Univ York C1 NCI, Bethesda, MD 20892 USA. EM obrien@ncifcrf.org NR 0 TC 0 Z9 0 U1 0 U2 0 PU B M J PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0022-2593 J9 J MED GENET JI J. Med. Genet. PY 2004 VL 41 SU 1 BP S27 EP S27 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 853VT UT WOS:000223857700050 ER PT J AU Kittler, AF Hobbs, J Volk, LA Kreps, GL Bates, DW AF Kittler, AF Hobbs, J Volk, LA Kreps, GL Bates, DW TI The Internet as a vehicle to communicate health information during a public health emergency: A survey analysis involving the anthrax scare of 2001 SO JOURNAL OF MEDICAL INTERNET RESEARCH LA English DT Article DE bioterrorism; public health; communication; electronic mail; inequality; behavior AB Background: The recent public health risks arising from bioterrorist threats and outbreaks of infectious diseases like SARS (Severe Acute Respiratory Syndrome) highlight the challenges of effectively communicating accurate health information to an alarmed public. Objective: To evaluate use of the Internet in accessing information related to the anthrax scare in the United States in late 2001, and to strategize about the most effective use of this technology as a communication vehicle during times of public health crises. Methods: A paper-based survey to assess how individuals obtained health information relating to bioterrorism and anthrax during late 2001.We surveyed 500 randomly selected patients from two ambulatory primary care clinics affiliated with the Brigham and Women's Hospital in Boston, Massachusetts. Results: The response rate was 42%. While traditional media provided the primary source of information on anthrax and bioterrorism, 21% (95% Cl, 15% - 27%) of respondents reported searching the Internet for this information during late 2001. Respondents reported trusting information from physicians the most, and information from health websites slightly more than information from any traditional media source. Over half of those searching the Internet reported changing their behavior as a result of information found online. Conclusions: Many people already look to the Internet for information during a public health crisis, and information found online can positively influence behavioral responses to such crises. However, the potential of the Internet to convey accurate health information and advice has not yet been realized. In order to enhance the effectiveness of public-health communication, physician practices could use this technology to pro-actively e-mail their patients validated information. Still, unless Internet access becomes more broadly available, its benefits will not accrue to disadvantaged populations. C1 Brigham & Womens Hosp, Div Gen Med & Primary Care, Dept Med, Boston, MA 02129 USA. Partners Healthcare Syst, Dept Clin & Qual Anal, Wellesley, MA 02481 USA. NCI, Hlth Commun & Informat Res Branch, Bethesda, MD 20892 USA. RP Bates, DW (reprint author), Brigham & Womens Hosp, Div Gen Med & Primary Care, Dept Med, 1620 Tremont St,3rd Floor,Room BC3-2M, Boston, MA 02129 USA. EM dbates@partners.org NR 12 TC 26 Z9 27 U1 3 U2 14 PU JOURNAL OF MEDICAL INTERNET RESEARCH PI TORONTO PA TORONTO GENERAL HOSPITAL, R FRASER ELLIOTT BLDG, 4TH FL, R 4S435, 190 ELIZABETH ST, TORONTO, ON M5G 2C4, CANADA SN 1438-8871 J9 J MED INTERNET RES JI J. Med. Internet Res. PD JAN-MAR PY 2004 VL 6 IS 1 AR e8 DI 10.2196/jmir.6.1.e8 PG 10 WC Health Care Sciences & Services; Medical Informatics SC Health Care Sciences & Services; Medical Informatics GA 870FM UT WOS:000225043000008 PM 15111274 ER PT J AU Yankaskas, BC Klabunde, CN Ancelle-Park, R Rennert, G Wang, H Fracheboud, J Pou, G Bulliard, JL AF Yankaskas, BC Klabunde, CN Ancelle-Park, R Rennert, G Wang, H Fracheboud, J Pou, G Bulliard, JL CA Int Breast Canc Screening Network TI International comparison of performance measures for screening mammography: can it be done? SO JOURNAL OF MEDICAL SCREENING LA English DT Article ID HORMONE REPLACEMENT THERAPY; BREAST-CANCER; RECALL RATES; PROGRAM; WOMEN; NETHERLANDS; SENSITIVITY; GUIDELINES; MORTALITY; VIEW AB Objective: Published screening mammography performance measures vary across countries. An international study was undertaken to assess the comparability of two performance measures: the recall rate and positive predictive value (PPV). These measures were selected because they do not require identification of all cancers in the screening population, which is not always possible. Setting: The screening mammography programs or data registries in 25 member countries of the International Breast Cancer Screening Network (IBSN). Methods: In 1999 an assessment form was distributed to IBSN country representatives in order to obtain information on how screening mammography was performed and what specific data related to recall rates and PPV were collected. Participating countries were then asked to provide data to allow calculation of recall rates, PPV and cancer detection rates for screening mammography by age group for women screened in the period 1997-1999. Results: Twenty-two countries completed the assessment form and 14 countries provided performance data. Differences in screening mammography delivery and data collection were evident. For most countries, recall rates were higher for initial than for subsequent mammograms. There was no consistent relationship of initial to subsequent PPV, although PPV generally decreased as the recall rate increased. Recall rates decreased with increasing age, while PPV increased as age increased. Conclusion: Similar patterns for mammography performance measures were evident across countries. However, the development of a more standardized approach to defining and collecting data would allow more valid international comparisons, with the potential to optimize mammography performance. At present, international comparisons of performance should be made with caution due to differences in defining and collecting mammography data. C1 Univ N Carolina, Dept Radiol, Chapel Hill, NC 27599 USA. NCI, Appl Res Program, Bethesda, MD 20892 USA. Inst Veille Sanitaire, St Maurice, France. CHS Natl Israeli Canc Control Ctr, Haifa, Israel. Natl Israeli Breast Canc Screening Program, Minist Hlth, Haifa, Israel. Israel Canc Soc, Haifa, Israel. Directorate Hlth & Social Affairs, Oslo, Norway. Univ Med Ctr, Dept Publ Hlth, Erasmus MC, Rotterdam, Netherlands. Pro Ciencia, Montevideo, Uruguay. Univ Lausanne, Inst Social & Prevent Med, Canc Epidemiol Unit, Lausanne, Switzerland. RP Yankaskas, BC (reprint author), Univ N Carolina, Dept Radiol, CB 7515,106 Mason Farm Rd, Chapel Hill, NC 27599 USA. EM bcy@med.unc.edu NR 39 TC 64 Z9 65 U1 0 U2 3 PU ROYAL SOC MEDICINE PRESS LTD PI LONDON PA 1 WIMPOLE STREET, LONDON W1G 0AE, ENGLAND SN 0969-1413 J9 J MED SCREEN JI J. Med. Screen. PY 2004 VL 11 IS 4 BP 187 EP 193 DI 10.1258/0969141042467430 PG 7 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 033CB UT WOS:000236822800006 PM 15624239 ER PT J AU Kunick, C Lauenroth, K Wieking, K Xie, X Schultz, C Gussio, R Zaharevitz, D Leost, M Meijer, L Weber, A Jorgensen, FS Lemcke, T AF Kunick, C Lauenroth, K Wieking, K Xie, X Schultz, C Gussio, R Zaharevitz, D Leost, M Meijer, L Weber, A Jorgensen, FS Lemcke, T TI Evaluation and comparison of 3D-QSAR CoMSIA models for CDK1, CDK5, and GSK-3 inhibition by paullones SO JOURNAL OF MEDICINAL CHEMISTRY LA English DT Article ID GLYCOGEN-SYNTHASE KINASE-3; CYCLIN-DEPENDENT KINASES; MOLECULAR SIMILARITY INDEXES; ALZHEIMERS-DISEASE; PROTEIN-KINASES; FORCE-FIELD; M-PHASE; POTENT; PHOSPHORYLATION; FAMILY AB With a view to the rational design of selective GSK-3beta inhibitors, 3D-QSAR CoMSIA models were developed for the inhibition of the three serine/threonine kinases CDK1/cyclin B, CDK5/p25, and GSK-3beta by compounds from the paullone inhibitor family. The models are based on the kinase inhibition data of 52 paullone entities, which were aligned by a docking routine into the ATP-binding cleft of a CDK1/cyclin B homology model. Variation of grid spacing and column filtering were used during the optimization of the models. The predictive ability of the models was shown by a leave-one-out cross-validation and the prediction of an independent set of test compounds, which were synthesized especially for this purpose. Besides paullones with the basic indolo [3,2-d] [1]benzazepine core, the test set comprised novel thieno [3',2':2,3]-azepino[4,5-b]indoles, pyrido[2',3':2,3]azepino[4,5-b]indoles, and a pyrido[3',2':4,5]pyrrolo[3,2-d] [1]benzazepine. The best statistical values for the CoMSIA were obtained for the CDK1-models (r(2) = 0.929 and q(2) = 0.699), which were clearly superior to the models for CDK5 (r(2) = 0.874 and q(2) = 0.652) and GSK-3 (r(2) = 0.871 and q(2) = 0.554). C1 Univ Hamburg, Inst Pharm, Abt Pharmazeut Chem, D-20146 Hamburg, Germany. NCI, Dev Therapeut Program, Div Canc Treatment & Diag, Rockville, MD 20852 USA. CNRS, Biol Stn, F-29682 Roscoff, France. Univ Marburg, Dept Pharmaceut Chem, D-35032 Marburg, Germany. Danish Univ Pharmaceut Sci, Dept Med Chem, DK-2100 Copenhagen, Denmark. RP Lemcke, T (reprint author), Univ Hamburg, Inst Pharm, Abt Pharmazeut Chem, Bundesstr 45, D-20146 Hamburg, Germany. EM lemcke@chemie.uni-hamburg.de OI Jorgensen, Flemming Steen/0000-0001-8040-2998 NR 59 TC 82 Z9 88 U1 2 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 JAN 1 PY 2004 VL 47 IS 1 BP 22 EP 36 DI 10.1021/jm0308904 PG 15 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA 780BD UT WOS:000189350400005 PM 14695817 ER PT J AU Blinova, K Combs, C Kellman, P Balaban, RS AF Blinova, K Combs, C Kellman, P Balaban, RS TI Fluctuation analysis of mitochondrial NADH fluorescence signals in confocal and two-photon microscopy images of living cardiac myocytes SO JOURNAL OF MICROSCOPY-OXFORD LA English DT Article DE correlation analysis; rabbit; temperature; time series; two-photon microscopy ID HEART-CELLS AB A fluctuation analysis was performed on the reduced nicotine adenine dinucleotide (NADH) fluorescence signal from resting rabbit myocytes using confocal and two-photon microscopy. The purpose of this study was to establish whether any co-ordinated biochemical processes, such as binding, metabolism and inner mitochondrial membrane potential, were contributing to NADH signal fluctuations above background instrument noise. After a basic characterization of the instrument noise, time series of cellular NADH fluorescence images were collected and compared with an internal standard composed of NADH in the bathing medium. The coefficient of variation as a function of mean signal amplitude of cellular NADH fluorescence and bathing media NADH was identical even as a function of temperature. These data suggest that the fluctuations in cellular NADH fluorescence in resting myocytes are dominated by sampling noise of these instruments and not significantly modified by biological processes. Further analysis revealed no significant spatial correlations within the cell, and Fourier analysis revealed no coherent frequency information. These data suggest that the impact of biochemical processes, which might affect cellular NADH fluorescence emission, are either too small in magnitude, occurring in the wrong temporal scale or too highly spatially localized for detection using these standard optical microscopy approaches. C1 NHLBI, Cardiac Energet Lab, NIH, US Dept HHS, Bethesda, MD 20892 USA. RP Blinova, K (reprint author), NHLBI, Cardiac Energet Lab, NIH, US Dept HHS, Bethesda, MD 20892 USA. NR 15 TC 14 Z9 14 U1 0 U2 2 PU BLACKWELL PUBLISHING LTD PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 0022-2720 J9 J MICROSC-OXFORD JI J. Microsc.-Oxf. PD JAN PY 2004 VL 213 BP 70 EP 75 DI 10.1111/j.1365-2818.2004.01278.x PN 1 PG 6 WC Microscopy SC Microscopy GA 755MU UT WOS:000187407300009 PM 14678514 ER PT J AU Lakatta, EG AF Lakatta, EG TI Failing human myocardium "fails" to translate performance demand signals SO JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY LA English DT Editorial Material ID FORCE-FREQUENCY-RELATIONSHIP; MAMMALIAN CARDIAC-MUSCLE; HUMAN DILATED CARDIOMYOPATHY; LENGTH-DEPENDENT ACTIVATION; NONFAILING HUMAN MYOCARDIUM; FERRET VENTRICULAR MUSCLE; RETICULUM CALCIUM RELEASE; HUMAN HEART-FAILURE; SARCOPLASMIC-RETICULUM; LIGHT FLUCTUATION C1 NIA, Cardiovasc Sci Lab, NIH, Ctr Gerontol Res, Baltimore, MD 21224 USA. RP Lakatta, EG (reprint author), NIA, Cardiovasc Sci Lab, NIH, Ctr Gerontol Res, 5600 Nathan Shock Dr, Baltimore, MD 21224 USA. EM LakattaE@grc.nia.nih.gov NR 46 TC 1 Z9 1 U1 0 U2 1 PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0022-2828 EI 1095-8584 J9 J MOL CELL CARDIOL JI J. Mol. Cell. Cardiol. PD JAN PY 2004 VL 36 IS 1 BP 1 EP 5 DI 10.1016/j.yjmcc.2003.10.014 PG 5 WC Cardiac & Cardiovascular Systems; Cell Biology SC Cardiovascular System & Cardiology; Cell Biology GA 772EN UT WOS:000188828500001 PM 14734039 ER PT J AU Xiao, RP Balke, CW AF Xiao, RP Balke, CW TI Na+/Ca2+ exchange linking beta(2)-adrenergic G(i) signaling to heart failure: associated defect of adrenergic contractile support SO JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY LA English DT Editorial Material ID RAT VENTRICULAR MYOCYTES; CARDIAC MYOCYTES; PERTUSSIS-TOXIN; G-PROTEIN; RECEPTOR SUBTYPES; CELL-DEATH; APOPTOSIS; STIMULATION; EXPRESSION; KINASE C1 Univ Maryland, Sch Med, Dept Physiol, Baltimore, MD 21201 USA. Univ Maryland, Div Cardiol, Dept Med, Baltimore, MD 21201 USA. NIA, Cardiovasc Sci Lab, NIH, Baltimore, MD 21224 USA. Peking Univ, Inst Cardiovasc Sci, Beijing 100083, Peoples R China. Johns Hopkins Univ, Sch Med, Dept Med, Baltimore, MD 21203 USA. RP Balke, CW (reprint author), Univ Maryland, Sch Med, Dept Physiol, Room 525,Howard Hall,660 W Redwood St, Baltimore, MD 21201 USA. EM bbalke@medicine.umaryland.edu NR 39 TC 9 Z9 11 U1 0 U2 2 PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0022-2828 EI 1095-8584 J9 J MOL CELL CARDIOL JI J. Mol. Cell. Cardiol. PD JAN PY 2004 VL 36 IS 1 BP 7 EP 11 DI 10.1016/j.yjmcc.2003.10.013 PG 5 WC Cardiac & Cardiovascular Systems; Cell Biology SC Cardiovascular System & Cardiology; Cell Biology GA 772EN UT WOS:000188828500002 PM 14734040 ER PT J AU Boissinot, SP Roos, C Furano, AV AF Boissinot, SP Roos, C Furano, AV TI Different rates of LINE-1 (L1) retrotransposon amplification and evolution in new world monkeys SO JOURNAL OF MOLECULAR EVOLUTION LA English DT Article DE LINE-1; non-LTR; retrotransposon; primate; new world monkeys ID REPEAT FAMILY; SEQUENCES; LINEAGES; PRIMATES; ELEMENTS; EVENTS; MOUSE; END AB LINE-1 (L1) elements constitute the major family of retrotransposons in mammalian genomes. Here we report the first investigation of L1 evolution in New World monkeys (NWM). Two regions of the second open-reading frame were analyzed by two methods in three NWM species, the squirrel monkey (Saimiri sciureus), the tamarin (Saguinus oedipus), and the spider monkey (Ateles paniscus). Since these three species diverged, L1 has amplified in the Saimiri and Saguinus lineages but L I activity seems to have been strongly reduced in the Ateles lineage. In addition, the active L1 lineage has evolved rapidly in Saimiri and Saguinus, generating species-specific subfamilies. In contrast, we found no evidence for a species-specific subfamily in Ateles, a result consistent with the low L1 activity in this species for the last similar to25 My. C1 NIDDKD, Sect Genom Struct & Funct, Mol & Cellular Biol Lab, NIH, Bethesda, MD 20892 USA. German Primate Ctr, D-37077 Gottingen, Germany. RP Furano, AV (reprint author), NIDDKD, Sect Genom Struct & Funct, Mol & Cellular Biol Lab, NIH, Bldg 8,Room 203,8 Ctr Dr,MSC 0830, Bethesda, MD 20892 USA. EM avf@helix.nih.gov NR 33 TC 15 Z9 15 U1 0 U2 2 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0022-2844 J9 J MOL EVOL JI J. Mol. Evol. PD JAN PY 2004 VL 58 IS 1 BP 122 EP 130 DI 10.1007/s00239-003-2539-x PG 9 WC Biochemistry & Molecular Biology; Evolutionary Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Evolutionary Biology; Genetics & Heredity GA 763QP UT WOS:000188112200011 PM 14743320 ER PT J AU Dibrov, P Dibrov, E Pierce, GN Galperin, MY AF Dibrov, P Dibrov, E Pierce, GN Galperin, MY TI Salt in the wound: A possible role of Na+ gradient in chlamydial infection SO JOURNAL OF MOLECULAR MICROBIOLOGY AND BIOTECHNOLOGY LA English DT Review DE Chlamydia; pneumonia; bronchitis; atherosclerosis; endocarditis; trachoma; vaginitis; proton-motive force; Na+/H+ exchanger; genome analysis; drug design; korormycin ID MARINE VIBRIO-ALGINOLYTICUS; NADH-QUINONE REDUCTASE; DEVELOPMENTAL CYCLE; GLUCOSE-METABOLISM; GENOME SEQUENCE; TRACHOMATIS; PNEUMONIAE; MEMBRANE; CELLS; H+ AB Genome analysis has revealed the presence of key components of the Na+ chemiosmotic cycle, including the primary Na+ pump (Na+-translocating NADH:ubiquinone oxidoreductase), in the cytoplasmic membrane of two ubiquitous human pathogens, Chlamydia trachomatis and Chlamydiophyla pneumoniae. This observation seemed paradoxical in the case of obligatory intracellular parasites because the Na+ cycle is thought to be primarily a mechanism that enhances the adaptive potential in free-living bacteria that are often facing drastic changes in the salinity and pH of the environment. We present a model suggesting that operation of the Na+ cycle may play an important role in the course of chlamydial infection, when the Na+ and H+ homeostasis of the host cell become severely impaired. This introduces the intriguing possibility of the application of drugs targeting Na+-transporting enzymes to chlamydial infections, which are notoriously difficult to treat. Copyright (C) 2004 S. Karger AG, Basel. C1 Univ Manitoba, Dept Microbiol, Winnipeg, MB R3T 2N2, Canada. Univ Manitoba, Div Stroke & Vasc Dis, St Boniface Gen Hosp Res Ctr, Winnipeg, MB, Canada. Univ Manitoba, Fac Med, Dept Physiol, Winnipeg, MB, Canada. NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD USA. RP Dibrov, P (reprint author), Univ Manitoba, Dept Microbiol, Winnipeg, MB R3T 2N2, Canada. EM dibrovp@ms.umanitoba.ca RI Galperin, Michael/B-5859-2013; OI Galperin, Michael/0000-0002-2265-5572; Pierce, Grant/0000-0001-7674-0142 NR 42 TC 13 Z9 13 U1 0 U2 3 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1464-1801 J9 J MOL MICROB BIOTECH JI J. Mol. Microbiol. Biotechnol. PY 2004 VL 8 IS 1 BP 1 EP 6 DI 10.1159/000082075 PG 6 WC Biotechnology & Applied Microbiology; Microbiology SC Biotechnology & Applied Microbiology; Microbiology GA 898PJ UT WOS:000227088400001 PM 15741735 ER PT J AU Zhou, FC Sari, Y Powrozek, TA Spong, CY AF Zhou, FC Sari, Y Powrozek, TA Spong, CY TI A neuroprotective peptide antagonizes fetal alcohol exposure-compromised brain growth SO JOURNAL OF MOLECULAR NEUROSCIENCE LA English DT Article DE fetal alcohol syndrome; fetal alcohol effect; microencephaly; brain development; neurotrophic factor ID DEPENDENT NEUROTROPHIC FACTOR; VASOACTIVE-INTESTINAL-PEPTIDE; FEMTOMOLAR-ACTING PEPTIDES; DEVELOPING MOUSE-BRAIN; CELL-DEATH; NEURAL-TUBE; ETHANOL; NEURONS; MICE; PREVENTION AB We evaluated a 9-amino-acid peptide, SALLRSIPA (SAL), an agonist of activity-dependent neurotrophic factor (ADNF), for its protective properties against fetal alcohol-related brain growth retardation, using an established liquid diet model of alcohol-related neurodevelopmental disorder (ARND) in C57BL/6 mice. Alcohol exposure during neurulation reduced body weight, head size, and specifically brain weight and volume. Major gross brain deficits include underdevelopment of brain areas, cortical thinning, ventricle enlargement, and restricted midline neural tissue growth leading to openings at the roof/floor plate. SALLRSIPA (SAL) treatment increased fetal body weight and restored brain weight, brain volume, and regional brain size. Furthermore, SAL restored cortical thickness, reduced the size and frequency of neural tube openings, and attenuated ventricular enlargement. The ability of SAL to antagonize alcohol-retarded brain growth and development of forebrain and midline neural tube at midgestation suggests its potential use as an antagonist against fetal alcohol-rendered microencephaly early in development. C1 Indiana Univ, Sch Med, Dept Anat & Cell Biol, Indianapolis, IN 46202 USA. Indiana Univ, Sch Med, Program Med Neurobiol, Indianapolis, IN 46202 USA. IUPUI, Dept Psychol, Indianapolis, IN 46202 USA. NICHD, Sect Dev & Mol Pharmacol, Dev Neurobiol Lab, Bethesda, MD 20892 USA. RP Zhou, FC (reprint author), Indiana Univ, Sch Med, Dept Anat & Cell Biol, Indianapolis, IN 46202 USA. EM imce100@iupui.edu FU NIAAA NIH HHS [U01 AA014829, R01AA12406, AA07462] NR 32 TC 27 Z9 29 U1 0 U2 0 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 USA SN 0895-8696 J9 J MOL NEUROSCI JI J. Mol. Neurosci. PY 2004 VL 24 IS 2 BP 189 EP 199 DI 10.1385/JMN:24:2:189 PG 11 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 864IX UT WOS:000224628300005 PM 15456932 ER PT J AU Loh, YP Kim, T Rodriguez, YM Cawley, NX AF Loh, YP Kim, T Rodriguez, YM Cawley, NX TI Secretory granule biogenesis and neuropeptide sorting to the regulated secretory pathway in neuroendocrine cells SO JOURNAL OF MOLECULAR NEUROSCIENCE LA English DT Article; Proceedings Paper CT 13th Annual Summer Neuropeptides Conference CY 2003 CL MONTAUK, NY DE secretory granule; pro-opiomelanocortin; chromogranin; neuropeptide sorting ID CARBOXYPEPTIDASE-E; CHROMOGRANIN-A; RECEPTOR; PROTEIN; PROOPIOMELANOCORTIN; PROENKEPHALIN; PROINSULIN; MECHANISM; SIGNAL AB Neuropeptide precursors synthesized at the rough endoplasmic reticulum are transported and sorted at the trans-Golgi network (TGN) to the granules of the regulated secretory pathway (RSP) of neuroendocrine cells. They are then processed into active peptides and stored in large dense-core granules (LDCGs) until secreted upon stimulation. We have studied the regulation of biogenesis of the LDCGs and the mechanism by which neuropeptide precursors, such as pro-opiomelanocortin (POMC), are sorted into these LDCGs of the RSP in neuroendocrine and endocrine cells. We provide evidence that chromogranin A (CgA), one of the most abundant acidic glycoproteins ubiquitously present in neuroendocrine/endocrine cells, plays an important role in the regulation of LDCG biogenesis. Specific depletion of CgA expression by antisense RNAs in PC12 cells led to a profound loss of secretory granule formation. Exogenously expressed POW was neither stored nor secreted in a regulated manner in these CgA-deficient PC12 cells. Overexpression of CgA in a CgA- and LDCG-deficient endocrine cell line, 6T3, restored regulated secretion of transfected POW and the presence of immunoreactive CgA at the tips of the processes of these cells. Unlike CgA, CgB, another granin protein, could not substitute for the role of CgA in regulating LDCG biogenesis. Thus, we conclude that CgA is a key player in the regulation of the biogenesis of LDCGs in neuroendocrine cells. To examine the mechanism of sorting POW to the LDCGs, we carried out site-directed mutagenesis, transfected the POW mutants into PC12 cells, and assayed for regulated secretion. Our previous molecular modeling studies predicted a three-dimensional sorting motif in POW that can bind to a sorting receptor, membrane carboxypeptidase E (CPE). The sorting signal consists of four conserved residues at the N-terminal loop structure of POMC: two acidic residues and two hydrophobic residues. The two acidic residues were predicted to bind to a domain on CPE (CPE254-273) containing two basic residues (R255 and K260) to effect sorting into immature secretory granules. Site-directed mutagenesis of the motif on POW resulted in accumulation of the mutant in the Golgi, as well as high basal secretion, indicating that the mutant POW was inefficiently sorted to the RSP These results support the model that POW is actively sorted to the RSP granules for processing and secretion by a sorting signal-mediated mechanism. C1 NICHHD, Cellular Neurobiol Sect, Dev Neurobiol Lab, NIH, Bethesda, MD 20892 USA. RP Loh, YP (reprint author), NICHHD, Cellular Neurobiol Sect, Dev Neurobiol Lab, NIH, Bethesda, MD 20892 USA. EM lohp@mail.nih.gov NR 16 TC 27 Z9 29 U1 0 U2 0 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 USA SN 0895-8696 J9 J MOL NEUROSCI JI J. Mol. Neurosci. PY 2004 VL 22 IS 1-2 BP 63 EP 71 DI 10.1385/JMN:22:1-2:63 PG 9 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 773LG UT WOS:000188924800008 PM 14742911 ER PT J AU Kovacs, M Toth, J Malnasi-Csizmadia, A Bagshaw, CR Nyitray, L AF Kovacs, M Toth, J Malnasi-Csizmadia, A Bagshaw, CR Nyitray, L TI Engineering lysine reactivity as a conformational sensor in the Dictyostelium myosin II motor domain SO JOURNAL OF MUSCLE RESEARCH AND CELL MOTILITY LA English DT Article ID X-RAY STRUCTURES; DEPENDENT ADENOSINE-TRIPHOSPHATASE; LEVER-ARM MOVEMENT; DISCOIDEUM MYOSIN; ACTIVE-SITE; SKELETAL-MUSCLE; ATP HYDROLYSIS; TRINITROPHENYLATED MYOSIN; ANGSTROM RESOLUTION; TRYPTOPHAN RESIDUE AB Lys84 of skeletal muscle myosin located at the interface between the motor and neck domains has long been utilized as a useful chemical probe sensing motor domain conformational changes and tilting of the lever arm. Here we report the first site-directed mutagenesis study on this side chain and its immediate chemical environment. We made Dictyostelium myosin II motor domain constructs in which Lys84 was replaced by either a methionine or a glutamic acid residue and another mutant containing an Arg704Glu substitution. By following trinitrophenylation of the mutant constructs, we first unambiguously identify Lys84 as the reactive lysine in Dictyostelium myosin. Analysis of the reaction profiles also reveals that the Lys84-Arg704 interaction at the interface of two subdomains of the myosin head has a significant effect on Lys84 reactivity, but it is not the only determinant of this property. Our findings imply that the nucleotide sensitivity of the trinitrophenylation reaction is a general feature of conventional myosins that reflects similar changes in the conformational dynamics of the different orthologs during the ATPase cycle. C1 Eotvos Lorand Univ, Dept Biochem, H-1117 Budapest, Hungary. Univ Leicester, Dept Biochem, Leicester LE1 7RH, Leics, England. RP Kovacs, M (reprint author), NHLBI, Mol Cardiol Lab, 9000 Rockville Pike, Bethesda, MD 20892 USA. EM kovacsm@nhlbi.nih.gov RI Kovacs, Mihaly/A-6841-2011; OI Bagshaw, Clive/0000-0002-5396-153X NR 57 TC 2 Z9 2 U1 0 U2 2 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0142-4319 J9 J MUSCLE RES CELL M JI J. Muscle Res. Cell Motil. PY 2004 VL 25 IS 1 BP 95 EP + DI 10.1023/B:JURE.0000021352.80800.b8 PG 9 WC Cell Biology SC Cell Biology GA 806CT UT WOS:000220412700011 PM 15160493 ER PT J AU Siegman, MJ Hartshorne, DJ Adelstein, RS Bond, M Casteels, R Ebashi, S Goldman, YE Kamm, K Stull, JT Leapman, R Sellers, J Trentham, DR Warshaw, DM Weber, A AF Siegman, MJ Hartshorne, DJ Adelstein, RS Bond, M Casteels, R Ebashi, S Goldman, YE Kamm, K Stull, JT Leapman, R Sellers, J Trentham, DR Warshaw, DM Weber, A TI Andrew P. Somlyo (1930-2004) - Obituary SO JOURNAL OF MUSCLE RESEARCH AND CELL MOTILITY LA English DT Biographical-Item C1 Thomas Jefferson Univ, Dept Physiol, Philadelphia, PA 19107 USA. Univ Arizona, Muscle Biol Grp, Tucson, AZ 85721 USA. NHLBI, Bethesda, MD 20892 USA. Univ Maryland, College Pk, MD 20742 USA. Katholieke Univ Leuven, Louvain, Belgium. Penn Muscle Inst, Philadelphia, PA USA. Univ Texas, SW Med Ctr, Dallas, TX USA. NIH, Bethesda, MD 20892 USA. Natl Inst Med Res, Mill Hill, England. RP Siegman, MJ (reprint author), Thomas Jefferson Univ, Dept Physiol, Philadelphia, PA 19107 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0142-4319 J9 J MUSCLE RES CELL M JI J. Muscle Res. Cell Motil. PY 2004 VL 25 IS 3 BP 193 EP 202 PG 10 WC Cell Biology SC Cell Biology GA 864NM UT WOS:000224640200001 PM 15505897 ER PT J AU Limouze, J Straight, AF Mitchison, T Sellers, JE AF Limouze, J Straight, AF Mitchison, T Sellers, JE TI Specificity of blebbistatin, an inhibitor of myosin II SO JOURNAL OF MUSCLE RESEARCH AND CELL MOTILITY LA English DT Article DE myosin; blebbistatin; inhibitors ID RABBIT SKELETAL-MUSCLE; 2,3-BUTANEDIONE MONOXIME; HEAVY-MEROMYOSIN; CONTRACTION; PHOSPHORYLATION; MECHANISM; ACTIN AB Blebbistatin is a small molecule inhibitor discovered in a screen for inhibitors of nonmuscle myosin IIA. We have examined the specificity and potency of the drug by assaying its effects on the actin-activated MgATPase assay of diverse members of the myosin superfamily. Blebbistatin potently inhibits several striated muscle myosins as well as vertebrate nonmuscle myosin IIA and IIB with IC50 values ranging from 0.5 to 5 muM. Interestingly, smooth muscle which is highly homologous to vertebrate nonmuscle myosin is only poorly inhibited (IC50=80 muM). The drug potently inhibits Dictyostelium myosin II, but poorly inhibits Acanthamoeba myosin II. Blebbistatin did not inhibit representative myosin superfamily members from classes I, V, and X. C1 NHLBI, Mol Cardiol Lab, Natl Inst Hlth, Bethesda, MD 20892 USA. Harvard Univ, Sch Med, Inst Chem & Cell Biol, Boston, MA 02115 USA. RP Sellers, JE (reprint author), NHLBI, Mol Cardiol Lab, Natl Inst Hlth, Bethesda, MD 20892 USA. EM sellersj@nhlbi.nih.gov OI Straight, Aaron/0000-0001-5885-7881 NR 24 TC 196 Z9 201 U1 5 U2 20 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0142-4319 J9 J MUSCLE RES CELL M JI J. Muscle Res. Cell Motil. PY 2004 VL 25 IS 4-5 BP 337 EP 341 DI 10.1007/s10974-004-6060-7 PG 5 WC Cell Biology SC Cell Biology GA 890NG UT WOS:000226517500008 PM 15548862 ER PT J AU Sellers, JR AF Sellers, JR TI Dedicated to the memory of Jean Hanson - Preface SO JOURNAL OF MUSCLE RESEARCH AND CELL MOTILITY LA English DT Editorial Material C1 NHLBI, Bethesda, MD 20892 USA. RP Sellers, JR (reprint author), NHLBI, Bldg 10, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0142-4319 J9 J MUSCLE RES CELL M JI J. Muscle Res. Cell Motil. PY 2004 VL 25 IS 6 BP 439 EP 439 DI 10.1007/s10974-004-4851-5 PG 1 WC Cell Biology SC Cell Biology GA 929AR UT WOS:000229315000001 ER PT J AU Sellers, JR AF Sellers, JR TI Fifty years of contractility research post sliding filament hypothesis SO JOURNAL OF MUSCLE RESEARCH AND CELL MOTILITY LA English DT Article; Proceedings Paper CT Symposium in Honor of Jean Hanson CY MAY 20-21, 2004 CL Kings Coll, London, ENGLAND HO Kings Coll ID ACTIN-BASED MOTILITY; MYOSIN MOTOR DOMAIN; SKELETAL-MUSCLE; CRYSTAL-STRUCTURE; STRIATED-MUSCLE; LIGHT-CHAIN; ADENOSINE-TRIPHOSPHATASE; MOLECULAR-MECHANISMS; WORKING STROKE; THIN-FILAMENTS C1 NHLBI, Mol Cardiol Lab, NIH, Bethesda, MD 20892 USA. RP Sellers, JR (reprint author), NHLBI, Mol Cardiol Lab, NIH, Bldg 10, Bethesda, MD 20892 USA. EM sellersj@nhlbi.nih.gov NR 101 TC 10 Z9 11 U1 1 U2 1 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0142-4319 J9 J MUSCLE RES CELL M JI J. Muscle Res. Cell Motil. PY 2004 VL 25 IS 6 BP 475 EP 482 DI 10.1007/s10974-004-4239-6 PG 8 WC Cell Biology SC Cell Biology GA 929AR UT WOS:000229315000008 PM 15630612 ER PT J AU Miller, FW AF Miller, FW TI Clinical presentation and therapy of idiopathic inflammatory myopathies SO JOURNAL OF MUSCULOSKELETAL PAIN LA English DT Article DE myositis; polymyositis; dermatomyositis; inclusion body myositis; therapy ID MYOSITIS-SPECIFIC AUTOANTIBODIES; MUSCLE DISEASE; CLASSIFICATION; PROGNOSIS AB The idiopathic inflammatory myopathies [IIM] are a group of systemic immune-mediated disorders characterized by chronic muscle weakness and inflammation. The most common forms are polymyositis, dermatomyositis, and inclusion body myositis; however, dividing the IIM into serologic groups is also useful for assessing and managing these syndromes. Although pathogeneses are unknown, evidence suggests that these acquired diseases result from environmental exposures in genetically susceptible individuals. Clinical presentations are quite diverse and range from slowly progressive nearly asymptomatic syndromes to acute life-threatening disorders. Signs and symptoms vary widely and often change over the course of the illness. Common signs and symptoms include: fatigue, muscle pain and atrophy, arthralgia and arthritis, rashes of many types, shortness of breath, dysphagia, edema, Raynaud's phenomenon, subcutaneous nodules and calcifications, dysphonia, fever, gastrointestinal pain, and weight loss. Therapy has been poorly studied due to the rarity and heterogeneity of IIM. The goals of therapy are to eliminate inflammation in involved tissues and to regain function through rehabilitation. Corticosteroids remain first line therapy, although in cases with poor prognostic features, additional immunosuppressives are often used from the beginning of disease. Methotrexate, azathioprine, and intravenous immunoglobulin are the best-studied agents, but other drugs reported to be useful include cyclosporin, tacrolimus, cyclophosphamide, hydroxychloroquine sulfate, mycophenolate mofetil, and combinations of the above. Case reports suggest that targeted biologic agents, including monoclonal antibodies or fusion proteins directed at TNF alpha, B cells or complement, as well as autologous stem cell transplantation, might be beneficial and research is ongoing in this area. Advances in understanding the pathology and immunology of myositis, the development of new agents for related conditions, and recent international consensus on the conduct and reporting of myositis clinical trials, should all add momentum to improving outcomes for these increasingly recognized disorders. C1 Natl Inst Environm Hlth Sci, Environm Autoimmun Grp, Off Clin Res, NIH, Bethesda, MD 20892 USA. RP Miller, FW (reprint author), Natl Inst Environm Hlth Sci, Environm Autoimmun Grp, Off Clin Res, NIH, 9000 Rockville Pike,NIH Bldg 9,Room 1W107,MSC 095, Bethesda, MD 20892 USA. EM millerf@mail.nih.gov OI Miller, Frederick/0000-0003-2831-9593 NR 15 TC 0 Z9 0 U1 0 U2 1 PU HAWORTH PRESS INC PI BINGHAMTON PA 10 ALICE ST, BINGHAMTON, NY 13904-1580 USA SN 1058-2452 J9 J MUSCULOSKELET PAIN JI J. Musculoskelet. Pain PY 2004 VL 12 IS 3-4 BP 85 EP 91 DI 10.1300/J094v12n03_13 PG 7 WC Rehabilitation; Rheumatology SC Rehabilitation; Rheumatology GA 009YY UT WOS:000235150800014 ER PT J AU Milanowski, DJ Gustafson, KR Kelley, JA McMahon, JB AF Milanowski, DJ Gustafson, KR Kelley, JA McMahon, JB TI Caulibugulones A-F, novel cytotoxic isoquinoline quinones and iminoquinones from the marine bryozoan Caulibugula intermis SO JOURNAL OF NATURAL PRODUCTS LA English DT Article ID SPONGE RENIERA SP; ANTINEOPLASTIC AGENTS; BUGULA-NERITINA; STREPTOMYCES-LAVENDULAE; METABOLITES; BRYOSTATIN-3; ALKALOIDS; STEREOCHEMISTRY; MIMOSAMYCIN; INHIBITORS AB An extract of the marine bryozoan Caulibugula intermis, collected in the Indo-Pacific off Palau, produced a distinct pattern of differential cytotoxicity in the National Cancer Institute's 60 cell line antitumor screen. Bioactivity-directed fractionation of the extract provided six new compounds, caulibugulones A-F (1-6). The structures of these novel metabolites were determined by spectrochemical analyses including LC-MS, HRFABMS, 1-D and 2-D NMR experiments, and by comparison with related compounds. The structures of compounds 2 and 3 were confirmed by chemical interconversion. The isolated compounds exhibited IC50's of 0.03-1.67 mug/mL against murine tumor cells in an in vitro cytotoxicity assay. C1 NCI, Ctr Canc Res, Mol Targets Dev Program, Frederick, MD 21702 USA. NCI, Ctr Canc Res, Med Chem Lab, Frederick, MD 21702 USA. RP Gustafson, KR (reprint author), NCI, Ctr Canc Res, Mol Targets Dev Program, Bldg 1052,Room 121, Frederick, MD 21702 USA. EM manuscripts@mail.ncifcrf.gov NR 38 TC 35 Z9 35 U1 2 U2 5 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0163-3864 J9 J NAT PROD JI J. Nat. Prod. PD JAN PY 2004 VL 67 IS 1 BP 70 EP 73 DI 10.1021/np030378l PG 4 WC Plant Sciences; Chemistry, Medicinal; Pharmacology & Pharmacy SC Plant Sciences; Pharmacology & Pharmacy GA 766GA UT WOS:000188364400015 PM 14738389 ER PT J AU Heinz, A Jones, DW Zajicek, K Gorey, JG Juckel, G Higley, JD Weinberger, DR AF Heinz, A Jones, DW Zajicek, K Gorey, JG Juckel, G Higley, JD Weinberger, DR TI Depletion and restoration of endogenous monoamines affects beta-CIT binding to serotonin but not dopamine transporters in non-human primates SO JOURNAL OF NEURAL TRANSMISSION-SUPPLEMENT LA English DT Article ID HEALTHY-HUMAN SUBJECTS; DORSAL RAPHE NUCLEUS; IN-VIVO; BRAIN; SPECT; AVAILABILITY; BIODISTRIBUTION; CITALOPRAM; DEPRESSION; TERMINALS AB The radioligand [I-123]beta-CIT binds to dopamine transporters in striatum and to serotonin transporters in brainstem. Endogenous dopamine or serotonin may compete with radioligand binding at monoamine transporters. We used alpha-methyl-p-tyrosine (AMPT) to block dopamine production and measured [I-123]beta-CIT binding before and after endogenous dopamine was restored by IV administration of the dopamine precursor L-dihydroxyphenylalanine (L-DOPA) in rhesus monkeys. P-chlorophenylalanine (pCPA) was used to inhibit serotonin production, and [I-123]beta-CIT binding was assessed before and after IV administration of the serotonin precursor 5-hydroxy-L-tryptophan (L-5-HTP) restored endogenous serotonin. Pretreatment with benserazide blocked peripheral decarboxylization in both paradigms. Serotonin restoration measurably displaced [I-123]beta-CIT binding to brainstem serotonin transporters but not to striatal dopamine transporters. Restoration of dopamine apparently did not affect [I-123]beta-CIT binding to striatal dopamine transporters. However, dopamine restoration reduced radioligand binding to brainstem serotonin transporters, most likely due to dopamine release from serotonin neurons following L-DOPA administration. The higher striatal density of dopamine transporters relative to dopamine concentrations may explain why [I-123]beta-CIT displacement by endogenous dopamine was not observed. This study indicates that [I-123]beta-CIT binding in brainstem (raphe area) is affected by endogenous serotonin release in vivo and that L-DOPA treatment may cause serotonin neurons in the brainstem to corelease dopamine. C1 Charite Univ Med Berlin, Dept Psychiat, D-10117 Berlin, Germany. NIMH, Clin Brain Disorders Branch, NIH, Bethesda, MD 20892 USA. NIAAA, Clin Studies Lab, DICBR, Bethesda, MD 20892 USA. RP Heinz, A (reprint author), Charite Univ Med Berlin, Dept Psychiat, Charite Campus Mitte,Schumannstr 20-21, D-10117 Berlin, Germany. EM andreas.heinz@charite.de NR 25 TC 13 Z9 13 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0303-6995 J9 J NEURAL TRANSM-SUPP JI J. Neural Transm.-Suppl. PY 2004 IS 68 BP 29 EP 38 PG 10 WC Neurosciences SC Neurosciences & Neurology GA 847QB UT WOS:000223408900005 PM 15354387 ER PT J AU Cai, JL Cheng, AW Luo, YQ Lu, CB Mattson, MP Rao, MS Furukawa, K AF Cai, JL Cheng, AW Luo, YQ Lu, CB Mattson, MP Rao, MS Furukawa, K TI Membrane properties of rat embryonic multipotent neural stem cells SO JOURNAL OF NEUROCHEMISTRY LA English DT Article DE calcium; gap junctions; glucose transporter; ion channel; precursor; progenitor ID HUMAN HEMATOPOIETIC PROGENITORS; EPIDERMAL-GROWTH-FACTOR; CENTRAL-NERVOUS-SYSTEM; ALDEHYDE DEHYDROGENASE; NEURONAL DIFFERENTIATION; POSTNATAL-DEVELOPMENT; POTASSIUM CHANNELS; GAP-JUNCTIONS; SPINAL-CORD; IN-VITRO AB We have characterized several potential stem cell markers and defined the membrane properties of rat fetal (E10.5) neural stem cells (NSC) by immunocytochemistry, electrophysiology and microarray analysis. Immunocytochemical analysis demonstrates specificity of expression of Sox1, ABCG2/Bcrp1, and shows that nucleostemin labels both progenitor and stem cell populations. NSCs, like hematopoietic stem cells, express high levels of aldehyde dehydrogenase (ALDH) as assessed by Aldefluor labeling. Microarray analysis of 96 transporters and channels showed that Glucose transporter 1 (Glut1/Slc2a1) expression is unique to fetal NSCs or other differentiated cells. Electrophysiological examination showed that fetal NSCs respond to acetylcholine and its agonists, such as nicotine and muscarine. NSCs express low levels of tetrodotoxin (TTX) sensitive and insensitive sodium channels and calcium channels while expressing at least three kinds of potassium channels. We find that gap junction communication is mediated by connexin (Cx)43 and Cx45, and is essential for NSC survival and proliferation. Overall, our results show that fetal NSCs exhibit a unique signature that can be used to determine their location and assess their ability to respond to their environment. C1 NIA, Neurosci Lab, Gerontol Res Ctr, NIH, Baltimore, MD 21224 USA. RP Furukawa, K (reprint author), NIA, Neurosci Lab, Gerontol Res Ctr, NIH, 5600 Nathan Shock Dr, Baltimore, MD 21224 USA. RI Mattson, Mark/F-6038-2012 NR 69 TC 123 Z9 134 U1 2 U2 11 PU BLACKWELL PUBLISHING LTD PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PD JAN PY 2004 VL 88 IS 1 BP 212 EP 226 DI 10.1046/j.1471-4159.2003.02184.x PG 15 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 753YJ UT WOS:000187275700022 PM 14675165 ER PT J AU Chalela, JA Kang, DW Warach, S AF Chalela, JA Kang, DW Warach, S TI Multiple cerebral microbleeds: MRI marker of a diffuse hemorrhage-prone state SO JOURNAL OF NEUROIMAGING LA English DT Article DE microbleeds; hemorrhage risk; gradient-echo imaging ID ISCHEMIC-STROKE; INTRACEREBRAL HEMORRHAGE; HEMATOMAS AB Background. Recent reports have indicated that cerebral microbleeds (CMBs) detected on gradient-echo (GRE) magnetic resonance imaging may be a risk factor for therapy-related intracranial hemorrhages (ICHs). Case Description. The authors describe 3 patients with multiple CMBs in whom ICHs occurred either after tissue plasminogen activator administration or after the initiation of antiplatelet therapy. Hemorrhages occurred in brain areas with normal appearances on GRE imaging and remote from the CMBs. Conclusion. Multiple CMBs may signal a diffuse hemorrhage-prone vasculopathy. C1 NINDS, Sect Stroke Diagnost & Therapeut, NIH, Bethesda, MD 20892 USA. RP Chalela, JA (reprint author), NINDS, Sect Stroke Diagnost & Therapeut, NIH, 10 Ctr Dr,Room B1D733,MSC 1063, Bethesda, MD 20892 USA. EM chalelaj@ninds.nih.gov NR 11 TC 32 Z9 34 U1 0 U2 1 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1051-2284 J9 J NEUROIMAGING JI J. Neuroimaging PD JAN PY 2004 VL 14 IS 1 BP 54 EP 57 DI 10.1177/1051228403258673 PG 4 WC Clinical Neurology; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 876CZ UT WOS:000225474800007 PM 14748209 ER PT J AU Wei, RT Sternberg, EM AF Wei, RT Sternberg, EM TI IL-1 beta-mediated neuropeptide and immediate early gene mRNA induction is defective in Lewis hypothalamic cell cultures SO JOURNAL OF NEUROIMMUNOLOGY LA English DT Article DE inbred rats; hypothalamic cultures; neuropeptide; immediate early gene; interleukin-1 beta ID CORTICOTROPIN-RELEASING-HORMONE; PITUITARY-ADRENAL AXIS; NITRIC-OXIDE SYNTHASE; PARAVENTRICULAR NUCLEUS; ARGININE-VASOPRESSIN; NGFI-B; INFLAMMATORY CYTOKINES; IMMUNE CHALLENGE; QUANTITATIVE PCR; C-FOS AB We previously found that Lewis (LEW/N) hypothalamic cells respond to interleukin-1beta (IL-1beta) with reduced corticotropin-releasing hormone (CRH) and arginine vasopressin (AVP) peptide synthesis and secretion compared to Fischer (F344/N) cells. To investigate whether this peptide hyporesponsiveness in LEW/N cells is secondary to their deficient mRNA expression, temporal mRNA expression patterns of CRH, AVP, and several hypothalamic neuropeptides induced by IL-1beta in LEWN and F344/N hypothalamic dissociated cell cultures were delineated by quantitative real-time polymerase chain reaction (RT-PCR). To investigate the molecular mechanisms underlying neuropeptide mRNA induction in cells of both strains, temporal mRNA expression patterns of immediate early genes (IEGs) and several signal transduction-associated molecules were also examined. We found that LEWN hypothalamic cells were hyporesponsive to IL-1beta induction of neuropeptide and IEG mRNA, while LEW/N cells transcribed more IL-1 receptor and inducible nitric oxide synthase (iNOS) compared to F344N/N cells, suggesting that LEW/N and F344/N hypothalamic cells are differentially activated by IL-1beta. (C) 2003 Elsevier B.V. All rights reserved. C1 NIMH, Integrat Neural Immune Program, NIH, Bethesda, MD 20892 USA. RP Sternberg, EM (reprint author), NIMH, Integrat Neural Immune Program, NIH, 36 Convent Dr,Room 1A23, Bethesda, MD 20892 USA. EM ems@codon.nih.gov NR 41 TC 9 Z9 9 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 JAN PY 2004 VL 146 IS 1-2 BP 114 EP 125 DI 10.1016/j.neuroim.2003.10.050 PG 12 WC Immunology; Neurosciences SC Immunology; Neurosciences & Neurology GA 767YC UT WOS:000188500600013 PM 14698853 ER PT J AU Sanchez-Pernaute, R Ferree, A Cooper, O Yu, MX Brownell, AL Isacson, O AF Sanchez-Pernaute, Rosario Ferree, Andrew Cooper, Oliver Yu, Meixiang Brownell, Anna-Liisa Isacson, Ole TI Selective COX-2 inhibition prevents progressive dopamine neuron degeneration in a rat model of Parkinson's disease SO JOURNAL OF NEUROINFLAMMATION LA English DT Article AB Several lines of evidence point to a significant role of neuroinflammation in Parkinson's disease (PD) and other neurodegenerative disorders. In the present study we examined the protective effect of celecoxib, a selective inhibitor of the inducible form of cyclooxygenase (COX-2), on dopamine (DA) cell loss in a rat model of PD. We used the intrastriatal administration of 6-hydroxydopamine (6-OHDA) that induces a retrograde neuronal damage and death, which progresses over weeks. Animals were randomized to receive celecoxib (20 mg/kg/day) or vehicle starting 1 hour before the intrastriatal administration of 6-OHDA. Evaluation was performed in vivo using micro PET and selective radiotracers for DA terminals and microglia. Post mortem analysis included stereological quantification of tyrosine hydroxylase, astrocytes and microglia. 12 days after the 6-OHDA lesion there were no differences in DA cell or fiber loss between groups, although the microglial cell density and activation was markedly reduced in animals receiving celecoxib (p < 0.01). COX-2 inhibition did not reduce the typical astroglial response in the striatum at any stage. Between 12 and 21 days, there was a significant progression of DA cell loss in the vehicle group (from 40 to 65%) that was prevented by celecoxib. Therefore, inhibition of COX-2 by celecoxib appears to be able, either directly or through inhibition of microglia activation to prevent or slow down DA cell degeneration. C1 [Sanchez-Pernaute, Rosario; Ferree, Andrew; Cooper, Oliver; Yu, Meixiang; Brownell, Anna-Liisa; Isacson, Ole] Harvard Univ, McLean Hosp, Udall Parkinsons Dis Res Ctr Excellence, Belmont, MA 02178 USA. [Sanchez-Pernaute, Rosario; Ferree, Andrew; Cooper, Oliver; Isacson, Ole] McLean Hosp, Neuroregenerat Labs, Belmont, MA 02178 USA. [Yu, Meixiang; Brownell, Anna-Liisa] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. RP Isacson, O (reprint author), Harvard Univ, McLean Hosp, Udall Parkinsons Dis Res Ctr Excellence, Belmont, MA 02178 USA. EM rosario_pernaute@hms.harvard.edu; aferree@mclean.harvard.edu; ocooper@mclean.harvard.edu; ymeixiang@partners.org; abrownell@partners.org; isacson@hms.harvard.edu FU NIH [R01NS41263]; Udall Parkinson's Disease Research Center [P50NS39793]; Kinetics Foundation; Parkinson Foundation National Capital Area; Consolidated Anti-Aging Foundation FX This work was supported by the NIH grants, R01NS41263 and Udall Parkinson's Disease Research Center P50NS39793 (OI). The support of the Kinetics Foundation, the Parkinson Foundation National Capital Area and the Consolidated Anti-Aging Foundation is also gratefully acknowledged. NR 68 TC 104 Z9 109 U1 0 U2 3 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1742-2094 J9 J NEUROINFLAMM JI J. Neuroinflamm. PY 2004 VL 1 AR 6 DI 10.1186/1742-2094-1-6 PG 11 WC Immunology; Neurosciences SC Immunology; Neurosciences & Neurology GA V29PB UT WOS:000208759200006 PM 15285796 ER PT J AU Cohen, L Smith, MJ Leroux-Hugon, V AF Cohen, L Smith, MJ Leroux-Hugon, V TI Paul Broca's thermometric crown SO JOURNAL OF NEUROLOGY NEUROSURGERY AND PSYCHIATRY LA English DT Editorial Material C1 Hop La Pitie Salpetriere, Serv Neurol 1, Inst Neurol, F-75651 Paris 13, France. NIH, Brain Simulat Unit, Bethesda, MD 20892 USA. RP Cohen, L (reprint author), Hop La Pitie Salpetriere, Serv Neurol 1, Inst Neurol, 47-83 Bd Hop, F-75651 Paris 13, France. NR 2 TC 2 Z9 2 U1 0 U2 0 PU B M J PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0022-3050 J9 J NEUROL NEUROSUR PS JI J. Neurol. Neurosurg. Psychiatry PD JAN 1 PY 2004 VL 75 IS 1 BP 32 EP 32 PG 1 WC Clinical Neurology; Psychiatry; Surgery SC Neurosciences & Neurology; Psychiatry; Surgery GA 760CC UT WOS:000187792300009 PM 14707302 ER PT J AU Becerra, L Iadarola, M Borsook, D AF Becerra, L Iadarola, M Borsook, D TI CNS activation by noxious heat to the hand or foot: Site-dependent delay in sensory but not emotion circuitry SO JOURNAL OF NEUROPHYSIOLOGY LA English DT Article ID A-DELTA FIBERS; CHRONIC PAIN; HUMAN BRAIN; CONDUCTION-VELOCITY; 1ST PAIN; THERMAL THRESHOLDS; NEURAL RESPONSES; NERVE-FIBERS; EVOKED PAIN; REWARD AB Recently, functional magnetic resonance imaging has been used as a novel method of evaluating the CNS response to noxious stimuli. In a previous study, a prolonged noxious thermal stimulus applied to the dorsum of the hand produced more than one hemodynamic response that was temporally segregated. The two major responses displayed activation in primary sensory regions (classic pain circuitry) and regions involved in emotion (reward/aversion circuitry), respectively. In the current study, we applied the same thermal stimulus separately to the dorsum of the left foot and the dorsum of the left hand in the same subjects and compared the hemodynamic responses to evaluate the effects of conduction distance on CNS activation within these two segregated systems. After stimulus delivery to the foot, the hemodynamic response in primary sensory networks occurs after a delay of 3.6+/-1.3 s as compared with the response after hand stimulation. The relative delay of the hemodynamic response in reward/aversion regions is not significantly different between hand and foot stimulation (0.6+/-2.1 s). These results within the primary sensory system are consistent with the greater conduction distance of the peripheral nerves from the hand versus the foot. The observation that the response within the reward/aversion pathways occurs with the same rapid temporal characteristics after either hand or foot stimulation supports the notion that the circuitry involved in the evaluation of aversive stimuli is rapid in onset and probably represents a major protective mechanism for survival. C1 Massachusetts Gen Hosp, Nucl Magnet Resonance Ctr, Dept Radiol, Ctr Funct Pain Neuroimaging & Therapy Res, Charlestown, MA 02129 USA. Natl Inst Dent & Craniofacial Res, Pain & Neurosci Mech Branch, NIH, Bethesda, MD 20892 USA. RP Borsook, D (reprint author), Descartes Therapeut Inc, 790 Mem Dr,Suite 104, Cambridge, MA 02139 USA. EM dborsook@dtrx.com FU PHS HHS [012581, 12650] NR 69 TC 16 Z9 16 U1 0 U2 2 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-3077 J9 J NEUROPHYSIOL JI J. Neurophysiol. PD JAN PY 2004 VL 91 IS 1 BP 533 EP 541 DI 10.1152/jn.00326.2003 PG 9 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA 762GW UT WOS:000187964500045 PM 14715722 ER PT J AU Joseph, J Behar, T AF Joseph, J Behar, T TI Viral and host genetic factors regulating HIV/CNS disease SO JOURNAL OF NEUROVIROLOGY LA English DT Editorial Material ID IMMUNODEFICIENCY-VIRUS TYPE-1; DEMENTIA; BRAIN; ENCEPHALITIS; MACROPHAGES; SEQUENCES; INFECTION; HIV-1 C1 NIMH, Ctr Mental Hlth Res AIDS, Bethesda, MD 20892 USA. NINDS, Bethesda, MD 20892 USA. RP Joseph, J (reprint author), NIMH, Ctr Mental Hlth Res AIDS, Bethesda, MD 20892 USA. NR 22 TC 2 Z9 2 U1 0 U2 0 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1355-0284 J9 J NEUROVIROL JI J. Neurovirol. PY 2004 VL 10 SU 1 BP 1 EP 6 DI 10.1080/13550280490427532 PG 6 WC Neurosciences; Virology SC Neurosciences & Neurology; Virology GA 801SC UT WOS:000220114600001 PM 14982732 ER PT J AU Lawrence, DM Seth, P Durham, LC Diaz, F Major, EO AF Lawrence, Diane M. Seth, Pankaj Durham, Linda C. Diaz, Frank Major, Eugene O. TI Regulation of monocyte chemoattractant protein-1 (MCP-1) in CNS-derived progenitor cells and differentiating astrocytes SO JOURNAL OF NEUROVIROLOGY LA English DT Meeting Abstract C1 Natl Inst Neurolog Disorders & Stroke, NIH, Bethesda, MD USA. Natl Brain Res Ctr, Manesar, India. NR 0 TC 0 Z9 0 U1 0 U2 0 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1355-0284 J9 J NEUROVIROL JI J. Neurovirol. PY 2004 VL 10 SU 3 BP 16 EP 16 PG 1 WC Neurosciences; Virology SC Neurosciences & Neurology; Virology GA V44GU UT WOS:000202992000021 ER PT J AU Jacobson, S AF Jacobson, Steven TI Association of human herpesvirus 6 and chronic, progressive neurologic disease SO JOURNAL OF NEUROVIROLOGY LA English DT Meeting Abstract C1 NINDS, Viral Immunol Sect, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1355-0284 J9 J NEUROVIROL JI J. Neurovirol. PY 2004 VL 10 SU 3 BP 35 EP 35 PG 1 WC Neurosciences; Virology SC Neurosciences & Neurology; Virology GA V44GU UT WOS:000202992000045 ER PT J AU Donati, D Bonwetsch, R Fotheringham, JA Akhyani, N Vortmeyer, A Heiss, JD Theodore, WH Jacobson, S AF Donati, Donatella Bonwetsch, Robert Fotheringham, Julie A. Akhyani, Nahid Vortmeyer, Alexander Heiss, John D. Theodore, William H. Jacobson, Steven TI HHV-6 active infection of astrocytes in mesial temporal sclerosis SO JOURNAL OF NEUROVIROLOGY LA English DT Meeting Abstract C1 NINDS, Virol Immunol Sect, Neuroimmunol Branch, NIH, Bethesda, MD 20892 USA. Univ Siena, Dipartimento Biol Mol, Sez Virol, I-53100 Siena, Italy. NINDS, Clin epilepsy Sect, NIH, Bethesda, MD 20892 USA. NINDS, Surg Neurol Branch, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1355-0284 J9 J NEUROVIROL JI J. Neurovirol. PY 2004 VL 10 SU 3 BP 52 EP 53 PG 2 WC Neurosciences; Virology SC Neurosciences & Neurology; Virology GA V44GU UT WOS:000202992000072 ER PT J AU Cobrs, RJ Graf, LL Cohen, JI Gilden, DH AF Cobrs, Randall J. Graf, Laurie L. Cohen, Jeffery I. Gilden, Donald H. TI Transcriptional analysis comparison of parental and vaccine OKA VZV by PCR-based macrorarrays SO JOURNAL OF NEUROVIROLOGY LA English DT Meeting Abstract C1 Univ Colorado, Hlth Sci Ctr, Boulder, CO 80309 USA. NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1355-0284 J9 J NEUROVIROL JI J. Neurovirol. PY 2004 VL 10 SU 3 BP 101 EP 101 PG 1 WC Neurosciences; Virology SC Neurosciences & Neurology; Virology GA V44GU UT WOS:000202992000157 ER PT J AU Donati, D Martinelli, E Akhyani, N Ahlqvist, J Hou, J Major, EO Jacobson, S AF Donati, Donatella Martinelli, Elena Akhyani, Nahid Ahlqvist, Jenny Hou, Jean Major, Eugene O. Jacobson, Steven TI HHV-6 variant-specific patterns of infection in human progenitor derived astrocytes SO JOURNAL OF NEUROVIROLOGY LA English DT Meeting Abstract C1 NINDS, Virol Immunol Sect, Neuroimmunol Branch, NIH, Bethesda, MD 20892 USA. Univ Siena, Dip Biol Mol, Sezione Virol, I-53100 Siena, Italy. NINDS, Lab Mol Med & Neurosci, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1355-0284 J9 J NEUROVIROL JI J. Neurovirol. PY 2004 VL 10 SU 3 BP 105 EP 106 PG 2 WC Neurosciences; Virology SC Neurosciences & Neurology; Virology GA V44GU UT WOS:000202992000165 ER PT J AU Donati, D Akhyani, N Yao, K Fotheringham, J Martinelli, E Ghedin, E Kashanchi, F Weil, R Jacobson, S AF Donati, Donatella Akhyani, Nahid Yao, Karen Fotheringham, Julie Martinelli, Elena Ghedin, Elodie Kashanchi, Fatah Weil, Robert Jacobson, Steven TI In situ detection of HHV-6 using a multi-component virus microarray chip in HHV-6 associated encephalitis brain material SO JOURNAL OF NEUROVIROLOGY LA English DT Meeting Abstract C1 NINDS, Viral Immunol Sect, Neuroimmunol Branch, NIH, Bethesda, MD 20892 USA. NINDS, Surg Neurol Branch, NIH, Bethesda, MD 20892 USA. Univ Siena, Sezione Virol, Dip Biol Mol, I-53100 Siena, Italy. Inst Genom Res, Rockville, MD USA. George Washington Univ, Sch Med & Hlth Sci, Dept Biochem & Mol Biol, Washington, DC 20037 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1355-0284 J9 J NEUROVIROL JI J. Neurovirol. PY 2004 VL 10 SU 3 BP 106 EP 106 PG 1 WC Neurosciences; Virology SC Neurosciences & Neurology; Virology GA V44GU UT WOS:000202992000166 ER PT J AU Fotheringham, J Ahlqvist, J Bonwetsch, R Akhyani, N Jacobson, S AF Fotheringham, Julie Ahlqvist, Jenny Bonwetsch, Robert Akhyani, Nahid Jacobson, Steven TI Infection of glia with human herpesvirus-6 dysregulates glutamate uptake SO JOURNAL OF NEUROVIROLOGY LA English DT Meeting Abstract C1 NINDS, Viral Immunol Sect, NIH, Bethesda, MD 20892 USA. NINDS, Clin Epilepsy Sect, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1355-0284 J9 J NEUROVIROL JI J. Neurovirol. PY 2004 VL 10 SU 3 BP 108 EP 109 PG 2 WC Neurosciences; Virology SC Neurosciences & Neurology; Virology GA V44GU UT WOS:000202992000172 ER PT J AU Hou, J Diaz, F Lawrence, D Schwartz, L Major, E AF Hou, Jean Diaz, Frank Lawrence, Diane Schwartz, Lynnae Major, Eugene TI Factors determining susceptibility to JCV and HIV-1 infection using a human CNS derived multipotential cell culture system: Implications for viral tropism SO JOURNAL OF NEUROVIROLOGY LA English DT Meeting Abstract C1 NIH, Baltimore, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1355-0284 J9 J NEUROVIROL JI J. Neurovirol. PY 2004 VL 10 SU 3 BP 112 EP 112 PG 1 WC Neurosciences; Virology SC Neurosciences & Neurology; Virology GA V44GU UT WOS:000202992000178 ER PT J AU Buch, S Sui, YJ Potula, R Pinson, D Adany, I Li, Z Huang, MZ Li, SP Dhillon, N Major, E Narayan, O AF Buch, S Sui, YJ Potula, R Pinson, D Adany, I Li, Z Huang, MZ Li, SP Dhillon, N Major, E Narayan, O TI Role of interleukin-4 and monocyte chemoattractant protein-1 in the neuropathogenesis of X4 simian human immunodeficiency virus infection in macaques SO JOURNAL OF NEUROVIROLOGY LA English DT Article; Proceedings Paper CT Joint Symposium on Viral and Host Genetic Factors Regulating HIV/CNS Disease CY NOV 20-22, 2002 CL WASHINGTON, DC SP Natl Inst Mental Hlth, Natl Inst Neurol Disorders & Stroke DE chemokine; macrophages; SHIV encephalitis ID PRODUCTIVE INFECTION; CHEMOKINE RECEPTORS; CEREBROSPINAL-FLUID; HIV-1 INFECTION; DEMENTIA; CCR5; MACROPHAGES; MICROGLIA; RECRUITMENT; EXPRESSION AB Recent studies on the coreceptor usage of human immunodeficiency virus [HIV) strains associated with acquired immunodeficiency syndrome (AIDS) dementia have shown that both X4 and R5 viruses are involved in the process. The disease is associated with enhanced virus replication and monocyte chemoattractant protein (MCP)-1 production in macrophages in the brain. Using the macaque model of the disease, the authors show here that X4, macrophage-tropic simian human immunodeficiency virus (SHIV) required the enhancing effect of interleukin (IL)-4 to achieve equivalent concentrations of virus and MCP-1 that are produced in macrophages infected with R5 viruses alone. Confocal microscopy showed that macrophages in the encephalitic brains were the major producers of MCP-1. The authors surmise, therefore, that whereas R5 viruses maybe capable of causing the disease as a primary pathogen, X4 viruses may require IL-4, induced by opportunistic pathogens, for induction of the neuropathological syndrome. C1 Univ Kansas, Med Ctr, Dept Microbiol Immunol & Mol Genet, Marion Merrell Dow Lab Viral Pathogenesis, Kansas City, KS 66160 USA. NINDS, Lab Mol Med & Neurosci, NIH, Bethesda, MD 20892 USA. RP Buch, S (reprint author), Univ Kansas, Med Ctr, Dept Microbiol Immunol & Mol Genet, Marion Merrell Dow Lab Viral Pathogenesis, 5000 Wahl Hall E,3901 Rainbow Blvd, Kansas City, KS 66160 USA. EM sbuch@kumc.edu OI Buch, Shilpa/0000-0002-3103-6685 FU NCRR NIH HHS [RR-13152, RR16443-02]; NIAID NIH HHS [AI-138492]; NIMH NIH HHS [MH62969]; NINDS NIH HHS [NS-32203]; PHS HHS [FF-06753] NR 25 TC 11 Z9 12 U1 0 U2 0 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1355-0284 J9 J NEUROVIROL JI J. Neurovirol. PY 2004 VL 10 SU 1 BP 118 EP 124 DI 10.1080/13550280490270798 PG 7 WC Neurosciences; Virology SC Neurosciences & Neurology; Virology GA 801SC UT WOS:000220114600019 PM 14982750 ER PT J AU Mandel, M Yao, K Pumfrey, A Akhyani, N Ahlqvist, J de la Fuente, C Miller, N Kashanchi, F Ghedin, E Jacobson, S AF Mandel, Matthew Yao, Karen Pumfrey, Anne Akhyani, Nahid Ahlqvist, Jenny de la Fuente, Cynthia Miller, Naomi Kashanchi, Fatah Ghedin, Elodie Jacobson, Steven TI Global temporal mapping of HHV-6A and the discovery of gene functions using a novel multiviral microarray SO JOURNAL OF NEUROVIROLOGY LA English DT Meeting Abstract C1 NINDS, Viral Immunol Sect, NIH, Bethesda, MD 20892 USA. Howard Hughes Med Inst, NIH, Res Scholars Program, Bethesda, MD 20817 USA. Inst Genom Res, Rockville, MD USA. George Washington Univ, Sch Med, Washington, DC USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1355-0284 J9 J NEUROVIROL JI J. Neurovirol. PY 2004 VL 10 SU 3 BP 118 EP 119 PG 2 WC Neurosciences; Virology SC Neurosciences & Neurology; Virology GA V44GU UT WOS:000202992000191 ER PT J AU Kim, MS Kim, CJ Jung, HS Seo, MR Juhnn, YS Shln, HY Ahn, HS Thiele, CJ Chi, JG AF Kim, MS Kim, CJ Jung, HS Seo, MR Juhnn, YS Shln, HY Ahn, HS Thiele, CJ Chi, JG TI Fibroblast growth factor 2 induces differentiation and apoptosis of Askin tumour cells SO JOURNAL OF PATHOLOGY LA English DT Article DE FGF2; apoptosis; differentiation; Ewing's sarcoma; peripheral primitive neuroectodermal tumour ID FIBROBLAST-GROWTH-FACTOR; EWINGS-SARCOMA CELLS; BCL-2 EXPRESSION; II RECEPTOR; NEUROBLASTOMA; GENE; HISTOGENESIS; ACTIVATION; EWS-FLI1; LINES AB Peripheral primitive neuroectodermal tumour (PNET)/Ewing's sarcoma (ES) and neuroblastoma (NB) are related tumours of neural crest origin with primitive neural characteristics. Fibroblast growth factor 2 (FGF2) is a critical signalling molecule for primitive neural crest cells. The treatment of NB cells with FGF2 variably affects biological characteristics such as growth and differentiation, while in PNET/ES, FGF2 predominantly induces apoptosis. The JK-GMS Askin tumour cell line can be induced to differentiate upon treatment with nerve growth factor (NGF), indicating the integrity of the cellular machinery necessary for differentiation. The present study assesses whether FGF2 can induce differentiation in JK-GMS cells. JK-GMS cells expressed high-affinity FGF receptors (FGFRs), and treatment with FGF2 induced phosphorylation of FGFR1 together with activation of extracellular signal-regulated kinases (ERK1/ERK2) and c-Jun N-terminal kinase (JNK). Subsequent biological effects were growth inhibition, neuronal differentiation, and apoptosis, and these changes were associated with increased expression of neurofilaments, reduction of c-myc and bcl-2 expression, and activation of caspase 3. Treatment of the cells with a specific inhibitor of the MAPK/extracellular signal-regulated kinase (MEK)-1, PD98059, predominantly inhibited the effects of FGF2 on growth, differentiation, and apoptosis, while an inhibitor of JNK reduced apoptosis, indicating that the ERK1/2 and JNK pathways are critical components of FGF2-mediated effects in JK-GMS cells. Additional comparative analyses of FGF2-mediated effects in two ES cell lines (CADO-ES, RD-ES) and a PNET cell line (SK-N-MC) showed pronounced differentiation in SK-N-MC, but not in CADO-ES or RD-ES cells. This study demonstrates that FGF2 can induce neuronal differentiation of PNET including Askin tumour. These findings clearly indicate that the FGF2-mediated signalling pathway plays a critical role in controlling the major properties of PNET cells and may provide a potential therapeutic target for PNET. Copyright (C) 2003 John Wiley Sons, Ltd. C1 Seoul Natl Univ, Coll Med, Dept Pathol, Seoul 110799, South Korea. Seoul Natl Univ Hosp, Clin Res Inst, Pathol Lab, Seoul 110744, South Korea. Seoul Natl Univ, Coll Med, Dept Biochem & Mol Biol, Seoul, South Korea. Seoul Natl Univ, Coll Med, Dept Pediat, Seoul, South Korea. NCI, Cell & Mol Biol Sect, Pediat Oncol Branch, NIH, Bethesda, MD 20892 USA. RP Kim, CJ (reprint author), Seoul Natl Univ, Coll Med, Dept Pathol, 28 Yongon Dong, Seoul 110799, South Korea. RI Library, JinyoungPark/F-3767-2011; Library, Park J/F-3768-2011; Chi, Je Geun/G-4989-2011; Seoul National University, Pathology/B-6702-2012; Juhnn, Yong-Sung/J-2790-2012; Shin, Hee Young/J-2766-2012; OI Library, JinyoungPark/0000-0003-0952-1374; Chi, Je-Geun/0000-0002-9950-2072 NR 37 TC 24 Z9 29 U1 1 U2 2 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 0022-3417 J9 J PATHOL JI J. Pathol. PD JAN PY 2004 VL 202 IS 1 BP 103 EP 112 DI 10.1002/path.1497 PG 10 WC Oncology; Pathology SC Oncology; Pathology GA 758UL UT WOS:000187668700013 PM 14694527 ER PT J AU Kaser, A Nieuwenhuis, EES Strober, W Fuss, I Colgan, L Blumberg, RS AF Kaser, A Nieuwenhuis, EES Strober, W Fuss, I Colgan, L Blumberg, RS TI CD1d-restricted T cell pathways at the epithelial-lymphocyte-luminal interface SO JOURNAL OF PEDIATRIC GASTROENTEROLOGY AND NUTRITION LA English DT Article; Proceedings Paper CT 1st ESPGAN Capri Meeting on Gut Inflammation CY MAY 27-29, 2004 CL Capri, ITALY ID COLITIS; MICE; CD1D AB The mucosal-associated lymphoid tissues, including the gut-associated lymphoid tissues, represent a tightly regulated environment that, on the one hand, must resist microbial invasions and on the other hand, when perturbed, causes inflammation such as that associated with inflammatory bowel disease. One type of regulatory cellular subset that has recently gained attention in this compartment is the Subset of T cells that are associated with CD1d-restricted responses. Recently, CD1d-restricted T cells have been increasingly appreciated to play a significant role in mucosal tissues of the intestine and lung, for example. In this review, we focus on recent observations in the characteristics of CD1d-restricted pathways in mucosal compartments after a brief introduction to the biology of CD1d and CD1d-restricted T cells. C1 Brigham & Womens Hosp, Div Gastroenterol, Boston, MA 02115 USA. NIAID, Mucosal Immun Sect, NIH, Bethesda, MD 20892 USA. Brighamon Womens Hosp, Ctr Expt Therapeut & Perfus Injury, Dept Anaesthesia, Boston, MA USA. RP Blumberg, RS (reprint author), Brigham & Womens Hosp, Div Gastroenterol, Thorn Bldg,Room 1410,75 Francis St, Boston, MA 02115 USA. EM rblumberg@partners.org NR 7 TC 2 Z9 2 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0277-2116 J9 J PEDIATR GASTR NUTR JI J. Pediatr. Gastroenterol. Nutr. PY 2004 VL 39 SU 3 BP S719 EP S722 DI 10.1097/00005176-200406003-00002 PG 4 WC Gastroenterology & Hepatology; Nutrition & Dietetics; Pediatrics SC Gastroenterology & Hepatology; Nutrition & Dietetics; Pediatrics GA 834XK UT WOS:000222444000002 PM 15167359 ER PT J AU Renner, ED Puck, JM Holland, SM Schmitt, M Weiss, M Frosch, M Bergmann, M Davis, J Belohradsky, BH Grimbacher, B AF Renner, ED Puck, JM Holland, SM Schmitt, M Weiss, M Frosch, M Bergmann, M Davis, J Belohradsky, BH Grimbacher, B TI Autosomal recessive hyperimmunoglobulin E syndrome: A distinct disease entity SO JOURNAL OF PEDIATRICS LA English DT Article ID HYPER-IGE SYNDROME; PRIMARY IMMUNODEFICIENCY DISEASES; COLD STAPHYLOCOCCAL ABSCESSES; JOBS SYNDROME; RECURRENT-INFECTION; CRANIAL SYNOSTOSIS; CHEMOTAXIS; DEFECT AB Objective The autosomal-dominant form of the hyperimmunoglobulin E syndrome (AD-HIES) has been described as a multisystem disorder including immune, skeletal, and dental abnormalities. Variants of AD-HIES are known but not well defined. Methods We evaluated 13 human immunodeficiency virus-seronegative patients from six consanguineous families with all autosomal-recessive form of hyperimmunoglobulin E syndrome (AR-HIES) and 68 of their relatives. Results Persons affected with AR-HIES presented with the classical immunologic findings of hyperimmunoglobulin E syndrome, including recurrent staphylococcal infections of the shin and respiratory tract, eczema, elevated serum immunoglobulin E, and hypereosinophilia. In addition, severe recurrent fungal and viral infections with. p molluscum contagiosum, herpes zoster, and herpes simplex were noted. Autoimmunity was seen in two patients. Central nervous system sequelae, including hemiplegia, ischemic infarction, and subarachnoid hemorrhages, were common and contributed to high mortality. Notably, patients with AR-HIES did not have skeletal or dental abnormalities and did not develop pneumatoceles, as seen in AD-HIES. In lymphocyte, proliferation assays, patients' cells responded poorly to mitogens and failed to proliferate in response to antigens, despite the presence of normal numbers of lymphocyte subpopulations. Conclusion The autosomal-recessive form of hyperimmunoglobulin E syndrome is a primary immunodeficiency with elevated immunoglobulin E, eosinophilia, vasculitis, autoimmunity, central nervous system symptoms, and high mortality. AR-HIES lacks several of the key findings of AD-HIES and therefore represents a different, previously unrecognized disease entity. C1 Univ Freiburg, Med Ctr, Dept Rheumatol & Clin Immunol, D-79106 Freiburg, Germany. Univ Munich, Dr Von Haunerschen Kinderspital, Dept Infect Dis & Clin Immunol, D-80337 Munich, Germany. Univ Childrens Hosp, Charite, Berlin, Germany. Childrens Hosp, Cologne, Germany. Univ Munster, Childrens Hosp, D-4400 Munster, Germany. Zentralkrankenhaus Bremen Ost, Inst Clin Neuropathol, Bremen, Germany. NHGRI, NIH, Bethesda, MD 20892 USA. NIAID, NIH, Bethesda, MD 20892 USA. RP Grimbacher, B (reprint author), Univ Freiburg, Med Ctr, Dept Rheumatol & Clin Immunol, Hugstetter Str 55, D-79106 Freiburg, Germany. EM grimbacher@mm61.ukl.uni-freiburg.de NR 26 TC 135 Z9 146 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0022-3476 EI 1097-6833 J9 J PEDIATR-US JI J. Pediatr. PD JAN PY 2004 VL 144 IS 1 BP 93 EP 99 DI 10.1016/S0022-3476(03)00449-9 PG 7 WC Pediatrics SC Pediatrics GA 763MZ UT WOS:000188091100017 PM 14722525 ER PT J AU Marshall, GR Che, Y Berg-Cross, S Ngu, HV Chen, ID AF Marshall, G. R. Che, Y. Berg-Cross, S. Ngu, H. V. Chen, I. D. TI ENGINEERING CYCLIC TETRAPEPTIDES CONTAINING CHIMERIC AMINO ACIDS AS PREFERRED SCAFFOLDS SO JOURNAL OF PEPTIDE SCIENCE LA English DT Meeting Abstract C1 [Marshall, G. R.; Berg-Cross, S.; Ngu, H. V.; Chen, I. D.] Washington Univ, St Louis, MO USA. [Che, Y.] NHLBI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 1075-2617 J9 J PEPT SCI JI J. Pept. Sci. PY 2004 VL 10 BP 111 EP 111 PG 1 WC Biochemistry & Molecular Biology; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA V05MV UT WOS:000207131000073 ER PT J AU Long, YQ Song, YL Roller, PP AF Long, Y. Q. Song, Y. L. Roller, P. P. TI DISCOVERY OF A NEW CLASS OF POTENT CYCLIC PENTAPEPTIDE ANTAGONISTS OF THE GRB2-SH2 DOMAIN BY THE UTILIZATION OF 3 '-SUBSTITUTED TYROSINE SO JOURNAL OF PEPTIDE SCIENCE LA English DT Meeting Abstract C1 [Long, Y. Q.; Song, Y. L.] Chinese Acad Sci, Shanghai Inst Mat Med, Shanghai Inst Biol Sci, State Key Lab Drug Res 1, Shanghai 200031, Peoples R China. [Roller, P. P.] NCI, Med Chem Lab, Frederick, MD 21701 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 1075-2617 J9 J PEPT SCI JI J. Pept. Sci. PY 2004 VL 10 BP 210 EP 210 PG 1 WC Biochemistry & Molecular Biology; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA V05MV UT WOS:000207131001235 ER PT J AU Paruszewski, R Rostafinska-Suchar, G Strupinska, M Stables, JP AF Paruszewski, R. Rostafinska-Suchar, G. Strupinska, M. Stables, J. P. TI NEW DERIVATIVES OF PICOLINIC ACID WITH ANTICONVULSANT ACTIVITY SO JOURNAL OF PEPTIDE SCIENCE LA English DT Meeting Abstract C1 [Paruszewski, R.; Rostafinska-Suchar, G.; Strupinska, M.] Med Univ, Dept Drug Chem, Warsaw, Poland. [Stables, J. P.] NINDS, Epilepsy Branch, Rockville, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1075-2617 J9 J PEPT SCI JI J. Pept. Sci. PY 2004 VL 10 SU S BP 213 EP 213 PG 1 WC Biochemistry & Molecular Biology; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA V05MV UT WOS:000207131001245 ER PT J AU Bryant, SD Jinsmaa, Y Lazarus, LH AF Bryant, S. D. Jinsmaa, Y. Lazarus, L. H. TI IDENTIFICATION OF OPIOID RECEPTOR-LIGAND INTERACTIONS USING STRUCTURALLY RELATED DELTA OPIOID RECEPTOR AGONISTS AND ANTAGONISTS AND MOLECULAR MODELING SO JOURNAL OF PEPTIDE SCIENCE LA English DT Meeting Abstract C1 [Bryant, S. D.] NIEHS, LCRBA, Res Triangle Pk, NC 27709 USA. [Jinsmaa, Y.; Lazarus, L. H.] NIEHS, Mc, Res Triangle Pk, NC 27709 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 1075-2617 J9 J PEPT SCI JI J. Pept. Sci. PY 2004 VL 10 BP 220 EP 220 PG 1 WC Biochemistry & Molecular Biology; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA V05MV UT WOS:000207131001273 ER PT J AU Nomizu, M Yokoyama, F Suzuki, N Nishi, N Oishi, S Fujii, N Kleinman, HK AF Nomizu, M. Yokoyama, F. Suzuki, N. Nishi, N. Oishi, S. Fujii, N. Kleinman, H. K. TI BIOLOGICAL ACTIVITIES OF CYCLIZED PEPTIDES DERIVED FROM LAMININS SO JOURNAL OF PEPTIDE SCIENCE LA English DT Meeting Abstract C1 [Nomizu, M.; Yokoyama, F.; Suzuki, N.; Nishi, N.] Hokkaido Univ, Grad Sch EES, Sapporo, Hokkaido, Japan. [Nomizu, M.] Tokyo Univ Pharm & Life Sci, Sch Pharm, Tokyo, Japan. [Oishi, S.; Fujii, N.] Kyoto Univ, Grad Sch Pharmaceut Sci, Kyoto, Japan. [Kleinman, H. K.] NIH, NIDCR, Bethesda, MD 20892 USA. RI Oishi, Shinya/C-1350-2011 OI Oishi, Shinya/0000-0002-2833-2539 NR 0 TC 0 Z9 0 U1 0 U2 0 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 1075-2617 J9 J PEPT SCI JI J. Pept. Sci. PY 2004 VL 10 BP 230 EP 230 PG 1 WC Biochemistry & Molecular Biology; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA V05MV UT WOS:000207131001310 ER PT J AU Fujita, Y Motoyama, T Li, T Miyazaki, A Yokoi, T Tsuda, Y Ambo, A Sasaki, Y Bryant, SD Lazarus, LH Okada, Y AF Fujita, Y. Motoyama, T. Li, T. Miyazaki, A. Yokoi, T. Tsuda, Y. Ambo, A. Sasaki, Y. Bryant, S. D. Lazarus, L. H. Okada, Y. TI THE STRUCTURE-ACTIVITY RELATIONSHIP OF DMT-NH-X ON OPIOID RECEPTOR AFFINITY SO JOURNAL OF PEPTIDE SCIENCE LA English DT Meeting Abstract C1 [Fujita, Y.; Li, T.; Yokoi, T.; Tsuda, Y.; Okada, Y.] Kobe Gakuin Univ, Grad Sch Food & Med Sci, Kobe, Hyogo 65121, Japan. [Motoyama, T.; Miyazaki, A.; Yokoi, T.; Tsuda, Y.; Okada, Y.] Kobe Gakuin Univ, Fac Pharmaceut Sci, Kobe, Hyogo, Japan. [Yokoi, T.; Tsuda, Y.; Okada, Y.] Kobe Gakuin Univ, High Technol Res Ctr, Kobe, Hyogo 65121, Japan. [Ambo, A.; Sasaki, Y.] Tohoku Pharmaceut Univ, Sendai, Miyagi, Japan. [Bryant, S. D.; Lazarus, L. H.] Natl Inst Environm Hlth Sci, LCBRA, Res Triangle Pk, NC USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 1075-2617 J9 J PEPT SCI JI J. Pept. Sci. PY 2004 VL 10 BP 244 EP 244 PG 1 WC Biochemistry & Molecular Biology; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA V05MV UT WOS:000207131001365 ER PT J AU Lazarus, LH Bryant, SD Jinsmaa, Y Okada, Y Fujita, Y Tsuda, Y Li, T Shiotani, K Sasaki, Y Ambo, A Negri, L Balboni, G Guerrini, R Salvadori, S AF Lazarus, L. H. Bryant, S. D. Jinsmaa, Y. Okada, Y. Fujita, Y. Tsuda, Y. Li, T. Shiotani, K. Sasaki, Y. Ambo, A. Negri, L. Balboni, G. Guerrini, R. Salvadori, S. TI DMT, THE PROGENITOR OF POTENT OPIOID BEHAVIOR: EVOLUTION OF BIFUNCTIONAL OPIOID MIMETIC COMPOUNDS SO JOURNAL OF PEPTIDE SCIENCE LA English DT Meeting Abstract C1 [Lazarus, L. H.; Bryant, S. D.; Jinsmaa, Y.] NIEHS, LCBRA, Res Triangle Pk, NC 27709 USA. [Okada, Y.; Fujita, Y.; Tsuda, Y.; Li, T.; Shiotani, K.] Kobe Gakuin Univ, Fac Pharmaceut Sci, Kobe, Hyogo, Japan. [Sasaki, Y.; Ambo, A.] Tohoku Pharmaceut Univ, Dept Biochem, Sendai, Miyagi, Japan. [Negri, L.] Univ Roma La Sapienza, Dept Human Physiol & Pharmacol, Rome, Italy. [Balboni, G.] Univ Cagliari, Dept Toxicol, Cagliari, Italy. [Guerrini, R.; Salvadori, S.] Univ Ferrara, Dept Pharmaceut Sci, I-44100 Ferrara, Italy. NR 0 TC 0 Z9 0 U1 0 U2 0 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 1075-2617 J9 J PEPT SCI JI J. Pept. Sci. PY 2004 VL 10 BP 252 EP 252 PG 1 WC Biochemistry & Molecular Biology; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA V05MV UT WOS:000207131001398 ER PT J AU Li, T Fujita, Y Tsuda, Y Bryant, SD Lazarus, LH Ambo, A Sasaki, Y Okada, Y AF Li, T. Fujita, Y. Tsuda, Y. Bryant, S. D. Lazarus, L. H. Ambo, A. Sasaki, Y. Okada, Y. TI DEVELOPMENT OF mu-OPIOID RECEPTOR LIGANDS BY USING UNIQUE L-TYROSINE ANALOGUES SO JOURNAL OF PEPTIDE SCIENCE LA English DT Meeting Abstract C1 [Li, T.; Fujita, Y.; Okada, Y.] Kobe Gakuin Univ, Grad Sch Food & Med Sci, Kobe, Hyogo 65121, Japan. [Tsuda, Y.; Okada, Y.] Kobe Gakuin Univ, Fac Pharmaceut Sci, Kobe, Hyogo, Japan. [Tsuda, Y.; Okada, Y.] Kobe Gakuin Univ, High Technol Res Ctr, Kobe, Hyogo, Japan. [Bryant, S. D.; Lazarus, L. H.] NIEHS, Med Chem Grp, LCBRA, Res Triangle Pk, NC 27709 USA. [Ambo, A.; Sasaki, Y.] Tohoku Pharmaceut Univ, Sendai, Miyagi, Japan. NR 1 TC 0 Z9 0 U1 0 U2 0 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 1075-2617 J9 J PEPT SCI JI J. Pept. Sci. PY 2004 VL 10 BP 253 EP 253 PG 1 WC Biochemistry & Molecular Biology; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA V05MV UT WOS:000207131001400 ER PT J AU Hyman, JJ Reid, BC AF Hyman, JJ Reid, BC TI Cigarette smoking, periodontal disease, and chronic obstructive pulmonary disease SO JOURNAL OF PERIODONTOLOGY LA English DT Article DE National Health and Nutrition Examination Survey III; periodontal diseases/etiology; pulmonary diseases; chronic obstructive/etiology; risk factors; smoking; adverse effects ID CORONARY HEART-DISEASE; LOW-BIRTH-WEIGHT; UNITED-STATES; NATIONAL-HEALTH; RISK-FACTORS; ATHEROSCLEROSIS; PREVALENCE; EPIDEMIOLOGY; ASSOCIATIONS; INFECTIONS AB Background: Cigarette smoking is a significant risk factor for both chronic obstructive pulmonary disease (COPD) and periodontal disease. The goal of this study was to better understand the role of smoking in a possible relationship between periodontal disease and COPD. Methods: The study population consisted of 7,625 participants in the Third National Health and Nutrition Examination Survey (NHANES III) during 1988-1994 who were aged 30 years or older when examined and who received a spirometric examination. The data analysis employed logistic regression models and accounted for the complex sampling design used in NHANES III. Results: After adjustment for potential confounders, there was no statistically significant association between periodontal disease and COPD among former or non-smokers. Current smokers with greater than or equal to4 mm mean loss of attachment had an odds ratio of 3.71 (95% confidence interval: 1.74, 7.89). Conclusions: These results suggest that cigarette smoking may be a cofactor in the relationship between periodontal disease and chronic obstructive pulmonary disease. The key role played by smoking in the etiology of both periodontal disease and chronic obstructive pulmonary disease suggests that much of the observed increase in risk may actually reflect the exposure to smoking. Additional research into smoking-related effect modification is needed to clarify the role of periodontal disease in the etiology of smoking-related systemic diseases. C1 NIDCR, Off Sci Policy & Anal, Bethesda, MD 20892 USA. Univ Maryland, Sch Dent, Dept Oral Hlth Care Delivery, Baltimore, MD 21201 USA. RP Hyman, JJ (reprint author), NIDCR, Off Sci Policy & Anal, Room 4AS-37K,MSC 6401,45 Ctr Dr, Bethesda, MD 20892 USA. EM hymanj@email.nidr.nih.gov NR 36 TC 24 Z9 26 U1 0 U2 4 PU AMER ACAD PERIODONTOLOGY PI CHICAGO PA 737 NORTH MICHIGAN AVENUE, SUITE 800, CHICAGO, IL 60611-2690 USA SN 0022-3492 J9 J PERIODONTOL JI J. Periodont. PD JAN PY 2004 VL 75 IS 1 BP 9 EP 15 DI 10.1902/jop.2004.75.1.9 PG 7 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 776HP UT WOS:000189110800002 PM 15025211 ER PT J AU Fukuishi, N Akagi, M Metcalfe, DD AF Fukuishi, N Akagi, M Metcalfe, DD TI The role of mast cell on allergic inflammation SO JOURNAL OF PHARMACOLOGICAL SCIENCES LA English DT Meeting Abstract CT 77th Annual Meeting of the Japanese-Pharmacological-Society CY MAR 08-10, 2004 CL Osaka, JAPAN SP Japanese Pharmacol Soc C1 Tokushima Bunri Univ, Fac Pharmaceut Sci, Dept Pharmacol, Yamashiro, Tokushima 7708514, Japan. NIAID, LAD, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU JAPANESE PHARMACOLOGICAL SOC PI KYOTO PA EDITORIAL OFF, KANTOHYA BLDG GOKOMACHI-EBISUGAWA NAKAGYO-KU, KYOTO, 604, JAPAN SN 1347-8613 J9 J PHARMACOL SCI JI J. Pharmacol. Sci. PY 2004 VL 94 SU 1 BP 22P EP 22P PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 802CT UT WOS:000220142300057 ER PT J AU Unno, T Sakamoto, T Arima, D Uchiyama, M Matsuyama, H Yamada, M Wess, J Komori, S AF Unno, T Sakamoto, T Arima, D Uchiyama, M Matsuyama, H Yamada, M Wess, J Komori, S TI Both M2 and M3 receptor subtypes are indispensable for activation of the muscarinic receptor-operated cation channels in mouse intestinal smooth muscle cells SO JOURNAL OF PHARMACOLOGICAL SCIENCES LA English DT Meeting Abstract CT 77th Annual Meeting of the Japanese-Pharmacological-Society CY MAR 08-10, 2004 CL Osaka, JAPAN SP Japanese Pharmacol Soc C1 Gifu Univ, Pharmacol Lab, Dept Vet Med, Gifu 5011193, Japan. RIKEN, Brain Sci Inst, Wako, Saitama 3510198, Japan. NIDDKD, Bioorgan Chem Lab, Bethesda, MD 20892 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU JAPANESE PHARMACOLOGICAL SOC PI KYOTO PA EDITORIAL OFF, KANTOHYA BLDG GOKOMACHI-EBISUGAWA NAKAGYO-KU, KYOTO, 604, JAPAN SN 1347-8613 J9 J PHARMACOL SCI JI J. Pharmacol. Sci. PY 2004 VL 94 SU 1 BP 101P EP 101P PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 802CT UT WOS:000220142300366 ER PT J AU Komori, S Matsuyama, H Sakamoto, T Arima, D Fujita, K Uchiyama, M Yamada, M Wess, J Unno, T AF Komori, S Matsuyama, H Sakamoto, T Arima, D Fujita, K Uchiyama, M Yamada, M Wess, J Unno, T TI Mechanical responses to carbachol of intestinal smooth muscle from knockout mice lacking either M-2 or M-3 muscarinic receptor subtype SO JOURNAL OF PHARMACOLOGICAL SCIENCES LA English DT Meeting Abstract CT 77th Annual Meeting of the Japanese-Pharmacological-Society CY MAR 08-10, 2004 CL Osaka, JAPAN SP Japanese Pharmacol Soc C1 Gifu Univ, Pharmacol Lab, Dept Vet Med, Gifu 5011193, Japan. RIKEN, Brain Sci Inst, Wako, Saitama 3510198, Japan. NIDDKD, Bioorgan Chem Lab, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU JAPANESE PHARMACOLOGICAL SOC PI KYOTO PA EDITORIAL OFF, KANTOHYA BLDG GOKOMACHI-EBISUGAWA NAKAGYO-KU, KYOTO, 604, JAPAN SN 1347-8613 J9 J PHARMACOL SCI JI J. Pharmacol. Sci. PY 2004 VL 94 SU 1 BP 144P EP 144P PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 802CT UT WOS:000220142300529 ER PT J AU Lawrence, JJ Grinspan, ZM McBain, CJ AF Lawrence, JJ Grinspan, ZM McBain, CJ TI Quantal transmission at mossy fibre targets in the CA3 region of the rat hippocampus SO JOURNAL OF PHYSIOLOGY-LONDON LA English DT Article ID METABOTROPIC GLUTAMATE RECEPTORS; EXCITATORY POSTSYNAPTIC CURRENTS; SHORT-TERM PLASTICITY; DENTATE GYRUS; SYNAPTIC PLASTICITY; IN-VIVO; SYNAPSES; INTERNEURONS; RELEASE; CELLS AB Recent anatomical evidence that inhibitory interneurones receive approximately 10 times more synapses from mossy fibres than do principal neurones (Acsady et al. 1998) has led to the re-examination of the extent to which interneurones are involved in CA3 network excitability. Although many of the anatomical and physiological properties of mossy fibre-CA3 interneurone synapses have been previously described (Acsady et al. 1998; Toth et al. 2000), an investigation into the quantal nature of transmission at this synapse has not yet been conducted. Here, we employed variance-mean (VM) analysis to compare the release probability, quantal size (q) and number of release sites (n) at mossy fibre target neurones in CA3. At six of seven interneurone synapses in which a high concentration of Ca2+ was experimentally imposed, the variance-mean relationship could be approximated by a parabola. Estimates of n were 1-2, and the weighted release probability in normal Ca2+ conditions ranged from 0.34 to 0.51. At pyramidal cell synapses, the variance-mean relationship approximated a linear relationship, suggesting that release probability was significantly lower. The weighted quantal amplitude was similar at interneurone synapses and pyramidal cell synapses, although the variability in quantal amplitude was larger at interneurone synapses. Mossy fibre transmission at CA3 interneurone synapses can be explained by a lower number of release sites, a broader range of release probabilities, and larger range of quantal amplitudes than at CA3 pyramidal synapses. Finally, quantal events on to interneurones elicited spike transmission, owing in part to the more depolarized membrane potential than pyramidal cells. These results suggest that although mossy fibre synapses on to pyramidal cells are associated with a larger number of release sites per synapse, the higher connectivity, higher initial release probability, and larger relative impact per quantum on to CA3 interneurones generate strong feedforward inhibition at physiological firing frequencies of dentate granule cells. Given the central role of CA3 interneurones in mossy fibre synaptic transmission, these details of mossy fibre synaptic transmission should provide insight into CA3 network dynamics under both physiological and pathophysiological. circumstances. C1 NICHD, LCSN, NIH, Bethesda, MD 20892 USA. RP Lawrence, JJ (reprint author), NICHD, LCSN, NIH, Bldg 49,Room 5A60, Bethesda, MD 20892 USA. EM lawrence@codon.nih.gov OI Grinspan, Zachary/0000-0001-6705-0932 NR 47 TC 78 Z9 78 U1 0 U2 2 PU BLACKWELL PUBLISHING LTD PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 0022-3751 J9 J PHYSIOL-LONDON JI J. Physiol.-London PD JAN 1 PY 2004 VL 554 IS 1 BP 175 EP 193 DI 10.1113/jphysiol.2003.049551 PG 19 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA 770XN UT WOS:000188756800018 PM 14678500 ER PT J AU Miao, FJP Green, PG Levine, JD AF Miao, FJP Green, PG Levine, JD TI Mechanosensitive duodenal afferents contribute to vagal modulation of inflammation in the rat SO JOURNAL OF PHYSIOLOGY-LONDON LA English DT Article ID INDUCED PLASMA EXTRAVASATION; EXPERIMENTALLY-INDUCED PAIN; GASTROINTESTINAL-TRACT; INTRATHECAL NICOTINE; VAGUS NERVE; INTERLEUKIN-1-BETA-INDUCED FEVER; NEUROENDOCRINE CONTROL; VASCULAR-PERMEABILITY; INDUCED HYPERALGESIA; SMOOTH-MUSCLE AB Noxious stimuli inhibit inflammation by activating neuroendocrine stress axes, an effect that is potently attenuated by ongoing activity in subdiaphragmatic vagal afferents. Because this vagal afferent activity is carried in the coeliac and coeliac accessory branches of the subdiaphragmatic vagus, we tested the hypothesis that the activity arises from vagal afferents that innervate a proximal segment of the gastrointestinal tract. Surgical removal of the duodenum, but not the stomach, produces a marked (six orders of magnitude) leftward shift in the dose-response curve for intraplantar capsaicin-induced inhibition of synovial plasma extravasation induced by the potent inflammatory mediator bradykinin, in the knee joint; this is similar in magnitude to the inhibition produced by subdiaphragmatic or by coeliac plus coeliac accessory branch vagotomy. Fasting, to unload mechanically sensitive polymodal afferents in the proximal gastrointestinal tract, produces a similar leftward shift in the dose-response curve for the inhibitory effect of capsaicin, an effect that is reversed by balloon distension in the duodenum in fasted rats, while balloon distension postvagotomy had no effect. These results suggest that activation of mechanically sensitive vagal afferents in the duodenum contributes vagal afferent activity that modulates neuroendocrine control of the inflammatory response. C1 Univ Calif San Francisco, NIH Pain Ctr, San Francisco, CA 94134 USA. Univ Calif San Francisco, Dept Oral & Maxillofacial Surg, San Francisco, CA 94134 USA. Univ Calif San Francisco, Dept Med, San Francisco, CA 94134 USA. Univ Calif San Francisco, Dept Anat, San Francisco, CA 94134 USA. RP Levine, JD (reprint author), Univ Calif San Francisco, NIH Pain Ctr, 521 Parnassus Ave,C-522,Box 0440, San Francisco, CA 94134 USA. EM levine@itsa.ucsf.edu RI Green, Paul/C-5943-2011 FU NIAMS NIH HHS [R01 AR032634, AR32634] NR 58 TC 7 Z9 7 U1 0 U2 0 PU BLACKWELL PUBLISHING LTD PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 0022-3751 J9 J PHYSIOL-LONDON JI J. Physiol.-London PD JAN 1 PY 2004 VL 554 IS 1 BP 227 EP 235 DI 10.1113/jphysiol.2003.056804 PG 9 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA 770XN UT WOS:000188756800022 PM 14678504 ER PT J AU Dorfel, D Werner, A Gerber, J Rabe, S von Kummer, R Schafer, M Karl, A AF Dorfel, D Werner, A Gerber, J Rabe, S von Kummer, R Schafer, M Karl, A TI Episodic memory recall in EEG and fMRI: A methodological pilot study SO JOURNAL OF PSYCHOPHYSIOLOGY LA English DT Meeting Abstract C1 Dresden Univ Technol, D-8027 Dresden, Germany. Natl Inst Neurol Disorders & Stroke, Washington, DC USA. RI Werner, 2509/C-4794-2013 NR 0 TC 0 Z9 0 U1 0 U2 0 PU HOGREFE & HUBER PUBLISHERS PI GOTTINGEN PA ROHNSWEG 25, D-37085 GOTTINGEN, GERMANY SN 0269-8803 J9 J PSYCHOPHYSIOL JI J. Psychophysiol. PY 2004 VL 18 IS 4 BP 223 EP 223 PG 1 WC Psychology, Biological; Neurosciences SC Psychology; Neurosciences & Neurology GA 884LU UT WOS:000226087400099 ER PT J AU Cohen, LK AF Cohen, LK TI Perspectives from the international community: NIDR, NIDCR, and beyond SO JOURNAL OF PUBLIC HEALTH DENTISTRY LA English DT Article ID SOCIAL-PSYCHOLOGICAL FINDINGS; OCCLUSAL RELATIONS; CHILDREN C1 Natl Inst Dent & Craniofacial Res, NIH, US Dept Hlth & Human Serv, Bethesda, MD 20892 USA. RP Cohen, LK (reprint author), Natl Inst Dent & Craniofacial Res, NIH, US Dept Hlth & Human Serv, 45 Ctr Dr,Room 4AS13, Bethesda, MD 20892 USA. EM lois.cohen@nih.gov NR 4 TC 0 Z9 0 U1 0 U2 0 PU AAPHD NATIONAL OFFICE PI PORTLAND PA 3760 SW LYLE COURT, PORTLAND, OR 97221 USA SN 0022-4006 J9 J PUBLIC HEALTH DENT JI J. Public Health Dent. PY 2004 VL 64 SI 1 BP 23 EP 25 DI 10.1111/j.1752-7325.2004.tb02770.x PG 3 WC Dentistry, Oral Surgery & Medicine; Public, Environmental & Occupational Health SC Dentistry, Oral Surgery & Medicine; Public, Environmental & Occupational Health GA 890JI UT WOS:000226507100008 ER PT J AU Horowitz, AM AF Horowitz, AM TI The Herschel S. Horowitz Memorial Special Issue - Concluding comments SO JOURNAL OF PUBLIC HEALTH DENTISTRY LA English DT Editorial Material C1 Natl Inst Dent & Craniofacial Res, NIH, Bethesda, MD 20892 USA. RP Horowitz, AM (reprint author), Natl Inst Dent & Craniofacial Res, NIH, Bldg 45,Room 4As-37A, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AAPHD NATIONAL OFFICE PI PORTLAND PA 3760 SW LYLE COURT, PORTLAND, OR 97221 USA SN 0022-4006 J9 J PUBLIC HEALTH DENT JI J. Public Health Dent. PY 2004 VL 64 SI 1 BP 30 EP 30 DI 10.1111/j.1752-7325.2004.tb02772.x PG 1 WC Dentistry, Oral Surgery & Medicine; Public, Environmental & Occupational Health SC Dentistry, Oral Surgery & Medicine; Public, Environmental & Occupational Health GA 890JI UT WOS:000226507100010 ER PT J AU Horowitz, AM AF Horowitz, AM TI Herschel S. Horowitz Memorial Symposium - Concluding remarks SO JOURNAL OF PUBLIC HEALTH DENTISTRY LA English DT Editorial Material C1 Natl Inst Dent & Craniofacial Res, NIH, Bethesda, MD 20892 USA. RP Horowitz, AM (reprint author), Natl Inst Dent & Craniofacial Res, NIH, Bldg 45,Room 4As-37A, Bethesda, MD 20892 USA. EM Alice.Horowitz@nih.gov NR 1 TC 0 Z9 0 U1 0 U2 0 PU AAPHD NATIONAL OFFICE PI PORTLAND PA 3760 SW LYLE COURT, PORTLAND, OR 97221 USA SN 0022-4006 J9 J PUBLIC HEALTH DENT JI J. Public Health Dent. PY 2004 VL 64 SI 1 BP 50 EP 50 DI 10.1111/j.1752-7325.2004.tb02779.x PG 1 WC Dentistry, Oral Surgery & Medicine; Public, Environmental & Occupational Health SC Dentistry, Oral Surgery & Medicine; Public, Environmental & Occupational Health GA 890JI UT WOS:000226507100017 ER PT J AU Cooper, GS Treadwell, EL Dooley, MA St Clair, EW Gilkeson, GS Taylor, JA AF Cooper, GS Treadwell, EL Dooley, MA St Clair, EW Gilkeson, GS Taylor, JA TI N-acetyl transferase genotypes in relation to risk of developing systemic lupus erythematosus SO JOURNAL OF RHEUMATOLOGY LA English DT Article DE systemic lupus erythematosus; autoimmune disease; N-acetyl transferase metabolism; tobacco; arylamines ID NAT1; POLYMORPHISMS; PHENOTYPE; CYP1A1 AB Objective. To examine the association between N-acetyl transferase (NAT) genotype (NAT1 and NAT2) and risk of developing systemic lupus erythematosus (SLE). Methods. DNA samples were collected from 243 recently diagnosed cases and 298 controls enrolled in a population based case-control study conducted in 60 counties in North Carolina and South Carolina, USA. Results. There was no association between SLE and NAT1 genotype (OR 0.96, 95% CI 0.65, 1.4 for the presence of a *10 allele) or NAT2 genotype (OR 1.1, 95 % CI 0.73, 1.6 for the slow- compared with fast-acetylation genotype). We saw some evidence of interaction between NAT genotypes and use of hair dyes (a source of arylamines), with higher risk seen among hair dye users who had both the *10 NAT1 allele and the NAT2 slow-acetylation genotype (OR 2.9, 95% CI 1.2, 6.9 in this subgroup compared with all others). Conclusion. Our results suggest that although there is little overall association between NAT genotypes and risk of developing SLE, the interaction between NAT1 and NAT2 and specific exposures such as hair dyes may be important. This finding highlights the need to consider exposure when assessing genetic susceptibility. C1 NIEHS, Epidemiol Branch, Res Triangle Pk, NC 27709 USA. Univ N Carolina, Div Rheumatol, Chapel Hill, NC 27515 USA. E Carolina Univ, Sch Med, Div Rheumatol, Greenville, NC 27858 USA. Duke Univ, Med Ctr, Div Rheumatol, Durham, NC 27706 USA. Ralph H Johnson Vet Adm Med Ctr, Med Res Serv, Charleston, SC USA. Med Univ S Carolina, Charleston, SC 29425 USA. RP Cooper, GS (reprint author), NIEHS, Epidemiol Branch, A3-05,POB 12233, Res Triangle Pk, NC 27709 USA. EM cooper1@niehs.nih.gov OI taylor, jack/0000-0001-5303-6398 NR 15 TC 8 Z9 12 U1 0 U2 0 PU J RHEUMATOL PUBL CO PI TORONTO PA 920 YONGE ST, SUITE 115, TORONTO, ONTARIO M4W 3C7, CANADA SN 0315-162X J9 J RHEUMATOL JI J. Rheumatol. PD JAN PY 2004 VL 31 IS 1 BP 76 EP 80 PG 5 WC Rheumatology SC Rheumatology GA 763GG UT WOS:000188066100015 PM 14705222 ER PT J AU Hartos, JL Shattuck, T Simons-Morton, BG Beck, KH AF Hartos, JL Shattuck, T Simons-Morton, BG Beck, KH TI An in-depth look at parent-imposed driving rules: Their strengths and weaknesses SO JOURNAL OF SAFETY RESEARCH LA English DT Article DE teen driving; parenting; driving rules; parent-teen agreement; parent-teen concordance ID ADOLESCENT COMMUNICATION; BRIEF INTERVENTION; MOTHERS AWARENESS; TEEN PERCEPTIONS; DRIVERS; PASSENGERS; DRINKING; RISKS; RESTRICTIONS; ADJUSTMENT AB Introduction: With a growing interest in increasing parental involvement in teen driving, it is important to find out what parents are already doing. Method: This study assessed the content, delivery, rigidity, and consequences of 143 driving rules reported by 24 parent-teen dyads. Results: Strengths included that driving rules covered the full range of concerns, especially night driving limits and passenger limits, and most parents and teens reported that violations would be followed by consequences, especially talklwarn or no driving. Weaknesses included that many rules were not very strict and only half showed parent-teen agreement on content. Conclusions: These findings suggest that teen driving rules are not clearly defined. (C) 2004 National Safety Council and Elsevier Ltd. All rights reserved. C1 Univ N Carolina, Charlotte, NC 28223 USA. NICHHD, Bethesda, MD 20892 USA. Univ Maryland, College Pk, MD 20742 USA. RP Hartos, JL (reprint author), Univ N Carolina, 9201 Univ City Blvd, Charlotte, NC 28223 USA. EM jlhartos@email.uncc.edu OI Simons-Morton, Bruce/0000-0003-1099-6617 NR 37 TC 29 Z9 29 U1 1 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0022-4375 J9 J SAFETY RES JI J. Saf. Res. PY 2004 VL 35 IS 5 BP 547 EP 555 DI 10.1016/j.jsr.2004.09.001 PG 9 WC Ergonomics; Public, Environmental & Occupational Health; Social Sciences, Interdisciplinary; Transportation SC Engineering; Public, Environmental & Occupational Health; Social Sciences - Other Topics; Transportation GA 871ZA UT WOS:000225174000007 PM 15530928 ER PT J AU Brown, LM Dobbins, H AF Brown, LM Dobbins, H TI Students' of color and European American students' stigma-relevant perceptions of university instructors SO JOURNAL OF SOCIAL ISSUES LA English DT Article; Proceedings Paper CT 12th Annual Meeting of the American-Psychological-Society CY JUN 08-11, 2000 CL MIAMI, FL SP Amer Psychol Soc ID ETHNIC-STEREOTYPES; AFRICAN-AMERICANS; SCHOOL; TEACHERS; IDENTITY; THREAT; RACE; IDENTIFICATION; PERFORMANCE; GENDER AB In classrooms students of color may experience stigma (i.e., concern about being stereotyped) because negative stereotypes of their intellect are salient. Two studies included African American, European American, and Latina/Latino female and male undergraduates. Study 1 (n = 86) demonstrated while students of color generally had positive expectations of teachers, their expectations declined when imagining class with a European American instructor who would repeatedly versus never evaluate their work or an ethnically matched instructor across conditions. Study 2 (n = 136) revealed all students had more positive expectations of culturally tolerant versus culturally intolerant instructors. Students of color more than European American students perceived that intolerant instructors could grade them unfairly. We discuss implications for ethnically diverse classrooms. C1 Univ Florida, NIMH, Ctr Study Emot & Attent, Gainesville, FL 32610 USA. DeCotiisErhard Inc, Colorado Springs, CO USA. RP Brown, LM (reprint author), Univ Florida, NIMH, Ctr Study Emot & Attent, POB 100165, Gainesville, FL 32610 USA. EM drb@ufl.edu NR 52 TC 11 Z9 11 U1 2 U2 4 PU BLACKWELL PUBLISHERS PI MALDEN PA 350 MAIN STREET, STE 6, MALDEN, MA 02148 USA SN 0022-4537 J9 J SOC ISSUES JI J. Soc. Issues PY 2004 VL 60 IS 1 BP 157 EP 174 DI 10.1111/j.0022-4537.2004.00104.x PG 18 WC Social Issues; Psychology, Social SC Social Issues; Psychology GA 779LZ UT WOS:000189303200009 ER PT J AU Carlson, GA Pine, DS Nottelmann, E Leibenluft, E AF Carlson, GA Pine, DS Nottelmann, E Leibenluft, E TI Defining subtypes of childhood bipolar illness - Response and commentary SO JOURNAL OF THE AMERICAN ACADEMY OF CHILD AND ADOLESCENT PSYCHIATRY LA English DT Letter C1 SUNY Stony Brook, Sch Med, Stony Brook, NY 11794 USA. NIMH, Dept Hlth & Human Serv, NIH, Bethesda, MD 20892 USA. RP Carlson, GA (reprint author), SUNY Stony Brook, Sch Med, Stony Brook, NY 11794 USA. NR 2 TC 8 Z9 8 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0890-8567 J9 J AM ACAD CHILD PSY JI J. Am. Acad. Child Adolesc. Psychiatr. PD JAN PY 2004 VL 43 IS 1 BP 3 EP 4 DI 10.1097/01.chi.0000100440.94687.f9 PG 2 WC Psychology, Developmental; Pediatrics; Psychiatry SC Psychology; Pediatrics; Psychiatry GA 759EB UT WOS:000187724400002 ER PT J AU Sahyoun, NR Pratt, CA Anderson, A AF Sahyoun, NR Pratt, CA Anderson, A TI Evaluation of nutrition education interventions for older adults: A proposed framework SO JOURNAL OF THE AMERICAN DIETETIC ASSOCIATION LA English DT Article ID RANDOMIZED CONTROLLED TRIAL; DIETARY BEHAVIOR-CHANGE; DIABETES-MELLITUS; NUTRIENT INTAKE; CONSUMPTION; WEIGHT; OUTCOMES; PROGRAM; PREVENTION; REDUCTION AB This study was undertaken to identify nutrition interventions that could provide a basis for designing effective and measurable nutrition education programs for older adults. The authors conducted a literature search of articles published from 1990-2003 using Medline and Agricola. Key words were "elderly," "older adults," "nutrition intervention," and "nutrition education." Of 128 references identified, 25 studies included intervention and/or evaluation components and targeted adults over age 55 years. Although interventions tended to report limited success in behavior change, certain features had positive outcomes. These included limiting educational messages to one or two; reinforcing and personalizing messages; providing hands-on activities, incentives, cues, and access to health professionals; and using appropriate theories of behavior change. Based on these findings, a theoretical framework that includes these features but is set within a social and environmental context is proposed as a guideline for designing nutrition interventions for older adults. C1 Univ Maryland, Dept Nutr & Food Sci, College Pk, MD 20742 USA. NHLBI, Div Epidemiol & Clin Applicat, Bethesda, MD 20892 USA. RP Sahyoun, NR (reprint author), Univ Maryland, Dept Nutr & Food Sci, 0112 Skinner Bldg, College Pk, MD 20742 USA. NR 43 TC 46 Z9 55 U1 3 U2 15 PU AMER DIETETIC ASSOC PI CHICAGO PA 216 W JACKSON BLVD #800, CHICAGO, IL 60606-6995 USA SN 0002-8223 J9 J AM DIET ASSOC JI J. Am. Diet. Assoc. PD JAN PY 2004 VL 104 IS 1 BP 58 EP 69 DI 10.1016/j.jada.2003.10.013 PG 12 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 758QU UT WOS:000187662300008 PM 14702585 ER PT J AU Simpson, CF Boyd, CM Carlson, MC Griswold, ME Guralnik, JM Fried, LP AF Simpson, CF Boyd, CM Carlson, MC Griswold, ME Guralnik, JM Fried, LP TI Agreement between self-report of disease diagnoses and medical record validation in disabled older women: Factors that modify agreement SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Article DE self-report; disabled; aged; disease; kappa statistic ID QUESTIONNAIRE INFORMATION; RISK-FACTORS; ACCURACY; COMMUNITY; RECALL; HEALTH AB OBJECTIVES: To determine the agreement between self-report of chronic disease and validated evidence of disease using multiple ascertainment methods and to assess effects of cognition, education, age, and comorbidity. DESIGN: Cross-sectional analysis. SETTING: Community Baltimore, Maryland. PARTICIPANTS: One thousand two community-dwelling disabled women aged 65 and older. MEASUREMENTS: Kappa statistics were calculated to determine the relationship between self-report of 14 diseases and standardized algorithms. Analyses were stratified using Mini-Mental State Examination score, education, number of chronic diseases, and age. RESULTS: Kappa was excellent for hip fracture (HF), Parkinson's disease (PD), diabetes mellitus (DM), cancer, stroke, and disc disease (DD); fair to good for angina pectoris, congestive heart failure, and myocardial infarction; and poor for peripheral arterial disease, spinal stenosis, osteoporosis, arthritis, and lung disease. Overall, kappa decreased with decreasing cognition and education, increasing age, and four or more diseases. CONCLUSION: In disabled older women, self-report of physician diagnosis of HF, PD, DM, cancer, stroke, and DD appears valid. In general, increasing comorbidity and age and decreasing cognition and education do not reduce validity for diseases where agreement was excellent overall. C1 Johns Hopkins Sch Med, Ctr Aging & Hlth, Baltimore, MD 21205 USA. Johns Hopkins Sch Med, Div Geriatr Med, Baltimore, MD 21205 USA. Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Dept Biostat, Baltimore, MD USA. Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Dept Mental Hyg, Baltimore, MD USA. NIA, Epidemiol & Demog Sect, Lab Epidemiol Demog & Biometry, Baltimore, MD 21224 USA. RP Simpson, CF (reprint author), Johns Hopkins Sch Med, Ctr Aging & Hlth, 2024 E Monument St,Suite 2-700, Baltimore, MD 21205 USA. FU NIA NIH HHS [T32AG00247, N01-AG-1-2112] NR 18 TC 182 Z9 184 U1 0 U2 5 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD JAN PY 2004 VL 52 IS 1 BP 123 EP 127 DI 10.1111/j.1532-5415.2004.52021.x PG 5 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 756DR UT WOS:000187451000020 PM 14687326 ER PT J AU Daugirdas, JT Greene, T Depner, TA Leypoldt, J Gotch, F Schulman, G Star, R AF Daugirdas, JT Greene, T Depner, TA Leypoldt, J Gotch, F Schulman, G Star, R TI Factors that affect postdialysis rebound in serum urea concentration, including the rate of dialysis: Results from the HEMO study SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Article ID REGIONAL BLOOD-FLOW; CHRONIC-HEMODIALYSIS PATIENTS; BODY WATER VOLUMES; EQUILIBRATED KT/V; SINGLE-POOL; RECIRCULATION; VALIDATION; EXERCISE; KINETICS; MODEL AB Previous studies have suggested that postdialysis urea rebound is related to K/V, the rate of dialysis, but a systematic analysis of factors that affect rebound has not been reported. With the use of 30-min and, in a subset, 60-min postdialysis samples, postdialysis urea rebound was measured to (1) determine how well previously proposed equations based on the rate of dialysis (K/V) predict rebound in a large sample of patients with varying characteristics, (2) determine whether other factors besides K/V affect rebound, and (3) estimate more precise values for coefficients in prediction equations for rebound. Rebound was calculated relative to both immediate and 20-s postdialysis samples to study early components of rebound unrelated to access recirculation. The equilibrated Kt/V (eKt/V) computed by fitting the two-pool variable volume model to the 30-min postdialysis sample agreed well with eKt/V based on the 60-min postdialysis sample. Using the pre-, post-, and 30-min postdialysis samples for 1245 patients with arteriovenous (AV) accesses, the median intercompartmental mass transfer coefficient (Kc) was 797 ml/min for rebound computed relative to the 20-s postdialysis samples and 592 ml/min relative to the immediate postdialysis samples. K/V was the strongest predictor of rebound among 22 factors considered. Other factors associated with greater rebound for 1331 patients using AV accesses or venous catheters included access type, black race, male gender, absence of congestive heart failure, greater age, ultrafiltration rate, and low predialysis or intradialysis systolic BP. Equations of the form eKt/V = single-pool Kt/V - B X (K/V) were fit to the data. With AV access, the optimum values for the slope term (B) were 0.39 and 0.46 (in h(-1)) for single-pool Kt/V calculated based on 20-s postdialysis or immediate postdialysis samples, respectively. For patients using venous catheters, the respective values for B were 0.22 and 0.29. Postdialysis urea rebound can be predicted with acceptable accuracy from a postdialysis sample using a zero-intercept, K/V-based rate equation. Several patient or treatment-specific factors predict enhanced or reduced rebound. Rate equation slope coefficients for K/V of 0.39 (AV access) and 0.22 (venous access) are proposed when a 15- to 20-s slow-flow method is used to draw the postdialysis blood. Slightly higher K/V slope coefficients (0.46 and 0.29, respectively) should be used if a shorter (e.g., 10 s) slow-flow period is used. C1 NIDDKD, NIH, Bethesda, MD 20892 USA. RP Daugirdas, JT (reprint author), Univ Illinois, Coll Med, Div Nephrol, 15W560 89th St, Hinsdale, IL 60527 USA. NR 31 TC 31 Z9 33 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD JAN PY 2004 VL 15 IS 1 BP 194 EP 203 DI 10.1097/01.ASN.0000103871.20736.0C PG 10 WC Urology & Nephrology SC Urology & Nephrology GA 757CP UT WOS:000187531500022 PM 14694173 ER PT J AU Levin, I Kovler, M Roizin, Y Vofsi, M Leapman, RD Goodman, G Kawada, N Funahashi, M AF Levin, I Kovler, M Roizin, Y Vofsi, M Leapman, RD Goodman, G Kawada, N Funahashi, M TI Structure, chemistry, and electrical performance of silicon oxide-nitride-oxide stacks on silicon SO JOURNAL OF THE ELECTROCHEMICAL SOCIETY LA English DT Article ID NITROGEN; FILMS; SIO2/SI3N4/SIO2; SPECTROSCOPY AB The structure and chemistry of silicon oxide-nitride-oxide (ONO) stacks on silicon with differently processed top oxide layers were analyzed using high-resolution transmission electron microscopy, electron energy loss spectroscopy, secondary ion mass spectroscopy, and X-ray specular reflectometry. The changes observed in the structure and chemistry of the ONO stacks were correlated with the electrical performance of these stacks in flash-memory devices. The results demonstrated that using larger thermal budgets to form the top oxide layer yields (i) broader N distribution across the nitride/oxide interfaces, ( ii) reduced H content at the Si/SiO2 interfaces, (iii) increased density of the top oxide layer, and ultimately, (iv) improved electrical performance of ONO-based memory devices. (C) 2004 The Electrochemical Society. C1 Natl Inst Stand & Technol, Div Ceram, Gaithersburg, MD 20899 USA. Tower Semicond Ltd, IL-23105 Migdal Haemeq, Israel. NIH, Div Bioengn & Phys Sci, Bethesda, MD 20892 USA. Charles Evans & Associates, Sunnyvale, CA 94086 USA. Rigaku Corp, Akishima, Tokyo 1968666, Japan. RP Natl Inst Stand & Technol, Div Ceram, Gaithersburg, MD 20899 USA. EM igor.levin@nist.gov RI Levin, Igor/F-8588-2010 NR 18 TC 12 Z9 12 U1 0 U2 3 PU ELECTROCHEMICAL SOC INC PI PENNINGTON PA 65 SOUTH MAIN STREET, PENNINGTON, NJ 08534 USA SN 0013-4651 EI 1945-7111 J9 J ELECTROCHEM SOC JI J. Electrochem. Soc. PY 2004 VL 151 IS 12 BP G833 EP G838 DI 10.1149/1.1811594 PG 6 WC Electrochemistry; Materials Science, Coatings & Films SC Electrochemistry; Materials Science GA 870OY UT WOS:000225068500068 ER PT J AU Abels, EG Cogdill, KW Zach, L AF Abels, EG Cogdill, KW Zach, L TI Identifying and communicating the contributions of library and information services in hospitals and academic health sciences centers SO JOURNAL OF THE MEDICAL LIBRARY ASSOCIATION LA English DT Article ID CARE AB Objective: This article introduces a systematic approach to identifying and communicating the value of library and information services (LIS) from the perspective of their contributions to achieving organizational goals. Methods: The contributions of library and information services (CLIS) approach for identifying and communicating the value of LIS draws on findings from a multimethod study of hospitals and academic health sciences centers. Results: The CLIS approach is based on the concept that an individual unit's value to an organization can be demonstrated by identifying and measuring its contributions to organizational goals. The CLIS approach involves seven steps: (1) selecting appropriate organizational goals that are meaningful in a specific setting; (2) linking LIS contributions to organizational goals; (3) obtaining data from users on the correspondence between LIS contributions and LIS services; (4) selecting measures for LIS services; (5) collecting and analyzing data for the selected measures; (6) planning and sustaining communication with administrators about LIS contributions; and (7) evaluating findings and revising selected goals, contributions, and services as necessary. Conclusions: The taxonomy of LIS contributions and the CLIS approach emerged from research conducted in hospitals and academic health sciences centers and reflect the mission and goals common in these organizations. However, both the taxonomy and the CLIS approach may be adapted for communicating the value of LIS in other settings. C1 Univ Maryland, Coll Informat Studies, College Pk, MD 20742 USA. Natl Lib Med, Natl Network Off, Bethesda, MD 20894 USA. Louisiana State Univ, Sch Lib & Informat Sci, Baton Rouge, LA 70803 USA. RP Abels, EG (reprint author), Univ Maryland, Coll Informat Studies, 4105 Hornbake Bldg, College Pk, MD 20742 USA. EM ega@umd.edu; cogdilk@mail.nlm.nih.gov; lzach@wam.umd.edu OI Cogdill, Keith/0000-0002-9863-1657 NR 17 TC 14 Z9 15 U1 1 U2 5 PU MEDICAL LIBRARY ASSOC PI CHICAGO PA 65 EAST WACKER PLACE, STE 1900, CHICAGO, IL 60601-7298 USA SN 1536-5050 J9 J MED LIBR ASSOC JI J. Med. Libr. Assoc. PD JAN PY 2004 VL 92 IS 1 BP 46 EP 55 PG 10 WC Information Science & Library Science SC Information Science & Library Science GA 773YH UT WOS:000188952600006 PM 14762462 ER PT J AU Butterfield, MI Bosworth, HB Stechuchak, KM Frothingham, R Bastian, LA Meador, KG Swartz, M Horner, RD AF Butterfield, MI Bosworth, HB Stechuchak, KM Frothingham, R Bastian, LA Meador, KG Swartz, M Horner, RD TI Racial differences in hepatitis B and hepatitis C and associated risk behaviors in veterans with severe mental illness SO JOURNAL OF THE NATIONAL MEDICAL ASSOCIATION LA English DT Article; Proceedings Paper CT VA Health Services Resarch and Development Annual Meeting CY FEB, 2002 CL WASHINGTON, D.C. DE race; hepatitis B; hepatitis C; veterans; mental illness ID NUTRITION EXAMINATION SURVEYS; VIRUS-INFECTION; UNITED-STATES; SEXUAL-BEHAVIOR; NATIONAL-HEALTH; COCAINE USE; PREVALENCE; ALPHA; HIV; SCHIZOPHRENIA AB Racial differences in the seroprevalence of and risks for hepatitis B (HBV) and hepatitis C (HCV) were examined in military veterans with severe mental illnesses (SMI). Participants (376; 155 Caucasian, 221 African American) were inpatients at a Veterans Affairs (VA) psychiatric unit in Durham, N.C., from 1998 to 2000. Prevalence rates of HBV and HCV were 21.3% and 18.9%, respectively. African Americans had a higher HBV seroprevalence than did Caucasians: 27.6% versus 12.3%; odds ratio (OR) 2.73; 95% confidence interval (Cl)=1.55, 4.79. Although not statistically significant, HCV seroprevalence was also higher for African Americans than it was for Caucasians: 21.3% versus 15.5%; OR=1.47; 95% CI=0.86, 2.53. No racial difference was observed for injection drug use (IDU), the strongest risk indicator for both HBV and HCV. Multivariable analyses indicated that African-American race, IDU, and multiple sex partners in the past six months were related to an increased risk of HBV, whereas IDU and smoking crack cocaine were both independently related to an increased risk of HCV. Thus, veterans with SMI-particularly African-American veterans-have high rates of HBV and HCV infection. African-American veterans have significantly higher rates of HBV than do Caucasian veterans, which persist after controlling for prominent risk behaviors. C1 Vet Affairs Med Ctr, HSR&D, Durham, NC 27705 USA. Duke Univ, Dept Psychiat & Behav Sci, Durham, NC 27706 USA. Duke Univ, Dept Med, Div Gen Med, Durham, NC 27706 USA. Duke Univ, Ctr Aging & Human Dev, Durham, NC 27706 USA. VAMC, Epidemiol Res & Informat Ctr, Durham, NC USA. VAMC, Med Serv, Durham, NC USA. VAMC, Mental Hlth Serv, Durham, NC USA. NINDS, Bethesda, MD 20892 USA. RP Butterfield, MI (reprint author), Vet Affairs Med Ctr, HSR&D, Bldg 16,Room 70,508 Fulton St, Durham, NC 27705 USA. EM mimi@duke.edu NR 59 TC 14 Z9 15 U1 1 U2 1 PU NATL MED ASSOC PI WASHINGON PA 1012 10TH ST, N W, WASHINGON, DC 20001 USA SN 0027-9684 J9 J NATL MED ASSOC JI J. Natl. Med. Assoc. PD JAN PY 2004 VL 96 IS 1 BP 43 EP 52 PG 10 WC Medicine, General & Internal SC General & Internal Medicine GA 890ZG UT WOS:000226549900003 PM 14746353 ER PT J AU Hwang, JJ Shoaf, G Uchio, EM Watson, J Pacak, K Linehan, WM Walther, MM AF Hwang, JJ Shoaf, G Uchio, EM Watson, J Pacak, K Linehan, WM Walther, MM TI Laparoscopic management of extra-adrenal pheochromocytoma SO JOURNAL OF UROLOGY LA English DT Article DE paraganglioma; extra-adrenal; pheochromocytoma; laparoscopy ID NONSEMINOMATOUS TESTICULAR-TUMOR; PARTIAL ADRENALECTOMY; PARAGANGLIOMAS; RESECTION; LOCALIZATION; DISSECTION; SURGERY AB Purpose: Laparoscopic management of extra-adrenal pheochromocytoma presents a unique surgical challenge due to variable anatomical presentation and potential catecholamine surge during operative manipulation. We report our experience with laparoscopic removal of extra-adrenal pheochromocytomas. Materials and Methods: Between 1999 and 2002, 5 patients presented with retroperitoneal extra-adrenal pheochromocytomas. Of the patients 2 had a history of von Hippel-Lindau disease, and the remaining 3 patients were diagnosed with sporadic extra-adrenal pheochromocytoma during hypertension evaluation. Although 4 patients had a history of hypertension, only 2 reported symptoms (episodic flushing, headaches, blurred vision) associated with excess catecholamine production. All patients had markedly increased preoperative urinary and plasma normetanephrine and/or norepinephrine levels, and 3 had positive I-131 metaiodobenzylguanidine scan. In each case tumor was accurately identified on computerized tomography before surgery. Results: Laparoscopic resection of extra-adrenal pheochromocytoma was successful in 4 patients. Open conversion was required in 1 patient, who also had von Hippel-Lindau related bilateral adrenal pheochromocytomas due to significant adhesion of the extra-adrenal tumor to the aorta and renal hilum, and a concern for possible local invasion. Mean laparoscopic operative time and blood loss were 273 minutes (range 240 to 350) and 119 cc (range 75 to 200), respectively. Three 10 mm ports in a standard triangular fashion were used for the left side tumors, in which the tumors were found lateral to the aorta. For the right side tumors located either in the inter-aortacaval or para-caval region, a fourth port (10 mm) was inserted for liver retraction as needed. Laparoscopic ultrasound was used to localize the tumor and to assess the retroperitoneum for possible metastasis (none detected) in 3 cases. None of the patients had a hypertensive crisis intraoperatively, and all had unremarkable postoperative recovery with an average hospital stay of 3.8 days (range 3 to 4). Plasma and/or urinary norepinephrine and normetanephrine levels returned to normal range postoperatively in all cases. One patient was noted to have left lower extremity lymphedema and gluteal hematoma due to a positional injury related to prolonged pressure from the operating table and was treated conservatively. There has been no tumor recurrence at a median followup of 14 months (range 9 to 36). Conclusions: With careful surgical planning and appropriate preoperative pharmacological blockade, laparoscopic surgery can be safely performed in patients with extra-adrenal pheochromocytomas with minimal morbidity. Laparoscopic ultrasound may be helpful in precise localization and evaluation of tumor extension. C1 NCI, Urol Oncol Branch, DCT, NIH, Bethesda, MD 20892 USA. NICHHD, Pediat & Reprod Endocrinol Branch, NIH, Bethesda, MD 20892 USA. RP Walther, MM (reprint author), NCI, Urol Oncol Branch, DCT, NIH, Bldg 10,Room 2B47,10 Ctr Dr,MSC 1501, Bethesda, MD 20892 USA. NR 18 TC 25 Z9 34 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0022-5347 J9 J UROLOGY JI J. Urol. PD JAN PY 2004 VL 171 IS 1 BP 72 EP 76 DI 10.1097/01.ju.0000102081.46348.a4 PG 5 WC Urology & Nephrology SC Urology & Nephrology GA 755EM UT WOS:000187390800016 PM 14665847 ER PT J AU Rundback, JH Dorfman, G Safriel, Y Mauro, M Wright, K Bonn, J Farahani, K Murthy, R AF Rundback, JH Dorfman, G Safriel, Y Mauro, M Wright, K Bonn, J Farahani, K Murthy, R TI Development of a research agenda for interventional oncology: Proceedings from an interdisciplinary consensus panel SO JOURNAL OF VASCULAR AND INTERVENTIONAL RADIOLOGY LA English DT Article ID UNRESECTABLE HEPATOCELLULAR-CARCINOMA; RADIOFREQUENCY TUMOR ABLATION; RADIATION-THERAPY; GENE-THERAPY; LIVER-CANCER; CHEMOEMBOLIZATION; OPPORTUNITIES; MICROSPHERES; EMBOLIZATION; CHALLENGES C1 Columbia Presbyterian Med Ctr, Dept Radiol, New York, NY 10032 USA. Univ Massachusetts, Dept Radiol, Amherst, MA 01003 USA. Yale Univ, Dept Radiol, New Haven, CT USA. Univ N Carolina, Dept Radiol, Chapel Hill, NC USA. Thomas Jefferson Univ Hosp, Dept Radiol, Philadelphia, PA 19107 USA. NCI, Rockville, MD USA. MD Anderson Canc Ctr, Dept Radiol, Houston, TX USA. RP Rundback, JH (reprint author), Columbia Presbyterian Med Ctr, Dept Radiol, 177 Ft Washington Ave, New York, NY 10032 USA. EM jr204l@columbia.edu RI Farahani, Keyvan/G-9069-2012 NR 20 TC 4 Z9 4 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1051-0443 J9 J VASC INTERV RADIOL JI J. Vasc. Interv. Radiol. PD JAN PY 2004 VL 15 IS 1 BP 7 EP 12 DI 10.1097/01.RVI.0000106389.63463.D3 PN 1 PG 6 WC Radiology, Nuclear Medicine & Medical Imaging; Peripheral Vascular Disease SC Radiology, Nuclear Medicine & Medical Imaging; Cardiovascular System & Cardiology GA 919EC UT WOS:000228600100002 PM 14709681 ER PT J AU Schonherr, E Sunderkotter, C Schaefer, L Thanos, S Grassel, S Oldberg, A Iozzo, RV Young, MF Kresse, H AF Schonherr, E Sunderkotter, C Schaefer, L Thanos, S Grassel, S Oldberg, A Iozzo, RV Young, MF Kresse, H TI Decorin deficiency leads to impaired angiogenesis in injured mouse cornea SO JOURNAL OF VASCULAR RESEARCH LA English DT Article DE inflammation; collagen; extracellular matrix; vascular endothelium; corneal epithelium ID GROWTH-FACTOR-BETA; ENDOTHELIAL-CELLS; EXTRACELLULAR-MATRIX; I COLLAGEN; DIFFERENTIAL EXPRESSION; TARGETED DISRUPTION; SKIN FRAGILITY; BIGLYCAN; PROTEOGLYCANS; FIBROMODULIN AB Small leucine-rich proteoglycans play important roles in the organization of the extracellular matrix as well as for the regulation of cell behavior; two biological processes that are essential for angiogenesis. We investigated consequences of the targeted ablation of decorin (DCN), biglycan (BGN) and fibromodulin (FMOD) genes on inflammation-induced angiogenesis in the cornea. In wildtype mice, DCN was localized exclusively to the corneal stroma, while FMOD and BGN were more prominently expressed in epithelial cells. Endothelial cells from limbus blood vessels expressed BGN and FMOD, but no DCN. However, after induction of angiogenesis by chemical cauterization, DCN was expressed in the newly formed capillaries, together with BGN and FMOD. Notably, in DCN-deficient mice, the growth of vessels was significantly diminished, whereas it did not significantly change in FMOD- or BGN-deficient animals. Moreover, blood vessels of DCN-deficient mice exhibited a similar expression level of BGN as control mice, while FMOD was increased on day 3 after injury. These results indicate that DCN, in addition to its effects on fibrillogenesis, plays a regulatory role in angiogenesis and that FMOD in endothelial cells may be able to partially substitute for DCN. Copyright (C) 2004 S. Karger AG, Basel. C1 Univ Wales Coll Med, Sch Dent, Matrix Biol & Tissue Repair Res Unit, Cardiff CF14 4XY, S Glam, Wales. Univ Munster, Inst Physiol Chem & Pathobiochem, D-4400 Munster, Germany. Univ Munster, Inst Expt Dermatol, D-4400 Munster, Germany. Univ Munster, Dept Dermatol, D-4400 Munster, Germany. Univ Munster, Dept Internal Med D, D-4400 Munster, Germany. Univ Munster, Dept Expt Ophthalmol, D-4400 Munster, Germany. Univ Hosp Munster, Munster, Germany. Univ Ulm, Dept Dermatol & Allergol, Ulm, Germany. Univ Hosp Ulm, Ulm, Germany. Orthoped Univ Hosp Regensburg, Regensburg, Germany. Lund Univ, Dept Cell & Mol Biol, Lund, Sweden. Thomas Jefferson Univ, Dept Pathol Anat & Cell Biol, Philadelphia, PA 19107 USA. Natl Inst Dent & Craniofacial Res, Craniofacial & Skeletal Dis Branch, NIH, Bethesda, MD USA. RP Schonherr, E (reprint author), Univ Wales Coll Med, Sch Dent, Matrix Biol & Tissue Repair Res Unit, Heath Pk, Cardiff CF14 4XY, S Glam, Wales. EM schonherreh@cardiff.ac.uk OI Iozzo, Renato/0000-0002-5908-5112 NR 42 TC 73 Z9 74 U1 0 U2 1 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1018-1172 J9 J VASC RES JI J. Vasc. Res. PY 2004 VL 41 IS 6 BP 499 EP 508 DI 10.1159/000081806 PG 10 WC Physiology; Peripheral Vascular Disease SC Physiology; Cardiovascular System & Cardiology GA 888ZE UT WOS:000226412300003 PM 15528932 ER PT J AU Horner, RD Oddone, EZ Stechuchak, KM Johnston, DCC Grambow, SC AF Horner, RD Oddone, EZ Stechuchak, KM Johnston, DCC Grambow, SC TI Who doesn't receive carotid endarterectomy when appropriate? SO JOURNAL OF VASCULAR SURGERY LA English DT Article ID CLINICAL INDICATIONS; RACIAL-DIFFERENCES; PHYSICIAN SCALE; RELIABILITY; VALIDITY; STROKE; TESTS; TRUST; RATES; RACE AB Objective: The purpose of this study was to identify clinical and nonclinical factors associated with failure to perform carotid endarterectomy (CEA) in patients with clinically appropriate indications. We analyzed data from a prospective cohort study performed at five Veterans Affairs medical centers. Patients were referred for carotid artery evaluation if they had at least 50% stenosis in one carotid artery, had no history of CEA, and were independently classified preoperatively as appropriate candidates for CEA, according to clinical criteria. The primary outcome was receipt of CEA within 6 months of evaluation. Data were collected by medical record review and interview regarding clinical status, and patient and physician perception of the risks and benefits of CEA. Results: Among clinically appropriate candidates for CEA, 66.8% (n = 233) did not undergo the operation. Compared with patients who did undergo CEA, a greater proportion of these patients had no symptoms (68.7% vs 45.7%; P < .001). A twofold greater proportion of patients who did not undergo CEA were in the highest quartile of reported aversion to surgery. Moreover, a fourfold greater proportion were perceived by their physicians to be at less than 5% risk for future stroke without the operation, and more than a twofold greater proportion were believed to experience less than 5% efficacy from the operation by their providers (P < .01). In multivariable analyses, four characteristics were significantly associated with whether an appropriate candidate did not receive CEA: asymptomatic disease, less than 70% stenosis, high expressed aversion to surgery score, and low (<5%) provider-perceived efficacy of the operation. Conclusion: Among patients in the Veterans Affairs health care system who are clinically appropriate candidates for CEA, those who did not receive the operation were less likely to have symptomatic disease or high-grade carotid artery stenosis, but were more likely to report high aversion to surgery and to have a provider who believed CEA would not be efficacious. C1 NINDS, Rockville, MD 20852 USA. Duke Univ, Med Ctr, Vet Affairs Med Ctr, Ctr Hlth Serv Res Primary Care, Durham, NC USA. Duke Univ, Med Ctr, Dept Med, Durham, NC 27710 USA. Duke Univ, Med Ctr, Div Gen Internal Med, Durham, NC 27710 USA. Duke Univ, Med Ctr, Dept Biostat & Bioinformat, Durham, NC 27710 USA. St Pauls Hosp, Ctr Hlth Evaluat & Outcome Sci, Vancouver, BC V6Z 1Y6, Canada. Univ British Columbia, Vancouver, BC V5Z 1M9, Canada. RP Horner, RD (reprint author), NINDS, Neurosci Ctr Bldg,Rm 2149,6001 Execut Blvd, Rockville, MD 20852 USA. RI Grambow, Steven/E-1422-2015 OI Grambow, Steven/0000-0001-6037-3253 NR 28 TC 6 Z9 6 U1 0 U2 0 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0741-5214 J9 J VASC SURG JI J. Vasc. Surg. PD JAN PY 2004 VL 39 IS 1 BP 162 EP 168 DI 10.1016/j.jvs.2003.08.004 PG 7 WC Surgery; Peripheral Vascular Disease SC Surgery; Cardiovascular System & Cardiology GA 760NN UT WOS:000187840600033 PM 14718834 ER PT J AU Jiao, X Wang, RYH Feng, Z Hu, G Alter, HJ Shih, JWK AF Jiao, X Wang, RYH Feng, Z Hu, G Alter, HJ Shih, JWK TI DNA immunization encoding the secreted nonstructural protein 3 (NS3) of hepatitis C virus and enhancing the Th1 type immune response SO JOURNAL OF VIRAL HEPATITIS LA English DT Article; Proceedings Paper CT 10th International Symposium on Viral Hepatitis and Liver Disease CY APR 09-13, 2000 CL ATLANTA, GEORGIA DE DNA immunization; HCVNS3; Th1 response ID ANTIBODY-RESPONSES; T-LYMPHOCYTES; GENETIC IMMUNIZATION; ANTIGEN SECRETION; VIRAL-HEPATITIS; CELL RESPONSES; INFECTION; MICE; VACCINATION; INDUCTION AB To induce a sustained and specific cellular immune response to hepatitis C virus (HCV), DNA immunization of mice was performed using plasmids containing the HCV nonstructural gene 3 (HCV/NS3). Plasmids were constructed such that the NS3 gene was expressed in a secreted form, a nonsecreted form or as a membrane-bound antigen. The plasmid encoding the secreted antigen induced the strongest humoral and cellular immunity and favoured the T-helper type 1 (Th1) pathway as shown by cytokine profiles and switching of antibody subclasses. Our study indicates that DNA immunization with a secreted form of HCV/NS3 is an effective means of inducing primary Th1 immune responses in the murine model. C1 NIH, Dept Transfus Med, Warren G Magnuson Clin Ctr, Bethesda, MD 20892 USA. RP Shih, JWK (reprint author), NIH, Dept Transfus Med, Warren G Magnuson Clin Ctr, Bldg 10, Bethesda, MD 20892 USA. EM jshih@mail.cc.nih.gov NR 37 TC 7 Z9 15 U1 0 U2 0 PU BLACKWELL PUBLISHING LTD PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 1352-0504 J9 J VIRAL HEPATITIS JI J. Viral Hepatitis PD JAN PY 2004 VL 11 IS 1 BP 18 EP 26 DI 10.1046/j.1352-0504.2003.00464.x PG 9 WC Gastroenterology & Hepatology; Infectious Diseases; Virology SC Gastroenterology & Hepatology; Infectious Diseases; Virology GA 766YL UT WOS:000188411300002 PM 14738554 ER PT J AU Szajner, P Weisberg, AS Moss, B AF Szajner, P Weisberg, AS Moss, B TI Evidence for an essential catalytic role of the F10 protein kinase in vaccinia virus morphogenesis SO JOURNAL OF VIROLOGY LA English DT Article ID TEMPERATURE-SENSITIVE MUTANTS; FORM IMMATURE VIRIONS; VIRAL MEMBRANES; ENVELOPE PROTEIN; DENSE VIROPLASM; A30L PROTEIN; GENE; RECOMBINANT; PROTEIN-KINASE-2; PHOSPHORYLATION AB Temperature-sensitive mutants of vaccinia virus, with genetic changes that map to the open reading frame encoding the F10 protein kinase, exhibit a defect at an early stage of viral morphogenesis. To further study the role of the enzyme, we constructed recombinant vaccinia virus vF10V5i, which expresses inducible V5 epitopetagged F10 and is dependent on a chemical inducer for plaque formation and replication. In the absence of inducer, viral membrane formation was delayed and crescents and occasional immature forms were detected only late in infection. When the temperature was raised from 37 to 39degreesC, the block in membrane formation persisted throughout the infection. The increased stringency may be explained by a mild temperature sensitivity of the wild-type F10 kinase, which reduced the activity of the very small amount expressed in the absence of inducer, or by the thermolability of an unphosphorylated kinase substrate or uncomplexed F10-interacting protein. Further analyses demonstrated that tyrosine and threonine phosphorylation of the A17 membrane component was inhibited in the absence of inducer. The phosphorylation defect could be overcome by transfection of plasmids that express wild-type F10, but not by plasmids that express F10 with single amino acid substitutions that abolished catalytic activity. Although the mutated forms of F10 were stable and concentrated in viral factories, only the wild-type protein complemented the assembly and replication defects of vF10V5i in the absence of inducer. These studies provide evidence for an essential catalytic role of the F10 kinase in vaccinia virus morphogenesis. C1 NIAID, Lab Viral Dis, NIH, Bethesda, MD 20892 USA. George Washington Univ, Dept Genet, Washington, DC 20052 USA. RP Moss, B (reprint author), NIAID, Lab Viral Dis, NIH, 4 Ctr Dr,MSC 0445, Bethesda, MD 20892 USA. NR 25 TC 25 Z9 26 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD JAN PY 2004 VL 78 IS 1 BP 257 EP 265 DI 10.1128/JVI.78.1.257-265.2004 PG 9 WC Virology SC Virology GA 756DZ UT WOS:000187451700026 PM 14671107 ER PT J AU Szajner, P Weisberg, AS Moss, B AF Szajner, P Weisberg, AS Moss, B TI Physical and functional interactions between vaccinia virus F10 protein kinase and virion assembly proteins A30 and G7 SO JOURNAL OF VIROLOGY LA English DT Article ID FORM IMMATURE VIRIONS; VIRAL MEMBRANES; DENSE VIROPLASM; RNA-POLYMERASE; MORPHOGENESIS; GENE; PHOSPHATASE; ENCODES; PROTEIN-KINASE-2; PHOSPHORYLATION AB An early step in vaccinia virus morphogenesis, the association of crescent membranes with electron-dense granular material, is perturbed when expression of the viral protein encoded by the A30L or G7L open reading frame is repressed. Under these conditions, we found that phosphorylation of the A17 membrane protein, which is mediated by the F10 kinase, was severely reduced. Furthermore, A30 and G7 stimulated F10-dependent phosphorylation of A17 in the absence of other viral late proteins. Evidence for physical interactions between A30, G7, and F10 was obtained by their coimmuno-precipitation with antibody against A30 or F10. In addition, phosphorylation of A30 was dependent on the F10 kinase and autophosphorylation of F10 was stimulated by A30 and G7. Nevertheless, the association of A30, G7, and F10 occurred even with mutated, catalytically inactive forms of F10. Just as A30 and G7 are mutually dependent on each other for stability, F10 was nearly undetectable in the absence of A30 and G7. The reverse is not true, however, as repression of F10 did not diminish A30 or G7. Interaction of F10 with A30 and G7 presumably occurred within the virus factory areas of the cytoplasm, where each was concentrated. F10 localized predominantly in the cortical region of immature virions, beneath the membrane where A17 is located. F10 remained associated with the particulate core fraction of mature virions after treatment with a nonionic detergent and reducing agent. The formation of protein complexes such as the one involving A30, G7, and F10 may be a mechanism for the regulated packaging and processing of virion components. C1 NIAID, Viral Dis Lab, NIH, Bethesda, MD 20892 USA. George Washington Univ, Dept Genet, Grad Program, Washington, DC 20052 USA. RP Moss, B (reprint author), NIAID, Viral Dis Lab, NIH, 4 Ctr Dr,MSC 0445, Bethesda, MD 20892 USA. NR 22 TC 21 Z9 23 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD JAN PY 2004 VL 78 IS 1 BP 266 EP 274 DI 10.1128/JVI.78.1.266-274.2004 PG 9 WC Virology SC Virology GA 756DZ UT WOS:000187451700027 PM 14671108 ER PT J AU Hirsch, VM Santra, S Goldstein, S Plishka, R Buckler-White, A Seth, A Ourmanov, I Brown, CR Engle, R Montefiori, D Glowczwskie, J Kunstman, K Wolinsky, S Letvin, NL AF Hirsch, VM Santra, S Goldstein, S Plishka, R Buckler-White, A Seth, A Ourmanov, I Brown, CR Engle, R Montefiori, D Glowczwskie, J Kunstman, K Wolinsky, S Letvin, NL TI Immune failure in the absence of profound CD4(+) T-lymphocyte depletion in simian immunodeficiency virus-infected rapid progressor macaques SO JOURNAL OF VIROLOGY LA English DT Article ID LONG-TERM SURVIVORS; END-STAGE DISEASE; RHESUS-MONKEYS; TYPE-1 INFECTION; VIRAL REPLICATION; IN-VIVO; CD8(+) LYMPHOCYTES; GENETIC EVOLUTION; HIV-1 INFECTION; RESPONSES AB A fraction of simian immunodeficiency virus (SIV)-infected macaques develop rapidly progressive disease in the apparent absence of detectable SIV-specific antibody responses. To characterize the immunopathogenesis of this syndrome, we studied viral load, CD4(+) T-lymphocyte numbers as well as cellular and humoral immune responses to SIV and other exogenous antigens in four SIVsm-infected rhesus macaques that progressed to AIDS 9 to 16 weeks postinoculation. Each of these animals exhibited high levels of viremia but showed relatively preserved CD4 T lymphocytes in blood and lymphoid tissues at the time of death. Transient SIV-specific antibody responses and cytotoxic T-lymphocyte responses were observed at 2 to 4 weeks postinoculation. Two of the macaques that were immunized sequentially with tetanus toxoid and hepatitis A virus failed to develop antibody to either antigen. These studies show that the SIV-infected rapid progressor macaques initially mounted an appropriate but transient cellular and humoral immune response. The subsequent immune defect in these animals appeared to be global, affecting both cellular and humoral immunity to SIV as well as immune responses against unrelated antigens. The lack of CD4 depletion and loss of humoral and cellular immune responses suggest that their immune defect may be due to an early loss in T helper function. C1 NIAID, Mol Microbiol Lab, NIH, Rockville, MD 20852 USA. NIAID, Hepatitis Sect, Infect Dis Lab, NIH, Rockville, MD 20852 USA. Beth Israel Deaconess Med Ctr, Div Viral Pathogenesis, Boston, MA 02215 USA. Duke Univ, Ctr Med, Dept Surg, Durham, NC USA. Northwestern Univ, Sch Med, Div Infect Dis, Dept Med, Chicago, IL 60611 USA. RP Hirsch, VM (reprint author), NIAID, Mol Microbiol Lab, NIH, Rockville, MD 20852 USA. EM vhirsch@nih.gov RI Wolinsky, Steven/B-2893-2012 FU NIAID NIH HHS [AI 20729, R01 AI020729, R37 AI020729]; NICHD NIH HHS [R01 HD037356, HD 37356] NR 54 TC 33 Z9 33 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD JAN PY 2004 VL 78 IS 1 BP 275 EP 284 DI 10.1128/JVI.78.1.275-284.2004 PG 10 WC Virology SC Virology GA 756DZ UT WOS:000187451700028 PM 14671109 ER PT J AU Feldman, SA Farrell, KB Murthy, RK Russ, JL Eiden, MV AF Feldman, SA Farrell, KB Murthy, RK Russ, JL Eiden, MV TI Identification of an extracellular domain within the human PiT2 receptor that is required for amphotropic murine leukemia virus binding SO JOURNAL OF VIROLOGY LA English DT Article ID CELL-SURFACE RECEPTOR; SARCOMA-ASSOCIATED VIRUS; GIBBON APE; PHOSPHATE TRANSPORTER; SUBGROUP C; RETROVIRUS INFECTION; REGION-A; SINGLE; ENTRY; GENE AB Human PiT2 (PiT2) is a multiple-membrane-spanning protein that functions as a type III sodium phosphate cotransporter and as the receptor for amphotropic murine leukemia virus (A-MuLV). Human PiT1 (PiT1), another type III sodium phosphate cotransporter, is a highly related protein that functions as a receptor for gibbon ape leukemia virus but not for A-MuLV. The ability of PiT1 and PiT2 to function as discrete viral receptors with unique properties presumably is reflected in critical residue differences between these two proteins. Early efforts to map the region(s) within PiT2 that is important for virus binding and/or entry relied on infection results obtained with PiT1-PiT2 chimeric cDNAs expressed in Chinese hamster ovary (CHOK1) cells. These attempts to localize the PiT2 virus-binding site were hampered because they were based on infectivity, not binding, assays, and therefore, receptors that bound but failed to facilitate virus entry could not be distinguished from receptors that did not bind virus. Using a more accurate topological model for PiT2 as well as an A-MuLV receptor-binding assay, we have identified extracellular domain one (ECD1) of the human PiT2 receptor as being important for A-MuLV binding and infection. C1 NIMH, Lab Cellular & Mol Regulat, Sect Mol Virol, Bethesda, MD 20892 USA. RP Eiden, MV (reprint author), NIMH, Lab Cellular & Mol Regulat, Sect Mol Virol, Bldg 36,Rm 2A11,9000 Rockville Pike, Bethesda, MD 20892 USA. EM eidenm@mail.nih.gov NR 37 TC 15 Z9 15 U1 0 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD JAN PY 2004 VL 78 IS 2 BP 595 EP 602 DI 10.1128/JVI.78.2.595-602.2004 PG 8 WC Virology SC Virology GA 762EG UT WOS:000187957700006 PM 14694091 ER PT J AU Lu, R Nakajima, N Hofmann, W Benkirane, M Teh-Jeang, K Sodroski, J Engelman, A AF Lu, R Nakajima, N Hofmann, W Benkirane, M Teh-Jeang, K Sodroski, J Engelman, A TI Simian virus 40-based replication of catalytically inactive human immunodeficiency virus type 1 integrase mutants in nonpermissive T cells and monocyte-derived macrophages SO JOURNAL OF VIROLOGY LA English DT Article ID SV40 LARGE-T; DNA-BINDING DOMAIN; GENE-THERAPY; MEDIATED TRANSFORMATION; NUCLEAR-LOCALIZATION; VIRAL REPLICATION; HIV DNA; INFECTION; ANTIGEN; MUTATIONS AB Integrase function is required for retroviral replication in most instances. Although certain permissive T-cell lines support human immunodeficiency virus type 1 (HIV-1) replication in the absence of functional integrase, most cell lines and primary human cells are nonpermissive for integrase mutant growth. Since unintegrated retroviral DNA is lost from cells following cell division, we investigated whether incorporating a functional origin of DNA replication into integrase mutant HIV-1 might overcome the block to efficient gene expression and replication in nonpermissive T-cell lines and primary cells. Whereas the Epstein-Barr virus (EBV) origin (oriP) did little to augment expression from an integrase mutant reporter virus in EBV nuclear antigen 1-expressing cells, simian virus 40 (SV40) oriT dramatically enhanced integrase mutant infectivity in T-antigen (Tag)-expressing cells. Incorporating oriT into the nef position of a full-length, integrase-defective virus strain yielded efficient replication in Tag-expressing nonpermissive Jurkat T cells without reversion to an integration-competent genotype. Adding Tag to integrase mutant-oriT viruses yielded 11.3-kb SV40-HIV chimeras that replicated in Jurkat cells and primary monocyte-derived macrophages. Real-time quantitative PCR analyses of Jurkat cell infections revealed that amplified copies of unintegrated DNA likely contributed to SV40-HIV integrase mutant replication. SV40-based HIV-1 integrase mutant replication in otherwise nonpermissive cells suggests alternative approaches to standard integrase-mediated retroviral gene transfer strategies. C1 Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Cambridge, MA 02138 USA. Harvard Univ, Sch Publ Hlth, Dept Immunol & Infect Dis, Cambridge, MA 02138 USA. Natl Inst Allergy & Infect Dis, Lab Mol Microbiol, Bethesda, MD 20892 USA. RP Engelman, A (reprint author), Dana Farber Canc Inst, Dept Canc Immunol & AIDS, 44 Binney St, Boston, MA 02115 USA. EM alan_engelman@dfci.harvard.edu FU NIAID NIH HHS [AI45313, AI28691, P30 AI028691] NR 56 TC 29 Z9 29 U1 0 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD JAN PY 2004 VL 78 IS 2 BP 658 EP 668 DI 10.1128/JVI.78.2.658-668.2004 PG 11 WC Virology SC Virology GA 762EG UT WOS:000187957700012 PM 14694097 ER PT J AU Tran, KC Collins, PL Teng, MN AF Tran, KC Collins, PL Teng, MN TI Effects of altering the transcription termination signals of respiratory syncytial virus on viral gene expression and growth in vitro and in vivo SO JOURNAL OF VIROLOGY LA English DT Article ID VESICULAR STOMATITIS-VIRUS; OPEN READING FRAME; MESSENGER-RNA; SH GENE; M2 GENE; PROTEIN; ATTENUATION; JUNCTIONS; GENOME; CDNA AB Nonsegmented negative-sense RNA viruses (mononegaviruses) control viral gene expression largely through a transcription gradient such that promoter-proximal genes are transcribed more abundantly than downstream genes. For some paramyxoviruses, naturally occurring differences in the levels of efficiency of transcription termination by various gene end (GE) signals provide an additional level of regulation of gene expression. The first two genes (NS1 and NS2) of respiratory syncytial virus (RSV) are particularly inefficient in termination. We investigated whether altering the termination efficiency (TE) of these two genes in infectious recombinant virus would affect transcription of promoter-proximal and promoter-distal genes, production of viral proteins, and viral replication in cell culture and in the respiratory tract of mice. Recombinant RSVs were constructed with mutations that increased or decreased the TE of the NS1 GE signal, increased that of the NS2 GE signal, or increased that of both signals. Increasing the TE of either or both GE signals resulted in decreased production of the related polycistronic readthrough mRNAs, which normally arise due to the failure of the viral polymerase to recognize the GE signal. This was accompanied by a small increase in the levels of monocistronic NS1 and NS2 mRNAs. Conversely, decreasing the TE of the NS1 GE increased the production of readthrough mRNAs concomitant with a decrease of monocistronic NSl and NS2 mRNA levels. These changes were reflected in the levels of NSl and NS2 protein. All of the mutant viruses displayed growth kinetics and virus yields similar to wild-type recombinant RSV (rA2) in both HEp-2 and Vero cells. In addition, all mutants grew similarly to rA2 in the upper- and lower-respiratory tract of BALB/c mice, though some of the mutants displayed slightly decreased replication. These data suggest that the natural inefficiencies of transcription termination by the NSl and NS2 GE signals do not play important roles in controlling the magnitude of RSV gene expression or the efficiency of virus replication. Furthermore, while changes in the TE of a GE signal clearly can affect the transcription of its gene as well as that of the one immediately downstream, these changes did not have a significant effect on the overall transcriptional gradient. C1 NIAID, Lab Infect Dis, Bethesda, MD 20892 USA. RP Collins, PL (reprint author), NIAID, Lab Infect Dis, Bldg 50,Room 6503,50 S Dr MSC 8007, Bethesda, MD 20892 USA. EM pcollins@niaid.nih.gov RI Teng, Michael/I-5006-2012 OI Teng, Michael/0000-0002-0722-3659 NR 28 TC 8 Z9 9 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD JAN PY 2004 VL 78 IS 2 BP 692 EP 699 DI 10.1128/JVI.78.2.692-699.2004 PG 8 WC Virology SC Virology GA 762EG UT WOS:000187957700015 PM 14694100 ER PT J AU Shehu-Xhilaga, M Ablan, S Demirov, DG Chen, CP Montelaro, RC Freed, EO AF Shehu-Xhilaga, M Ablan, S Demirov, DG Chen, CP Montelaro, RC Freed, EO TI Late domain-dependent inhibition of equine infectious anemia virus budding SO JOURNAL OF VIROLOGY LA English DT Article ID VESICULAR STOMATITIS-VIRUS; ROUS-SARCOMA-VIRUS; UBIQUITIN-PROTEASOME SYSTEM; MURINE LEUKEMIA-VIRUS; PROLINE-RICH MOTIF; TSG101 UEV DOMAIN; IMMUNODEFICIENCY-VIRUS; MULTIVESICULAR-BODY; GAG POLYPROTEIN; MATRIX PROTEIN AB The Gag proteins of a number of different retroviruses contain late or L domains that promote the release of virions from the plasma membrane. Three types of L domains have been identified to date: Pro-Thr-Ala-Pro (PTAP), Pro-Pro-X-Tyr, and Tyr-Pro-Asp-Leu. It has previously been demonstrated that overexpression of the N-terminal, E2-like domain of the endosomal sorting factor TSG101 (TSG-5') inhibits human immunodeficiency virus type 1 (HIV-1) release but does not affect the release of the PPPY-containing retrovirus murine leukemia virus (MLV), whereas overexpression of the C-terminal portion of TSG101 (TSG-3') potently disrupts both HIV-1 and MLV budding. In addition, it has been reported that, while the release of a number of retroviruses is disrupted by proteasome inhibitors, equine infectious anemia virus (EIAV) budding is not affected by these agents. In this study, we tested the ability of TSG-5', TSG-3', and full-length TSG101 (TSG-F) overexpression, a dominant negative form of the AAA ATPase Vps4, and proteasome inhibitors to disrupt the budding of EIAV particles bearing each of the three types of L domain. The results indicate that (i) inhibition by TSG-5' correlates with dependence on PTAP; (ii) the release of wild-type EIAV (EIAV/WT) is insensitive to TSG-3', whereas this C-terminal TSG101 fragment potently impairs the budding of EIAV when it is rendered PTAP or PPPY dependent; (iii) budding of all EIAV clones is blocked by dominant negative Vps4; and (iv) EIAV/WT release is not impaired by proteasome inhibitors, while EIAV/PTAP and EIAV/PPPY release is strongly disrupted by these compounds. These findings highlight intriguing similarities and differences in host factor utilization by retroviral L domains and suggest that the insensitivity of EIAV to proteasome inhibitors is conferred by the L domain itself and not by determinants in Gag outside the L domain. C1 NIAID, Lab Mol Microbiol, NIH, Bethesda, MD 20892 USA. Univ Pittsburgh, Sch Med, Dept Mol Genet & Biochem, Pittsburgh, PA 15261 USA. RP Freed, EO (reprint author), NIH, HIV Drug Resistance Program, Virus Cell Interact Sect, Bg 535 Rm 124, Ft Detrick, MD 21702 USA. EM efreed@mail.nih.gov FU NCI NIH HHS [R01 CA049296, 2R01 CA49296]; NIAID NIH HHS [T32 AI49820, T32 AI049820] NR 85 TC 51 Z9 51 U1 0 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD JAN PY 2004 VL 78 IS 2 BP 724 EP 732 DI 10.1128/JVI.78.2.724-732.2004 PG 9 WC Virology SC Virology GA 762EG UT WOS:000187957700019 PM 14694104 ER PT J AU Buck, CB Pastrana, DV Lowy, DR Schiller, JT AF Buck, CB Pastrana, DV Lowy, DR Schiller, JT TI Efficient intracellular assembly of papillomaviral vectors SO JOURNAL OF VIROLOGY LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; L2 CAPSID PROTEINS; BOVINE PAPILLOMAVIRUS; GENE-EXPRESSION; L1/L2 CAPSIDS; TRANSFER-RNA; PLASMID DNA; TYPE-16 L1; PARTICLES; PSEUDOVIRIONS AB Although the papillomavirus structural proteins, L1 and L2, can spontaneously coassemble to form virus like particles, currently available methods for production of L1/L2 particles capable of transducing reporter plasmids into mammalian cells are technically demanding and relatively low-yield. In this report, we describe a simple 293 cell transfection method for efficient intracellular production of papillomaviral-based gene transfer vectors carrying reporter plasmids. Using bovine papillomavirus type 1 (BPV1) and human papillomavirus type 16 as model papillomaviruses, we have developed a system for producing papillomaviral vector stocks with titers of several billion transducing units per milliliter. Production of these vectors requires both L1 and L2, and transduction can be prevented by papillomavirus-neutralizing antibodies. The stocks can be purified by an iodixanol (OptiPrep) gradient centrifugation procedure that is substantially more effective than standard cesium chloride gradient purification. Although earlier data had suggested a potential role for the viral early protein E2, we found that E2 protein expression did not enhance the intracellular production of BPV1 vectors. It was also possible to encapsidate reporter plasmids devoid of BPV1 DNA sequences. BPV1 vector production efficiency was significantly influenced by the size of the target plasmid being packaged. Use of 6-kb target plasmids resulted in BPV1 vector yields that were higher than those with target plasmids closer to the native 7.9-kb size of papillomavirus genomes. The results suggest that the intracellular assembly of papillomavirus structural proteins around heterologous reporter plasmids is surprisingly promiscuous and may be driven primarily by a size discrimination mechanism. C1 NCI, Lab Cellular Oncol, Bethesda, MD 20892 USA. RP Schiller, JT (reprint author), NCI, Lab Cellular Oncol, Bldg 37,Room 4106, Bethesda, MD 20892 USA. EM schillej@dc37a.nci.nih.gov OI Buck, Christopher/0000-0003-3165-8094 NR 50 TC 277 Z9 291 U1 1 U2 6 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD JAN PY 2004 VL 78 IS 2 BP 751 EP 757 DI 10.1128/JVI.78.2.751-757.2004 PG 7 WC Virology SC Virology GA 762EG UT WOS:000187957700022 PM 14694107 ER PT J AU Persaud, D Siberry, GK Ahonkhai, A Kajdas, J Monie, D Hutton, N Watson, DC Quinn, TC Ray, SC Siliciano, RF AF Persaud, D Siberry, GK Ahonkhai, A Kajdas, J Monie, D Hutton, N Watson, DC Quinn, TC Ray, SC Siliciano, RF TI Continued production of drug-sensitive human immunodeficiency virus type 1 in children on combination antiretroviral therapy who have undetectable viral loads SO JOURNAL OF VIROLOGY LA English DT Article ID CD4(+) T-CELLS; LATENT RESERVOIR; HIV-1 INFECTION; IN-VIVO; GENETIC-CHARACTERIZATION; IMMUNE-RESPONSES; PLASMA VIREMIA; REPLICATION; PERSISTENCE; INDINAVIR AB Highly active antiretroviral therapy (HAART) can suppress plasma human immunodeficiency virus type 1 (HIV-1) levels to below the detection limit of ultrasensitive clinical assays. However, HIV-1 persists in cellular reservoirs, and in adults, persistent low-level viremia is detected with more sensitive assays. The nature of this viremia is poorly understood, and it is unclear whether viremia persists in children on HAART, particularly those who start therapy shortly after birth. We therefore developed a reverse transcriptase PCR (RT-PCR) assay that allows genotyping of HIV-1 protease even when viremia is present at levels as low as 5 copies of HIV-1 RNA/ml. We demonstrated that viremia persists in children with plasma virus levels below the limit of detection of clinical assays. Viremia was detected even in children who began HAART in early infancy and maintained such strong suppression of viremia that HIV-1-specific antibody responses were absent or minimal. The low-level plasma virus lacked protease inhibitor resistance mutations despite the frequent use of nelfinavir, which has a low mutational barrier to resistance. Protease sequences resembled those of viruses in the latent reservoir in resting CD4(+) T cells. Thus, in most children on HAART with clinically undetectable viremia, there is continued virus production without evolution of resistance in the protease gene. C1 Johns Hopkins Univ, Sch Med, Dept Pediat, Baltimore, MD 21205 USA. Johns Hopkins Univ, Sch Med, Dept Med, Baltimore, MD 21205 USA. Univ Maryland, Sch Med, Dept Pediat, Baltimore, MD 21201 USA. Howard Hughes Med Inst, Baltimore, MD USA. NIAID, NIH, Bethesda, MD 20892 USA. RP Persaud, D (reprint author), Johns Hopkins Univ, Sch Med, Dept Pediat, Pk 256,600 N Wolfe St, Baltimore, MD 21205 USA. EM dpers@jhmi.edu RI Ray, Stuart/B-7527-2008 OI Ray, Stuart/0000-0002-1051-7260 FU NIAID NIH HHS [R01 AI051178, AI43222, AI51178, R01 AI043222, R37 AI051178] NR 47 TC 70 Z9 72 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD JAN PY 2004 VL 78 IS 2 BP 968 EP 979 DI 10.1128/JVI.78.2.968-979.2004 PG 12 WC Virology SC Virology GA 762EG UT WOS:000187957700043 PM 14694128 ER PT J AU Murakami, T Ablan, S Freed, EO Tanaka, Y AF Murakami, T Ablan, S Freed, EO Tanaka, Y TI Regulation of human immunodeficiency virus type 1 Env-mediated membrane fusion by viral protease activity SO JOURNAL OF VIROLOGY LA English DT Article ID NEWCASTLE-DISEASE VIRUS; ENVELOPE GLYCOPROTEIN INCORPORATION; GP41 CYTOPLASMIC TAIL; CELL-FUSION; TRANSMEMBRANE PROTEIN; MATRIX PROTEIN; MONOCLONAL-ANTIBODIES; CD4 INDEPENDENCE; T-CELLS; INFECTIVITY AB We and others have presented evidence for a direct interaction between the matrix (MA) domain of the human immunodeficiency virus type 1 (HIV-1) Gag protein and the cytoplasmic tail of the transmembrane envelope (Env) glycoprotein gp41. In addition, it has been postulated that the MA domain of Gag undergoes a conformational change following Gag processing, and the cytoplasmic tail of gp41 has been shown to modulate Env-mediated membrane fusion activity. Together, these results raise the possibility that the interaction between the gp41 cytoplasmic tail and MA is regulated by protease (PR)-mediated Gag processing, perhaps affecting Env function. To examine whether Gag processing affects Env-mediated fusion, we compared the ability of wild-type (WT) HIV-1 Env and a mutant lacking the gp41 cytoplasmic tail to induce fusion in the context of an active (PR+) or inactive (PR-) viral PR. We observed that PR- virions bearing WT Env displayed defects in cell-cell fusion. Impaired fusion did not appear to be due to differences in the levels of virion associated Env, in CD4-dependent binding to target cells, or in the formation of the CD4-induced gp41 six-helix bundle. Interestingly, truncation of the gp41 cytoplasmic tail reversed the fusion defect. These results suggest that interactions between unprocessed Gag and the gp41 cytoplasmic tail suppress fusion. C1 Univ Ryukyus, Dept Immunol, Grad Sch Med, Nishihara, Okinawa 9030215, Japan. Univ Ryukyus, Dept Immunol, Fac Med, Nishihara, Okinawa 9030215, Japan. NIAID, Mol Microbiol Lab, Bethesda, MD 20892 USA. RP Murakami, T (reprint author), Univ Ryukyus, Dept Immunol, Grad Sch Med, Uehara 207, Nishihara, Okinawa 9030215, Japan. EM tmura@med.u-ryukyu.ac-jp NR 60 TC 96 Z9 96 U1 0 U2 3 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD JAN PY 2004 VL 78 IS 2 BP 1026 EP 1031 DI 10.1128/JVI.78.2.1026-1031.2004 PG 6 WC Virology SC Virology GA 762EG UT WOS:000187957700050 PM 14694135 ER PT J AU Cen, S Niu, MJ Saadatmand, J Guo, F Huang, Y Nabel, GJ Kleiman, L AF Cen, S Niu, MJ Saadatmand, J Guo, F Huang, Y Nabel, GJ Kleiman, L TI Incorporation of Pol into human immunodeficiency virus type 1 Gag virus-like particles occurs independently of the upstream Gag domain in Gag-Pol SO JOURNAL OF VIROLOGY LA English DT Article ID MEMBRANE-BINDING DOMAIN; MURINE LEUKEMIA-VIRUS; HIV-1 CAPSID PROTEIN; REVERSE-TRANSCRIPTASE; VIRAL INFECTIVITY; TRANSFER-RNAS; PRIMER TRNA(LYS3); PLASMA-MEMBRANE; MATRIX PROTEIN; WILD-TYPE AB By using particle-associated reverse transcriptase (RT) activity as an assay for Poll incorporation into human immunodeficiency virus type 1 (HIV-1) Gag virus-like particles (VLPs), it has been found that truncated, protease-negative, Gag-Poll missing cis Gag sequences is still incorporated into Gag VLPs, albeit at significantly reduced levels (10 to 20% of the level of wild-type Gag-Poll). In this work, we have directly measured the incorporation of truncated Gag-Pol species into Gag VLPs and have found that truncated Gag-Poll that is missing all sequences upstream of RT is still incorporated into Gag VLPs at levels approximating 70% of that achieved by wild-type Gag-Pol. Neither protease nor integrase regions in Pol are required for its incorporation, implying an interaction between Gag and RT sequences in the Pol protein. While the incorporation of Gag-Poll into Gag VLPs is reduced 12-fold by the replacement of the nucleocapsid within Gag with a leucine zipper motif, this mutation does not affect Pol incorporation. However, the deletion of p6 in Gag reduces Pot incorporation into Gag VLPs four- to fivefold. Pol shows the same ability as Gag-Pol to selectively package tRNA(Lys) into Gag VLPs, and primer tRNA(3)(Lys) is found annealed to the viral genomic RNA. These data suggest that after the initial separation of Gag from Pol during cleavage of Gag-Pol by viral protease, the Poll species still retains the capacity to bind to both Gag and tRNA(3)(Lys), which may be required for Poll and tRNA(3)(Lys) to be retained in the assembling virion until budding is completed. C1 McGill Univ, Lady Davis Inst Med Res, Jewish Gen Hosp, Montreal, PQ H3T 1E2, Canada. McGill Univ, McGill AIDS Ctr, Jewish Gen Hosp, Montreal, PQ H3T 1E2, Canada. McGill Univ, Dept Med, Montreal, PQ H3T 1E2, Canada. McGill Univ, Dept Microbiol, Montreal, PQ H3T 1E2, Canada. McGill Univ, Dept Immunol, Montreal, PQ H3T 1E2, Canada. NIAID, NIH, Bethesda, MD 20892 USA. RP Kleiman, L (reprint author), McGill Univ, Lady Davis Inst Med Res, Jewish Gen Hosp, 3755 Cote Str Catherine Rd, Montreal, PQ H3T 1E2, Canada. EM lawrence.kleiman@mcgill.ca NR 56 TC 26 Z9 26 U1 1 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD JAN PY 2004 VL 78 IS 2 BP 1042 EP 1049 DI 10.1128/JVI.78.2.1042-1049.2004 PG 8 WC Virology SC Virology GA 762EG UT WOS:000187957700053 PM 14694138 ER PT J AU Munson, L Marker, L Dubovi, E Spencer, JA Evermann, JF O'Brien, SJ AF Munson, L Marker, L Dubovi, E Spencer, JA Evermann, JF O'Brien, SJ TI Serosurvey of viral infections in free-ranging Namibian cheetahs (Acinonyx jubatus) SO JOURNAL OF WILDLIFE DISEASES LA English DT Article DE Acinonyx jubatus; canine distemper virus; cheetah; feline coronavirus; Namibia; serosurvey ID CANINE-DISTEMPER VIRUS; CAPTIVE CHEETAHS; GENETIC-CHARACTERIZATION; PHYLOGENETIC ASPECTS; ANTIBODY-RESPONSE; PERITONITIS; WILD; CARNIVORES; PREVALENCE; VACCINE AB Cheetahs (Acinonyx jubatus) in captivity have unusually high morbidity and mortality from infectious diseases, a trait that could be an outcome of population homogeneity or the immunomodulating effects of chronic stress. Free-ranging Namibian cheetahs share ancestry with captive cheetahs, but their susceptibility to infectious diseases has not been investigated. The largest remaining population of free-ranging cheetahs resides on Namibian farmlands, where they share habitat with domestic dogs and cats known to carry viruses that affect cheetah health. To assess the extent to which free-ranging cheetahs are exposed to feline and canine viruses, sera from 81 free-ranging cheetahs sampled between 1992 and 1998 were evaluated for antibodies against canine distemper virus (CDV), feline coronavirus (feline infectious peritonitis virus; FCoV/FIPV), feline herpesvirus 1 (FHV1), feline panleukopenia virus (FPV), feline immunodeficiency virus (FIV), and feline calicivirus (FCV) and for feline leukemia virus (FeLV) antigens. Antibodies against CDV, FCoV/FIPV, FHV1, FPV, and FCV were detected in 24, 29, 12, 48, and 65% of the free-ranging population, respectively, although no evidence of viral disease was present in any animal at the time of sample collection. Neither FIV antibodies nor FeLV antigens were present in any free-ranging cheetah tested. Temporal variation in FCoV/FIPV seroprevalence during the study period suggested that this virus is not endemic in the free-ranging population. Antibodies against CDV were detected in cheetahs of all ages sampled between 1995 and 1998, suggesting the occurrence of an epidemic in Namibia during the time when CDV swept through other parts of sub-Saharan Africa. This evidence in free-ranging Namibian cheetahs of exposure to viruses that cause severe disease in captive cheetahs should direct future guidelines for translocations, including quarantine of seropositive cheetahs and preventing contact between cheetahs and domestic pets. C1 Univ Calif Davis, Sch Vet Med, Dept Pathol Microbiol & Immunol, Davis, CA 95616 USA. Cheetah Conservat Fund, Otjiwarongo, Namibia. Cornell Univ, New York State Diagnost Lab, Ithaca, NY 14853 USA. Med Univ S Africa, ZA-0204 Medunsa, South Africa. Washington State Univ, Washington Anim Dis Diagnost Lab, Pullman, WA 99164 USA. NCI, Lab Genom Divers, Frederick, MD 21702 USA. RP Munson, L (reprint author), Univ Calif Davis, Sch Vet Med, Dept Pathol Microbiol & Immunol, Davis, CA 95616 USA. EM lmunson@ucdavis.edu NR 34 TC 31 Z9 32 U1 1 U2 15 PU WILDLIFE DISEASE ASSN, INC PI LAWRENCE PA 810 EAST 10TH ST, LAWRENCE, KS 66044-8897 USA SN 0090-3558 J9 J WILDLIFE DIS JI J. Wildl. Dis. PD JAN PY 2004 VL 40 IS 1 BP 23 EP 31 PG 9 WC Veterinary Sciences SC Veterinary Sciences GA 811IU UT WOS:000220766400003 PM 15137485 ER PT J AU Brommelhoff, JA Conway, K Merikangas, K Levy, BR AF Brommelhoff, JA Conway, K Merikangas, K Levy, BR TI Higher rates of depression in women: Role of gender bias within the family SO JOURNAL OF WOMENS HEALTH LA English DT Article ID PRIMARY-CARE; CAUSAL ATTRIBUTIONS; DIAGNOSTIC INTERVIEW; AFFECTIVE-DISORDERS; MENTAL-DISORDERS; RECOGNITION; SCHIZOPHRENIA; RELIABILITY; SCHEDULE AB Objective: We sought to examine whether higher rates of depression in women than in men can be explained partially by the artifact hypothesis, which suggests that when both sexes have the same depressive symptoms, women are more likely than men to be diagnosed with depression. We hypothesized that (1) this gender bias in identifying depression exists within families and (2) family members will be more likely to attribute depressive symptoms to internal causes for women and external causes for men. Methods: Our sample consisted of 205 adults, generated from the family members of 46 probands who participated in the Yale Family Study. To determine whether bias exists in the family, we compared self-reports of depressive symptoms with family reports of depressive symptoms for the same individual. Results: As predicted, we found that compared with men, women were more likely to be reported as depressed by a family member when they report themselves as not depressed. We also found that family members were more likely to attribute depressive symptoms of females to internal causes. We did not, however, find any differences by gender in attribution of depression to external causes. Conclusions: Our findings suggest that gender bias within the family may contribute to the higher recorded rates of depression in women. C1 Yale Univ, Sch Med, Dept Epidemiol & Publ Hlth, New Haven, CT 06520 USA. Natl Inst Drug Abuse, Bethesda, MD USA. NIMH, Bethesda, MD 20892 USA. RP Levy, BR (reprint author), Yale Univ, Sch Med, Dept Epidemiol & Publ Hlth, POB 208034, New Haven, CT 06520 USA. EM becca.levy@yale.edu OI Conway, Kevin/0000-0002-7638-339X NR 35 TC 9 Z9 9 U1 1 U2 4 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA SN 1540-9996 J9 J WOMENS HEALTH JI J. Womens Health PD JAN-FEB PY 2004 VL 13 IS 1 BP 69 EP 76 DI 10.1089/154099904322836474 PG 8 WC Public, Environmental & Occupational Health; Medicine, General & Internal; Obstetrics & Gynecology; Women's Studies SC Public, Environmental & Occupational Health; General & Internal Medicine; Obstetrics & Gynecology; Women's Studies GA 780AF UT WOS:000189345700008 PM 15006279 ER PT J AU Leveille, SG Fried, LP McMullen, W Guralnik, JM AF Leveille, SG Fried, LP McMullen, W Guralnik, JM TI Advancing the taxonomy of disability in older adults SO JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL SCIENCES LA English DT Article ID MINI-MENTAL-STATE; SEVERE WALKING DISABILITY; LOWER-EXTREMITY FUNCTION; SUBSEQUENT DISABILITY; PHYSICAL-DISABILITY; WOMENS HEALTH; CARDIOVASCULAR HEALTH; MUSCULOSKELETAL PAIN; MEXICAN-AMERICANS; FUNCTIONAL STATUS AB Background. Refinement of the traditional task-based classification of disability is needed to advance the field of disability research and to inform clinical practice. We propose an enhancement of the taxonomy of disability that incorporates information about symptoms and impairments that directly contribute to disability. In the first step of this new development, we present evidence to support five categories of disability related to pain, balance, weakness, endurance, and other symptoms. Methods. The Women's Health and Aging Study, begun in 1992, was a population-based study of older disabled women living in the Eastern region of Baltimore and surrounds. In-home examinations were conducted every 6 months for 3 years. During the second examination, the 879 participants were asked the main symptom cause of their disability for each activity with which they had difficulty. Symptom causes of disability in activities of daily living were grouped into five nonmutually exclusive categories as stated above. Descriptive analyses were used to compare groups according to sociodemographic, health, disease, and physical performance information. Results. Women with pain-related disability were younger, more obese, and had high prevalence of widespread pain and symptomatic osteoarthritis. Balance-related disability was related to having an age of 85 years or older, being Caucasian, and poor performance in tests of standing balance and gait. Women with weakness-related disability were older, more often African American and sedentary, had high prevalence of stroke and diabetes, and performed poorly in chair-stands and knee strength tests. Endurance-related disability was associated with low self-rated energy, depressive symptoms, smoking history, and lung and cardiovascular diseases. Conclusions. The proposed refinement of the taxonomy of disability describes a set of empirically derived symptom and impairment-related disability groupings that have criterion and face validity. Further research about symptom and impairment-related disability in other populations of older persons is warranted. C1 Hebrew Rehabil Ctr Aged, Boston, MA 02131 USA. Harvard Univ, Sch Med, Boston, MA USA. Johns Hopkins Univ, Sch Med, Baltimore, MD USA. Johns Hopkins Univ, Sch Publ Hlth, Baltimore, MD USA. NIA, Lab Epidemiol Demog & Biometry, Bethesda, MD 20892 USA. RP Leveille, SG (reprint author), Res & Training Inst, 1200 Ctr St, Boston, MA 02131 USA. EM leveille@mail.hrca.harvard.edu FU NIA NIH HHS [N01 AG 12112] NR 44 TC 23 Z9 23 U1 2 U2 2 PU GERONTOLOGICAL SOCIETY AMER PI WASHINGTON PA 1275 K STREET NW SUITE 350, WASHINGTON, DC 20005-4006 USA SN 1079-5006 J9 J GERONTOL A-BIOL JI J. Gerontol. Ser. A-Biol. Sci. Med. Sci. PD JAN PY 2004 VL 59 IS 1 BP 86 EP 93 PG 8 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 763MR UT WOS:000188090200013 PM 14718492 ER PT J AU Hashimoto, S Kawata, T Schnermann, J Koike, T AF Hashimoto, S Kawata, T Schnermann, J Koike, T TI Chloride channel blockade attenuates the effect of angiotensin II on tubuloglomerular feedback in WKY but not spontaneously hypertensive rats SO KIDNEY & BLOOD PRESSURE RESEARCH LA English DT Article DE IAA-94; tubuloglomerular feedback; micropuncture; interstitial perfusion ID SMOOTH-MUSCLE CELLS; MESANGIAL CELLS; PERITUBULAR INFUSIONS; CALCIUM; ADENOSINE; RESPONSES; CONDUCTANCE; ARTERY; RENIN AB Recent studies have shown that calcium-dependent chloride channels may play a crucial role in the modulation of the vascular effects of angiotensin II (ANG II). Thus, alterations in the function of these channels may be responsible for the enhanced renal vasoconstrictor and tubuloglomerular feedback (TGF) response to ANG II in spontaneously hypertensive rats (SHR). We investigated the effect of the calcium-dependent chloride channel blocker IAA-94 on renal hemodynamics and TGF responses. The renal interstitium was perfused with control solution, with ANG II, and with both ANG II and IAA-94. In Wistar Kyoto rats (WKY), perfusion with ANG II significantly increased renal vascular resistance (RVR), but the effect was significantly attenuated by perfusion with ANG II/IAA-94. In SHR, ANG II caused a significant elevation of RVR that was not altered by the simultaneous infusion of IAA-94. Proximal tubular stop flow pressure (P-sf) was monitored during perfusion of peritubular capillaries with control solution, and subsequently with IAA-94, ANG II or both ANG II and IAA-94. TGF response magnitude of WKY rats was significantly augmented with ANG II, and this effect was suppressed by perfusion with ANG II/IAA-94. However, in SHR peritubular perfusion with ANG II/IAA-94 did not suppress the TGF response. We conclude that chloride channels susceptible to IAA-94 may play a significant role in modulating the effects of ANG II on renal hemodynamics, and that this modulation is absent in SHR. C1 NIDDK, NIH, Bethesda, MD 20892 USA. Hokkaido Univ, Sch Med, Dept Internal Med 2, Kita Ku, Sapporo, Hokkaido 060, Japan. RP Hashimoto, S (reprint author), NIDDK, NIH, Bldg 10,Room 4D51,10 Ctr Dr,MSC 1370, Bethesda, MD 20892 USA. EM Seijih@intra.niddk.nih.gov NR 28 TC 6 Z9 7 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1420-4096 J9 KIDNEY BLOOD PRESS R JI Kidney Blood Pressure Res. PY 2004 VL 27 IS 1 BP 35 EP 42 DI 10.1159/000075621 PG 8 WC Physiology; Urology & Nephrology; Peripheral Vascular Disease SC Physiology; Urology & Nephrology; Cardiovascular System & Cardiology GA 767FX UT WOS:000188430500005 PM 14679313 ER PT J AU Grinevich, V Knepper, MA Verbalis, J Reyes, I Aguilera, G AF Grinevich, V Knepper, MA Verbalis, J Reyes, I Aguilera, G TI Acute endotoxemia in rats induces down-regulation of V2 vasopressin receptors and aquaporin-2 content in the kidney medulla SO KIDNEY INTERNATIONAL LA English DT Article DE kidney; lipopolysaccharide; V2 vasopressin receptors; aquaporin-2; urine concentration; interleukin-1 beta; interleukin 6 ID PITUITARY-ADRENAL AXIS; NITRIC-OXIDE SYNTHASE; THICK ASCENDING LIMB; COLLECTING DUCT; INDUCED ANTIDIURESIS; WATER CHANNEL; LIPOPOLYSACCHARIDE LPS; ENDOTHELIN-RECEPTOR; RENAL AQUAPORINS; EXPRESSION AB Background. Endotoxemia can lead to fluid metabolism alterations despite unchanged or elevated plasma vasopressin (VP) levels, suggesting a refractoriness of the kidney to the effect of the peptide. To test this hypothesis, we examined the effect of lipopolysaccharide (LPS) injection on the expression of V2 receptors and aquaporin-2 in the kidney. Methods. Plasma VP and urine osmolality, and binding of [H-3] VP to kidney membranes, Western blot, and immunohistochemical analysis of aquaporin-2, in situ hybridization for V2 VP receptors and cytokines mRNAs were measured in the kidney 3 to 24 hours after LPS injection, 250 mug/100 g, intraperitoneally. Results. LPS injection caused prolonged decreases in urine osmolality (up to 24 hours) without significant changes in plasma levels of sodium or VP. This was associated with marked decreases in V2 VP receptor mRNA and VP receptor number in the kidney, which were evident for up to 12 hours after LPS injection. Aquaporin-2 in kidney inner medulla was also reduced by about 50%. LPS induced interleukin (IL)-1beta in the kidney medulla by 3 hours, reached maximum at 6 hours, and started to decline by 12 hours, while it increased IL-6 mRNA significantly only at 3 hours. Interleukin mRNA expression was absent in kidneys of control rats. In vitro incubation of kidney medulla slices with IL-1beta reduced VP binding. Conclusion. The inflammatory response to acute endotoxemia down regulates V2 VP receptors and aquaporin-2 of the kidney inner medulla resulting in prolonged impairment of the renal capacity to concentrate urine. C1 NICHD, Sect Endocrine Physiol, DEB, NIH, Bethesda, MD 20892 USA. NIHLB, Kidney & Electrolyte Metab Lab, NIH, Bethesda, MD USA. Georgetown Univ, Dept Med, Washington, DC USA. RP Aguilera, G (reprint author), NICHD, Sect Endocrine Physiol, DEB, NIH, Bldg 10,Rm 10N262,10 Ctr Dr,MSC 1862, Bethesda, MD 20892 USA. FU Intramural NIH HHS [Z01 HL001285-21, Z99 HL999999] NR 50 TC 57 Z9 63 U1 0 U2 2 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0085-2538 J9 KIDNEY INT JI Kidney Int. PD JAN PY 2004 VL 65 IS 1 BP 54 EP 62 DI 10.1111/j.1523-1755.2004.00378.x PG 9 WC Urology & Nephrology SC Urology & Nephrology GA 753YP UT WOS:000187276200006 PM 14675036 ER PT J AU Adams, KM Navarro, AM Hutchinson, EK Weed, JL AF Adams, KM Navarro, AM Hutchinson, EK Weed, JL TI A canine socialization and training program at the national institutes of health SO LAB ANIMAL LA English DT Article ID ENRICHMENT; BEHAVIOR AB Well-socialized and obedient dogs are easier to handle and may make better research models. The authors describe the program they have implemented at the NIH, which has benefited both the animals and their caretakers. C1 NIH, Behav & Environm Enrichment Program, Div Vet Resources, Off Res Serv, Poolesville, MD 20837 USA. RP Adams, KM (reprint author), USDA ARS, NAL, Anim Welf Informat Ctr, 10301 Baltimore Ave, Beltsville, MD 20705 USA. EM kadams@nal.usda.gov; weedj@exchange.nih.gov NR 19 TC 6 Z9 7 U1 2 U2 11 PU NATURE PUBLISHING GROUP PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 0093-7355 J9 LAB ANIMAL JI Lab Anim. PD JAN PY 2004 VL 33 IS 1 BP 32 EP 36 DI 10.1038/laban0104-32 PG 5 WC Veterinary Sciences SC Veterinary Sciences GA 761JQ UT WOS:000187867100008 PM 14752529 ER PT J AU Lu, SY Watts, P Chin, FT Hong, J Musachio, JL Briard, E Pike, VW AF Lu, SY Watts, P Chin, FT Hong, J Musachio, JL Briard, E Pike, VW TI Syntheses of C-11- and F-18-labeled carboxylic esters within a hydrodynamically-driven micro-reactor SO LAB ON A CHIP LA English DT Article ID POSITRON-EMISSION-TOMOGRAPHY; HUMAN-BRAIN; TIME; NCA; PET AB Carboxylic esters were successfully labeled with one of two short-lived positron-emitters, carbon-11 or fluorine-18, within a hydrodynamically-driven micro-reactor. The non-radioactive methyl ester 4a was obtained at room temperature; its yield increased with higher substrate concentration and with reduced infusion rate. Radioactive methyl ester 4b was obtained from the reaction of 1 (10 mM) with 2b in 56% decay-corrected radiochemical yield (RCY) at an infusion rate of 10 muL min(-1), and when the infusion rate was reduced to 1 muL min(-1), the RCY increased to 88%. The synthesis of the non-radioactive fluoroethyl ester 5a from 1 and 3a required heating of the micro-reactor on a heating block at 80 degreesC (14-17% RCY), whilst the corresponding radioactive 5b from 1 and 3b was obtained in 10% RCY. The radioactive 'peripheral' benzodiazepine receptor ligand 7b was obtained from the reaction of acid 6 with labeling agent 2b in 45% RCY at an infusion rate of 10 muL min(-1). When the infusion rate was reduced to 1 muL min(-1), the RCY increased to 65%. The results exemplify a new methodology for producing radiotracers for imaging with positron emission tomography that has many potential advantages, including a requirement for small quantities of substrates, enhanced reaction, rapid reaction optimisation and easy product purification. C1 NIMH, PET Radiopharmaceut Sci, Mol Imaging Branch, NIH, Bethesda, MD 20892 USA. Univ Hull, Dept Chem, Kingston Upon Hull HU6 7RX, N Humberside, England. RP Lu, SY (reprint author), NIMH, PET Radiopharmaceut Sci, Mol Imaging Branch, NIH, Room B3,C346,10 Ctr Dr, Bethesda, MD 20892 USA. EM Shuiyu.Lu@mail.nih.gov OI Lu, Shuiyu/0000-0003-0310-4318 FU Intramural NIH HHS [Z01 MH002793-06] NR 26 TC 70 Z9 73 U1 2 U2 16 PU ROYAL SOC CHEMISTRY PI CAMBRIDGE PA THOMAS GRAHAM HOUSE, SCIENCE PARK, MILTON RD, CAMBRIDGE CB4 0WF, CAMBS, ENGLAND SN 1473-0189 J9 LAB CHIP JI Lab Chip PY 2004 VL 4 IS 6 BP 523 EP 525 DI 10.1039/b407938h PG 3 WC Biochemical Research Methods; Chemistry, Multidisciplinary; Nanoscience & Nanotechnology SC Biochemistry & Molecular Biology; Chemistry; Science & Technology - Other Topics GA 874XB UT WOS:000225382800001 PM 15570360 ER PT J AU Dayan, A Goren, A Gannot, I AF Dayan, A Goren, A Gannot, I TI Theoretical and experimental investigation of the thermal effects within body cavities during transendoscopical CO2, laser-based surgery SO LASERS IN SURGERY AND MEDICINE LA English DT Article DE laser-tissue interaction; endoscopy; infrared waveguides and thermal imaging bundle ID CO2-LASER TISSUE ABLATION; SILVER-HALIDE FIBERS; HOLLOW WAVE-GUIDES; BARRETTS-ESOPHAGUS; ORDERED BUNDLES; OPTICAL PHANTOM; THERAPY; DELIVERY; POWER; TRANSMISSION AB Background and Objectives: The recent development of flexible hollow waveguides for MID-IR lasers may be utilized transendoscopically to ablate selectively neoplastic, superficial tissues within body cavities. Study goals are to investigate theoretically and experimentally heat distribution and thermal response of cavity lining, during CO2 laser minimally invasive surgery (MIS), and to thermally optimize the procedure under practical conditions. Study Design/Materials and Methods: Mathematical model was developed to predict temperature distribution along cavity lining. Experimental setup was built, including all the necessary components for a fully feedback-controlled MIS, i.e., laser generator, gas insufflating system, surgical suction, and infrared imaging feedback mechanism, all controlled by central PC-based program. Thermal images of cavity lining were recorded and analyzed throughout varying conditions. Results: Thermal gradients along the cavity lining, during and after the laser irradiation, were obtained mathematically and experimentally. Diverse modes of heat dispersions were observed, as well as the relative contributions of user-controlled parameters to the maximal heat of cavity lining. The software-controlled setup has demonstrated the capacity to instantly manage varying conditions, by which it automatically protects cavity lining from getting overheated. Conclusions: Analytical predictions and experimental measurements were highly correlated. The software-controlled system may serve a powerful tool to control thermal side effects during MIS within body cavities. (C) 2004 Wiley-Liss, Inc. C1 Tel Aviv Univ, Fac Engn, Dept Biomed Engn, Lasers & Opt Med Lab, IL-69978 Tel Aviv, Israel. NIH, Lab Integrat & Med Biophys, Bethesda, MD 20892 USA. RP Gannot, I (reprint author), Tel Aviv Univ, Fac Engn, Dept Biomed Engn, Lasers & Opt Med Lab, IL-69978 Tel Aviv, Israel. EM gannot@eng.tau.ac.il NR 44 TC 5 Z9 5 U1 0 U2 1 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0196-8092 J9 LASER SURG MED JI Lasers Surg. Med. PY 2004 VL 35 IS 1 BP 18 EP 27 DI 10.1002/lsm.20061 PG 10 WC Dermatology; Surgery SC Dermatology; Surgery GA 845FU UT WOS:000223223500003 PM 15278924 ER PT J AU Gannot, I Ron, I Hekmat, F Chernomordik, V Gandjbakhche, A AF Gannot, I Ron, I Hekmat, F Chernomordik, V Gandjbakhche, A TI Functional optical detection based on pH dependent fluorescence lifetime SO LASERS IN SURGERY AND MEDICINE LA English DT Article DE minimal invasive optical detection; time resolved fluorescence; physiological parameters in tissue ID INTRACELLULAR PH; DECAY TIME; RESOLUTION; SENSORS; TUMORS; MEDIA; MODEL AB Background and Objectives: Detection of possible alterations of physiological parameters (e.g., pH and temperature), resulting from malignant transformation of initially healthy tissue, can be a powerful diagnostic tool for earlier cancer detection. Such variations can be observed by comparing these parameters with those of healthy tissue surrounding the abnormality. Time-resolved spectroscopy of specifically targeted fluorescent labeled antibodies can be sensitive to such variations and provide a high resolution functional image of the region of interest. The goal of this study was to establish a forward experimental setup for calibration of the lifetime dependencies of near-IR fluorescent dyes on physiological parameters, and to develop analytical solutions, taking into account the effects of light propagation in turbid media (e.g., tissue), that was able to extract an original lifetime fluorescence signal from time-of-flight intensity distributions, measured in vivo from a deeply embedded live organ for further analysis. Study Design/Materials - and Methods: Tissue-like phantoms with embedded fluorescent dyes and background optical properties simulating those of live tissues were designed and created. Fluorescence decay curves were measured for different fluorophore positions, and pH values. Those measurements were made with a system based on a time-correlated single photon counting (TCSPC) instrument and a tunable femtosecond Ti-Sapphire system built by our group. Results: Decay curves were recorded for fluorophore depths of up to 5 mm and source-detector separation of 7 mm. It was shown that a forward model, based on the random walk theory, adequately described the experimental data. Measured pH dependencies of the fluorescence lifetime were characterized for two different dyes. Conclusions: Good correlation between experimental data and predictions of the theoretical model allows the use of close-form analytical solutions to separate the effects of photon time delays due to multiple scattering in tissues from the original intensity fluorescence time decay curve, determined by the fluorophore itself and its immediate surroundings. It is the latter dependence that can be diagnostically important. Experimentally obtained scaling between lifetime and a parameter of interest can be used in vivo to obtain a map of physiological parameter changes which can serve as a base for an in vivo specific diagnostic system. C1 Tel Aviv Univ, Fac Engn, Dept Biomed Engn, Lasers & Opt Med Lab, IL-69978 Tel Aviv, Israel. NIH, Lab Integrat & Med Biophys, Bethesda, MD 20892 USA. RP Gannot, I (reprint author), Tel Aviv Univ, Fac Engn, Dept Biomed Engn, Lasers & Opt Med Lab, IL-69978 Tel Aviv, Israel. EM gannoti@mail.nih.gov NR 22 TC 30 Z9 30 U1 2 U2 11 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0196-8092 J9 LASER SURG MED JI Lasers Surg. Med. PY 2004 VL 35 IS 5 BP 342 EP 348 DI 10.1002/lsm.20101 PG 7 WC Dermatology; Surgery SC Dermatology; Surgery GA 888KK UT WOS:000226372600003 PM 15611954 ER PT J AU Chudasama, Y Dalley, JW Nathwani, F Bouger, P Robbins, TW AF Chudasama, Y Dalley, JW Nathwani, F Bouger, P Robbins, TW TI Cholinergic modulation of visual attention and working memory: Dissociable effects of basal forebrain 192-IgG-saporin lesions and intraprefrontal infusions of scopolamine SO LEARNING & MEMORY LA English DT Article ID REACTION-TIME-TASK; DORSAL ANTERIOR CINGULATE; SHORT-TERM-MEMORY; NUCLEUS BASALIS; RESPONSE SELECTION; PREFRONTAL CORTEX; SENILE DEMENTIA; DIFFERENTIAL INVOLVEMENT; CORTICAL ACETYLCHOLINE; SUBSTANTIA INNOMINATA AB Two experiments examined the effects of reductions in cortical cholinergic function on performance of a novel task that allowed for the simultaneous assessment of attention to a visual stimulus and memory for that stimulus over a variable delay within the same test session. In the first experiment, infusions of the muscarinic receptor antagonist scopolamine into the medial prefrontal cortex (mPFC) produced many omissions but did not impair rats' ability to correctly detect a brief visual stimulus. However, these animals were highly impaired in remembering the location of that stimulus following a delay period, although in a delay-independent manner. In the second experiment, another group of animals with selective 192 IgG-saporin lesions of the nucleus basalis magnocellularis (nBM) were. not impaired under conditions of low-attentional demand. However, when the stimulus duration was reduced, a significant memory impairment was observed, but similar to the results of the first experiment, the nBM-lesioned animals were not impaired in attentional accuracy, although aspects of attention were compromised (e.g., omissions). These findings demonstrate that (1) cortical cholinergic depletion produces dissociable deficits in attention and memory, depending on the task demands, (2) delay-independent mnemonic deficits produced by scopolamine are probably due to impairments other than simple inattention, and (3) working memory deficits are not simply dependent on attentional difficulties per se. Together, these findings implicate the nBM cortical cholinergic system in both attentional and mnemonic processing. C1 Univ Cambridge, Dept Expt Psychol, Cambridge CB2 3EB, England. RP Chudasama, Y (reprint author), NIMH, Neuropsychol Lab, Bethesda, MD 20892 USA. EM Yogita@ln.nimh.nih.gov NR 69 TC 81 Z9 83 U1 0 U2 3 PU COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT PI WOODBURY PA 500 SUNNYSIDE BLVD, WOODBURY, NY 11797-2924 USA SN 1072-0502 J9 LEARN MEMORY JI Learn. Mem. PD JAN-FEB PY 2004 VL 11 IS 1 BP 78 EP 86 DI 10.1101/lm.70904 PG 9 WC Neurosciences; Psychology, Experimental SC Neurosciences & Neurology; Psychology GA 769JK UT WOS:000188646800010 PM 14747520 ER PT B AU Alter, HJ AF Alter, HJ BE Blum, HE Maier, KP Rodes, J Sauerbruch, T TI State of the Art II: Emerging hepatitis viruses SO LIVER DISEASES: ADVANCES IN TREATMENT AND PREVENTION: IN HONOUR OF HANS POPPER'S 100TH BIRTHDAY SE Falk Symposium LA English DT Proceedings Paper CT 12th International Falk Liver Week CY OCT 15-21, 2003 CL Freiburg, GERMANY SP Falk Fdn ID BLOOD MONONUCLEAR-CELLS; CHRONIC LIVER-DISEASE; TRANSFUSION-ASSOCIATED HEPATITIS; IN-SITU HYBRIDIZATION; A-E HEPATITIS; TT VIRUS; UNKNOWN ETIOLOGY; C VIRUS; POSTTRANSFUSION HEPATITIS; GBV-C/HGV C1 NIH, Warren Grant Magnuson Clin Ctr, Dept Transfus Med, Bethesda, MD 20892 USA. RP Alter, HJ (reprint author), NIH, Warren Grant Magnuson Clin Ctr, Dept Transfus Med, Bldg 10,Room 1C-711,10 Ctr Dr, Bethesda, MD 20892 USA. NR 59 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI DORDRECHT PA PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS BN 0-7923-8794-5 J9 FALK SYMP PY 2004 VL 137 BP 96 EP 107 PG 12 WC Gastroenterology & Hepatology; Medicine, General & Internal SC Gastroenterology & Hepatology; General & Internal Medicine GA BBO74 UT WOS:000226751700011 ER PT B AU Hoofnagle, JH AF Hoofnagle, JH BE Blum, HE Maier, KP Rodes, J Sauerbruch, T TI Interferon for hepatitis C: yesterday, today and tomorrow SO LIVER DISEASES: ADVANCES IN TREATMENT AND PREVENTION: IN HONOUR OF HANS POPPER'S 100TH BIRTHDAY SE Falk Symposium LA English DT Proceedings Paper CT 12th International Falk Liver Week CY OCT 15-21, 2003 CL Freiburg, GERMANY SP Falk Fdn C1 NIDDK, NIH, Bethesda, MD 20892 USA. RP Hoofnagle, JH (reprint author), NIDDK, NIH, Bldg 21,Room 9A23, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI DORDRECHT PA PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS BN 0-7923-8794-5 J9 FALK SYMP PY 2004 VL 137 BP 233 EP 235 PG 3 WC Gastroenterology & Hepatology; Medicine, General & Internal SC Gastroenterology & Hepatology; General & Internal Medicine GA BBO74 UT WOS:000226751700024 ER PT J AU Dorner, T Lipsky, P AF Dorner, T Lipsky, P TI Correlation of circulating CD27(high) plasma cells and disease activity in systemic lupus erythematosus SO LUPUS LA English DT Article DE autoimmunity; B cells; plasma cells; SLE ID MEMORY B-CELLS; CONNECTIVE-TISSUE DISEASES; PRIMARY SJOGRENS-SYNDROME; BLOOD MONONUCLEAR-CELLS; CONSENSUS-STUDY-GROUP; PERIPHERAL-BLOOD; CD27/CD70 INTERACTION; SOLUBLE CD27; AUTOANTIBODY PRODUCTION; LYMPHOCYTE HOMEOSTASIS AB CD27 is a useful marker in assessing the number of circulating B cells and B cell subsets because it permits one step identification of the major B cell compartments, CD27(-) naive and CD27(+) memory B cells as well as CD27(high) plasma cells. Abnormalities in the distribution of CD27(+) B cell subsets are useful in assessing disease activity in patients with systemic lupus erythematosus (SLE). In particular, the frequency of CD27(high) plasma cells significantly correlates with lupus activity in both children and adults with SLE. Conventional immuno suppressive therapies affect the number of CD27(-) naive B cells and CD27(high) plasma cells, but do not target CD27(+) memory B cells. These results suggest that disease flares may relate to the retention of CD27(+) memory B cells after conventional immuno suppressive therapy and that new therapies that target these cells specifically may offer new opportunities to induce remission in SLE. C1 Univ Med Berlin, Charite, Dept Med, D-10098 Berlin, Germany. NIAMS, NIH, Bethesda, MD USA. RP Dorner, T (reprint author), Univ Med Berlin, Charite, Dept Med, Schumannstr 20-21, D-10098 Berlin, Germany. EM thomas.doemer@web.de NR 65 TC 33 Z9 33 U1 0 U2 0 PU ARNOLD, HODDER HEADLINE PLC PI LONDON PA 338 EUSTON ROAD, LONDON NW1 3BH, ENGLAND SN 0961-2033 J9 LUPUS JI Lupus PY 2004 VL 13 IS 5 BP 283 EP 289 DI 10.1191/0961203304lu1014oa PG 7 WC Rheumatology SC Rheumatology GA 830VS UT WOS:000222152800001 PM 15230280 ER PT J AU Tackey, E Lipsky, PE Illei, GG AF Tackey, E Lipsky, PE Illei, GG TI Rationale for interleukin-6 blockade in systemic lupus erythematosus SO LUPUS LA English DT Article DE autoinummity; biologic therapy; cytokines; experimental treatment ID EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS; ANTI-DNA AUTOANTIBODIES; B-CELL DIFFERENTIATION; AUTOREACTIVE T-CELL; MESANGIAL CELLS; TNF-ALPHA; URINARY INTERLEUKIN-6; IL-6-DEFICIENT MICE; CYTOKINE PRODUCTION; ENDOTHELIAL-CELLS AB Interleukin-6 (IL-6) is a pleiotropic cytokine with a wide range of biological activities that plays an important role in immune regulation and inflammation. Among other actions, it induces terminal differentiation of B lymphocytes into antibody-forming cells and the differentiation of T cells into effector cells. IL-6 also has multiple potent proinflammatory effects. An association between IL-6 and lupus was demonstrated in murine models of SLE and blocking IL-6 improved lupus in all models tested. Data from several studies suggest that IL-6 plays a critical role in the B cell hyperactivity and immunopathology of human SLE, and may have a direct role in mediating tissue damage. Based on these data, we propose that blocking the effect of IL-6 in humans may improve lupus by interacting with the autoinflammatory process both systemically and locally. C1 Natl Inst Arthritis & Musculoskeletal & Skin Dis, Dept Hlth & Human Serv, NIH, Bethesda, MD 20892 USA. RP Illei, GG (reprint author), Natl Inst Arthritis & Musculoskeletal & Skin Dis, Dept Hlth & Human Serv, NIH, 10 Ctr Dr,9S205, Bethesda, MD 20892 USA. EM illeig@mail.nih.gov FU Intramural NIH HHS [Z99 DE999999] NR 46 TC 121 Z9 134 U1 1 U2 3 PU ARNOLD, HODDER HEADLINE PLC PI LONDON PA 338 EUSTON ROAD, LONDON NW1 3BH, ENGLAND SN 0961-2033 J9 LUPUS JI Lupus PY 2004 VL 13 IS 5 BP 339 EP 343 DI 10.1191/0961203304lu1023oa PG 5 WC Rheumatology SC Rheumatology GA 830VS UT WOS:000222152800010 PM 15230289 ER PT J AU Parks, CG Hudson, LL Cooper, GS Dooley, MA Treadwell, EL St Clair, EW Gilkeson, GS Pandey, JP AF Parks, CG Hudson, LL Cooper, GS Dooley, MA Treadwell, EL St Clair, EW Gilkeson, GS Pandey, JP TI CTLA-4 gene polymorphisms and systemic lupus erythematosus in a population-based study of whites and African-Americans in the southeastern United States SO LUPUS LA English DT Article DE CTLA-4; effect modification; genetics; polymorphism; population-based; systemic lupus erythematosus ID PROMOTER REGION; SIGNIFICANT ASSOCIATION; AUTOIMMUNE-DISEASE; SOLUBLE FORM; T-CELLS; EXPRESSION; EXON-1; SUSCEPTIBILITY; NEPHRITIS; BLOCKADE AB Cytotoxic lymphocyte antigen-4 (CTLA-4) plays an important role in regulating T cell activation, and may help to limit T cell response under conditions of inflammation. Genetic variability in CTLA-4 has been implicated in the development of several autoimmune diseases. Some studies have described associations between CTLA-4 polymorphisms and systemic lupus erythematosus (SLE), but findings have been inconsistent. We examined polymorphisms in the CTLA-4 gene promoter region (-1722T/C, -1661A/G, -318C/T) and exon 1 (+49G/A) with respect to SLE in a population-based case - control study in the southeastern US. Genotypes from 230 recently diagnosed cases and 276 controls were examined separately for African-Americans and whites. We observed no overall associations between SLE and the four CTLA-4 polymorphisms examined. Subgroup analyses revealed effect modification by age for the presence of the -1661G allele, yielding a significant positive association with SLE in younger (less than or equal to 35 years) African-Americans ( OR = 3.3). CTLA-4 genotypes also interacted with HLA-DR2 and GM allotype to contribute to risk of SLE. These findings suggest allelic variation in this region of CTLA-4 is not a major independent risk factor for SLE, but may contribute to risk of disease in younger African-Americans or in the presence of certain immunogenetic markers. C1 NIEHS, Epidemiol Branch, NIH, DHHS, Res Triangle Pk, NC 27709 USA. Med Univ S Carolina, Charleston, SC 29425 USA. Univ N Carolina, Sch Med, Chapel Hill, NC USA. E Carolina Univ, Sch Med, Greenville, NC USA. Duke Univ, Med Ctr, Durham, NC USA. RP Parks, CG (reprint author), NIEHS, Epidemiol Branch, NIH, DHHS, A3-05,POB 12233, Res Triangle Pk, NC 27709 USA. EM parks@niehs.nih.gov OI Parks, Christine/0000-0002-5734-3456 NR 42 TC 32 Z9 36 U1 0 U2 4 PU ARNOLD, HODDER HEADLINE PLC PI LONDON PA 338 EUSTON ROAD, LONDON NW1 3BH, ENGLAND SN 0961-2033 J9 LUPUS JI Lupus PY 2004 VL 13 IS 10 BP 784 EP 791 DI 10.1191/0961203304lu1085oa PG 8 WC Rheumatology SC Rheumatology GA 867ID UT WOS:000224835100005 PM 15540511 ER PT J AU Silveira, JR Caughey, B Baron, GS AF Silveira, JR Caughey, B Baron, GS TI Prion protein and the molecular features of transmissible spongiform encephalopathy agents SO MAD COW DISEASE AND RELATED SPONGIFORM ENCEPHALOPATHIES SE CURRENT TOPICS IN MICROBIOLOGY AND IMMUNOLOGY LA English DT Review ID CHRONIC WASTING DISEASE; SCRAPIE-ASSOCIATED FIBRILS; CREUTZFELDT-JAKOB-DISEASE; MOUSE NEUROBLASTOMA-CELLS; IN-VITRO CONVERSION; INTERMOLECULAR DISULFIDE BONDS; STRAUSSLER-SCHEINKER DISEASE; N-TERMINAL TRUNCATION; CLATHRIN-COATED PITS; ROCKY-MOUNTAIN ELK AB Transmissible spongiform encephalopathy (TSE) diseases, or prion diseases, are neuro degenerative diseases found in a number of mammals, including man. Although. they are generally rare, TSEs are always fatal, and as of yet there are no practical therapeutic avenues to slow the course of disease. The epidemic of bovine spongiform encephalopathy (BSE) in the UK greatly increased the awareness of TSE diseases. Although it appears that BSE has not spread to North America, chronic wasting disease (CWD), a TSE found in cervids, is causing significant concern. Despite decades of investigation, the exact nature of the infectious agent of the TSEs is still controversial. Although many questions remain, substantial efforts have been made to understand the molecular features of TSE agents, with the hope of enhancing diagnosis and treatment of disease, as well as understanding the fundamental nature of the infectious agent itself. This review summarizes the current understanding of these molecular features, focusing on the role of the prion protein (PrPC) and its relationship to the disease-associated isoform (PrPSc). C1 NIAID, Persistent Viral Dis Lab, Rocky Mt Labs, NIH, Hamilton, MT 59840 USA. RP Silveira, JR (reprint author), NIAID, Persistent Viral Dis Lab, Rocky Mt Labs, NIH, 903 S 4th St, Hamilton, MT 59840 USA. EM gbaron@niaid.nih.gov NR 234 TC 19 Z9 20 U1 1 U2 3 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY SN 0070-217X J9 CURR TOP MICROBIOL JI Curr.Top.Microbiol.Immunol. PY 2004 VL 284 BP 1 EP 50 PG 50 WC Immunology; Microbiology SC Immunology; Microbiology GA BAE67 UT WOS:000221885700001 PM 15148986 ER PT J AU de Zwart, JA Ledden, PJ van Gelderen, P Bodurka, J Chu, RX Duyn, JH AF de Zwart, JA Ledden, PJ van Gelderen, P Bodurka, J Chu, RX Duyn, JH TI Signal-to-noise ratio and parallel Imaging performance of a 16-channel receive-only brain coil array at 3.0 Tesla SO MAGNETIC RESONANCE IN MEDICINE LA English DT Article ID RADIOFREQUENCY COIL; SENSE; MRI AB The performance of a 16-channel receive-only RF coil for brain imaging at 3.0 Tesla was investigated using a custom-built 16-channel receiver. Both the image signal-to-noise ratio (SNR) and the noise amplification (g-factor) in sensitivity-encoding (SENSE) parallel imaging applications were quantitatively evaluated. Furthermore, the performance was compared with that of hypothetical coils with one, two, four, and eight elements (n) by combining channels in software during image reconstruction. As expected, both the g-factor and SNR improved substantially with n. Compared to an equivalent (simulated) single-element coil, the 16-channel coil showed a 1.87-fold average increase in brain SNR. This was mainly due to an increase in SNR in the peripheral brain (an up to threefold SNR increase), whereas the SNR increase in the center of the brain was 4%. The incremental SNR gains became relatively small at large n, with a 9% gain observed when n was increased from 8 to 16. Compared to the (larger) product birdcage head coil, SNR increased by close to a factor of 2 in the center, and by up to a factor of 6 in the periphery of the brain. For low SENSE acceleration (rate-2), g-factors leveled off for n > 4, and improved only slightly (1.4% averaged over brain) going from n = 8 to n = 16. Improvements in g for n > 8 were larger for higher acceleration rates, with the improvement for rate-3 averaging 12.0%. Published 2003 Wiley-Liss, Inc. C1 NINDS, AMRI Sect, LFMI, NIH, Bethesda, MD 20892 USA. Nova Med Inc, Wakefield, MA USA. NIMH, Funct MRI Facil, NIH, Bethesda, MD 20892 USA. RP de Zwart, JA (reprint author), NINDS, AMRI Sect, LFMI, NIH, 10 Ctr Dr,Bldg 10,Rm B1D-118, Bethesda, MD 20892 USA. EM Jacco.deZwart@nih.gov RI Duyn, Jozef/F-2483-2010 NR 12 TC 116 Z9 117 U1 0 U2 8 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0740-3194 J9 MAGNET RESON MED JI Magn. Reson. Med. PD JAN PY 2004 VL 51 IS 1 BP 22 EP 26 DI 10.1002/mrm.10678 PG 5 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 762ZE UT WOS:000188041500005 PM 14705041 ER PT J AU Larson, AC White, RD Laub, G McVeigh, ER Li, DB Simonetti, OP AF Larson, AC White, RD Laub, G McVeigh, ER Li, DB Simonetti, OP TI Self-gated cardiac cine MRI SO MAGNETIC RESONANCE IN MEDICINE LA English DT Article DE CMRI; gating; triggering; cine; cardiac ID UNDERSAMPLED PROJECTION RECONSTRUCTION; NUCLEAR MAGNETIC-RESONANCE; ANGIOGRAPHY; INTERFERENCE; SUPPRESSION; RESOLUTION; ARTIFACTS; CONTRAST; IMAGES; PHASE AB The need for ECG gating presents many difficulties in cardiac magnetic resonance imaging (CMRI). Real-time imaging techniques eliminate the need for ECG gating in cine CMRI, but they cannot off er the spatial and temporal resolution provided by segmented acquisition techniques. Previous MR signal-based techniques have demonstrated an ability to provide cardiac gating information; however, these techniques result in decreased imaging efficiency. The purpose of this work was to develop a new "self-gated" (SG) acquisition technique that eliminates these efficiency deficits by extracting the motion synchronization signal directly from the same MR signals used for image reconstruction. Three separate strategies are proposed for deriving the SG signal from data acquired using radial k-space sampling: echo peak magnitude, kymogram, and 2D correlation. The SG techniques were performed on seven normal volunteers. A comparison of the results showed that they provided cine image series with no significant differences in image quality compared to that obtained with conventional ECG gating techniques. SG techniques represent an important practical advance in clinical MRI because they enable the acquisition of high temporal and spatial resolution cardiac cine images without the need for ECG gating and with no loss in imaging efficiency. (C) 2003 Wiley-Liss, Inc. C1 NHLBI, Cardiac Energet Lab, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. Northwestern Univ, Dept Biomed Engn, Chicago, IL 60611 USA. Northwestern Univ, Dept Radiol, Chicago, IL 60611 USA. Cleveland Clin Fdn, Div Radiol, Sect Cardiovasc Imaging, Cleveland, OH 44195 USA. Siemens Med Solut, Malvern, PA USA. RP Larson, AC (reprint author), 10 Ctr Dr,Bldg 10, Rm,B1D416 MSC 1061, Bethesda, MD 20892 USA. EM larsona@nhibi.nih.gov RI Li, Debiao/B-7622-2009; Simonetti, Orlando/E-4098-2011; OI White, Richard D./0000-0002-1133-7819 FU Intramural NIH HHS [Z01 HL004608-08] NR 34 TC 185 Z9 193 U1 2 U2 7 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0740-3194 J9 MAGNET RESON MED JI Magn. Reson. Med. PD JAN PY 2004 VL 51 IS 1 BP 93 EP 102 DI 10.1002/mrm.10664 PG 10 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 762ZE UT WOS:000188041500013 PM 14705049 ER PT J AU Rohde, GK Barnett, AS Basser, PJ Marenco, S Pierpaoli, C AF Rohde, GK Barnett, AS Basser, PJ Marenco, S Pierpaoli, C TI Comprehensive approach for correction of motion and distortion in diffusion-weighted MRI SO MAGNETIC RESONANCE IN MEDICINE LA English DT Article DE image registration; mutual information; distortion correction; motion correction; eddy currents ID ECHO-PLANAR IMAGES; TENSOR MRI; HUMAN BRAIN; REGISTRATION; ARTIFACTS; TISSUES AB Patient motion and image distortion induced by eddy currents cause artifacts in maps of diffusion parameters computed from diffusion-weighted (DW) images. A novel and comprehensive approach to correct for spatial misalignment of DW imaging (DWI) volumes acquired with different strengths and orientations of the diffusion sensitizing gradients is presented. This approach uses a mutual information-based registration technique and a spatial transformation model containing parameters that correct for eddy current-induced image distortion and rigid body motion in three dimensions. All parameters are optimized simultaneously for an accurate and fast solution to the registration problem. The images can also be registered to a normalized template with a single interpolation step without additional computational cost. Following registration, the signal amplitude of each DWI volume is corrected to account for size variations of the object produced by the distortion correction, and the b-matrices are properly recalculated to account for any rotation applied during registration. Both qualitative and quantitative results show that this approach produces a significant improvement of diffusion tensor imaging (DTI) data acquired in the human brain. Published 2003 Wiley-Liss, Inc. C1 NICHD, NIH, Bethesda, MD 20892 USA. NIMH, NIH, Bethesda, MD 20892 USA. Univ Maryland, Appl Math & Sci Computat Program, College Pk, MD 20742 USA. RP NICHD, NIH, Bldg 13,Rm 3W16,13 South Dr, Bethesda, MD 20892 USA. EM rohdeg@helix.nih.gov RI Marenco, Stefano/A-2409-2008; Pierpaoli, Carlo/E-1672-2011; Basser, Peter/H-5477-2011 OI Marenco, Stefano/0000-0002-2488-2365; NR 27 TC 254 Z9 259 U1 4 U2 20 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0740-3194 EI 1522-2594 J9 MAGN RESON MED JI Magn. Reson. Med. PD JAN PY 2004 VL 51 IS 1 BP 103 EP 114 DI 10.1002/mrm.10677 PG 12 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 762ZE UT WOS:000188041500014 PM 14705050 ER PT J AU Bodurka, J Ledden, PJ van Gelderen, P Chu, RX de Zwart, JA Morris, D Duyn, JH AF Bodurka, J Ledden, PJ van Gelderen, P Chu, RX de Zwart, JA Morris, D Duyn, JH TI Scalable multichannel MRI data acquisition system SO MAGNETIC RESONANCE IN MEDICINE LA English DT Article DE MRI receiver; array coil; parallel imaging; SENSE; fMRI ID PHASED-ARRAY; COIL ARRAYS; SENSE; NOISE; EPI AB A scalable multichannel digital MRI receiver system was designed to achieve high bandwidth echo-planar imaging (EPI) acquisitions for applications such as BOLD-fMRI. The modular system design allows for easy extension to an arbitrary number of channels. A 16-channel receiver was developed and integrated with a General Electric (GE) Signa 3T VH/3 clinical scanner. Receiver performance was evaluated on phantoms and human volunteers using a custom-built 16-element receive-only brain surface coil array. At an output bandwidth of 1 MHz, a 100% acquisition duty cycle was achieved. Overall system noise figure and dynamic range were better than 0.85 dB and 84 dB, respectively. During repetitive EPI scanning on phantoms, the relative temporal standard deviation of the image intensity time-course was below 0.2%. As compared to the product birdcage head coil, 16-channel reception with the custom array yielded a nearly 6-fold SNR gain in the cerebral cortex and a 1.8-fold SNR gain in the center of the brain. The excellent system stability combined with the increased sensitivity and SENSE capabilities of 16-channel coils are expected to significantly benefit and enhance fMRI applications. Published 2003 Wiley-Liss, lnc.(dagger). C1 NINDS, Adv MRI Sect, LFMI, NIH, Bethesda, MD 20892 USA. NIMH, Funct MRI Facil, NIH, Bethesda, MD 20892 USA. Nova Med Inc, Wakefield, MA USA. NINDS, NMR Facil, NIH, Bethesda, MD 20892 USA. RP Duyn, JH (reprint author), NINDS, Adv MRI Sect, LFMI, NIH, Bldg 10,Rm B1d-724-MSC 1065,10 Ctr Dr, Bethesda, MD 20892 USA. EM jhd@helix.nih.gov RI Duyn, Jozef/F-2483-2010 NR 16 TC 57 Z9 58 U1 1 U2 7 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0740-3194 J9 MAGNET RESON MED JI Magn. Reson. Med. PD JAN PY 2004 VL 51 IS 1 BP 165 EP 171 DI 10.1002/mrm.10693 PG 7 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 762ZE UT WOS:000188041500021 PM 14705057 ER PT J AU Kellman, P Derbyshire, JA Agyeman, KO McVeigh, ER Arai, AE AF Kellman, P Derbyshire, JA Agyeman, KO McVeigh, ER Arai, AE TI Extended coverage first-pass perfusion imaging using slice-interleaved TSENSE SO MAGNETIC RESONANCE IN MEDICINE LA English DT Article DE MRI; heart; perfusion; contrast agent; SENSE; TSENSE ID MYOCARDIAL-PERFUSION; MRI; UNFOLD AB Parallel imaging applied to first-pass, contrast-enhanced cardiac MR can yield greater spatial coverage for a fixed temporal resolution. The method combines rate R = 2 acceleration using TSENSE with shot-to-shot interleaving of two slices. The rootR SNR loss is largely compensated for by a longer effective repetition time (TR) and increased flip angle associated with slice interleaving. In this manner, increased spatial coverage is achieved while comparable or better image quality is maintained. Single-heartbeat temporal resolution was accomplished with spatial coverage of eight slices at heart rates up to 71 bpm, six slices up to 95 bpm, and four slices up to 143 bpm. Experiments in normal subjects (N = 6) were performed to assess signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR) values. Published 2003 Wiley-Liss, Inc.(dagger). C1 NHLBI, Cardiac Energet Lab, DHHS, NIH, Bethesda, MD 20892 USA. RP Kellman, P (reprint author), NHLBI, Cardiac Energet Lab, DHHS, NIH, 10 Ctr Dr,MSC-1061,Bldg 10,Rm B1D416, Bethesda, MD 20892 USA. EM kellman@nih.gov FU Intramural NIH HHS [Z01 HL004608-08] NR 11 TC 55 Z9 57 U1 0 U2 2 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0740-3194 J9 MAGNET RESON MED JI Magn. Reson. Med. PD JAN PY 2004 VL 51 IS 1 BP 200 EP 204 DI 10.1002/mrm.10663 PG 5 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 762ZE UT WOS:000188041500026 PM 14705062 ER PT B AU Ginis, I Hallenbeck, J AF Ginis, I Hallenbeck, J BE Buchan, AM Ito, U Colbourne, F Kuroiwa, T Klatzo, I TI Tumor necrosis factor-alpha (TNF-alpha) and ceramide induce tolerance to ischemic and hypoxic insults to brain and brain cells associated with changes in NF kappa B function SO MATURATION PHENOMENON IN CEREBRAL ISCHEMIA V LA English DT Proceedings Paper CT 5th International Workshop on Maturation Phenomenon in Cerebral Ischemia CY APR 28-MAY 01, 2002 CL Banff, CANADA DE astrocytes; tolerance; NF kappa B; signaling; cell culture ID SPONTANEOUSLY HYPERTENSIVE-RATS; TRANSCRIPTIONAL ACTIVITY; ACTIVATION; P65; PHOSPHORYLATION; COACTIVATOR; CBP/P300 AB In-vivo and in-vitro studies by our group have shown that TNF-alpha and ceramide are involved in the regulation of tolerance to hypoxia and ischemia of brain. Preconditioning with these signaling molecules alters the function of NFkappaB. Although the nuclear translocation and DNA binding of the NFkappaB heterodimer, p50 and p65/RelA, are unaffected, p65 binding to the coactivator, p300/CBP, becomes disrupted. C1 NINDS, Stroke Branch, NIH, Bethesda, MD 20892 USA. RP Hallenbeck, J (reprint author), NINDS, Stroke Branch, NIH, Bldg 36,Room 4A03,MSC 4128,Convent Dr, Bethesda, MD 20892 USA. NR 20 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY BN 3-540-40874-6 PY 2004 BP 105 EP 111 PG 7 WC Cell Biology; Neurosciences SC Cell Biology; Neurosciences & Neurology GA BY63Q UT WOS:000189426700010 ER PT B AU Spatz, M Chen, Y Golech, S Strasser, A Bembry, J Lenz, E Mechoulam, R McCarron, RM AF Spatz, M Chen, Y Golech, S Strasser, A Bembry, J Lenz, E Mechoulam, R McCarron, RM BE Buchan, AM Ito, U Colbourne, F Kuroiwa, T Klatzo, I TI A role for cerebrovascular endothelium in ischemia and reperfusion SO MATURATION PHENOMENON IN CEREBRAL ISCHEMIA V LA English DT Proceedings Paper CT 5th International Workshop on Maturation Phenomenon in Cerebral Ischemia CY APR 28-MAY 01, 2002 CL Banff, CANADA DE 2-Arachidonoyl glycerol; brain endothelium; cerebral blood flow; endothelin-1; hydrogen peroxide (H2O2); ischemia; reperfusion ID CANNABINOID CB1 RECEPTOR; NITRIC-OXIDE; ACTIN CYTOSKELETON; CEREBRAL-ISCHEMIA; HUMAN BRAIN; DEPENDENT HYPERPOLARIZATION; 2-ARACHIDONOYL GLYCEROL; CA2+ MOBILIZATION; OXYGEN RADICALS; CELLS C1 NINDS, NIH, Stroke Branch, Bethesda, MD 20892 USA. RP Spatz, M (reprint author), NINDS, NIH, Stroke Branch, 36 Convent Dr,MSC 4128, Bethesda, MD 20892 USA. NR 50 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY BN 3-540-40874-6 PY 2004 BP 121 EP 132 PG 12 WC Cell Biology; Neurosciences SC Cell Biology; Neurosciences & Neurology GA BY63Q UT WOS:000189426700012 ER PT J AU Nemade, RV Bierie, B Nozawa, M Bry, C Smith, GH Vasioukhin, V Fuchs, E Hennighausen, L AF Nemade, RV Bierie, B Nozawa, M Bry, C Smith, GH Vasioukhin, V Fuchs, E Hennighausen, L TI Biogenesis and function of mouse mammary epithelium depends on the presence of functional alpha-catenin SO MECHANISMS OF DEVELOPMENT LA English DT Article DE mammary development; alpha-catenin; WAP-Cre; MMTV-Cre; conditional deletion ID E-CADHERIN; GLAND DEVELOPMENT; TRANSGENIC MICE; GAMMA-CATENIN; CELLS; GENE; METASTASIS; EXPRESSION; DIFFERENTIATION; MORPHOGENESIS AB Alpha-catenin is a structural molecule and essential to the function of epithelial adherents junctions. Its role in the morphogenesis of mammary epithelium was explored using experimental mouse genetics. Since loss of alpha-catenin in mice leads to embryonic lethality, the a.-catenin gene was flanked by loxP sites and inactivated in mammary epithelium using the WAP-Cre and MMTV-Cre transgenes. Loss of a-catenin arrested alveolar epithelial expansion. These cells lacked proper polarity and markers of functional differentiation, which resulted in impaired milk protein gene expression. Without alpha-catenin, increased epithelial cell death was observed at parturition and the tissue resembled an involuted gland that is normally observed after weaning. Lastly, no tumors were detected in mammary tissue lacking a-catenin. (C) 2003 Elsevier Ireland Ltd. All rights reserved. C1 NIDDKD, Lab Genet & Physiol, NIH, Bethesda, MD 20892 USA. NCI, Basic Res Lab, NIH, Bethesda, MD 20892 USA. Fred Hutchinson Canc Res Ctr, Human Biol Div, Seattle, WA 98109 USA. Rockefeller Univ, New York, NY 10021 USA. RP Hennighausen, L (reprint author), NIDDKD, Lab Genet & Physiol, NIH, Bldg 8,Room 101,8 Ctr Dr, Bethesda, MD 20892 USA. EM mammary@nih.gov FU NIAMS NIH HHS [R01 AR027883-29, R01 AR027883, R37 AR027883] NR 20 TC 28 Z9 28 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0925-4773 J9 MECH DEVELOP JI Mech. Dev. PD JAN PY 2004 VL 121 IS 1 BP 91 EP 99 DI 10.1016/j.mod.2003.09.007 PG 9 WC Developmental Biology SC Developmental Biology GA 767DX UT WOS:000188425900009 PM 14706703 ER PT B AU Kitani, A AF Kitani, A BE Duchmann, R Blumberg, RS Neurath, MF Scholmerich, J Strober, W Zeitz, M TI Regulation of mucosal inflammation by TGF-beta(1) plasmid SO MECHANISMS OF INTESTINAL INFLAMMATION: IMPLICATIONS FOR THERAPEUTIC INTERVENTION IN IBD SE FALK SYMPOSIUM LA English DT Proceedings Paper CT Falk Symposium on Mechanisms of Intestinal Inflammation - Implications for Therapeutic Intervention in IBD CY JUN 10-11, 2003 CL Berlin, GERMANY SP Falk Fdn ID T-CELLS; DOWN-REGULATION; TGF-BETA; COLITIS; INTERLEUKIN-10; INHIBITION; ACTIVATION; FIBROSIS; IL-10; CHAIN C1 NIAID, NIH, Mucosal Immun Sect, Clin Invest Lab, Bethesda, MD 20892 USA. RP Kitani, A (reprint author), NIAID, NIH, Mucosal Immun Sect, Clin Invest Lab, Bldg 10,11N 242,10 Ctr Dr, Bethesda, MD 20892 USA. NR 19 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI DORDRECHT PA PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS BN 0-7923-8787-2 J9 FALK SYMP PY 2004 VL 133 BP 107 EP 110 PG 4 WC Cell Biology; Gastroenterology & Hepatology; Immunology SC Cell Biology; Gastroenterology & Hepatology; Immunology GA BAG79 UT WOS:000222134600013 ER PT B AU Fuss, IJ Mannon, PJ Strober, W AF Fuss, IJ Mannon, PJ Strober, W BE Duchmann, R Blumberg, RS Neurath, MF Scholmerich, J Strober, W Zeitz, M TI Effector mechanisms governing experimental mucosal inflammation and human inflammatory bowel disease; new targets for anticytokine therapy SO MECHANISMS OF INTESTINAL INFLAMMATION: IMPLICATIONS FOR THERAPEUTIC INTERVENTION IN IBD SE FALK SYMPOSIUM LA English DT Proceedings Paper CT Falk Symposium on Mechanisms of Intestinal Inflammation - Implications for Therapeutic Intervention in IBD CY JUN 10-11, 2003 CL Berlin, GERMANY SP Falk Fdn ID PROPRIA MONONUCLEAR-CELLS; NECROSIS-FACTOR-ALPHA; CROHNS-DISEASE; ULCERATIVE-COLITIS; T-CELLS; TH1 RESPONSES; INTERLEUKIN-12; CYTOKINE; EXPRESSION; ACTIVATION C1 NIAID, NIH, Mucosal Immun Sect, Bethesda, MD 20892 USA. RP Fuss, IJ (reprint author), NIAID, NIH, Mucosal Immun Sect, Bldg 10,Room 11N 242, Bethesda, MD 20892 USA. NR 27 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI DORDRECHT PA PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS BN 0-7923-8787-2 J9 FALK SYMP PY 2004 VL 133 BP 156 EP 165 PG 10 WC Cell Biology; Gastroenterology & Hepatology; Immunology SC Cell Biology; Gastroenterology & Hepatology; Immunology GA BAG79 UT WOS:000222134600019 ER PT J AU Krahn, M Wong, JB Heathcote, J Scully, L Seeff, L AF Krahn, M Wong, JB Heathcote, J Scully, L Seeff, L TI Estimating the prognosis of hepatitis C patients infected by transfusion in Canada between 1986 and 1990 SO MEDICAL DECISION MAKING LA English DT Article; Proceedings Paper CT 23rd Annual Meeting of the Society-for-Medical-Decision-Making CY OCT 21-24, 2001 CL SAN DIEGO, CALIFORNIA SP Soc Med Decis Making DE hepatitis C; Markov model; decision making ID NON-B-HEPATITIS; TERM FOLLOW-UP; NON-A; POSTTRANSFUSION HEPATITIS; COST-EFFECTIVENESS; PROBABILISTIC ANALYSIS; BLOOD-TRANSFUSION; NATURAL-HISTORY; CLINICAL-TRIALS; VIRUS AB Objective. To develop a natural history model for chronic hepatitis C virus (HCV) infection to determine allocation of compensatory funds to Canadians who acquired HCV through the blood supply from 1986 through 1990. Methods. A Markov cohort simulation model for HCV prognosis was developed, using content experts, published data, posttransfusion look-back data, and a national survey. Results. The mortality Fate in transfusees is high (46% at 10 years), although HCV-related deaths are rare. Only 14% develop cirrhosis at 20 years (95% confidence interval, 0%-44%), but 1 in 4 will eventually develop cirrhosis, and 1 in 8 will die of liver disease. Conclusions. This unique application of Markov cohort simulation and epidemiologic methods provides a state-of-the-art estimate of HCV prognosis and has allowed compensation decisions to be based on the best available evidence. C1 Univ Toronto, Dept Med, Toronto, ON, Canada. Univ Toronto, Program Clin Epidemiol, Toronto, ON, Canada. Univ Toronto, Hlth Care Res, Toronto, ON, Canada. Tufts Univ, New England Med Ctr, Dept Med, Boston, MA 02111 USA. Univ Ottawa, Dept Med, Ottawa, ON, Canada. NIH, Bethesda, MD 20892 USA. RP Krahn, M (reprint author), Toronto Gen Hosp, ES9 408,200 Elizabeth St, Toronto, ON M5G 2C4, Canada. EM murray.krahn@uhn.on.ca OI Krahn, Murray/0000-0001-5836-397X NR 67 TC 33 Z9 33 U1 0 U2 1 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0272-989X J9 MED DECIS MAKING JI Med. Decis. Mak. PD JAN-FEB PY 2004 VL 24 IS 1 BP 20 EP 29 DI 10.1177/0272989X03261568 PG 10 WC Health Care Sciences & Services; Medical Informatics SC Health Care Sciences & Services; Medical Informatics GA 768TW UT WOS:000188552000002 PM 15005951 ER PT J AU Becker, KG AF Becker, KG TI The common variants/multiple disease hypothesis of common complex genetic disorders SO MEDICAL HYPOTHESES LA English DT Article ID EXPERIMENTAL ALLERGIC ENCEPHALOMYELITIS; AUTOIMMUNE-DISEASES; BIPOLAR-DISORDER; SUSCEPTIBILITY LOCI; GENOME SCAN; RHEUMATOID-ARTHRITIS; DIABETES-MELLITUS; LINKAGE DISEQUILIBRIUM; PSYCHOTIC SYMPTOMS; SCHIZOPHRENIA AB Unlike simple rare Mendelian disorders, the genetic basis for common disorders is unclear. A general model of the genetics of common complex disorders is proposed which emphasizes the shared nature of common alleles in related common disorders, such as schizophrenia and bipolar disorder, Type II diabetes and obesity, and among autoimmune diseases. This model, the common variants/multiple disease hypothesis, emphasizes that many disease genes may not be disease specific. Common deleterious alleles, found at a relatively high frequency in the population may play a role in related clinical phenotypes in the context of different genetic backgrounds and under different environmental conditions. Published by Elsevier Ltd. C1 NIA, Gene Express & Genom Unit, TRIAD Technol Ctr, NIH, Baltimore, MD 21224 USA. RP Becker, KG (reprint author), NIA, Gene Express & Genom Unit, Ctr Gerontol Res, NIH, 5600 Nathan Shock Dr, Baltimore, MD 21224 USA. EM beckerk@grc.nia.nih.gov OI Becker, Kevin/0000-0002-6794-6656 NR 82 TC 103 Z9 113 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 0306-9877 J9 MED HYPOTHESES JI Med. Hypotheses PY 2004 VL 62 IS 2 BP 309 EP 317 DI 10.1016/S0306-9877(03)00332-3 PG 9 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 779KE UT WOS:000189293200029 PM 14962646 ER PT J AU Yang, Q AF Yang, Q TI Human immunodeficiency virus reservoir might be actively eradicated as residual malignant cells by cytotoxic chemotherapy SO MEDICAL HYPOTHESES LA English DT Article ID ACUTE LYMPHOBLASTIC-LEUKEMIA; BONE-MARROW TRANSPLANTATION; ANTIRETROVIRAL THERAPY; HIV-INFECTION; T-CELLS; REPLICATION; DRUGS; HYDROXYUREA; COMBINATION; LYMPHOMA AB A unique characteristic of human immunodeficiency virus (HIV) infection is that the virus must incorporate its cDNA into the host genomic DNA for replication. Once the virus gets into the host genome and becomes a part of the host genetic materials, elimination of the virus without killing the infected cells is virtually impossible. The use of highly active antiretroviral therapy (HAART) can result in a substantial decline in viremia. However, HAART does not eradicate HIV. The progressive HIV infection wilt unavoidably rebound after a cessation of the treatment. Searching for a new combination therapeutic strategy with cytotoxic agents that eliminate or significantly reduce the HIV reservoir is a potential way for better control of the disease. Theoretically, the HIV reservoir can be gradually eradicated by long-term use of certain antimetabolic cytotoxic drugs coupled with proper activation of latently infected cells, if viral replication is completely blocked by antiretroviral chemotherapy to protect uninfected, susceptible cells. (C) 2003 Elsevier Ltd. All rights reserved. C1 SAIC Frederick Inc, Natl Canc Inst, Lab Antiviral Drug Mech, Frederick, MD 21702 USA. RP Yang, Q (reprint author), SAIC Frederick Inc, Natl Canc Inst, Lab Antiviral Drug Mech, Frederick, MD 21702 USA. EM yangq@dtpax2.ncifcrf.gov FU NCI NIH HHS [N01-CO-12400] NR 39 TC 6 Z9 6 U1 0 U2 0 PU CHURCHILL LIVINGSTONE PI EDINBURGH PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE, LEITH WALK, EDINBURGH EH1 3AF, MIDLOTHIAN, SCOTLAND SN 0306-9877 J9 MED HYPOTHESES JI Med. Hypotheses PY 2004 VL 62 IS 3 BP 358 EP 363 DI 10.1016/j.mehy.2003.10.012 PG 6 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 805UR UT WOS:000220391700007 PM 14975503 ER PT S AU Tosun, D Rettmann, ME Naiman, DQ Resnick, SM Kraut, MA Prince, JL AF Tosun, D Rettmann, ME Naiman, DQ Resnick, SM Kraut, MA Prince, JL BE Barillot, C Haynor, DR Hellier, P TI Cortical reconstruction using implicit surface evolution: A landmark validation study SO MEDICAL IMAGE COMPUTING AND COMPUTER-ASSISTED INTERVENTION - MICCAI 2004, PT 1, PROCEEDINGS SE LECTURE NOTES IN COMPUTER SCIENCE LA English DT Article; Proceedings Paper CT 7th International Conference on Medical Image Computing and Computer-Assisted Intervention (MICCAI 2004) CY SEP 26-29, 2004 CL St Malo, FRANCE SP IRISA, CNRS, Univ Rennes ID CORTEX AB A validation study was conducted to assess the accuracy of an algorithm developed for automatic reconstruction of the cerebral cortex from T1-weighted magnetic resonance (MR) brain images. Manually selected landmarks on different sulcal regions throughout the cortex were used to analyze the accuracy of three reconstructed nested surfaces - the inner, central, and pial surfaces. We conclude that the algorithm can find these surfaces with subvoxel accuracy, typically with an accuracy of one third of a voxel, although this varies by brain region and cortical geometry. Parameters were adjusted on the basis of this analysis in order to improve the algorithm's overall performance(1). C1 Johns Hopkins Univ, Dept Elect & Comp Engn, Baltimore, MD 21218 USA. NIA, NIH, Bethesda, MD 20892 USA. Johns Hopkins Univ, Dept Appl Math & Stat, Baltimore, MD 21218 USA. Johns Hopkins Univ Hosp, Dept Radiol, Baltimore, MD 21287 USA. RP Tosun, D (reprint author), Johns Hopkins Univ, Dept Elect & Comp Engn, Baltimore, MD 21218 USA. RI Prince, Jerry/A-3281-2010 OI Prince, Jerry/0000-0002-6553-0876 NR 8 TC 5 Z9 5 U1 0 U2 0 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY SN 0302-9743 BN 3-540-22976-0 J9 LECT NOTES COMPUT SC PY 2004 VL 3216 BP 384 EP 392 PN 1 PG 9 WC Computer Science, Interdisciplinary Applications; Computer Science, Theory & Methods; Imaging Science & Photographic Technology; Radiology, Nuclear Medicine & Medical Imaging SC Computer Science; Imaging Science & Photographic Technology; Radiology, Nuclear Medicine & Medical Imaging GA BAZ60 UT WOS:000224321100047 ER PT S AU Balogh, E Deguet, A Susil, RC Krieger, A Viswanathan, A Menard, C Coleman, JA Fichtinger, G AF Balogh, E Deguet, A Susil, RC Krieger, A Viswanathan, A Menard, C Coleman, JA Fichtinger, G BE Barillot, C Haynor, DR Hellier, P TI Visualization, planning, and monitoring software for MRI-guided prostate intervention robot SO MEDICAL IMAGE COMPUTING AND COMPUTER-ASSISTED INTERVENTION - MICCAI 2004, PT 2, PROCEEDINGS SE LECTURE NOTES IN COMPUTER SCIENCE LA English DT Article; Proceedings Paper CT 7th International Conference on Medical Image Computing and Computer-Assisted Intervention (MICCAI 2004) CY SEP 26-29, 2004 CL St Malo, FRANCE SP IRISA, CNRS, Univ Rennes ID BIOPSY; CANCER; GUIDANCE AB This paper reports an interactive software interface for visualization, planning, and monitoring of intra-prostatic needle placement procedures performed with a robotic assistant device inside standard cylindrical high-field magnetic resonance imaging (MRI) scanner. We use anatomical visualization and image processing techniques to plan the process and apply active tracking coils to localize the robot in realtime to monitor its motion relative to the anatomy. The interventional system is in Phase-I clinical trials for prostate biopsy and marker seed placement. The system concept, mechanical design, and in-vivo canine studies have been presented earlier [6,10,14]. The software architecture and three-dimensional application software interface discussed in this paper are new additions. This software was tested on pre-recorded patient data. C1 Johns Hopkins Univ, Engn Res Ctr, Baltimore, MD 21218 USA. Johns Hopkins Univ, Dept Biomed Engn, Baltimore, MD 21218 USA. Johns Hopkins Univ, Dept Radiol, Baltimore, MD 21218 USA. NCI, Radiat Oncol Branch, NIH, Bethesda, MD 20892 USA. Univ Szeged, Dept Informat, Szeged, Hungary. RP Balogh, E (reprint author), Johns Hopkins Univ, Engn Res Ctr, Baltimore, MD 21218 USA. EM emese@cs.jhu.edu OI Viswanathan, Anand/0000-0003-3810-6217; Coleman, Jonathan/0000-0002-6428-7835 NR 14 TC 2 Z9 2 U1 0 U2 0 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY SN 0302-9743 BN 3-540-22977-9 J9 LECT NOTES COMPUT SC PY 2004 VL 3217 BP 73 EP 80 PN 2 PG 8 WC Computer Science, Interdisciplinary Applications; Computer Science, Theory & Methods; Imaging Science & Photographic Technology; Radiology, Nuclear Medicine & Medical Imaging SC Computer Science; Imaging Science & Photographic Technology; Radiology, Nuclear Medicine & Medical Imaging GA BAZ67 UT WOS:000224322400010 ER PT S AU Yao, JH Summers, RM AF Yao, JH Summers, RM BE Amini, AA Manduca, A TI 3D colonic polyp segmentation using dynamic deformable surfaces SO MEDICAL IMAGING 2004: PHYSIOLOGY, FUNCTION, AND STRUCTURE FROM MEDICAL IMAGES SE PROGRESS IN BIOMEDICAL OPTICS AND IMAGING LA English DT Proceedings Paper CT Medical Imaging 2004 Conference CY FEB 17-19, 2004 CL San Diego, CA SP SPIE, Amer Assoc Phys Med, Amer Physiol Soc, Ctr Devices & Radiol Hlth, Soc Imaging Sci & Technol, Natl Elect Mfg Assoc, Diagnost Imaging & Therapy Syst Div, Radiol Soc N Amer, Soc Comp Applicat Radiol DE colonic polyp segmentation; deformable surface; CT colonography ID CT COLONOGRAPHY AB An improved 3D method for colonic polyp segmentation was developed based on previous 2D method. The method is based on combination of 3D knowledge-guided intensity adjustment, fuzzy clustering, and dynamic deformable surfaces. After intensity adjustment and fuzzy clustering, a deformable surface is employed to locate the polyp boundaries. The surface is also dynamically maintained to preserve the resolution and topology. The deformable surface is operated on a sub-volume of the data set and driven by image forces, balloon forces and internal spline forces. Compared to previous 2D method, the improved method produces much smoother polyp boundaries, and 3D features can be derived from the segmentation, such as 3D aspect ratio, curvatures, and polyp wall thickness etc. The computer segmentations were validated with manual segmentations. Preliminary results showed that the average volume overlap percentage among 25 polyp detections was 80.6%. C1 NIH, Dept Diagnost Radiol, Ctr Clin, Bethesda, MD 20892 USA. RP Yao, JH (reprint author), NIH, Dept Diagnost Radiol, Ctr Clin, Bethesda, MD 20892 USA. NR 11 TC 0 Z9 0 U1 0 U2 0 PU SPIE-INT SOC OPTICAL ENGINEERING PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98227-0010 USA SN 1605-7422 BN 0-8194-5282-3 J9 PRO BIOMED OPT IMAG PY 2004 VL 5 IS 23 BP 280 EP 289 DI 10.1117/12.536691 PG 10 WC Engineering, Biomedical; Physiology; Radiology, Nuclear Medicine & Medical Imaging SC Engineering; Physiology; Radiology, Nuclear Medicine & Medical Imaging GA BAF37 UT WOS:000221994400028 ER PT S AU Bitter, I Brown, JE Brickman, D Summers, RM AF Bitter, I Brown, JE Brickman, D Summers, RM BE Amini, AA Manduca, A TI Large scale validation of a computer aided polyp detection algorithm for CT colonography using cluster computing SO MEDICAL IMAGING 2004: PHYSIOLOGY, FUNCTION, AND STRUCTURE FROM MEDICAL IMAGES SE PROGRESS IN BIOMEDICAL OPTICS AND IMAGING LA English DT Proceedings Paper CT Medical Imaging 2004 Conference CY FEB 17-19, 2004 CL San Diego, CA SP SPIE, Amer Assoc Phys Med, Amer Physiol Soc, Ctr Devices & Radiol Hlth, Soc Imaging Sci & Technol, Natl Elect Mfg Assoc, Diagnost Imaging & Therapy Syst Div, Radiol Soc N Amer, Soc Comp Applicat Radiol DE cluster computing; beowulf; multi platform software development; computed tomographic virtual colonoscopy; polyp detection; computer aided detection; algorithm validation ID COLONOSCOPY AB The presented method significantly reduces the time necessary to validate a computed tomographic colonography (CTC) computer aided detection (CAD) algorithm of colonic polyps applied to a large patient database. As the algorithm is being developed on Windows PCs and our target, a Beowulf cluster, is running on Linux PCs, we made the application dual platform compatible using a single source code tree. To maintain, share, and deploy source code, we used CVS (concurrent versions system) software. We built the libraries from their sources for each operating system. Next, we made the CTC CAD algorithm dual-platform compatible and validate that both Windows and Linux produced the same results. Eliminating system dependencies was mostly achieved using the Qt programming library, which encapsulates most of the system dependent functionality in order to present the same interface on either platform. Finally, we wrote scripts to execute the CTC CAD algorithm in parallel. Running hundreds of simultaneous copies of the CTC CAD algorithm on a Beowulf cluster computing network enables execution in less than four hours on our entire collection of over 2400 CT scans, as compared to a month a single PC. As a consequence, our complete patient dataase can be processed daily, boosting research productivity. Large scale validation of a computer aided polyp detection algorithm for CT colonography using cluster computing significantly improves the round trip time of algorithm improvement and revalidation. C1 NIH, Warren Grant Magnuson Clin Ctr, Dept Diagnost Radiol, Bethesda, MD 20892 USA. RP Bitter, I (reprint author), NIH, Warren Grant Magnuson Clin Ctr, Dept Diagnost Radiol, Bethesda, MD 20892 USA. NR 2 TC 1 Z9 1 U1 0 U2 0 PU SPIE-INT SOC OPTICAL ENGINEERING PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98227-0010 USA SN 1605-7422 BN 0-8194-5282-3 J9 PRO BIOMED OPT IMAG PY 2004 VL 5 IS 23 BP 290 EP 294 DI 10.1117/12.536917 PG 5 WC Engineering, Biomedical; Physiology; Radiology, Nuclear Medicine & Medical Imaging SC Engineering; Physiology; Radiology, Nuclear Medicine & Medical Imaging GA BAF37 UT WOS:000221994400029 ER PT S AU Cannata, JM Shung, KK AF Cannata, JM Shung, KK BE Walker, WF Emelianov, SY TI Development of a high frequency (35-MHz) linear ultrasonic array SO MEDICAL IMAGING 2004: ULTRASONIC IMAGING AND SIGNAL PROCESSING SE PROCEEDINGS OF THE SOCIETY OF PHOTO-OPTICAL INSTRUMENTATION ENGINEERS (SPIE) LA English DT Proceedings Paper CT Medical Imaging 2004 Conference CY FEB 17-19, 2004 CL San Diego, CA SP SPIE, Amer Assoc Phys Med, Amer Physiol Soc, Ctr Devices & Radiol Hlth, Soc Imaging Sci & Technol, Natl Elect Mfg Assoc, Diagnost Imaging & Therapy Syst Div, Radiol Soc N Amer, Soc Comp Applicat Radiol DE high frequency ultrasound; linear array; fine grain piezoelectric ceramic; finite element analysis ID TRANSDUCERS AB Methods for fabricating and modeling of a high frequency linear ultrasonic array are presented. This array was designed primarily for human eye imaging, and features elements mechanically diced out of a fine grain high density PZT-5H ceramic. Array elements were spaced with a 50 micron pitch, interconnected via a flexible circuit and matched to the 50 Ohm system electronics via a 85 Ohm transmission line coaxial cable. The current array design was based upon tradeoffs between the time domain response bandwidth and sensitivity, as well as, the level of array encapsulation and suppression acoustic crosstalk. A prototype four element array was constructed with promising results. An average center frequency of 34 MHz with a -6 dB bandwidth of at least 45% per element was achieved with a 20 dB pulse length of 105 ns. The array performance was compared to a time domain finite element analysis program and excellent agreement between theory and experiment was achieved. C1 Univ So Calif, NIH, Resource Med Ultrason Transducer Technol, Los Angeles, CA 90089 USA. RP Cannata, JM (reprint author), Univ So Calif, NIH, Resource Med Ultrason Transducer Technol, Los Angeles, CA 90089 USA. NR 8 TC 0 Z9 0 U1 0 U2 0 PU SPIE-INT SOC OPTICAL ENGINEERING PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98227-0010 USA SN 0277-786X BN 0-8194-5286-6 J9 P SOC PHOTO-OPT INS PY 2004 VL 5373 BP 18 EP 23 DI 10.1117/12.537062 PG 6 WC Engineering, Biomedical; Imaging Science & Photographic Technology SC Engineering; Imaging Science & Photographic Technology GA BAE49 UT WOS:000221852600002 ER PT J AU Gibril, F Schumann, M Pace, A Jensen, RT AF Gibril, F Schumann, M Pace, A Jensen, RT TI Multiple endocrine neoplasia type 1 and Zollinger-Ellison syndrome - A prospective study of 107 cases and comparison with 1009 cases from the literature SO MEDICINE LA English DT Review ID ISLET-CELL TUMORS; GASTRIC-ACID-SECRETION; SOMATOSTATIN RECEPTOR SCINTIGRAPHY; LONG-TERM TREATMENT; SYNDROME TYPE-I; ENTEROCHROMAFFIN-LIKE CELLS; PRIMARY HYPER-ALDOSTERONISM; INTRACTABLE PEPTIC ULCER; MEN1 GENE-MUTATIONS; ADENOMATOSIS TYPE-I AB In patients with multiple endocrine neoplasia type 1 (MEN1), the most common functional pancreatic endocrine tumor (PET) syndrome is Zollinger-Ellison syndrome (ZES). ZES has been well studied in its sporadic form (that is, without MEN 1); however, there are limited data on patients with MEN1 and ZES (MEN 1/ZES), and the long-term natural history is largely unknown. To address this issue we report the results of a prospective long-term National Institutes of Health (NIH) study of 107 MEN1/ZES patients and compare our results with those of 1009 MEN1/ZES patients in 278 case reports and small series in the literature. Patients were clinically, radiologically, and biochemically evaluated yearly for all MEN1 manifestations (mean follow-up, 10 yr; range, 0.1-31 yr). Compared with patients from the literature, the NIH MEN1/ZES patients more frequently had pituitary (60%) and adrenal (45%) disease and carcinoid tumors (30%), but had equal frequency of hyperparathyroidism (94%), thyroid disease (6%), or lipomas (5%). Twenty-five percent of both the NIH and the literature patients lacked a family history of MEN1; ZES was the initial clinical manifestation of MEN1 in 40%. ZES onset preceded the diagnosis of hyperparathyroidism in 45%. However, ZES was rarely (8%) the only initial manifestation of MEN1 if careful testing was done. ZES occurred before age 40 years in 50%-60% of the current patients, in contrast to older studies. The diagnosis of ZES is delayed 3-5 years from its onset and is delayed as long as in sporadic ZES cases. Pituitary disease and carcinoid tumors (gastric > bronchial, thymic) are more frequent than generally reported, whereas a second functional PET is uncommon. In patients with MEN1/ZES without a family history of MEN1, the MEN1 manifestations are not as severe. This study shows that MEN1/ZES patients differ in many aspects from those commonly reported in older studies involving few MEN1/ZES patients. In this study we have identified a number of important clinical and laboratory features of MEN1/ZES that were not previously appreciated, which should contribute to earlier diagnosis and improve both short- and long-term management. C1 NIDDK, Digest Dis Branch, NIH, Bethesda, MD 20892 USA. RP Jensen, RT (reprint author), NIDDK, Digest Dis Branch, NIH, Bldg 10,Rm 9C-103,10 Ctr Dr,MSC 1804, Bethesda, MD 20892 USA. EM robertj@bdg10.niddk.nih.gov RI Schumann, Michael/K-6426-2013 OI Schumann, Michael/0000-0001-6391-9979 NR 504 TC 129 Z9 129 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0025-7974 J9 MEDICINE JI Medicine (Baltimore) PD JAN PY 2004 VL 83 IS 1 BP 43 EP 83 DI 10.1097/01.md.0000112297.72510.32 PG 41 WC Medicine, General & Internal SC General & Internal Medicine GA 766KB UT WOS:000188374600004 PM 14747767 ER PT S AU de Coronado, S Haber, MW Sioutos, N Tuttle, MS Wright, LW AF de Coronado, S Haber, MW Sioutos, N Tuttle, MS Wright, LW BE Fieschi, M Coiera, E Li, YCJ TI NCI thesaurus: Using science-based terminology to integrate cancer research results SO MEDINFO 2004: PROCEEDINGS OF THE 11TH WORLD CONGRESS ON MEDICAL INFORMATICS, PT 1 AND 2 SE STUDIES IN HEALTH TECHNOLOGY AND INFORMATICS LA English DT Proceedings Paper CT 11th World Congress on Medical Informatics CY SEP 07-11, 2004 CL Amer Med Informat Assoc, San Francisco, CA SP Int Med Informat Assoc HO Amer Med Informat Assoc DE terminology; cancer; research; information systems; description logic; terminology server; terminology modeling AB Cancer researchers need to be able to organize and report their results in a way that others can find, build upon, and relate to the specific clinical conditions of individual patients. NCI Thesaurus (TM) is a description logic terminology based on current science that helps individuals and software applications connect and organize the results of cancer research, e.g., by disease and underlying biology. Currently containing some 34,000 concepts covering chemicals, drugs and other therapies, diseases, genes and gene products, anatomy, organisms, animal models, techniques, biologic processes, and administrative categories - NCI Thesaurus serves applications and the Web from a terminology server. As a scalable, formal terminology, the deployed Thesaurus, and associated applications and interfaces, are a model for some of the standards required for the NHII (National Health Information Infrastructure) and the Semantic Web. C1 NCI, Ctr Bioinformat, Rockville, MD USA. RP de Coronado, S (reprint author), 6116 Execut Blvd 403, Bethesda, MD 20892 USA. NR 19 TC 26 Z9 26 U1 0 U2 0 PU I O S PRESS PI AMSTERDAM PA NIEUWE HEMWEG 6B, 1013 BG AMSTERDAM, NETHERLANDS SN 0926-9630 BN 1-58603-444-8 J9 ST HEAL T PY 2004 VL 107 BP 33 EP 37 PG 5 WC Computer Science, Information Systems; Medical Informatics SC Computer Science; Medical Informatics GA BBO53 UT WOS:000226723300007 PM 15360769 ER PT S AU Kingsland, LC Prettyman, MF Shooshan, SE AF Kingsland, LC Prettyman, MF Shooshan, SE BE Fieschi, M Coiera, E Li, YCJ TI The NLM Gateway: a metasearch engine for disparate resources SO MEDINFO 2004: PROCEEDINGS OF THE 11TH WORLD CONGRESS ON MEDICAL INFORMATICS, PT 1 AND 2 SE STUDIES IN HEALTH TECHNOLOGY AND INFORMATICS LA English DT Proceedings Paper CT 11th World Congress on Medical Informatics CY SEP 07-11, 2004 CL Amer Med Informat Assoc, San Francisco, CA SP Int Med Informat Assoc HO Amer Med Informat Assoc DE information storage and retrieval; medical informatics applications; medical informatics computing; databases; bibliographic; systems integration; automatic data processing; systems theory; computing methodologies AB The U.S. National Library of Medicine (NLM) has created a metasearch engine called the NLM Gateway at the URL 'gateway.nlm.nih.gov". The Gateway allows the user to issue one search that takes place on multiple NLM retrieval engines. A composite result set is presented in several categories of information: journal citations; books, serials and audiovisuals; consumer health; meeting abstracts; and other collections. C1 Natl Lib Med, Bethesda, MD 20894 USA. RP Kingsland, LC (reprint author), Natl Lib Med, 8600 Rockville Pike, Bethesda, MD 20894 USA. NR 9 TC 1 Z9 1 U1 0 U2 0 PU I O S PRESS PI AMSTERDAM PA NIEUWE HEMWEG 6B, 1013 BG AMSTERDAM, NETHERLANDS SN 0926-9630 BN 1-58603-444-8 J9 ST HEAL T PY 2004 VL 107 BP 52 EP 56 PG 5 WC Computer Science, Information Systems; Medical Informatics SC Computer Science; Medical Informatics GA BBO53 UT WOS:000226723300011 PM 15360773 ER PT S AU Nelson, SJ Schopen, M Savage, AG Schulman, JL Arluk, N AF Nelson, SJ Schopen, M Savage, AG Schulman, JL Arluk, N BE Fieschi, M Coiera, E Li, YCJ TI The MeSH translation maintenance system: Structure, interface design, and implementation SO MEDINFO 2004: PROCEEDINGS OF THE 11TH WORLD CONGRESS ON MEDICAL INFORMATICS, PT 1 AND 2 SE STUDIES IN HEALTH TECHNOLOGY AND INFORMATICS LA English DT Proceedings Paper CT 11th World Congress on Medical Informatics CY SEP 07-11, 2004 CL Amer Med Informat Assoc, San Francisco, CA SP Int Med Informat Assoc HO Amer Med Informat Assoc DE MEDLINE; translations; subject headings; unified medical language system; databases; user-computer interface AB The National Library of Medicine (NLM) produces annual editions of the Medical Subject Headings (MeSH (R)). Translations of MeSH are often done to make the vocabulary useful for non-English users. However, MeSH translators have encountered difficulties with entry vocabulary as they maintain and update their translation. Tracking MeSH changes and updating their translations in a reasonable time frame is cumbersome. NLM has developed and implemented a concept-centered vocabulary maintenance system for MeSH. This system has been extended to create an interlingual database of translations, the MeSH Translation Maintenance System (MTMS). This database allows continual updating of the translations, as well as facilitating tracking of the changes within MeSH from one year to another. The MTMS interface uses a Web-based design with multiple colors and fonts to indicate concepts needing translation or review. Concepts for which there is no exact English equivalent can be added. The system software encourages compliance with the Unicode standard in order to ensure that character sets with native alphabets and full orthography are used consistently. C1 Natl Lib Med, Bethesda, MD USA. RP Nelson, SJ (reprint author), Natl Lib Med, Bethesda, MD USA. NR 6 TC 36 Z9 36 U1 0 U2 0 PU I O S PRESS PI AMSTERDAM PA NIEUWE HEMWEG 6B, 1013 BG AMSTERDAM, NETHERLANDS SN 0926-9630 BN 1-58603-444-8 J9 ST HEAL T PY 2004 VL 107 BP 67 EP 69 PG 3 WC Computer Science, Information Systems; Medical Informatics SC Computer Science; Medical Informatics GA BBO53 UT WOS:000226723300014 PM 15360776 ER PT S AU Aronson, AR Mork, JG Gay, CW Humphrey, SM Rogers, WJ AF Aronson, AR Mork, JG Gay, CW Humphrey, SM Rogers, WJ BE Fieschi, M Coiera, E Li, YCJ TI The NLM indexing initiative's Medical Text Indexer SO MEDINFO 2004: PROCEEDINGS OF THE 11TH WORLD CONGRESS ON MEDICAL INFORMATICS, PT 1 AND 2 SE STUDIES IN HEALTH TECHNOLOGY AND INFORMATICS LA English DT Proceedings Paper CT 11th World Congress on Medical Informatics CY SEP 07-11, 2004 CL Amer Med Informat Assoc, San Francisco, CA SP Int Med Informat Assoc HO Amer Med Informat Assoc DE abstracting and indexing; evaluation studies; MEDLINE; unied medical language system; natural language processing; information storage and retrieval AB The Medical Text Indexer (MTI) is a program for producing MeSH (R) indexing recommendations. It is the major product of NLM's Indexing Initiative and has been used in both semi-automated and fully automated indexing environments at the Library since mid 2002. We report here on an experiment conducted with MEDLINE (R) indexers to evaluate MTIs performance and to generate ideas for its improvement as a tool for user-assisted indexing. We also discuss some Itering techniques developed to improve MTIs accuracy for use primarily in automatically producing the indexing for several abstracts collections. C1 Natl Lib Med, Bethesda, MD 20894 USA. RP Aronson, AR (reprint author), Natl Lib Med, Bldg 38A,MS 548600 Rockville Pike, Bethesda, MD 20894 USA. NR 5 TC 36 Z9 36 U1 0 U2 0 PU I O S PRESS PI AMSTERDAM PA NIEUWE HEMWEG 6B, 1013 BG AMSTERDAM, NETHERLANDS SN 0926-9630 BN 1-58603-444-8 J9 ST HEAL T PY 2004 VL 107 BP 268 EP 272 PG 5 WC Computer Science, Information Systems; Medical Informatics SC Computer Science; Medical Informatics GA BBO53 UT WOS:000226723300054 PM 15360816 ER PT S AU Bodenreider, O Burgun, A AF Bodenreider, O Burgun, A BE Fieschi, M Coiera, E Li, YCJ TI Aligning knowledge sources in the UMLS: Methods, quantitative results, and applications SO MEDINFO 2004: PROCEEDINGS OF THE 11TH WORLD CONGRESS ON MEDICAL INFORMATICS, PT 1 AND 2 SE Studies in Health Technology and Informatics LA English DT Proceedings Paper CT 11th World Congress on Medical Informatics CY SEP 07-11, 2004 CL Amer Med Informat Assoc, San Francisco, CA SP Int Med Informat Assoc HO Amer Med Informat Assoc DE UMLS; alignment; hierarchical relationships. ID LANGUAGE AB The UMLS Semantic Network and Metathesaurus are two complementary knowledge sources. While many studies compare relationships across the two structures, their alignment has never been attempted. We applied two methods based on lexical and conceptual similarity to aligning the Semantic Network with the UMLS Metathesaurus. Approximately two thirds of the semantic types could be aligned by lexical similarity. Conceptual similarity suggested mappings in all but ten cases. Potential applications enabled by the alignment are discussed, namely auditing the consistency between the Semantic Network and the Metathesaurus and extending the Semantic Network downwards. The relative contribution and limitations of the two methods used for the alignment are also discussed. C1 Natl Lib Med, NIH, Bethesda, MD 20894 USA. RP Natl Lib Med, NIH, 8600 Rockville Pike,MS 43, Bethesda, MD 20894 USA. EM olivier@nlm.nih.gov FU Intramural NIH HHS [Z99 LM999999] NR 10 TC 4 Z9 4 U1 0 U2 0 PU IOS PRESS PI AMSTERDAM PA NIEUWE HEMWEG 6B, 1013 BG AMSTERDAM, NETHERLANDS SN 0926-9630 BN 1-58603-444-8 J9 STUD HEALTH TECHNOL PY 2004 VL 107 BP 327 EP 331 PG 5 WC Computer Science, Information Systems; Medical Informatics SC Computer Science; Medical Informatics GA BBO53 UT WOS:000226723300066 PM 15360828 ER PT S AU Hole, WT Carlsen, BA Tuttle, MS Srinivasan, S Lipow, SS Olson, NE Sherertz, DD Humphreys, BL AF Hole, WT Carlsen, BA Tuttle, MS Srinivasan, S Lipow, SS Olson, NE Sherertz, DD Humphreys, BL BE Fieschi, M Coiera, E Li, YCJ TI Achieving "source transparency" in the UMLS (R) Metathesaurus (R) SO MEDINFO 2004: PROCEEDINGS OF THE 11TH WORLD CONGRESS ON MEDICAL INFORMATICS, PT 1 AND 2 SE STUDIES IN HEALTH TECHNOLOGY AND INFORMATICS LA English DT Proceedings Paper CT 11th World Congress on Medical Informatics CY SEP 07-11, 2004 CL Amer Med Informat Assoc, San Francisco, CA SP Int Med Informat Assoc HO Amer Med Informat Assoc DE unified medical language system; medical Informatics; controlled vocabulary; information systems; Metathesaurus AB The UMLS Metathesaurus is a syntactically uniform, concept based, semantically enhanced representation of many of the world's authoritative biomedical vocabularies. Released several times a year, the Metathesaurus is becoming a common, longitudinally maintained source of the current versions of these vocabularies. As vocabularies become standards for reimbursement, reporting, interoperation, and use by applications, the vocabulary obtained from the Metathesaurus must be consistent with that obtainable from each vocabulary's authority. Effective with the first 2004 release, the Metathesaurus represents new and updated sources "transparently" - both users and applications are able to "see" each vocabulary in the Metathesaurus without any of the small losses of information introduced by abstractions used in previous versions. Thus, the Metathesaurus can continue to provide its many semantic and lexical value-added features while guaranteeing that original sources will be "visible" in intact form. Vocabulary users and application developers will benefit from the enhancements and economies of scale offered by the Metathesaurus, while preserving distinctions between content provided by external authorities and content added as part of the Metathesaurus development and maintenance process. C1 Natl Lib Med, Bethesda, MD 20894 USA. RP Hole, WT (reprint author), Natl Lib Med, 8600 Rockville Pike, Bethesda, MD 20894 USA. NR 5 TC 2 Z9 2 U1 0 U2 0 PU I O S PRESS PI AMSTERDAM PA NIEUWE HEMWEG 6B, 1013 BG AMSTERDAM, NETHERLANDS SN 0926-9630 BN 1-58603-444-8 J9 ST HEAL T PY 2004 VL 107 BP 371 EP 375 PG 5 WC Computer Science, Information Systems; Medical Informatics SC Computer Science; Medical Informatics GA BBO53 UT WOS:000226723300075 PM 15360837 ER PT S AU Rodgers, RPC Sherwin, Z Lamberts, H Okkes, IM AF Rodgers, RPC Sherwin, Z Lamberts, H Okkes, IM BE Fieschi, M Coiera, E Li, YCJ TI ICPC Multilingual Collaboratory: A web-and unicode-based system for distributed editing/translating/viewing of the multilingual International Classification of Primary Care SO MEDINFO 2004: PROCEEDINGS OF THE 11TH WORLD CONGRESS ON MEDICAL INFORMATICS, PT 1 AND 2 SE STUDIES IN HEALTH TECHNOLOGY AND INFORMATICS LA English DT Proceedings Paper CT 11th World Congress on Medical Informatics CY SEP 07-11, 2004 CL Amer Med Informat Assoc, San Francisco, CA SP Int Med Informat Assoc HO Amer Med Informat Assoc DE classification; collaboration; ICPC; Internet; language; medical Informatics; unicode; World Wide Web; ICPC Multilingual Collaboratory; a web- and unicode-based system AB The International Classification of Primary Care (ICPC) is a clinical classification containing 726 clinical concepts, available in over 20 languages, augmented by links to ICD-10 concepts. It is employed in clinical information systems in several European countries, Israel, Japan, and Australia. In translating ICPC, it has been challenging to manage the flow of multilingual information, maintain its quality, and optimize its portability, particularly in light of the numerous character encodings used to represent its content. The ICPC Multilingual Collaboratory (IMC) is a World Wide Web-based environment, created to allow the viewing, maintenance, and translation of ICPC content by a dispersed international editorial staff. Based upon open-source software, it represents ICPC content using the Unicode standard for character encoding. The system implements three interfaces to ICPC data: 1) a password-protected editorial interface which instantiates a hierarchical authority model and communication channels for review and control of content, including a means of uploading new candidate translations; 2) an openly accessible read-only interface, with email access to the editors (providing another level of content review); and, 3) a management interface for the system administrator. The completed system powerfully demonstrates the ability of the World Wide Web, open-source software, and Unicode to expedite and simplify international multilingual collaboration, even in a world in which Unicode support is incomplete on existing computing platforms. C1 Natl Lib Med, Off High Performance Comp & Commun, Lister Hill Natl Ctr Biomed Commun, Bethesda, MD 20894 USA. RP Rodgers, RPC (reprint author), Natl Lib Med, Off High Performance Comp & Commun, Lister Hill Natl Ctr Biomed Commun, Bldg 38,Room B1N-30D,8600 Rockville Pike, Bethesda, MD 20894 USA. NR 18 TC 2 Z9 3 U1 0 U2 0 PU I O S PRESS PI AMSTERDAM PA NIEUWE HEMWEG 6B, 1013 BG AMSTERDAM, NETHERLANDS SN 0926-9630 BN 1-58603-444-8 J9 ST HEAL T PY 2004 VL 107 BP 425 EP 429 PG 5 WC Computer Science, Information Systems; Medical Informatics SC Computer Science; Medical Informatics GA BBO53 UT WOS:000226723300086 PM 15360848 ER PT S AU Zhang, SM Bodenreider, O AF Zhang, SM Bodenreider, O BE Fieschi, M Coiera, E Li, YCJ TI Comparing associative relationships among equivalent concepts across ontologies SO MEDINFO 2004: PROCEEDINGS OF THE 11TH WORLD CONGRESS ON MEDICAL INFORMATICS, PT 1 AND 2 SE Studies in Health Technology and Informatics LA English DT Proceedings Paper CT 11th World Congress on Medical Informatics CY SEP 07-11, 2004 CL Amer Med Informat Assoc, San Francisco, CA SP Int Med Informat Assoc HO Amer Med Informat Assoc DE ontology; associative relationship; hierarchical relationship; ontology matching; anatomy; GALEN; Foundational Model of Anatomy AB Methods for comparing associative relationships across ontologies often rely solely on lexical similarity between the names of the relationships, which may lead to missed matches and inaccurate matches. In this paper, we propose a novel method based on the analysis of paths between equivalent concepts across ontologies. Patterns of relationships are identified for each associative relationship. The most frequent patterns indicate a correspondence between an associative relationship in one ontology and one relationship (or combination thereof) in the other. We applied this method to two ontologies of anatomy. Our method was able to identify the correspondence between relationships even in the absence of lexical similarity between relationship names. The various types of matches identified are discussed as well as the application of this method to detecting inconsistencies across the ontologies. C1 Natl Lib Med, NIH, Bethesda, MD 20894 USA. RP Natl Lib Med, NIH, 8600 Rockville Pike,MS 43, Bethesda, MD 20894 USA. EM szhang@nlm.nih.gov; olivier@nlm.nih.gov FU Intramural NIH HHS [Z99 LM999999] NR 14 TC 4 Z9 4 U1 0 U2 0 PU IOS PRESS PI AMSTERDAM PA NIEUWE HEMWEG 6B, 1013 BG AMSTERDAM, NETHERLANDS SN 0926-9630 BN 1-58603-444-8 J9 STUD HEALTH TECHNOL PY 2004 VL 107 BP 459 EP 463 PG 5 WC Computer Science, Information Systems; Medical Informatics SC Computer Science; Medical Informatics GA BBO53 UT WOS:000226723300093 PM 15360855 ER PT S AU Fiszman, M Rindflesch, TC Kilicoglu, H AF Fiszman, M Rindflesch, TC Kilicoglu, H BE Fieschi, M Coiera, E Li, YCJ TI Summarization of an online medical encyclopedia SO MEDINFO 2004: PROCEEDINGS OF THE 11TH WORLD CONGRESS ON MEDICAL INFORMATICS, PT 1 AND 2 SE STUDIES IN HEALTH TECHNOLOGY AND INFORMATICS LA English DT Proceedings Paper CT 11th World Congress on Medical Informatics CY SEP 07-11, 2004 CL Amer Med Informat Assoc, San Francisco, CA SP Int Med Informat Assoc HO Amer Med Informat Assoc DE natural language processing; automatic summarization; knowledge representation ID SYSTEM AB We explore a knowledge-rich (abstraction) approach to summarization and apply it to multiple documents from an online medical encyclopedia. A semantic processor functions as the source interpreter and produces a list of predications. A transformation stage then generalizes and condenses this list, ultimately generating a conceptual condensate for a given disorder topic. We provide a preliminary evaluation of the quality of the condensates produced for a sample of four disorders. The overall precision of the disorder conceptual condensates was 87%, and the compression ratio from the base list of predications to the final condensate was 98%. The conceptual condensate could be used as input to a text generator to produce a natural language summary for a given disorder topic. C1 Natl Lib Med, Dept Hlth & Human Serv, NIH, Bethesda, MD 20894 USA. RP Fiszman, M (reprint author), Natl Lib Med, Dept Hlth & Human Serv, NIH, Bldg 38A,8600 Rockville Pike MS 43, Bethesda, MD 20894 USA. NR 15 TC 4 Z9 4 U1 0 U2 0 PU I O S PRESS PI AMSTERDAM PA NIEUWE HEMWEG 6B, 1013 BG AMSTERDAM, NETHERLANDS SN 0926-9630 BN 1-58603-444-8 J9 ST HEAL T PY 2004 VL 107 BP 506 EP 510 PG 5 WC Computer Science, Information Systems; Medical Informatics SC Computer Science; Medical Informatics GA BBO53 UT WOS:000226723300102 PM 15360864 ER PT S AU Demner-Fushman, D Hauser, SE Ford, G Thoma, GR AF Demner-Fushman, D Hauser, SE Ford, G Thoma, GR BE Fieschi, M Coiera, E Li, YCJ TI Organizing literature information for clinical decision support SO MEDINFO 2004: PROCEEDINGS OF THE 11TH WORLD CONGRESS ON MEDICAL INFORMATICS, PT 1 AND 2 SE STUDIES IN HEALTH TECHNOLOGY AND INFORMATICS LA English DT Proceedings Paper CT 11th World Congress on Medical Informatics CY SEP 07-11, 2004 CL Amer Med Informat Assoc, San Francisco, CA SP Int Med Informat Assoc HO Amer Med Informat Assoc DE handheld computer; computer-assisted decision making ID QUESTIONS AB Answers to clinical questions occurring during healthcare practitioner/patient interaction can be often found in National Library of Medicine's (NLM) databases. The recent advances in wireless handheld computers promise to make them a widely used tool to deliver needed information to the practitioner at the point of service. This paper addresses challenges in organizing and presenting information obtained from NLM's MEDLINe (R) database of indexed citations in a way that will help practitioners reduce literature search time on handheld computers. We study two clustering algorithms and two methods of labeling document clusters. C1 Lister Hill Natl Ctr Biomed Commun, Natl Lib Med, Bethesda, MD 20894 USA. RP Demner-Fushman, D (reprint author), Lister Hill Natl Ctr Biomed Commun, Natl Lib Med, Bethesda, MD 20894 USA. NR 16 TC 1 Z9 1 U1 0 U2 0 PU I O S PRESS PI AMSTERDAM PA NIEUWE HEMWEG 6B, 1013 BG AMSTERDAM, NETHERLANDS SN 0926-9630 BN 1-58603-444-8 J9 ST HEAL T PY 2004 VL 107 BP 602 EP 606 PG 5 WC Computer Science, Information Systems; Medical Informatics SC Computer Science; Medical Informatics GA BBO53 UT WOS:000226723300121 PM 15360883 ER PT S AU Divita, G Tse, T Roth, L AF Divita, G Tse, T Roth, L BE Fieschi, M Coiera, E Li, YCJ TI Failure analysis of MetaMap Transfer (MMTx) SO MEDINFO 2004: PROCEEDINGS OF THE 11TH WORLD CONGRESS ON MEDICAL INFORMATICS, PT 1 AND 2 SE STUDIES IN HEALTH TECHNOLOGY AND INFORMATICS LA English DT Proceedings Paper CT 11th World Congress on Medical Informatics CY SEP 07-11, 2004 CL Amer Med Informat Assoc, San Francisco, CA SP Int Med Informat Assoc HO Amer Med Informat Assoc DE natural language processing; unified medical language system; information storage and retrieval; evaluation studies AB A pilot study was conducted to evaluate the performance of the MetaMap Transfer (MMTx), a tool that extracts terms from free text and suggests' matches to concepts in the Unified Medical Language System, (UMLS,). Five participants, including a content domain expert and a UMLS Expert, manually extracted and mapped terms to UMLS concepts for two disease summary documents from NLM's consumer health site, Genetic Home Reference. The resulting adjudicated annotations were used as a gold standard. Differences in automated term extraction and mapping between MMTx and MetaMap were noted A failure analysis was conducted to categorize the types of terms not correctly mapped by MMTx. The most frequent type of failure (30%) resulted from missing inferential or world knowledge. Characteristics of each category are discussed We distinguish between classes of failures that may be easily rectified, such as alternative retrieval strategies to extract exact matches, and ones that require additional research, such as coordinating conjunctions, co-reference resolution, and word sense disambiguation. C1 Natl Lib Med, Lister Hill Natl Ctr Biomed Commun, Bethesda, MD USA. RP Divita, G (reprint author), Natl Lib Med, Lister Hill Natl Ctr Biomed Commun, Bethesda, MD USA. NR 8 TC 11 Z9 11 U1 1 U2 2 PU I O S PRESS PI AMSTERDAM PA NIEUWE HEMWEG 6B, 1013 BG AMSTERDAM, NETHERLANDS SN 0926-9630 BN 1-58603-444-8 J9 ST HEAL T PY 2004 VL 107 BP 763 EP 767 PG 5 WC Computer Science, Information Systems; Medical Informatics SC Computer Science; Medical Informatics GA BBO53 UT WOS:000226723300153 PM 15360915 ER PT S AU Antani, S Long, LR Thoma, GR AF Antani, S Long, LR Thoma, GR BE Fieschi, M Coiera, E Li, YCJ TI Content-based image retrieval for large biomedical image archives SO MEDINFO 2004: PROCEEDINGS OF THE 11TH WORLD CONGRESS ON MEDICAL INFORMATICS, PT 1 AND 2 SE STUDIES IN HEALTH TECHNOLOGY AND INFORMATICS LA English DT Proceedings Paper CT 11th World Congress on Medical Informatics CY SEP 07-11, 2004 CL Amer Med Informat Assoc, San Francisco, CA SP Int Med Informat Assoc HO Amer Med Informat Assoc DE image processing; information storage and retrieval; multimedia databases; medical informatics applications ID EXTRACTION AB Content-Based Image Retrieval (CBIR) has been a topic of research interest for nearly a decade. Approaches to date use image features for describing content. A survey of the literature shows that progress has been limited to prototype systems that make gross assumptions and approximations. Additionally, research attention has been largely focused on stock image collections. Advances in medical imaging have led to growth in large image collections. At the Lister Hill National Center for Biomedical Communication, an R&D division of the National Library of Medicine, we are conducting research on CBIR for biomedical images. We maintain an archive of over 17, 000 digitized x-rays of the cervical and lumbar spine from the second National Health and Nutrition Examination Survey (NHANES II). In addition, we are developing an archive of a large number of digitized 35 mm color slides of the uterine cervix. Our research focuses on developing techniques for hybrid text/image query-retrieval from the survey text and image data. In this paper we present the challenges in developing CBIR of biomedical images and results from our research efforts. C1 Natl Lib Med, Lister Hill Natl Ctr Biomed Commun, US Dept HHS, NIH, Bethesda, MD 20894 USA. RP Antani, S (reprint author), Natl Lib Med, Lister Hill Natl Ctr Biomed Commun, US Dept HHS, NIH, 8600 Rockville Pike,Mail Stop 55, Bethesda, MD 20894 USA. OI Antani, Sameer/0000-0002-0040-1387 NR 13 TC 2 Z9 2 U1 0 U2 1 PU I O S PRESS PI AMSTERDAM PA NIEUWE HEMWEG 6B, 1013 BG AMSTERDAM, NETHERLANDS SN 0926-9630 BN 1-58603-444-8 J9 ST HEAL T PY 2004 VL 107 BP 829 EP 833 PG 5 WC Computer Science, Information Systems; Medical Informatics SC Computer Science; Medical Informatics GA BBO53 UT WOS:000226723300166 PM 15360928 ER PT S AU Gemoets, D Rosemblat, G Tse, T Logan, R AF Gemoets, D Rosemblat, G Tse, T Logan, R BE Fieschi, M Coiera, E Li, YCJ TI Assessing readability of consumer health information: An exploratory study SO MEDINFO 2004: PROCEEDINGS OF THE 11TH WORLD CONGRESS ON MEDICAL INFORMATICS, PT 1 AND 2 SE STUDIES IN HEALTH TECHNOLOGY AND INFORMATICS LA English DT Proceedings Paper CT 11th World Congress on Medical Informatics CY SEP 07-11, 2004 CL Amer Med Informat Assoc, San Francisco, CA SP Int Med Informat Assoc HO Amer Med Informat Assoc DE readability; patient education; linguistics; evaluation studies; communication barriers ID QUALITY AB Researchers and practitioners frequently use readability formulas to predict the suitability of health-related texts for consumers (e.g., patient instructions, informed consent documents). However, the appropriateness of using readability formulas-originally developed for students and educational texts-for lay audiences and health-related texts remains to be validated In this exploratory study, we compared two methods of assessing the readability of consumer health materials: the Cloze procedure, using actual readers, and readability formulas, using our Readability Analyzer program. A statistically significant inverse correlation (r = -0.581, p = 0.01) was found, suggesting that the Readability Analyzer may provide a reasonable "first approximation" for predicting readability of consumer health texts. We also identified several linguistic factors associated with increased reading ease as candidates for improving the performance of the Readability Analyzer. Our ultimate objective is to develop tools to support the design and evaluation of health information that is comprehensible and accessible to laypersons. C1 Natl Lib Med, Lister Hill Natl Ctr Biomed Commun, Bethesda, MD USA. RP Gemoets, D (reprint author), Natl Lib Med, Lister Hill Natl Ctr Biomed Commun, Bethesda, MD USA. NR 15 TC 14 Z9 14 U1 0 U2 2 PU I O S PRESS PI AMSTERDAM PA NIEUWE HEMWEG 6B, 1013 BG AMSTERDAM, NETHERLANDS SN 0926-9630 BN 1-58603-444-8 J9 ST HEAL T PY 2004 VL 107 BP 869 EP 873 PG 5 WC Computer Science, Information Systems; Medical Informatics SC Computer Science; Medical Informatics GA BBO53 UT WOS:000226723300174 PM 15360936 ER PT S AU Logan, RA AF Logan, RA BE Fieschi, M Coiera, E Li, YCJ TI Evaluating consumer informatics: Learning from health campaign research SO MEDINFO 2004: PROCEEDINGS OF THE 11TH WORLD CONGRESS ON MEDICAL INFORMATICS, PT 1 AND 2 SE STUDIES IN HEALTH TECHNOLOGY AND INFORMATICS LA English DT Proceedings Paper CT 11th World Congress on Medical Informatics CY SEP 07-11, 2004 CL Amer Med Informat Assoc, San Francisco, CA SP Int Med Informat Assoc HO Amer Med Informat Assoc DE consumer health informatics; opinion/future vision paper; evaluation studies; communication barriers AB This paper suggests that some conceptual models used in health communication campaigns as well as the '' uses and gratifications '' approach might be successfully integrated into the evaluation of consumer informatics. These models and tools are especially pertinent when the desired outcomes of media health interventions are therapeutic changes in public knowledge, motivations, attitudes and patient behavior. C1 Natl Lib Med, Lister Hill Natl Ctr Biomed Commun, Bethesda, MD USA. RP Logan, RA (reprint author), Natl Lib Med, Lister Hill Natl Ctr Biomed Commun, Bethesda, MD USA. NR 23 TC 1 Z9 1 U1 0 U2 0 PU I O S PRESS PI AMSTERDAM PA NIEUWE HEMWEG 6B, 1013 BG AMSTERDAM, NETHERLANDS SN 0926-9630 BN 1-58603-444-8 J9 ST HEAL T PY 2004 VL 107 BP 1147 EP 1151 PG 5 WC Computer Science, Information Systems; Medical Informatics SC Computer Science; Medical Informatics GA BBO53 UT WOS:000226723300231 PM 15360992 ER PT S AU McCray, AT Ide, NC Loane, RR Tse, T AF McCray, AT Ide, NC Loane, RR Tse, T BE Fieschi, M Coiera, E Li, YCJ TI Strategies for supporting consumer health information seeking SO MEDINFO 2004: PROCEEDINGS OF THE 11TH WORLD CONGRESS ON MEDICAL INFORMATICS, PT 1 AND 2 SE STUDIES IN HEALTH TECHNOLOGY AND INFORMATICS LA English DT Proceedings Paper CT 11th World Congress on Medical Informatics CY SEP 07-11, 2004 CL Amer Med Informat Assoc, San Francisco, CA SP Int Med Informat Assoc HO Amer Med Informat Assoc DE databases; information services; information storage and retrieval; Internet; terminology ID RETRIEVAL; USERS AB Despite a growing number of available Web-based health information resources, consumers continue to face a variety of barriers as they attempt to access these resources. Developing a system that appropriately responds to user queries poses several challenges. Guided by an earlier study that analyzed a large number of queries submitted to ClinicalTrials.gov, we developed a variety of techniques to assist user information seeking. We tested the efficacy of these techniques by submitting the original user queries to our new search engine to determine if these techniques would result in better system performance. Overall, the number of query failures was reduced, but the largest improvement was found in the system's query suggestion capability. For a subset of query failures, the current system was able to cut the earlier failure rate almost in half in most cases providing a suggestion rather than directly finding records. The techniques described here provide a new approach for responding to user queries. The techniques are tolerant of certain types of errors. and provide feedback to assist users in reformulating their queries. C1 Natl Lib Med, Bethesda, MD USA. RP McCray, AT (reprint author), Natl Lib Med, Bethesda, MD USA. NR 10 TC 7 Z9 7 U1 1 U2 2 PU I O S PRESS PI AMSTERDAM PA NIEUWE HEMWEG 6B, 1013 BG AMSTERDAM, NETHERLANDS SN 0926-9630 BN 1-58603-444-8 J9 ST HEAL T PY 2004 VL 107 BP 1152 EP 1156 PG 5 WC Computer Science, Information Systems; Medical Informatics SC Computer Science; Medical Informatics GA BBO53 UT WOS:000226723300232 PM 15360993 ER PT S AU Hauser, SE Demner-Fushman, D Ford, G Thoma, GR AF Hauser, SE Demner-Fushman, D Ford, G Thoma, GR BE Fieschi, M Coiera, E Li, YCJ TI PubMed on tap: Discovering design principles for online information delivery to handheld computers SO MEDINFO 2004: PROCEEDINGS OF THE 11TH WORLD CONGRESS ON MEDICAL INFORMATICS, PT 1 AND 2 SE STUDIES IN HEALTH TECHNOLOGY AND INFORMATICS LA English DT Proceedings Paper CT 11th World Congress on Medical Informatics CY SEP 07-11, 2004 CL Amer Med Informat Assoc, San Francisco, CA SP Int Med Informat Assoc HO Amer Med Informat Assoc DE handheld computer; computer-assisted decision making ID MEDICINE AB Online access to biomedical information front handheld computers will be a valuable adjunct to other popular medical applications if information delivery systems are designed with handheld computers in mind The goal of this project is to discover design principles to facilitate practitioners' access to online medical information at the point-of-care. A prototype system was developed to serve as a testbed for this research. Using the testbed, an initial evaluation has yielded several user interface design principles. Continued research is expected to discover additional user interface design principles as well as guidelines for results organization and system performance. C1 Lister Hill Natl Ctr Biomed Commun, Natl Lib Med, Bethesda, MD 20894 USA. RP Hauser, SE (reprint author), Lister Hill Natl Ctr Biomed Commun, Natl Lib Med, Bethesda, MD 20894 USA. NR 12 TC 1 Z9 1 U1 0 U2 0 PU I O S PRESS PI AMSTERDAM PA NIEUWE HEMWEG 6B, 1013 BG AMSTERDAM, NETHERLANDS SN 0926-9630 BN 1-58603-444-8 J9 ST HEAL T PY 2004 VL 107 BP 1430 EP 1433 PG 4 WC Computer Science, Information Systems; Medical Informatics SC Computer Science; Medical Informatics GA BBO53 UT WOS:000226723300290 PM 15361051 ER PT S AU Gillen, JE Tse, T Ide, NC McCray, AT AF Gillen, JE Tse, T Ide, NC McCray, AT BE Fieschi, M Coiera, E Li, YCJ TI Design, implementation and management of a web-based data entry system for ClinicalTrials.gov SO MEDINFO 2004: PROCEEDINGS OF THE 11TH WORLD CONGRESS ON MEDICAL INFORMATICS, PT 1 AND 2 SE STUDIES IN HEALTH TECHNOLOGY AND INFORMATICS LA English DT Proceedings Paper CT 11th World Congress on Medical Informatics CY SEP 07-11, 2004 CL Amer Med Informat Assoc, San Francisco, CA SP Int Med Informat Assoc HO Amer Med Informat Assoc DE software design; user-computer interface; online systems; Internet; clinical trials; information management AB We describe the development and deployment of a web-based authoring capability, the first implementation of which is used for data entry and management in support of the ClinicalTrials.gov web site. The system facilitates efficient collection of summary protocol information from multiple geographically-dispersed organizations. We explain the motivation for developing this capability, and cite critical design goals. We then describe system design, implementation and operation, focusing on essential aspects of each. We conclude with a summary of the extent to which we met our stated objectives. C1 US Natl Lib Med, Lister Hill Natl Ctr Biomed Commun, Bethesda, MD 20894 USA. RP McCray, AT (reprint author), US Natl Lib Med, Lister Hill Natl Ctr Biomed Commun, 8600 Rockville Pike, Bethesda, MD 20894 USA. NR 8 TC 17 Z9 17 U1 0 U2 0 PU I O S PRESS PI AMSTERDAM PA NIEUWE HEMWEG 6B, 1013 BG AMSTERDAM, NETHERLANDS SN 0926-9630 BN 1-58603-444-8 J9 ST HEAL T PY 2004 VL 107 BP 1466 EP 1470 PG 5 WC Computer Science, Information Systems; Medical Informatics SC Computer Science; Medical Informatics GA BBO53 UT WOS:000226723300297 PM 15361058 ER PT J AU Crawley, JN AF Crawley, JN TI Designing mouse behavioral tasks relevant to autistic-like behaviors SO MENTAL RETARDATION AND DEVELOPMENTAL DISABILITIES RESEARCH REVIEWS LA English DT Review DE autism; mice; social interaction; ultrasonic vocalizatons; olfactory communication; reversal learning; social approach; anxiety ID ANXIETY-LIKE BEHAVIOR; OVEREXPRESSING TRANSGENIC MICE; FRAGILE-X-SYNDROME; SENSORIMOTOR GATING ABNORMALITIES; QUANTITATIVE TRAIT LOCUS; LEMLI-OPITZ-SYNDROME; ANIMAL-MODELS; KNOCKOUT MICE; CANDIDATE GENES; MUTANT MICE AB The importance of genetic factors in autism has prompted the development of mutant mouse models to advance our understanding of biological mechanisms underlying autistic behaviors. Mouse models of human neuropsychiatric diseases are designed to optimize (1) face validity, i.e., resemblance to the human symptoms; (2) construct validity, i.e., similarity to the underlying causes of the disease; and (3) predictive validity, i.e., expected responses to treatments that are effective in the human disease. There is a growing need for mouse behavioral tasks with all three types of validity for modeling the symptoms of autism. We are in the process of designing a set of tasks with face validity for the defining features of autism: deficits in appropriate reciprocal social interactions, deficits in verbal social communication, and high levels of ritualistic repetitive behaviors. Social approach is tested in an automated three-chambered apparatus that offers the subject a choice between a familiar environment, a novel environment, and a novel environment containing a stranger mouse. Preference for social novelty is tested in the same apparatus, with a choice between the start chamber, the chamber containing a familiar mouse, and the chamber containing a stranger mouse. Social communication is evaluated by measuring the ultrasonic distress vocalizations emitted by infant mouse pups and the parental response of retrieving the pup to the nest. Resistance to change in ritualistic repetitive behaviors is modeled by forcing a change in habit, including reversal of the spatial location of a reinforcer in a T-maze task and in the Morris water maze. Mouse behavioral tasks that may model additional features of autism are discussed, including tasks relevant to anxiety, seizures, sleep disturbances, and sensory hypersensitivity. Applications of these tests include (1) behavioral phenotyping of transgenic and knockout mice with mutations in genes relevant to autism, (2) characterization of mutant mice derived from random chemical mutagenesis, (3) DNA microarray analyses of genes in inbred strains of mice that differ in social interaction, social communication and resistance to change in habit, and (4) evaluation of proposed therapeutics for the treatment of autism. Published 2004 Wiley-Liss, Inc. C1 Univ N Carolina, Mouse Behav Phenotyping Lab, Neurodev Disorders Res Ctr, Chapel Hill, NC 27514 USA. NIMH, Lab Behav Neurosci, Intramural Res Program, Bethesda, MD USA. RP Crawley, JN (reprint author), Univ N Carolina, Mouse Behav Phenotyping Lab, Neurodev Disorders Res Ctr, Chapel Hill, NC 27514 USA. EM crawleyj@intra.nimh.nih.gov FU NIMH NIH HHS [MH66418] NR 174 TC 197 Z9 204 U1 18 U2 33 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1080-4013 J9 MENT RETARD DEV D R JI Ment. Retard. Dev. Disabil. Res. Rev. PY 2004 VL 10 IS 4 BP 248 EP 258 DI 10.1002/mrdd.20039 PG 11 WC Clinical Neurology; Neurosciences; Pediatrics; Psychiatry SC Neurosciences & Neurology; Pediatrics; Psychiatry GA 892VA UT WOS:000226676900004 PM 15666335 ER PT J AU Lawler, CP Croen, LA Grether, JK Van de Water, J AF Lawler, CP Croen, LA Grether, JK Van de Water, J TI Identifying environmental contributions to autism: Provocative clues and false leads SO MENTAL RETARDATION AND DEVELOPMENTAL DISABILITIES RESEARCH REVIEWS LA English DT Review DE autism; epidemiology; prevalence; neurotoxicology; surveillance; toxicokinetics; environmental response genes; gene-environment interaction; genetic susceptibility; immunology; children's environmental health; epigenetics; exposure assessment ID CENTRAL-NERVOUS-SYSTEM; POLYCYCLIC AROMATIC-HYDROCARBONS; MENTAL-RETARDATION; NEURODEVELOPMENTAL DISORDERS; ALPHA-NAPHTHOFLAVONE; MULTIPLE-SCLEROSIS; CHILDRENS HEALTH; ANIMAL-MODELS; PREVALENCE; CYTOKINES AB The potential role of environmental factors in autism spectrum disorders (ASD) is an area of emerging interest within the public and scientific communities. The high degree of heritability of ASD suggests that environmental influences are likely to operate through their interaction with genetic susceptibility during vulnerable periods of development. Evaluation of the plausibility of specific neurotoxicants as etiological agents in ASD should be guided by toxicological principles, including dose-effect dependency and pharmacokinetic parameters. Clinical and epidemiological investigations require the use of sufficiently powered study designs with appropriate control groups and unbiased case ascertainment and exposure assessment. Although much of the existing data that have been used to implicate environmental agents in ASD are limited by methodological shortcomings, a number of efforts are underway that will allow more rigorous evaluation of the role of environmental exposures in the etiology and/or phenotypic expression of the disorder. Surveillance systems are now in place that will provide reliable prevalence estimates going forward in time. Anticipated discoveries in genetics, brain pathology, and the molecular/cellular basis of functional impairment in ASD are likely to provide new opportunities to explore environmental aspects of this disorder. (C) 2004 Wiley-Liss, Inc. C1 NIEHS, Div Extramural Res & Training, Res Triangle Pk, NC 27709 USA. Kaiser Permanente No California, Div Res, Oakland, CA USA. Calif Dept Hlth Serv, Environm Hlth Invest Branch, Oakland, CA USA. Univ Calif Davis, Dept Internal Med, Davis, CA 95616 USA. RP Lawler, CP (reprint author), NIEHS, Div Extramural Res & Training, POB 1123,MD EC 23, Res Triangle Pk, NC 27709 USA. EM lawler@niehs.nih.gov NR 87 TC 50 Z9 53 U1 2 U2 7 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1080-4013 J9 MENT RETARD DEV D R JI Ment. Retard. Dev. Disabil. Res. Rev. PY 2004 VL 10 IS 4 BP 292 EP 302 DI 10.1002/mrdd.20043 PG 11 WC Clinical Neurology; Neurosciences; Pediatrics; Psychiatry SC Neurosciences & Neurology; Pediatrics; Psychiatry GA 892VA UT WOS:000226676900008 PM 15666339 ER PT J AU Hopkins, JCA Radda, GK Veech, RL Clarke, K AF Hopkins, JCA Radda, GK Veech, RL Clarke, K TI Accumulation of 2-deoxy-D-glucose-6-phosphate as a measure of glucose uptake in the isolated perfused heart: a P-31 NMR study SO METABOLIC ENGINEERING LA English DT Article DE 2-deoxy-D-glucose; 2-deoxy-D-glucose-6-phosphate accumulation; [2-H-3]glucose uptake; P-31 NMR spectroscopy ID POSITRON-EMISSION-TOMOGRAPHY; RAT-HEART; SKELETAL-MUSCLE; 2-DEOXYGLUCOSE UPTAKE; CONTRACTILE FUNCTION; PRESSURE-OVERLOAD; LUMPED CONSTANT; IN-VIVO; INSULIN; SENSITIVITY AB The accumulation of 2-deoxy-D-glucose-6-phosphate (2DG6P), detected using P-31 NMR spectroscopy, has been used as a measure of the rate of glucose uptake, yet the accuracy of this measurement has not been verified. In this study, isolated rat hearts were perfused with different substrates or isoproterenol for 30 min before measurement of either 2DG6P accumulation or [2-H-3]glucose uptake, without and with insulin. Basal contractile function and metabolite concentrations were the same for all hearts. The basal rates of 2DG6P accumulation differed significantly, depending on the preceding perfusion protocol, and were 38-60% of the [2-H-3]glucose uptake rates, whereas insulin-stimulated 2DG6P accumulation was the same or 71% higher than the [2-H-3]glucose uptake rates. Therefore the ratio of 2DG6P accumulation/[2-H-3]glucose uptake rates varied from 0.38 to 1.71, depending on the prior perfusion conditions or the presence of insulin. The rates of 2DG6P hydrolysis were found to be proportional to the intracellular 2DG6P concentrations, with a K-m of 17.5 mM and V-max of 1.4 mumol/g dry weight/min. We conclude that the rates of 2DG6P accumulation do not accurately reflect glucose uptake rates under all physiological conditions in the isolated heart and should be used with caution. (C) 2003 Elsevier Inc. All rights reserved. C1 Univ Oxford, Physiol Lab, Oxford OX1 3PT, England. NIAAA, Lab Membrane Biochem & Biophys, Rockville, MD 20852 USA. RP Clarke, K (reprint author), Univ Oxford, Physiol Lab, S Parks Rd, Oxford OX1 3PT, England. EM kieran.clarke@bioch.ox.ac.uk FU British Heart Foundation [PS/02/002/14893] NR 34 TC 3 Z9 3 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 1096-7176 J9 METAB ENG JI Metab. Eng. PD JAN PY 2004 VL 6 IS 1 BP 36 EP 43 DI 10.1016/j.ymben.2003.10.002 PG 8 WC Biotechnology & Applied Microbiology SC Biotechnology & Applied Microbiology GA 769QR UT WOS:000188661700005 PM 14734254 ER PT S AU Tchounwou, PB Ayensu, WK AF Tchounwou, PB Ayensu, WK BE Cser, MA Laszlo, IS Etienne, JC Maymard, Y Centeno, JA Khassanova, L Collery, P TI Health risk assessment and management of mercury poisoning SO METAL IONS IN BIOLOGY AND MEDICINE, VOL 8 SE METAL IONS IN BIOLOGY AND MEDICINE LA English DT Proceedings Paper CT 8th International Symposium on Metal Ions in Biology and Medicine CY MAY 18-22, 2004 CL Hungarian Acad Sci, Budapest, HUNGARY SP Bethesda Childrens Hosp Hungarian Reformed Church, KFKI Atom Energy Res Inst, Armed Forces Inst Pathol, Faustus Canc Res Inst HO Hungarian Acad Sci ID EXPOSURE; METHYLMERCURY; SYSTEM; RAT AB Mercury is an environmental contaminant derived from volcanic eruptions, erosions, as well as from anthropogenic activities such as metal smelting, and industrial production and use. Catastrophic outbreaks of mercury-induced diseases and mortalities have occurred in many areas of the world including Japan, Iraq, Ghana, the Seychelles, and the Faroe islands over the years. Human exposure to mercury is primarily through the diet and drinking water, and to a lesser extent through inhalation, and dermal contact. Cardiovascular disease, anemia, developmental abnormalities, neurobehavioral disorders, kidney damage, and death in some cases have been associated with mercury exposure. Its creeping neurotoxicity is highly devastating particularly in the central and peripheral nervous systems of children. Necrotizing bronchitis and pneumonitis arising from inhalation of mercury vapor can result in respiratory failure. Mercury toxicity depends on its chemical species, with the methylated form causing the most damage. Its biohazard has been associated with its ability to interact with sulfhydryl groups of proteins and enzymes, to damage DNA, and to modulate cell cycle progression and/or apoptosis. In this review, we provide useful information with regard to mercury toxicology, and the important considerations for health risk assessment and management. C1 Jackson State Univ, Coll Sci Engn & Technol, Cellom & Toxicogenom Res Lab, NIH,Ctr Environm Hlth, Jackson, MS 39217 USA. RP Tchounwou, PB (reprint author), Jackson State Univ, Coll Sci Engn & Technol, Cellom & Toxicogenom Res Lab, NIH,Ctr Environm Hlth, 1400 Lynch St,Box 18540, Jackson, MS 39217 USA. NR 20 TC 0 Z9 0 U1 0 U2 5 PU JOHN LIBBEY EUROTEXT PI MONTROUGE PA 127 AVE DE LA REPUBLIQUE, 92120 MONTROUGE, FRANCE SN 1257-2535 BN 2-7420-0522-6 J9 METAL IONS BIOL MED PY 2004 VL 8 BP 8 EP 13 PG 6 WC Biochemistry & Molecular Biology; Chemistry, Inorganic & Nuclear; Nutrition & Dietetics; Toxicology SC Biochemistry & Molecular Biology; Chemistry; Nutrition & Dietetics; Toxicology GA BBU67 UT WOS:000227913400002 ER PT S AU Tchounwou, PB Patlolla, AK Centeno, JA AF Tchounwou, PB Patlolla, AK Centeno, JA BE Cser, MA Laszlo, IS Etienne, JC Maymard, Y Centeno, JA Khassanova, L Collery, P TI Health risk assessment and management of arsenic toxicity and carcinogenesis SO METAL IONS IN BIOLOGY AND MEDICINE, VOL 8 SE METAL IONS IN BIOLOGY AND MEDICINE LA English DT Proceedings Paper CT 8th International Symposium on Metal Ions in Biology and Medicine CY MAY 18-22, 2004 CL Hungarian Acad Sci, Budapest, HUNGARY SP Bethesda Childrens Hosp Hungarian Reformed Church, KFKI Atom Energy Res Inst, Armed Forces Inst Pathol, Faustus Canc Res Inst HO Hungarian Acad Sci DE arsenic; health risk; assessment; management ID DRINKING-WATER; ENDEMIC AREA; BLADDER; CANCER; TAIWAN; CELLS AB Arsenic is one of the most important environmental toxicants. Cardiovascular diseases, developmental abnormalities, neurologic and neurobehavioral disorders, diabetes, hearing loss, heamatologic disorders, and various types of cancer, including skin, and lung neoplasms, have all been associated with human exposure to arsenic. Both acute and chronic exposures have been reported in several countries of the world, where a large proportion of drinking water is contaminated with high concentrations of arsenic. Recent epidemiologic studies have demonstrated a strong correlation between arsenic exposure and the increase in incidence of human cancer. Research has also pointed out significantly higher standardized mortality rates for cancers of the bladder, kidney, skin, liver, and colon in many areas of arsenic pollution. There is therefore a great need for developing a comprehensive risk assessment (RA) model, to be used in the management of health risks associated with arsenic exposure. This paper aims at using the National Academy of Scienceis RA paradigm as a guide; to present a conceptual RA framework for managing the potential risks of toxicity and carcinogenesis associated with arsenic exposure. C1 Jackson State Univ, Coll Sci Engn & Technol, Mol Toxicol Res Lab, NIH,Ctr Environm Hlth, Jackson, MS 39217 USA. RP Tchounwou, PB (reprint author), Jackson State Univ, Coll Sci Engn & Technol, Mol Toxicol Res Lab, NIH,Ctr Environm Hlth, Jackson, MS 39217 USA. NR 27 TC 0 Z9 0 U1 1 U2 1 PU JOHN LIBBEY EUROTEXT PI MONTROUGE PA 127 AVE DE LA REPUBLIQUE, 92120 MONTROUGE, FRANCE SN 1257-2535 BN 2-7420-0522-6 J9 METAL IONS BIOL MED PY 2004 VL 8 BP 14 EP 18 PG 5 WC Biochemistry & Molecular Biology; Chemistry, Inorganic & Nuclear; Nutrition & Dietetics; Toxicology SC Biochemistry & Molecular Biology; Chemistry; Nutrition & Dietetics; Toxicology GA BBU67 UT WOS:000227913400003 ER PT S AU Tchounwou, PB Sutton, DJ AF Tchounwou, PB Sutton, DJ BE Cser, MA Laszlo, IS Etienne, JC Maymard, Y Centeno, JA Khassanova, L Collery, P TI Mercury-induced externalization of phosphaticlylserine in human liver carcinoma (HEPG(2)) cells SO METAL IONS IN BIOLOGY AND MEDICINE, VOL 8 SE METAL IONS IN BIOLOGY AND MEDICINE LA English DT Proceedings Paper CT 8th International Symposium on Metal Ions in Biology and Medicine CY MAY 18-22, 2004 CL Hungarian Acad Sci, Budapest, HUNGARY SP Bethesda Childrens Hosp Hungarian Reformed Church, KFKI Atom Energy Res Inst, Armed Forces Inst Pathol, Faustus Canc Res Inst HO Hungarian Acad Sci DE mercury; early-stage apoptosis; flow cytometry; HepG(2) cells ID APOPTOSIS AB Programmed cell death (apoptosis) is a normal physiologic process, which occurs during embryonic development as well as in the maintenance of tissue homeostasis. It functions as a mechanism to eliminate unwanted or irreparably damaged cells. However, inappropriate induction of apoptosis by environmental agents has broad ranging pathologic implications and has been associated with several diseases including cancer. The toxicity of several heavy metals such as mercury has been attributed to their high affinity to sulfhydryl groups of proteins and enzymes, and their ability to disrupt cell cycle progression and/or apoptosis in various tissues. The aim of this study was to assess the potential for mercury to induce early-stage apoptosis in human liver carcinoma (HepG(2)) cells. Annexin-V assay was performed by flow cytometry to determine the extent of phosphatidylserine externalization in mercury-treated HepG(2) cells. Cells were exposed to mercury for 10 hours at doses of 0, 1, 2, and 3 mu g/mL based on previous cytotoxicity results in our laboratory indicating an LD50 of 3.5 +/- 0.6 mu g/mL for mercury in HepG(2) cells. The study data indicated a dose response relationship between mercury exposure and the degree of early apoptosis in HepG(2) cells. The percentages of cells undergoing early apoptosis were 0.03 +/- 0.03%, 5.19 +/- 0.04%, 6.36 +/- 0.04%, and 8.84 +/- 0.02% for 0, 1, 2, and 3 mu g/mL of mercury respectively, indicating a gradual increase in apoptotic cells with increasing doses of mercury. C1 Jackson State Univ, Dept Chem, Coll Sci Engn & Technol, NIH,Ctr Environm Hlth,Mol Toxicol Res Lab, Jackson, MS 39217 USA. RP Tchounwou, PB (reprint author), Jackson State Univ, Dept Chem, Coll Sci Engn & Technol, NIH,Ctr Environm Hlth,Mol Toxicol Res Lab, 1400 Lynch St,Box 18540, Jackson, MS 39217 USA. NR 11 TC 1 Z9 1 U1 0 U2 1 PU JOHN LIBBEY EUROTEXT PI MONTROUGE PA 127 AVE DE LA REPUBLIQUE, 92120 MONTROUGE, FRANCE SN 1257-2535 BN 2-7420-0522-6 J9 METAL IONS BIOL MED PY 2004 VL 8 BP 123 EP 126 PG 4 WC Biochemistry & Molecular Biology; Chemistry, Inorganic & Nuclear; Nutrition & Dietetics; Toxicology SC Biochemistry & Molecular Biology; Chemistry; Nutrition & Dietetics; Toxicology GA BBU67 UT WOS:000227913400024 ER PT S AU Tchounwou, PB Patlolla, AK Centeno, JA AF Tchounwou, PB Patlolla, AK Centeno, JA BE Cser, MA Laszlo, IS Etienne, JC Maymard, Y Centeno, JA Khassanova, L Collery, P TI Serum aminotransferases as biomarkers of arsenic-induced hepatotoxicity in Sprague-Dawley rats SO METAL IONS IN BIOLOGY AND MEDICINE, VOL 8 SE METAL IONS IN BIOLOGY AND MEDICINE LA English DT Proceedings Paper CT 8th International Symposium on Metal Ions in Biology and Medicine CY MAY 18-22, 2004 CL Hungarian Acad Sci, Budapest, HUNGARY SP Bethesda Childrens Hosp Hungarian Reformed Church, KFKI Atom Energy Res Inst, Armed Forces Inst Pathol, Faustus Canc Res Inst HO Hungarian Acad Sci DE arsenic; aminotransferases; biornarkers; hepatotoxicity; Sprague-Dawley rats AB One of the major mechanisms by which arsenic exerts its toxic effect is through an impairment of cellular respiration by inhibition of various mitochondrial enzymes, and the uncoupling of oxidative phosphorylation. Most toxicity of arsenic results from its ability to interact with sulfhydryl groups of proteins and enzymes, and to substitute phosphorus in a variety of biochemical reactions. Although the evidence of carcinogenicity of arsenic seems strong, the mechanism by which it produces tumors is not completely understood. The aim of the study was to conduct biochemical analyses to determine the effect of arsenic trioxide on the activities of specific enzymes including alanine and aspartate aminotransferases, which may be useful as biomarkers of sensitivity and effect associated with arsenic exposure. Four groups of six male rats each weighing approximately 60 g were injected intraperitoneally, once a day for five days with doses of 5, 10, 15, 20 mg/kg body weight of arsenic trioxide dissolved in distilled water. A control group was also made of 6 animals injected with distilled water without chemical. Following anaesthetization, Blood specimens were immediately collected using heparinized syringes, and enzyme identification and quantification were performed in serum samples by spectrophotometry. Arsenic trioxide induced statistically significant increase (p < 0.05) in the activities of both alanine aminotransferases-glutamate pyruvate transaminase (GPT), and aspartate aminotransferase-glutamate oxaloacetate transaminase (GOT). Optical density readings of 0.568 +/- 0.005, 0.572 +/- 0.003, 0.585 +/- 0.010, 0.602 +/- 0.003, and 0.618 +/- 0.007 (GPT), and of 0.657 +/- 0.005, 0.683 +/- 0.004, 0.693 +/- 0.019, 0.706 +/- 0.010, and 0.791 +/- 0.025 (GOT) were recorded for 0, 5, 10, 15, and 20 rng/kg, respectively; indicating a gradual increase in aminotransferases activities with increasing doses of arsenic. These findings indicate that aminotransferases are candidate biomarkers for arsenic-induced hepatotoxicity in Sprague-Dawley rats. C1 Jackson State Univ, Coll Sci Engn & Technol, Mol Toxicol Res Lab, NIH Ctr Environm Hlth, Jackson, MS USA. RP Tchounwou, PB (reprint author), Jackson State Univ, Coll Sci Engn & Technol, Mol Toxicol Res Lab, NIH Ctr Environm Hlth, Jackson, MS USA. NR 14 TC 2 Z9 2 U1 0 U2 0 PU JOHN LIBBEY EUROTEXT PI MONTROUGE PA 127 AVE DE LA REPUBLIQUE, 92120 MONTROUGE, FRANCE SN 1257-2535 BN 2-7420-0522-6 J9 METAL IONS BIOL MED PY 2004 VL 8 BP 284 EP 288 PG 5 WC Biochemistry & Molecular Biology; Chemistry, Inorganic & Nuclear; Nutrition & Dietetics; Toxicology SC Biochemistry & Molecular Biology; Chemistry; Nutrition & Dietetics; Toxicology GA BBU67 UT WOS:000227913400062 ER PT J AU Cho, NH Choi, CY Seong, SY AF Cho, NH Choi, CY Seong, SY TI Down-regulation of gp96 by Orientia tsutsugamushi SO MICROBIOLOGY AND IMMUNOLOGY LA English DT Article DE gp96; Orientia tsutsugamushi ID HEAT-SHOCK PROTEINS; RECEPTOR-MEDIATED ENDOCYTOSIS; CYTOTOXIC T-LYMPHOCYTE; CLASS-I MOLECULES; DENDRITIC CELLS; RICKETTSIA-TSUTSUGAMUSHI; ENDOPLASMIC-RETICULUM; ANTIGEN PRESENTATION; SURFACE EXPRESSION; PEPTIDE COMPLEXES AB gp96 plays a central role in innate as well as acquired immunity, maturation and chemotaxis of dendritic cells, Ab production, and cross-priming, and is a peptide acceptor in endoplasmic reticulum and an accessory to peptide loading of MHC class I molecules. The remarkable conservation of essential immunological properties of gp96 suggests their important roles during the evolution of the immune system. Considering their importance in immunity, immune evasion mechanisms of pathogens by modulating gp96 expression have been speculated. By differential display PCR, we observed that obligate intracellular bacteria, Orientia tsutsugamushi, inhibit gp96 expression of a macrophage cell line, J774A.1. Not only gp96 transcripts but also protein was lower than for null-infected cells. The down-regulation was also consistent in an endothelial cell line, HMEC-1, and in murine peritoneal cells. These data support the idea that gp96 may be one of the target molecules for the immune evasion by intracellular bacteria. C1 Seoul Natl Univ, Coll Med, Dept Microbiol & Immunol, Seoul 110799, South Korea. NIAID, Cellular & Mol Immunol Lab, Bethesda, MD 20892 USA. NICHHD, Lab Gene Regulat & Dev, NIH, Rockville, MD 20852 USA. RP Seong, SY (reprint author), Seoul Natl Univ, Coll Med, Dept Microbiol & Immunol, Seoul 110799, South Korea. EM seongsy@snu.ac.kr RI Cho, Nam-Hyuk/D-6032-2012; Seong, Seung Yong /J-2764-2012 NR 55 TC 10 Z9 11 U1 0 U2 4 PU CENTER ACADEMIC PUBL JAPAN PI TOKYO PA 2-4-16 YAYOI, BUNKYO-KU, TOKYO, 113-0032, JAPAN SN 0385-5600 J9 MICROBIOL IMMUNOL JI Microbiol. Immunol. PY 2004 VL 48 IS 4 BP 297 EP 305 PG 9 WC Immunology; Microbiology SC Immunology; Microbiology GA 810CU UT WOS:000220683200010 PM 15107540 ER PT J AU Ramachandran, S Kumar, MP Rami, RMV Chinnaiah, HB Nutman, T Kaliraj, P McCarthy, J AF Ramachandran, S Kumar, MP Rami, RMV Chinnaiah, HB Nutman, T Kaliraj, P McCarthy, J TI The larval specific lymphatic filarial ALT-2: Induction of protection using protein or DNA vaccination SO MICROBIOLOGY AND IMMUNOLOGY LA English DT Article DE ALT-2; lymphatic filariasis; DNA vaccination ID ONCHOCERCA-VOLVULUS INFECTION; GLUTATHIONE-S-TRANSFERASE; BRUGIA-MALAYI INFECTION; PAPUA-NEW-GUINEA; BANCROFTIAN FILARIASIS; PUTATIVELY IMMUNE; MERIONES-UNGUICULATUS; ANTIBODY-RESPONSES; BALB/C MICE; ANTIGENS AB Genes from the infective stage of lymphatic filarial parasites expressed at the time of host invasion have been identified as potential vaccine candidates. By screening an L3 cDNA library with sera from uninfected longstanding residents of an area endemic for onchocerciasis, so-called "endemic normals" (EN), we have cloned and characterized one such gene termed the abundant larval transcript two (ALT-2). The stage specificity of ALT-2 gene transcription and protein synthesis was confirmed by PCR using gene-specific primers, and by western blot analysis of protein extracts from various stages of the parasite life cycle using specific antisera. Significant differences in antibody response to the recombinant ALT-2 were observed in endemic populations with differing clinical manifestations of lymphatic filariasis with an antibody response present in sera from 18 of 25 (72%) EN subjects compared to 9 of 25 (36%) with subclinical microfilaracmia (MF) and 14 of 25 (52%) of those with chronic lymphatic obstruction (CP) (P=0.01 for comparison of EN to CP or to MF). This differential responsiveness suggests that the protective immunity postulated to account for their uninfected status might be associated with a response to this protein. When the utility of ALT-2 as a vaccine candidate was tested in a murine model using either recombinant protein or a DNA vaccine construct, statistically significant protection was observed when compared to a control filarial gene product expressed across all stages of the parasite lifecycle (SXP-1; P=0.02 for protein and P=0.01 for the DNA vaccine) or compared to adjuvant alone. This level of protection indicates that this vaccine is a promising candidate for further development. C1 Anna Univ, Ctr Biotechnol, Madras 600025, Tamil Nadu, India. Mahatma Gandhi Inst Med Sci, Jamnalal Bajaj Trop Dis Res Ctr, Sevagram, India. NIAID, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA. Univ Western Australia, Hosp Fremantle, Dept Med, Fremantle, WA 6009, Australia. RP Kaliraj, P (reprint author), Anna Univ, Ctr Biotechnol, Madras 600025, Tamil Nadu, India. EM pkaliraj@annauniv.edu RI McCarthy, James/C-1681-2009; Mishra, Pankaj/H-4191-2011 NR 45 TC 48 Z9 48 U1 0 U2 2 PU CENTER ACADEMIC PUBL JAPAN PI TOKYO PA 2-4-16 YAYOI, BUNKYO-KU, TOKYO, 113-0032, JAPAN SN 0385-5600 J9 MICROBIOL IMMUNOL JI Microbiol. Immunol. PY 2004 VL 48 IS 12 BP 945 EP 955 PG 11 WC Immunology; Microbiology SC Immunology; Microbiology GA 880OX UT WOS:000225800200004 PM 15611611 ER PT J AU Isenberg, JS AF Isenberg, JS TI Let it be: Salvage of exposed hemodialysis grafts with fasciocutaneous island flaps SO MICROSURGERY LA English DT Article ID VASCULAR ACCESS; FASCIOSUBCUTANEOUS FLAP; RADIAL ARTERY; FOREARM; COVERAGE; HAND; INFECTION; PATIENT; ELBOW; WRIST AB Contaminated and exposed prosthetic implants have traditionally required surgical explantation. This has been standard treatment, particularly for implants in the central circulation or those bridging major vascular structures, such as hemodialysis grafts. We present our experience in salvaging exposed hemodialysis grafts utilizing regional fascio- and septo-cutaneous flaps. In 5 of 6 cases, graft salvage was achieved, obviating the need for explantation and de novo insertion at another location. In selected instances of hemodialysis graft exposure, wound coverage and graft function can be obtained with regionally based flaps. (C) 2004 Wiley-Liss, Inc. C1 Univ Oklahoma, Dept Oral & Maxillofacial Surg, Norman, OK 73019 USA. RP Isenberg, JS (reprint author), NCI, NIH, Bldg 10,Room 2A29,10 Ctr Dr, Bethesda, MD 20892 USA. NR 27 TC 1 Z9 2 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0738-1085 J9 MICROSURG JI Microsurgery PY 2004 VL 24 IS 2 BP 134 EP 138 DI 10.1002/micr.20010 PG 5 WC Surgery SC Surgery GA 811KE UT WOS:000220770000009 PM 15038019 ER PT J AU Isenberg, JS AF Isenberg, JS TI Nitric oxide modulation of early angiogenesis SO MICROSURGERY LA English DT Article ID ENDOTHELIAL GROWTH-FACTOR; L-ARGININE; IN-VITRO; SYNTHASE; OVEREXPRESSION; PERMEABILITY; ISCHEMIA; PATHWAY AB Angiogenesis is the process of new vessel formation from an existing vasculature network. In all but a few circumstances it is tightly controlled and suppressed. Precise understanding of the factors involved in modulation of angiogenesis has significant potential clinical value. One agent believed to play a role in angiogenesis is nitric oxide. However, there remain substantial uncertainties concerning the specifics of this role. The present study was undertaken to better define the role nitric oxide plays in angiogenesis associated with acute wound healing. Muscle biopsies from the pectoralis major of C57B6 mice were embedded in 500 mul of type I collagen matrix, and incubated in the presence of growth medium for 14 days. Treatment wells received L-Arginine (2 mM), L-NAME (300 muM), or SNAP (10-20 muM). Angiogenic response was quantified as the measure of cell migration through the matrix and as the total cells recovered from the matrix. Whole lung specimens and aorfic segments served as sources of endothelial and vascular smooth muscle cells respectively for proliferation studies under similar treatment conditions. Nitric oxide was found to exert either a stimulatory or inhibitory effect on angiogenesis and cell proliferation that was subject to the assay system and specific vascular cell types present. These results suggest that the role of nitric oxide in angiogenesis is context dependent. (C) 2004 Wiley-Liss, Inc. C1 NCI, NIH, Lab Pathol, Bethesda, MD 20892 USA. RP Isenberg, JS (reprint author), NCI, NIH, Lab Pathol, Bldg 10,Room 2A27,10 Ctr Dr, Bethesda, MD 20892 USA. EM isenberj@mail.nih.gov NR 27 TC 19 Z9 19 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0738-1085 J9 MICROSURG JI Microsurgery PY 2004 VL 24 IS 5 BP 385 EP 391 DI 10.1002/micr.20051 PG 7 WC Surgery SC Surgery GA 859BH UT WOS:000224236500008 PM 15378585 ER PT J AU Jaffe, ES Banks, PM Nathwani, B Said, J Swerdlow, SH AF Jaffe, ES Banks, PM Nathwani, B Said, J Swerdlow, SH CA Ad Hoc Comm reporting lymphoid neo TI Recommendations for the reporting of lymphoid neoplasms: A report from the Association of Directors of Anatomic and Surgical Pathology SO MODERN PATHOLOGY LA English DT Article DE lymph node; lymphoma; Immunohistochemistry; molecular diagnostics; quality assurance; laboratory management AB In this report, the Association of Directors of Anatomic and Surgical Pathology (ADASP) provides guidelines for the reporting of lymphoid neoplasms. The World Health Organization Classification of Tumors of the Haematopoietic and Lymphoid Tissues is the preferred international standard for diagnostic criteria ( disease definition) and nomenclature. Ancillary studies are often required, and the Association recommends that immunophenotypic and genotypic information be integrated into the final report, to the extent possible. C1 NCI, Hematopathol Sect, Pathol Lab, NIH, Bethesda, MD 20892 USA. Carolinas Med Ctr, Charlotte, NC 28203 USA. Univ So Calif, Sch Med, Los Angeles, CA USA. Univ Calif Los Angeles, Med Ctr Hlth Sci, Los Angeles, CA USA. Univ Pittsburgh, Med Ctr, Pittsburgh, PA USA. RP Jaffe, ES (reprint author), NCI, Hematopathol Sect, Pathol Lab, NIH, Bldg 10,Room 2N202,10 Ctr Dr MSC-1500, Bethesda, MD 20892 USA. EM elainejaffe@nih.gov NR 6 TC 20 Z9 24 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD JAN PY 2004 VL 17 IS 1 BP 131 EP 135 DI 10.1038/modpathol.3800028 PG 5 WC Pathology SC Pathology GA 773KE UT WOS:000188922300021 PM 14657953 ER PT J AU Fang, J Zhou, H Rathore, D Sullivan, M Su, XZ McCutchan, TF AF Fang, J Zhou, H Rathore, D Sullivan, M Su, XZ McCutchan, TF TI Ambient glucose concentration and gene expression in Plasmodium falciparum SO MOLECULAR AND BIOCHEMICAL PARASITOLOGY LA English DT Article DE plasmodium falciparum; glucose; PfEMP (var); microarray; malaria; transcription ID RNA HELICASE; FISSION YEAST; LIFE-CYCLE; MALARIA; ERYTHROCYTES; HYPOGLYCEMIA; PARASITES; CHILDREN; PATHWAY C1 NIAID, Lab Malaria & Vector Res, Mol Biol Sect, NIH, Bethesda, MD 20892 USA. RP McCutchan, TF (reprint author), NIAID, Lab Malaria & Vector Res, Mol Biol Sect, NIH, 4 Ctr Dr,Room 4-126, Bethesda, MD 20892 USA. EM tmccutchan@niaid.nih.gov OI Su, Xinzhuan/0000-0003-3246-3248 NR 30 TC 22 Z9 22 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0166-6851 J9 MOL BIOCHEM PARASIT JI Mol. Biochem. Parasitol. PD JAN PY 2004 VL 133 IS 1 BP 125 EP 129 DI 10.1016/j.molbiopara.2003.09.004 PG 5 WC Biochemistry & Molecular Biology; Parasitology SC Biochemistry & Molecular Biology; Parasitology GA 760JC UT WOS:000187807000013 PM 14668019 ER PT J AU Xie, YX Liu, J Liu, YP Klaassen, CD Waalkes, MP AF Xie, YX Liu, J Liu, YP Klaassen, CD Waalkes, MP TI Toxicokinetic and genomic analysis of chronic arsenic exposure in multidrug-resistance mdr1a/1b(-/-) double knockout mice SO MOLECULAR AND CELLULAR BIOCHEMISTRY LA English DT Article; Proceedings Paper CT Conference on Molecular Mechanisms of Metal Toxicity and carcinogenesis CY SEP 08-11, 2002 CL MORGANTOWN, VIRGINIA DE arsenic; genomics; toxicokinetics; mice; multidrug-resistance ID BILIARY-EXCRETION; OXIDATIVE STRESS; EPITHELIAL-CELLS; GLUTATHIONE; OVEREXPRESSION; TRANSPORTER; TOXICOLOGY; MECHANISMS; INDUCTION; TOLERANCE AB Multidrug- resistance gene knockout mdr1a/ 1b( -/ -) mice, which are deficient in P- glycoproteins, are more sensitive than wildtype ( WT) mice to acute arsenic toxicity. This study assessed toxic manifestations of chronic oral arsenic in mdr1a/ 1b( -/ -) mice, including oxidative stress and altered gene expression, and investigated altered toxicokinetics as a potential basis of enhanced arsenic toxicity. Thus, mdr1a/ 1b( -/ -) and WT mice were exposed to sodium arsenite ( 0 - 80 ppm as arsenic) in the drinking water for 10 weeks at which time hepatic arsenic accumulation, lipid peroxidation ( LPO), redox status and change in gene expression level were assessed. All mice survived the arsenic exposure, but body weight gain in the highest dose group was reduced in both mdr1a/ 1b( -/ -) and WT mice. Arsenic induced pathological changes, elevated LPO levels and enhanced glutathione S- transferase ( GST) activity, in the liver to a greater extent in mdr1a/ 1b( -/ -) than in WT mice. Arsenic also decreased Cu/ Zn superoxide dismutase activity in both mdr1a/ 1b( -/ -) and WT mice. The expressions of certain genes, such as those encoding cell proliferation, GST, acute- phase proteins and metabolic enzymes, were modestly altered in arsenic- exposed mice. The expression of cyclin D1, a potential hepatic oncogene, was enhanced in arsenic- exposed mdr1a/ 1b( -/ -) mice only. At the highest level of exposure, hepatic arsenic content was higher in mdr1a/ 1b( -/ -) than in WT mice, suggesting that enhanced accumulation due to transport deficiency may, in part, account for the enhanced toxicity in these mice. In summary, this study shows that chronic arsenic toxicity, including liver pathology and oxidative stress, is enhanced in mdr1a/ 1b( -/ -) mice, possibly due to enhanced accumulation of arsenic as a result of transport system deficiency. C1 NIEHS, Inorgan Carcinogenesis Sect, Comparat Carcinogenesis Lab, NCI, Res Triangle Pk, NC 27709 USA. Univ Kansas, Med Ctr, Kansas City, KS 66103 USA. RP Waalkes, MP (reprint author), NIEHS, Inorgan Carcinogenesis Sect, Comparat Carcinogenesis Lab, NCI, Mail Drop F0-09,111 Alexander Dr, Res Triangle Pk, NC 27709 USA. NR 27 TC 23 Z9 27 U1 0 U2 1 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0300-8177 J9 MOL CELL BIOCHEM JI Mol. Cell. Biochem. PD JAN PY 2004 VL 255 IS 1-2 BP 11 EP 18 DI 10.1023/B:MCBI.0000007256.44450.8c PG 8 WC Cell Biology SC Cell Biology GA 751LP UT WOS:000187068800003 PM 14971641 ER PT J AU Tchounwou, PB Centeno, JA Patlolla, AK AF Tchounwou, PB Centeno, JA Patlolla, AK TI Arsenic toxicity, mutagenesis, and carcinogenesis a health risk assessment and management approach SO MOLECULAR AND CELLULAR BIOCHEMISTRY LA English DT Article; Proceedings Paper CT Conference on Molecular Mechanisms of Metal Toxicity and carcinogenesis CY SEP 08-11, 2002 CL MORGANTOWN, VIRGINIA DE arsenic; contamination; health effects; risk assessment and management ID INDUCED CELL-TRANSFORMATION; DRINKING-WATER; SODIUM ARSENITE; GENE-EXPRESSION; DOSE-RESPONSE; ENDEMIC AREA; INDUCTION; EXPOSURE; CANCER; CARCINOMA AB A comprehensive analysis of published data indicates that arsenic exposure induces cardiovascular diseases, developmental abnormalities, neurologic and neurobehavioral disorders, diabetes, hearing loss, hematologic disorders, and various types of cancer. Although exposure may occur via the dermal, and parenteral routes, the main pathways of exposure include ingestion, and inhalation. The severity of adverse health effects is related to the chemical form of arsenic, and is also time- and dose-dependent. Recent reports have pointed out that arsenic poisoning appears to be one of the major public health problems of pandemic nature. Acute and chronic exposure to arsenic has been reported in several countries of the world where a large proportion of drinking water ( groundwater) is contaminated with high concentrations of arsenic. Research has also pointed significantly higher standardized mortality rates for cancers of the bladder, kidney, skin, liver, and colon in many areas of arsenic pollution. There is therefore a great need for developing a comprehensive health risk assessment ( RA) concept that should be used by public health officials and environmental managers for an effective management of the health effects associated with arsenic exposure. With a special emphasis on arsenic toxicity, mutagenesis, and carcinogenesis, this paper is aimed at using the National Academy of Science's RA framework as a guide, for developing a RA paradigm for arsenic based on a comprehensive analysis of the currently available scientific information on its physical and chemical properties, production and use, fate and transport, toxicokinetics, systemic and carcinogenic health effects, regulatory and health guidelines, analytical guidelines and treatment technologies. C1 Jackson State Univ, Sch Sci & Technol, NIH, Ctr Environm Hlth,Mol Toxicol Res Lab, Jackson, MS 39217 USA. Armed Forces Inst Pathol, Environm & Toxicol Pathol Lab, Washington, DC 20306 USA. RP Tchounwou, PB (reprint author), Jackson State Univ, Sch Sci & Technol, NIH, Ctr Environm Hlth,Mol Toxicol Res Lab, Jackson, MS 39217 USA. FU NCRR NIH HHS [1G12RR13459] NR 74 TC 126 Z9 132 U1 0 U2 30 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0300-8177 J9 MOL CELL BIOCHEM JI Mol. Cell. Biochem. PD JAN PY 2004 VL 255 IS 1-2 BP 47 EP 55 DI 10.1023/B:MCBI.0000007260.32981.b9 PG 9 WC Cell Biology SC Cell Biology GA 751LP UT WOS:000187068800007 PM 14971645 ER PT J AU Tchounwou, PB Yedjou, CG Foxx, DN Ishaque, AB Shen, E AF Tchounwou, PB Yedjou, CG Foxx, DN Ishaque, AB Shen, E TI Lead-induced cytotoxicity and transcriptional activation of stress genes in human liver carcinoma (HepG(2)) cells SO MOLECULAR AND CELLULAR BIOCHEMISTRY LA English DT Article; Proceedings Paper CT Conference on Molecular Mechanisms of Metal Toxicity and carcinogenesis CY SEP 08-11, 2002 CL MORGANTOWN, VIRGINIA DE lead; cytotoxicity; gene expression; human liver carcinoma cells ID NF-KAPPA-B; ESTROGEN-RECEPTOR; AH RECEPTOR; INDUCIBLE TRANSCRIPTION; SIGNALING PATHWAYS; BINDING ACTIVITY; INDUCTION; TOXICITY; METALLOTHIONEIN; EXPRESSION AB Lead is a non-essential element that exhibits a high degree of toxicity, especially in children. Most research on lead has focused on its effects on organ systems such as the nervous system, the red blood cells, and the kidneys which are considered to be the primary targets of lead toxicity. However, the molecular mechanisms by which it induces toxicity, and carcinogenesis remain to be elucidated. In this research, we performed the MTT assay to assess the cytotoxicity, and the CAT-Tox assay to assess the transcriptional responses associated with lead exposure to thirteen different recombinant cell lines generated from human liver carcinoma cells (HepG(2)), by creating stable transfectants of mammalian promoter chloramphenicol (CAT) gene fusions. Study results indicated that lead nitrate is cytotoxic to HepG(2) cells, showing LD50 values of 49.0 +/- 18.0 mug/mL, 37.5 +/- 9.2 mug/mL, and 3.5 +/- 0.7 mug/mL for cell mortality upon 24, 48 and 72 h of exposure, respectively; indicating a dose- and time-dependent response with regard to the cytotoxic effect of lead nitrate. A dose- response relationship was also recorded with respect to the induction of stress genes in HepG(2) cells exposed to lead nitrate. Overall, six out of the thirteen recombinant cell lines tested showed inductions to statistically significant levels (p < 0.05). At 50 μg/mL of lead nitrate, the average fold inductions were: 2.1 &PLUSMN; 1.0, 5.4 &PLUSMN; 0.4, 12.1 &PLUSMN; 6.2, 5.0 &PLUSMN; 1.7, 2.5 &PLUSMN; 1.3, and 4.8 &PLUSMN; 4.5 for XRE, HSP70, CRE, GADD153, and GRP78, respectively. These results indicate the potential for lead nitrate to undergo biotransformation in the liver (XRE), to cause cell proliferation (c-fos), protein damage (HSP70, GRP78), metabolic perturbation (CRE), and growth arrest and DNA damage (GADD153). Marginal but not significant inductions were also obtained with the GSTYa (1.5 &PLUSMN; 0.8), and GADD45 (5.7 &PLUSMN; 8.1) promoters, and the NF-κB (2.0 &PLUSMN; 1.7) response element, indicating the potential for oxidative stress. No significant inductions (p 0.05) were recorded for CYP1A1, HMTIIA, p53RE, and RARE. C1 Jackson State Univ, NIH Ctr Environm Hlth, Sch Sci & Technol, Mol Toxicol Res Lab, Jackson, MS 39217 USA. Xenometrix Inc, Xenometrix Res Lab, Boulder, CO USA. RP Tchounwou, PB (reprint author), Jackson State Univ, NIH Ctr Environm Hlth, Sch Sci & Technol, Mol Toxicol Res Lab, 1400 Lynch St,POB 18540, Jackson, MS 39217 USA. FU NCRR NIH HHS [1G12RR13459] NR 68 TC 24 Z9 27 U1 1 U2 3 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0300-8177 J9 MOL CELL BIOCHEM JI Mol. Cell. Biochem. PD JAN PY 2004 VL 255 IS 1-2 BP 161 EP 170 DI 10.1023/B:MCBI.0000007272.46923.12 PG 10 WC Cell Biology SC Cell Biology GA 751LP UT WOS:000187068800019 PM 14971657 ER PT J AU Kowara, R Salnikow, K Diwan, BA Bare, RM Waalkes, MP Kasprzak, KS AF Kowara, R Salnikow, K Diwan, BA Bare, RM Waalkes, MP Kasprzak, KS TI Reduced Fhit protein expression in nickel-transformed mouse cells and in nickel-induced murine sarcomas SO MOLECULAR AND CELLULAR BIOCHEMISTRY LA English DT Article; Proceedings Paper CT Conference on Molecular Mechanisms of Metal Toxicity and carcinogenesis CY SEP 08-11, 2002 CL MORGANTOWN, VIRGINIA DE Fhit; nickel; carcinogenesis; murine sarcomas ID FRAGILE HISTIDINE TRIAD; TUMOR-SUPPRESSOR GENE; TRANSGENIC MICE; METALLOTHIONEIN; APOPTOSIS; CANCER; LOCUS; CARCINOGENESIS; TUMORIGENICITY; HYDROXYLATION AB Nickel compounds are carcinogenic and induce malignant transformation of cultured cells. Since nickel has low mutagenic potential, it may act predominantly through epigenetic mechanisms, including down-regulation of tumor suppressor genes. FHIT is a tumor suppressor gene whose expression is frequently reduced or lost in tumors and pre-malignant lesions. Previously, we have shown that the phosphohydrolase activity of Fhit protein, associated with its tumor suppressor action, is inhibited by nickel [12]. In cells, such effect would assist in carcinogenesis. The latter could be further enhanced if nickel also lowered cellular levels of Fhit protein itself, e. g. by down-regulation of FHIT gene. To test this possibility, we determined Fhit protein and Fhit-mRNA levels in a nickel-transformed mouse cell line and in nickel-induced murine sarcomas. In B200 cells, derived by nickel treatment of BALB/c-3T3 cells and exhibiting a malignant phenotype, Fhit protein levels were 50% of those in the parental cells, while Fhit-mRNA expression remained unchanged. A decrease of up to >90% in Fhit protein levels was also observed in 22 local sarcomas (mostly fibrosarcomas) induced by i.m. injection of nickel subsulfide in C57BL/6 and MT+ (C57BL/6 overexpressing metallothionein) mice, as compared with normal muscles. Moreover, Fhit was absent in 3 out of 10 sarcomas from MT+ mice and in 1 of 12 sarcomas from C57BL/6 mice. The lack of Fhit protein coincided with the absence of the Fhit-mRNA transcript in these tumors. However, in the other tumors, the decreased Fhit levels were not always accompanied by reduced expression of Fhit-mRNA. Thus, the observed lowering of Fhit protein levels is mostly associated with changes in mRNA expression and protein translation or turnover rates, and rarely with a full silencing of the gene itself. Overall, the decline of Fhit in cells or tissues malignantly transformed by nickel may indicate possible involvement of this effect in the mechanisms of nickel carcinogenesis. C1 NCI, Comparat Carcinogenesis Lab, Frederick, MD 21702 USA. NYU, Sch Med, Dept Environm Med, Lab Mol Toxicol & Carcinogenesis, New York, NY USA. SAIC Frederick, Basic Res Program, Frederick, MD USA. NIEHS, Res Triangle Pk, NC 27709 USA. RP Kasprzak, KS (reprint author), NCI, Comparat Carcinogenesis Lab, Bldg 538,Room 205E, Frederick, MD 21702 USA. FU NCI NIH HHS [N01-CO-12400] NR 39 TC 13 Z9 15 U1 1 U2 3 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0300-8177 J9 MOL CELL BIOCHEM JI Mol. Cell. Biochem. PD JAN PY 2004 VL 255 IS 1-2 BP 195 EP 202 DI 10.1023/B:MCBI.0000007275.22785.91 PG 8 WC Cell Biology SC Cell Biology GA 751LP UT WOS:000187068800022 PM 14971660 ER PT J AU Miller, AC Brooks, K Smith, J Page, N AF Miller, AC Brooks, K Smith, J Page, N TI Effect of the militarily-relevant heavy metals, depleted uranium and heavy metal tungsten-alloy on gene expression in human liver carcinoma cells (HepG2) SO MOLECULAR AND CELLULAR BIOCHEMISTRY LA English DT Article; Proceedings Paper CT Conference on Molecular Mechanisms of Metal Toxicity and carcinogenesis CY SEP 08-11, 2002 CL MORGANTOWN, VIRGINIA DE depleted uranium; heavy-metals; tungsten alloy metals; HEPG2 cells; gene expression ID HUMAN OSTEOBLAST CELLS; NEOPLASTIC TRANSFORMATION; TUMORIGENIC PHENOTYPE; COBALT METAL; PARTICLES; EXPOSURE; DAMAGE AB Depleted uranium (DU) and heavy-metal tungsten alloys (HMTAs) are dense heavy-metals used primarily in military applications. Chemically similar to natural uranium, but depleted of the higher activity 235U and 234U isotopes, DU is a low specific activity, high-density heavy metal. In contrast, the non-radioactive HMTAs are composed of a mixture of tungsten (91-93%), nickel (3-5%), and cobalt (2-4%) particles. The use of DU and HMTAs in military munitions could result in their internalization in humans. Limited data exist however, regarding the long-term health effects of internalized DU and HMTAs in humans. Both DU and HMTAs possess a tumorigenic transforming potential and are genotoxic and mutagenic in vitro. Using insoluble DU-UO2 and a reconstituted mixture of tungsten, nickel, cobalt (rWNiCo), we tested their ability to induce stress genes in thirteen different recombinant cell lines generated from human liver carcinoma cells (HepG2). The commercially available CAT-Tox (L) cellular assay consists of a panel of cell lines stably transfected with reporter genes consisting of a coding sequence for chloramphenicol acetyl transferase (CAT) under transcriptional control by mammalian stress gene regulatory sequences. DU, (5-50 mug/ml) produced a complex profile of activity demonstrating significant dose-dependent induction of the hMTIIA FOS, p53RE, Gadd153, Gadd45, NFkappaBRE, CRE, HSP70, RARE, and GRP78 promoters. The rWNiCo mixture (5-50 mug/ml) showed dose-related induction of the GSTYA, hMTIIA, p53RE, FOS, NFkappaBRE, HSP70, and CRE promoters. An examination of the pure metals, tungsten (W), nickel (Ni), and cobalt (Co), comprising the rWNiCo mixture, demonstrated that each metal exhibited a similar pattern of gene induction, but at a significantly decreased magnitude than that of the rWNiCo mixture. These data showed a synergistic activation of gene expression by the metals in the rWNiCo mixture. Our data show for the first time that DU and rWNiCo can activate gene expression through several signal transduction pathways that may be involved in the toxicity and tumorigenicity of both DU and HMTAs. C1 AFRRI, Appl Cellular Radiobiol Dept, Bethesda, MD 20889 USA. NCI, Mol Oncol Branch, Div Canc Treatment, NIH, Bethesda, MD 20892 USA. RP Miller, AC (reprint author), AFRRI, Appl Cellular Radiobiol Dept, 8901 Wisconsin Ave, Bethesda, MD 20889 USA. NR 18 TC 49 Z9 50 U1 1 U2 3 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0300-8177 J9 MOL CELL BIOCHEM JI Mol. Cell. Biochem. PD JAN PY 2004 VL 255 IS 1-2 BP 247 EP 256 DI 10.1023/B:MCBI.0000007280.72510.96 PG 10 WC Cell Biology SC Cell Biology GA 751LP UT WOS:000187068800027 PM 14971665 ER PT J AU O'Leary, KA Mendrysa, SM Vaccaro, A Perry, ME AF O'Leary, KA Mendrysa, SM Vaccaro, A Perry, ME TI Mdm2 regulates p53 independently of p19(ARF) in homeostatic tissues SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID ARF TUMOR-SUPPRESSOR; MYC-INDUCED LYMPHOMAGENESIS; EXPRESSION; APOPTOSIS; STRESS; LOCUS; DISRUPTION; MUTATIONS; PRODUCT; P19ARF AB Tumor suppressor proteins must be exquisitely regulated since they can induce cell death while preventing cancer. For example, the p19(ARF) tumor suppressor (p14(ARF) in humans) appears to stimulate the apoptotic function of the p53 tumor suppressor to prevent lymphomagenesis and carcinogenesis induced by oncogene overexpression. Here we present a genetic approach to defining the role of p19(ARF) in regulating the apoptotic function of p53 in highly proliferating, homeostatic tissues. In contrast to our expectation, p19(ARF) did not activate the apoptotic function of p53 in lymphocytes or epithelial cells. These results demonstrate that the mechanisms that control p53 function during homeostasis differ from those that are critical for tumor suppression. Moreover, the Mdm2/p53/p19(ARF) pathway appears to exist only under very restricted conditions. C1 Univ Wisconsin, Dept Oncol, Madison, WI 53706 USA. NCI, Regulat Prot Funct Lab, Ctr Canc Res, Frederick, MD 21702 USA. RP Perry, ME (reprint author), NCI, EPN Rm 5034,6130 Execut Blvd, Bethesda, MD 20892 USA. FU NCI NIH HHS [CA09135, CA14520, CA70718, P30 CA014520, T32 CA009135, CA07175] NR 22 TC 23 Z9 24 U1 1 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD JAN PY 2004 VL 24 IS 1 BP 186 EP 191 DI 10.1128/MCB.24.1.186.191.2004 PG 6 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 757CL UT WOS:000187531200017 PM 14673154 ER PT J AU Wan, J Sun, LG Mendoza, JW Chui, YL Huang, DP Chen, ZJJ Suzuki, N Suzuki, S Yeh, WC Akira, S Matsumoto, K Liu, ZG Wu, ZG AF Wan, J Sun, LG Mendoza, JW Chui, YL Huang, DP Chen, ZJJ Suzuki, N Suzuki, S Yeh, WC Akira, S Matsumoto, K Liu, ZG Wu, ZG TI Elucidation of the c-Jun N-terminal kinase pathway mediated by Epstein-Barr virus-encoded latent membrane protein SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID LYMPHOCYTE GROWTH TRANSFORMATION; KAPPA-B ACTIVATION; SIGNAL-TRANSDUCTION; NASOPHARYNGEAL CARCINOMA; HONG-KONG; TNF RECEPTOR-1; JNK PATHWAY; TARGETED DISRUPTION; CUTTING EDGE; TAK1 MAPKKK AB Epstein-Barr virus (EBV) is associated with several human diseases including infectious mononucleosis and nasopharyngeal carcinoma. EBV-encoded latent membrane protein 1 (LMP1) is oncogenic and indispensable for cellular transformation caused by EBV. Expression of LMP1 in host cells constitutively activates both the c-Jun N-terminal kinase (JNK) and NF-kappaB pathways, which contributes to the oncogenic effect of LMP1. However, the underlying signaling mechanisms are not very well understood. Based mainly on overexpression studies with various dominant-negative constructs, LMP1 was generally thought to functionally mimic members of the tumor necrosis factor (TNF) receptor superfamily in signaling. In contrast to the prevailing paradigm, using embryonic fibroblasts from different knockout mice and the small interfering RNA technique, we find that the LMP1-mediated JNK pathway is distinct from those mediated by either TNF-alpha or interleukin-1. Moreover, we have further elucidated the LMP1-mediated JNK pathway by demonstrating that LMP1 selectively utilizes TNF receptor-associated factor 6, TAK1/TAB1, and c-Jun N-terminal kinase kinases 1 and 2 to activate JNK. C1 Hong Kong Univ Sci & Technol, Dept Biochem, Kowloon, Hong Kong, Peoples R China. Chinese Univ Hong Kong, Prince Wales Hosp, Clin Immunol Unit, Hong Kong, Hong Kong, Peoples R China. Chinese Univ Hong Kong, Prince Wales Hosp, Dept Anat & Cellular Pathol, Hong Kong, Hong Kong, Peoples R China. NCI, Cell & Canc Biol Branch, NIH, Bethesda, MD 20892 USA. Univ Texas, SW Med Ctr, Dept Mol Biol, Dallas, TX 75230 USA. Univ Toronto, Dept Med Biophys, Toronto, ON, Canada. Osaka Univ, Dept Host Def, Osaka, Japan. Nagoya Univ, Dept Mol Biol, Nagoya, Aichi, Japan. RP Wu, ZG (reprint author), Hong Kong Univ Sci & Technol, Dept Biochem, Clearwater Bay, Kowloon, Hong Kong, Peoples R China. RI Akira, Shizuo/C-3134-2009; Wu, Zhenguo/B-8144-2013 NR 46 TC 52 Z9 54 U1 1 U2 7 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD JAN PY 2004 VL 24 IS 1 BP 192 EP 199 DI 10.1128/MCB.24.1.192-199.2004 PG 8 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 757CL UT WOS:000187531200018 PM 14673155 ER PT J AU Ward, Y Spinelli, B Quon, MJ Chen, H Ikeda, SR Kelly, K AF Ward, Y Spinelli, B Quon, MJ Chen, H Ikeda, SR Kelly, K TI Phosphorylation of critical serine residues in gem separates cytoskeletal reorganization from down-regulation of calcium channel activity SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID KINASE C-ZETA; GTP-BINDING; PHOSPHATIDYLINOSITOL 3-KINASE; HETEROLOGOUS EXPRESSION; SYMPATHETIC NEURONS; 14-3-3 PROTEINS; RAS FAMILY; MEMBER; INTERACTS; GTPASES AB Gem is a small GTP-binding protein that has a ras-like core and extended chains at each terminus. The primary structure of Gem and other RGK family members (Rad, Rem, and Rem2) predicts a GTPase deficiency, leading to the question of how Gem functional activity is regulated. Two functions for Gem have been demonstrated, including inhibition of voltage-gated calcium channel activity and inhibition of Rho kinase-mediated cytoskeletal reorganization, such as stress fiber formation and neurite retraction. These functions for Gem have been ascribed to its interaction with the calcium channel beta subunit and Rho kinase beta, respectively. We show here that these functions are separable and regulated by distinct structural modifications to Gem. Phosphorylation of serines 261 and 289, located in the C-terminal extension, is required for Gem-mediated cytoskeletal reorganization, while GTP and possibly calmodulin binding are required for calcium channel inhibition. In addition to regulating cytoskeletal reorganization, phosphorylation of serine 289 in conjunction with serine 23 results in bidentate 14-3-3 binding, leading to increased Gem protein half-life. Evidence presented shows that phosphorylation of serine 261 is mediated via a cdc42/protein kinase C dependent pathway. These data demonstrate that phosphorylation of serines 261 and 289, outside the GTP-binding region of Gem, controls its inhibition of Rho kinase beta and associated changes in the cytoskeleton. C1 NCI, CCR, NIH, Bethesda, MD 20892 USA. Natl Ctr Complementary & Alternat Med, Lab Clin Invest, Diabet Unit, Bethesda, MD 20892 USA. NIAAA, Lab Mol Physiol, Bethesda, MD 20892 USA. RP Kelly, K (reprint author), NCI, CCR, NIH, Bldg 10,Room 3B43, Bethesda, MD 20892 USA. EM kkelly@helix.nih.gov RI Quon, Michael/B-1970-2008; OI Quon, Michael/0000-0002-9601-9915; Ikeda, Stephen/0000-0002-4088-9508; Quon , Michael /0000-0002-5289-3707 NR 32 TC 58 Z9 58 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD JAN PY 2004 VL 24 IS 2 BP 651 EP 661 DI 10.1128/MCB.24.2.651-661.2004 PG 11 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 764MT UT WOS:000188211200015 PM 14701738 ER PT J AU Zhang, JR Willers, H Feng, ZH Ghosh, JC Kim, S Weaver, DT Chung, JH Powell, SN Xia, F AF Zhang, JR Willers, H Feng, ZH Ghosh, JC Kim, S Weaver, DT Chung, JH Powell, SN Xia, F TI Chk2 phosphorylation of BRCA1 regulates DNA double-strand break repair SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID CELL-FREE-EXTRACTS; HOMOLOGOUS RECOMBINATION; DAMAGE RESPONSE; CANCER SUSCEPTIBILITY; CHROMOSOME STABILITY; IONIZING IRRADIATION; V(D)J RECOMBINATION; KINASE-ACTIVITY; MEIOTIC CELLS; MRE11 COMPLEX AB The pathway determining malignant cellular transformation, which depends upon mutation of the BRCA1 tumor suppressor gene, is poorly defined. A growing body of evidence suggests that promotion of DNA double-strand break repair by homologous recombination (HR) may be the means by which BRCA1 maintains genomic stability, while a role of BRCA1 in error-prone nonhomologous recombination (NHR) processes has just begun to be elucidated. The BRCA1 protein becomes phosphorylated in response to DNA damage, but the effects of phosphorylation on recombinational repair are unknown. In this study, we tested the hypothesis that the BRCA1-mediated regulation of recombination requires the Chk2- and ATM-dependent phosphorylation sites. We studied Rad51-dependent HR and random chromosomal integration of linearized plasmid DNA, a subtype of NHR, which we demonstrate to be dependent on the Mre11-Rad50-Nbs1 complex. Prevention of Chk2-mediated phosphorylation via mutation of the serine 988 residue of BRCA1 disrupted both the BRCA1-dependent promotion of HR and the suppression of NHR. Similar results were obtained when endogenous Chk2 kinase activity was inhibited by expression of a dominant-negative Chk2 mutant. Surprisingly, the opposing regulation of HR and NHR did not require the ATM phosphorylation sites on serines 1423 and 1524. Together, these data suggest a functional link between recombination control and breast cancer predisposition in carriers of Chk2 and BRCA1 germ line mutations. We propose a dual regulatory role for BRCA1 in maintaining genome integrity, whereby BRCA1 phosphorylation status controls the selectivity of repair events dictated by HR and error-prone NHR. C1 Massachusetts Gen Hosp, Dept Radiat Oncol, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Charlestown, MA 02129 USA. Ctr Blood Res, Boston, MA 02115 USA. Natl Heart Lung & Blood Inst, Lab Biochem Genet, NIH, Bethesda, MD 20892 USA. RP Powell, SN (reprint author), Massachusetts Gen Hosp, Dept Radiat Oncol, 149 13th St, Charlestown, MA 02129 USA. EM snpowell@partners.org; fen.xia@vanderbilt.edu RI Xia, Fen/G-3708-2013 NR 76 TC 209 Z9 214 U1 0 U2 5 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD JAN PY 2004 VL 24 IS 2 BP 708 EP 718 DI 10.1128/MCB.24.2.708-718.2004 PG 11 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 764MT UT WOS:000188211200020 PM 14701743 ER PT J AU Nielsen, JA Berndt, JA Hudson, LD Armstrong, RC AF Nielsen, JA Berndt, JA Hudson, LD Armstrong, RC TI Myelin transcription factor 1 (Myt1) modulates the proliferation and differentiation of oligodendrocyte lineage cells SO MOLECULAR AND CELLULAR NEUROSCIENCE LA English DT Article ID CENTRAL-NERVOUS-SYSTEM; DNA-BINDING PROTEIN; ZINC-FINGER; IN-VIVO; EXPRESSION; PROGENITORS; NEURONS; GENE; ASTROCYTE; MOUSE AB Myelin transcription factor 1 (Myt1) is a zinc finger DNA-binding protein that is expressed in neural progenitors and oligodendrocyte lineage cells. This study examines the role of Myt1 in oligodendrocyte lineage cells by overexpressing putative functional domains, a four-zinc finger DNA-binding region (4FMyt1) or a central protein-protein interaction domain (CDMyt1), without the predicted transcriptional activation domain. In the presence of mitogens, overexpression of 4FMyt1 inhibited proliferation of oligodendrocyte progenitors, but not cell types (astrocytes and NIH3T3 cells) lacking endogenous Myt1. Expression of 4FMyt1 inhibited the differentiation of oligodendrocyte progenitors into oligodendrocytes as assessed by morphology, immunostaining, and myelin gene expression. Progenitor differentiation was similarly inhibited by expression of CDMyt1 but only partially suppressed by overexpression of the intact Myt1. These data indicate that Myt1 may regulate a critical transition point in oligodendrocyte lineage development by modulating oligodendrocyte progenitor proliferation relative to terminal differentiation and up-regulation of myelin gene transcription. Published by Elsevier Inc. C1 Uniformed Serv Univ Hlth Sci, Dept Anat Physiol & Genet, Program Neurosci, Bethesda, MD 20814 USA. Uniformed Serv Univ Hlth Sci, Program Mol & Cell Biol, Bethesda, MD 20814 USA. NINDS, Lab Dev Neurogenet, Sect Dev Genet, NIH, Bethesda, MD 20892 USA. RP Armstrong, RC (reprint author), Uniformed Serv Univ Hlth Sci, Dept Anat Physiol & Genet, Program Neurosci, 4301 Jones Bridge Rd, Bethesda, MD 20814 USA. EM rarmstrong@usuhs.mil FU NINDS NIH HHS [NS39293] NR 37 TC 61 Z9 62 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 1044-7431 J9 MOL CELL NEUROSCI JI Mol. Cell. Neurosci. PD JAN PY 2004 VL 25 IS 1 BP 111 EP 123 DI 10.1016/j.mcn.2003.10.001 PG 13 WC Neurosciences SC Neurosciences & Neurology GA 779PQ UT WOS:000189309600011 PM 14962745 ER PT B AU Klion, AD Rioux, JD Law, M Nutman, TB AF Klion, AD Rioux, JD Law, M Nutman, TB BE Petrides, PE Pahl, HL TI Familial hypereosinophilic syndrome SO MOLECULAR BASIS OF CHRONIC MYELOPROLIFERATIVE DISORDERS LA English DT Proceedings Paper CT International Conference on Towards an Understanding of the Molecular Basis of Myeloproliferative Disorders CY SEP 23-28, 2000 CL Frauenchiemsee, GERMANY ID EOSINOPHILIA; INTERLEUKIN-5; IMATINIB; DISORDER; REGION; FUSION C1 NIH, Parasit Dis Lab, Bethesda, MD 20892 USA. RP Klion, AD (reprint author), NIH, Parasit Dis Lab, Bldg 10, Bethesda, MD 20892 USA. NR 22 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY BN 3-540-22485-8 PY 2004 BP 189 EP 194 PG 6 WC Hematology; Pathology SC Hematology; Pathology GA BBI99 UT WOS:000225713400022 ER PT J AU Perry, ME AF Perry, ME TI Mdrn2 in the response to radiation SO MOLECULAR CANCER RESEARCH LA English DT Review ID DEPENDENT PROTEIN-KINASE; CELL-CYCLE CHECKPOINT; WILD-TYPE P53; DAMAGE-INDUCED PHOSPHORYLATION; TRANSCRIPTION COUPLED REPAIR; EARLY EMBRYONIC LETHALITY; TUMOR-SUPPRESSOR PROTEIN; OPEN READING FRAMES; DNA-DAMAGE; P53-DEPENDENT APOPTOSIS AB Murine double minute 2 (Mdm2) is a critical component of the responses to both ionizing and UV radiation. The level of Mdm2 expression determines the extent to which radiation induces an increase in the activity of the p53 tumor suppressor. Mdm2 acts as a survival factor in many cell types by limiting the apoptotic function of p53. In addition, expression of mdm2 is induced in response to DNA damage, and the resulting high levels of Mdm2 protein are thought to shorten the length of the cell cycle arrest established by p53 in the radiation response. Increased levels of Mdm2 appear to ensure that the activity of p53 returns to its low basal levels in surviving cells. Decreased levels of Mdm2 sensitize cells to ionizing radiation. Thus, Mdm2 is a potential target for therapeutic intervention because its inhibition may radiosensitize the subset of human tumors expressing wild-type p53 such that radiotherapy is more efficacious. C1 NCI, Div Canc Biol, Bethesda, MD 20892 USA. NCI, Regulat Prot Funct Lab, Bethesda, MD 20892 USA. RP Perry, ME (reprint author), NCI, Div Canc Biol, 6130 Execut Blvd,Room 5034, Bethesda, MD 20892 USA. EM perryma@mail.nih.gov NR 109 TC 59 Z9 62 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1541-7786 J9 MOL CANCER RES JI Mol. Cancer Res. PD JAN PY 2004 VL 2 IS 1 BP 9 EP 19 PG 11 WC Oncology; Cell Biology SC Oncology; Cell Biology GA 770HU UT WOS:000188717800002 PM 14757841 ER PT J AU Srinivas, G Annab, LA Gopinath, G Banerji, A Srinivas, P AF Srinivas, G Annab, LA Gopinath, G Banerji, A Srinivas, P TI Antisense blocking of BRCA1 enhances sensitivity to plumbagin but not tamoxifen in BG-1 ovarian cancer cells SO MOLECULAR CARCINOGENESIS LA English DT Article DE ovarian cancer; BRCA1; plumbagin; tamoxifen; apoptosis ID APOPTOSIS-INDUCING FACTOR; ESTROGEN-RECEPTOR ACTIVITY; SUSCEPTIBILITY GENE BRCA1; GROWTH IN-VITRO; BREAST-CANCER; DNA-DAMAGE; INHIBITION; EXPRESSION; EMODIN; DEATH AB Previous studies have shown that reduction in BRCA1 mRNA and protein can result in increased proliferation of BG-1 ovarian cancer cells in both in vitro and in vivo conditions, suggesting that BRCA1 may normally act as a growth inhibitor in these cells. Also, there are other reports that suggest that wild-type BRCA1 protein may repress estrogen receptor (ER) function either directly or indirectly. However, response to antiestrogen drugs in BRCA1-blocked ER-positive ovarian cancer cells has not been reported, and this served as the rationale for this study. We analyzed the effect of tamoxifen, emodin, and plumbagin in BRCA1-blocked ER-positive BG-1 ovarian cancer cells. For all three drugs, BRCA1-blocked cells were more sensitive than the corresponding control cells as assessed by MTT assay; however, only plumbagin showed a statistically significant difference in mean viability (P<0.05). All three drugs induced loss of mitochondrial membrane potential (&UDelta;&UPsi;(m)), nuclear condensation, DNA fragmentation, and morphological changes, as observed after 6 h of drug treatment, suggesting apoptosis induction in both BRCA1-blocked and control cells. However, apoptosis induction was greater in BRCA1-blocked cells, the efficacy being in the order of plumbagin > tamoxifen > emodin. The dose of plumbagin needed to kill 50% was 5 muM in the control cells and 2.68 muM for the BRCA1-blocked cells, indicating that the latter was about twofold more sensitive to plumbagin than the wild-type cells. This throws light on the fact that plumbagin may have chemotherapeutic potential as an anticancer agent in BRCA1-mutated ovarian cancer patients. (C) 2003 Wiley-Liss, Inc. C1 Rajiv Gandhi Ctr Biotechnol, Div Canc Biol, Thiruvananthapuram 695014, Kerala, India. Natl Inst Environm Hlth Sci, Mol Carcinogenesis Lab, Res Triangle Pk, NC USA. Univ Calicut, Dept Biotechnol, Calicut 673635, Kerala, India. Reg Res Lab, Phytochem Res Unit, Thiruvananthapuram, Kerala, India. RP Srinivas, P (reprint author), Rajiv Gandhi Ctr Biotechnol, Div Canc Biol, Thycaud PO, Thiruvananthapuram 695014, Kerala, India. RI TVM, NIIST/E-5132-2012 OI TVM, NIIST/0000-0002-5814-466X NR 59 TC 28 Z9 31 U1 0 U2 2 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0899-1987 J9 MOL CARCINOGEN JI Mol. Carcinog. PD JAN PY 2004 VL 39 IS 1 BP 15 EP 25 DI 10.1002/mc.10164 PG 11 WC Biochemistry & Molecular Biology; Oncology SC Biochemistry & Molecular Biology; Oncology GA 762JQ UT WOS:000187968800003 PM 14694444 ER PT J AU Thameem, F Farook, VS Yang, XL Lee, YH Permana, PA Bogardus, C Prochazka, M AF Thameem, F Farook, VS Yang, XL Lee, YH Permana, PA Bogardus, C Prochazka, M TI The transcribed endosulfine alpha gene is located within a type 2 diabetes-linked region on 1q: sequence and expression analysis in Pima Indians SO MOLECULAR GENETICS AND METABOLISM LA English DT Article DE endosulfine alpha gene; chromosome 1q; variants; expression; type 2 diabetes mellitus; Pima Indians ID AUTOSOMAL GENOMIC SCAN; K-ATP CHANNELS; ENDOSULPHINE; LOCALIZATION; REGULATOR; CLONING AB Endosulfine alpha (ENSA) is an endogenous ligand of the sulfonylurea receptor 1 (SUR1) that can stimulate insulin secretion by pancreatic beta cells. Originally, an intronless gene coding for this protein was assigned to Chr. 14q, but more recent information available in public databases indicated the position of ENSA on 1q21. We show here that the 1q21 locus represents the expressed gene consisting of 6 exons, whereas the locus on Chr. 14q is apparently a pseudogene. The ENSA gene on 1q21 produces several alternatively spliced transcripts, and is located within a region linked with T2DM in diverse populations including the Pima Indians. We analyzed ENSA in this Native American population and identified seven variants, which fall into three linkage disequilibrium groups. Analysis of representative markers in over 1200 Pima Indians did not reveal any significant association with T2DM, or with differences in insulin action and insulin secretion in a subset of approximately 270 non-diabetic subjects. In addition, we did not detect any significant correlation of skeletal muscle ENSA transcript levels with differences in insulin action in 49 non-diabetic subjects. We conclude that sequence alterations in ENSA are an unlikely cause for the linkage of T2DM with 1q21-q23 in the Pima Indians. (C) 2003 Elsevier Inc. All rights reserved. C1 NIDDKD, Clin Diabet & Nutr Sect, Phoenix Epidemiol & Res Branch, NIH, Phoenix, AZ 85016 USA. Sahlgrens Univ Hosp, Lundberg Lab Diabet Res, S-41345 Gothenburg, Sweden. Carl T Hyaden Vet Affairs Med Ctr, Phoenix, AZ USA. RP Prochazka, M (reprint author), NIDDKD, Clin Diabet & Nutr Sect, Phoenix Epidemiol & Res Branch, NIH, 4212 N 16th St, Phoenix, AZ 85016 USA. EM mprochazka@phx.niddk.nih.gov NR 15 TC 3 Z9 5 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 1096-7192 J9 MOL GENET METAB JI Mol. Genet. Metab. PD JAN PY 2004 VL 81 IS 1 BP 16 EP 21 DI 10.1016/j.ymgme.2003.09.013 PG 6 WC Endocrinology & Metabolism; Genetics & Heredity; Medicine, Research & Experimental SC Endocrinology & Metabolism; Genetics & Heredity; Research & Experimental Medicine GA 768JP UT WOS:000188540100004 PM 14728987 ER PT J AU Harding, CO Neff, M Wild, K Jones, K Elzaouk, L Thony, B Milstien, S AF Harding, CO Neff, M Wild, K Jones, K Elzaouk, L Thony, B Milstien, S TI The fate of intravenously administered tetrahydrobiopterin and its implications for heterologous gene therapy of phenylketonuria SO MOLECULAR GENETICS AND METABOLISM LA English DT Article ID PHENYLALANINE-HYDROXYLASE; GTP CYCLOHYDROLASE; TRANSPORT; BIOPTERIN; CELLS; METABOLISM; TISSUES; FLUIDS; SERUM; BRAIN AB Tetrahydrobiopterin (BH4) is a required cofactor for the enzymatic activity of phenylalanine, hydroxylase (PAH) and is synthesized de novo from GTP in several tissues. Heterologous expression of PAH in tissues other than liver is a potential novel therapy for human phenylketonuria that is completely dependent upon BH4 supply in the PAH-expressing tissue. Previous experiments with liver PAH-deficient transgenic mice that expressed PAH in skeletal muscle demonstrated transient correction of hyperphenylataninernia only with hourly parenteral BH4 administration. In this report, the fate of intravenously administered BH4 is examined. The conclusions are that (1) BH4 administered intravenously is rapidly taken up by liver and kidney, and (2) uptake of BH4 into muscle is relatively low. The levels of BH4 achieved in skeletal muscle following IV injection are only 10% of the amount expected were BH4 freely and equally distributed across all tissues. The half-life of BH4 in muscle is approximately 30 min, necessitating repeated injections to maintain muscle BH4 content sufficient to support phenylalanine hydroxylation. The efficacy of heterologous muscle-directed gene therapy for the treatment of PKU will likely be limited by the BH4 supply in PAH-expressing muscle. (C) 2003 Elsevier Inc. All rights reserved. C1 Oregon Hlth Sci Univ, Dept Pediat, Portland, OR 97201 USA. Oregon Hlth Sci Univ, Dept Mol & Med Genet, Portland, OR 97201 USA. Univ Zurich, Childrens Hosp, Div Clin Chem & Biochem, Zurich, Switzerland. NIMH, Bethesda, MD 20892 USA. RP Harding, CO (reprint author), Oregon Hlth Sci Univ, Dept Pediat, 3181 SW Sam Jackson Pk Rd, Portland, OR 97201 USA. EM hardingc@ohsu.edu FU NIDDK NIH HHS [R01 DK059371, R01 DK/HD59371, R01 DK059371-02, K08 DK02405] NR 21 TC 12 Z9 12 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 1096-7192 J9 MOL GENET METAB JI Mol. Genet. Metab. PD JAN PY 2004 VL 81 IS 1 BP 52 EP 57 DI 10.1016/j.ymgme.2003.10.002 PG 6 WC Endocrinology & Metabolism; Genetics & Heredity; Medicine, Research & Experimental SC Endocrinology & Metabolism; Genetics & Heredity; Research & Experimental Medicine GA 768JP UT WOS:000188540100008 PM 14728991 ER PT J AU Lwin, A Orvisky, E Goker-Alpan, O LaMarca, ME Sidransky, E AF Lwin, A Orvisky, E Goker-Alpan, O LaMarca, ME Sidransky, E TI Glucocerebrosidase mutations in subjects with parkinsonism SO MOLECULAR GENETICS AND METABOLISM LA English DT Article DE Gaucher disease; parkinsonism; glucocerebrosidase; heterozygotes; risk factors; autopsy; genotyping ID GAUCHER-DISEASE; TRAITS AB Recent studies showing an association between glucocerebrosidase deficiency and parkinsonism in Gaucher disease prompted an examination of the glucocerebrosidase gene sequence (GBA) and enzyme activity in brain samples from 57 subjects carrying the diagnosis of Parkinson disease. Alterations in GBA were identified in 12 samples (21%) and were more frequent among the younger subjects. These included eight with mutations (N370S, L444P, K198T, and R329C) and four with probable polymorphisms (T369M and E326K). Our findings suggest that mutations in glucocerebrosidase may be a risk factor for the development of parkinsonism. (C) 2003 Elsevier Inc. All rights reserved. C1 NIMH, Sect Mol Neurogenet, NIH, Bethesda, MD 20892 USA. NHGRI, Med Genet Branch, NIH, Bethesda, MD 20892 USA. RP Sidransky, E (reprint author), NIMH, Sect Mol Neurogenet, NIH, Bethesda, MD 20892 USA. EM sidranse@irp.nimh.nih.gov NR 17 TC 186 Z9 191 U1 0 U2 8 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1096-7192 J9 MOL GENET METAB JI Mol. Genet. Metab. PD JAN PY 2004 VL 81 IS 1 BP 70 EP 73 DI 10.1016/j.ymgme.2003.11.004 PG 4 WC Endocrinology & Metabolism; Genetics & Heredity; Medicine, Research & Experimental SC Endocrinology & Metabolism; Genetics & Heredity; Research & Experimental Medicine GA 768JP UT WOS:000188540100011 PM 14728994 ER PT J AU McCarron, JA Pike, VW Halldin, C Sandell, J Sovago, J Gulyas, BS Cselenyi, Z Wikstrom, HV Marchais-Oberwinkler, S Nowicki, B Dolle, F Farde, L AF McCarron, JA Pike, VW Halldin, C Sandell, J Sovago, J Gulyas, BS Cselenyi, Z Wikstrom, HV Marchais-Oberwinkler, S Nowicki, B Dolle, F Farde, L TI The pyridinyl-6 position of WAY-100635 as a site for radiofluorination-effect on 5-HT1A receptor radioligand behavior in vivo SO MOLECULAR IMAGING AND BIOLOGY LA English DT Article DE 5-HT1A receptor; radioligand; fluorine-18; PET; [F-18]6FPWAY; brain; monkey ID HUMAN BRAIN; RADIOACTIVE METABOLITES; MPPF BINDING; FLUORO ANALOG; HUMAN PLASMA; PET; ANTAGONISTS; MONKEY; LIGAND; C-11 AB PURPOSE: We aimed to evaluate radiofluorination at the pyridinyl-6 position of the selective 5-HT1A receptor antagonist, WAY-100635 [N-(2-(1-(4-(2-methoxyphenyl)piperazinyl)ethyl))-N-(2-pyridinyl)cyclohexanecarboxamide)], on 5-HT1A receptor radioligand behavior in vivo. PROCEDURES: The pyridinyl-6 [F-18]fluoro derivative of WAY-100635 ([F-18]6FPWAY) was obtained by direct nucleophilic substitution with [F-18]fluoride ion in a bromo precursor. After intravenous injection of [F-18]6FPWAY into Cynomolgus monkey, the uptake of radioactivity into brain regions was assessed with positron emission tomography (PET) and blood samples analyzed by high performance liquid chromatography (HPLC) for parent radioligand and radioactive metabolites. The experiment was repeated after pretreatment of the monkey with a dose of WAY-100635 that blocks brain 5-HT1A receptors. RESULTS: After intravenous injection of [F-18]6FPWAY into Cynomolgus monkey, the uptake of radioactivity into whole brain reached 4.33% of injected dose at 7.5 min. Uptake was highest in 5-HT1A receptor-rich regions. Pretreatment with WAY-100635 reduced uptake in these regions to near the levels in receptor-devoid cerebellum. [F-18]6FPWAY was rapidly metabolized in vivo, as evidenced by the rapid appearance of radioactive metabolites in plasma. CONCLUSION: [F-18]6FPWAY is selective and moderately useful for imaging brain 5-HT1A receptors in vivo. The pyridinyl-6 position is resistant to defluorination and may be an attractive site for the F-18-labeling of 6FPWAY analogs that resist hydrolysis. (C) 2004 Elsevier Inc. All rights reserved. C1 NIMH, PET Radiopharmaceut Sci Sect, Mol Imaging Branch, Natl Inst Hlth, Bethesda, MD 20892 USA. Karolinska Hosp, Karolinska Inst, Dept Clin Neurosci, Psychiat Sect, S-10401 Stockholm, Sweden. Univ Groningen, Dept Med Chem, Univ Ctr Pharm, Groningen, Netherlands. CEA, Serv Hosp Frederic Joliot, Dept Rech Med, F-91406 Orsay, France. RP McCarron, JA (reprint author), NIMH, PET Radiopharmaceut Sci Sect, Mol Imaging Branch, Natl Inst Hlth, Bldg 10,Rm B3 C346,10 Ctr Dr, Bethesda, MD 20892 USA. EM mccarroj@intra.nimh.nih.gov RI Sovago, Judit/G-7961-2011; Gulyas, Balazs/F-9508-2015 NR 41 TC 14 Z9 14 U1 0 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1536-1632 J9 MOL IMAGING BIOL JI Mol. Imaging. Biol. PD JAN-FEB PY 2004 VL 6 IS 1 BP 17 EP 26 DI 10.1016/j.mibio.2003.12.001 PG 10 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 842XW UT WOS:000223039000004 PM 15018825 ER PT J AU Stratakis, CA Matyakhina, L Courkoutsakis, N Patronas, N Voutetakis, A Stergiopoulos, S Bossis, J Carney, JA AF Stratakis, CA Matyakhina, L Courkoutsakis, N Patronas, N Voutetakis, A Stergiopoulos, S Bossis, J Carney, JA TI Pathology and molecular genetics of the pituitary gland in patients with the 'Complex of spotty skin pigmentation, myxomas, endocrine overactivity and Schwannomas' (Carney complex) SO MOLECULAR PATHOLOGY OF THE PITUITARY SE FRONTIERS OF HORMONE RESEARCH LA English DT Article ID MCCUNE-ALBRIGHT SYNDROME; NODULAR ADRENOCORTICAL DISEASE; GROWTH-HORMONE; PRKAR1A GENE; ACTIVATING MUTATIONS; SOMATOSTATIN ANALOG; REGULATORY SUBUNIT; NEOPLASIA TYPE-1; CARDIAC MYXOMAS; TUMORS AB Carney complex (CNC) is a familial multiple neoplasia and lentiginosis syndrome with features overlapping those of McCune-Albright syndrome (MAS) and other multiple endocrine neoplasia (MEN) syndromes like MEN type 1 (MEN 1). Pituitary tumors have been described in a number of patients with CNC; all have been growth hormone (GH) and prolactin (PRL)-producing. In at least some patients, pituitary gland involvement is manifested by hyperplastic areas; hyperplasia appears to involve somatomammotrophs only and to precede GH-producing tumor formation, in a pathway similar to that seen in MAS-related pituitary tumors (and in oncogenesis in other CNC tissues). One patient with CNC and advanced acromegaly had a GH-producing macroadenoma that showed extensive genetic changes at the chromosomal level. These changes appeared to represent secondary or tertiary genetic 'hits' involved in pituitary oncogenesis and were confirmed at the molecular level. So far, almost half of the patients with CNC have germiline-inactivating mutations in the PRKAR1A gene; in their pituitary tumors, the normal allele of the PRKAR1A gene is lost. Loss of heterozygosity suggests that PRKAR1A, which codes for the regulatory subunit type 1alpha of the cAMP-dependent protein kinase A (PKA), may act as a tumor-suppressor gene in pituitary tissue. These data provide evidence for a PKA-induced somatomammotroph hyperplasia in the pituitary tissue of CNC patients; hyperplasia leads to additional genetic changes at the somatic level, which in turn cause the formation of adenomas in some, but not all, patients. Copyright (C) 2004 S. Karger AG, Basel. C1 NICHD, DEB, Sect Endocrinol & Genet, NIH, Bethesda, MD 20892 USA. RP Stratakis, CA (reprint author), NICHD, DEB, Sect Endocrinol & Genet, NIH, Bldg 10,Room 10N262,10 Ctr Dr,MSC 1862, Bethesda, MD 20892 USA. EM stratakc@cc1.nichd.nih.gov RI Bossis, Ioannis/J-6883-2012 NR 45 TC 10 Z9 10 U1 1 U2 2 PU KARGER PI BASEL PA POSTFACH, CH-4009 BASEL, SWITZERLAND SN 0301-3073 J9 FRONT HORM RES JI Front.Horm.Res. PY 2004 VL 32 BP 253 EP 264 PG 12 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA BAM39 UT WOS:000222824600015 PM 15281351 ER PT J AU Okada, M Northrup, JK Ozaki, N Russell, JT Linnoila, M Goldman, D AF Okada, M Northrup, JK Ozaki, N Russell, JT Linnoila, M Goldman, D TI Modification of human 5-HT2C receptor function by Cys23Ser, an abundant, naturally occurring amino-acid substitution SO MOLECULAR PSYCHIATRY LA English DT Article DE serotonin receptor; polymorphism; 5-HT; m-CPP ID LUTEINIZING-HORMONE RECEPTOR; PROTEIN-COUPLED RECEPTOR; 2C RECEPTOR; ANTIPSYCHOTIC-DRUGS; SEROTONIN RECEPTOR; AFFECTIVE-DISORDER; INVERSE AGONISTS; MESSENGER-RNA; MUTANT MICE; GENE AB A human serotonin (5-HT)(2C) receptor gene polymorphism leads to the substitution of cysteine for serine at codon 23 (Cys23Ser); the frequency of the Ser23 allele in unrelated Caucasians is approximately 0.13. In the present study, we assessed whether Cys23Ser could affect receptor function. The two alleles were functionally compared following expression in COS-7 cells. The constitutive activity of the receptor in an in situ reconstitution system was also evaluated following expression of each allele in Sf9 cells. Using radioligands, Ser23-expressed membranes showed reduced high-affinity binding to meta-chlorophenylpiperazine (m-CPP) and 5-HT. Although the amplitude of the 5-HT-induced intracellular Ca2+ peak did not differ between the alleles, Ser23 required higher 5-HT concentrations to elicit the same response. These differences might be due to more extensive desensitization in the Ser23 form. In the in situ reconstitution system, the 5-HT2C receptor displayed considerable constitutive activity, with the Ser23 allele being significantly higher in this regard than the Cys23 form. After prolonged serum deprivation in order to resensitize the receptor, four of the 15 cells expressing Ser23 showed abnormally higher m-CPP-induced sensitivity of the Ca2+ response. These results indicate that the Ser23 allele may be constitutively more active than Cys23. Thus, Ser23 appears to be an abundant candidate allele capable of directly influencing interindividual variation in behavior, susceptibility to mental disorder, and response to drugs including atypical antipsychotic and some antidepressant drugs that are potent 5-HT2C inverse agonists or antagonists. C1 Osaka City Univ, Fac Med, Dept Publ Hlth, Abeno Ku, Osaka 5458585, Japan. NIAAA, Neurogenet Lab, NIH, Rockville, MD 20852 USA. Natl Inst Deafness & Other Commun Disorders, Lab Cellular Biol, NIH, Rockville, MD USA. NICHHD, Lab Cellular Mol Neurophysiol, NIH, Bethesda, MD 20892 USA. NIAAA, Clin Studies Lab, NIH, Rockville, MD 20852 USA. Fujita Hlth Univ, Dept Psychiat, Toyoake, Aichi, Japan. RP Okada, M (reprint author), Osaka City Univ, Fac Med, Dept Publ Hlth, Abeno Ku, 1-4-3 Asahi Machi, Osaka 5458585, Japan. RI Ozaki, Norio/M-8908-2014; Goldman, David/F-9772-2010 OI Ozaki, Norio/0000-0002-7360-4898; Goldman, David/0000-0002-1724-5405 NR 47 TC 65 Z9 66 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1359-4184 J9 MOL PSYCHIATR JI Mol. Psychiatr. PY 2004 VL 9 IS 1 BP 55 EP 64 DI 10.1038/sj.mp.4001357 PG 10 WC Biochemistry & Molecular Biology; Neurosciences; Psychiatry SC Biochemistry & Molecular Biology; Neurosciences & Neurology; Psychiatry GA 757PH UT WOS:000187570300010 PM 14699441 ER PT J AU Dick, DM Li, TK Edenberg, HJ Hesselbrock, V Kramer, J Kuperman, S Porjesz, B Bucholz, K Goate, A Nurnberger, J Foroud, T AF Dick, DM Li, TK Edenberg, HJ Hesselbrock, V Kramer, J Kuperman, S Porjesz, B Bucholz, K Goate, A Nurnberger, J Foroud, T TI A genome-wide screen for genes influencing conduct disorder SO MOLECULAR PSYCHIATRY LA English DT Article DE conduct disorder; linkage analysis; genetics; alcohol dependence ID ATTENTION-DEFICIT/HYPERACTIVITY DISORDER; OPPOSITIONAL DEFIANT DISORDER; ENVIRONMENTAL-INFLUENCES; DISRUPTIVE BEHAVIOR; ANTISOCIAL-BEHAVIOR; ALCOHOL DEPENDENCE; FAMILIAL AGGREGATION; COMPLEX TRAITS; RISK-FACTORS; DIAGNOSIS AB While behavioral genetic studies have suggested that childhood conduct disorder is under genetic influence, studies aimed at gene identification are lacking. This study represents the first genome-wide linkage analysis directed toward identifying genes contributing to conduct disorder. Genome screens of retrospectively reported childhood conduct disorder and conduct disorder symptomatology were carried out in the genetically informative adult sample collected as part of the Collaborative Study on the Genetics of Alcoholism (COGA). The results suggest that regions on chromosomes 19 and 2 may contain genes conferring risk to conduct disorder. Interestingly, the same region on chromosome 2 has also been linked to alcohol dependence in this sample. Childhood conduct disorder is known to be associated with the susceptibility for future alcohol problems. Taken together, these findings suggest that some of the genes contributing to alcohol dependence in adulthood may also contribute to conduct disorder in childhood. C1 Indiana Univ, Sch Med, Dept Med & Mol Genet, Indianapolis, IN 46202 USA. NIAAA, Bethesda, MD 20892 USA. Univ Connecticut, Ctr Hlth, Dept Psychiat, Farmington, CT 06030 USA. Univ Iowa, Coll Med, Iowa City, IA 52242 USA. Suny Downstate Med Ctr, Dept Psychiat, Neurodynam Lab, Brooklyn, NY 11203 USA. Washington Univ, Dept Psychiat, St Louis, MO 63108 USA. RP Foroud, T (reprint author), Indiana Univ, Sch Med, Dept Med & Mol Genet, 975 W Walnut St,IB-130, Indianapolis, IN 46202 USA. OI Nurnberger, John/0000-0002-7674-1767; Edenberg, Howard/0000-0003-0344-9690 FU NCRR NIH HHS [M01 RR6192]; NIAAA NIH HHS [AA13358, K02 AA00285, U10 AA08403] NR 40 TC 54 Z9 57 U1 6 U2 7 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1359-4184 J9 MOL PSYCHIATR JI Mol. Psychiatr. PY 2004 VL 9 IS 1 BP 81 EP 86 DI 10.1038/sj.mp.4001368 PG 6 WC Biochemistry & Molecular Biology; Neurosciences; Psychiatry SC Biochemistry & Molecular Biology; Neurosciences & Neurology; Psychiatry GA 757PH UT WOS:000187570300013 PM 14699444 ER PT J AU Chen, YS Akula, N Detera-Wadleigh, SD Schulze, TG Thomas, J Potash, JB DePaulo, JR McInnis, MG Cox, NJ McMahon, FJ AF Chen, YS Akula, N Detera-Wadleigh, SD Schulze, TG Thomas, J Potash, JB DePaulo, JR McInnis, MG Cox, NJ McMahon, FJ TI Findings in an independent sample support an association between bipolar affective disorder and the G72/G30 locus on chromosome 13q33 SO MOLECULAR PSYCHIATRY LA English DT Article DE mood disorder; genetics; allele frequency ID SINGLE NUCLEOTIDE POLYMORPHISMS; LINKAGE DISEQUILIBRIUM; GENOME; GENE; POPULATION; SCHIZOPHRENIA; GUIDELINES; ACCURACY; ALLELES; ERRORS AB Markers near the nested genes G72 and G30 on chromosome 13q33 have been implicated in the etiology of schizophrenia and, recently, bipolar affective disorder (BPAD). Hattori et al (2003) reported that single-nucleotide polymorphisms (SNPs) near the G72/G30 locus were associated with BPAD in a sample of 22 pedigrees, and that SNP haplotypes were associated in a second, larger sample of triads. The present study attempts to replicate this finding in an independent case-control sample. Six SNPs near the G72/G30 locus, including the most strongly associated markers in the previous study, were tested in 139 cases and 113 ethnically matched controls. Significant association was detected between BPAD and two adjacent SNPs (smallest P=0.007; global P=0.024). Haplotype analysis produced additional support for association (smallest P=0.004; global P=0.004). Analysis of 31 unlinked microsatellite markers detected no population stratification in the cases or controls studied. Although the associated alleles and haplotypes differ from those previously reported, these new results provide further evidence, in an independent sample, for an association between BPAD and genetic variation in the vicinity of the genes G72 and G30. C1 NIMH, Mood & Anxiety Program, Intramural Res Program, NIH,US Dept HHS, Bethesda, MD 20892 USA. Univ Chicago, Dept Human Genet, Chicago, IL 60637 USA. Cent Inst Mental Hlth, Div Genet Epidemiol Psychiat, D-6800 Mannheim, Germany. Johns Hopkins Univ, Sch Med, Dept Psychiat & Behav Sci, Baltimore, MD 21205 USA. RP McMahon, FJ (reprint author), NIMH, Mood & Anxiety Program, Intramural Res Program, NIH,US Dept HHS, 36 Convent Dr,Room 4C08,MSC 4095, Bethesda, MD 20892 USA. RI McMahon, Francis/A-7290-2009; McInnis, Melvin/F-6963-2012; Schulze, Thomas/H-2157-2013; OI McInnis, Melvin/0000-0002-0375-6247; McMahon, Francis/0000-0002-9469-305X NR 34 TC 96 Z9 100 U1 0 U2 3 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1359-4184 J9 MOL PSYCHIATR JI Mol. Psychiatr. PY 2004 VL 9 IS 1 BP 87 EP 92 DI 10.1038/sj.mp.4001453 PG 6 WC Biochemistry & Molecular Biology; Neurosciences; Psychiatry SC Biochemistry & Molecular Biology; Neurosciences & Neurology; Psychiatry GA 757PH UT WOS:000187570300014 PM 14699445 ER PT J AU Buchholz, DR Fu, LZ Shi, YB AF Buchholz, DR Fu, LZ Shi, YB TI Cryopreservation of Xenopus transgenic lines SO MOLECULAR REPRODUCTION AND DEVELOPMENT LA English DT Article DE Xenopus laevis; sperm cryopreservation; transgenesis ID IN-VITRO FERTILIZATION; EMBRYOS; SPERM; SPERMATOZOA; METAMORPHOSIS; EFFICIENT; LAEVIS AB Xenopus laevis has been widely used for molecular, cellular, and developmental studies. With the development of the sperm-mediated transgenic method, it is now possible to study gene function during vertebrate development by using this popular model. On the other hand, like other animal species, it is labor intensive, and the maintenance of transgenic lines is expensive. In this article, we investigated the possibility of using sperm-cryopreservation as a means to preserve transgenic frog lines. We demonstrated that cryopreserved sperms are viable but not fertile under our in vitro fertilization (IVF) conditions. However, by microinjecting cryopreserved sperm nuclei, we successfully regenerated a transgenic line carrying a double promoter transgene construct, where the marker gene encoding the green fluorescent protein (GFP) is driven by the gamma-crystallin gene promoter and a gene of interest, encoding a fusion protein of GFP with the matrix metalloproteinase stromelysin-3 (ST3-GFP), is driven by a heat shock-inducible promoter, We demonstrated the functional transmission of the ST3-GFP transgene by analyzing the phenotype of the F1 animals after heat-shock to induce its expression. Our method thus provides an inexpensive means to preserve transgenic frog lines and a convenient way for distribution of transgenic lines. Furthermore, the ease with which to microinject nuclei compared to the technically demanding transgenesis procedure with variable outcome should facilitate more laboratories to use transgenic Xenopus laevis for functional studies in vivo. C1 NICHHD, Unit Mol Morphogenesis, Lab Gene Regulat & Dev, NIH, Bethesda, MD 20892 USA. RP Shi, YB (reprint author), NICHD, LGRD, NIH, Bldg 18 T,Rm 106, Bethesda, MD 20892 USA. NR 21 TC 13 Z9 13 U1 1 U2 1 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 1040-452X J9 MOL REPROD DEV JI Mol. Reprod. Dev. PD JAN PY 2004 VL 67 IS 1 BP 65 EP 69 DI 10.1002/mrd.20005 PG 5 WC Biochemistry & Molecular Biology; Cell Biology; Developmental Biology; Reproductive Biology SC Biochemistry & Molecular Biology; Cell Biology; Developmental Biology; Reproductive Biology GA 748GR UT WOS:000186854600007 PM 14648875 ER PT S AU Wise, RA AF Wise, RA BE Bevins, RA Bardo, MT TI Drive, incentive, and reinforcement: The antecedents and consequences of motivation SO MOTIVATIONAL FACTORS IN THE ETIOLOGY OF DRUG ABUSE SE NEBRASKA SYMPOSIUM ON MOTIVATION LA English DT Article; Proceedings Paper CT 50th Annual Nebraska Symposium on Motivation CY MAR 28-29, 2002 CL Univ Nebraska, Lincoln, NE HO Univ Nebraska ID OPPONENT-PROCESS THEORY; INTRACRANIAL SELF-STIMULATION; NUCLEUS-ACCUMBENS DOPAMINE; DRUG-INDUCED REINSTATEMENT; D-AMPHETAMINE; MESOLIMBIC DOPAMINE; CONDITIONED ENHANCEMENT; ADMINISTRATION BEHAVIOR; MOLECULAR-MECHANISMS; ANHEDONIA HYPOTHESIS C1 NIDA, NIH, Bethesda, MD USA. RP Wise, RA (reprint author), NIDA, NIH, Bethesda, MD USA. RI Wise, Roy/A-6465-2012 NR 149 TC 23 Z9 23 U1 1 U2 4 PU UNIV NEBRASKA PRESS PI LINCOLN PA 901 NORTH 17TH ST, LINCOLN, NE 68588 USA SN 0146-7875 BN 0-8032-1340-9 J9 NEBR SYM MOTIV PY 2004 VL 50 BP 159 EP 195 PG 37 WC Substance Abuse; Psychology, Social SC Substance Abuse; Psychology GA BBZ99 UT WOS:000228445700007 PM 15160641 ER PT B AU Grieder, FB Schoneboom, BA AF Grieder, FB Schoneboom, BA BE MasComa, S TI Bioterrorism: Viral agents as weapons of mass destruction SO Multidisciplinarity for Parasites, Vectors and Parasitic Diseases, Vol 1 LA English DT Proceedings Paper CT 9th European Multicolloquium of Parasitology CY JUL 18-23, 2004 CL Valencia, SPAIN ID WEST-NILE AB Many different viruses from a wide range of viral families have the potential use as weapons of mass destruction for use by terrorists. Key characteristics that may indicate an attack include an outbreak of disease outside its naturally occurring geographic area, a high incidence or unusual presentation of disease, and identification in domesticated animals or wildlife that serve as reservoirs. Areas that are in urgent need of research include early detection methods, vaccines for immunization, and chemotherapeutic treatment modalities. C1 NIH, Bethesda, MD 20892 USA. RP Grieder, FB (reprint author), NIH, Bldg 10, Bethesda, MD 20892 USA. NR 9 TC 0 Z9 0 U1 0 U2 1 PU MEDIMOND PUBLISHING CO PI BOLOGNA PA VIA RUBBIANI 6/2, 40124 BOLOGNA, ITALY BN 88-7587-115-9 PY 2004 BP 11 EP 16 PG 6 WC Parasitology; Tropical Medicine SC Parasitology; Tropical Medicine GA BDT80 UT WOS:000235290700003 ER PT J AU Healey, KM Pavletic, SZ Al-Omaishi, J Leuschen, MP Pirruccello, SJ Filipi, ML Enke, C Ursick, MM Hahn, F Bowen, JD Nash, RA AF Healey, KM Pavletic, SZ Al-Omaishi, J Leuschen, MP Pirruccello, SJ Filipi, ML Enke, C Ursick, MM Hahn, F Bowen, JD Nash, RA TI Discordant functional and inflammatory parameters in multiple sclerosis patients after autologous haematopoietic stem cell transplantation SO MULTIPLE SCLEROSIS LA English DT Article DE autologous stem cell transplantation; functional outcomes; multiple sclerosis ID BONE-MARROW-TRANSPLANTATION; EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS; EXPERIMENTAL ALLERGIC ENCEPHALOMYELITIS; TOTAL-BODY IRRADIATION; INDUCTION; TOLERANCE; TOXICITY; THERAPY; RATS; MRI AB This article describes outcomes in four patients with advanced multiple sclerosis up to two years after autologous haematopoietic stem cell transplantation using a total-body irradiation-based preparative regimen. MRI and CSF analyses demonstrated clear suppression of the inflammatory processes. The results demonstrate however, a dissociation of inflammation parameters and functional disability findings raising questions about optimal future stem cell transplantation strategies for this disease. C1 Univ Nebraska, Med Ctr, Dept Neurol Sci, Omaha, NE USA. Univ Nebraska, Med Ctr, Dept Internal Med, Omaha, NE USA. Univ Nebraska, Med Ctr, Dept Cell Biol & Anat, Omaha, NE USA. Univ Nebraska, Med Ctr, Dept Pathol & Microbiol, Omaha, NE USA. Univ Nebraska, Med Ctr, Dept Radiat Oncol, Omaha, NE USA. Univ Nebraska, Med Ctr, Dept Radiol, Omaha, NE 68105 USA. Univ Washington, Dept Neurol, Seattle, WA 98195 USA. Univ Washington, Fred Hutchinson Canc Res Ctr, Seattle, WA 98195 USA. RP Pavletic, SZ (reprint author), NCI, Graft Versus Host & Autoimmun Unit, Expt Transplantat & Immunol Branch, Bldg 10,Room 12S241, Bethesda, MD 20892 USA. EM pavletis@mail.nih.gov NR 23 TC 6 Z9 7 U1 0 U2 0 PU ARNOLD, HODDER HEADLINE PLC PI LONDON PA 338 EUSTON ROAD, LONDON NW1 3BH, ENGLAND SN 1352-4585 J9 MULT SCLER JI Mult. Scler. PY 2004 VL 10 IS 3 BP 284 EP 289 DI 10.1191/1352458504ms1022oa PG 6 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 827HU UT WOS:000221891100007 PM 15222693 ER PT J AU Basso, O Campi, R Frydenberg, M Koch-Henriksen, N Bronnum-Hansen, H Olsen, J AF Basso, O Campi, R Frydenberg, M Koch-Henriksen, N Bronnum-Hansen, H Olsen, J TI Multiple sclerosis in women having children by multiple partners. A population-based study in Denmark SO MULTIPLE SCLEROSIS LA English DT Article DE multiple sclerosis; longitudinal study; multiple partners; microchimerism ID AUTOIMMUNE-DISEASE; MICROCHIMERISM; INFECTION; PREGNANCY; RISK AB We investigated whether having children with multiple men is a risk factor for being diagnosed with multiple sclerosis (MS). We studied a cohort of 151 328 women, of whom 64 704 had different men fathering their children and 86 624 the same partner for all births. Women were included if they had a second or higher parity child between 1973 and 1996. The follow-up for MS ended in 1997. There were a total of 213 cases of MS diagnosed during the study period. We analysed data through Poisson regression models. Women having children with different men were not at higher risk of being diagnosed with MS, with the possible exception of a short period after having a baby with a new partner. Women having children with more than one man may have a higher risk of a pregnancy accelerating the diagnosis of MS but are probably not at an overall higher risk of MS. C1 Univ Aarhus, Dept Epidemiol & Social Med, Danish Epidemiol Sci Ctr, Aarhus, Denmark. Ist Ric Farmacol Mario Negri, Lab Mother & Child Hlth, Milan, Italy. Univ Aarhus, Dept Biostat, Aarhus, Denmark. Aalborg Hosp N, Dept Neurol, N Aalborg, Denmark. Natl Inst Publ Hlth, Copenhagen, Denmark. RP Basso, O (reprint author), NIEHS, Epidemiol Branch MDA 3 05, POB 12233,111 TW Alexander Dr, Res Triangle Pk, NC 27709 USA. EM basso2@niehs.nih.gov RI Basso, Olga/E-5384-2010 OI Basso, Olga/0000-0001-9298-4921 NR 17 TC 6 Z9 6 U1 0 U2 0 PU ARNOLD, HODDER HEADLINE PLC PI LONDON PA 338 EUSTON ROAD, LONDON NW1 3BH, ENGLAND SN 1352-4585 J9 MULT SCLER JI Mult. Scler. PY 2004 VL 10 IS 6 BP 621 EP 625 DI 10.1191/1352458504ms1099oa PG 5 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 871AQ UT WOS:000225101700005 PM 15584485 ER PT S AU Hummer, G AF Hummer, G BE Lai, WYC Pau, S Lopez, OD TI Simulations of nanoscale flow: Water, proton, and, biopolymer transport through carbon nanotube membranes SO NANOFABRICATION: TECHNOLOGIES, DEVICES AND APPLICATIONS SE Proceedings of SPIE LA English DT Proceedings Paper CT 1st International Conference on Nanofabrication CY OCT 25-28, 2004 CL Philadelphia, PA SP SPIE, New Jersey Nanotechnol Consortium, JEOL, Quantachrome Instruments, IEICE, Commun Soc, IEICE, Elect Soc DE nanofluidics; nanotubes; membranes; molecular dynamics; nucleic acids; proton transfer; water ID CAVITY-CREATING MUTATIONS; CYTOCHROME-C-OXIDASE; HYDROPHOBIC CAVITIES; MOLECULAR-DYNAMICS; TRANSFER PATHWAYS; DISORDERED WATER; PROTEIN; CHANNEL; BACTERIORHODOPSIN; TRANSLOCATION AB The transport of water, protons, and nucleic acids through carbon nanotubes was studied with an-atom molecular dynamics simulations. Water is found to fill even narrow pores of sub-nanometer diameter, but the filling is sensitive to the strength of attractive pore-water interactions. Motions of the resulting water wires is fast on a molecular scale. Protons were also found to move rapidly along one-dimensionally ordered water chains with a hopping mechanism. The transport of nucleic acids through nanotube membranes is dominated by polymer conformational dynamics during entry, and hydrophobic attachment to the pore walls during exit. C1 NIDDKD, Phys Chem Lab, NIH, Bethesda, MD 20892 USA. RP NIDDKD, Phys Chem Lab, NIH, Bethesda, MD 20892 USA. EM gerhard.hummer@nih.gov NR 51 TC 0 Z9 0 U1 0 U2 7 PU SPIE-INT SOC OPTICAL ENGINEERING PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98227-0010 USA SN 0277-786X BN 0-8194-5545-8 J9 PROC SPIE PY 2004 VL 5592 BP 214 EP 219 DI 10.1117/12.580242 PG 6 WC Instruments & Instrumentation; Optics SC Instruments & Instrumentation; Optics GA BBR38 UT WOS:000227355700024 ER PT B AU Suomi, SJ AF Suomi, SJ BE Coll, CG Bearer, EL Lerner, RM TI How gene-environment interactions influence emotional development in rhesus monkeys SO NATURE AND NURTURE: THE COMPLEX INTERPLAY OF GENETIC AND ENVIRONMENTAL INFLUENCES ON HUMAN BEHAVIOR AND DEVELOPMENT LA English DT Proceedings Paper CT Interdisciplinary Conference on Genetic Influences on Human Behavior and Development CY APR 05-06, 2001 CL Brown Univ, Providence, RI SP Ctr Study Human Dev, Mittlemann Family Directorship, John D & Catherine T MacArthus Fdn Res Network Successful Pathways Middle Childhood HO Brown Univ ID 5-HYDROXYINDOLEACETIC ACID CONCENTRATIONS; NONHUMAN PRIMATE MODEL; ALCOHOL-CONSUMPTION; SEVERE AGGRESSION; PLASMA-CORTISOL; BEHAVIOR; SEPARATION; RESPONSES; EXPERIENCES; ASSOCIATION C1 NIH, Bethesda, MD 20892 USA. RP Suomi, SJ (reprint author), NIH, Bldg 10, Bethesda, MD 20892 USA. NR 63 TC 9 Z9 9 U1 0 U2 2 PU LAWRENCE ERLBAUM ASSOC PUBL PI MAHWAH PA 10 INDUSTRIAL AVE, MAHWAH, NJ 07430 USA BN 0-8058-4387-6 PY 2004 BP 35 EP 51 PG 17 WC Behavioral Sciences; Developmental Biology; Genetics & Heredity SC Behavioral Sciences; Developmental Biology; Genetics & Heredity GA BY80R UT WOS:000189467600003 ER PT J AU Podbilewicz, B AF Podbilewicz, B TI Sweet control of cell migration, cytokinesis and organogenesis SO NATURE CELL BIOLOGY LA English DT Editorial Material ID DISTAL TIP CELLS; CAENORHABDITIS-ELEGANS; C-ELEGANS; METALLOPROTEASE; DISINTEGRIN; PROTEIN; PROTEOGLYCANS; MUTATIONS; FISSION; FUSION AB Why are proteins glycosylated? On the basis of new studies, I propose two models to clarify the specific functions of glycosylation in worms. The first explains how intra- and inter-cellular trafficking of an N-glycosylated disintegrin-metalloprotease guides somatic gonadal cells through their migratory route, determining the shape of an organ. The second explains how rigid coats of secreted chondroitin proteoglycans bend membranes to drive cytokinesis and epithelial invagination. C1 Technion Israel Inst Technol, Dept Biol, IL-32000 Haifa, Israel. RP Podbilewicz, B (reprint author), NICHD, Sect Membrane Biol, Lab Cellular & Mol Biophys, NIH, Bethesda, MD 20892 USA. RI Podbilewicz, Benjamin/N-4825-2014; OI Podbilewicz, Benjamin/0000-0002-0411-4182 NR 17 TC 7 Z9 9 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1465-7392 J9 NAT CELL BIOL JI Nat. Cell Biol. PD JAN PY 2004 VL 6 IS 1 BP 9 EP 11 DI 10.1038/ncb0104-9 PG 3 WC Cell Biology SC Cell Biology GA 760GE UT WOS:000187802600004 PM 14704673 ER PT J AU Huang, QJ Yang, JH Lin, Y Walker, C Cheng, JK Liu, ZG Su, B AF Huang, QJ Yang, JH Lin, Y Walker, C Cheng, JK Liu, ZG Su, B TI Differential regulation of interleukin 1 receptor and Toll-like receptor signaling by MEKK3 SO NATURE IMMUNOLOGY LA English DT Article ID NF-KAPPA-B; ACTIVATED PROTEIN-KINASE; INNATE IMMUNE RECOGNITION; TRANSDUCTION PATHWAY; ERK KINASE; INDUCTION; ADAPTER; BETA; JNK; ALPHA AB Interleukin 1 receptor (IL-1R) and Toll-like receptors (TLRs) induce inflammatory genes through the complex of MyD88, IL-1R-associated protein kinase (IRAK) and tumor necrosis factor receptor-associated factor 6 (TRAF6), which is believed to function 'upstream' of the cascades of IkappaB kinase (IKK) and nuclear factor-kappaB (NF-kappaB); extracellular signal-regulated protein kinase (ERK); c-Jun N-terminal kinase (JNK); and p38 mitogen-activated protein kinase (MAPK). Here we show that MAPK-ERK kinase kinase (MEKK3) is an essential signal transducer of the MyD88-IRAK-TRAF6 complex in IL-1R-TLR4 signaling. MEKK3 forms a complex with TRAF6 in response to IL-1 and lipopolysaccharide (LPS) but not CpG, and is required for IL-1R- and TLR4-induced IL-6 production. Furthermore, MEKK3 is crucial for IL-1- and LPS-induced activation of NF-kappaB and JNK-p38 but not ERK, indicating that MAPKs are differentially activated during IL-1R-TLR4 signaling. These data demonstrate that MEKK3 is crucial for IL-1R and TLR4 signaling through the IKK-NF-kappaB and JNK-p38 MAPK pathways. C1 Univ Texas, MD Anderson Canc Ctr, Dept Immunol, Houston, TX 77030 USA. NCI, Dept Cell & Canc Biol, Bethesda, MD 20892 USA. RP Su, B (reprint author), Univ Texas, MD Anderson Canc Ctr, Dept Immunol, Houston, TX 77030 USA. FU NCI NIH HHS [CA16672]; NHLBI NIH HHS [HL070225]; NIAID NIH HHS [AI44016] NR 35 TC 166 Z9 188 U1 0 U2 8 PU NATURE PUBLISHING GROUP PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 1529-2908 J9 NAT IMMUNOL JI Nat. Immunol. PD JAN PY 2004 VL 5 IS 1 BP 98 EP 103 DI 10.1038/ni1014 PG 6 WC Immunology SC Immunology GA 758LL UT WOS:000187635800019 PM 14661019 ER PT J AU Wang, LH Yang, XY Zhang, XH Mihalic, K Fan, YX Xiao, WH Howard, OMZ Appella, E Maynard, AT Farrar, WL AF Wang, LH Yang, XY Zhang, XH Mihalic, K Fan, YX Xiao, WH Howard, OMZ Appella, E Maynard, AT Farrar, WL TI Suppression of breast cancer by chemical modulation of vulnerable zinc fingers in estrogen receptor SO NATURE MEDICINE LA English DT Article ID CELL-CYCLE PROGRESSION; DNA-BINDING DOMAIN; NUCLEOCAPSID PROTEIN; MOLECULAR-MECHANISMS; ANTITUMOR-ACTIVITY; GENE-EXPRESSION; TRICHOSTATIN-A; TUMOR-GROWTH; MCF-7 CELLS; NUDE-MICE AB Current antiestrogen therapy for breast cancer is limited by the mixed estrogenic and antiestrogenic activity of selective estrogen receptor modulators. Here we show that the function of zinc fingers in the estrogen receptor DNA-binding domain (DBD) is susceptible to chemical inhibition by electrophilic disulfide benzamide and benzisothiazolone derivatives, which selectively block binding of the estrogen receptor to its responsive element and subsequent transcription. These compounds also significantly inhibit estrogen-stimulated cell proliferation, markedly reduce tumor mass in nude mice bearing human MCF-7 breast cancer xenografts, and interfere with cell-cycle and apoptosis regulatory gene expression. Functional assays and computational analysis support a molecular mechanism whereby electrophilic agents preferentially disrupt the vulnerable C-terminal zinc finger, thus suppressing estrogen receptor-mediated breast carcinoma progression. Our results provide the proof of principle for a new strategy to inhibit breast cancer at the level of DNA binding, rather than the classical antagonism of estrogen binding. C1 NCI, Basic Res Program, SAIC Frederick, NIH, Frederick, MD 21702 USA. NCI, Cytokine Mol Mech Sect, NIH, Frederick, MD 21702 USA. US FDA, Div Therapeut Prot, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. NCI, Mol Immunoregulat Lab, NIH, Frederick, MD 21702 USA. NCI, Cell Biol Lab, NIH, Bethesda, MD 20892 USA. RP Wang, LH (reprint author), NCI, Basic Res Program, SAIC Frederick, NIH, POB B, Frederick, MD 21702 USA. RI Xiao, Weihua/N-2775-2013; Howard, O M Zack/B-6117-2012 OI Xiao, Weihua/0000-0001-9102-6326; Howard, O M Zack/0000-0002-0505-7052 FU NCI NIH HHS [N01-CO-12400] NR 45 TC 61 Z9 62 U1 2 U2 9 PU NATURE PUBLISHING GROUP PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 1078-8956 J9 NAT MED JI Nat. Med. PD JAN PY 2004 VL 10 IS 1 BP 40 EP 47 DI 10.1038/nm969 PG 8 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA 759NK UT WOS:000187743600037 PM 14702633 ER PT J AU Bonifacino, JS AF Bonifacino, JS TI The GGA proteins: Adaptors on the move SO NATURE REVIEWS MOLECULAR CELL BIOLOGY LA English DT Review ID TRANS-GOLGI NETWORK; MANNOSE 6-PHOSPHATE RECEPTORS; GUANINE-NUCLEOTIDE EXCHANGE; DOMAIN-CONTAINING PROTEIN; CLATHRIN-COATED PITS; FACTOR-II RECEPTOR; GAMMA-ADAPTIN; STRUCTURAL BASIS; VHS DOMAINS; ACIDIC-CLUSTER AB The GGA proteins are a family of ubiquitously expressed, Arf-dependent clathrin adaptors that mediate the sorting of mannose-6-phosphate receptors between the trans-Golgi network and endosomes. Recent studies have elucidated the biochemical and structural bases for the interaction of the GGA proteins with many binding partners, and have shed light on the molecular and cellular mechanisms by which the GGA proteins participate in protein sorting. C1 NICHHD, Cell Biol & Metab Branch, NIH, Bethesda, MD 20892 USA. RP Bonifacino, JS (reprint author), NICHHD, Cell Biol & Metab Branch, NIH, Bldg 18T,Room 101, Bethesda, MD 20892 USA. EM juan@helix.nih.gov OI Bonifacino, Juan S./0000-0002-5673-6370 NR 88 TC 248 Z9 252 U1 0 U2 4 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1471-0072 J9 NAT REV MOL CELL BIO JI Nat. Rev. Mol. Cell Biol. PD JAN PY 2004 VL 5 IS 1 BP 23 EP 32 DI 10.1038/nrm1279 PG 10 WC Cell Biology SC Cell Biology GA 762QK UT WOS:000187993500012 PM 14708007 ER PT J AU Turk, BE Wong, TY Schwarzenbacher, R Jarrell, ET Leppla, SH Collier, RJ Liddington, RC Cantley, LC AF Turk, BE Wong, TY Schwarzenbacher, R Jarrell, ET Leppla, SH Collier, RJ Liddington, RC Cantley, LC TI The structural basis for substrate and inhibitor selectivity of the anthrax lethal factor SO NATURE STRUCTURAL & MOLECULAR BIOLOGY LA English DT Article ID MATRIX-METALLOPROTEINASE INHIBITORS; STROMELYSIN CATALYTIC DOMAIN; BACILLUS-ANTHRACIS; CRYSTAL-STRUCTURE; FACTOR CLEAVES; KINASE-KINASE; MAP KINASES; ACTIVE-SITE; TNF-ALPHA; MACROPHAGES AB Recent events have created an urgent need for new therapeutic strategies to treat anthrax. We have applied a mixture-based peptide library approach to rapidly determine the optimal peptide substrate for the anthrax lethal factor (LF), a metalloproteinase with an important role in the pathogenesis of the disease. Using this approach we have identified peptide analogs that inhibit the enzyme in vitro and that protect cultured macrophages from LF-mediated cytolysis. The crystal structures of LF bound to an optimized peptide substrate and to peptide-based inhibitors provide a rationale for the observed selectivity and may be exploited in the design of future generations of LF inhibitors. C1 Beth Israel Deaconess Med Ctr, Dept Med, Div Signal Transduct, Boston, MA 02215 USA. Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02215 USA. Burnham Inst, La Jolla, CA 92037 USA. NIAID, Bethesda, MD 20892 USA. Harvard Univ, Sch Med, Dept Microbiol & Mol Genet, Boston, MA 02115 USA. RP Cantley, LC (reprint author), Beth Israel Deaconess Med Ctr, Dept Med, Div Signal Transduct, 330 Brookline Ave, Boston, MA 02215 USA. EM rlidding@burnham.org; lewis_cantley@hms.harvard.edu RI Cantley, Lewis/D-1800-2014; OI Cantley, Lewis/0000-0002-1298-7653; Collier, R John/0000-0002-2427-4239 FU NIGMS NIH HHS [R01 GM056203] NR 43 TC 147 Z9 153 U1 0 U2 5 PU NATURE PUBLISHING GROUP PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 1545-9985 J9 NAT STRUCT MOL BIOL JI Nat. Struct. Mol. Biol. PD JAN PY 2004 VL 11 IS 1 BP 60 EP 66 DI 10.1038/nsmb708 PG 7 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA 802DJ UT WOS:000220143900014 PM 14718924 ER PT J AU Panchal, RG Hermone, AR Nguyen, TL Wong, TY Schwarzenbacher, R Schmidt, J Lane, D McGrath, C Turk, BE Burnett, J Aman, MJ Little, S Sausville, EA Zaharevitz, DW Cantley, LC Liddington, RC Gussio, R Bavari, S AF Panchal, RG Hermone, AR Nguyen, TL Wong, TY Schwarzenbacher, R Schmidt, J Lane, D McGrath, C Turk, BE Burnett, J Aman, MJ Little, S Sausville, EA Zaharevitz, DW Cantley, LC Liddington, RC Gussio, R Bavari, S TI Identification of small molecule inhibitors of anthrax lethal factor SO NATURE STRUCTURAL & MOLECULAR BIOLOGY LA English DT Article ID TOXIN PROTECTIVE ANTIGEN; ELECTRON-DENSITY; RECEPTOR; CLEAVES; KINASE; FURIN AB The virulent spore-forming bacterium Bacillus anthracis secretes anthrax toxin composed of protective antigen (PA), lethal factor(LF) and edema factor (EF). LF is a Zn-dependent metalloprotease that inactivates key signaling molecules, such as mitogen-activated protein kinase kinases (MAPKK), to ultimately cause cell death. We report here the identification of small molecule (nonpeptidic) inhibitors of LF. Using a two-stage screening assay, we determined the LF inhibitory properties of 19 compounds. Here, we describe six inhibitors on the basis of a pharmacophoric relationship determined using X-ray crystallographic data, molecular docking studies and three-dimensional (3D) database mining from the US National Cancer Institute (NCI) chemical repository. Three of these compounds have K-i values in the 0.5-5 muM range and show competitive inhibition. These molecular scaffolds may be used to develop therapeutically viable inhibitors of LF. C1 NCI Frederick, Dev Therapeut Program, Frederick, MD 21702 USA. Burnham Inst, La Jolla, CA 92037 USA. USA, Med Res Inst Infect Dis, Frederick, MD 21702 USA. Harvard Inst Med, Beth Israel Deaconess Med Ctr, Div Signal Transduct, Boston, MA 02115 USA. RP Panchal, RG (reprint author), NCI Frederick, Dev Therapeut Program, Frederick, MD 21702 USA. EM panchal@dtpax2.ncifcrf.gov; bavaris@ncifcrf.gov RI Cantley, Lewis/D-1800-2014 OI Cantley, Lewis/0000-0002-1298-7653 FU NIGMS NIH HHS [R01 GM056203] NR 25 TC 111 Z9 117 U1 0 U2 7 PU NATURE PUBLISHING GROUP PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 1545-9985 J9 NAT STRUCT MOL BIOL JI Nat. Struct. Mol. Biol. PD JAN PY 2004 VL 11 IS 1 BP 67 EP 72 DI 10.1038/nsmb711 PG 6 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA 802DJ UT WOS:000220143900015 PM 14718925 ER PT S AU Kasabov, NK Chan, ZSH Jain, V Sidorov, I Dimitrov, DS AF Kasabov, NK Chan, ZSH Jain, V Sidorov, I Dimitrov, DS BE Pal, NR Kasabov, N Mudi, RK Pal, S Parui, SK TI Gene regulatory network discovery from time-series gene expression data - A computational intelligence approach SO NEURAL INFORMATION PROCESSING SE LECTURE NOTES IN COMPUTER SCIENCE LA English DT Article; Proceedings Paper CT 11th International Conference on Neural Information Processing CY NOV 22-25, 2004 CL Calcutta, INDIA SP Indian Stat Inst, Jadavpur Univ ID FUNCTIONAL GENOMICS AB The interplay of interactions between DNA, RNA and proteins leads to genetic regulatory networks (GRN) and in turn controls the gene regulation. Directly or indirectly in a cell such molecules either interact in a positive or in repressive manner therefore it is hard to obtain the accurate computational models through which the final state of a cell can be predicted with certain accuracy. This paper describes biological behaviour of actual regulatory systems and we propose a novel method for GRN discovery of a large number of genes from multiple time series gene expression observations over small and irregular time intervals. The method integrates a genetic algorithm (GA) to select a small number of genes and a Kalman filter to derive the GRN of these genes. After GRNs of smaller number of genes are obtained, these GRNs may be integrated in order to create the GRN of a larger group of genes of interest. C1 Auckland Univ Technol, KEDRI, Auckland, New Zealand. Natl Canc Inst, Washington, DC USA. RP Kasabov, NK (reprint author), Auckland Univ Technol, KEDRI, Private Bag 92006, Auckland, New Zealand. EM nkasabov@aut.ac.nz; shchan@aut.ac.nz; vishal.jain@aut.ac.nz; sidorovi@ncifcrf.gov; dimitrov@ncifcrf.gov NR 21 TC 12 Z9 12 U1 0 U2 2 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY SN 0302-9743 BN 3-540-23931-6 J9 LECT NOTES COMPUT SC PY 2004 VL 3316 BP 1344 EP 1353 PG 10 WC Computer Science, Artificial Intelligence; Computer Science, Theory & Methods SC Computer Science GA BBK50 UT WOS:000225878300208 ER PT J AU Prados, MD Yung, WKA Fine, HA Greenberg, HS Junck, L Chang, SM Nicholas, MK Robins, HI Mehta, MP Fink, KL Jaeckle, KA Kuhn, J Hess, KR Schold, SC AF Prados, MD Yung, WKA Fine, HA Greenberg, HS Junck, L Chang, SM Nicholas, MK Robins, HI Mehta, MP Fink, KL Jaeckle, KA Kuhn, J Hess, KR Schold, SC TI Phase 2 study of BCNU and temozolomide for recurrent glioblastoma multiforme: North American Brain Tumor Consortium study SO NEURO-ONCOLOGY LA English DT Article ID 1ST RELAPSE; 1,3-BIS(2-CHLOROETHYL)-1-NITROSOUREA; ASTROCYTOMA; TRIAL AB The purpose of this study was to evaluate the activity, measured in terms of progression-free survival (PFS) and response rates, of 1,3-bis(chloro-ethyl)-1-nitrosourea (BCNU) plus temozolomide in adult patients with recurrent glioblastoma multiforme. The phase 2 dose and schedule for this trial was BCNU 150 mg/m(2) i.v. followed in 2 h by temozolomide 550 mg/m(2) as a single oral dose. Treatment was repeated every 6 weeks for up to 8 cycles unless tumor progression was documented. The primary end point was PFS at 6 months (PFS-6). Response was a secondary end point, measured by MR imaging, neurological status, and steroid requirements prior to each 6-week cycle. The median age of eligible patients was 53, and 89.5% had no prior chemotherapy. All patients were evaluable for toxicity and time to progression. The PFS-6 was 21%. Overall survival was 68% at 6 months and 26% at 1 year. The MRI response for 36 patients was 2 partial responses, 2 minor responses, 19 cases of stable disease, and 13 immediate progressions. Median survival was 34 weeks, and median PFS was 11 weeks. Toxicity was primarily myelosuppression; no toxic deaths occurred. Historical phase 2 study data in this patient population show a PFS-6 of 15%. Recent data for use of temozolomide alone have shown a PFS-6 of 21%. We conclude that BCNU plus temozolomide when used in these doses and schedule has only modest activity, with significant toxicity, and appears to be no more effective than single-agent temozolomide. C1 Univ Calif San Francisco, Dept Neurol Surg, San Francisco, CA 94143 USA. Univ Calif San Francisco, Dept Neurooncol, San Francisco, CA 94143 USA. Univ Texas, MD Anderson Canc Ctr, Dept Neurooncol, Houston, TX 77030 USA. Univ Texas, MD Anderson Canc Ctr, Dept Biostat, Houston, TX 77030 USA. NCI, Neurooncol Branch, Bethesda, MD 20892 USA. Univ Michigan, Dept Neurol, Ann Arbor, MI 48109 USA. Univ Wisconsin, Dept Med, Madison, WI 53792 USA. Univ Wisconsin, Dept Radiotherapy, Madison, WI 53792 USA. Univ Texas, SW Med Ctr, Dept Neurol, Dallas, TX 75390 USA. Mayo Clin Jacksonville, Dept Neurol, Jacksonville, FL 32224 USA. Mayo Clin Jacksonville, Dept Hematol Oncol, Jacksonville, FL 32224 USA. Univ Texas, Hlth Sci Ctr, Coll Pharm, San Antonio, TX 78229 USA. Univ Pittsburgh, Off Clin Res, Pittsburgh, PA 15261 USA. RP Prados, MD (reprint author), Univ Calif San Francisco, Dept Neurol Surg, 400 Parnassus Ave,Room A808, San Francisco, CA 94143 USA. OI mehta, minesh/0000-0002-4812-5713 FU NCI NIH HHS [CA62455, CA62399, CA62405, CA62407, CA62412, CA62421, CA62422, CA62426, U01 CA062399, U01 CA062405, U01 CA062407, U01 CA062412, U01 CA062421, U01 CA062421-07, U01 CA062422, U01 CA062426]; NCRR NIH HHS [M01 RR000042, M01 RR000056, M01 RR000079, M01 RR000633, M01 RR003186, M01-RR00042, M01-RR00056, M01-RR00079, M01-RR00633, M01-RR03186] NR 12 TC 45 Z9 47 U1 0 U2 2 PU DUKE UNIV PRESS PI DURHAM PA 905 W MAIN ST, STE 18-B, DURHAM, NC 27701 USA SN 1522-8517 J9 NEURO-ONCOLOGY JI Neuro-Oncology PD JAN PY 2004 VL 6 IS 1 BP 33 EP 37 DI 10.1215/S1152.8517.03.00030.9 PG 5 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA 757WE UT WOS:000187583800006 PM 14769138 ER PT J AU Prados, MD Yung, WKA Jaeckle, KA Robins, HI Mehta, MP Fine, HA Wen, PY Cloughesy, TF Chang, SM Nicholas, MK Schiff, D Greenberg, HS Junck, L Fink, KL Hess, KR Kuhn, J AF Prados, MD Yung, WKA Jaeckle, KA Robins, HI Mehta, MP Fine, HA Wen, PY Cloughesy, TF Chang, SM Nicholas, MK Schiff, D Greenberg, HS Junck, L Fink, KL Hess, KR Kuhn, J TI Phase 1 trial of irinotecan (CPT-11) in patients with recurrent malignant glioma: A North American Brain Tumor Consortium study SO NEURO-ONCOLOGY LA English DT Article ID HUMAN LIVER; ACTIVE METABOLITE; GLUCURONIDATION; SN-38; CARBOXYLESTERASE; TRANSPORTERS; MICROSOMES; EXPRESSION; RESISTANCE; HUMANS AB This study was conducted to determine the maximum tolerated dose and dose-limiting toxicity of irinotecan (CPT-11) administered every 3 weeks to adults with progressive malignant glioma who were treated with enzyme-inducing antiepileptic drug (EIAED) therapy, and to compare the pharmacokinetics with those in patients not on EIAED therapy treated at the recommended phase 2 dose for other cancers. The CPT-11 dose was 350 mg/m(2) i.v. every 3 weeks and remained fixed in patients not on EIAED therapy, but the dose was escalated by 50-mg/m(2) increments in patients on EIAED therapy. CPT-11 and its metabolites SN-38, SN-38 glucuronide (SN-38G), and APC (7-ethyl-10[4-N-(5 aminopentanoic acid)-1-piperidine]-carbonyloxycamptothecin) were characterized in both groups. Patients on EIAEDs received 350 to 800 mg/m(2) of CPT-11. Dose-limiting toxicity was due to grade 3 diarrhea despite maximal doses of loperamide. The systemic levels of CPT-11, APC, SN-38G, and SN-38 were all lower in the EIAED group. There was a moderate-to-fair relationship between CPT-11 dose and the area under the curve (AUC) for CPT-11 and APC over the dosage range of 350 to 800 mg/m(2), but no relationship between CPT-11 dose and the AUC for SN-38 or SN-38G. At the 750-mg/m(2) dose, the AUC for CPT-11 (21.6 mug x h/ml) matched the AUC (21.6 mug x h/ml) in the non-EIAED group treated with 350 mg/m(2) of CPT-11. We conclude that the recommended phase 2 dose of CPT-11 for patients on EIAEDs is 750 mg/m(2) when given every 3 weeks. A phase 2 study of patients with recurrent malignant glioma is ongoing to assess the efficacy of CPT-11 when the dose is stratified according to the use of EIAEDs. C1 Univ Calif San Francisco, Dept Neurol Surg, San Francisco, CA 94143 USA. Univ Calif San Francisco, Dept Neurooncol, San Francisco, CA 94143 USA. Univ Texas, MD Anderson Canc Ctr, Dept Neurooncol, Houston, TX 77030 USA. Univ Texas, MD Anderson Canc Ctr, Dept Biostat, Houston, TX 77030 USA. Mayo Clin Jacksonville, Dept Neurol, Jacksonville, FL 32224 USA. Mayo Clin Jacksonville, Dept Hematol Oncol, Jacksonville, FL 32224 USA. Univ Wisconsin, Dept Med, Madison, WI 53792 USA. Univ Wisconsin, Dept Radiotherapy, Madison, WI 53792 USA. NCI, Neurooncol Branch, Bethesda, MD 20892 USA. Dana Farber Canc Inst, Ctr Neurooncol, Boston, MA 02115 USA. Univ Calif Los Angeles, Neurooncol Program, Los Angeles, CA 90095 USA. Univ Virginia, Hlth Sci Ctr, Div Neurooncol, Charlottesville, VA 22908 USA. Univ Michigan, Dept Neurol, Ann Arbor, MI 48109 USA. Univ Texas, SW Med Ctr, Dept Neurol, Dallas, TX 75390 USA. Univ Texas, Hlth Sci Ctr, Coll Pharm, San Antonio, TX 78229 USA. RP Prados, MD (reprint author), Univ Calif San Francisco, Dept Neurol Surg, 400 Parnassus Ave,Room A808, San Francisco, CA 94143 USA. OI mehta, minesh/0000-0002-4812-5713 FU NCRR NIH HHS [M01 RR003186-15S30327, M01 RR003186] NR 23 TC 49 Z9 49 U1 1 U2 1 PU DUKE UNIV PRESS PI DURHAM PA 905 W MAIN ST, STE 18-B, DURHAM, NC 27701 USA SN 1522-8517 J9 NEURO-ONCOLOGY JI Neuro-Oncology PD JAN PY 2004 VL 6 IS 1 BP 44 EP 54 DI 10.1215/S1152.8517.03.00029.2 PG 11 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA 757WE UT WOS:000187583800008 PM 14769140 ER PT J AU Benjamin, RK Hochberg, FH Fox, E Bungay, PM Elmquist, WF Stewart, CF Gallo, JM Collins, JM Pelletier, RP de Groot, JF Hickner, RC Cavus, I Grossman, SA Colvin, OM AF Benjamin, RK Hochberg, FH Fox, E Bungay, PM Elmquist, WF Stewart, CF Gallo, JM Collins, JM Pelletier, RP de Groot, JF Hickner, RC Cavus, I Grossman, SA Colvin, OM TI Review of microdialysis in brain tumors, from concept to application: First Annual Carolyn Frye-Halloran Symposium SO NEURO-ONCOLOGY LA English DT Review ID ANGIOGENESIS INHIBITOR TNP-470; IN-VIVO MICRODIALYSIS; HEAD-INJURED PATIENTS; CEREBRAL BLOOD-FLOW; INTRACEREBRAL MICRODIALYSIS; MALIGNANT GLIOMA; EXTRACELLULAR GLUTAMATE; CEREBROSPINAL-FLUID; DRUG TRANSPORT; GRADE GLIOMAS AB In individuals with brain tumors, pharmacodynamic and pharmacokinetic studies of therapeutic agents have historically used analyses of drug concentrations in serum or cerebrospinal fluid, which unfortunately do not necessarily reflect concentrations within the tumor and adjacent brain. This review article introduces to neurological and medical oncologists, as well as pharmacologists, the application of microdialysis in monitoring drug metabolism and delivery within the fluid of the interstitial space of brain tumor and its surroundings. Microdialysis samples soluble molecules from the extracellular fluid via a semipermeable membrane at the tip of a probe. In the past decade, it has been used predominantly in neurointensive care in the setting of brain trauma, vasospasm, epilepsy, and intracerebral hemorrhage. At the first Carolyn Frye-Halloran Symposium held at Massachusetts General Hospital in March 2002, the concept of microdialysis was extended to specifically address its possible use in treating brain tumor patients. In doing so we provide a rationale for the use of this technology by a National Cancer Institute consortium, New Approaches to Brain Tumor Therapy, to measure levels of drugs in brain tissue as part of phase 1 trials. C1 Massachusetts Gen Hosp, Brain Tumor Ctr, Boston, MA 02114 USA. NCI, Bethesda, MD 20892 USA. NIH, Bethesda, MD 20892 USA. Univ Minnesota, Dept Pharmaceut, Minneapolis, MN 55455 USA. St Jude Childrens Res Hosp, Memphis, TN 38105 USA. Fox Chase Canc Ctr, Dept Pharmacol, Philadelphia, PA 19111 USA. US FDA, Ctr Drug Evaluat & Res, Lab Clin Pharmacol, Rockville, MD 20857 USA. Univ Texas, MD Anderson Canc Ctr, Houston, TX 77030 USA. CMA Microdialysis, N Chelmsford, MA 01863 USA. E Carolina Univ, Human Performance Lab, Greenville, NC 27858 USA. Yale Univ, Dept Psychiat, New Haven, CT 06519 USA. Johns Hopkins, Sidney Kimmel Comprehens Canc Ctr, Dept Neurooncol, Baltimore, MD 21231 USA. Duke Univ, Med Ctr, Dept Med, Durham, NC 27710 USA. RP Benjamin, RK (reprint author), Carolina Neurosurg & Spine Associates, Neurooncol Ctr, 1628 E Morehead Rd,Suite 200, Charlotte, NC 28207 USA. EM Ramsis.benjamin@cnsa.co NR 66 TC 25 Z9 27 U1 2 U2 6 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1522-8517 J9 NEURO-ONCOLOGY JI Neuro-Oncology PD JAN PY 2004 VL 6 IS 1 BP 65 EP 74 DI 10.1215/S1152.8517.03.00010.3 PG 10 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA 757WE UT WOS:000187583800011 PM 14769143 ER PT J AU Bhaskar, K Shareef, MM Sharma, VM Shetty, APK Ramamohan, Y Pant, HC Raju, TR Shetty, KT AF Bhaskar, K Shareef, MM Sharma, VM Shetty, APK Ramamohan, Y Pant, HC Raju, TR Shetty, KT TI Co-purification and localization of Munc18-1 (p67) and Cdk5 with neuronal cytoskeletal proteins SO NEUROCHEMISTRY INTERNATIONAL LA English DT Article DE Munc 18-1 (p67); Cdk5; neurofilaments and microtubules ID AMYLOID PRECURSOR PROTEIN; CYCLIN-DEPENDENT KINASE-5; NEUROFILAMENT PHOSPHORYLATION; INTERMEDIATE FILAMENTS; MICROTUBULE DYNAMICS; NF-H; ASSOCIATION; BRAIN; SUBUNIT; OOCYTES AB Munc 18-1 (p67, nSec1, rbSec1), a neuron-specific 67kDa protein was independently identified as a syntaxin-binding protein, and as a component that co-purifies with, and regulates the kinase activity of cyclin dependent kinase (Cdk5). Gene knockout studies have demonstrated a role for Munc 18-1 in synaptic vesicle docking and neurotransmitter release. Mice lacking Munc 18-1 gene were synaptically silent, but the gene deletion did not prevent normal brain assembly, including the formation of layered structures, fiber pathways and morphologically defined synapses. Previous study has shown that Munc 18-1 facilitates Cdk5 mediated phosphorylation of KSPXK domains of the neuronal cytoskeletal elements, suggesting that Munc 18-1 may function in the regulation of cytoskeletal dynamics. Present study demonstrates the co-purification and co-localization of Munc 18 with cytoskeletal elements and forms first step towards understanding the role for Munc18-1 in cytoskeletal dynamics. Conversely, the cytoskeletal proteins and Cdk5 co-purifies with Munc 18-1 in a Munc 18-1 immuno-affinity chromatography, suggesting a strong protein-protein interaction. Findings from immunofluorescence studies in PC 12 cells have shown co-localization of Munc 18-1 and Cdk5 with neurofilaments and microtubules. Further, immunohistochemical and immuno-electron microscopic studies of rat olfactory bulb also demonstrated co-localization of Munc 18-1 and Cdk5 with cytoskeletal elements. Thus, the biochemical evidence of strong interaction between Munc 18-1 with cytoskeletal proteins and morphological evidence of their (Munc18 and cytoskeletal elements) identical sub-cellular localization is suggestive of the possible role for Munc 18-1 in cytoskeletal dynamics. (C) 2003 Elsevier Science Ltd. All rights reserved. C1 Natl Inst Mental Hlth & Neurosci, Dept Neurochem, Bangalore 560029, Karnataka, India. Natl Inst Mental Hlth & Neurosci, Dept Neuropathol, Bangalore 560029, Karnataka, India. NINDS, Neurochem Lab, NIH, Bethesda, MD USA. Natl Inst Mental Hlth & Neurosci, Dept Neurophysiol, Bangalore 560029, Karnataka, India. RP Shetty, KT (reprint author), Natl Inst Mental Hlth & Neurosci, Dept Neurochem, Bangalore 560029, Karnataka, India. RI SHETTY, PAVAN/B-9804-2012; OI Shetty, Pavan/0000-0002-6484-7417 NR 41 TC 25 Z9 26 U1 1 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0197-0186 J9 NEUROCHEM INT JI Neurochem. Int. PD JAN PY 2004 VL 44 IS 1 BP 35 EP 44 DI 10.1016/S0197-0186(03)00099-8 PG 10 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 725RM UT WOS:000185556200005 PM 12963086 ER PT J AU Schellinger, PD Fiebach, AB AF Schellinger, PD Fiebach, AB TI Intracranial hemorrhage - The role of magnetic resonance imaging SO NEUROCRITICAL CARE LA English DT Review DE MRI; intracranial hemorrhage; perihemorrhagic penumbra; diagnosis; subarachnoid hemorrhage ID ACUTE SUBARACHNOID HEMORRHAGE; SPONTANEOUS INTRACEREBRAL HEMORRHAGE; CEREBRAL BLOOD-FLOW; ACUTE ISCHEMIC-STROKE; RECOVERY PULSE SEQUENCES; COMPUTED-TOMOGRAPHY; WEIGHTED MRI; RISK-FACTORS; NO EVIDENCE; DIFFUSION AB The initial and exclusive use of MRI in patients with a stroke syndrome is feasible, probably cost-effective, and even time saving when considering its potential wealth of information. MRI maybe the diagnostic tool of choice in patients with all stages of stroke, especially in the hyperacute assessment of ICH, and could be equivalent to CT and CTA in SAH diagnosis. The authors' aim is to provide a comprehensive review about the potential role of MRI in evaluating ICH and SAH. Emerging applications, such as the assessment of microbleeds as a risk factor for secondary hemorrhage after thrombolysis and perihemorrhagic ischemic changes as a potential marker for patients likely to benefit from hematoma evacuation, are reviewed. C1 Univ Heidelberg, Neurol Klin, Dept Neurol, D-69120 Heidelberg, Germany. NINDS, Sect Stroke Diagnost & Therapeut, NIH, Bethesda, MD 20892 USA. Univ Heidelberg, Dept Neuroradiol, D-6900 Heidelberg, Germany. RP Schellinger, PD (reprint author), Univ Heidelberg, Neurol Klin, Dept Neurol, Neuenheimer Feld 400, D-69120 Heidelberg, Germany. EM Peter-Schellinger@med.un-i-heidelberg.de NR 98 TC 12 Z9 13 U1 0 U2 7 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 USA SN 1541-6933 J9 NEUROCRIT CARE JI Neurocrit. Care PY 2004 VL 1 IS 1 BP 31 EP 45 DI 10.1385/NCC:1:1:31 PG 15 WC Critical Care Medicine; Clinical Neurology SC General & Internal Medicine; Neurosciences & Neurology GA 945FL UT WOS:000230488300004 PM 16174896 ER PT J AU Chalela, JA Haymore, J Schellinger, PD Kong, DW Warach, S AF Chalela, JA Haymore, J Schellinger, PD Kong, DW Warach, S TI Acute stroke patients are being underfed - A nitrogen balance study SO NEUROCRITICAL CARE LA English DT Article DE acute stroke; nutrition; nitrogen balance; catabolic response ID HEAD-INJURY; CYTOKINES; CORTISOL; SERUM AB Introduction: Patients with acute neurological illness may be hypercatabolic. The Harris-Benedict Equation (HBE) is used to estimate energy needs in acute stroke. A "stress factor" for stroke does not exist, and it is not known if the HBE accurately estimates the energy expenditure needs in acute ischemic or hemorrhagic stroke. We sought to assess nitrogen balance in patients with acute stroke and to determine the variables associated with negative nitrogen balance. Materials and Methods: This was a case series, single-center study. Eligibility criteria included acute stroke requiring enteral nutrition, tolerating tube feedings at goal, normal urine output, and no underlying catabolic illness. Enteral feeding was adjusted to meet HBE requirements. After 24 hours of goal feeding, a 12-hour urine collection for nitrogen excretion was done. We determined if any of the following variables were associated with negative nitrogen balance: gender, glucose 6.6 mmol/L or more, age 80 years or older, National Institutes of Health Stroke Scale (NIHSS) 20 or higher, mechanical ventilation, and diabetes mellitus. Results: We studied 27 patients (10 with intracranial hemorrhages and 17 with ischemic strokes) during an 18-month period. The median age was 80 (range: 48-90), and the median NIHSS was 19 (range: 4-38). The median time to feeding was 2 days (range: 1-8), the median time from onset to nitrogen balance was 5 days (range: 2-11), and the median interval between initiation of feeding and nitrogen collection was 2 days (range: 1-5) Negative nitrogen balance was seen in 12 of 27 (44%) patients. There was no relation between age, NIHSS, stroke type, admission glucose, history of diabetes, and mechanical ventilation use and nitrogen balance. Only 11 of 27 patients were anabolic. Conclusion: Critically ill stroke patients are being underfed using the current methods to estimate caloric needs. Hypercatabolism is common in acute stroke; clinical variables do not seem to allow prediction of this catabolic state. C1 Natl Inst Neurol Disorders & Stroke, Sect Stroke Diagnost & Therapeut, NIH, Bethesda, MD 20892 USA. RP Chalela, JA (reprint author), Natl Inst Neurol Disorders & Stroke, Sect Stroke Diagnost & Therapeut, NIH, 10 Ctr Dr,Bldg 10,Room B1D 733,MSC 1063, Bethesda, MD 20892 USA. EM chalelaj@ninds.nih.gov NR 11 TC 14 Z9 15 U1 1 U2 2 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 USA SN 1541-6933 J9 NEUROCRIT CARE JI Neurocrit. Care PY 2004 VL 1 IS 3 BP 331 EP 334 DI 10.1385/NCC:1:3:331 PG 4 WC Critical Care Medicine; Clinical Neurology SC General & Internal Medicine; Neurosciences & Neurology GA 945FQ UT WOS:000230488800007 PM 16174930 ER PT J AU Chalela, JA Ezzeddine, MA Davis, L Warach, S AF Chalela, JA Ezzeddine, MA Davis, L Warach, S TI Myocardial injury in acute stroke - A troponin I study SO NEUROCRITICAL CARE LA English DT Article DE acute stroke; troponin; cardic injury; stroke severity ID CREATINE-KINASE; LESIONS; DAMAGE AB Introduction: Acute cerebrovascular insults can induce a variety of cardiac changes. We sought to describe the findings in a cohort of patients who had an acute stroke in whom Troponin I (TI) was sampled to determine the presence of associated myocardial damage. Materials and Methods: This is a retrospective case series study. The investigators identified all patients who had an acute stroke in whom TI had been sampled. Demographics, stroke severity as determined by National Institutes of Health Stroke Scale (NIHSS), stroke location, electrocardiogram (EKG) results, echocardiography results, and cardiology evaluation were obtained from the stroke database or the medical records. Logistic regression analysis was performed to determine the clinical and paraclinical variables associated with TI elevation. Results: During a 14-month period, 191 patients were studied, but TI levels were available in only 160 (84%) of the 191 patients. The sample was composed of 89 (55%) men and 71 (45%) women, with a median age of 76 years. Elevated TI occurred in 10 (6%) of the 160 patients. EKG changes suggestive of cardiac ischemia occurred in 2 of the 10 patients with high TI who had a stroke. In the remainder patients' TI elevations occurred in the absence of EKG or echocardiographic abnormalities. High NIHSS but no other variable was associated with TI elevation (p =.02). Ventricular arrhythmias, congestive heart failure, post-infarct pericarditis, and sudden death did not occur. Conclusion: In this limited sample, elevated TI occurred in 6% of the patients with acute stroke and was associated with severe stroke. Although in some patients who have acute stroke, TI elevation may represent coronary ischemia, in others it may reflect neurogenic-induced cardiac injury. C1 Natl Inst Neurol Disorders & Stroke, NIH, Bethesda, MD 20892 USA. RP Chalela, JA (reprint author), Natl Inst Neurol Disorders & Stroke, NIH, 10 Ctr Dr,Bldg 10,Room B1D 733,MSC 1063, Bethesda, MD 20892 USA. EM chalelaj@ninds.nih.go NR 10 TC 29 Z9 32 U1 0 U2 2 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 USA SN 1541-6933 J9 NEUROCRIT CARE JI Neurocrit. Care PY 2004 VL 1 IS 3 BP 343 EP 346 DI 10.1385/NCC:1:3:343 PG 4 WC Critical Care Medicine; Clinical Neurology SC General & Internal Medicine; Neurosciences & Neurology GA 945FQ UT WOS:000230488800009 PM 16174932 ER PT J AU Cucchiara, B Sinson, G Kasner, SE Chalela, JA AF Cucchiara, B Sinson, G Kasner, SE Chalela, JA TI Pseudo-subarachnoid hemorrhage - Report of three cases and review of the literature SO NEUROCRITICAL CARE LA English DT Article DE pseudo-subarachnoid hemorrhage; computed tomography (CT); subarachnoid hemorrhage (SAH); cerebral edema; false-positive appearance ID INTER-HEMISPHERIC FISSURE; AXIAL CT; FALX; PITFALL; EDEMA AB Subarachnoid hemorrhage (SAH) appears on CT as hyperdensity in the subarachnoid space. In rare circumstances a similar appearance may occur in the absence of subarachnoid blood, a finding that has been termed "pseudo-subarachnoid hemorrhage." We describe three patients who presented with abrupt alterations in mental status in whom CT falsely suggested SAH, and we review the literature regarding this imaging finding. In contrast to prior reports, all three of our patients had a favorable outcome. C1 Univ Penn, Med Ctr, Dept Neurol, Philadelphia, PA 19104 USA. Med Coll Wisconsin, Dept Neurosurg, Milwaukee, WI 53226 USA. NIH, Stroke Diagnost & Therapeut Sect, Bethesda, MD 20892 USA. Natl Inst Neurol Disorders & Stroke, Bethesda, MD 20892 USA. RP Cucchiara, B (reprint author), Univ Penn, Med Ctr, Dept Neurol, 3400 Spruce St, Philadelphia, PA 19104 USA. EM cucchiar@mail.med.upenn.edu RI Kasner, Scott/C-6109-2011 FU NINDS NIH HHS [K23 NS02147] NR 12 TC 8 Z9 8 U1 1 U2 2 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 USA SN 1541-6933 J9 NEUROCRIT CARE JI Neurocrit. Care PY 2004 VL 1 IS 3 BP 371 EP 374 DI 10.1385/NCC:1:3:371 PG 4 WC Critical Care Medicine; Clinical Neurology SC General & Internal Medicine; Neurosciences & Neurology GA 945FQ UT WOS:000230488800014 PM 16174937 ER PT J AU Hardy, J Myers, A Wavrant-De Vrieze, F AF Hardy, John Myers, Amanda Wavrant-De Vrieze, Fabienne TI Problems and Solutions in the Genetic Analysis of Late-Onset Alzheimer's Disease SO NEURODEGENERATIVE DISEASES LA English DT Article DE Alzheimer's disease; Apolipoprotein E; Amyloid protein precursor; Presenilin AB The identification of the apolipoprotein E gene as a risk factor for late-onset Alzheimer's disease was a spectacularly successful application of genetic analysis to a complex trait, and it led to the hope and expectation that other risk loci for the disease would soon be forthcoming. Twelve years later, despite a huge amount of work, no other loci have been identified. In this article, we discuss the complexity of the problem and the pitfalls in the analytical methods that have been used and how we are approaching this problem. Copyright (C) 2004 S. Karger AG, Basel C1 [Hardy, John; Myers, Amanda; Wavrant-De Vrieze, Fabienne] NIA, Neurogenet Lab, NIH, Bethesda, MD 20892 USA. RP Hardy, J (reprint author), NIA, Neurogenet Lab, NIH, Bldg 35,Room 1A1015,MSC3707,Convent Dr, Bethesda, MD 20892 USA. EM hardyj@mail.nih.gov RI Myers, Amanda/B-1796-2010; Hardy, John/C-2451-2009 OI Myers, Amanda/0000-0002-3100-9396; FU European Union, Key Action 3 'The Cell Factory' [QLK3-CT-2001-02362]; Verum Foundation FX This work and collaborations to follow this workup were supported by the European Union under the programme 'Quality of Life and Management of Living Resources', Key Action 3 'The Cell Factory', Contract No. QLK3-CT-2001-02362 and through the Verum Foundation. Collaborations with Dr. Lars Lannfelt and Dr. Andreas Papassotiropoulos through this EU grant are gratefully acknowledged. NR 25 TC 10 Z9 11 U1 0 U2 3 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1660-2854 J9 NEURODEGENER DIS JI Neurodegener. Dis. PY 2004 VL 1 IS 4-5 BP 213 EP 217 DI 10.1159/000080988 PG 5 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA V21SA UT WOS:000208226100009 PM 16908992 ER PT J AU Contoreggi, C Rice, KC Chrousos, G AF Contoreggi, C Rice, KC Chrousos, G TI Nonpeptide corticotropin-releasing hormone receptor type 1 antagonists and their applications in psychosomatic disorders SO NEUROENDOCRINOLOGY LA English DT Review DE stress; corticotropin-releasing hormone; corticotropin-releasing hormone receptors; hypothalamic-pituitary-adrenal axis; autoimmune diseases; Cushing's syndrome; Nelson's syndrome; inflammation; psychosomatic disorders; neuroimmune interactions ID PITUITARY-ADRENAL AXIS; DIAGNOSED RHEUMATOID-ARTHRITIS; IRRITABLE-BOWEL-SYNDROME; HYPOTHALAMIC-PITUITARY; ABDOMINAL OBESITY; CUSHINGS-SYNDROME; CORTISOL SECRETION; INSULIN-RESISTANCE; FACTOR CRF; GLUCOCORTICOID-RECEPTOR AB Overproduction of corticotropin-releasing hormone (CRH) and stress system abnormalities are seen in psychiatric diseases such as depression, anxiety, eating disorders, and addiction. Investigations of CRH type 1 receptor (CRHR1) nonpeptide antagonists suggest therapeutic potential for treatment of these and other neuropsychiatric diseases. However, overproduction of CRH in the brain and on its periphery and disruption of the hypothalamic-pituitary-adrenal axis are also found in 'somatic' disorders. Some rare forms of Cushing's disease and related pituitary/adrenal disorders are obvious applications for CRHR1 antagonists. In addition, however, these antagonists may also be effective in treating more common somatic diseases. Patients with obesity and metabolic syndrome who often have subtle, but chronic hypothalamic-pituitary-adrenal hyperactivity, which may reflect central dysregulation of CRH and consequently glucocorticoid hypersecretion, could possibly be treated by administration of CRHR1 antagonists. Hormonal, autonomic, and immune aberrations are also present in chronic inflammatory, autoimmune, and allergic diseases, with considerable evidence linking CRH with the observed abnormalities. Furthermore, autonomic dysregulation is a prominent feature of common gastrointestinal disorders, such as irritable bowel syndrome and peptic ulcer disease. Patients with irritable bowel syndrome and other gastrointestinal disorders frequently develop altered pain perception and affective symptoms. CRH acts peripherally to modulate bowel activity both directly through the autonomic system and centrally by processing viscerosensory and visceromotor neural signals. This review presents clinical and preclinical evidence for the role of CRH in the pathophysiology of these disorders and for potential diagnostic and therapeutic applications of CRHR1 antagonists. Recognition of a dysfunctional stress system in these and other diseases will alter the understanding and treatment of 'psychosomatic' disorders. Copyright (C) 2004 S. Karger AG, Basel. C1 NIDA, Intramural Res Program, Baltimore, MD 21224 USA. NIDDKD, Intramural Res Program, Bethesda, MD 20892 USA. NICHHD, Intramural Res Program, Bethesda, MD 20892 USA. NIH, US Dept HHS, Bethesda, MD 20892 USA. RP Contoreggi, C (reprint author), NIDA, Intramural Res Program, 5500 Nathan Shock Dr, Baltimore, MD 21224 USA. EM ccontore@intra.nida.nih.gov NR 115 TC 12 Z9 14 U1 1 U2 9 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0028-3835 J9 NEUROENDOCRINOLOGY JI Neuroendocrinology PY 2004 VL 80 IS 2 BP 111 EP 123 DI 10.1159/000081785 PG 13 WC Endocrinology & Metabolism; Neurosciences SC Endocrinology & Metabolism; Neurosciences & Neurology GA 873DD UT WOS:000225258600005 PM 15523186 ER PT J AU Jain, P Armando, I Juorio, AV Barden, N Benicky, J Saavedra, JM AF Jain, P Armando, I Juorio, AV Barden, N Benicky, J Saavedra, JM TI Decreased hypothalamic and adrenal angiotensin II receptor expression and adrenomedullary catecholamines in transgenic mice with impaired glucocorticoid receptor function SO NEUROENDOCRINOLOGY LA English DT Article DE angiotensin receptors; paraventricular nucleus; median eminence; supraoptic nucleus; corticotropin-releasing hormone; vasopressin; adrenal medulla; tyrosine hydroxylase; transgenic mice; adrenal steroids; catecholamines ID CORTICOTROPIN-RELEASING-FACTOR; PARAVENTRICULAR NUCLEUS; MESSENGER-RNA; ANTISENSE RNA; RAT-BRAIN; QUANTITATIVE AUTORADIOGRAPHY; VASOPRESSIN RELEASE; SUBFORNICAL ORGAN; RIBONUCLEIC-ACID; GENE-EXPRESSION AB In transgenic mice expressing an antisense mRNA against the glucocorticoid receptor (GR), which partially blocks GR expression, impaired glucocorticoid feedback efficacy is accompanied by reduced hypothalamic corticotropin-releasing hormone (CRH) and vasopressin (AVP) activity and reduced peripheral sympathetic tone, indications of a shift in the balance of hypothalamic CRH and sympathetic regulation. As angiotensin II (Ang II) regulates CRH, AVP and sympathetic activity, we studied the expression of Ang II receptors in the hypothalamus and adrenal gland of GR transgenic and wild-type mice, adrenal catecholamines and mRNA for their rate-limiting enzyme, tyrosine hydroxylase (TH). We found that transgenic mice expressed significantly less numbers of Ang II AT(1) receptors in the hypothalamic paraventricular nucleus and median eminence, lower numbers of AT(2) receptors in supraoptic and paraventricular nuclei and lower numbers of AT(2) receptors in the adrenal medulla when compared with wild-type controls. The expression of TH mRNA and the concentration of adrenomedullary epinephrine and norepinephrine were also lower in transgenic mice when compared with wild-type controls. Decreased hypothalamic and adrenal Ang II receptor stimulation as a result of decreased GR expression may explain the decreased hypothalamic CRH and AVP and decreased adrenomedullary and sympathetic activities in this model. Copyright (C) 2004 S. Karger AG, Basel. C1 NIMH, Pharmacol Sect, Div Intramural Res Programs, NIH,DHHS, Bethesda, MD 20892 USA. Univ Laval, Dept Physiol, St Foy, PQ G1K 7P4, Canada. Univ Laval, CHUL Res Ctr, Neurosci Res Sect, St Foy, PQ G1K 7P4, Canada. RP Saavedra, JM (reprint author), NIMH, Pharmacol Sect, Div Intramural Res Programs, NIH,DHHS, 10 Ctr dr,Bldg 10,Room 2D-57, Bethesda, MD 20892 USA. EM Saavedrj@mail.nih.gov NR 48 TC 5 Z9 5 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0028-3835 J9 NEUROENDOCRINOLOGY JI Neuroendocrinology PY 2004 VL 80 IS 3 BP 171 EP 180 DI 10.1159/000082358 PG 10 WC Endocrinology & Metabolism; Neurosciences SC Endocrinology & Metabolism; Neurosciences & Neurology GA 886QW UT WOS:000226244400005 PM 15583474 ER PT J AU Pohorecky, LA Baumann, MH Benjamin, D AF Pohorecky, LA Baumann, MH Benjamin, D TI Effects of chronic social stress on neuroendocrine responsiveness to challenge with ethanol, dexamethasone and corticotropin-releasing hormone SO NEUROENDOCRINOLOGY LA English DT Article DE prolactin; ethanol; aggression; adrenal steroids; corticotropin-releasing hormone; psychosocial stress; behavior ID CHRONIC PSYCHOSOCIAL STRESS; LUTEINIZING-HORMONE; MALE-RATS; PROLACTIN RESPONSE; INDUCED INHIBITION; SERUM PROLACTIN; ACTH-SECRETION; BETA-ENDORPHIN; RHESUS-MONKEYS; PLASMA-LEVELS AB Neuroendocrine and behavioral profiles of group-housed rodents differ from those of singly-housed ones. Subordinate rats have elevated plasma corticosterone ( CORT) concentration and impaired activity of the hypothalamic-pituitary-adrenal (HPA) axis compared to dominant cagemates. However, little is known about the effects of social hierarchy on other stress-related hormones. We examined plasma prolactin (PRL) and CORT responses to saline and ethanol ( EtOH) injections, and 1 month later to dexamethasone (DEX) and corticotropin-releasing hormone (CRH) challenges of group- ( triad) and single-housed male rats over a period of 225 days. Social status was determined from behaviors displayed upon initial triad housing. Subordinate rats had lower basal PRL and higher CORT compared to dominant rats. The injection of EtOH (1.25 g/kg) depressed PRL and elevated CORT levels significantly more than the saline injection only in dominant and singly-housed rats. DEX increased PRL levels, most strikingly in dominant rats, and suppressed CORT only in dominant rats. After CRH challenge, plasma CORT increased in all groups, subdominant and subordinate rats displaying blunted responses. Our data demonstrate that social rank and housing conditions affect plasma PRL and CORT concentrations, and modify responses to EtOH, possibly reflecting impairments of HPA axis regulation in socially-housed rats. Copyright (C) 2004 S. Karger AG, Basel. C1 Rutgers State Univ, Ctr Alcohol Studies, Piscataway, NJ 08855 USA. NIDA, IRP, NIH, Baltimore, MD USA. RP Pohorecky, LA (reprint author), Rutgers State Univ, Ctr Alcohol Studies, 607 Alison Rd, Piscataway, NJ 08855 USA. EM Larissa@rci.rutgers.edu FU NIAAA NIH HHS [AAA10124] NR 65 TC 21 Z9 23 U1 0 U2 2 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0028-3835 J9 NEUROENDOCRINOLOGY JI Neuroendocrinology PY 2004 VL 80 IS 5 BP 332 EP 342 DI 10.1159/000083682 PG 11 WC Endocrinology & Metabolism; Neurosciences SC Endocrinology & Metabolism; Neurosciences & Neurology GA 901PY UT WOS:000227295600006 PM 15692218 ER PT J AU Thompson, PM Hayashi, KM Sowell, ER Gogtay, N Giedd, JN Rapoport, JL de Zubicaray, GI Janke, AL Rose, SE Semple, J Doddrell, DM Wang, YL van Erp, TGM Cannon, TD Toga, AW AF Thompson, PM Hayashi, KM Sowell, ER Gogtay, N Giedd, JN Rapoport, JL de Zubicaray, GI Janke, AL Rose, SE Semple, J Doddrell, DM Wang, YL van Erp, TGM Cannon, TD Toga, AW TI Mapping cortical change in Alzheimer's disease, brain development, and schizophrenia SO NEUROIMAGE LA English DT Article; Proceedings Paper CT Conference on Mathermatics in Brain Imaging CY JUL 12-23, 2004 CL Univ Calif Los Angeles, Inst Pure & Appl Math, Los Angeles, CA HO Univ Calif Los Angeles, Inst Pure & Appl Math DE Alzheimer's disease; brain development; schizophrenia ID VOXEL-BASED MORPHOMETRY; HUMAN CEREBRAL-CORTEX; MAGNETIC-RESONANCE IMAGES; PRENATAL ALCOHOL EXPOSURE; GRAY-MATTER LOSS; IN-VIVO; STATISTICAL-ANALYSIS; ONSET SCHIZOPHRENIA; SURFACE; ASYMMETRY AB This paper describes algorithms that can identify patterns of brain structure and function associated with Alzheimer's disease, schizophrenia, normal aging, and abnormal brain development based on imaging data collected in large human populations. Extraordinary information can be discovered with these techniques: dynamic brain maps reveal how the brain grows in childhood, how it changes in disease, and how it responds to medication. Genetic brain maps can reveal genetic influences on brain structure, shedding light on the nature-nurture debate, and the mechanisms underlying inherited neurobehavioral disorders. Recently, we created time-lapse movies of brain structure for a variety of diseases. These identify complex, shifting patterns of brain structural deficits, revealing where, and at what rate, the path of brain deterioration in illness deviates from normal. Statistical criteria can then identify situations in which these changes are abnormally accelerated, or when medication or other interventions slow them. In this paper, we focus on describing our approaches to map structural changes in the cortex. These methods have already been used to reveal the profile of brain anomalies in studies of dementia, epilepsy, depression, childhood and adult-onset schizophrenia, bipolar disorder, attention-deficit/ hyperactivity disorder, fetal alcohol syndrome, Tourette syndrome, Williams syndrome, and in methamphetamine abusers. Specifically, we describe an image analysis pipeline known as cortical pattern matching that helps compare and pool cortical data over time and across subjects. Statistics are then defined to identify brain structural differences between groups, including localized alterations in cortical thickness, gray matter density (GMD), and asymmetries in cortical organization. Subtle features, not seen in individual brain scans, often emerge when population-based brain data are averaged in this way. Illustrative examples are presented to show the profound effects of development and various diseases on the human cortex. Dynamically spreading waves of gray matter loss are tracked in dementia and schizophrenia, and these sequences are related to normally occurring changes in healthy subjects of various ages. (C) 2004 Published by Elsevier Inc. C1 Univ Calif Los Angeles, Sch Med, Reed Neurol Res Ctr, Lab Neuro Imaging,Brain Mapping Div,Dept Neurol, Los Angeles, CA 90095 USA. NIMH, Child Psychiat Branch, Bethesda, MD 20892 USA. Univ Queensland, Ctr Magnet Resonance, Brisbane, Qld 4072, Australia. Addenbrookes Hosp, GlaxoSmithKline Pharmaceut Plc, Addenbrookes Ctr Clin Invest, Cambridge, England. Univ Calif Los Angeles, Dept Math, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, Sch Med, Dept Psychol Psychiat & Human Genet, Los Angeles, CA 90095 USA. RP Thompson, PM (reprint author), Univ Calif Los Angeles, Sch Med, Reed Neurol Res Ctr, Lab Neuro Imaging,Brain Mapping Div,Dept Neurol, Room 4238,710 Westwood Plaza, Los Angeles, CA 90095 USA. EM thompson@loni.ucla.edu RI Gogtay, Nitin/A-3035-2008; Giedd, Jay/A-3080-2008; Rose, Stephen/C-8044-2009; Giedd, Jay/B-7302-2012; de Zubicaray, Greig/B-1763-2008; Janke, Andrew/E-6149-2011; Giedd, Jay/J-9644-2015 OI Giedd, Jay/0000-0003-0827-3460; de Zubicaray, Greig/0000-0003-4506-0579; Janke, Andrew/0000-0003-0547-5171; Giedd, Jay/0000-0003-2002-8978 FU NCRR NIH HHS [P41 RR13642, R21 RR019771, RR00827]; NIA NIH HHS [P50 AG016570]; NIBIB NIH HHS [R21 EB01651]; NIDA NIH HHS [R21 DA15878]; NIMH NIH HHS [K01 MH01733, P20 MH/DA52176, P20 MH65166, R01 MH52857] NR 131 TC 225 Z9 225 U1 10 U2 26 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1053-8119 J9 NEUROIMAGE JI Neuroimage PY 2004 VL 23 SU 1 BP S2 EP S18 DI 10.1016/j.neuroimage.2004.07.071 PG 17 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 874UA UT WOS:000225374100002 PM 15501091 ER PT J AU Tosun, D Rettmann, ME Han, X Tao, XD Xu, CY Resnick, SM Pham, DL Prince, JL AF Tosun, D Rettmann, ME Han, X Tao, XD Xu, CY Resnick, SM Pham, DL Prince, JL TI Cortical surface segmentation and mapping SO NEUROIMAGE LA English DT Article; Proceedings Paper CT Conference on Mathermatics in Brain Imaging CY JUL 12-23, 2004 CL Univ Calif Los Angeles, Inst Pure & Appl Math, Los Angeles, CA HO Univ Calif Los Angeles, Inst Pure & Appl Math DE cerebral cortex; cortical surface; cortical thickness; surface flattening ID MAGNETIC-RESONANCE IMAGES; HUMAN CEREBRAL-CORTEX; LEVEL SET METHOD; EFFICIENT ALGORITHM; COORDINATE SYSTEM; HUMAN BRAIN; MRI; RECONSTRUCTION; TOPOLOGY; WATERSHEDS AB Segmentation and mapping of the human cerebral cortex from magnetic resonance (MR) images plays an important role in neuroscience and medicine. This paper describes a comprehensive approach for cortical reconstruction, flattening, and sulcal segmentation. Robustness to imaging artifacts and anatomical consistency are key achievements in an overall approach that is nearly fully automatic and computationally fast. Results demonstrating the application of this approach to a study of cortical thickness changes in aging are presented. (C) 2004 Elsevier Inc. All rights reserved. C1 Johns Hopkins Univ, Dept Elect & Comp Engn, Baltimore, MD 21218 USA. NIA, NIH, Baltimore, MD 21224 USA. Johns Hopkins Univ Hosp, Dept Radiol, Baltimore, MD 21287 USA. Siemens Corp Res, Imaging & Visualisat Dept, Princeton, NJ 08540 USA. RP Prince, JL (reprint author), Johns Hopkins Univ, Dept Elect & Comp Engn, Baltimore, MD 21218 USA. EM prince@jhu.edu RI Prince, Jerry/A-3281-2010 OI Prince, Jerry/0000-0002-6553-0876 FU NINDS NIH HHS [R01 NS037747, R01NS37747] NR 44 TC 35 Z9 35 U1 2 U2 3 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1053-8119 J9 NEUROIMAGE JI Neuroimage PY 2004 VL 23 SU 1 BP S108 EP S118 DI 10.1016/j.neuroimage.2004.07.042 PG 11 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 874UA UT WOS:000225374100010 PM 15501080 ER PT J AU Bain, EE Nugent, A Carson, RE Lang, LX Eckelman, W Neumeister, A Bonne, O Charney, DS Drevets, WC AF Bain, EE Nugent, A Carson, RE Lang, LX Eckelman, W Neumeister, A Bonne, O Charney, DS Drevets, WC TI Reduced 5-HT1A receptor binding with [F-18]-FCWAY in bipolar depression SO NEUROIMAGE LA English DT Meeting Abstract CT 5th International Symposium on Functional Neuroreceptor Mapping of the Living Brain CY JUL 15-17, 2004 CL Vancouver, CANADA SP Concorde Microsyst Inc, CPS Innovat, Imanet C1 NIMH, Mood & Anxiety Disorders Program, Bethesda, MD 20892 USA. NIH, PET Dept, Bethesda, MD 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 ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1053-8119 J9 NEUROIMAGE JI Neuroimage PY 2004 VL 22 SU 2 BP T167 EP T168 PG 2 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 845MC UT WOS:000223245800102 ER PT J AU Cai, LS Ye, D Pike, V Liow, JS Tipre, D Crescenzo, M Hong, JS Zoghbi, S Vines, D Park, K Cohen, R Ichise, M Innis, R AF Cai, LS Ye, D Pike, V Liow, JS Tipre, D Crescenzo, M Hong, JS Zoghbi, S Vines, D Park, K Cohen, R Ichise, M Innis, R TI Synthesis and evaluation of [C-11]MeBrMPY in the development of radioligands for beta-amyloid SO NEUROIMAGE LA English DT Meeting Abstract CT 5th International Symposium on Functional Neuroreceptor Mapping of the Living Brain CY JUL 15-17, 2004 CL Vancouver, CANADA SP Concorde Microsyst Inc, CPS Innovat, Imanet ID IMAGING AGENTS C1 NIMH, Mol Imaging Branch, NIH, Bethesda, MD 20892 USA. NIMH, Geriatr Psychiat Branch, NIH, Bethesda, MD 20892 USA. NR 3 TC 0 Z9 0 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 1053-8119 J9 NEUROIMAGE JI Neuroimage PY 2004 VL 22 SU 2 BP T171 EP T172 PG 2 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 845MC UT WOS:000223245800105 ER PT J AU Cai, LS Park, K Pike, V AF Cai, LS Park, K Pike, V TI Beta-Amyloid ligand binding assay using fluorescence titration SO NEUROIMAGE LA English DT Meeting Abstract CT 5th International Symposium on Functional Neuroreceptor Mapping of the Living Brain CY JUL 15-17, 2004 CL Vancouver, CANADA SP Concorde Microsyst Inc, CPS Innovat, Imanet ID ALZHEIMERS-DISEASE; DERIVATIVES; PROBES C1 NIMH, Mol Imaging Branch, Bethesda, MD 20892 USA. NIH, Bethesda, MD 20892 USA. NR 6 TC 0 Z9 0 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 1053-8119 J9 NEUROIMAGE JI Neuroimage PY 2004 VL 22 SU 2 BP T141 EP T142 PG 2 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 845MC UT WOS:000223245800082 ER PT J AU Cannon, DM Nugent, AC Carson, RE Eckelman, WC Kiesewetter, D Bain, EE Solorio, G Charney, D Drevets, WC AF Cannon, DM Nugent, AC Carson, RE Eckelman, WC Kiesewetter, D Bain, EE Solorio, G Charney, D Drevets, WC TI Reduced muscarinic cholinergic2 receptor binding in bipolar disorder using PET and [F-18]FP-TZTP SO NEUROIMAGE LA English DT Meeting Abstract CT 5th International Symposium on Functional Neuroreceptor Mapping of the Living Brain CY JUL 15-17, 2004 CL Vancouver, CANADA SP Concorde Microsyst Inc, CPS Innovat, Imanet ID DEPRESSION C1 NIMH, NIH, Bethesda, MD 20892 USA. NIH, Ctr Clin, Bethesda, MD 20892 USA. RI Cannon, Dara/C-1323-2009; Carson, Richard/H-3250-2011 OI Cannon, Dara/0000-0001-7378-3411; Carson, Richard/0000-0002-9338-7966 NR 7 TC 0 Z9 0 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 1053-8119 J9 NEUROIMAGE JI Neuroimage PY 2004 VL 22 SU 2 BP T41 EP T42 PG 2 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 845MC UT WOS:000223245800020 ER PT J AU Chefer, S Pavlova, O Horti, A Hall, A Kurian, V Mukhin, A AF Chefer, S Pavlova, O Horti, A Hall, A Kurian, V Mukhin, A TI In vivo imaging of nAChRs receptor with 2-[18F]F-A-85380 under isoflurane and saffan anesthesia SO NEUROIMAGE LA English DT Meeting Abstract CT 5th International Symposium on Functional Neuroreceptor Mapping of the Living Brain CY JUL 15-17, 2004 CL Vancouver, CANADA SP Concorde Microsyst Inc, CPS Innovat, Imanet C1 NIDA, Neuroimaging Res Branch, IRP, NIH,DHHS, Baltimore, MD 21224 USA. NR 0 TC 1 Z9 1 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 1053-8119 J9 NEUROIMAGE JI Neuroimage PY 2004 VL 22 SU 2 BP T107 EP T107 PG 1 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 845MC UT WOS:000223245800060 ER PT J AU Chefer, S Zhang, Y Pavlova, O Vaupel, B Kimes, AS Kurian, V Horti, A Mukhin, A AF Chefer, S Zhang, Y Pavlova, O Vaupel, B Kimes, AS Kurian, V Horti, A Mukhin, A TI New high affinity radioligands for imaging extrathalamic nicotinic receptors with PET SO NEUROIMAGE LA English DT Meeting Abstract CT 5th International Symposium on Functional Neuroreceptor Mapping of the Living Brain CY JUL 15-17, 2004 CL Vancouver, CANADA SP Concorde Microsyst Inc, CPS Innovat, Imanet C1 NIDA, Neuroimaging Res Branch, IRP, NIH,DHHS, Baltimore, MD 21224 USA. NR 0 TC 0 Z9 0 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 1053-8119 J9 NEUROIMAGE JI Neuroimage PY 2004 VL 22 SU 2 BP T36 EP T36 PG 1 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 845MC UT WOS:000223245800016 ER PT J AU Finnem, SJ Seneca, N Gulyas, B Sovago, J Farde, L Innis, RB Wikstrom, HV Halldin, C AF Finnem, SJ Seneca, N Gulyas, B Sovago, J Farde, L Innis, RB Wikstrom, HV Halldin, C TI PET evaluation of the dopamine D2 receptor agonist SO NEUROIMAGE LA English DT Meeting Abstract CT 5th International Symposium on Functional Neuroreceptor Mapping of the Living Brain CY JUL 15-17, 2004 CL Vancouver, CANADA SP Concorde Microsyst Inc, CPS Innovat, Imanet C1 Karolinska Hosp, Karolinska Inst, Inst Clin Neurosci, Psychiat Sect, S-17176 Stockholm, Sweden. Univ Groningen, Dept Med Chem, Univ Ctr Pharm, NL-9700 AB Groningen, Netherlands. NIMH, Mol Imaging Branch, Bethesda, MD 20892 USA. RI Sovago, Judit/G-7961-2011 NR 2 TC 0 Z9 0 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 1053-8119 J9 NEUROIMAGE JI Neuroimage PY 2004 VL 22 SU 2 BP T175 EP T175 PG 1 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 845MC UT WOS:000223245800107 ER PT J AU Fujita, M Ichise, M Zoghbi, S Liow, JS Ghose, S Vines, D Sangare, J Crawley, A Gillespie, M Bara-Jimenez, W Lu, JQ Cropley, V Szczepanik, J Iida, H Kim, KM Cohen, R Ravina, B Innis, R AF Fujita, M Ichise, M Zoghbi, S Liow, JS Ghose, S Vines, D Sangare, J Crawley, A Gillespie, M Bara-Jimenez, W Lu, JQ Cropley, V Szczepanik, J Iida, H Kim, KM Cohen, R Ravina, B Innis, R TI Decrease of nicotinic acetylcholine receptors in Parkinson's disease SO NEUROIMAGE LA English DT Meeting Abstract CT 5th International Symposium on Functional Neuroreceptor Mapping of the Living Brain CY JUL 15-17, 2004 CL Vancouver, CANADA SP Concorde Microsyst Inc, CPS Innovat, Imanet ID HUMAN BRAIN; SPET C1 NIMH, Bethesda, MD 20892 USA. NINDS, Bethesda, MD 20892 USA. Natl Cardiovasc Ctr, Res Inst, Suita, Osaka 565, Japan. RI Ghose, Subroto/J-6732-2016 NR 5 TC 0 Z9 0 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 1053-8119 J9 NEUROIMAGE JI Neuroimage PY 2004 VL 22 SU 2 BP T110 EP T111 PG 2 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 845MC UT WOS:000223245800063 ER PT J AU Fujita, M Zoghbi, S Crescenzo, M Hong, JS Musachio, J Lu, JQ Liow, JS Seneca, N Tipre, D Cropley, V Gee, A Seidel, J Green, M Pike, V Innis, R AF Fujita, M Zoghbi, S Crescenzo, M Hong, JS Musachio, J Lu, JQ Liow, JS Seneca, N Tipre, D Cropley, V Gee, A Seidel, J Green, M Pike, V Innis, R TI PET imaging of brain phosphodiesterase 4 in rats using [C-11]rolipram SO NEUROIMAGE LA English DT Meeting Abstract CT 5th International Symposium on Functional Neuroreceptor Mapping of the Living Brain CY JUL 15-17, 2004 CL Vancouver, CANADA SP Concorde Microsyst Inc, CPS Innovat, Imanet ID ROLIPRAM; BINDING C1 NIMH, Bethesda, MD 20892 USA. Addenbrookes Hosp, GlaxoSmithKline Pharmaceut, Cambridge, England. NIH, Bethesda, MD 20892 USA. NR 5 TC 0 Z9 0 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 1053-8119 J9 NEUROIMAGE JI Neuroimage PY 2004 VL 22 SU 2 BP T72 EP T73 PG 2 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 845MC UT WOS:000223245800039 ER PT J AU Giovacchini, G Lang, LX Ma, Y Herscovitch, P Eckelamn, WC Carson, RE AF Giovacchini, G Lang, LX Ma, Y Herscovitch, P Eckelamn, WC Carson, RE TI Differential effects of the selective serotonin reuptake inhibitor paroxetine on raphe and cortical 5-HT1A binding: a PET study in monkeys with [18F]FPWAY SO NEUROIMAGE LA English DT Meeting Abstract CT 5th International Symposium on Functional Neuroreceptor Mapping of the Living Brain CY JUL 15-17, 2004 CL Vancouver, CANADA SP Concorde Microsyst Inc, CPS Innovat, Imanet ID BRAIN C1 NIH, PET Dept, Bethesda, MD 20892 USA. RI Carson, Richard/H-3250-2011 OI Carson, Richard/0000-0002-9338-7966 NR 4 TC 2 Z9 2 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1053-8119 J9 NEUROIMAGE JI Neuroimage PY 2004 VL 22 SU 2 BP T25 EP T26 PG 2 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 845MC UT WOS:000223245800009 ER PT J AU Ichise, M Fujita, M Zoghbi, SS Vines, D Liow, JS Ghose, S Lu, JQ Cropley, V Sangare, J Bara-Jimenez, W Burger, C Kim, KM Iida, H Ravina, B Cohen, RM Sunderland, T Innis, RB AF Ichise, M Fujita, M Zoghbi, SS Vines, D Liow, JS Ghose, S Lu, JQ Cropley, V Sangare, J Bara-Jimenez, W Burger, C Kim, KM Iida, H Ravina, B Cohen, RM Sunderland, T Innis, RB TI Parametric imaging of distribution volume and tracer delivery by noise-resistant linear regression analysis: Application to [I-123]5-I-A-85380 SPECT imaging of alpha 4 beta 2 nicotinic acetylcholine receptors in human SO NEUROIMAGE LA English DT Meeting Abstract CT 5th International Symposium on Functional Neuroreceptor Mapping of the Living Brain CY JUL 15-17, 2004 CL Vancouver, CANADA SP Concorde Microsyst Inc, CPS Innovat, Imanet C1 NIMH, Bethesda, MD 20892 USA. Univ Zurich, Zurich, Switzerland. NINDS, Bethesda, MD 20892 USA. Natl Cardiovasc Ctr, Res Inst, Osaka, Japan. NR 2 TC 1 Z9 1 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 1053-8119 J9 NEUROIMAGE JI Neuroimage PY 2004 VL 22 SU 2 BP T180 EP T181 PG 2 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 845MC UT WOS:000223245800111 ER PT J AU Ichise, M Cohen, RM Liow, JS Innis, RB Carson, RE AF Ichise, M Cohen, RM Liow, JS Innis, RB Carson, RE TI Estimation of normalized distribution volume without receptor-free reference region or arterial input function: Application to the muscarinic-2 ligand [F-18]FP-TZTP SO NEUROIMAGE LA English DT Meeting Abstract CT 5th International Symposium on Functional Neuroreceptor Mapping of the Living Brain CY JUL 15-17, 2004 CL Vancouver, CANADA SP Concorde Microsyst Inc, CPS Innovat, Imanet C1 NIMH, Mol Imaging Branch, Bethesda, MD 20892 USA. NIMH, Geriatr Psychiat Branch, Bethesda, MD 20892 USA. NIH, PET Dept, Bethesda, MD 20892 USA. RI Carson, Richard/H-3250-2011 OI Carson, Richard/0000-0002-9338-7966 NR 2 TC 1 Z9 1 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 1053-8119 J9 NEUROIMAGE JI Neuroimage PY 2004 VL 22 SU 2 BP T149 EP T150 PG 2 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 845MC UT WOS:000223245800088 ER PT J AU Kime, AS Chefer, SI Matochik, JA Pavlova, OA Contoreggi, CS Horti, AG Kurian, V Vaupel, DB Koren, AO Ernst, M London, ED Mukhin, AG AF Kime, AS Chefer, SI Matochik, JA Pavlova, OA Contoreggi, CS Horti, AG Kurian, V Vaupel, DB Koren, AO Ernst, M London, ED Mukhin, AG TI PET quantitation of nicotinic acetylcholine receptors in the human brain SO NEUROIMAGE LA English DT Meeting Abstract CT 5th International Symposium on Functional Neuroreceptor Mapping of the Living Brain CY JUL 15-17, 2004 CL Vancouver, CANADA SP Concorde Microsyst Inc, CPS Innovat, Imanet C1 NIDA, Neuroimaging Res Branch, IRP, DHHS, Baltimore, MD USA. NIMH, IRP, NIH, DHHS, Bethesda, MD 20892 USA. Univ Calif Los Angeles, Los Angeles, CA USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1053-8119 J9 NEUROIMAGE JI Neuroimage PY 2004 VL 22 SU 2 BP T79 EP T80 PG 2 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 845MC UT WOS:000223245800043 ER PT J AU Krasikova, RN Seneca, N Ryzhikov, NN Gomzina, NA Fedorova, OS Shchukin, E Gulyas, B Hall, H Savic, I Halldin, C AF Krasikova, RN Seneca, N Ryzhikov, NN Gomzina, NA Fedorova, OS Shchukin, E Gulyas, B Hall, H Savic, I Halldin, C TI A preliminary PET comparison of [18F]flumazenil and [11C]flumazenil SO NEUROIMAGE LA English DT Meeting Abstract CT 5th International Symposium on Functional Neuroreceptor Mapping of the Living Brain CY JUL 15-17, 2004 CL Vancouver, CANADA SP Concorde Microsyst Inc, CPS Innovat, Imanet C1 Russian Acad Sci, Inst Human Brain, St Petersburg 197376, Russia. Karolinska Hosp, Karolinska Inst, Dept Clin Neurosci, Psychiat Sect, S-17176 Stockholm, Sweden. NIMH, Mol Imaging Branch, Bethesda, MD 20892 USA. RI Krasikova, Raisa/A-2561-2014 NR 0 TC 0 Z9 0 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 1053-8119 J9 NEUROIMAGE JI Neuroimage PY 2004 VL 22 SU 2 BP T152 EP T152 PG 1 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 845MC UT WOS:000223245800090 ER PT J AU Lerner, A Boudreau, E Bagic, A Hanakawa, T Pagan, F Garraux, G Mari, Z Bara-Jimenez, W Aksu, M Sato, S Murphy, D Hallett, M AF Lerner, A Boudreau, E Bagic, A Hanakawa, T Pagan, F Garraux, G Mari, Z Bara-Jimenez, W Aksu, M Sato, S Murphy, D Hallett, M TI H2O15PET study of tics generation and suppression in patients with Tourette's syndrome and suppression of blinking in normal subjects. SO NEUROIMAGE LA English DT Meeting Abstract CT 5th International Symposium on Functional Neuroreceptor Mapping of the Living Brain CY JUL 15-17, 2004 CL Vancouver, CANADA SP Concorde Microsyst Inc, CPS Innovat, Imanet C1 NIMH, NIH, Bethesda, MD 20892 USA. NINDS, NIH, Bethesda, MD 20892 USA. Kyoto Univ, Human Brain Res Ctr, Sch Med, Kyoto, Japan. RI Garraux, Gaetan/G-9050-2011 NR 0 TC 0 Z9 0 U1 1 U2 2 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1053-8119 J9 NEUROIMAGE JI Neuroimage PY 2004 VL 22 SU 2 BP T186 EP T186 PG 1 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 845MC UT WOS:000223245800114 ER PT J AU Lu, JQ Rodriguez-Gomez, JA Velasco, I Zoghbi, SS Liow, JS Musachio, JL Shah, J Chin, FT Toyama, H Seidel, J Green, MV Ichise, M Pike, VW McKay, R Innis, RB AF Lu, JQ Rodriguez-Gomez, JA Velasco, I Zoghbi, SS Liow, JS Musachio, JL Shah, J Chin, FT Toyama, H Seidel, J Green, MV Ichise, M Pike, VW McKay, R Innis, RB TI PET imaging of DAT with [F-18]FECNT in naive and Parkinsonian rats following embryonic stem cell transplantation SO NEUROIMAGE LA English DT Meeting Abstract CT 5th International Symposium on Functional Neuroreceptor Mapping of the Living Brain CY JUL 15-17, 2004 CL Vancouver, CANADA SP Concorde Microsyst Inc, CPS Innovat, Imanet C1 NIMH, Mol Imaging Branch, Bethesda, MD 20892 USA. NINDS, Mol Biol Lab, Bethesda, MD 20892 USA. NIH, Ctr Clin, Bethesda, MD 20892 USA. RI Rodriguez-Gomez, Jose/C-8313-2015 NR 3 TC 3 Z9 3 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 1053-8119 J9 NEUROIMAGE JI Neuroimage PY 2004 VL 22 SU 2 BP T27 EP T28 PG 2 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 845MC UT WOS:000223245800010 ER PT J AU McCarron, JA Chin, FT Pike, VW Hong, J Musachio, JL Ichise, M Zoghbi, SS Vines, DC Vermeulen, ES Wikstrom, HV Halldin, C Innis, RB AF McCarron, JA Chin, FT Pike, VW Hong, J Musachio, JL Ichise, M Zoghbi, SS Vines, DC Vermeulen, ES Wikstrom, HV Halldin, C Innis, RB TI New candidate PET radioligands for brain 5-HT1A receptors based on 2,3,4,5,6,7-hexahydro-1{4-[1[4-(2-methoxyphenyl)-piperazinyl]]-2-phenylb utyryl}-m-azepine (RWAY) SO NEUROIMAGE LA English DT Meeting Abstract CT 5th International Symposium on Functional Neuroreceptor Mapping of the Living Brain CY JUL 15-17, 2004 CL Vancouver, CANADA SP Concorde Microsyst Inc, CPS Innovat, Imanet C1 NIMH, Mol Imaging Branch, NIH, Bethesda, MD 20892 USA. Univ Groningen, Univ Ctr Pharm, Dept Med Chem, NL-9713 AV Groningen, Netherlands. Karolinska Inst, Dept Clin Neurosci, Psychiat Sect, S-17176 Stockholm, Sweden. NR 2 TC 3 Z9 3 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 1053-8119 J9 NEUROIMAGE JI Neuroimage PY 2004 VL 22 SU 2 BP T34 EP T35 PG 2 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 845MC UT WOS:000223245800015 ER PT J AU Schou, M Halldin, C Sovago, J Pike, VW Hall, H Gulyas, B Mozley, PD Dobson, D Innis, RB Shchukin, E Farde, L AF Schou, M Halldin, C Sovago, J Pike, VW Hall, H Gulyas, B Mozley, PD Dobson, D Innis, RB Shchukin, E Farde, L TI A PET comparison of the NET tracers (S,S)-[11C]MeNER and (S,S)[18F]FMeNER-D2 in monkeys SO NEUROIMAGE LA English DT Meeting Abstract CT 5th International Symposium on Functional Neuroreceptor Mapping of the Living Brain CY JUL 15-17, 2004 CL Vancouver, CANADA SP Concorde Microsyst Inc, CPS Innovat, Imanet ID NOREPINEPHRINE TRANSPORTER C1 Karolinska Hosp, Karolinska Inst, Dept Clin Neurosci, Psychiat Sect, S-17176 Stockholm, Sweden. NIMH, Mol Imaging Branch, NIH, Bethesda, MD 20892 USA. Eli Lilly & Co, Indianapolis, IN 46285 USA. RI Sovago, Judit/G-7961-2011 NR 4 TC 0 Z9 0 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 1053-8119 J9 NEUROIMAGE JI Neuroimage PY 2004 VL 22 SU 2 BP T32 EP T32 PG 1 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 845MC UT WOS:000223245800013 ER PT J AU Theodore, W Giovacchini, G Toczek, M Bonwetsch, R Eckelman, W Lang, LX Herscovitch, P Carson, R AF Theodore, W Giovacchini, G Toczek, M Bonwetsch, R Eckelman, W Lang, LX Herscovitch, P Carson, R TI The effect of carbamazepine on PET 5-HT1A ligand binding in patients with temporal lobe epilepsy. SO NEUROIMAGE LA English DT Meeting Abstract CT 5th International Symposium on Functional Neuroreceptor Mapping of the Living Brain CY JUL 15-17, 2004 CL Vancouver, CANADA SP Concorde Microsyst Inc, CPS Innovat, Imanet ID RECEPTOR-BINDING C1 NINDS, NIH, Clin Epilepsy Sect, Bethesda, MD 20892 USA. NIH, PET Dept, Ctr Clin, Bethesda, MD USA. RI Carson, Richard/H-3250-2011 OI Carson, Richard/0000-0002-9338-7966 NR 3 TC 1 Z9 1 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 1053-8119 J9 NEUROIMAGE JI Neuroimage PY 2004 VL 22 SU 2 BP T162 EP T163 PG 2 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 845MC UT WOS:000223245800099 ER PT J AU Lao, ZQ Shen, DG Xue, Z Karacali, B Resnick, SM Davatzikos, C AF Lao, ZQ Shen, DG Xue, Z Karacali, B Resnick, SM Davatzikos, C TI Morphological classification of brains via high-dimensional shape transformations and machine learning methods SO NEUROIMAGE LA English DT Article DE morphological classification; high-dimensional shape transformations; machine learning methods ID MILD ALZHEIMERS-DISEASE; MEDIAL TEMPORAL-LOBE; OLDER-ADULTS; ELASTIC REGISTRATION; ENTORHINAL CORTEX; LONGITUDINAL MRI; AGE-CHANGES; IMAGES; MORPHOMETRY; ADOLESCENCE AB A high-dimensional shape transformation posed in a mass-preserving framework is used as a morphological signature of a brain image. Population differences with complex spatial patterns are then determined by applying a nonlinear support vector machine (SVM) pattern classification method to the morphological signatures. Significant reduction of the dimensionality of the morphological signatures is achieved via wavelet decomposition and feature reduction methods. Applying the method to MR images with simulated atrophy shows that the method can correctly detect subtle and spatially complex atrophy, even when the simulated atrophy represents only a 5% variation from the original image. Applying this method to actual MR images shows that brains can be correctly determined to be male or female with a successful classification rate of 97%, using the leave-one-out method. This proposed method also shows a high classification rate for old adults' age classification, even under difficult test scenarios. The main characteristic of the proposed methodology is that, by applying multivariate pattern classification methods, it can detect subtle and spatially complex patterns of morphological group differences which are often not detectable by voxel-based morphometric methods, because these methods analyze morphological measurements voxel-by-voxel and do not consider the entirety of the data simultaneously. (C) 2003 Elsevier Inc. All rights reserved. C1 Univ Penn, Dept Radiol, Sect Biomed Image Anal, Philadelphia, PA 19104 USA. NIA, Lab Personal & Cognit, Baltimore, MD 21224 USA. RP Davatzikos, C (reprint author), Univ Penn, Dept Radiol, Sect Biomed Image Anal, Philadelphia, PA 19104 USA. EM zqlao@rad.upenn.edu; christos@rad.upenn.edu RI Xue, Zhong/I-3414-2012 FU NIA NIH HHS [AG-93-07, R01 AG14971] NR 48 TC 182 Z9 184 U1 1 U2 12 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1053-8119 J9 NEUROIMAGE JI Neuroimage PD JAN PY 2004 VL 21 IS 1 BP 46 EP 57 DI 10.1016/j.neuroimage.2003.09.027 PG 12 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 768XY UT WOS:000188597500005 PM 14741641 ER PT J AU Smaniotto, S Ribeiro-Carvalho, MM Dardenne, M Savino, W de Mello-Coelho, V AF Smaniotto, S Ribeiro-Carvalho, MM Dardenne, M Savino, W de Mello-Coelho, V TI Growth hormone stimulates the selective trafficking of thymic CD4+CD8-emigrants to peripheral lymphoid organs SO NEUROIMMUNOMODULATION LA English DT Article DE growth hormone; thymus-derived T cell homing; L-selectin; Integrins; peripheral lymphoid organs ID SPLENIC WHITE PULP; HUMAN T-CELLS; IN-VIVO; IMMUNE-SYSTEM; MIGRATION; LYMPHOCYTES; EXPRESSION; ADHESION; RECEPTOR; MICE AB Growth hormone (GH) has been shown to stimulate T cell development. However, its mechanisms of action on the peripheral T cell pool remain unknown. To address this question, intrathymic injection of GH in combination with fluorescein isothiocyanate ( FITC) was used to assess the effects of GH on T cell trafficking from the thymus to the periphery. GH promoted a significant increase in the percentage and differential distribution of thymic CD4+ CD8 - FITC+ cells in secondary lymphoid organs. A significantly higher percentage of CD4+ CD8 FITC+ cells was observed in the lymph nodes, while a relative decrease of these cells was found in the spleen. Moreover, we verified that GH treatment resulted in increased numbers of CD62L+ CD4+ CD8 - FITC+ T cells in the lymph nodes, while the same treatment resulted in a decline in the percentage of VLA- 6+ CD4+ CD8 - FITC+ T cells in the spleen. Together, these findings suggest that GH is a potent immunoregulatory molecule which selectively stimulates the preferential homing of CD4+ CD8 - thymic emigrants to the subcutaneous lymph nodes possibly via the differential expression of CD62L and VLA-6. Copyright (C) 2004 S. Karger AG, Basel. C1 Oswaldo Cruz Fdn, Inst Oswaldo Cruz, Dept Immunol, Lab Thymus Res, Rio De Janeiro, Brazil. Fed Univ Alagoas, Ctr Biol Sci, Dept Morphol, Maceio, Brazil. Hop Necker Enfants Malad, CNRS, UMR 8147, Paris, France. Hop Necker Enfants Malad, INSERM, U344, Paris, France. RP de Mello-Coelho, V (reprint author), NIA, Immunol Lab, Gerontol Res Ctr, NIH, 5600 Nathan Shock Dr,Rm 4C04, Baltimore, MD 21224 USA. EM CoelhoVa@grc.nia.nih.gov NR 45 TC 20 Z9 21 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1021-7401 J9 NEUROIMMUNOMODULAT JI Neuroimmunomodulation PY 2004 VL 11 IS 5 BP 299 EP 306 DI 10.1159/000079410 PG 8 WC Endocrinology & Metabolism; Immunology; Neurosciences SC Endocrinology & Metabolism; Immunology; Neurosciences & Neurology GA 848TM UT WOS:000223490100003 PM 15316240 ER PT S AU Takeda, H Spatz, M Ruetzler, C McCarron, R Becker, K Hallenbeck, J AF Takeda, H Spatz, M Ruetzler, C McCarron, R Becker, K Hallenbeck, J BE Dirnagl, U Elger, B TI Induction of mucosal tolerance to E-selectin targets immunomodulation to activating vessel segments and prevents ischemic and hemorrhagic stroke SO NEUROINFLAMMATION IN STROKE SE ERNST SCHERING RESEARCH FOUNDATION WORKSHOP LA English DT Proceedings Paper CT Workshop on Neuroinflammation in Stroke CY APR 02-04, 2003 CL Berlin, GERMANY ID ANTIENDOTHELIAL CELL ANTIBODIES; LEUKOCYTE ADHESION MOLECULE-1; FOCAL CEREBRAL-ISCHEMIA; GROWTH-FACTOR-BETA; ORAL TOLERANCE; ENDOTHELIAL-CELL; AUTOIMMUNE ENCEPHALOMYELITIS; T-CELLS; EXPRESSION; MECHANISMS C1 NINDS, Stroke Branch, NIH, Bethesda, MD 20892 USA. RP Takeda, H (reprint author), NINDS, Stroke Branch, NIH, Bldg,36,Room 4A03,36 Convent Dr,MSC 4128, Bethesda, MD 20892 USA. NR 38 TC 2 Z9 2 U1 0 U2 0 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY SN 0947-6075 BN 3-540-40348-5 J9 E SCHERING RES FDN W PY 2004 VL 47 BP 117 EP 132 PG 16 WC Immunology; Clinical Neurology SC Immunology; Neurosciences & Neurology GA BY73F UT WOS:000189449800007 ER PT J AU Busby, V Goossens, S Nowotny, P Hamilton, G Smemo, S Harold, D Turic, D Jehu, L Myers, A Womick, M Woo, D Compton, D Doil, LM Tacey, KM Lau, KF Al-Saraj, S Killick, R Pickering-Brown, S Moore, P Hollingworth, P Archer, N Foy, C Walter, S Lendon, C Iwatsubo, T Morris, JC Norton, J Mann, D Janssens, B Hardy, J O'Donovan, M Jones, L Williams, J Holmans, P Owen, MJ Grupe, A Powell, J van Hengel, J Goate, A Van Roy, F Lovestone, S AF Busby, V Goossens, S Nowotny, P Hamilton, G Smemo, S Harold, D Turic, D Jehu, L Myers, A Womick, M Woo, D Compton, D Doil, LM Tacey, KM Lau, KF Al-Saraj, S Killick, R Pickering-Brown, S Moore, P Hollingworth, P Archer, N Foy, C Walter, S Lendon, C Iwatsubo, T Morris, JC Norton, J Mann, D Janssens, B Hardy, J O'Donovan, M Jones, L Williams, J Holmans, P Owen, MJ Grupe, A Powell, J van Hengel, J Goate, A Van Roy, F Lovestone, S TI alpha-T-catenin is expressed in human brain and interacts with the Wnt signaling pathway but is not responsible for linkage to chromosome 10 in Alzheimer's disease SO NEUROMOLECULAR MEDICINE LA English DT Article DE CTNNA3; alpha-T-catenin; Alzheimer's disease; chromosome 10; amyloid; A beta; age of onset; APOE; Wn ID AMYLOID PRECURSOR PROTEIN; BETA-CATENIN; XENOPUS-EMBRYOS; LOCUS; GENE; PEDIGREES; BINDING; ALLELE; CELLS AB The gene encoding alpha-T-catenin, CTNNA3, is positioned within a region on chromosome 10, showing strong evidence of linkage to Alzheimer's disease (AD), and is therefore a good positional candidate gene for this disorder. We have demonstrated that alpha-T-catenin is expressed in human brain, and like other alpha-catenins, it inhibits Wnt signaling and is therefore also a functional candidate. We initially genotyped two single-nucleotide polymorphisms (SNPs) in the gene, in four independent samples comprising over 1200 cases and controls but failed to detect an association with either SNP. Similarly, we found no evidence for association between CTNNA3 and AD in a sample of subjects showing linkage to chromosome 10, nor were these SNPs associated with Abeta deposition in brain. To comprehensively screen the gene, we genotyped 30 additional SNPs in a subset of the cases and controls (n > 700). None of these SNPs was associated with disease. Although an excellent candidate, we conclude that CTNNA3 is unlikely to account for the AD susceptibility locus on chromosome 10. C1 Inst Psychiat, Dept Neurosci, London SE5 8AF, England. State Univ Ghent VIB, Dept Mol Biomed Res, Mol Cell Biol Unit, B-9000 Ghent, Belgium. Washington Univ, Sch Med, Dept Psychiat, St Louis, MO 63110 USA. Washington Univ, Sch Med, Dept Neurol, St Louis, MO 63110 USA. Washington Univ, Sch Med, Dept Genet, St Louis, MO 63110 USA. Univ Wales Coll Med, Dept Psychol Med, Cardiff CF4 4XN, S Glam, Wales. NIA, Neurogenet Lab, NIH, Bethesda, MD 20892 USA. Univ Birmingham, Queen Elizabeth Psychiat Hosp, Dept Psychiat, Birmingham B15 2QZ, W Midlands, England. Univ Tokyo, Grad Sch Pharmaceut Sci, Dept Neuropathol & Neurosci, Bunkyo Ku, Tokyo 1130033, Japan. Hope Hosp, Greater Manchester Neurosci Ctr, Salford M6 8HD, Lancs, England. Inst Publ Hlth, MRC, Biostat Unit, Cambridge CB2 2SR, England. Celera Diagnost, Alameda, CA USA. RP Lovestone, S (reprint author), Inst Psychiat, Dept Neurosci, De Crespigny Pk, London SE5 8AF, England. EM s.lovestone@iop.kcl.ac.uk RI Pickering-Brown, Stuart/D-4008-2009; Lovestone, Simon/E-8725-2010; Myers, Amanda/B-1796-2010; turton, miranda/F-4682-2011; Powell, John/G-4412-2011; Morris, John/A-1686-2012; Hardy, John/C-2451-2009; van Roy, Frans/C-6123-2009; Hunter, Gillian/A-1952-2015; Holmans, Peter/F-4518-2015; OI Pickering-Brown, Stuart/0000-0003-1561-6054; Myers, Amanda/0000-0002-3100-9396; Powell, John/0000-0001-6124-439X; van Roy, Frans/0000-0003-4358-1039; Holmans, Peter/0000-0003-0870-9412; O'Donovan, Michael/0000-0001-7073-2379; Harold, Denise/0000-0001-5195-0143 FU NIA NIH HHS [AG 06786, AG 16208, AG 16574, AG 5681, U24 AG021886] NR 28 TC 32 Z9 32 U1 0 U2 0 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 USA SN 1535-1084 J9 NEUROMOL MED JI Neuromol. Med. PY 2004 VL 5 IS 2 BP 133 EP 146 DI 10.1385/NMM:5:2:133 PG 14 WC Neurosciences SC Neurosciences & Neurology GA 814ZN UT WOS:000221012700002 PM 15075440 ER PT J AU Guo, ZH Iyun, T Fu, WM Zhang, PS Mattson, MP AF Guo, ZH Iyun, T Fu, WM Zhang, PS Mattson, MP TI Bone marrow transplantation reveals roles for brain macrophage/microglia TNF signaling and nitric oxide production in excitotoxic neuronal death SO NEUROMOLECULAR MEDICINE LA English DT Article DE apoptosis; bone marrow; transplantation; excitotoxicity; hippocampus; microglia; tumor necrosis factor ID CENTRAL-NERVOUS-SYSTEM; HEMATOPOIETIC STEM-CELLS; HIPPOCAMPAL-NEURONS; MICROGLIAL CELLS; DOPAMINERGIC NEURODEGENERATION; SUPEROXIDE-DISMUTASE; ALZHEIMERS-DISEASE; OXIDATIVE STRESS; GROWTH-FACTOR; MICE LACKING AB The signaling mechanisms by which brain macrophages and microglia (BMM) respond to injury and disease, and how their responses affect neurodegenerative processes are largely unknown. Here we show that bone marrow transplantation can be used to introduce genetically modified BMM into the adult mouse brain to reveal the functions of one or more BMM genes in neuronal injury responses. Mice in which endogenous BMM were replaced with cells from mice lacking p55 and p75 tumor necrosis factor (TNF) receptors exhibit increased vulnerability of hippocampal neurons to excitotoxic injury suggesting a role for TNF signaling in BMM in the excitotoxic injury response. Neurons in the brains of mice with BMM lacking nitric oxide synthase exhibit reduced protein nitration and are less vulnerable to excitotoxic damage, indicating a pivotal role for BMM nitric oxide production in excitotoxic neuronal damage. C1 Natl Inst Aging Intramural Res Program, Neurosci Lab, Baltimore, MD 21224 USA. Johns Hopkins Univ, Sch Med, Dept Neurosci, Baltimore, MD 21205 USA. RP Mattson, MP (reprint author), Natl Inst Aging Intramural Res Program, Neurosci Lab, 5600 Nathan Shock Dr, Baltimore, MD 21224 USA. EM mattsonm@grc.nia.nih.gov RI Mattson, Mark/F-6038-2012 NR 58 TC 14 Z9 15 U1 0 U2 2 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 USA SN 1535-1084 J9 NEUROMOL MED JI Neuromol. Med. PY 2004 VL 5 IS 3 BP 219 EP 234 DI 10.1385/NMM:5:3:219 PG 16 WC Neurosciences SC Neurosciences & Neurology GA 885SB UT WOS:000226176100004 PM 15626822 ER PT J AU Miller, DW Cookson, MR Dickson, DW AF Miller, David W. Cookson, Mark R. Dickson, Dennis W. TI Glial cell inclusions and the pathogenesis of neurodegenerative diseases SO NEURON GLIA BIOLOGY LA English DT Review DE Protein aggregation; tau; alpha-synuclein; SOD1 AB In this review, we discuss examples that show how glial-cell pathology is increasingly recognized in several neurodegenerative diseases. We also discuss the more provocative idea that some of the disorders that are currently considered to be neurodegenerative diseases might, in fact, be due to primary abnormalities in glia. Although the mechanism of glial pathology (i.e. modulating glutamate excitotoxicity) might be better established for amyotrophic lateral sclerosis (ALS), a role for neuronal-glial interactions in the pathogenesis of most neurodegenerative diseases is plausible. This burgeoning area of neuroscience will receive much attention in the future and it is expected that further understanding of basic neuronal-glial interactions will have a significant impact on the understanding of the fundamental nature of human neurodegenerative disorders. C1 [Cookson, Mark R.] NIA, Neurogenet Lab, NIH, Bethesda, MD 20892 USA. [Dickson, Dennis W.] Mayo Clin Jacksonville, Dept Neurosci, Jacksonville, FL 32224 USA. RP Cookson, MR (reprint author), NIA, Neurogenet Lab, NIH, Bldg 10,Room 6C103,MSC1589,9000 Rockville Pike, Bethesda, MD 20892 USA. EM Cookson@mail.nih.gov FU Intramural NIH HHS [Z01 AG000953-04] NR 87 TC 29 Z9 30 U1 0 U2 2 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 32 AVENUE OF THE AMERICAS, NEW YORK, NY 10013-2473 USA SN 1740-925X J9 NEURON GLIA BIOL JI Neuron Glia Biol. PY 2004 VL 1 BP 13 EP 21 DI 10.1017/s1740925x04000043 PG 9 WC Neurosciences SC Neurosciences & Neurology GA V04OU UT WOS:000207068500003 PM 16614753 ER PT J AU Stevens, B Ishibashi, T Chen, JF Fields, RD AF Stevens, Beth Ishibashi, Tomoko Chen, Jiang-Fan Fields, R. Douglas TI Adenosine: an activity-dependent axonal signal regulating MAP kinase and proliferation in developing Schwann cells SO NEURON GLIA BIOLOGY LA English DT Article DE Purinergic receptor; Schwann-cell development; cell proliferation; ERK/MAPK; adenosine; ATP; neuron-glia interactions; myelination AB Nonsynaptic release of ATP from electrically stimulated dorsal root gangion (DRG) axons inhibits Schwann cell (SC) proliferation and arrests SC development at the premyelinating stage, but the specific types of purinergic receptor(s) and intracellular signaling pathways involved in this form of neuron-glia communication are not known. Recent research shows that adenosine is a neuron-glial transmitter between axons and myelinating glia of the CNS. The present study investigates the Possibility that adenosine might have a similar function in communicating between axons and premyelinating SCs. Using a combination of pharmacological and molecular approaches, we found that mouse SCs in culture express functional adenosine receptors and ATP receptors, a far more complex array of purinergic receptors than thought previously. Adenosine, but not ATP, activates ERK/MAPK through stimulation of cAMP-linked A2(A) adenosine receptors. Both ATP and adenosine inhibit proliferation of SCs induced by platelet-derived growth factor (PDGF), via mechanisms that are partly independent. In contrast to ATP, adenosine failed to inhibit the differentiation of SCs to the O(4)+ stage. This indicates that, in addition to ATP, adenosine is an activity-dependent signaling molecule between axons and premyelinating Schwann cells, but that electrical activity, acting through adenosine, has opposite effects on the differentiation of myelinating glia in the PNS and CNS. C1 [Stevens, Beth; Ishibashi, Tomoko; Fields, R. Douglas] NICHD, Nervous Syst Dev & Plast Sect, Natl Inst Hlth, Bethesda, MD 20892 USA. [Stevens, Beth] Univ Maryland, Neurosci & Cognit Sci Program, College Pk, MD 20742 USA. [Chen, Jiang-Fan] Massachusetts Gen Hosp, Dept Neurol, Mol Neurobiol Lab, Boston, MA 02114 USA. [Chen, Jiang-Fan] Harvard Univ, Sch Med, Boston, MA USA. RP Fields, RD (reprint author), NICHD, Nervous Syst Dev & Plast Sect, Natl Inst Hlth, Bldg 49,Room 5A78,MSC 4495, Bethesda, MD 20892 USA. EM fieldsd@mail.nih.gov FU Intramural NIH HHS [Z01 HD000713-11] NR 49 TC 47 Z9 49 U1 0 U2 2 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 32 AVENUE OF THE AMERICAS, NEW YORK, NY 10013-2473 USA SN 1740-925X J9 NEURON GLIA BIOL JI Neuron Glia Biol. PY 2004 VL 1 BP 23 EP 34 DI 10.1017/s1740925x04000055 PG 12 WC Neurosciences SC Neurosciences & Neurology GA V04OU UT WOS:000207068500004 PM 16429616 ER PT J AU Marta, CB Taylor, CM Cheng, S Quarles, RH Bansal, R Pfeiffer, SE AF Marta, C. B. Taylor, C. M. Cheng, S. Quarles, R. H. Bansal, R. Pfeiffer, S. E. TI Myelin associated glycoprotein cross-linking triggers its partitioning into lipid rafts, specific signaling events and cytoskeletal rearrangements in oligodendrocytes SO NEURON GLIA BIOLOGY LA English DT Article DE Antibody cross-linking; axo-glia interactions; fyn; fodrin AB Myelin-associated glycoprotein (MAG) has been implicated in inhibition of nerve regeneration in the CNS. This results from interactions between MAG and the Nogo receptor and gangliosides on the apposing axon, which generates intracellular inhibitory signals in the neuron. However, because myelin-axon signaling is bidirectional, we undertook an analysis of potential MAG-activated signaling in oligodendrocytes (OLs). lit this study, we show that antibody cross-linking of MAG on the surface of OLs (to mimic axonal binding) leads to the redistribution of MAG into detergent (TX-100)-insoluble complexes, hyperphosphorylation of Fyn, dephosphorylation of serine and threonine residues in specific proteins, including lactate dehydrogenase and the beta subunit of the trimeric G-protein-complex, and cleavage of alpha-fodrin followed by a transient depolymerization of actin. We propose that these changes are part of a signaling cascade in OLs associated with MAG function as a mediator Of axon-glial communication which might have implications for the mutual regulation of the formation and stability of axons and myelin. C1 [Marta, C. B.; Taylor, C. M.; Bansal, R.; Pfeiffer, S. E.] Univ Connecticut, Dept Neurosci, Sch Med, Farmington, CT 06030 USA. [Cheng, S.; Quarles, R. H.] NINDS, Myelin & Brain Dev Sect, Lab Mol & Cellular Neurobiol, Bethesda, MD 20892 USA. RP Marta, CB (reprint author), Univ Connecticut, Dept Neurosci, Sch Med, 263 Farmington Ave, Farmington, CT 06030 USA. EM Marta@up.uchc.edu FU NIH [NS10861, NS45440, NS41078]; National Multiple Sclerosis Society [FG1423A] FX We would like to acknowledge A. Taylor and M. Montano for excellent technical support. Supported by grants from NIH NS10861, NS45440 and NS41078. This investigation was supported in part by a Postdoctoral Fellowship from the National Multiple Sclerosis Society FG1423A. NR 83 TC 19 Z9 20 U1 0 U2 0 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 32 AVENUE OF THE AMERICAS, NEW YORK, NY 10013-2473 USA SN 1740-925X J9 NEURON GLIA BIOL JI Neuron Glia Biol. PY 2004 VL 1 BP 35 EP 46 DI 10.1017/s1740925x04000067 PG 12 WC Neurosciences SC Neurosciences & Neurology GA V04OU UT WOS:000207068500005 PM 16998591 ER PT J AU Lepore, AC Han, SSW Tyler-Polsz, CJ Cai, JL Rao, MS Fischer, I AF Lepore, Angelo C. Han, Steven S. W. Tyler-Polsz, Carla J. Cai, Jingli Rao, Mahendra S. Fischer, Itzhak TI Differential fate of multipotent and lineage-restricted neural precursors following transplantation into the adult CNS SO NEURON GLIA BIOLOGY LA English DT Article DE Stem cells; neurons; glial cells; neural progenitors; spinal cord injury AB Multiple classes of precursor cells have been isolated and characterized from the developing spinal cord including multipotent neuroepithelial (NEP) stern cells and lineage-restricted precursors for neurons (NRPs) and glia (GRPs). We have compared the survival, differentiation and integration of multipotent NEP cells with lineage-restricted NRPs and GRPs using cells isolated from transgenic rats that express the human placental alkaline phosphatase gene. Our results demonstrate that grafted NEP cells survive poorly, with no cells observed 3 days after transplant in the adult hippocampus, striatum and spinal cord, indicating that most CNS regions are not compatible with transplants of multipotent cells derived from fetal CNS. By contrast, at 3 weeks and 5 weeks post-engraftment, lineage-restricted precursors showed selective migration along white-matter tracts and robust survival in all three CNS regions. The grafted precursors expressed the mature neuronal markets NeuN and MAP2, the astrocytic marker GFAP, the oligodendrocytic markets RIP, NG2 and Sox-10, and the synaptic marker synaptophysin. Similar behavior was observed when these precursors were transplanted into the injured spinal cord. Predifferentiated, multipotent NEP cells also survive and integrate, which indicates that lineage-restricted CNS precursors are well suited for transplantation into the adult CNS and provide a promising cellular replacement candidate. C1 [Lepore, Angelo C.; Han, Steven S. W.; Tyler-Polsz, Carla J.; Fischer, Itzhak] Drexel Univ, Coll Med, Dept Neurobiol & Anat, Philadelphia, PA 19129 USA. [Cai, Jingli; Rao, Mahendra S.] NIA, Neurosci Lab, Baltimore, MD 21224 USA. RP Fischer, I (reprint author), Drexel Univ, Coll Med, Dept Neurobiol & Anat, 2900 W Queen Lane, Philadelphia, PA 19129 USA. EM Itzhak.Fischer@drexel.edu RI Fischer, Itzhak/D-1080-2012 OI Fischer, Itzhak/0000-0003-3187-8740 FU IRTA; NIH [NS24707, NS 37515]; NIA; CNS Foundation; Packard Center FX We would like to acknowledge all members of our laboratories for stimulating discussions, particularly Dr Barry Himes and Theresa Connors for their technical expertise. A.C.L. thanks Dr Birgit Neuhuber for discussion and constructive criticism, the Neuroscience graduate program for its support and John, Paul, George and Richard for their incalculable assistance. J.C. was supported by an IRTA fellowship from the NIA. M.S.R. was supported by the NIH, NIA, CNS Foundation and Packard Center. M.S.R. acknowledges the contributions of Dr. S. Rao that made this project possible. I.F. was supported by NIH grants NS24707 and NS 37515. NR 45 TC 58 Z9 67 U1 0 U2 1 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 32 AVENUE OF THE AMERICAS, NEW YORK, NY 10013-2473 USA SN 1740-925X J9 NEURON GLIA BIOL JI Neuron Glia Biol. PY 2004 VL 1 BP 113 EP 126 DI 10.1017/S1740925X04000213 PG 14 WC Neurosciences SC Neurosciences & Neurology GA V04OV UT WOS:000207068600003 PM 16520830 ER PT J AU Lee, PR Cohen, JE Tendi, EA Farrer, R De Vries, GH Becker, KG Fields, RD AF Lee, Philip R. Cohen, Jonathan E. Tendi, Elisabetta A. Farrer, Robert De Vries, George H. Becker, Kevin G. Fields, R. Douglas TI Transcriptional profiling in an MPNST-derived cell line and normal human Schwann cells SO NEURON GLIA BIOLOGY LA English DT Article DE Cancer; NF1; MPNST; T265; Schwann cell; cDNA microarray AB cDNA microarrays were utilized to identify abnormally expressed genes in a malignant peripheral nerve sheath tumor (MPNST)-derived cell line, T265, by comparing the mRNA abundance profiles with that of normal human Schwann cells (nhSCs). The findings characterize the molecular phenotype of this important cell-line model of MPNSTs, and elucidate the contribution of Schwann cells in MPNSTs. In total, 4608 cDNA sequences were screened and hybridizations replicated on custom cDNA microarrays. In order to verify the microarray data, a large selection of differentially expressed mRNA transcripts were subjected to semi-quantitative reverse transcription PCR (LightCycler). Western blotting was performed to investigate a selection of genes and signal transduction pathways, as a further validation of the microarray data. The data generated from multiple microarray screens, semi-quantitative RT-PCR and Western blotting are in broad agreement. This study represents a comprehensive gene-expression analysis of an MPNST-derived cell line and the first comprehensive global mRNA profile of nhSCs in culture. This study has identified similar to 900 genes that are expressed abnormally in the T265 cell line and detected many genes not previously reported to be expressed in nhSCs. The results provide crucial information oil the T265 cells that is essential for investigation using this cell line in experimental studies in neurofibromatosis type I (NF1), and important information oil normal human Schwann cells that is applicable to a wide range of studies oil Schwann cells in cell culture. C1 [Farrer, Robert; De Vries, George H.] Loyola Univ, Dept Cell Biol Neurobiol & Anat, Chicago Stritch Sch Med, Chicago, IL 60611 USA. [Becker, Kevin G.] NIA, Gene Express & Genom Unit, NIH, Baltimore, MD 21224 USA. [Lee, Philip R.; Cohen, Jonathan E.; Tendi, Elisabetta A.; Fields, R. Douglas] NICHD, Sect Nervous Syst Dev & Plast, NIH, Bethesda, MD 20892 USA. RP Fields, RD (reprint author), NICHD, Sect Nervous Syst Dev & Plast, NIH, Bldg 35,Rm 2A211,MSC 3713, Bethesda, MD 20892 USA. EM Fieldsd@mail.nih.gov RI Moyal, Elizabeth/A-9802-2015 OI Moyal, Elizabeth/0000-0002-6593-9276 FU Intramural NIH HHS [Z01 HD000713-11] NR 35 TC 21 Z9 21 U1 0 U2 5 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 32 AVENUE OF THE AMERICAS, NEW YORK, NY 10013-2473 USA SN 1740-925X J9 NEURON GLIA BIOL JI Neuron Glia Biol. PY 2004 VL 1 BP 135 EP 147 DI 10.1017/S1740925X04000274 PG 13 WC Neurosciences SC Neurosciences & Neurology GA V04OV UT WOS:000207068600005 PM 16429615 ER PT J AU Furman, S Steingart, RA Mandel, S Hauser, JM Brenneman, DE Gozes, I AF Furman, Sharon Steingart, Ruth A. Mandel, Shmuel Hauser, Janet M. Brenneman, Douglas E. Gozes, Illana TI Subcellular localization and secretion of activity-dependent neuroprotective protein in astrocytes SO NEURON GLIA BIOLOGY LA English DT Article DE ADNP; homeobox; brain development; microtubules; secreted proteins AB Activity-dependent neuroprotective protein (ADNP, similar to 123562.8 Da), is synthesized in astrocytes and expression of A DNP mRNA is regulated by the neuroprotective peptide vasoactive intestinal peptide (VIP). The gene that encodes ADNP is conserved in human, rat and mouse, and contains a homeobox domain profile that includes a nuclear-export signal and a nuclear-localization signal. ADNP is essential for embryonic brain development, and NAP, an eight-amino acid peptide that is derived from ADNP, confers potent neuroprotection. Here, we investigate the subcellular localization of ADNP through cell fractionation, gel electrophoresis, immunoblotting and immunocytochemistry using alpha-CNAP, an antibody directed to the neuroprotective NAP fragment that constitutes part of an N-terminal epitope of ADNP. Recombinant ADNP was used as a competitive ligand to measure antibody specificity. ADNP-like immunoreactivity was found in the nuclear cell fraction of astrocytes and in the cytoplasm. In the cytoplasm, ADNP-like immunoreactivity colocalized with tubulin-like immunoreactivity and with microtubular structures, but not with actin microfilaments. Because microtubules are key components of developing neurons and brain, possible interaction between tubulin and ADNP might indicate a functional correlate to the role of ADNP in the brain. In addition, ADNP-like immunoreactivity in the extracellular milieu of astrocytes increased by similar to 1.4 fold after incubation of the astrocytes with VIP. VIP is known to cause astrocytes to secrete neuroprotective/neurotrophic factors, and we suggest that ADNP constitutes part of this VIP-stimulated protective milieu. C1 [Furman, Sharon; Steingart, Ruth A.; Mandel, Shmuel; Gozes, Illana] Tel Aviv Univ, Sackler Fac Med, Dept Clin Biochem, IL-69978 Tel Aviv, Israel. [Hauser, Janet M.; Brenneman, Douglas E.] NICHHD, Sect Dev & Mol Pharmacol, Dev Neurobiol Lab, Bethesda, MD 20892 USA. RP Gozes, I (reprint author), Tel Aviv Univ, Sackler Fac Med, Dept Clin Biochem, Einstein St, IL-69978 Tel Aviv, Israel. EM igozes@post.tau.ac.il FU US-Israel Bi-National Science Foundation; Neufeld Award; National Institutes of Health; Sackler Faculty of Medicine/Tel-Aviv University in Women's Health; Israel Science Foundation; Institute for the Study of Aging; Allon Therapeutics Inc FX The authors would like to thank Dr. Leonid Mittelman for invaluable help with the confocal microscopy and Ms. I. Divinski for assistance with fluorescent immunostaining. We thank Prof. M. Fridkin and Ms. S. Rubinraut for VIP and Prof C.J. Barnstable for the help with the tubulin antibodies, and Dr. R. Zamostiano and Ms. I. Zemlyak who helped in the initial stages of the work. This work is in partial fulfillment of the requirements towards the Ph.D. degrees of S.F. and S.M. This study was supported by the US-Israel Bi-National Science Foundation, the Neufeld Award, the Combined Program of the National Institutes of Health and the Sackler Faculty of Medicine/Tel-Aviv University in Women's Health, the Israel Science Foundation, the Institute for the Study of Aging, and Allon Therapeutics Inc. I.G. holds the Lily and Avraham Gildor Chair for the Investigation of Growth Factors. ADNP is under patent protection. NR 39 TC 59 Z9 63 U1 2 U2 3 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 32 AVENUE OF THE AMERICAS, NEW YORK, NY 10013-2473 USA SN 1740-925X J9 NEURON GLIA BIOL JI Neuron Glia Biol. PY 2004 VL 1 BP 193 EP 199 DI 10.1017/S1740925X05000013 PG 7 WC Neurosciences SC Neurosciences & Neurology GA V04OW UT WOS:000207068700002 PM 16845437 ER PT J AU Du, J Quiroz, J Yuan, PX Zarate, C Manji, HK AF Du, Jing Quiroz, Jorge Yuan, Peixiong Zarate, Carlos Manji, Husseini K. TI Bipolar disorder: involvement of signaling cascades and AMPA receptor trafficking at synapses SO NEURON GLIA BIOLOGY LA English DT Review DE Lithium; valproate; antidepressant; bipolar disorder; glutamatergic system AB There is increasing evidence that severe mood disorders (ire associated with impartment of structural plasticity and cellular resilience. Cumulative data demonstrate that mood stabilizers regulate intracellular signaling cascades, including protein kinase C (PKC), PKA, mitogen-activated protein (MAP) kinase, glycogen synthase kinase 3-beta (GSK(3)-beta) and intracellular calcium, which are signaling pathways that regulate synaptic plasticity. lit this context, it is noteworthy that a growing body of data indicates that the glutamatergic system, has a major role in neuronal plasticity and cellular resilience, might be involved in the pathophysiology and treatment of mood disorders. AMPA glutamate-receptor trafficking is important in synaptic plasticity and might play crucial roles in maintaining critical neuronal circuits associated with mood. Two clinically effective, structurally dissimilar, antimanic agents, lithium and valproate (VPA), down-regulate synaptic expression of AMPA receptor subunit GluR1 in hippocampus in chronically treated rats. This reduction in synaptic GluR1 by lithium and VPA is (lite to attennuated phosphorylation of GluR1 at a specific PKA site (residue 845 of GluR1 which is crucial for AMPA receptor insertion. By contrast, imipramine, which can provoke mania increases synaptic expression of GluR1 in lite hippocampus in vivo. Further more, there is ample evidence from preclinical and clinical research that the glutamatergic system is involved in the pathophysiology of mood disorders and that many of the somatic treatments used for mood disorders including antidepressants, mood stabilizers, atypical antipsychotic drugs and electroconvulsive therapy have both direct and indirect effects on the glutamatergic system. Given these findings, further research with medications that specifically affect the glutamatergic system is warranted. Recent studies in our lab have shown that riluzole, a FDA approved medicine that regulates the glutamatergic system, shows antidepressant efficacy in unipolar and bipolar depression. These studies indicate that regulation of glutamate-mediated synaptic plasticity might play a role in the treatment of mood disorders, and raise new avenues for novel therapies for this devastating illness. C1 [Du, Jing] NIMH, Mol Pathophysiol Lab, Mood & Anxiety Disorders Program, Bethesda, MD 20892 USA. RP Du, J (reprint author), NIMH, Mol Pathophysiol Lab, Mood & Anxiety Disorders Program, 9000 Rockville Pike Bldg 35,Room 1BC909, Bethesda, MD 20892 USA. EM duj@mail.nih.gov FU Intramural NIH HHS [Z01 MH002831-05] NR 115 TC 16 Z9 17 U1 0 U2 4 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 32 AVENUE OF THE AMERICAS, NEW YORK, NY 10013-2473 USA SN 1740-925X J9 NEURON GLIA BIOL JI Neuron Glia Biol. PY 2004 VL 1 BP 231 EP 243 DI 10.1017/S1740925X05000098 PG 13 WC Neurosciences SC Neurosciences & Neurology GA V04OW UT WOS:000207068700006 PM 18634600 ER PT J AU Lu, B Chang, JH AF Lu, Bai Chang, Jay H. TI Regulation of neurogenesis by neurotrophins: implications in hippocampus-dependent memory SO NEURON GLIA BIOLOGY LA English DT Review DE BDNF; NT-3; dentate gyrus; neurogenesis; learning and memory; LTP; neural stem cells AB Neurogenesis, the generation of new neurons from neural precursor cells (NPCs), is a multi-step process that includes the proliferation of NPCs, fate determination, migration, and neuronal maturation. Neurogenesis is regulated by several extrinsic factors, such as enriched environment, physical exercise, hormones and stress, many of which also induce the expression of neurotrophins. In this review, we summarize studies on the role of neurotrophins in neurogenesis during development and in adults. We discuss the functional significance of neurogenesis in learning and memory, and how neurotrophins regulate this process. In this context, we describe recent experiments linking adult neurogenesis to long-term synaptic plasticity in the hippocampal dentate gyrus. Further study of the relationship between neurotrophins, adult neurogenesis and dentate synaptic plasticity might provide new insights into the mechanisms by which gene-environment interactions control cognition and brain plasticity. C1 [Lu, Bai; Chang, Jay H.] NICHD, Sect Neural Dev & Plast, NIH, Bethesda, MD 20892 USA. RP Lu, B (reprint author), NICHD, Sect Neural Dev & Plast, NIH, 35 Convent Dr,MSC 3714, Bethesda, MD 20892 USA. EM bailu@mail.nih.gov NR 101 TC 1 Z9 1 U1 1 U2 7 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 32 AVENUE OF THE AMERICAS, NEW YORK, NY 10013-2473 USA SN 1740-925X J9 NEURON GLIA BIOL JI Neuron Glia Biol. PY 2004 VL 1 BP 377 EP 384 DI 10.1017/S1740925X05000232 PG 8 WC Neurosciences SC Neurosciences & Neurology GA V04OX UT WOS:000207068800007 PM 18634594 ER PT J AU Volkow, ND Fowler, JS Wang, GJ AF Volkow, ND Fowler, JS Wang, GJ TI The addicted human brain viewed in the light of imaging studies: brain circuits and treatment strategies SO NEUROPHARMACOLOGY LA English DT Article DE striatum; dopamine; reward; motivation; predisposition; salience; nucleus accumbens (NAc); orbitofrontal cortex (OFC); cingulate gyrus ID MAGNETIC-RESONANCE-SPECTROSCOPY; PRIMATE ORBITOFRONTAL CORTEX; NUCLEUS-ACCUMBENS; DRUG-ADDICTION; COCAINE DEPENDENCE; FRONTAL-CORTEX; DOPAMINE-D-2 RECEPTORS; CONTROLLED-TRIAL; SUBSTANCE-ABUSE; MEMORY-CIRCUITS AB Imaging studies have provided evidence of how the human brain changes as an individual becomes addicted. Here, we integrate the findings from imaging studies to propose a model of drug addiction. The process of addiction is initiated in part by the fast and high increases in DA induced by drugs of abuse. We hypothesize that this supraphysiological effect of drugs trigger a series of adaptations in neuronal circuits involved in saliency/reward, motivation/drive, memory/conditioning, and control/disinhibition, resulting in an enhanced (and long lasting) saliency value for the drug and its associated cues at the expense of decreased sensitivity for salient events of everyday life (including natural reinforcers). Although acute drug intake increases DA neurotransmission, chronic drug consumption results in a marked decrease in DA activity, associated with, among others, dysregulation of the orbitofrontal cortex (region involved with salience attribution) and cingulate gyrus (region involved with inhibitory control). The ensuing increase in motivational drive for the drug, strengthened by conditioned responses and the decrease in inhibitory control favors emergence of compulsive drug taking. This view of how drugs of abuse affect the brain suggests strategies for intervention, which might include: (a) those that will decrease the reward value of the drug of choice; (b) interventions to increase the saliency value of non-drug reinforcers; (c) approaches to weaken conditioned drug behaviors; and (d) methods to strengthen frontal inhibitory and executive control. Though this model focuses mostly on findings from PET studies of the brain DA system it is evident that other neurotransmitters are involved and that a better understanding of their roles in addiction would expand the options for therapeutic targets. (C) 2004 Elsevier Ltd. All rights reserved. C1 NIDA, Bethesda, MD 20892 USA. NIAAA, Bethesda, MD 20892 USA. Brookhaven Natl Lab, Dept Med, Upton, NY 11973 USA. Brookhaven Natl Lab, Dept Chem, Upton, NY 11973 USA. RP Volkow, ND (reprint author), NIDA, 6001 Execut Blvd,Room 5274,MSC 9581, Bethesda, MD 20892 USA. EM nvolkow@nida.nih.gov NR 87 TC 287 Z9 309 U1 6 U2 27 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0028-3908 J9 NEUROPHARMACOLOGY JI Neuropharmacology PY 2004 VL 47 SU S BP 3 EP 13 DI 10.1016/j.neuropharm.2004.07.019 PG 11 WC Neurosciences; Pharmacology & Pharmacy SC Neurosciences & Neurology; Pharmacology & Pharmacy GA 866TV UT WOS:000224797200002 PM 15464121 ER PT J AU Uhl, GR AF Uhl, GR TI Molecular genetic underpinnings of human substance abuse vulnerability: likely contributions to understanding addiction as a mnemonic process SO NEUROPHARMACOLOGY LA English DT Article DE drug abuse; complex genetics; association genome scanning ID GENOME-WIDE SEARCH; ALCOHOL DEPENDENCE; DRUG-ABUSE; ENVIRONMENTAL-INFLUENCES; COGNITIVE PERFORMANCE; POLYSUBSTANCE ABUSERS; BRAIN VOLUMES; FEMALE TWINS; SAMPLE; MEN AB Classical genetic studies document strong complex genetic contributions to abuse of multiple addictive substances. These genetic influences are more prominent in the later phases of individuals' progressions toward substance dependence. Individual differences in human addiction vulnerability could thus derive, in part, from individual differences in mnemonic systems. These variations could add to allelic variations that could produce effects on addiction vulnerability phenotypes by other routes that could include (1) differences in drug metabolism or biodistribution, (2) differences in drug's rewarding properties, (3) differences in traits manifest by the addict, including personality differences and (4) differences in the addict's psychiatric comorbidities. Data from linkage and association genome scans now identify chromosomal regions that are likely to contain allelic gene variants that contribute to human addiction vulnerability. Converging positive results are found in several different substance-abusing populations studied in several laboratories. This convergence supports the idea that common allelic variants contribute to individual differences in vulnerability to substance dependence. Genomic markers that identify allelic variants that reproducibly alter addiction vulnerability in several populations provide tools for research in addictions, tools to improve addiction treatments, tools to improve addiction prevention, clues to the genetic bases of individual differences in mnemonic processes and clues to the genetic bases of individual differences in the other traits and disorders that co-occur with substance dependencies. Published by Elsevier Ltd. C1 NIDA, Mol Neurobiol Branch, IRP, NIH, Baltimore, MD 21224 USA. RP Uhl, GR (reprint author), NIDA, Mol Neurobiol Branch, IRP, NIH, POB 5180, Baltimore, MD 21224 USA. EM guhl@intra.nida.nih.gov NR 47 TC 38 Z9 39 U1 5 U2 7 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0028-3908 J9 NEUROPHARMACOLOGY JI Neuropharmacology PY 2004 VL 47 SU S BP 140 EP 147 DI 10.1016/j.neuropharm.2004.07.029 PG 8 WC Neurosciences; Pharmacology & Pharmacy SC Neurosciences & Neurology; Pharmacology & Pharmacy GA 866TV UT WOS:000224797200014 PM 15464133 ER PT J AU Ikemoto, S Wise, RA AF Ikemoto, S Wise, RA TI Mapping of chemical trigger zones for reward SO NEUROPHARMACOLOGY LA English DT Article DE nucleus accumbens; ventral tegmental area; dopamine; reinforcement; intracranial self-administration ID VENTRAL TEGMENTAL AREA; MEDIAL PREFRONTAL CORTEX; NUCLEUS-ACCUMBENS SHELL; ALCOHOL-PREFERRING RATS; IN-VIVO MICRODIALYSIS; 6-HYDROXYDOPAMINE LESIONS; WISTAR RATS; REINFORCING PROPERTIES; COCAINE REINFORCEMENT; LATERAL HYPOTHALAMUS AB Addictive drugs are thought to activate brain circuitry that normally mediates more natural rewards such as food or water. Drugs activate this circuitry at synaptic junctions within the brain; identifying the junctions at which this occurs provides clues to the neurochemical and anatomical characteristics of the circuitry. One approach to identifying the junctions at which drugs interact with this circuitry is to determine if animals will lever-press for site-specific microinjections of addictive drugs. This approach has identified GABAergic, dopaminergic, glutamatergic, and cholinergic trigger zones within meso-corticolimbic circuitry important for natural reward function. Published by Elsevier Ltd. C1 NIDA, Behav Neurosci Branch, NIH, Dept Hlth & Human Serv, Baltimore, MD 21224 USA. RP Ikemoto, S (reprint author), NIDA, Behav Neurosci Branch, NIH, Dept Hlth & Human Serv, 5500 Nathan Shock Dr, Baltimore, MD 21224 USA. EM sikemoto@intra.nida.nih.gov RI Wise, Roy/A-6465-2012; OI Ikemoto, Satoshi/0000-0002-0732-7386 NR 87 TC 101 Z9 101 U1 1 U2 5 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0028-3908 J9 NEUROPHARMACOLOGY JI Neuropharmacology PY 2004 VL 47 SU S BP 190 EP 201 DI 10.1016/j.neuropharm.2004.07.012 PG 12 WC Neurosciences; Pharmacology & Pharmacy SC Neurosciences & Neurology; Pharmacology & Pharmacy GA 866TV UT WOS:000224797200018 PM 15464137 ER PT J AU Lu, L Grimm, JW Hope, BT Shaham, Y AF Lu, L Grimm, JW Hope, BT Shaham, Y TI Incubation of cocaine craving after withdrawal: a review of preclinical data SO NEUROPHARMACOLOGY LA English DT Article DE BDNF; craving; cocaine cues; extinction; incubation; glutamate receptors; neuroadaptations; priming; reinstatement; relapse; review; sucrose; withdrawal ID VENTRAL TEGMENTAL AREA; OPPONENT-PROCESS THEORY; TIME-DEPENDENT CHANGES; STRESS-INDUCED RELAPSE; DRUG-SEEKING BEHAVIOR; NEUROTROPHIC FACTOR; INDUCED REINSTATEMENT; NUCLEUS-ACCUMBENS; EXTRACELLULAR DOPAMINE; TYROSINE-HYDROXYLASE AB Using a rat model of drug craving and relapse, we recently found that cocaine seeking induced by re-exposure to drug-associated cues progressively increases over the first 2 months after withdrawal from cocaine self-administration, suggesting that drug craving incubates over time [Nature 412 (2001) 141]. Here, we summarize data from studies that further characterized this incubation phenomenon and briefly discuss its implications for drug addiction. The main findings of our ongoing research are: 1. Incubation of cocaine craving is long-lasting, but not permanent: cocaine seeking induced by exposure to cocaine cues remains elevated for up to 3 months of withdrawal, but decreases after 6 months. 2. Incubation of reward craving is not drug specific: sucrose seeking induced by re-exposure to the reward cues also increases after withdrawal, but for a time period that is shorter than that of cocaine. 3. Incubation of cocaine craving is not evident after acute re-exposure to cocaine itself: cocaine seeking induced by cocaine priming injections remains essentially unchanged over the first 6 months of withdrawal. 4. Incubation of cocaine craving after withdrawal is associated with increases in the levels of brain-derived neurotrophic factor (BDNF) in meso-limbic dopamine areas. Published by Elsevier Ltd. C1 NIDA, Behav Neurosci Branch, IRP,NIH, DHHS, Baltimore, MD 21224 USA. Western Washington Univ, Dept Psychol, Bellingham, WA 98225 USA. RP Shaham, Y (reprint author), NIDA, Behav Neurosci Branch, IRP,NIH, DHHS, 5500 Nathan Shock Dr, Baltimore, MD 21224 USA. EM yshaham@intra.nida.nih.gov RI Hope, Bruce/A-9223-2010; shaham, yavin/G-1306-2014 OI Hope, Bruce/0000-0001-5804-7061; NR 99 TC 220 Z9 223 U1 2 U2 13 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0028-3908 J9 NEUROPHARMACOLOGY JI Neuropharmacology PY 2004 VL 47 SU S BP 214 EP 226 DI 10.1016/j.neuropharm.2004.06.027 PG 13 WC Neurosciences; Pharmacology & Pharmacy SC Neurosciences & Neurology; Pharmacology & Pharmacy GA 866TV UT WOS:000224797200020 PM 15464139 ER PT J AU Poeppel, D Guillemin, A Thompson, J Fritz, J Bavelier, D Braun, AR AF Poeppel, D Guillemin, A Thompson, J Fritz, J Bavelier, D Braun, AR TI Auditory lexical decision, categorical perception, and FM direction discrimination differentially engage left and right auditory cortex SO NEUROPSYCHOLOGIA LA English DT Article DE hemispheric asymmetry; speech perception; word recognition; spectral; temporal ID POSITRON-EMISSION-TOMOGRAPHY; INFERIOR FRONTAL-CORTEX; FUNCTIONAL NEUROANATOMY; SPEECH-PERCEPTION; TEMPORAL-LOBE; LATERALIZATION; BRAIN; PET; LANGUAGE; SOUNDS AB Recent neuroimaging and neuropsychological data suggest that speech perception is supported in bilaterally auditory areas. We evaluate this issue building on well-known behavioral effects. While undergoing positron emission tomography (PET), subjects performed standard auditory tasks: direction discrimination of frequency-modulated (FM) tones, categorical perception (CP) of consonant-vowel (CV) syllables, and word/nod-word judgments (lexical decision, LD). Compared to rest, the three conditions led to bilateral activation of the auditory cortices. However, lateralization patterns differed as a function of stimulus type: the LID task generated stronger responses in the left, the FM task a stronger response in the right hemisphere. Contrasts between either words or syllables versus FM were associated with significantly greater activity bilaterally in superior temporal gyrus (STG) ventro-lateral to Heschl's gyrus. These activations extended into the superior temporal sulcus (STS) and the middle temporal gyrus (MTG) and were greater in the left. The same areas were more active in the LD than the CP task. In contrast, the FM task was associated with significantly greater activity in the right lateral-posterior STG and lateral MTG. The findings argue for a view in which speech perception is mediated bilaterally in the auditory cortices and that the well-documented lateralization is likely associated with processes subsequent to the auditory analysis of speech. (C) 2003 Elsevier Ltd. All rights reserved. C1 Univ Maryland, Dept Linguist, Cognit Neurosci & Language Lab, College Pk, MD 20742 USA. Univ Maryland, Dept Biol, College Pk, MD 20742 USA. Univ Rochester, Dept Brain & Cognit Sci, Rochester, NY 14627 USA. Univ Maryland, Syst Res Inst, College Pk, MD 20742 USA. Natl Inst Deafness & Other Commun Disorders, Language Sect, Voice Speech & Language Branch, Bethesda, MD 20892 USA. RP Poeppel, D (reprint author), Univ Maryland, Dept Linguist, Cognit Neurosci & Language Lab, 1401 Marie Mt Hall, College Pk, MD 20742 USA. OI Bavelier, Daphne/0000-0002-5904-1240 FU NIDCD NIH HHS [DC04638, DC05660] NR 55 TC 101 Z9 104 U1 0 U2 4 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0028-3932 J9 NEUROPSYCHOLOGIA JI Neuropsychologia PY 2004 VL 42 IS 2 BP 183 EP 200 DI 10.1016/j.neuropsychologia.2003.07.010 PG 18 WC Behavioral Sciences; Neurosciences; Psychology, Experimental SC Behavioral Sciences; Neurosciences & Neurology; Psychology GA 753FC UT WOS:000187220600006 PM 14644105 ER PT J AU Elvevag, B Fisher, JE Weickert, TW Weinberger, DR Goldberg, TE AF Elvevag, B Fisher, JE Weickert, TW Weinberger, DR Goldberg, TE TI Lack of false recognition in schizophrenia: a consequence of poor memory? SO NEUROPSYCHOLOGIA LA English DT Article DE false memory; recall; recognition; schizophrenia ID SHORT-TERM-MEMORY; NEUROPSYCHOLOGICAL FUNCTION; SERIAL ORDER; OLDER-ADULTS; IMPAIRMENT; RECALL; HIPPOCAMPUS; PREDICTION; DISORDER; LESIONS AB The tendency to falsely recognize items as ones previously presented is increased in patients with frontal lesions and in older participants, whereas patients with medial temporal lobe damage may display such poor memory that they are not especially susceptible to false recognition. Since patients with schizophrenia are often compared to these groups neurocognitively, we explored the extent to which they are more susceptible to false memory. Participants were presented with word lists along a semantic theme, such as "bread". After list presentation, recognition tasks were administered which contained both the studied words as well as unstudied words. Some of the unstudied words were related to the theme of the previously studied words, but never actually presented (e.g. semantic "lures"). In a separate test, free recall of these lists of words was assessed. Interestingly, it was control participants who made more errors at recall, and were especially susceptible to intrusions of the semantic lures. Patients with schizophrenia did not make more false recognition errors in general, and surprisingly they made disproportionately fewer false recognition errors to semantic lures specifically. We conclude that despite poor memory, patients with schizophrenia are not especially susceptible to interference from previous tasks and are not particularly prone to false recollections. Published by Elsevier Ltd. C1 NIMH, Clin Brain Disorders Branch, NIH, Bethesda, MD 20892 USA. RP Elvevag, B (reprint author), NIMH, Clin Brain Disorders Branch, NIH, Bldg 10,Room 4S235,MSC 1379, Bethesda, MD 20892 USA. EM elvevaab@intra.nimh.nih.gov NR 54 TC 36 Z9 36 U1 1 U2 8 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0028-3932 J9 NEUROPSYCHOLOGIA JI Neuropsychologia PY 2004 VL 42 IS 4 BP 546 EP 554 DI 10.1016/j.neuropsychologia.2003.08.013 PG 9 WC Behavioral Sciences; Neurosciences; Psychology, Experimental SC Behavioral Sciences; Neurosciences & Neurology; Psychology GA 772LG UT WOS:000188842900011 PM 14728926 ER PT J AU Ernst, M Nelson, EE McClure, EB Monk, CS Munson, S Eshel, N Zarahn, E Leibenluft, E Zametkin, A Towbin, K Blair, J Charney, D Pine, DS AF Ernst, M Nelson, EE McClure, EB Monk, CS Munson, S Eshel, N Zarahn, E Leibenluft, E Zametkin, A Towbin, K Blair, J Charney, D Pine, DS TI Choice selection and reward anticipation: an fMRI study SO NEUROPSYCHOLOGIA LA English DT Article DE decision-making; expectation; motivation; ventral striatum; neuroimaging; fMRI ID ANTERIOR CINGULATE CORTEX; VENTROMEDIAL PREFRONTAL CORTEX; EVENT-RELATED FMRI; DECISION-MAKING; ORBITOFRONTAL CORTEX; NEURAL RESPONSES; WORKING-MEMORY; HUMAN AMYGDALA; NUCLEUS-ACCUMBENS; PARIETAL CORTEX AB We examined neural activations during decision-making using fMRI paired with the wheel of fortune task, a newly developed two-choice decision-making task with probabilistic monetary gains. In particular, we assessed the impact of high-reward/risk events relative to low-reward/risk events on neural activations during choice selection and during reward anticipation. Seventeen healthy adults completed the study. We found, in line with predictions, that (i) the selection phase predominantly recruited regions involved in visuo-spatial attention (occipito-parietal pathway), conflict (anterior cingulate), manipulation of quantities (parietal cortex), and preparation for action (premotor area), whereas the anticipation phase prominently recruited regions engaged in reward processes (ventral striatum); and (ii) high-reward/risk conditions relative to low-reward/risk conditions were associated with a greater neural response in ventral striatum during selection, though not during anticipation. Following an a priori ROI analysis focused on orbitofrontal cortex, we observed orbitofrontal cortex activation (BA-11 and 47) during selection (particularly to high-risk/reward options), and to a more limited degree, during anticipation. These findings support the notion that (1) distinct, although overlapping, pathways subserve the processes of selection and anticipation in a two-choice task of probabilistic monetary reward; (2) taking a risk and awaiting the consequence of a risky decision seem to affect neural activity differently in selection and anticipation; and thus (3) common structures, including the ventral striatum, are modulated differently by risk/reward during selection and anticipation. Published by Elsevier Ltd. C1 NIMH, Mood & Anxiety Disorders Program, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. RP Ernst, M (reprint author), NIMH, Mood & Anxiety Disorders Program, NIH, Dept Hlth & Human Serv, 15K N Dr, Bethesda, MD 20892 USA. EM ernstm@intra.nimh.nih.gov RI Nelson, Eric/B-8980-2008; Monk, Christopher/J-1805-2014; OI Nelson, Eric/0000-0002-3376-2453; Eshel, Neir/0000-0002-5976-2013 NR 69 TC 204 Z9 210 U1 7 U2 21 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0028-3932 J9 NEUROPSYCHOLOGIA JI Neuropsychologia PY 2004 VL 42 IS 12 BP 1585 EP 1597 DI 10.1016/j.neuropsychologia.2004.05.011 PG 13 WC Behavioral Sciences; Neurosciences; Psychology, Experimental SC Behavioral Sciences; Neurosciences & Neurology; Psychology GA 856LV UT WOS:000224047600001 PM 15327927 ER PT J AU Gerton, BK Brown, TT Meyer-Lindenberg, A Kohn, P Holt, JL Olsen, RK Berman, KF AF Gerton, BK Brown, TT Meyer-Lindenberg, A Kohn, P Holt, JL Olsen, RK Berman, KF TI Shared and distinct neurophysiological components of the digits forward and backward tasks as revealed by functional neuroimaging SO NEUROPSYCHOLOGIA LA English DT Article DE working memory; prefrontal cortex; phonological processing; visuospatial processing; Occipital cortex; PET ID SHORT-TERM-MEMORY; POSITRON-EMISSION-TOMOGRAPHY; ANTERIOR CINGULATE CORTEX; WORKING-MEMORY; RESPONSE CONFLICT; SPAN PERFORMANCE; PET; BRAIN; INFORMATION; NEGLECT AB The digits forward (DF) and backward (DB) tasks are widely used neuropsychological measures believed to tap overlapping systems of phonological processing and working memory. Studies of focal brain lesions have partially elucidated the brain regions essential for these tasks; however relatively little information exists on the underlying functional neuroanatomy in the intact brain. We therefore examined the shared and separate neural systems of these tasks in two positron emission tomography (PET) experiments. In Experiment 1, eight healthy participants performed verbal DF, DB, and a sensorimotor control task during measurement of regional cerebral blood flow (rCBF). DF and DB each activated frontal, parietal, and cerebellar regions as well as prominently activating medial occipital cortex. To eliminate possible visuospatial confounds. Experiment 2 replicated the first experiment in six additional healthy participants who were blindfolded during the study. No differences in activation were found between the two experimental groups. Combined data from both experiments demonstrate that DF and DB rely upon a largely overlapping functional neural system associated with working memory, most notably right dorsolateral prefrontal cortex (DLPFC) and bilateral inferior parietal lobule (IPL) as well as the anterior cingulate, a region associated with attentional effort. The degree of activation increased linearly with increasing task difficulty in DF. DB additionally recruited bilateral DLPFC, left IPL, and Broca's area. Medial occipital cortex (including higher and lower visual processing areas) was robustly activated in both DF and DB and could not be attributed to visual processing per se, suggesting a possible visual imagery strategy for these aural-verbal tasks. Published by Elsevier Ltd. C1 NIMH, Intramural Res Program, Clin Brain Disorders Branch, Unit Inegrat Neuroimaging,NIH, Bethesda, MD 20892 USA. RP Berman, KF (reprint author), NIMH, Intramural Res Program, Clin Brain Disorders Branch, Unit Inegrat Neuroimaging,NIH, Bethesda, MD 20892 USA. EM karen.berman@nih.gov OI Olsen, Rosanna/0000-0002-2918-4152; Meyer-Lindenberg, Andreas/0000-0001-5619-1123 NR 37 TC 94 Z9 96 U1 4 U2 8 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0028-3932 J9 NEUROPSYCHOLOGIA JI Neuropsychologia PY 2004 VL 42 IS 13 BP 1781 EP 1787 DI 10.1016/j.neuropsychologia.2004.04.023 PG 7 WC Behavioral Sciences; Neurosciences; Psychology, Experimental SC Behavioral Sciences; Neurosciences & Neurology; Psychology GA 858XJ UT WOS:000224225500005 PM 15351627 ER PT J AU Chen, JS Newton, SS Zeng, L Adams, DH Dow, AL Madsen, TM Nestler, EJ Duman, RS AF Chen, JS Newton, SS Zeng, L Adams, DH Dow, AL Madsen, TM Nestler, EJ Duman, RS TI Downregulation of the CCAAT-enhancer binding protein beta in Delta FosB transgenic mice and by electroconvulsive seizures SO NEUROPSYCHOPHARMACOLOGY LA English DT Article DE antidepressant; Delta FosB; C/EBP beta; hippocampus; microarray; memory ID ANTIDEPRESSANT TREATMENT; SYNAPTIC PLASTICITY; MAJOR DEPRESSION; MOOD DISORDERS; EXPRESSION; BRAIN; TRANSCRIPTION; HIPPOCAMPUS; CREB; GENE AB Previous studies demonstrate that chronic, but not acute electroconvulsive seizures (ECS), increases levels of DeltaFosB, a long-lasting transcription factor, in the hippocampus. and this effect correlates with the slow onset and long-lasting clinical effects of antidepressant treatment. To understand how DeltaFosB mediates long-term plasticity in the hippocampus, we analyzed the gene expression profile of inducible transgenic mice expressing DeltaFosB with a highly sensitive microarray assay and a customized computer analysis program. The CCAAT-enhancing binding protein-beta (C/EBPbeta) was identified as one of the genes downregulated by DeltaFosB in the hippocampus. The downregulation of C/EBPbeta in the inducible DeltaFosB transgenic mice was confirmed by other quantitative assays including real-time RT-PCR and low density dot blotting. Analysis of the C/EBPbeta expression in the hippocampus of rats treated with ECS revealed that the C/EBPbeta mRNA was also downregulated by chronic, but not acute ECS administration, the most effective treatment for depression. Given the reported role of C/EBPbeta in behavioral conditioning models, it is possible that the DeltaFosB-mediated downregulation of C/EBPbeta in the hippocampus may be a molecular mechanism by which antidepressants alleviate some of the symptoms of depressed patients. C1 Yale Univ, Sch Med, Dept Psychiat, Div Mol Psychiat, New Haven, CT 06508 USA. Univ Texas, SW Med Ctr, Dept Psychiat, Dallas, TX USA. Univ Texas, SW Med Ctr, Ctr Basic Neurosci, Dallas, TX USA. NIMH, Clin Brain Disorders Branch, Bethesda, MD 20892 USA. RP Duman, RS (reprint author), Yale Univ, Sch Med, Dept Psychiat, Div Mol Psychiat, 34 Pk St, New Haven, CT 06508 USA. EM ronald.duman@yale.edu FU NIMH NIH HHS [P01 MH25642, MH45481] NR 38 TC 13 Z9 13 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0893-133X J9 NEUROPSYCHOPHARMACOL JI Neuropsychopharmacology PD JAN PY 2004 VL 29 IS 1 BP 23 EP 31 DI 10.1038/sj.npp.1300289 PG 9 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 762QL UT WOS:000187993600003 PM 14532910 ER PT J AU Gould, TD Chen, G Manji, HK AF Gould, TD Chen, G Manji, HK TI In vivo evidence in the brain for lithium inhibition of glycogen synthase kinase-3 SO NEUROPSYCHOPHARMACOLOGY LA English DT Article DE valproic acid; GSK-3; Writ pathway; mania; depression; manic-depressive illness ID CHRONIC CARBAMAZEPINE; TAU-PHOSPHORYLATION; SIGNALING PATHWAY; VALPROIC ACID; P-31 NMR; NEURONS; RAT; COMPETITION; MECHANISM; MUTATIONS AB There is considerable interest in the possibility that small-molecule glycogen synthase kinase-3 inhibitors may have utility in the treatment of bipolar disorder, since glycogen synthase kinase-3 is a target of lithium. Although the in vitro inhibition of glycogen synthase kinase-3 by lithium occurs with a K-i of 1-2 mM, the degree of inhibition of this enzyme in the mammalian brain at therapeutically relevant concentrations has not fully been established, The transcription factor beta-catenin is an established marker of glycogen synthase kinase-3 inactivation because cytoplasmic levels are increased by inhibition of the enzyme. In this study, we measured beta-catenin protein levels after treatment with therapeutically relevant doses of lithium, valproate, and carbamazepine. Western blot revealed that 9 days of treatment with lithium and valproate, but not carbamazepine, increased beta-catenin protein levels in soluble fractions from the frontal cortex. The level of beta-catenin in the particulate fraction, which is not directly regulated by glycogen synthase kinase-3, did not change with any of the three drugs. Furthermore, real-time PCR revealed that lithium significantly decreased beta-catenin mRNA levels, which may represent compensation for an increase in beta-catenin stability. These results strongly suggest that lithium significantly inhibits brain glycogen synthase kinase-3 in vivo at concentrations relevant for the treatment of bipolar disorder. C1 NIMH, Mol Pathophysiol Lab, Mood & Anxiety Disorders Program, Bethesda, MD 20892 USA. RP Manji, HK (reprint author), NIMH, Mol Pathophysiol Lab, Mood & Anxiety Disorders Program, Bldg 49,Room B1EE16,49 Convent Dr, Bethesda, MD 20892 USA. EM manji@nih.gov RI Chen, Guang/A-2570-2017 NR 54 TC 130 Z9 133 U1 0 U2 2 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0893-133X J9 NEUROPSYCHOPHARMACOL JI Neuropsychopharmacology PD JAN PY 2004 VL 29 IS 1 BP 32 EP 38 DI 10.1038/sj.npp.1300283 PG 7 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 762QL UT WOS:000187993600004 PM 12942141 ER PT J AU Ghose, S Weickert, CS Colvin, SM Coyle, JT Herman, MM Hyde, TM Kleinman, JE AF Ghose, S Weickert, CS Colvin, SM Coyle, JT Herman, MM Hyde, TM Kleinman, JE TI Glutamate carboxypeptidase gene expression in the human frontal and temporal lobe in schizophrenia SO NEUROPSYCHOPHARMACOLOGY LA English DT Article DE NAALADase; NAAG; CA3; polymorphic; glia; mRNA ID N-ACETYLASPARTYLGLUTAMATE NAAG; ACIDIC DIPEPTIDASE NAALADASE; MESSENGER-RNA; RECEPTOR AGONIST; RETINAL NEURONS; RAT HIPPOCAMPUS; NMDA RECEPTORS; NERVOUS-SYSTEM; HUMAN BRAIN; LOCALIZATION AB There is decreased activity of glutamate carboxypeptidase II (GCP II) in the dorsolateral prefrontal cortex (DLPFC) and hippocampus of patients with schizophrenia. GCP II hydrolzses N-acetyl-alpha L-aspartyl-L-glutamate (NAAG), a peptide in the mammalian brain that binds to the N-methyl D-aspartate (NMDA) receptor and a group II metabotropic glutamate receptor, both of which have been implicated in the pathophysiology of schizophrenia. We examined the expression of GCP II mRNA in the DLPFC, entorhinal cortex (ERC), and hippocampus in postmortem samples from patients with schizophrenia and normal controls using in situ hybridization followed by silver grain detection. GCP II mRNA was detected in glial cells. Glial-rich regions, specifically the DLPFC and ERC white matter and the molecular and polymorphic layers in the hippocampus, express high levels of GCP II mRNA. Given the earlier finding of decreased GCP II activity in brains of subjects with schizophrenia, we expected to find lower GCP II mRNA levels in schizophrenia. Contrary to this expectation, we found a significantly higher expression of GCP II mRNA in one of the brain areas examined, the hippocampal CA3 polymorphic region. This may reflect a compensatory increase to correct for the decreased activity of GCP II activity. Our findings support the notion that the hydrolysis of NAAG is disrupted in schizophrenia and that specific anatomical regions may show discrete abnormalities in GCP II synthesis. C1 NIMH, Clin Brain Disorders Branch, IRP, NIH, Bethesda, MD 20892 USA. Harvard Univ, Sch Med, McLean Dept Psychiat, Belmont, MA 02178 USA. RP Kleinman, JE (reprint author), NIMH, Clin Brain Disorders Branch, IRP, NIH, 9000 Rockville Pike,Bldg 10,Rm 4S 237A, Bethesda, MD 20892 USA. EM kleinmaj@intra.nimh.nih.gov RI Shannon Weickert, Cynthia/G-3171-2011; Ghose, Subroto/J-6732-2016 NR 47 TC 29 Z9 32 U1 1 U2 1 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0893-133X J9 NEUROPSYCHOPHARMACOL JI Neuropsychopharmacology PD JAN PY 2004 VL 29 IS 1 BP 117 EP 125 DI 10.1038/sj.npp.1300304 PG 9 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 762QL UT WOS:000187993600014 PM 14560319 ER PT J AU Wang, X Xu, H Rothman, RB AF Wang, X Xu, H Rothman, RB TI Intracerebroventrcular administration of anti-endothelin-1 lgG selectively upregulates endothelin-A and kappa opioid receptors SO NEUROSCIENCE LA English DT Article DE opioid receptor; endothelin; endothelin receptor; cerebrospinal fluid; neuropeptide ID ANTI-OPIATE PEPTIDES; MORPHINE ANALGESIA; BINDING-SITES; RAT; NOCICEPTION; ANTAGONIST; MODEL; MICE AB Endothelin (ET) type A receptor antagonists enhance morphine-induced antinociception and restore morphine analgesia in morphine tolerant rats [Peptides 23 (2002) 1837; Peptides 24 (2003) 553]. These studies suggest that the central ET and opioid systems functionally interact. To explore this idea further, we determined the effect of i.c.v. administration of anti-ET-1 IgG (rabbit) on brain opioid receptor and ET receptor expression. Three days after implanting cannula into the lateral ventricle, male Sprague-Dawley rats were administered 10 mul (i.c.v.) of either control rabbit IgG (2.5 mug/mul) or anti-ET IgG (2.5 mug/mul) on day 1, day 3, and day 5. On day 6, animals were killed and the caudate and hippocampus collected. Anti-ET IgG had no significant effect on expression, measured by Western blots, of mu, 8 or ET-B receptors, but increased K opioid (59%) and ET-A (33%) receptor protein expression in the caudate. [S-35] -GTP-gamma-S binding assays demonstrated that anti-ET IgG decreased [D-Ala(2)-MePhe(4), Gly-ol(5)]enkephalin efficacy, but not potency in the caudate. Control experiments showed that there was no detectable rabbit IgG in caudate and hippocampal samples. These results suggest that ET in the CSF negatively regulates K opioid and ET-A receptors in certain brain regions. These findings support the hypothesis that CSF neuropeptides have regulatory effects and further demonstrate a link between ET and the opioid receptor system. (C) 2004 IBRO. Published by Elsevier Ltd. All rights reserved. C1 NIDA, Clin Psychopharmacol Sect, Intramural Res Program, NIH, Baltimore, MD 21224 USA. RP Rothman, RB (reprint author), NIDA, Clin Psychopharmacol Sect, Intramural Res Program, NIH, POB 5180,5500 Nathan Shock Dr, Baltimore, MD 21224 USA. EM rrothman@intra.nida.nih.gov NR 21 TC 7 Z9 8 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0306-4522 J9 NEUROSCIENCE JI Neuroscience PY 2004 VL 129 IS 3 BP 751 EP 756 DI 10.1016/j.neuroscience.2004.09.004 PG 6 WC Neurosciences SC Neurosciences & Neurology GA 876QA UT WOS:000225511000024 PM 15541896 ER PT J AU Banks, WA Robinson, SM Wolf, KM Bess, JW Arthur, LO AF Banks, WA Robinson, SM Wolf, KM Bess, JW Arthur, LO TI Binding, internalization, and membrane incorporation of human immunodeficiency virus-1 at the blood-brain barrier is differentially regulated SO NEUROSCIENCE LA English DT Article DE HIV-1; blood-brain barrier; brain; neuroAIDS; transport; CNS ID CAPILLARY ENDOTHELIAL-CELLS; GUINEA-PIG BRAIN; HIV-1 INFECTION; ADSORPTIVE ENDOCYTOSIS; ENVELOPED VIRUSES; CYCLOPHILIN-A; TYPE-1; HEPARIN; TRANSPORT; MOUSE AB Human immunodeficiency virus (HIV)-1 within the CNS induces neuro-acquired immunodeficiency syndrome and acts as a reservoir for reinfection of peripheral tissues. HIV-1 crosses the blood-brain barrier (BBB) within infected immune cells and as cell-free virus by a CD4-independent mechanism. Which proteins control free virus transport across the BBB are unknown, but work with wheatgerm agglutinin (WGA) and heparin suggests that heparan sulfate proteoglycans, sialic acid, and N-acetyl-beta-D-glucosaminyl acid bind HIV-1. Here, we found that an HIV-1 T-tropic virus was taken up by mouse brain endothelial cells in vitro and crossed the BBB in vivo and could be effluxed as intact virus. Uptake was stimulated by WGA and protamine sulfate (PS) and inhibited by heparin. BBB uptake of virus involved four distinguishable binding sites: i) reversible cell surface binding involving gp120 and sensitive to PS/heparin but insensitive to WGA; internalization with a ii) WGA-sensitive site binding gp120 and iii) a PS/heparin-sensitive site not involving gp120; iv) membrane incorporation not affected by WGA, heparin, or PS. In conclusion, binding, internalization, and membrane incorporation are separately regulated steps likely determining whether HIV-1 is incorporated into brain endothelial cells, transported across them, or returned to the circulation. Published by Elsevier Ltd on behalf of IBRO. C1 Vet Affairs Med Ctr, GRECC, St Louis, MO 63106 USA. St Louis Univ, Sch Med, Div Geriatr, Dept Internal Med, St Louis, MO 63106 USA. Frederick Canc Res & Dev Ctr, AIDS Vaccine Program, SAIC, Frederick, MD 21702 USA. RP Banks, WA (reprint author), Vet Affairs Med Ctr, GRECC, St Louis, MO 63106 USA. EM bankswa@slu.edu RI Bess, Jr., Julian/B-5343-2012 FU NCI NIH HHS [N01-CO-12400]; NINDS NIH HHS [R01 NS41863] NR 44 TC 20 Z9 21 U1 0 U2 3 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0306-4522 J9 NEUROSCIENCE JI Neuroscience PY 2004 VL 128 IS 1 BP 143 EP 153 DI 10.1016/j.neuroscience.2004.06.021 PG 11 WC Neurosciences SC Neurosciences & Neurology GA 855EE UT WOS:000223955100014 PM 15450361 ER PT J AU Yang, LX Nelson, PG AF Yang, LX Nelson, PG TI Glia cell line-derived neurotrophic factor regulates the distribution of acetylcholine receptors in mouse primary skeletal muscle cells SO NEUROSCIENCE LA English DT Article DE neuromuscular junction; cell signaling; protein phosphorylation; synaptotrophic modulator; quantitative imaging; autocrine ID ANTEROGRADE AXONAL-TRANSPORT; DEVELOPING NEUROMUSCULAR-JUNCTIONS; LEUKEMIA INHIBITORY FACTOR; ACTIVATED PROTEIN-KINASE; GDNF FAMILY LIGANDS; TYROSINE KINASE; RET RECEPTOR; N-CAM; NEURTURIN RECEPTOR; SURVIVAL FACTOR AB It was recently reported that glia cell line-derived neurotrophic factor (GDNF) facilitates presynaptic axonal growth and neurotransmitter release at neuromuscular synapses. Little is known, however, whether GDNF can also act on the postsynaptic apparatus and its underlying mechanisms. Using biochemical cold blocking of existing membrane acetylcholine receptors (AchRs) and biotinylation of newly inserted receptors we demonstrate that GDNF increases the insertion of AChRs into the surface membrane of mouse primary cultured muscle cells and that this does not require protein synthesis. Quantitative data from double-label imaging indicate that GDNF induces a quick and substantial increase in AchR insertion as well as lateral movement into AchR aggregates, relative to a weak effect on reducing the loss of receptors from pre-existing AchR aggregates, which in contrast to the effect of PMA. These effects occur in both innervated and un-innervated muscles, and GDNF affects nerve-muscle co-cultures more than it affects muscle-only cultures. Neurturin, another member of GDNF-family ligands has similar effects on AchRs as GDNF but the unrelated growth factor, EGF does not. Studies on protein phosphorylation and specific inhibitors of cell signal transduction indicate that GDNF function is mediated by receptor GFRalpha1 and involves MAPK, cAMP/cAMP responsive element-binding factor and Src kinase activities. GDNF may signal through c-Ret as well as NCAM-140 pathways since both the signaling receptors are expressed in the neuromuscular junction (NMJ). These data suggest that GDNF is an autocrine regulator of NMJ to promote the insertion and stabilization of postsynaptic AchRs. In vivo, GDNF may function as a synaptotrophic modulator for both pre- and postsynaptic differentiation to strengthen the functional and structural connections between nerve and muscle, and contribute to the synaptogenesis and plasticity of neuromuscular synapses. Published by Elsevier Ltd on behalf of IBRO. C1 Univ Pittsburgh, Dept Human Genet, Pittsburgh, PA 15261 USA. NICHHD, Neurobiol Sect, Dev Neurobiol Lab, NIH, Bethesda, MD 20892 USA. RP Yang, LX (reprint author), Univ Pittsburgh, Dept Human Genet, 633 Parran Hall,130 Desoto St, Pittsburgh, PA 15261 USA. EM lixia.yang@hgen.pitt.edu NR 68 TC 23 Z9 25 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0306-4522 J9 NEUROSCIENCE JI Neuroscience PY 2004 VL 128 IS 3 BP 497 EP 509 DI 10.1016/j.neuroscience.2004.06.067 PG 13 WC Neurosciences SC Neurosciences & Neurology GA 861CK UT WOS:000224393500004 PM 15381279 ER PT J AU Ong, WY Sundaram, RK Huang, E Ghoshal, S Kumar, U Pentchev, PG Patel, SC AF Ong, WY Sundaram, RK Huang, E Ghoshal, S Kumar, U Pentchev, PG Patel, SC TI Neuronal localization and association of Niemann pick C-2 protein (HE1/NPC2) with the postsynaptic density SO NEUROSCIENCE LA English DT Article DE Niemann-Pick type C disease; cholesterol; neurodegeneration; dendrites; postsynaptic density; neurotransmission ID MAJOR SECRETORY PROTEIN; C DISEASE; HUMAN EPIDIDYMIS; CHOLESTEROL; HE-1; RECEPTOR; BRAIN; ORGANIZATION; GENE; NPC1 AB Niemann-Pick disease type C (NP-C) is an inherited disorder that is characterized biochemically by cellular cholesterol and glycolipid storage, and clinically by progressive neurodegeneration. Most cases of NP-C are caused by inactivating mutations of the npc1 gene, but about 5% are linked to npc2, which encodes a soluble cholesterol binding protein, previously identified as epididymal secretory glycoprotein 1 (He1). The present study was carried out to investigate the immunocytochemical localization of HE1/NPC2 protein in the mouse brain. Using an antibody against recombinant HE1/NPC2, we found HE1/NPC2 to be localized predominantly in neurons in the brain. Immunoreactivity for HE1/NPC2 was observed in pyramidal or projection neurons in the cerebral cortex and amygdala, and Purkinje neurons in the cerebellum. Neurons in the thalamus, hypothalamus, and globus pallidus were lightly labeled, or unlabeled. This regional pattern of expression of HE1/ NPC2 is similar to our previous findings with NPC1, with a low level of expression of both NPC1 and HE1/NPC2 proteins in regions derived from the diencephalon, such as the thalamus and hypothalamus. In contrast to NPC1, however, which is predominantly in astrocytes, HE1/NPC2 was observed mainly in neurons. Electron microscopic immunocytochemistry showed that HE1/NPC2 is present in the cytosol of dendrites and on post-synaptic densities (PSD). The occurrence of HE1/NPC2 in the PSD was confirmed by Western blots of PSD-enriched brain subcellular fractions that showed the presence of HE1/NPC2 together with the PSD-associated protein, PSD-95. These results suggest that NPC1 and HE1/NPC2 are differentially enriched in astrocytes and neurons, respectively, and that HE1/ NPC2 may function in supporting the integrity of the PSD of neurons. (C) 2004 IBRO. Published by Elsevier Ltd. All rights reserved. C1 New England Biomed Res Ctr, Newington, CT 06111 USA. Natl Univ Singapore, Dept Anat, Singapore 119260, Singapore. McGill Univ, Fraser Labs, Montreal, PQ H3A 1A1, Canada. Yale Univ, Sch Med, New Haven, CT USA. NIDDKD, Lab Cell Biochem & Biol, NIH, Bethesda, MD 20892 USA. VA Connecticut Healthcare Syst, Newington, CT 06111 USA. RP Patel, SC (reprint author), New England Biomed Res Ctr, 677 N Mt Rd, Newington, CT 06111 USA. EM scp@nebrc.org FU NIA NIH HHS [AG 19521]; NINDS NIH HHS [NS 34339] NR 23 TC 19 Z9 19 U1 0 U2 3 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0306-4522 J9 NEUROSCIENCE JI Neuroscience PY 2004 VL 128 IS 3 BP 561 EP 570 DI 10.1016/j.neuroscience.2004.07.001 PG 10 WC Neurosciences SC Neurosciences & Neurology GA 861CK UT WOS:000224393500010 PM 15381285 ER PT J AU Law, AJ Weickert, CS Hyde, TM Kleinman, JE Harrison, PJ AF Law, AJ Weickert, CS Hyde, TM Kleinman, JE Harrison, PJ TI Neuregulin-1 (NRG-1) mRNA and protein in the adult human brain SO NEUROSCIENCE LA English DT Article DE in situ hybridization; immunocytochemistry; heregulin; hippocampus; schizophrenia; neuregulin ID NEU DIFFERENTIATION FACTOR; CEREBELLAR GRANULE CELLS; GLIAL GROWTH-FACTOR; RAT-BRAIN; PREFRONTAL CORTEX; SYNAPTIC-TRANSMISSION; NEURITE OUTGROWTH; RECEPTOR SUBUNIT; CEREBRAL-CORTEX; NERVOUS-SYSTEM AB Neuregulin-1 (NRG-1) plays important roles in the development and plasticity of the brain, and it has recently been identified as a susceptibility gene for schizophrenia. Though there are rodent data, little is known about its distribution in the human brain. The aim of this study was to ascertain the localization of NRG-1 and its mRNA in multiple regions of the normal adult human brain. We investigated NRG-1 mRNA in 11 subjects using in situ hybridization and northern analysis, and NRG-1 protein in six subjects using immunohistochemistry and Western blotting. NRG-1 mRNA was present as bands of approximately 2, 3 and 6 kb. It was clearly detected in the prefrontal cortex (middle laminae), hippocampal formation (except CA1), cerebellum, oculomotor nucleus, superior colliculus, red nucleus and substantia nigra pars compacta. At the cellular level, NRG1 mRNA was abundant in hippocampal and cortical pyramidal neurons and some interneurons, and in cerebellar Purkinje cells and Golgi cells. NRG-1 protein was detected as bands of approximately 140, 110, 95 and 60 kD. Immunohistochemistry revealed NRG-1 in many cell populations, consistent with the mRNA data, being prominent in pyramidal neurons, Purkinje cells, several brainstem nuclei, and white matter neurons. Moderate NRG-1 immunoreactivity was also observed in cerebellar and dentate gyrus granule cells, and some glia. Within neurons, NRG-1 staining was primarily somatodendritic; in the cell body staining was granular, with clustering close to the plasma and nuclear membranes. There was also labeling of some fiber tracts, and local areas of neuropil (e.g. in the dentate nucleus) suggestive of a pre-synaptic location of NRG-1. The data show a widespread expression of NRG-1 in the adult human brain, including, but not limited to, brain areas and cell populations implicated in schizophrenia. Using these normative data, future studies can ascertain whether the role of NRG-1 in the disease is mediated, or accompanied, via alterations in its expression. (C) 2004 IBRO. Published by Elsevier Ltd. All rights reserved. C1 Univ Oxford, Warneford Hosp, Dept Psychiat, Oxford OX3 7JX, England. NIMH, Clin Brain Disorders Branch, Intramural Res Program, NIH, Bethesda, MD 20892 USA. RP Law, AJ (reprint author), Univ Oxford, Warneford Hosp, Dept Psychiat, Neurosci Bldg, Oxford OX3 7JX, England. EM amanda.law@psych.ox.ac.uk RI Shannon Weickert, Cynthia/G-3171-2011; Law, Amanda/G-6372-2012 NR 57 TC 93 Z9 100 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0306-4522 J9 NEUROSCIENCE JI Neuroscience PY 2004 VL 127 IS 1 BP 125 EP 136 DI 10.1016/j.neuroscience.2004.04.026 PG 12 WC Neurosciences SC Neurosciences & Neurology GA 838LS UT WOS:000222715400013 PM 15219675 ER PT J AU Kreuter, JD Mattson, BJ Wang, B You, ZB Hope, BT AF Kreuter, JD Mattson, BJ Wang, B You, ZB Hope, BT TI Cocaine-induced fos expression in rat striatum is blocked by chloral hydrate or urethane SO NEUROSCIENCE LA English DT Article DE dopamine; glutamate; microdialysis; intracranial injections; anesthetic ID EARLY GENE-EXPRESSION; FREELY MOVING RATS; MULTIPLE-UNIT-ACTIVITY; C-FOS; NUCLEUS-ACCUMBENS; RECEPTOR SUPERSENSITIVITY; DOPAMINERGIC MODULATION; MEDIATED EXPRESSION; NEOSTRIATAL NEURONS; ROTATIONAL BEHAVIOR AB Anesthetics used in electrophysiological studies alter the effects of cocaine and amphetamine on neural activity in the striatum. However, the mechanism underlying this alteration has not been established. In the present study, we examined the effects of anesthetics on cocaine-induced neural activity in the striatum. We first assayed the ability of 20 mg/kg cocaine to induce Fos expression in the striatum following pretreatment with 400 mg/kg chloral hydrate or 1.3 g/kg urethane, two of the most commonly used anesthetics for in vivo electrophysiology. Chloral hydrate blocked, while urethane strongly attenuated cocaine-induced Fos expression without affecting basal levels of expression. We then examined dopaminergic and glutamatergic mechanisms for anesthetic effects on cocaine-induced Fos expression. Chloral hydrate and urethane did not attenuate basal or cocaine-induced increases of dopamine levels as assessed by microdialysis in dorsal striatum. In contrast, chloral hydrate attenuated glutamatergic neurotransmission as assessed by microdialysis in the presence of the glutamate transport blocker L-trans-pyrrolidone-2,4-dicarboxylic acid. Chloral hydrate attenuated basal levels of glutamate by 70%, while cocaine had no effect on glutamate levels. Since glutamate levels were tetrodotoxin-sensitive, the majority of glutamate measured in our assay was by synaptic release. To assess a causal role for a reduction of glutamatergic neurotransmission in anesthetic effects on cocaine-induced Fos expression, we injected the glutamate receptor agonists AMPA and NMDA into the dorsal striatum of chloral hydrate-anesthetized rats. The glutamate receptor agonists partially reinstated cocaine-induced Fos expression in anesthetized rats. We conclude anesthetics attenuate cocaine-induced neuronal activity by reducing glutamatergic neurotransmission. Published by Elsevier Ltd on behalf of IBRO. C1 Natl Inst Drug Abuse, Behav Neurosci Branch, Intramural Res Program, Dept Hlth & Human Serv,NIH, Baltimore, MD 21224 USA. RP Hope, BT (reprint author), Natl Inst Drug Abuse, Behav Neurosci Branch, Intramural Res Program, Dept Hlth & Human Serv,NIH, 5500 Nathan Shock Dr, Baltimore, MD 21224 USA. EM bhope@intra.nida.nih.gov RI Hope, Bruce/A-9223-2010 OI Hope, Bruce/0000-0001-5804-7061 NR 62 TC 30 Z9 31 U1 0 U2 6 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0306-4522 J9 NEUROSCIENCE JI Neuroscience PY 2004 VL 127 IS 1 BP 233 EP 242 DI 10.1016/j.neuroscience.2004.04.047 PG 10 WC Neurosciences SC Neurosciences & Neurology GA 838LS UT WOS:000222715400023 PM 15219685 ER PT J AU Bratincsak, A Palkovits, M AF Bratincsak, A Palkovits, M TI Activation of brain areas in rat following warm and cold ambient exposure SO NEUROSCIENCE LA English DT Article DE c-fos; Fos immunohistochemistry; stress; thermoregulation; preoptic nucleus; peritrigeminal nucleus ID THERMOREGULATORY VASOMOTOR CONTROL; C-FOS EXPRESSION; TEMPERATURE REGULATION; PREOPTIC AREA; THERMAL-STIMULATION; BODY-TEMPERATURE; NERVOUS-SYSTEM; NEURONS; THERMOSENSITIVITY; RESPONSES AB Environmental thermal stimuli result in specific and coordinated thermoregulatory response in homeothermic animals. Warm exposure activates numerous brain areas within the cortex, hypothalamus, pons and medulla oblongata. We identified these thermosensitive cell groups in the medulla and pons that were suggested but not outlined by previous physiological studies. Using Fos immunohistochemistry, we localized all the nuclei and cell groups in the rat brain that were activated by warm and cold ambient exposure. These neurons located in the hypothalamus and the brainstem, are part of a network responsible for the thermospecific response elicited by thermal stress. Comparison of the distribution of Fos-immunoreactive cells throughout the rat brain revealed topographical differences between the patterns of activated cells following warm and cold environmental exposure. Among several brain regions, warm exposure elicited c-fos expression specifically in the ventrolateral part of the medial preoptic area, the central subdivision of the lateral parabrachial nucleus and the caudal part of the peritrigeminal nucleus, whereas cold stress resulted in c-fos expression in the ventromedial part of the medial preoptic area, the external subdivision of the lateral parabrachial nucleus and the rostral part of the peritrigeminal nucleus. These neurons are part of a network coordinating specific response to warm or cold exposure. The topographical differences suggest that well-defined cell groups and subdivisions of nuclei are responsible for the specific physiological (endocrine, autonomic and behavioral) changes observed in different thermal environment. Published by Elsevier Ltd on behalf of IBRC. C1 NIMH, Genet Lab, Natl Inst Hlth, Bethesda, MD 20892 USA. Semmelweis Univ, Neuromorphol Lab, Dept Anat, Fac Med, H-1085 Budapest, Hungary. Hungarian Acad Sci, Budapest, Hungary. RP Bratincsak, A (reprint author), NIMH, Genet Lab, Natl Inst Hlth, 36 Convent Dr,Bldg 36,Room 3D06, Bethesda, MD 20892 USA. EM bratinca@mail.nih.edu RI Palkovits, Miklos/F-2707-2013; OI Palkovits, Miklos/0000-0003-0578-0387 NR 47 TC 56 Z9 61 U1 0 U2 4 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0306-4522 J9 NEUROSCIENCE JI Neuroscience PY 2004 VL 127 IS 2 BP 385 EP 397 DI 10.1016/j.neuroscience.2004.05.016 PG 13 WC Neurosciences SC Neurosciences & Neurology GA 844KG UT WOS:000223156400013 PM 15262329 ER PT J AU Chefer, VI Kieffer, BL Shippenberg, TS AF Chefer, VI Kieffer, BL Shippenberg, TS TI Contrasting effects of mu opioid receptor and delta opioid receptor deletion upon the behavioral and neurochemical effects of cocaine SO NEUROSCIENCE LA English DT Article DE conventional microdialysis; mu- and Delta-opioid receptors; cocaine; knockout mice ID NUCLEUS-ACCUMBENS; DOPAMINE RELEASE; KNOCKOUT MICE; ANTAGONIST NALTRINDOLE; EXTRACELLULAR DOPAMINE; LOCOMOTOR-ACTIVITY; MESOLIMBIC SYSTEM; MOTOR-ACTIVITY; SENSITIZATION; INVOLVEMENT AB Conventional brain microdialysis was used to assess basal and cocaine-induced dopamine (DA) levels in the nucleus accumbens of wildtype (WT) C57BL/6J mice and mice with constitutive deletion of ether mu- or delta-opioid receptors (MOR or DOR knockout [KO], respectively). Locomotor activity was assessed in these same animals. Basal locomotor activity of DOR KO was elevated relative to MOR KO, but did not differ from that of WT mice. DOR mice, but not WT or MOR KO, exhibited a significant increase in activity in response to an injection of saline. The acute administration of cocaine produced a dose-related increase in locomotor activity in the three genotypes. The locomotor activating effects of a low dose (10 mg/kg) of cocaine were enhanced in DOR KO mice whereas the locomotor activating effects of both a low and higher (20 mg/kg) dose of cocaine were reduced in MOR KO animals. Microdialysis studies revealed no difference between genotypes in basal DA levels. Acute administration of cocaine, but not saline, increased DA levels in WT and KO animals. Paradoxically, however, the magnitude of this effect was smaller in DOR KO as compared with that in either WT or MOR KO. These data indicate that constitutive deletion of either MOR or DOR results in contrasting effects upon responsiveness to cocaine, which is consistent with the distinct phenotypes previously described for these mutants. Published by Elsevier Ltd on behalf of IBRO. C1 NIDA, Integrat Neurosci Sect, Behav Neurosci Branch, DHHS,IRP BNRB INS,NIH, Baltimore, MD 21224 USA. ULP, INSERM, CNRS, Inst Genet & Biol Mol & Cellulaire, F-67404 Illkirch Graffenstaden, France. RP Chefer, VI (reprint author), NIDA, Integrat Neurosci Sect, Behav Neurosci Branch, DHHS,IRP BNRB INS,NIH, 5500 Nathan Shock Dr, Baltimore, MD 21224 USA. EM vchefer@intra.nida.nih.gov NR 35 TC 21 Z9 24 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0306-4522 J9 NEUROSCIENCE JI Neuroscience PY 2004 VL 127 IS 2 BP 497 EP 503 DI 10.1016/j.neuroscience.2004.05.021 PG 7 WC Neurosciences SC Neurosciences & Neurology GA 844KG UT WOS:000223156400022 PM 15262338 ER PT J AU Klein, RC Yakel, JL AF Klein, RC Yakel, JL TI Inhibition of nicotinic acetylcholine receptors by Apolipoprotein E-derived peptides in rat hippocampal slices SO NEUROSCIENCE LA English DT Article DE Apolipoprotein E (ApoE); Alzheimer's disease (AD); nicotinic; acetylcholine (ACh); hippocampus; electrophysiology ID ALZHEIMERS-DISEASE; TRANSGENIC MICE; NEUROTOXICITY; NEURONS; BRAINS AB Apolipoprotein E (ApoE) is a well-known genetic risk factor for Alzheimer's disease (AD). Dysfunctions in cholinergic signaling, and in particular in the function of neuronal nicotinic acetylcholine receptors (nAChRs), have also been linked with AD and cognition. To address whether there is a link between ApoE and nAChR function, we used electrophysiological techniques to test the effects of synthetic ApoE-mimetic peptides derived from the low-density lipoprotein receptor (LDLR) binding domain for the ability to modulate nAChR activity in hippocampal interneurons. ApoE(133-149) completely inhibited ACh-evoked responses in a dose-dependent manner, yielding an IC50 value of 720 +/- 70 nM. A shorter peptide spanning residues 141-148 mimicked this effect while a second peptide spanning residues 133-140 was without effect, indicating that the arginine-rich domain is responsible for nAChR interaction. Inhibition of ACh-evoked responses was voltage-independent, and displayed partial receptor specificity as no effect on glycine- or GABA-evoked responses occurred. These results demonstrate that peptides derived from the LDLR binding domain of ApoE block the function of nAChRs in hippocampal slices, an interaction that may have implications for AD. (C) 2004 IBRO. Published by Elsevier Ltd. All rights reserved. C1 NIEHS, Neurobiol Lab, Natl Inst Hlth, Dept Hlth & Human Serv, Res Triangle Pk, NC 27709 USA. RP Yakel, JL (reprint author), NIEHS, Neurobiol Lab, Natl Inst Hlth, Dept Hlth & Human Serv, POB 12233,F2-08,111 TW Alexander Dr, Res Triangle Pk, NC 27709 USA. EM yakel@niehs.nih.gov NR 16 TC 21 Z9 21 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0306-4522 J9 NEUROSCIENCE JI Neuroscience PY 2004 VL 127 IS 3 BP 563 EP 567 DI 10.1016/j.neuroscience.2004.05.045 PG 5 WC Neurosciences SC Neurosciences & Neurology GA 846OI UT WOS:000223324700002 PM 15283956 ER PT J AU Li, Z Ding, M Thiele, CJ Luo, J AF Li, Z Ding, M Thiele, CJ Luo, J TI Ethanol inhibits brain-derived neurotrophic factor-mediated intracellular signaling and activator protein-1 activation in cerebellar granule neurons SO NEUROSCIENCE LA English DT Article DE apoptosis; development; fetal alcohol syndrome; neurotrophins; signal transduction; transcription factor ID NERVE GROWTH-FACTOR; INSULIN-STIMULATED SURVIVAL; BAX-DEPENDENT APOPTOSIS; NEONATAL-RAT CEREBELLUM; FETAL ALCOHOL EXPOSURE; CELL-DEATH; C-JUN; PHOSPHATIDYLINOSITOL 3-KINASE; FACTOR RECEPTOR; MESSENGER-RNA AB Developmental exposure to ethanol causes profound damage to the cerebellum, ranging from aberration in neuronal differentiation to cell loss. As a major neurotrophic factor, brain-derived neurotrophic factor (BDNF) and its receptor TrkB are expressed in the developing, as well as adult, cerebellum. Many neurotrophic effects of BDNF are mediated by gene transcription. We hypothesized that ethanol interfered with BDNF signaling and disrupted BDNF-regulated transcriptional activity. Using a transgenic mouse model expressing an activator protein-1 (AP-1) luciferase reporter construct, we demonstrated that BDNF stimulated AP-1 transactivation in cultured cerebellar granule neurons. This observation was validated by the study using a human neuronal cell line expressing inducible TrkB (TB8 neuroblastoma cells). BDNF induced AP-1 transactivation, as well as increased the binding activity of AP-1 protein complex to a DNA sequence containing AP-1 sites in TB8 cells. BDNF-mediated AP-1 activation was mediated by PI3K/Akt and JNK pathways; BDNF activated Akt and JNKs, and blocking these pathways significantly inhibited BDNF-stimulated AP-1 transactivation. More importantly, ethanol inhibited BDNF-mediated activation of PI3K/Akt and JNKs, and blocked BDNF-stimulated AP-1 activation. Since ethanol did not affect either the expression or autophosphorylation of TrkB, it could be concluded that the site of ethanol action was downstream of TrkB. The present study establishes that this AP-1 reporter transgenic mouse model is valuable for assessing AP-1 activity in the CNS neurons. Our results provide an insight into molecular mechanism(s) of ethanol action. (C) 2004 IBRO. Published by Elsevier Ltd. All rights reserved. C1 W Virginia Univ, Sch Med, Robert C Brd Hlth Sci Ctr, Dept Microbiol Immunol & Cell Biol, Morgantown, WV 26506 USA. Natl Inst Occupat Safety & Hlth, Pathol & Physiol Res Branch, Morgantown, WV 26506 USA. NCI, Pediat Oncol Branch, Bethesda, MD 20892 USA. Chinese Acad Sci, SIBS, Inst Nutr Sci, Shanghai, Peoples R China. RP Luo, J (reprint author), W Virginia Univ, Sch Med, Robert C Brd Hlth Sci Ctr, Dept Microbiol Immunol & Cell Biol, Morgantown, WV 26506 USA. EM jluo@hsc.wvu.edu RI Luo, Jia/E-4674-2012 FU NCI NIH HHS [CA90385]; NIAAA NIH HHS [AA12968] NR 98 TC 28 Z9 31 U1 0 U2 3 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0306-4522 J9 NEUROSCIENCE JI Neuroscience PY 2004 VL 126 IS 1 BP 149 EP 162 DI 10.1016/j.neuroscience.2004.03.028 PG 14 WC Neurosciences SC Neurosciences & Neurology GA 824SP UT WOS:000221707100014 PM 15145081 ER PT J AU Radley, JJ Sisti, HM Hao, J Rocher, AB McCall, T Hof, PR McEwen, BS Morrison, JH AF Radley, JJ Sisti, HM Hao, J Rocher, AB McCall, T Hof, PR McEwen, BS Morrison, JH TI Chronic behavioral stress induces apical dendritic reorganization in pyramidal neurons of the medial prefrontal cortex SO NEUROSCIENCE LA English DT Article DE stress; prefrontal; glucocorticoid; dendrite; cell loading; post-traumatic stress disorder ID HIPPOCAMPAL CA3C NEURONS; INDUCED ATROPHY; DISORDER; MORPHOLOGY; RESPONSES AB Both the hippocampus and the medial prefrontal cortex (mPFC) play an important role in the negative feedback regulation of hypothalamic-pituitary-adrenal (HPA) activity during physiologic and behavioral stress. Moreover, chronic behavioral stress is known to affect the morphology of CA3c pyramidal neurons in the rat, by reducing total branch number and length of apical dendrites. In the present study, we investigated the effects of behavioral stress on the mPFC, using the repeated restraint stress paradigm. Animals were perfused after 21 days of daily restraint, and intracellular iontophoretic injections of Lucifer Yellow were carried out in pyramidal neurons of layer II/III of the anterior cingulate cortex and prelimbic area. Cellular reconstructions were performed on apical and basal dendrites of pyramidal neurons in layer II/III of the anterior cingulate and prelimbic cortices. We observed a significant reduction on the total length (20%) and branch numbers (17%) of apical dendrites, and no significant reduction in basal dendrites. These cellular changes may impair the capacity of the mPFC to suppress the response of the HPA axis to stress, and offer an experimental model of stress-induced neocortical reorganization that may provide a structural basis for the cognitive impairments observed in post-traumatic stress disorder. (C) 2004 IBRO. Published by Elsevier Ltd. All rights reserved. C1 CUNY Mt Sinai Sch Med, Kastor Neurobiol Aging Labs, New York, NY 10029 USA. CUNY Mt Sinai Sch Med, Fishberg Res Ctr Neurobiol, New York, NY 10029 USA. Rockefeller Univ, Neuroendocrinol Lab, New York, NY 10021 USA. NIMH, Ctr Fear & Anxiety, New York, NY USA. RP Radley, JJ (reprint author), CUNY Mt Sinai Sch Med, Kastor Neurobiol Aging Labs, Box 1639,1 Gustave L Levy Pl, New York, NY 10029 USA. EM jason.radley@mssm.edu; john.morrison@mssm.edu RI Morrison, John/F-9229-2012 FU NIMH NIH HHS [MH58911] NR 21 TC 377 Z9 391 U1 1 U2 20 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0306-4522 J9 NEUROSCIENCE JI Neuroscience PY 2004 VL 125 IS 1 BP 1 EP 6 DI 10.1016/j.neuroscience.2004.01.006 PG 6 WC Neurosciences SC Neurosciences & Neurology GA 812SA UT WOS:000220858000001 PM 15051139 ER PT J AU Ganeshina, O Berry, RW Petralia, RS Nicholson, DA Geinisman, Y AF Ganeshina, O Berry, RW Petralia, RS Nicholson, DA Geinisman, Y TI Synapses with a segmented, completely partitioned postsynaptic density express more AMPA receptors than other axospinous synaptic junctions SO NEUROSCIENCE LA English DT Article DE axospinous synapses; postembedding immunogold electron microscopy; synaptic plasticity; LTP; hippocampus ID LONG-TERM POTENTIATION; SMALL PYRAMIDAL NEURON; RAT CEREBRAL CORTEX; DENDRITIC SPINES; NMDA RECEPTORS; 3-DIMENSIONAL STRUCTURE; GLUTAMATE RECEPTORS; PERFORATED SYNAPSES; TRANSMISSION ZONES; STRATUM-RADIATUM AB Axospinous perforated synapses of one morphological subtype exhibit multiple transmission zones, each one being formed by an axon terminal protrusion apposing a postsynaptic density (PSD) segment and separated from others by complete spine partitions. Such segmented, completely partitioned (SCP) synapses have been implicated in synaptic plasticity and postulated to be exceptionally efficacious. The present study explored the validity of this supposition. Postembedding immunogold electron microscopy was used for quantifying the postsynaptic AMPA receptor (AMPAR) expression, which is widely regarded as a major determinant of synaptic efficacy. Various subtypes of axospi-nous synapses were examined in the rat CA1 stratum radia-tum. The results showed that the number of immunogold particles for AMPARs in SCP synapses markedly and significantly exceeded that in other perforated subtypes (by 101% on the average) and in nonperforated immunopositive synapses (by 1086%). Moreover, the particle number per single PSD segment, each of which also contained NMDA receptors, was significantly higher than that per nonperforated PSD (by 485%). SCP synapses also exhibited a higher particle density per unit PSD area, as well as a larger overall PSD area as compared with other synaptic subtypes. Analysis of covari-ance revealed that the high AMPAR expression in SCP synapses was related to the segmented PSD configuration, not only to the PSD size. Moreover, the subpopulations of SCP and other perforated synapses with either overlapping or equal PSD sizes differed in AMPAR content and concentration, with both measures being significantly higher in SCP synapses. Thus, the elevated AMPAR expression in SCP synapses is associated with the presence of separate PSD segments, not only with their large PSD area. These findings are consistent with the idea that SCP synapses have a relatively greater efficacy and may support maximal levels of synaptic enhancement characteristic of certain forms of synaptic plasticity such as the early LTP phase. (C) 2004 IBRO. Published by Elsevier Ltd. All rights reserved. C1 Northwestern Univ, Feinberg Sch Med, Dept Cell & Mol Biol, Chicago, IL 60611 USA. Natl Inst Deafness & Other Commun Disorders, Neurochem Lab, NIH, Bethesda, MD 20892 USA. RP Geinisman, Y (reprint author), Northwestern Univ, Feinberg Sch Med, Dept Cell & Mol Biol, Chicago, IL 60611 USA. EM yurig@northwestern.edu OI Nicholson, Dan/0000-0002-1963-0569 FU NIA NIH HHS [AG17139] NR 56 TC 51 Z9 57 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0306-4522 J9 NEUROSCIENCE JI Neuroscience PY 2004 VL 125 IS 3 BP 615 EP 623 DI 10.1016/j.neuroscience.2004.02.025 PG 9 WC Neurosciences SC Neurosciences & Neurology GA 818XO UT WOS:000221278000010 PM 15099675 ER PT J AU Baumann, MH Milchanowski, AB Rothman, RB AF Baumann, MH Milchanowski, AB Rothman, RB TI Evidence for alterations in alpha 2-adrenergic receptor sensitivity in rats exposed to repeated cocaine administration SO NEUROSCIENCE LA English DT Article DE stimulant; withdrawal; clonidine; growth hormone; norepinephrine; depression ID GROWTH-HORMONE-SECRETION; VENTRAL TEGMENTAL AREA; FREELY MOVING RATS; NUCLEUS-ACCUMBENS; LOCUS-CERULEUS; SEROTONIN TRANSPORTERS; EXTRACELLULAR DOPAMINE; NEUROENDOCRINE CONTROL; INTRAVENOUS COCAINE; MAJOR DEPRESSION AB It is well established that cocaine stimulates monoamine transmission by blocking reuptake of norepinephrine (NE), dopamine and serotonin into nerve cells, yet few investigations have addressed the effects of chronic cocaine on NE function. In the present study, we examined the effects of repeated cocaine injections on neuroendocrine responses evoked by the alpha2-adrenergic receptor agonist, clonidine. Previous findings show that clonidine increases pituitary growth hormone (GH) secretion by a central mechanism involving postsynaptic a2-adrenergic receptors. Male rats previously fitted with indwelling jugular catheters received two daily injections of cocaine (15 mg/kg, i.p.) or saline for 7 days. At 42 h and 8 days after treatment, rats were challenged with clonidine (25 mug/kg, i.v.) or saline, and serial blood samples were withdrawn. Plasma GH and corticosterone levels were measured by radioimmunoassay. Prior cocaine exposure did not affect basal levels of either hormone. However, coca in e-p retreated rats displayed a significant reduction in clonidine-evoked GH secretion at 42 h, and this blunted response was still apparent 8 days later. Corticosterone responses produced by clonidine were similar regardless of pretreatment. The present data suggest that withdrawal from repeated cocaine injections may be accompanied by desensitization of postsynaptic alpha2-adrenoreceptors coupled to GH secretion. Since human patients with depression often exhibit blunted GH responses to clonidine, our findings provide evidence that cocaine withdrawal might produce depressive-like symptoms via dysregulation of NE mechanisms. Published by Elsevier Ltd on behalf of IBRO. C1 Natl Inst Drug Abuse, Intramural Res Program, Clin Psychopharmacol Sect, NIH, Baltimore, MD 21224 USA. RP Baumann, MH (reprint author), Natl Inst Drug Abuse, Intramural Res Program, Clin Psychopharmacol Sect, NIH, POB 5180,5500 Nathan Shock Dr, Baltimore, MD 21224 USA. EM mbaumann@irp.nida.nih.gov NR 64 TC 27 Z9 27 U1 2 U2 2 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0306-4522 J9 NEUROSCIENCE JI Neuroscience PY 2004 VL 125 IS 3 BP 683 EP 690 DI 10.1016/j.neuroscience.2004.02.013 PG 8 WC Neurosciences SC Neurosciences & Neurology GA 818XO UT WOS:000221278000017 PM 15099682 ER PT J AU Quintero, EM Willis, LM Zaman, V Lee, J Boger, HA Tomac, A Hoffer, BJ Stromberg, I Granholm, AC AF Quintero, EM Willis, LM Zaman, V Lee, J Boger, HA Tomac, A Hoffer, BJ Stromberg, I Granholm, AC TI Glial cell line-derived neurotrophic factor is essential for neuronal survival in the locus coeruleus-hippocampal noradrenergic pathway SO NEUROSCIENCE LA English DT Article DE noradrenergic neurons; locus coeruleus; glial cell line-derived neurotrophic factor; hippocampal formation; neuroplasticity; transplantation ID MICE LACKING GDNF; MIDBRAIN DOPAMINERGIC-NEURONS; PARKINSONS-DISEASE; NERVOUS SYSTEMS; AGED RATS; IN-VIVO; BRAIN; EXPRESSION; STRIATUM; CERULEUS AB It has been shown that the noradrenergic (NE) locus coeruleus (LC)-hippocampal pathway plays an important role in learning and memory processing, and that the development of this transmitter pathway is influenced by neurotrophic factors. Although some of these factors have been discovered, the regulatory mechanisms for this developmental event have not been fully elucidated. Glial cell line-derived neurotrophic factor (GDNF) is a potent neurotrophic factor influencing LC-NE neurons. We have utilized a GDNF knockout animal model to explore its function on the LC-NE transmitter system during development, particularly with respect to target innervation. By transplanting various combinations of brainstem (including LC) and hippocampal tissues from wildtype or GDNF knockout fetuses into the brains of adult wildtype mice, we demonstrate that normal postnatal development of brainstem LC-NE neurons is disrupted as a result of the GDNF null mutation. Tyrosine hydroxylase immunohistochemistry revealed that brainstem grafts had markedly reduced number and size of LC neurons in transplants from knockout fetuses. NE fiber innervation into the hippocampal co-transplant from an adjacent brainstem graft was also influenced by the presence of GDNF, with a significantly more robust innervation observed in transplants from wildtype fetuses. The most successful LC-hippocampal co-grafts were generated from fetuses expressing the wildtype GDNF background, whereas the most severely affected transplants were derived from double transplants from null-mutated fetuses. Our data suggest that development of the NE LC-hippocampal pathway is dependent on the presence of GDNF, most likely through a target-derived neurotrophic function. (C) 2004 IBRO. Published by Elsevier Ltd. All rights reserved. C1 Med Univ S Carolina, Dept Physiol & Neurosci, Charleston, SC 29425 USA. Med Univ S Carolina, Ctr Aging, Charleston, SC 29425 USA. Med Univ S Carolina, Dept Neurol, Charleston, SC 29425 USA. NIDA, Bethesda, MD 20892 USA. Umea Univ, Umea, Sweden. RP Granholm, AC (reprint author), Med Univ S Carolina, Dept Physiol & Neurosci, 26 Bee St, Charleston, SC 29425 USA. EM granholm@musc.edu FU NIA NIH HHS [R01 AG015239, AG15239] NR 45 TC 14 Z9 14 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0306-4522 J9 NEUROSCIENCE JI Neuroscience PY 2004 VL 124 IS 1 BP 137 EP 146 DI 10.1016/j.neuroscience.2003.11.001 PG 10 WC Neurosciences SC Neurosciences & Neurology GA 778QC UT WOS:000189251400013 PM 14960346 ER PT J AU Khiroug, SS Khiroug, L Yakel, JL AF Khiroug, SS Khiroug, L Yakel, JL TI Rat nicotinic acetylcholine receptor alpha 2 beta 2 channels: Comparison of functional properties with alpha 4 beta 2 channels in Xenopus oocytes SO NEUROSCIENCE LA English DT Article DE acetylcholine receptors; two-electrode voltage-clamp; Xenopus oocytes; ion channels; pharmacology ID CENTRAL-NERVOUS-SYSTEM; HIPPOCAMPAL INTERNEURONS; DISTINCT SUBTYPES; ACH RECEPTORS; NEURONS; SUBUNIT; ALPHA; ACTIVATION; CELLS; SENSITIVITY AB Rat hippocampal interneurons express diverse subtypes of nicotinic acetylcholine receptors (nAChRs), including alpha7- and non-alpha7-containing receptors. Although the major subtype of non-alpha7 nAChRs in the hippocampus is thought to be composed of alpha4beta2 subunits, the molecular makeup of these non-a7 receptors is likely to be more complicated. Previously, we reported a high level of expression of the alpha2 nAChR subunit in individual rat hippocampal CA1 stratum oriens interneurons. In addition, the non-alpha7 nAChRs from these neurons are less sensitive to block by dihydro-beta-erythroidine (DHbetaE; the broad spectrum non-alpha7 nAChR antagonist) than that expected for alpha4beta2 receptors. We studied the functional properties of rat alpha2beta2 channels expressed in Xenopus oocytes using two-electrode voltage-clamp, and compared these to those properties of the more widely expressed and studied alpha4beta2 channels. Dose-response curves for both receptor subtypes indicated that there are at least two different affinity sites for ACh, the fractional contribution of which depended on the ratio of injected RNA. DHPE blocked both receptor subtypes, although the sensitivity to block of alpha4beta2 channels was significantly higher than that for alpha2beta2. Finally, the current-voltage (I-V) relationship for the alpha2beta2 channels more strongly rectified than for the alpha4beta2 channels. These data suggest that functional properties, in particular the sensitivity to block by DHPE, might be useful indicators to differentiate between native alpha4beta2 and alpha2beta2 channels. In addition, these data suggest that the relative balance between the high- and low-affinity components being determined by the relative levels of the alpha and beta subunits might be a general property of the heteromeric non-alpha7 nAChRs. By comparing the properties of expressed nAChRs with those of the native channels, we might be able to learn what role alpha2-containing nAChRs may be playing in forming functional channels in the hippocampus. Published by Elsevier Ltd on behalf of IBRO. C1 NIEHS, Lab Signal Transduct, NIH, Dept Hlth & Human Serv, Res Triangle Pk, NC 27709 USA. RP Yakel, JL (reprint author), NIEHS, Lab Signal Transduct, NIH, Dept Hlth & Human Serv, F2-08,POB 12233,111 TW Alexander Dr, Res Triangle Pk, NC 27709 USA. EM yakel@njehs.nih.gov NR 33 TC 39 Z9 40 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0306-4522 J9 NEUROSCIENCE JI Neuroscience PY 2004 VL 124 IS 4 BP 817 EP 822 DI 10.1016/j.neuroscience.2004.01.017 PG 6 WC Neurosciences SC Neurosciences & Neurology GA 807VQ UT WOS:000220529400011 PM 15026122 ER PT J AU Miao, FJP Green, PG Benowitz, N Levine, JD AF Miao, FJP Green, PG Benowitz, N Levine, JD TI Central terminals of nociceptors are targets for nicotine suppression of inflammation SO NEUROSCIENCE LA English DT Article DE plasma extravasation; opioid; alpha-adrenergic; descending; antinociceptive controls ID INDUCED PLASMA EXTRAVASATION; ACETYLCHOLINE-RECEPTOR SUBTYPES; ENVIRONMENTAL TOBACCO-SMOKE; EXCITATORY AMINO-ACIDS; RAT DORSAL-ROOT; RHEUMATOID-ARTHRITIS; CIGARETTE-SMOKING; INTRATHECAL NICOTINE; GANGLION NEURONS; SENSORY NEURONS AB Spinal intrathecal administration of nicotine inhibits bradykinin-induced plasma extravasation, a component of the inflammatory response, in the knee joint of the rat in a dose-related fashion. Nociceptors contain nicotinic receptors and activation of a nociceptor at its peripheral terminal, by capsaicin, also produces inhibition of inflammation. Therefore the aim of this study was to test the hypothesis that the spinal target for this effect of nicotine is the central terminal of the primary afferent nociceptor. Intrathecal administration of the neurokinin-1 receptor antagonist, (3aR,7aR)-7,7-diphenyl-2-(1-imino-2(2-methoxyphenyl)-ethyl) perhydroisoindol-4-1 hydrochloride or the N-methyl-D-aspartate receptor antagonist, DL-2-amino-5-phosphono-valeric acid, both antagonists of the action of primary afferent neurotransmitters, markedly attenuated the inhibition of bradykinin-induced plasma extravasation produced by both intrathecal nicotine and intraplantar capsaicin. Conversely, intrathecal administration of an alpha-adrenoceptor antagonist, phentolamine or an opioid receptor antagonist, naloxone, to block descending antinociceptive controls, which provide inhibitory input to primary afferent nociceptors, enhanced the action of both nicotine and capsaicin. These findings support the hypothesis that the central terminal of the primary afferent nociceptor is a CNS target at which nicotine acts to inhibit inflammation. (C) 2003 IBRO. Published by Elsevier Ltd. All rights reserved. C1 Univ Calif San Francisco, NIH, Pain Ctr, Sch Med & Dent, San Francisco, CA 94143 USA. Univ Calif San Francisco, NIH, Pain Ctr, Sch Med & Dent,Dept Oral & Maxillofacial Surg, San Francisco, CA 94143 USA. Univ Calif San Francisco, NIH, Pain Ctr, Sch Med & Dent,Dept Med,Div Clin Pharmacol, San Francisco, CA 94143 USA. Univ Calif San Francisco, NIH, Pain Ctr, Sch Med & Dent,Dept Med,Div Rheumatol, San Francisco, CA 94143 USA. Univ Calif San Francisco, NIH, Pain Ctr, Sch Med & Dent,Dept Anat, San Francisco, CA 94143 USA. RP Levine, JD (reprint author), Univ Calif San Francisco, NIH, Pain Ctr, Sch Med & Dent, 521 Parnassus Ave,C-522,Box 0440, San Francisco, CA 94143 USA. EM levine@itsa.ucsf.edu RI Green, Paul/C-5943-2011 NR 70 TC 21 Z9 22 U1 1 U2 2 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0306-4522 J9 NEUROSCIENCE JI Neuroscience PY 2004 VL 123 IS 3 BP 777 EP 784 DI 10.1016/j.neuroscience.2003.10.027 PG 8 WC Neurosciences SC Neurosciences & Neurology GA 761YF UT WOS:000187942500022 PM 14706790 ER PT J AU Frascella, J Lynch, MR Pilotte, N Thomas, D AF Frascella, J Lynch, MR Pilotte, N Thomas, D TI Foundations and innovations in the neuroscience of drug abuse - In honor of the work of Roger Brown SO NEUROSCIENCE AND BIOBEHAVIORAL REVIEWS LA English DT Biographical-Item C1 NIDA, Clin Neurobiol Branch, MSC, Bethesda, MD 20892 USA. NIDA, Behav & Cognit Sci Res Branch, Div Neurosci & Behav Res, NIH, Bethesda, MD 20892 USA. RP Frascella, J (reprint author), NIDA, Clin Neurobiol Branch, MSC, Room 4234, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0149-7634 J9 NEUROSCI BIOBEHAV R JI Neurosci. Biobehav. Rev. PD JAN PY 2004 VL 27 IS 8 BP 691 EP 691 DI 10.1016/j.neubiorev.2003.11.016 PG 1 WC Behavioral Sciences; Neurosciences SC Behavioral Sciences; Neurosciences & Neurology GA 775WG UT WOS:000189083200001 ER PT J AU Jacobowitz, DM AF Jacobowitz, DM TI Professional biographical sketch SO NEUROTOXICITY RESEARCH LA English DT Biographical-Item C1 NIMH, Clin Sci Lab, NIH, Bethesda, MD 20892 USA. Uniformed Serv Univ Hlth Sci, Dept Anat Physiol & Genet, Bethesda, MD 20814 USA. RP Jacobowitz, DM (reprint author), NIMH, Clin Sci Lab, NIH, Bldg 10, Bethesda, MD 20892 USA. EM dwj@helix.nih.gov NR 0 TC 0 Z9 0 U1 0 U2 0 PU F P GRAHAM PUBLISHING CO PI MOUNTAIN HOME PA PO BOX 370, MOUNTAIN HOME, TN 37684 USA SN 1029-8428 J9 NEUROTOX RES JI Neurotox. Res. PY 2004 VL 6 IS 4 BP I EP XIV PG 14 WC Neurosciences SC Neurosciences & Neurology GA 880OH UT WOS:000225798600001 PM 15614981 ER PT J AU Jacobowitz, DM Kallarakal, AT AF Jacobowitz, DM Kallarakal, AT TI Flotillin-1 in the substantia nigra of the Parkinson brain and a predominant localization in catecholaminergic nerves in the rat brain SO NEUROTOXICITY RESEARCH LA English DT Article DE dopamine; norepinephrine; differential display; locus coeruleus; striatum; cortex ID ACETYLCHOLINESTERASE-CONTAINING NEURONS; RETINAL GANGLION-CELLS; LOCUS-COERULEUS; STRIATAL DOPAMINE; AXON REGENERATION; TOPOGRAPHIC ATLAS; LIPID RAFTS; DISEASE; PROTEINS; IDENTIFICATION AB The substantia nigra cells of a normal and Parkinson's disease human brain were obtained by the micropunch procedure and total RNA was isolated. Differential display RT-PCR of the total RNA revealed differentially expressed cDNAs that were identified by sequencing. This resulted in the identification of a panel of known and unknown differentially expressed genes. Complex I (NADH ubiquinone oxidoreductase) and Complex IV (cytochrome oxidase) whose expressions are decreased in Parkinson's disease were reduced in the Parkinson brain. Of the various differentially expressed genes, flotillin-1, also known as reggie-2, was of great interest to us. It is a relatively new protein which is an integral membrane component of lipid rafts and has been implicated in signal transduction pathway events. In situ hybridization histochemical studies with human and rat brain sections revealed the presence of this mRNA in discrete neuronal (and possibly glial) cells of the substantia nigra, locus coeruleus, cortex, hippocampus, hypothalamus, thalamus, motor nuclei, nucleus basalis, raphe nucleus, and other brain regions. Immunohistochemical studies revealed that flotillin-1 is not present in all the regions where the message was found. In the rat brain, the most prominent observation was the revelation of all catecholamine cells (dopamine, norepinephrine, epinephrine) by the flotillin-1 antibody (1:100 dilution). At a more concentrated dilution (1:10) other neuronal cells (e.g., cortex, thalamus, hindbrain) were observed. At both dilutions dense dopaminergic fibers were observed in the rat caudate-putamen, nigrostriatal tract, and substantia nigra. It is significant that there is an increased gene expression of flotillin-1 in the Parkinson substantia nigra/ventral tegmental area. The role of flotillin in these cells is unclear although it is interesting that the reggie-2/flotillin-1 gene was upregulated during retinal axon regeneration in the goldfish visual pathway (Schulte et al., Development 124:577-87, 1997) which suggests that flotillin-1/reggie-2 might play a role in axonal growth from the remaining substantia nigra cells of the Parkinson brain. C1 NIMH, Clin Sci Lab, NIH, Bethesda, MD 20892 USA. Uniformed Serv Univ Hlth Sci, Dept Anat Physiol & Genet, Bethesda, MD 20814 USA. RP Jacobowitz, DM (reprint author), NIMH, Clin Sci Lab, NIH, Bldg 10, Bethesda, MD 20892 USA. EM dwj@helix.nih.gov NR 38 TC 18 Z9 18 U1 0 U2 3 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1029-8428 EI 1476-3524 J9 NEUROTOX RES JI Neurotox. Res. PY 2004 VL 6 IS 4 BP 245 EP 257 PG 13 WC Neurosciences SC Neurosciences & Neurology GA 880OH UT WOS:000225798600003 PM 15545008 ER PT J AU Zhu, DM Jiang, XY Wu, X Tian, F Mearow, K Lipsky, RH Marini, AM AF Zhu, DM Jiang, XY Wu, X Tian, F Mearow, K Lipsky, RH Marini, AM TI Inhibition of protein kinase C promotes neuronal survival in low potassium through an Akt-dependent pathway SO NEUROTOXICITY RESEARCH LA English DT Article DE BDNF; PKC; PKC alpha; phosphatidylinositol 3-kinase/Akt; low potassium; rat cerebellar granule neurons ID CEREBELLAR GRANULE NEURONS; METHYL-D-ASPARTATE; K+-INDUCED APOPTOSIS; NERVE GROWTH-FACTOR; CELL-DEATH; PHOSPHATIDYLINOSITOL 3-KINASE; SIGNAL-TRANSDUCTION; FACTOR-I; ACTIVATION; DEPOLARIZATION AB Cerebellar granule cell neurons undergo apoptotic cell death when subjected to serum-free conditions at physiological concentrations of potassium (5 mM). Protein kinase C (PKC) is known to play a role in preventing neuronal apoptosis under trophic factor deprivation, but its role in protecting cerebellar neurons from cell death under conditions of low potassium is unknown. This study sought to determine the involvement of PKC in neuronal survival and to determine if PKC regulated the phosphatidylinositol 3-kinase (PI 3-K)/Akt pathway in low physiologic concentrations of potassium. Incubation with a pan-PKC inhibitor, Ro-31-8220 (2 muM), or a specific PKCalpha inhibitor, Go6976, protected cerebellar granule cell neurons from low potassium-mediated cell death. In contrast, phorbol ester (TPA, 100 nM), a PKC activator, increased cell death. Incubation with, Ro-31-8220 rescued neurons from cell death induced by the PI 3-K inhibitor, LY294002, suggesting that Ro-31-8220 may affect Akt phosphorylation. Western blot analysis showed that serum-free, low potassium conditions decreased Akt phosphorylation, which was exacerbated by treatment with LY294002. In contrast, PKC inhibitors, Go6976 or Ro-31-8220, increased Akt phosphorylation approximately two and fourfold, respectively, in low potassium conditions. Because Akt activation appears to be critical in promoting neuronal survival under these culture conditions, increased Akt phosphorylation brought about by inhibiting PKC promotes neuronal survival. C1 Uniformed Serv Univ Hlth Sci, Dept Neurol & Neurosci, Bethesda, MD 20814 USA. NIAAA, NIH, Neurogenet Lab, Mol Genet Sect, Rockville, MD 20852 USA. RP Marini, AM (reprint author), Uniformed Serv Univ Hlth Sci, Dept Neurol & Neurosci, Bethesda, MD 20814 USA. EM amarini@usuhs.mil OI Lipsky, Robert/0000-0001-7753-1473 NR 47 TC 16 Z9 16 U1 0 U2 2 PU F P GRAHAM PUBLISHING CO PI MOUNTAIN HOME PA PO BOX 370, MOUNTAIN HOME, TN 37684 USA SN 1029-8428 J9 NEUROTOX RES JI Neurotox. Res. PY 2004 VL 6 IS 4 BP 281 EP 289 PG 9 WC Neurosciences SC Neurosciences & Neurology GA 880OH UT WOS:000225798600006 PM 15545011 ER PT J AU Harry, GJ McPherson, CA Wine, RN Atkinson, K d'Hellencourt, CL AF Harry, GJ McPherson, CA Wine, RN Atkinson, K d'Hellencourt, CL TI Trimethyltin-induced neurogenesis in the murine hippocampus SO NEUROTOXICITY RESEARCH LA English DT Article DE trimethyltin; neurogenesis; hippocampus; neurodegeneration; apoptosis; microglia ID GRANULE NEURON APOPTOSIS; NECROSIS-FACTOR-ALPHA; DENTATE GYRUS; ADULT NEUROGENESIS; MESSENGER-RNA; MOUSE; CELLS; MICE; NEURODEGENERATION; EXPRESSION AB Neurogenesis continues to occur in the mature rodent brain with one of the most prominent sources for new neurons being the subgranular layer (SGL) of the dentate gyrus (DG) in the hippocampus. A number of factors can stimulate this process including synaptic activity and injury. To determine if this process would occur upon a direct injury to the dentate region, we exposed young, 21 day old male CD-1 mice to the hippocampal toxicant, trimethyltin (TMT). An acute i.p. injection of TMT (2 mg/kg) produced extensive damage and loss of dentate granule neurons within 72 h. This active period of degeneration was accompanied by an increase in the generation of progenitor cells within the SGL as identified by BrdU uptake and Ki-67 immunostaining. As additional markers for neurogenesis, both nestin and doublecortin showed increased staining patterns within the blades of the dentate. In these young weanling mice, the level of proliferation was sufficient to significantly repopulate the dentate region by 4 weeks post-TMT, suggesting a high level of regenerative potential. Our data indicate a significant level of neurogenesis occurring during the active process of degeneration and in an environment of microglia activation. The TMT-induced injury offers a model system for further examination of the process of neurogenesis, neural adaptation, and the influence of inflammatory factors and glia interactions. C1 NIEHS, Neurotoxicol Grp, Mol Toxicol Lab, Dept Hlth & Human Serv,NIH, Res Triangle Pk, NC 27709 USA. RP Harry, GJ (reprint author), NIEHS, Neurotoxicol Grp, Mol Toxicol Lab, Dept Hlth & Human Serv,NIH, POB 12233,MD C1-04, Res Triangle Pk, NC 27709 USA. EM harry@niehs.nih.gov FU NIEHS NIH HHS [Z01 ES021164-09] NR 22 TC 25 Z9 26 U1 2 U2 5 PU F P GRAHAM PUBLISHING CO PI MOUNTAIN HOME PA PO BOX 370, MOUNTAIN HOME, TN 37684 USA SN 1029-8428 J9 NEUROTOX RES JI Neurotox. Res. PY 2004 VL 5 IS 8 BP 623 EP 627 PG 5 WC Neurosciences SC Neurosciences & Neurology GA 809YI UT WOS:000220671600007 PM 15111239 ER PT J AU He, N Bai, J Champoux, M Suomi, SJ Lidow, MS AF He, N Bai, J Champoux, M Suomi, SJ Lidow, MS TI Neurobehavioral deficits in neonatal rhesus monkeys exposed to cocaine in utero SO NEUROTOXICOLOGY AND TERATOLOGY LA English DT Article DE cocaine; prenatal exposure; neurobehavioral assessment; nonhuman primates; cerebral cortex ID PRENATAL COCAINE; NEUROMOTOR DEVELOPMENT; MACACA-MULATTA; CEREBRAL WALL; PREGNANCY; INFANTS; PHARMACOKINETICS; PRIMATE; STRESS; ATTENTION AB In spite of significant efforts, the neurobehavioral deficits in infants born from cocaine-abusing mothers have not been clearly defined. In the present study, we examined the presence of these abnormalities in a rhesus monkey model of prenatal cocaine exposure using a nonhuman primate adaptation of the Neonatal Behavioral Assessment Scale (NBAS). Pregnant monkeys (n = 14) received 10 mg/kg cocaine twice a day orally (in fruit treats) from the 40th through 102nd postconception days (PCD40-PCD102), which is the period of cerebral cortical neuronogenesis ( similar to second trimester). The control consisted of pregnant monkeys (n = 14) receiving fruit treats only. The animals were allowed to deliver vaginally at term (similar to PCD 165). The first testing session was conducted on PCD 171 (within the first week after birth); the second testing session was conducted on PCD177 (within the second week after birth); the third test was conducted on PCD183 (within the third week after birth); and the fourth testing session was conducted on PCD189 (within the fourth week after birth). The prenatally cocaine-exposed infants showed deficits in orientation, state control, and motor maturity, which were detectable during the second, third, and fourth testing sessions. The same testing sessions also revealed a significant reduction in the time devoted to toy manipulation, which points to impaired attention. None of these abnormalities were seen during the first testing session. The first session, however, revealed increased tremulousness (one of the indicators of autonomic stability) in the prenatally cocaine-exposed infants. This impairment disappeared by the third testing session. The present findings demonstrate the potential of prenatal cocaine exposure to induce neurobehavioral deficits detectable by NBAS-like testing in primate infants. (C) 2003 Elsevier Inc. All rights reserved. C1 Univ Maryland, Div Neurosci, Dept Biomed Sci, Baltimore, MD 21201 USA. NICHHD, Comparat Ethol Lab, NIH, Anim Ctr, Poolesville, MD 20837 USA. RP Lidow, MS (reprint author), Univ Maryland, Div Neurosci, Dept Biomed Sci, 5-A-12,HHH,666 W Baltimore St, Baltimore, MD 21201 USA. EM mlidow@umaryland.edu FU NIDA NIH HHS [R01 DA08057] NR 51 TC 17 Z9 19 U1 1 U2 2 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0892-0362 J9 NEUROTOXICOL TERATOL JI Neurotoxicol. Teratol. PD JAN-FEB PY 2004 VL 26 IS 1 BP 13 EP 21 DI 10.1016/j.ntt.2003.08.003 PG 9 WC Neurosciences; Toxicology SC Neurosciences & Neurology; Toxicology GA 803NG UT WOS:000220237200002 PM 15001210 ER PT J AU Levin, ED Brunssen, S Wolfe, GW Harry, GJ AF Levin, ED Brunssen, S Wolfe, GW Harry, GJ TI Neurobehavioral assessment of mice after developmental AZT exposure SO NEUROTOXICOLOGY AND TERATOLOGY LA English DT Article DE azidothymidine; AZT; prenatal; learning; mice ID RADIAL-ARM MAZE; ALPHA-4-BETA-2 NICOTINIC RECEPTORS; LONG RETENTION INTERVALS; ANTI-HIV DRUGS; WORKING-MEMORY; SPATIAL MEMORY; ZIDOVUDINE TREATMENT; AGGRESSIVE-BEHAVIOR; HIPPOCAMPAL ALPHA-7; PRENATAL EXPOSURE AB Azidothymidine (AZT) is administered to pregnant women with HIV to prevent the spread of infection to their fetuses. Since gestation is a period of critical neurodevelopment, it is important to determine the risk AZT exposure may pose to neurobehavioral function of the offspring. The current study focused on teratological risks of developmental AZT exposure to neurocognitive function. Male and female Swiss mice were administered AZT or vehicle (0, 100, or 200 mg/kg/day po given twice daily in equal amounts for 32 weeks before and during gestation). Adult male and female offspring (n = 10/sex/treatment group) underwent neurobehavioral testing focused on determining learning and memory capabilities in the radial-arm maze. AZT exposure did not cause significant deficits during radial-arm maze acquisition. No impairment was seen in asymptotic levels of choice accuracy indicative of working memory function. Attempts to unmask subtle learning impairments following developmental AZT by the introduction of behavioral challenges such as reduction of motivational state (food restriction either 4-6 h or 22-24 h) or imposition of intrasession delays of 1.5 min to 2.5 h were unsuccessful. With a 4-week intersession delay, a significant AZT Treatment X Delay effect was seen with a significantly greater decline seen in the controls as compared to the 100 mg/kg/day AZT group. Locomotor activity on the radial-arm maze was significantly affected by AZT treatment (100 mg/kg/day) during the acquisition phase, but not during the other test phases. No behavioral alterations were seen related to stress as measured by the elevated plus maze. Vestibulomotor functioning on the balance beam remained unaltered. Using an extended dosing regimen including dosing of both sires and dams, as well as placing a greater demand on reproductive system performance with three continuous breedings, this study detected only subtle neurobehavioral impairments in mice after prenatal AZT exposure at clinically relevant doses. (C) 2003 Elsevier Inc. All rights reserved. C1 Duke Univ, Med Ctr, Dept Psychiat, Durham, NC 27710 USA. Univ N Carolina, Chapel Hill, NC USA. TherImmune Inc, Gaithersburg, MD USA. Natl Inst Environm Hlth Sci, Res Triangle Pk, NC USA. RP Levin, ED (reprint author), Duke Univ, Med Ctr, Dept Psychiat, Box 3412, Durham, NC 27710 USA. EM edlevin@duke.edu NR 31 TC 3 Z9 3 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0892-0362 J9 NEUROTOXICOL TERATOL JI Neurotoxicol. Teratol. PD JAN-FEB PY 2004 VL 26 IS 1 BP 65 EP 71 DI 10.1016/j.ntt.2003.10.001 PG 7 WC Neurosciences; Toxicology SC Neurosciences & Neurology; Toxicology GA 803NG UT WOS:000220237200007 PM 15001215 ER PT J AU Weber, AM Buchsbaum, GM Chen, B Clark, AL Damaser, MS Daneshgari, F Davis, G DeLancey, J Kenton, K Weidner, AC Word, RA AF Weber, AM Buchsbaum, GM Chen, B Clark, AL Damaser, MS Daneshgari, F Davis, G DeLancey, J Kenton, K Weidner, AC Word, RA TI Basic science and translational research in female pelvic floor disorders: Proceedings of an NIH-sponsored meeting SO NEUROUROLOGY AND URODYNAMICS LA English DT Review DE fecal incontinence; laboratory research; pelvic organ prolapse; urinary incontinence ID LEVATOR ANI MUSCLE; SIMULATED BIRTH TRAUMA; SPHINCTER MECHANISM INCOMPETENCE; URINARY-INCONTINENCE PREVALENCE; GENUINE STRESS-INCONTINENCE; MAGNETIC-RESONANCE IMAGES; REGULATORY FACTOR GENES; ANTERIOR VAGINAL WALL; PUDENDAL NERVE CRUSH; ORGAN PROLAPSE AB Aims: To report the findings of a multidisciplinary group of scientists focusing on issues in basic science and translational research related to female pelvic floor disorders, and to produce recommendations for a research agenda for investigators studying female pelvic floor disorders. Methods: A National Institutes of Health (NIH)-sponsored meeting was held on November 14-15, 2002, bringing together scientists in diverse fields including obstetrics, gynecology, urogynecology, urology, gastroenterology, biomechanical engineering, neuroscience, endocrinology, and molecular biology. Recent and ongoing studies were presented and discussed, key gaps in knowledge were identified, and recommendations were made for research that would have the highest impact in making advances in the field of female pelvic floor disorders. Results: The meeting included presentations and discussion on the use of animal models to better understand physiology and pathophysiology; neuromuscular injury (such as at childbirth) as a possible pathogenetic factor and mechanisms for recovery of function after injury; the use of biomechanical concepts and imaging to better understand the relationship between structure and function; and molecular and biochemical mechanisms that may underlie the development of female pelvic floor disorders. Conclusions: While the findings of current research will help elucidate the pathophysiologic pathways leading to the development of female pelvic floor disorders, much more research is needed for full understanding that will result in better care for patients through specific rather than empiric therapy, and lead to the potential for prevention on primary and secondary levels. (C) 2004 Wiley-Liss, Inc. C1 NICHHD, Populat Res Ctr, Contracept & Reprod Hlth Branch, Pittsburgh, PA USA. Univ Rochester, Dept Obstet & Gynecol, Rochester, NY 14627 USA. Stanford Univ, Med Ctr, Dept Obstet & Gynecol, Stanford, CA 94305 USA. Oregon Hlth Sci Univ, Dept Obstet & Gynecol, Portland, OR 97201 USA. Edward Hines Jr Vet Adm Hosp, Hines, IL 60141 USA. Cleveland Clin Fdn, Dept Urol, Cleveland, OH 44195 USA. Walter Reed Army Med Ctr, Dept Obstet & Gynecol, Washington, DC 20307 USA. Univ Michigan, Dept Obstet & Gynecol, Ann Arbor, MI 48109 USA. Loyola Univ, Med Ctr, Dept Obstet & Gynecol, Maywood, IL 60153 USA. Duke Univ, Dept Obstet & Gynecol, Durham, NC 27706 USA. Univ Texas SW, Dept Obstet & Gynecol, Dallas, TX USA. RP Weber, AM (reprint author), Magee Womens Hosp, 300 Halket St, Pittsburgh, PA 15238 USA. EM aweber@magee.edu NR 114 TC 41 Z9 45 U1 0 U2 2 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0733-2467 J9 NEUROUROL URODYNAM JI Neurourol. Urodyn. PY 2004 VL 23 IS 4 BP 288 EP 301 DI 10.1002/nau.20048 PG 14 WC Urology & Nephrology SC Urology & Nephrology GA 835KG UT WOS:000222481100002 PM 15227643 ER PT S AU Lu, B AF Lu, B BE Aloe, L Calza, L TI Acute and long-term synaptic modulation by neurotrophins SO NGF AND RELATED MOLECULES IN HEALTH AND DISEASE SE PROGRESS IN BRAIN RESEARCH LA English DT Article; Proceedings Paper CT 7th International Conference on NGF and Related Molecules CY MAY 15-19, 2002 CL Modena, ITALY SP Assoc Levi Montalcini, Assoc Promoz Sociale DE neurotrophins; neuromuscular junction; hippocampus; visual cortex; synaptic transmission; synaptogenesis; synaptic plasticity ID NERVE GROWTH-FACTOR; RAT VISUAL-CORTEX; CULTURED HIPPOCAMPAL-NEURONS; FACTOR MESSENGER-RNA; DOMINANCE COLUMN FORMATION; APLYSIA SENSORY NEURONS; DEVELOPING NEUROMUSCULAR SYNAPSES; MONOCULAR DEPRIVATION DECREASES; CORTICAL DENDRITIC GROWTH; CAMP-RESPONSIVE ELEMENT AB While it has now been well accepted that neurotrophins play an important role in synapse development and plasticity, the specific effects of each neurotrophin on different populations of neurons at different developmental stages have just begun to be worked out. Moreover, the cellular and molecular mechanisms underlying the synaptic function of neurotrophins remain poorly understood. In general, synaptic effects of neurotrophins could be divided into two categories: acute effect on synaptic transmission and plasticity occurring within seconds or minutes after cells are exposed to a neurotrophin, and long-term effect on synaptic structures and function that takes days to accomplish. In this review I have considered the previous findings on neurotrophic regulation of synapses in view of these two categories. Acute and long-term effects of neurotrophins are reexamined in detail in three model systems: the neuromuscular junction, the hippocampus and the visual cortex. Potential molecular mechanisms that mediate the acute or long-term neurotrophic regulation are discussed. Efforts are made to understand the mechanistic differences between the two effects and their relationships. Further study of these mechanisms will help us better understand how neurotrophins can achieve diverse and synapse-specific modulation. C1 NICHD, Sect Neuroal Dev & Plast, NIH, Bethesda, MD 20892 USA. RP Lu, B (reprint author), NICHD, Sect Neuroal Dev & Plast, NIH, Bldg 49,Rm 6A80,49 Convent Dr,MSC4480, Bethesda, MD 20892 USA. EM bailu@mail.nih.gov NR 154 TC 71 Z9 73 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA SARA BURGERHARTSTRAAT 25, PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0079-6123 BN 0-444-51472-4 J9 PROG BRAIN RES PY 2004 VL 146 BP 137 EP 150 DI 10.1016/S0079-6123(03)46010-X PG 14 WC Cell Biology; Medicine, Research & Experimental; Neurosciences SC Cell Biology; Research & Experimental Medicine; Neurosciences & Neurology GA BY65Y UT WOS:000189432300010 PM 14699962 ER PT S AU Fritzsch, B Tessarollo, L Coppola, E Reichardt, LF AF Fritzsch, B Tessarollo, L Coppola, E Reichardt, LF BE Aloe, L Calza, L TI Neurotrophins in the ear: their roles in sensory neuron survival and fiber guidance SO NGF AND RELATED MOLECULES IN HEALTH AND DISEASE SE Progress in Brain Research LA English DT Review CT 7th International Conference on NGF and Related Molecules CY MAY 15-19, 2002 CL Modena, ITALY SP Assoc Levi Montalcini, Assoc Promoz Sociale DE BDNF; NT-3; TrkB; TrkC; ear innervation; mutant mice ID INNER-EAR; HAIR-CELLS; TARGET INNERVATION; VESTIBULAR GANGLION; MUTANT MICE; TRKC; BDNF; GENE; RECEPTORS; BRAIN AB We review the history of neurotrophins in the ear and the current understanding of the function of neurotrophins in ear innervation, development and maintenance. Only two neurotrophins, brain-derived neurotrophic factor (BDNF) and neurotrophin-3 (NT-3), and their receptors, tyrosine kinase B (TrkB) and TrkC, appear to provide trophic support for inner ear sensory neuron afferents. Mice lacking either both receptors or both ligands lose essentially all sensory innervation of targets in the vestibular and auditory systems of the ear. Analyzes of single mutants show less complete and differential effects on innervation of the different sensory organs within the ear. BDNF and TrkB are most important for survival of vestibular sensory neurons whereas NT-3 and TrkC are most important for survival of cochlear sensory neurons. The largely complementary roles of BDNF to TrkB and NT-3 to TrkC signaling do not reflect specific requirements for innervation of different classes of hair cells. Most neurons express both receptors. Instead, the losses observed in single mutants are related to the spatio-temporal expression pattern of the two neurotrophins. In an area where only one neurotrophin is expressed at a particular time in development, the other neurotrophin is not present to compensate for this absence, resulting in death of neurons innervating that region. Decisive evidence for this suggestion is provided by transgenic mice in which the BDNF coding region has been inserted into the NT-3 gene, resulting in expression of BDNF instead of NT-3. The expression of BDNF in the spatio-temporal pattern of NT-3 results in survival of almost all neurons that are normally lost in the NT-3 mutant. Thus, BDNF and NT-3 have a high level of functional equivalence for inner ear sensory neuron survival. Further analysis of the patterns of afferent fiber losses in mutations that do not develop differentiated hair cells shows that the expression of neurotrophins is remarkably strong and can support afferent innervation. Indeed, BDNF may be one of the earliest genes expressed selectively in hair cells and it appears to be regulated somewhat independently of the genes needed for hair cell differentiation. C1 Creighton Univ, Dept Biomed Sci, Omaha, NE 68178 USA. NCI, FCDRC, Frederick, MD USA. Univ Calif San Francisco, Howard Hughes Med Inst, San Francisco, CA 94143 USA. RP Fritzsch, B (reprint author), Creighton Univ, Dept Biomed Sci, Omaha, NE 68178 USA. EM Fritzsch@Creighton.edu RI Coppola, Vincenzo/E-2917-2011; OI Coppola, Vincenzo/0000-0001-6163-1779; Fritzsch, Bernd/0000-0002-4882-8398 FU NIDCD NIH HHS [R01 DC005950, 2P01 DC00215]; NINDS NIH HHS [P01 NS016033] NR 46 TC 118 Z9 126 U1 2 U2 6 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA SARA BURGERHARTSTRAAT 25, PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0079-6123 BN 0-444-51472-4 J9 PROG BRAIN RES JI Prog. Brain Res. PY 2004 VL 146 BP 265 EP 278 DI 10.1016/S0079-6123(03)46017-2 PG 14 WC Cell Biology; Medicine, Research & Experimental; Neurosciences SC Cell Biology; Research & Experimental Medicine; Neurosciences & Neurology GA BY65Y UT WOS:000189432300017 PM 14699969 ER PT B AU Choi, EJ Jin, AJ Niu, SL Smith, PD Litman, BJ AF Choi, EJ Jin, AJ Niu, SL Smith, PD Litman, BJ BE Laudon, M Romanowicz, B TI Visualizing individual rhodopsin (a G protein-coupled receptor) molecules in native disk and reconstituted membranes via atomic force microscopy SO NSTI NANOTECH 2004, VOL 1, TECHNICAL PROCEEDINGS LA English DT Proceedings Paper CT Nanotechnology Conference and Trade Show (Nanotech 2004) CY MAR 07-11, 2004 CL Boston, MA SP Nano Sci & Technol Inst, Intel Corp, Motorola, Texas Instruments, Ciphergen Biosyst Inc, iMediasoft Grp, Frontier Carbon Corp, Veeco Instruments, Hitachi High Technologies Amer Inc, Racepoint Grp Inc, Int SEMATECH, FEI Co, Keithley, St Gobain High Performance Mat, Zyvex Corp, Accelrys, ANSYS Inc, Atomistix, PolyInsight, GA Dept Ind & Trade, Swiss Business Hub USA, Australian Govt, Invest Australia, State Bavaria, Germany, United States Off Econ Dev, m+w zander, Engis Corp, COMSOL, Engelhard Corp, Nanonex Inc, nanoTITAN, Tegal Corp, Umech Technologies, MEMSCAP, Swiss House Adv Res & Educ SHARE, Basel Area Business, Dev, Dev Econ Western Switzerland, Nanoworld AG, Nanosensors, Nanofair, Burns, Doane, Swecker & Mathis, LLP, Mintz Levin Cohn Ferris Glovsky & Popeo, PC, Jackson Walker LLP, Greater Zurich Area DE atomic force microscopy; rhodopsin; G-protein-coupled receptor; cell membrane AB Individual rhodopsin molecules have been resolved with atomic force microscopy as both monomers and various oligomeric organizations that are sensitively dependent upon the physical state of membranes and environmental conditions. In intact native disk membranes, rhodopsin molecules are observed as randomly dispersed monomers and small oligomers. In reconstituted rhodopsin-DPPC (dipaimitoylphosphatidylcholine, di16:0-PC) membranes, phase separation of lipid and rhodopsin results in paracrystalline arrays of rhodopsin molecules. Since the coupling of rhodopsin and G proteins is an essential step in visual transduction, the results from this study could provide further insight into the structural relationship of rhodopsin to its function in vision and may have applications in nanotechnology. C1 NIH, OD, ORS, Div Bioengn & Phys Sci,IRDR, Bethesda, MD 20892 USA. RP Choi, EJ (reprint author), NIH, OD, ORS, Div Bioengn & Phys Sci,IRDR, Bethesda, MD 20892 USA. OI Jin, Albert/0000-0003-3826-1081 NR 11 TC 0 Z9 0 U1 0 U2 0 PU NANO SCIENCE & TECHNOLOGY INST PI CAMBRIDGE PA ONE KENDALL SQUARE, PMB 308, CAMBRIDGE, MA 02139 USA BN 0-9728422-7-6 PY 2004 BP 63 EP 66 PG 4 WC Biotechnology & Applied Microbiology; Instruments & Instrumentation; Materials Science, Multidisciplinary SC Biotechnology & Applied Microbiology; Instruments & Instrumentation; Materials Science GA BAO45 UT WOS:000223073000016 ER EF